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Sample records for enhances non-functional neovascularization

  1. Dye-enhanced diode laser photocoagulation of choroidal neovascularizations

    Science.gov (United States)

    Klingbeil, Ulrich; Puliafito, Carmen A.; McCarthy, Dan; Reichel, Elias; Olk, Joseph; Lesiecki, Michael L.

    1994-06-01

    Dye-enhanced diode laser photocoagulation, using the dye indocyanine green (ICG), has shown some potential in the treatment of choroidal neovascularizations (CNV). A diode laser system was developed and optimized to emit at the absorption maximum of ICG. In a clinical study at two retinal centers, more than 70 patients, the majority of which had age-related macular degeneration, were treated. Eighteen cases with ill-defined subfoveal CNV were followed an average of 11 months after laser treatment. The results show success in resolving the CNV with an average long-term preservation of visual function equal to or superior to data provided by the Macular Photocoagulation Study for confluent burns of low intensity applied to the CNV. Details of the technique and discussion of the controversies inherent in such a treatment strategy will be presented.

  2. Placental Growth Factor Promotes Cardiac Muscle Repair via Enhanced Neovascularization

    Directory of Open Access Journals (Sweden)

    Jianfeng Zhang

    2015-06-01

    Full Text Available Background/Aims: Transplantation of mesenchymal stem cells (MSCs improves post-injury cardiac muscle repair using ill-defined mechanisms. Recently, we have shown that production and secretion of placental growth factor (PLGF by MSCs play a critical role in the MSCs-mediated post-injury cardiac muscle repair. In this study, we addressed the underlying molecular mechanisms, focusing specifically on the interactions between MSCs, macrophages and endothelial cells. Methods: We isolated macrophages (BM-MΦ from mouse bone-marrow derived cells based on F4/80 expression by flow cytometry. BM-MΦ were treated with different doses of PLGF. Cell number was analyzed by a MTT assay. Macrophage polarization was examined based on CD206 expression by flow cytometry. PLGF levels in macrophage subpopulations were analyzed by RT-qPCR and ELISA. Effects of macrophages on vascularization were evaluated by a collagen gel assay using Human umbilical vein endothelial cells (HUVECs co-cultured with PLGF-treated macrophages. Results: PLGF did not increase macrophage number, but dose-dependently polarized macrophages into a M2 subpopulation. M2 macrophages expressed high levels of PLGF. PLGF-polarized M2 macrophages significantly increased tubular structures in the collagen gel assay. Conclusion: Our data suggest that MSCs-derived PLGF may induce macrophage polarization into a M2 subpopulation, which in turn releases more PLGF to promote local neovascularization for augmenting post-injury cardiac muscle repair. This study thus sheds novel light on the role of PLGF in cardiac muscle regeneration.

  3. Gold nanoparticle enhancement of stereotactic radiosurgery for neovascular age-related macular degeneration

    Science.gov (United States)

    Ngwa, Wilfred; Makrigiorgos, G. Mike; Berbeco, Ross I.

    2012-10-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries for people over the age of 50. In this work, the dosimetric feasibility of using gold nanoparticles (AuNP) as radiosensitizers to enhance kilovoltage stereotactic radiosurgery for neovascular AMD is investigated. Microdosimetry calculations at the sub-cellular level were carried out to estimate the radiation dose enhancement to individual nuclei in neovascular AMD endothelial cells (nDEF) due to photon-induced photo-/Auger electrons from x-ray-irradiated AuNP. The nDEF represents the ratio of radiation doses to the endothelial cell nuclei with and without AuNP. The calculations were carried out for a range of feasible AuNP local concentrations using the clinically applicable 100 kVp x-ray beam parameters employed by a commercially available x-ray therapy system. The results revealed nDEF values of 1.30-3.26 for the investigated concentration range of 1-7 mg g-1, respectively. In comparison, for the same concentration range, nDEF values of 1.32-3.40, 1.31-3.33, 1.29-3.19, 1.28-3.12 were calculated for 80, 90, 110 and 120 kVp x-rays, respectively. Meanwhile, calculations as a function of distance from the AuNP showed that the dose enhancement, for 100 kVp, is markedly confined to the targeted neovascular AMD endothelial cells where AuNP are localized. These findings provide impetus for considering the application of AuNP to enhance therapeutic efficacy during stereotactic radiosurgery for neovascular AMD.

  4. Enhancing Web Service Selection by User Preferences of Non-Functional Features

    OpenAIRE

    Badr , Youakim; Abraham , Ajith; Biennier , Frédérique; Grosan , Crina

    2008-01-01

    International audience; Selection of an appropriate Web service for a particular task has become a difficult challenge due to the increasing number of Web services offering similar functionalities. The functional properties describe what the service can do and the nonfunctional properties depict how the service can do it. Non-functional properties involving qualitative or quantitative features have become essential criteria to enhance the selection process of services making the selection pro...

  5. Nanoparticle-mediated delivery of pioglitazone enhances therapeutic neovascularization in a murine model of hindlimb ischemia.

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    Nagahama, Ryoji; Matoba, Tetsuya; Nakano, Kaku; Kim-Mitsuyama, Shokei; Sunagawa, Kenji; Egashira, Kensuke

    2012-10-01

    Critical limb ischemia is a severe form of peripheral artery disease (PAD) for which neither surgical revascularization nor endovascular therapy nor current medicinal therapy has sufficient therapeutic effects. Peroxisome proliferator activated receptor-γ agonists present angiogenic activity in vitro; however, systemic administration of peroxisome proliferator-activated receptor-γ agonists is hampered by its side effects, including heart failure. Here, we demonstrate that the nanoparticle (NP)-mediated delivery of the peroxisome proliferator activated receptor-γ agonist pioglitazone enhances its therapeutic efficacy on ischemia-induced neovascularization in a murine model. In a nondiabetic murine model of hindlimb ischemia, a single intramuscular injection of pioglitazone-incorporated NP (1 µg/kg) into ischemic muscles significantly improved the blood flow recovery in the ischemic limbs, significantly increasing the number of CD31-positive capillaries and α-smooth muscle actin-positive arterioles. The therapeutic effects of pioglitazone-incorporated NP were diminished by the peroxisome proliferator activated receptor-γ antagonist GW9662 and were not observed in endothelial NO synthase-deficient mice. Pioglitazone-incorporated NP induced endothelial NO synthase phosphorylation, as demonstrated by Western blot analysis, as well as expression of multiple angiogenic growth factors in vivo, including vascular endothelial growth factor-A, vascular endothelial growth factor-B, and fibroblast growth factor-1, as demonstrated by real-time polymerase chain reaction. Intramuscular injection of pioglitazone (1 µg/kg) was ineffective, and oral administration necessitated a >500 μg/kg per day dose to produce therapeutic effects equivalent to those of pioglitazone-incorporated NP. NP-mediated drug delivery is a novel modality that may enhance the effectiveness of therapeutic neovascularization, surpassing the effectiveness of current treatments for peripheral artery

  6. Apelin enhances cardiac neovascularization after myocardial infarction by recruiting aplnr+ circulating cells

    NARCIS (Netherlands)

    Tempel, D.; de Boer, M.; van Deel, E.D.; Haasdijk, R.A.; Duncker, D.J.G.M.; Cheng, C.; Schulte-Merker, S.; Duckers, H.J.

    2012-01-01

    RATIONALE: Neovascularization stimulated by local or recruited stem cells after ischemia is a key process that salvages damaged tissue and shows similarities with embryonic vascularization. Apelin receptor (Aplnr) and its endogenous ligand apelin play an important role in cardiovascular development.

  7. Apelin Enhances Cardiac Neovascularization After Myocardial Infarction By Recruiting Aplnr+ Circulating Cells

    NARCIS (Netherlands)

    Tempel, D.; Boer, de M.; Deel, van E.D.; Haasdijk, A.; Duncker, D.J.; Cheng, C.; Schulte-Merker, S.; Duckers, H.J.

    2012-01-01

    Rationale: Neovascularization stimulated by local or recruited stem cells after ischemia is a key process that salvages damaged tissue and shows similarities with embryonic vascularization. Apelin receptor (Aplnr) and its endogenous ligand apelin play an important role in cardiovascular development.

  8. Both Autocrine Signaling and Paracrine Signaling of HB-EGF Enhance Ocular Neovascularization.

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    Inoue, Yuki; Shimazawa, Masamitsu; Nakamura, Shinsuke; Takata, Shinsuke; Hashimoto, Yuhei; Izawa, Hiroshi; Masuda, Tomomi; Tsuruma, Kazuhiro; Sakaue, Tomohisa; Nakayama, Hironao; Higashiyama, Shigeki; Hara, Hideaki

    2018-01-01

    The incidence of blindness is increasing because of the increase in abnormal ocular neovascularization. Anti-VEGF (vascular endothelial growth factor) therapies have led to good results, although they are not a cure for the blindness. The purpose of this study was to determine what role HB-EGF (heparin-binding epidermal growth factor-like growth factor) plays in ocular angiogenesis. We examined the role played by HB-EGF in ocular neovascularization in 2 animal models of neovascularization: laser-induced choroidal neovascularization (CNV) and oxygen-induced retinopathy. We also studied human retinal microvascular endothelial cells in culture. Our results showed that the neovascularization was decreased in both the CNV and oxygen-induced retinopathy models in HB-EGF conditional knockout mice compared with that in wild-type mice. Moreover, the expressions of HB-EGF and VEGF were increased after laser-induced CNV and oxygen-induced retinopathy, and their expression sites were located around the neovascular areas. Exposure of human retinal microvascular endothelial cells to HB-EGF and VEGF increased their proliferation and migration, and CRM-197 (cross-reactive material-197), an HB-EGF inhibitor, decreased the HB-EGF-induced and VEGF-induced cell proliferation and migration. VEGF increased the expression of HB-EGF mRNA. VEGF-dependent activation of EGFR (epidermal growth factor receptor)/ERK1/2 (extracellular signal-regulated kinase 1/2) signaling and cell proliferation of endothelial cells required stimulation of the ADAM17 (a disintegrin and metalloprotease) and ADAM12. CRM-197 decreased the grades of the fluorescein angiograms and size of the CNV areas in marmoset monkeys. These findings suggest that HB-EGF plays an important role in the development of CNV. Therefore, further investigations of HB-EGF are needed as a potential therapeutic target in the treatment of exudative age-related macular degeneration. © 2017 American Heart Association, Inc.

  9. Relationship between Plaque Echo, Thickness and Neovascularization Assessed by Quantitative and Semi-quantitative Contrast-Enhanced Ultrasonography in Different Stenosis Groups.

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    Song, Yan; Feng, Jun; Dang, Ying; Zhao, Chao; Zheng, Jie; Ruan, Litao

    2017-12-01

    The aim of this study was to determine the relationship between plaque echo, thickness and neovascularization in different stenosis groups using quantitative and semi-quantitative contrast-enhanced ultrasound (CEUS) in patients with carotid atherosclerosis plaque. A total of 224 plaques were divided into mild stenosis (Quantitative and semi-quantitative methods were used to assess plaque neovascularization and determine the relationship between plaque echo, thickness and neovascularization. Correlation analysis revealed no relationship of neovascularization with plaque echo in the groups using either quantitative or semi-quantitative methods. Furthermore, there was no correlation of neovascularization with plaque thickness using the semi-quantitative method. The ratio of areas under the curve (RAUC) was negatively correlated with plaque thickness (r = -0.317, p = 0.001) in the mild stenosis group. With the quartile method, plaque thickness of the mild stenosis group was divided into four groups, with significant differences between the 1.5-2.2 mm and ≥3.5 mm groups (p = 0.002), 2.3-2.8 mm and ≥3.5 mm groups (p quantitative and quantitative CEUS methods characterizing neovascularization of plaque are equivalent with respect to assessing relationships between neovascularization, echogenicity and thickness. However, the quantitative method could fail for plaque <3.5 mm because of motion artifacts. Copyright © 2017 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.

  10. The inter-observer agreement in the assessment of carotid plaque neovascularization by contrast-enhanced ultrasonography: The impact of plaque thickness.

    Science.gov (United States)

    Chen, Jian; Zhang, Yan-Ming; Song, Ze-Zhou; Fu, Yan-Fei; Geng, Yu

    2018-04-10

    The interobserver agreement in the assessment of the grade of carotid plaque neovascularization by contrast-enhanced ultrasonography is poorly established. We examined 140 carotid plaques in 66 patients (all patients had bilateral plaques, and 8 patients had 2 plaques on one side). We performed conventional and contrast-enhanced ultrasonography to analyze the presence of carotid plaque neovascularization, which was graded by two independent observers whose interobserver agreement (κ) was evaluated according to the thickness of carotid plaque. For all carotid plaques, the mean κ was 0.689 (95% confidence interval 0.604-0.774). It was 0.689 (0.569-0.808), 0.637 (0.487-0.787), and 0.740 (0.585-0.896), respectively for carotid plaques with maximal thickness 3 mm. The interobserver agreement for assessing carotid plaque neovascularization by using contrast-enhanced ultrasonography is substantial and acceptable for research purposes, regardless of the maximal thickness of the plaque. © 2018 Wiley Periodicals, Inc.

  11. Neovascularization in Vertebral Artery Atheroma-A Dynamic Contrast-Enhanced Magnetic Resonance Imaging-Based Comparative Study in Patients with Symptomatic and Asymptomatic Carotid Artery Disease.

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    Usman, Ammara; Yuan, Jianmin; Patterson, Andrew J; Graves, Martin J; Varty, Kevin; Sadat, Umar; Gillard, Jonathan H

    2018-05-24

    Atherosclerosis is a systemic inflammatory disease intertwined with neovascularization. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) enables the assessment of plaque neovascularization. This study aimed to explore the systemic nature of atherosclerosis by assessing difference in severity of neovascularization as quantified by DCE-MRI of vertebral arteries (VAs) between patients with symptomatic and asymptomatic carotid artery disease. Ten consecutive patients with asymptomatic VA stenosis and concomitant symptomatic carotid artery disease (group 1) and 10 consecutive patients with asymptomatic VA stenosis and concomitant asymptomatic carotid artery disease (group 2) underwent 3-dimensional DCE-MRI of their cervical segment of VAs. A previously validated pharmacokinetic modeling approach was used for DCE-MRI analysis. K trans was calculated in the adventitia and plaque as a measure of neovessel permeability. Both patient groups were comparable for demographics and comorbidities. Mean luminal stenosis was comparable for both groups (54.4% versus 52.27%, P = .32). Group 1 had higher adventitial K trans and plaque K trans (.08 ± .01 min -1 , .07 ± .01 min -1 ) compared with Group 2 (.06 ± .01 min -1 , .06 ± .01 min -1 ) (P = .004 and .03, respectively). Good correlation was present among the two image analysts (intraclass correlation coefficient = .78). Vertebral Artery atheroma of patients with symptomatic carotid artery disease had increased neovessel permeability compared with the patients with asymptomatic carotid artery disease. These findings are consistent with the hypothesis that atherosclerosis is a systemic inflammatory disease. The VA atherosclerosis is likely to have increased severity of neovascularization if another arterial territory is symptomatic in the same patient cohort. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  12. High-resolution blood-pool-contrast-enhanced MR angiography in glioblastoma: tumor-associated neovascularization as a biomarker for patient survival. A preliminary study

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    Puig, Josep; Blasco, Gerard; Remollo, Sebastian; Hernandez, David; Pedraza, Salvador [Hospital Universitari Dr Josep Trueta, Research Unit of Diagnostic Imaging Institute (IDI), Department of Radiology [Girona Biomedical Research Institute] IDIBGI, Girona (Spain); Daunis-i-Estadella, Josep; Mateu, Gloria [University of Girona, Department of Computer Science, Applied Mathematics and Statistics, Girona (Spain); Alberich-Bayarri, Angel [La Fe Polytechnics and University Hospital, Biomedical Imaging Research Group (GIBI230), La Fe Health Research Institute, Valencia (Spain); Essig, Marco [University of Manitoba, Department of Radiology, Winnipeg (Canada); Jain, Rajan [NYU School of Medicine, Division of Neuroradiology, Department of Radiology, New York, NY (United States); Puigdemont, Montserrat [Hospital Universitari Dr Josep Trueta, Catalan Institute of Oncology (ICO), Hospital Cancer Registry, Girona (Spain); Sanchez-Gonzalez, Javier [Philips Healthcare Iberica, Madrid (Spain); Wintermark, Max [Stanford University, Department of Radiology, Neuroradiology Division, Palo Alto, CA (United States)

    2016-01-15

    The objective of the study was to determine whether tumor-associated neovascularization on high-resolution gadofosveset-enhanced magnetic resonance angiography (MRA) is a useful biomarker for predicting survival in patients with newly diagnosed glioblastomas. Before treatment, 35 patients (25 men; mean age, 64 ± 14 years) with glioblastoma underwent MRI including first-pass dynamic susceptibility contrast (DSC) perfusion and post-contrast T1WI sequences with gadobutrol (0.1 mmol/kg) and, 48 h later, high-resolution MRA with gadofosveset (0.03 mmol/kg). Volumes of interest for contrast-enhancing lesion (CEL), non-CEL, and contralateral normal-appearing white matter were obtained, and DSC perfusion and DWI parameters were evaluated. Prognostic factors were assessed by Kaplan-Meier survival and Cox proportional hazards model. Eighteen (51.42 %) glioblastomas were hypervascular on high-resolution MRA. Hypervascular glioblastomas were associated with higher CEL volume and lower Karnofsky score. Median survival rates for patients with hypovascular and hypervascular glioblastomas treated with surgery, radiotherapy, and chemotherapy were 15 and 9.75 months, respectively (P < 0.001). Tumor-associated neovascularization was the best predictor of survival at 5.25 months (AUC = 0.794, 81.2 % sensitivity, 77.8 % specificity, 76.5 % positive predictive value, 82.4 % negative predictive value) and yielded the highest hazard ratio (P < 0.001). Tumor-associated neovascularization detected on high-resolution blood-pool-contrast-enhanced MRA of newly diagnosed glioblastoma seems to be a useful biomarker that correlates with worse survival. (orig.)

  13. Data on consistency among different methods to assess atherosclerotic plaque echogenicity on standard ultrasound and intraplaque neovascularization on contrast-enhanced ultrasound imaging in human carotid artery

    Directory of Open Access Journals (Sweden)

    Mattia Cattaneo

    2016-12-01

    Full Text Available Here we provide the correlation among different carotid ultrasound (US variables to assess echogenicity n standard carotid US and to assess intraplaque neovascularization on contrast enhanced US. We recruited 45 consecutive subjects with an asymptomatic≥50% carotid artery stenosis. Carotid plaque echogenicity at standard US was visually graded according to Gray–Weale classification (GW and measured by the greyscale median (GSM, a semi-automated computerized measurement performed by Adobe Photoshop®. On CEUS imaging IPNV was graded according to the visual appearance of contrast within the plaque according to three different methods: CEUS_A (1=absent; 2=present; CEUS_B a three-point scale (increasing IPNV from 1 to 3; CEUS_C a four-point scale (increasing IPNV from 0 to 3. We have also implemented a new simple quantification method derived from region of interest (ROI signal intensity ratio as assessed by QLAB software. Further information is available in “Contrast-enhanced ultrasound imaging of intraplaque neovascularization and its correlation to plaque echogenicity in human carotid arteries atherosclerosis (M. Cattaneo, D. Staub, A.P. Porretta, J.M. Gallino, P. Santini, C. Limoni et al., 2016 [1].

  14. [OCT and neovascular glaucoma].

    Science.gov (United States)

    Bellotti, A; Labbé, A; Fayol, N; El Mahtoufi, A; Baudouin, C

    2007-06-01

    Neovascular glaucoma is a chronic and sight-threatening disease. Four different grades have been described. Anterior chamber optical coherence tomography (OCT) is a new imaging technique allowing the visualization of the anterior segment. The purpose of our study was to describe the appearance of the different neovascular glaucoma grades with the OCT in order to refine the clinical analysis of this disease. Eleven patients (nine men and two women) with different grades of neovascular glaucoma were analyzed in this study. Neovascular glaucoma complicated central retinal vein occlusion in seven patients and diabetic retinopathy in four patients. All patients had bilateral biomicroscopical examination and OCT analysis. OCT images and clinical examination were then compared. No modifications could be observed using OCT in patients with grade 1 neovascular glaucoma. For grade 2, a slightly hyper-reflective linear iris secondary to neovascularization was observed. For grade 3, OCT images showed a thickened hyper-reflective iridocorneal angle with possible iridocorneal synechiae. For grade 4, the iridocorneal angle was closed and associated with iris contraction and uveae ectropion. OCT is a new promising technique for the precise analysis of different grades of neovascular glaucoma. It certainly helps in the management of such cases.

  15. A new animal model of choriodal neovascularization

    DEFF Research Database (Denmark)

    Kiilgaard, J.F.; Andersen, Mads V. Nis; Wiencke, A.K.

    2005-01-01

    ophthalmology, age-related macular degeneration, Bruch's membrane, retinal pigment epithelium, choroidal neovascularization, subretinal neovascularization......ophthalmology, age-related macular degeneration, Bruch's membrane, retinal pigment epithelium, choroidal neovascularization, subretinal neovascularization...

  16. Combined administration of mesenchymal stem cells overexpressing IGF-1 and HGF enhances neovascularization but moderately improves cardiac regeneration in a porcine model.

    Science.gov (United States)

    Gómez-Mauricio, Guadalupe; Moscoso, Isabel; Martín-Cancho, María-Fernanda; Crisóstomo, Verónica; Prat-Vidal, Cristina; Báez-Díaz, Claudia; Sánchez-Margallo, Francisco M; Bernad, Antonio

    2016-07-16

    Insulin-like growth factor 1 (IGF-1) and hepatocyte growth factor (HGF) are among the most promising growth factors for promoting cardiorepair. Here, we evaluated the combination of cell- and gene-based therapy using mesenchymal stem cells (MSC) genetically modified to overexpress IGF-1 or HGF to treat acute myocardial infarction (AMI) in a porcine model. Pig MSC from adipose tissue (paMSC) were genetically modified for evaluation of different therapeutic strategies to improve AMI treatment. Three groups of infarcted Large White pigs were compared (I, control, non-transplanted; II, transplanted with paMSC-GFP (green fluorescent protein); III, transplanted with paMSC-IGF-1/HGF). Cardiac function was evaluated non-invasively using magnetic resonance imaging (MRI) for 1 month. After euthanasia and sampling of the animal, infarcted areas were studied by histology and immunohistochemistry. Intramyocardial transplant in a porcine infarct model demonstrated the safety of paMSC in short-term treatments. Treatment with paMSC-IGF-1/HGF (1:1) compared with the other groups showed a clear reduction in inflammation in some sections analyzed and promoted angiogenic processes in ischemic tissue. Although cardiac function parameters were not significantly improved, cell retention and IGF-1 overexpression was confirmed within the myocardium. The simultaneous administration of IGF-1- and HGF-overexpressing paMSC appears not to promote a synergistic effect or effective repair. The combined enhancement of neovascularization and fibrosis in paMSC-IGF-1/HGF-treated animals nonetheless suggests that sustained exposure to high IGF-1 + HGF levels promotes beneficial as well as deleterious effects that do not improve overall cardiac regeneration.

  17. Choroidal neovascular membrane

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    Bhatt Nitul; Diamond James; Jalali Subhadra; Das Taraprasad

    1998-01-01

    Choroidal neovascular membrane in the macular area is one of the leading causes of severe visual loss. Usually a manifestation in elderly population, it is often associated with age-related macular degeneration. The current mainstay of management is early diagnosis, usually by fundus examination, aided by angiography and photocoagulation in selected cases. Various other modalities of treatment including surgery are being considered as alternate options, but with limited success. The purpose o...

  18. Neovascularization in Purtscher's retinopathy

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    Chan A

    2011-11-01

    Full Text Available Annie Chan, Douglas R Fredrick, Theodore Leng Department of Ophthalmology, Byers Eye Institute at Stanford University, Stanford University School of Medicine, Stanford, CA, USA Abstract: We report a case of neovascularization secondary to Purtscher's retinopathy that showed minimal improvement with photocoagulation treatment. A 14-year-old boy with a history of cerebellar medulloblastoma presented with blurry vision and floaters after being struck by a motor vehicle while riding his bike. At presentation, visual acuity was 20/400 in his right eye and counting fingers in his left eye. Fundus examination showed disk edema, retinal whitening, and retinal hemorrhages in both eyes. Optical coherence tomography demonstrated thinning of the temporal retina and disruption of the inner segment–outer segment junction of the photoreceptor layer in the right eye and thickening and edema of the nasal macula, as well as a central foveal hyper-reflectivity, in the left eye. At the initial visit, there was no ischemia or neovascularization (NV. One month later, the patient developed NV of the disk and ischemia in the mid-periphery of the left eye. The patient underwent treatment with pan-retinal photocoagulation. The NV regressed, but visual outcome remained poor at his 5-month follow-up visit. Keywords: Purtscher's retinopathy, neovascularization, laser photocoagulation, disk edema

  19. Choroidal neovascular membrane

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    Bhatt Nitul

    1998-01-01

    Full Text Available Choroidal neovascular membrane in the macular area is one of the leading causes of severe visual loss. Usually a manifestation in elderly population, it is often associated with age-related macular degeneration. The current mainstay of management is early diagnosis, usually by fundus examination, aided by angiography and photocoagulation in selected cases. Various other modalities of treatment including surgery are being considered as alternate options, but with limited success. The purpose of this review is to briefly outline the current concepts and the management strategy from a clinician′s viewpoint.

  20. Choroidal neovascular membrane.

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    Bhatt, N S; Diamond, J G; Jalali, S; Das, T

    1998-06-01

    Choroidal neovascular membrane in the macular area is one of the leading causes of severe visual loss. Usually a manifestation in elderly population, it is often associated with age-related macular degeneration. The current mainstay of management is early diagnosis, usually by fundus examination, aided by angiography and photocoagulation in selected cases. Various other modalities of treatment including surgery are being considered as alternate options, but with limited success. The purpose of this review is to briefly outline the current concepts and the management strategy from a clinician's viewpoint.

  1. Inhibition of Mef2a Enhances Neovascularization via Post-transcriptional Regulation of 14q32 MicroRNAs miR-329 and miR-494

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    Sabine M.J. Welten

    2017-06-01

    Full Text Available Improving the efficacy of neovascularization is a promising strategy to restore perfusion of ischemic tissues in patients with peripheral arterial disease. The 14q32 microRNA cluster is highly involved in neovascularization. The Mef2a transcription factor has been shown to induce transcription of the microRNAs within this cluster. We inhibited expression of Mef2a using gene-silencing oligonucleotides (GSOs in an in vivo hind limb ischemia model. Treatment with GSO-Mef2a clearly improved blood flow recovery within 3 days (44% recovery versus 25% recovery in control and persisted until 14 days after ischemia induction (80% recovery versus 60% recovery in control. Animals treated with GSO-Mef2a showed increased arteriogenesis and angiogenesis in the relevant muscle tissues. Inhibition of Mef2a decreased expression of 14q32 microRNAs miR-329 (p = 0.026 and miR-494 (trend, p = 0.06, but not of other 14q32 microRNAs, nor of 14q32 microRNA precursors. Because Mef2a did not influence 14q32 microRNA transcription, we hypothesized it functions as an RNA-binding protein that influences processing of 14q32 microRNA miR-329 and miR-494. Mef2A immunoprecipitation followed by RNA isolation and rt/qPCR confirmed direct binding of MEF2A to pri-miR-494, supporting this hypothesis. Our study demonstrates a novel function for Mef2a in post-ischemic neovascularization via post-transcriptional regulation of 14q32 microRNAs miR-329 and miR-494.

  2. Enhanced adsorption of hydroxyl contained/anionic dyes on non functionalized Ni@SiO{sub 2} core–shell nanoparticles: Kinetic and thermodynamic profile

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    Jiang, Zhifeng, E-mail: ntjiangzf@sina.com; Xie, Jimin, E-mail: xiejm391@sohu.com; Jiang, Deli, E-mail: jiangdeli100@yahoo.com; Yan, Zaoxue, E-mail: yanzaoxue@163.com; Jing, Junjie, E-mail: jingjj1975@163.com; Liu, Dong, E-mail: 919457966@qq.com

    2014-02-15

    A green and low-cost adsorbent with both magnetic property and high adsorption capacity was prepared on the basis of nickel magnetic core with silica shell. The surface of the prepared Ni@SiO{sub 2} composite was not modified. The influence of different functional groups and different charged of the dyes on the adsorption process on the non functionalized Ni@SiO{sub 2} have been studied. The results indicated that synthesized adsorbent exhibited higher adsorption capacity for dyes with negative charge/hydroxyl groups as compared to dyes with positive charge/without hydroxyl groups due to the hydrogen bonding interaction and electrostatic interaction between the adsorbent and dyes. Adsorption kinetics and isotherms experiments were carried out and the results indicated that the adsorption process was fitted by pseudo second order kinetics and Freundlich model. The binding of these dyes with magnetic adsorbent surface mainly involves physical adsorption according to D–R model. Furthermore, the adsorption process is spontaneous and endothermic as studied from adsorption thermodynamics. The value of ΔH° and mean free energy further confirmed that physical adsorption is the major adsorption process. After regeneration, the adsorbent still shows high adsorption capacity even for 4 cycles of desorption–adsorption.

  3. Parametric imaging of tumor perfusion and neovascular morphology using ultrasound

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    Hoyt, Kenneth

    2015-03-01

    A new image processing strategy is detailed for the simultaneous measurement of tumor perfusion and neovascular morphology parameters from a sequence of dynamic contrast-enhanced ultrasound (DCE-US) images. A technique for locally mapping tumor perfusion parameters using skeletonized neovascular data is also introduced. Simulated images were used to test the neovascular skeletonization technique and variance (error) of relevant parametric estimates. Preliminary DCE-US image datasets were collected in 6 female patients diagnosed with invasive breast cancer and using a Philips iU22 ultrasound system equipped with a L9-3 MHz transducer and Definity contrast agent. Simulation data demonstrates that neovascular morphology parametric estimation is reproducible albeit measurement error can occur at a lower signal-to-noise ratio (SNR). Experimental results indicate the feasibility of our approach to performing both tumor perfusion and neovascular morphology measurements from DCE-US images. Future work will expand on our initial clinical findings and also extent our image processing strategy to 3-dimensional space to allow whole tumor characterization.

  4. Non-functional Avionics Requirements

    Science.gov (United States)

    Paulitsch, Michael; Ruess, Harald; Sorea, Maria

    Embedded systems in aerospace become more and more integrated in order to reduce weight, volume/size, and power of hardware for more fuel-effi ciency. Such integration tendencies change architectural approaches of system ar chi tec tures, which subsequently change non-functional requirements for plat forms. This paper provides some insight into state-of-the-practice of non-func tional requirements for developing ultra-critical embedded systems in the aero space industry, including recent changes and trends. In particular, formal requi re ment capture and formal analysis of non-functional requirements of avionic systems - including hard-real time, fault-tolerance, reliability, and per for mance - are exemplified by means of recent developments in SAL and HiLiTE.

  5. CCR7 signaling pathway and retinal neovascularization

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    Lin-Hui Yuan

    2015-11-01

    Full Text Available Retinal neovascularization diseases are the major causes of blindness. C-C chemokine receptor type 7(CCR7can promote the expression of vascular endothelial growth factor(VEGFthrough the extracellular signal regulated kinase(ERKpathway, leading to vascular leakage, proliferation of vascular endothelial cell, neovascularization and etc. The detection of CCR7 can guide the diagnosis and treatments of retinal neovascularization diseases.

  6. Neovascularization of the iris in retinoschisis

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    Geraldine R. Slean

    2017-09-01

    Conclusions and importance: Chronic bullous retinoschisis can be associated with anterior segment neovascularization such as rubeosis iridis, presumably due to non-perfusion within the retinoschisis cavity.

  7. A new animal model of choroidal neovascularization

    DEFF Research Database (Denmark)

    Kiilgaard, Jens Folke; Andersen, Mads Varis Nis; Wiencke, Anne

    2005-01-01

    The purpose of this study was to evaluate the ability of different methods to induce choroidal neovascularization (CNV) in the domestic pig.......The purpose of this study was to evaluate the ability of different methods to induce choroidal neovascularization (CNV) in the domestic pig....

  8. Cathepsin L is required for endothelial progenitor cell-induced neovascularization

    Energy Technology Data Exchange (ETDEWEB)

    Urbich, Carmen; Heeschen, Christopher; Aicher, Alexandra; Sasaki, Ken-ichiro; Bruhl, Thomas; Hofmann, Wolf K.; Peters, Christoph; Reinheckel, Thomas; Pennacchio, Len A.; Abolmaali, Nasreddin D.; Chavakis, Emmanouil; Zeiher, Andreas M.; Dimmeler, Stefanie

    2004-01-15

    Infusion of endothelial progenitor cells (EPCs), but not of mature endothelial cells (ECs), promotes neovascularization after ischemia. We performed a gene expression profiling of EPCs and ECs to identify genes, which might be important for the neovascularization capacity of EPCs. Intriguingly, the protease cathepsin L (CathL) was highly expressed in EPCs as opposed to ECs and is essential for matrix degradation and invasion by EPCs in vitro. CathL deficient mice showed impaired functional recovery after hind limb ischemia supporting the concept for an important role of CathL in postnatal neovascularization. Infused CathL deficient progenitor cells failed to home to sites of ischemia and to augment neovascularization. In contrast, over expression of CathL in mature ECs significantly enhanced their invasive activity and induced their neovascularization capacity in vivo. Taken together, CathL plays a crucial role for the integration of circulating EPCs into the ischemic tissue and is required for neovascularization mediated by EPCs.

  9. Human tears reveal insights into corneal neovascularization.

    Science.gov (United States)

    Zakaria, Nadia; Van Grasdorff, Sigi; Wouters, Kristien; Rozema, Jos; Koppen, Carina; Lion, Eva; Cools, Nathalie; Berneman, Zwi; Tassignon, Marie-José

    2012-01-01

    Corneal neovascularization results from the encroachment of blood vessels from the surrounding conjunctiva onto the normally avascular cornea. The aim of this study is to identify factors in human tears that are involved in development and/or maintenance of corneal neovascularization in humans. This could allow development of diagnostic tools for monitoring corneal neovascularization and combination monoclonal antibody therapies for its treatment. In an observational case-control study we enrolled a total of 12 patients with corneal neovascularization and 10 healthy volunteers. Basal tears along with reflex tears from the inferior fornix, superior fornix and using a corneal bath were collected along with blood serum samples. From all patients, ocular surface photographs were taken. Concentrations of the pro-angiogenic cytokines interleukin (IL)-6, IL-8, Vascular Endothelial Growth Factor (VEGF), Monocyte Chemoattractant Protein 1 (MCP-1) and Fas Ligand (FasL) were determined in blood and tear samples using a flow cytometric multiplex assay. Our results show that the concentration of pro-angiogenic cytokines in human tears are significantly higher compared to their concentrations in serum, with highest levels found in basal tears. Interestingly, we could detect a significantly higher concentration of IL- 6, IL-8 and VEGF in localized corneal tears of patients with neovascularized corneas when compared to the control group. This is the first study of its kind demonstrating a significant difference of defined factors in tears from patients with neovascularized corneas as compared to healthy controls. These results provide the basis for future research using animal models to further substantiate the role of these cytokines in the establishment and maintenance of corneal neovascularization.

  10. Experimentation on accuracy of non functional requirement prioritization approaches for different complexity projects

    OpenAIRE

    Raj Kumar Chopra; Varun Gupta; Durg Singh Chauhan

    2016-01-01

    Non functional requirements must be selected for implementation together with functional requirements to enhance the success of software projects. Three approaches exist for performing the prioritization of non functional requirements using the suitable prioritization technique. This paper performs experimentation on three different complexity versions of the industrial software project using cost-value prioritization technique employing three approaches. Experimentation is conducted to analy...

  11. Host immune cellular reactions in corneal neovascularization

    Directory of Open Access Journals (Sweden)

    Nizar S. Abdelfattah

    2016-04-01

    Full Text Available Corneal neovascularization (CNV is a global important cause of visual impairment. The immune mechanisms leading to corneal heme- and lymphangiogenesis have been extensively studied over the past years as more attempts were made to develop better prophylactic and therapeutic measures. This article aims to discuss immune cells of particular relevance to CNV, with a focus on macrophages, Th17 cells, dendritic cells and the underlying immunology of common pathologies involving neovascularization of the cornea. Hopefully, a thorough understanding of these topics would propel the efforts to halt the detrimental effects of CNV.

  12. Honokiol inhibits pathological retinal neovascularization in oxygen-induced retinopathy mouse model

    Energy Technology Data Exchange (ETDEWEB)

    Vavilala, Divya Teja [Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, MO (United States); O’Bryhim, Bliss E. [Department of Ophthalmology, University of Kansas Medical Center, Kansas City, KS (United States); Ponnaluri, V.K. Chaithanya [Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, MO (United States); White, R. Sid; Radel, Jeff [Department of Ophthalmology, University of Kansas Medical Center, Kansas City, KS (United States); Symons, R.C. Andrew [Department of Ophthalmology, University of Kansas Medical Center, Kansas City, KS (United States); Ophthalmology Department, Royal Melbourne Hospital, University of Melbourne, Victoria (Australia); Department of Surgery, Royal Melbourne Hospital, University of Melbourne, Victoria (Australia); Mukherji, Mridul, E-mail: mukherjim@umkc.edu [Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, MO (United States)

    2013-09-06

    Highlights: •Aberrant activation of HIF pathway is the underlying cause of ischemic neovascularization. •Honokiol has better therapeutic index as a HIF inhibitor than digoxin and doxorubicin. •Daily IP injection of honokiol in OIR mouse model reduced retinal neovascularization. •Honokiol also prevents vaso-obliteration, the characteristic feature of the OIR model. •Honokiol enhanced physiological revascularization of the retinal vascular plexuses. -- Abstract: Aberrant activation of the hypoxia inducible factor (HIF) pathway is the underlying cause of retinal neovascularization, one of the most common causes of blindness worldwide. The HIF pathway also plays critical roles during tumor angiogenesis and cancer stem cell transformation. We have recently shown that honokiol is a potent inhibitor of the HIF pathway in a number of cancer and retinal pigment epithelial cell lines. Here we evaluate the safety and efficacy of honokiol, digoxin, and doxorubicin, three recently identified HIF inhibitors from natural sources. Our studies show that honokiol has a better safety to efficacy profile as a HIF inhibitor than digoxin and doxorubicin. Further, we show for the first time that daily intraperitoneal injection of honokiol starting at postnatal day (P) 12 in an oxygen-induced retinopathy (OIR) mouse model significantly reduced retinal neovascularization at P17. Administration of honokiol also prevents the oxygen-induced central retinal vaso-obliteration, characteristic feature of the OIR model. Additionally, honokiol enhanced physiological revascularization of the retinal vascular plexuses. Since honokiol suppresses multiple pathways activated by HIF, in addition to the VEGF signaling, it may provide advantages over current treatments utilizing specific VEGF antagonists for ocular neovascular diseases and cancers.

  13. Type 3 Neovascularization Associated with Retinitis Pigmentosa.

    Science.gov (United States)

    Sayadi, Jihene; Miere, Alexandra; Souied, Eric H; Cohen, Salomon Y

    2017-01-01

    To report a case of type 3 neovascular lesion in a patient with retinitis pigmentosa (RP) complicated by macular edema. A 78-year-old man with a long follow-up for RP was referred for painless visual acuity decrease in the right eye. Best-corrected visual acuity was 20/125 in the right eye and 20/40 in the left. Fundus examination showed typical RP and macular edema in both eyes. In the right eye, spectral domain optical coherence tomography revealed a marked cystic macular edema associated with disruption of the Bruch membrane/retinal pigment epithelium complex overlying a pigmentary epithelium detachment, with a vascular structure which appeared to originate from the deep capillary plexus and to be connected with the subretinal pigment epithelium space. Optical coherence tomography angiography showed a high-flow vessel infiltrating the outer retinal layers in the deep capillary plexus segmentation, and a tuft-shaped, bright, high-flow network that seemed to be connected with the subretinal pigment epithelium space in the outer retinal layer segmentation. This presentation was consistent with an early type 3 neovascular lesion in the right eye. Type 3 neovascularization may be considered a possible complication of RP.

  14. Type 3 Neovascularization Associated with Retinitis Pigmentosa

    Directory of Open Access Journals (Sweden)

    Jihene Sayadi

    2017-04-01

    Full Text Available Purpose: To report a case of type 3 neovascular lesion in a patient with retinitis pigmentosa (RP complicated by macular edema. Case Report: A 78-year-old man with a long follow-up for RP was referred for painless visual acuity decrease in the right eye. Best-corrected visual acuity was 20/125 in the right eye and 20/40 in the left. Fundus examination showed typical RP and macular edema in both eyes. In the right eye, spectral domain optical coherence tomography revealed a marked cystic macular edema associated with disruption of the Bruch membrane/retinal pigment epithelium complex overlying a pigmentary epithelium detachment, with a vascular structure which appeared to originate from the deep capillary plexus and to be connected with the subretinal pigment epithelium space. Optical coherence tomography angiography showed a high-flow vessel infiltrating the outer retinal layers in the deep capillary plexus segmentation, and a tuft-shaped, bright, high-flow network that seemed to be connected with the subretinal pigment epithelium space in the outer retinal layer segmentation. This presentation was consistent with an early type 3 neovascular lesion in the right eye. Conclusion: Type 3 neovascularization may be considered a possible complication of RP.

  15. Purtscher's retinopathy followed by neovascular glaucoma

    Directory of Open Access Journals (Sweden)

    Kuroda M

    2013-11-01

    Full Text Available Masasko Kuroda,1 Akihiro Nishida,1 Masashi Kikuchi,2 Yasuo Kurimoto11Department of Ophthalmology, Kobe City Medical Center General Hospital, Kobe, Hyogo, Japan; 2Kikuchi Eye Clinic, Kobe, Hyogo, JapanAbstract: We report the case of a 66-year-old Japanese man who developed neovascular glaucoma secondary to Purtscher's retinopathy following a head injury. The patient presented at our hospital with blurred vision and a visual field abnormality in his left eye 1 month after suffering from a head injury. Upon initial presentation, his best-corrected visual acuity on a decimal chart was 1.5 oculus dexter and 0.6 oculus sinister. The intraocular pressure (IOP was 12 mmHg in both eyes. Fundus examination of the left eye revealed multiple white lesions in the posterior pole. Optical coherence tomography demonstrated retinal edema, particularly in the inner retina. On the basis of these findings, a diagnosis of Purtscher's retinopathy was made. One month after the initial examination, the visual acuity in the left eye deteriorated to 0.01 in decimal chart, and the IOP increased to 37 mmHg. Gonioscopy showed angle neovascularization. The patient received an intravitreal bevacizumab injection and panretinal photocoagulation. Subsequently, the IOP normalized and the angle neovascularization regressed.Keywords: blurred vision, visual field, retinal edema, head injury, head trauma

  16. Photoacoustic detection of neovascularities in skin graft

    Science.gov (United States)

    Yamazaki, Mutsuo; Sato, Shunichi; Saitoh, Daizo; Ishihara, Miya; Okada, Yoshiaki; Ashida, Hiroshi; Obara, Minoru

    2005-04-01

    We previously proposed a new method for monitoring adhesion of skin graft by measuring photoacoustic (PA) signal originated from the neovascularities. In this study, immunohistochemical staining (IHC) with CD31 antibody was performed for grafted skin tissue to observe neovascularity, and the results were compared with PA signals. We also used a laser Doppler imaging (LDI) to observe blood flow in the grafted skin, and sensitivity of PA measurement and that of LDI were compared. In rat autograft models, PA signals were measured for the grafted skin at postgrafting times of 0-48 h. At 6 h postgrafting, PA signal was observed in the skin depth region of 500-600 mm, while the results of IHC showed that angiogenesis occurred at the depth of about 600 mm. Depths at which PA signal and angiogenesis were observed decreased with postgrafting time. These indicate that the PA signal observed at 6 h postgrafting originated from the neovascularities in the skin graft. Results of LDI showed no blood-originated signal before 48 h postgrafting. These findings suggest that PA measurement is effective in monitoring the adhesion of skin graft in early stage after transplantation.

  17. Pachychoroid neovasculopathy in extramacular choroidal neovascularization

    Directory of Open Access Journals (Sweden)

    Gupta MP

    2016-07-01

    Full Text Available Mrinali Patel Gupta, Irene Rusu, Carly Seidman, Anton Orlin, Donald J D’Amico, Szilard Kiss Department of Ophthalmology, Weill Cornell Medicine, New York-Presbyterian Hospital, New York, NY, USA Purpose: To review a series of extramacular choroidal neovascular membranes (CNVMs in the context of their choroidal features, as determined by optical coherence tomography (OCT.Methods: Patients with extramacular CNVMs were identified from a tertiary care center through a review of records. The charts and cases were reviewed using multimodal imaging including fundus photography, OCT, fluorescein angiography (FA, and indocyanine angio­graphy (ICG.Results: Of six patients with extramacular CNVMs evaluated in this series, four patients (66.7% exhibited pachychoroidopathy on OCT imaging under or adjacent to the extramacular CNVM. All four of these patients also exhibited pachychoroidopathy in the macular OCT distant from the CNVM.Conclusion: Pachychoroidopathy is implicated in some cases of extramacular CNVMs. This represents the first report, to our knowledge, of pachychoroidopathy in extramacular CNVM. Keywords: choroidal neovascularization, pachychoroidopathy, pachychoroid neovasculopathy, peripheral disciform lesions, extramacular choroidal neovascularization, polypoidal choroidal vasculopathy

  18. Minocycline inhibits alkali burn-induced corneal neovascularization in mice.

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    Ou Xiao

    Full Text Available The purpose of this study was to investigate the effects of minocycline on alkali burn-induced corneal neovascularization (CNV. A total of 105 mice treated with alkali burns were randomly divided into three groups to receive intraperitoneal injections of either phosphate buffered saline (PBS or minocycline twice a day (60 mg/kg or 30 mg/kg for 14 consecutive days. The area of CNV and corneal epithelial defects was measured on day 4, 7, 10, and14 after alkali burns. On day 14, a histopathological examination was performed to assess morphological change and the infiltration of polymorphonuclear neutrophils (PMNs. The mRNA expression levels of vascular endothelial growth factor (VEGF and its receptors (VEGFRs, basic fibroblast growth factor (bFGF, matrix metalloproteinases (MMPs, interleukin-1α, 1β, 6 (IL-1α, IL-1β, IL-6 were analyzed using real-time quantitative polymerase chain reaction. The expression of MMP-2 and MMP-9 proteins was determined by gelatin zymography. In addition, enzyme-linked immunosorbent assay was used to analyze the protein levels of VEGFR1, VEGFR2, IL-1β and IL-6. Minocycline at a dose of 60 mg/kg or 30 mg/kg significantly enhanced the recovery of the corneal epithelial defects more than PBS did. There were significant decreases of corneal neovascularization in the group of high-dosage minocycline compared with the control group at all checkpoints. On day 14, the infiltrated PMNs was reduced, and the mRNA expression of VEGFR1, VEGFR2, bFGF, IL-1β, IL-6, MMP-2, MMP-9, -13 as well as the protein expression of VEGFR2, MMP-2, -9, IL-1β, IL-6 in the corneas were down-regulated with the use of 60 mg/kg minocycline twice a day. Our results showed that the intraperitoneal injection of minocycline (60 mg/kg b.i.d. can significantly inhibit alkali burn-induced corneal neovascularization in mice, possibly by accelerating corneal wound healing and by reducing the production of angiogenic factors, inflammatory cytokines and MMPs.

  19. A Chinese 2-herb formula (NF3) promotes hindlimb ischemia-induced neovascularization and wound healing of diabetic rats.

    Science.gov (United States)

    Tam, Jacqueline Chor-Wing; Ko, Chun-Hay; Lau, Kit-Man; To, Ming-Ho; Kwok, Hin-Fai; Chan, Yuet-Wa; Siu, Wing-Sum; Etienne-Selloum, Nelly; Lau, Ching-Po; Chan, Wai-Yee; Leung, Ping-Chung; Fung, Kwok-Pui; Schini-Kerth, Valérie B; Lau, Clara Bik-San

    2014-01-01

    Diabetic foot ulcer is closely associated with peripheral vascular disease. Enhancement of tissue oxidative stress, reduction of nitric oxide (NO) and angiogenic growth factors, and abnormal matrix metalloproteinase (MMP) activity are pathophysiological factors in post-ischemic neovascularization and diabetic wound healing. Our previous study demonstrated that the Chinese 2-herb formula, NF3, showed significant wound healing effects on diabetic foot ulcer rats. A novel rat diabetic foot ulcer with hindlimb ischemia model was established in order to strengthen our claims on the diabetic wound healing and post-ischemic neovascularization effects of NF3. Our results demonstrate that NF3 can significantly reduce the wound area of the diabetic foot ulcer rat with hindlimb ischemia by 21.6% (phealing and post-ischemic neovascularization in diabetes. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Subretinal neovascularization from the retina in radiation retinopathy

    International Nuclear Information System (INIS)

    Boozalis, G.T.; Schachat, A.P.; Green, W.R.

    1987-01-01

    In a 66-year-old woman with radiation retinopathy, subretinal neovascularization was present, originating from telangiectatic retinal vessels in the macular area. The patient showed no clinical or histologic evidence of age-related macular degeneration or other conditions that may have contributed to the subretinal neovascularization

  1. Type 1 neovascularization with polypoidal lesions complicating dome shaped macula

    OpenAIRE

    Naysan, Jonathan; Dansingani, Kunal K; Balaratnasingam, Chandrakumar; Freund, K Bailey

    2015-01-01

    Dome-shaped macula is described as an inward bulge of the macula within a posterior staphyloma in highly myopic eyes. Choroidal neovascularization is a known complication that can cause visual loss in dome-shaped macula. Herein, we describe a patient who presented with features of polypoidal choroidal neovascularization that developed on a background of high myopia with dome-shaped macula.

  2. Research on inhibition of corneal neovascularization

    Directory of Open Access Journals (Sweden)

    Zhang-Hui Yang

    2015-12-01

    Full Text Available Corneal transparency is the basis of the normal physiological functions.However, corneal neovascularization(CNVmay occur in the infection, mechanical and chemical injury or under other pathological conditions,which make the cornea lose original transparency and severe visual impairment. In recent years, along with the development of immunology, molecular biology, biochemistry and other disciplines, there is more in-depth understanding on the CNV, and clinical treatment of CNV has made new breakthroughs. This article provides an overview of the inhibition of CNV.

  3. Lonafarnib is a potential inhibitor for neovascularization.

    Directory of Open Access Journals (Sweden)

    Linlin Sun

    Full Text Available Atherosclerosis is a common cardiovascular disease that involves the build-up of plaque on the inner walls of the arteries. Intraplaque neovacularization has been shown to be essential in the pathogenesis of atherosclerosis. Previous studies showed that small-molecule compounds targeting farnesyl transferase have the ability to prevent atherosclerosis in apolipoprotein E-deficient mice, but the underlying mechanism remains to be elucidated. In this study, we found that lonafarnib, a specific inhibitor of farnesyl transferase, elicits inhibitory effect on vascular endothelial capillary assembly in vitro in a dose-dependent manner. In addition, we showed that lonafarnib treatment led to a dose-dependent decrease in scratch wound closure in vitro, whereas it had little effect on endothelial cell proliferation. These data indicate that lonafarnib inhibits neovascularization via directly targeting endothelial cells and disturbing their motility. Moreover, we demonstrated that pharmacological inhibition of farnesyl transferase by lonafarnib significantly impaired centrosome reorientation toward the leading edge of endothelial cells. Mechanistically, we found that the catalytic β subunit of farnesyl transferase associated with a cytoskeletal protein important for the establishment and maintenance of cell polarity. Additionally, we showed that lonafarnib remarkably inhibited the expression of the cytoskeletal protein and interrupted its interaction with farnesyl transferase. Our findings thus offer novel mechanistic insight into the protective effect of farnesyl transferase inhibitors on atherosclerosis and provide encouraging evidence for the potential use of this group of agents in inhibiting plaque neovascularization.

  4. Homoisoflavonoids as potential antiangiogenic agents for retinal neovascularization.

    Science.gov (United States)

    Amin, Sk Abdul; Adhikari, Nilanjan; Gayen, Shovanlal; Jha, Tarun

    2017-11-01

    A number of people worldwide have been suffering from ocular neovascularization that may be treated by a variety of drugs but these may possess adverse effects. Therefore, small antiangiogenic molecules with higher potency and lower toxic effects are intended. However, homoisoflavonoids of natural origin show the potential antiangiogenic effect in ocular neovascularization. These homoisoflavonoids are judged quantitatively in terms of statistical validation through multi-chemometric modeling approaches for the betterment and refinement of their structures required for higher antiangiogenic activity targeted to ocular neovascularization. These approaches may be utilized to design better antiangiogenic homoisoflavonoids. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  5. Targeting Neovascularization in Ischemic Retinopathy: Recent Advances

    Science.gov (United States)

    Al-Shabrawey, Mohamed; Elsherbiny, Mohamed; Nussbaum, Julian; Othman, Amira; Megyerdi, Sylvia; Tawfik, Amany

    2014-01-01

    Pathological retinal neovascularization (RNV) is a common micro-vascular complication in several retinal diseases including retinopathy of prematurity, diabetic retinopathy, age-related macular degeneration and central vein occlusion. The current therapeutic modalities of RNV are invasive and although they may slow or halt the progression of the disease they are unlikely to restore normal acuity. Therefore, there is an urgent need to develop treatment modalities, which are less invasive and therefore associated with fewer procedural complications and systemic side effects. This review article summarizes our understanding of the pathophysiology and current treatment of RNV in ischemic retinopathies; lists potential therapeutic targets; and provides a framework for the development of future treatment modalities. PMID:25598837

  6. Beals–Hecht syndrome and choroidal neovascularization

    Directory of Open Access Journals (Sweden)

    Roberto Gallego-Pinazo

    2010-07-01

    Full Text Available Roberto Gallego-Pinazo1, Ruth López-Lizcano1, José María Millán2,3, J Fernando Arevalo5, J Luis Mullor6, Manuel Díaz-Llopis1,3,41Department of Ophthalmology, 2Department of Genetics, Unit of Experimental Opthalmology, Hospital Universitario La Fe, Valencia, Spain; 3Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER, Valencia, Spain; 4Faculty of Medicine, University of Valencia, Valencia, Spain; 5Retina and Vitreous Service, Clínica Oftalmológica Centro Caracas, Caracas, Venezuela; 6Unit of Experimental Opthalmology, Fundación Parala Investigación del Hospital La Fe, Valencia, SpainPurpose: To describe a case of choroidal neovascularization (CNV in a female diagnosed with Beals–Hecht syndrome.Methods: A retrospective, interventional case is described in a 26-year-old female complaining of metamorphopsia and visual loss in her left eye (counting fingers. The fluorescein angiogram and the optical coherence tomography supported the diagnosis of CNV. Intravitreal ranibizumab was administered.Results: After the third intravitreal ranibizumab, her visual acuity improved to 0.8 and the morphology of the macular area was restored.Conclusions: To our knowledge this is the first report of CNV in Beals–Hecht syndrome treated with ranibizumab. Self-monitoring by periodically performing Amsler grid test is strongly recommended in these patients in order to achieve an early diagnosis of eventual CNV and avoid visual acuity loss.Keywords: Beals–Hecht syndrome, connective tissue disease, choroidal neovascularization, ranibizumab

  7. Non-Functional Requirements Elicitation and Incorporation into Class Diagrams

    OpenAIRE

    Song , Xiaoyu; Duan , Zhenhua; Tian , Cong

    2010-01-01

    International audience; Top-quality software architecture should consider both functional and non-functional aspects of systems and their association. In the the existing literature, considerable efforts have been directed at functional requirement analysis and design, regardless of the non-functional aspects. This disassociation makes architecture comprehension and evolution hard. This paper proposes a strategy on how to elicit non-functional requirements and incorporate them into the design...

  8. Neovascular glaucoma after helium ion irradiation for uveal melanoma

    International Nuclear Information System (INIS)

    Kim, M.K.; Char, D.H.; Castro, J.L.; Saunders, W.M.; Chen, G.T.; Stone, R.D.

    1986-01-01

    Neovascular glaucoma developed in 22 of 169 uveal melanoma patients treated with helium ion irradiation. Most patients had large melanomas; no eyes containing small melanomas developed anterior segment neovascularization. The mean onset of glaucoma was 14.1 months (range, 7-31 months). The incidence of anterior segment neovascularization increased with radiation dosage; there was an approximately three-fold increase at 80 GyE versus 60 GyE of helium ion radiation (23% vs. 8.5%) (P less than 0.05). Neovascular glaucoma occurred more commonly in larger tumors; the incidence was not affected by tumor location, presence of subretinal fluid, nor rate of tumor regression. Fifty-three percent of patients had some response with intraocular pressures of 21 mmHg or less to a combination of antiglaucoma treatments

  9. Inhibition of Corneal Neovascularization by Topical and Subconjunctival Tigecycline

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    Sertan Goktas

    2014-01-01

    Full Text Available Objective. To investigate the effects of topical and subconjunctival tigecycline on the prevention of corneal neovascularization. Materials and Methods. Following chemical burn, thirty-two rats were treated daily with topical instillation of 1 mg/mL tigecycline (group 1 or subconjunctival instillation of 1 mg/mL tigecycline (group 3 for 7 days. Control rats received topical (group 2 or subconjunctival (group 4 0.9% saline. Digital photographs of the cornea were taken on the eighth day after treatment and analyzed to determine the percentage area of the cornea covered by neovascularization. Corneal sections were analyzed histopathologically. Results. The median percentages of corneal neovascularization in groups 1 and 3 were 48% (95% confidence interval (CI, 44.2–55.8% and 33.5% (95% CI, 26.6–39.2%, respectively. The median percentages of corneal neovascularization of groups 1 and 3 were significantly lower than that of the control group (P=0.03 and P<0.001, resp.. Histologic examination of samples from groups 1 and 3 showed lower vascularity than that of control groups. Conclusion. Topical and subconjunctival administration of tigecycline seems to be showing promising therapeutic effects on the prevention of corneal neovascularization. Furthermore, subconjunctival administration of tigecycline is more potent than topical administration in the inhibition of corneal neovascularization.

  10. Prediction Error During Functional and Non-Functional Action Sequences

    DEFF Research Database (Denmark)

    Nielbo, Kristoffer Laigaard; Sørensen, Jesper

    2013-01-01

    recurrent networks were made and the results are presented in this article. The simulations show that non-functional action sequences do indeed increase prediction error, but that context representations, such as abstract goal information, can modulate the error signal considerably. It is also shown...... that the networks are sensitive to boundaries between sequences in both functional and non-functional actions....

  11. Neovascular events in eyes with central retinal vein occlusion undergoing serial bevacizumab or ranibizumab intravitreal injections: A retrospective review

    Directory of Open Access Journals (Sweden)

    Francis Char DeCroos

    2014-01-01

    Conclusion: Neovascular events occur in eyes with CRVO undergoing serial anti-VEGF therapy, and these events may be delayed compared to the natural history of CRVO-associated neovascularization. Iris neovascularization occurred most frequently.

  12. Experimentation on accuracy of non functional requirement prioritization approaches for different complexity projects

    Directory of Open Access Journals (Sweden)

    Raj Kumar Chopra

    2016-09-01

    Full Text Available Non functional requirements must be selected for implementation together with functional requirements to enhance the success of software projects. Three approaches exist for performing the prioritization of non functional requirements using the suitable prioritization technique. This paper performs experimentation on three different complexity versions of the industrial software project using cost-value prioritization technique employing three approaches. Experimentation is conducted to analyze the accuracy of individual approaches and the variation of accuracy with the complexity of the software project. The results indicate that selecting non functional requirements separately, but in accordance with functionality has higher accuracy amongst the other two approaches. Further, likewise other approaches, it witnesses the decrease in accuracy with increase in software complexity but the decrease is minimal.

  13. An assessment of the vulnerability of carotid plaques: a comparative study between intraplaque neovascularization and plaque echogenicity

    International Nuclear Information System (INIS)

    Zhou, Yangyang; Li, Yan; Bai, Yang; Chen, Ying; Sun, Xiaofeng; Zhu, Yingqiao; Wu, Jiang

    2013-01-01

    Carotid plaque echolucency as detected by Color Doppler ultrasonography (CDUS) has been used as a potential marker of plaque vulnerability. However, contrast-enhanced ultrasound (CEUS) has recently been shown to be a valuable method to evaluate the vulnerability and neovascularization within carotid atherosclerotic plaques. The aim of this study was to compare CEUS and CDUS in the assessment of plaque vulnerability using transcranial color Doppler (TCD) monitoring of microembolic signals (MES) as a reference technique. A total of 46 subjects with arterial stenosis (≥ 50%) underwent a carotid duplex ultrasound, TCD monitoring of MES and CEUS (SonoVue doses of 2.0 mL) within a span of 3 days. The agreement between the CEUS, CDUS, and MES findings was assessed with a chi-square test. A p-value less than 0.05 was considered statistically significant. Neovascularization was observed in 30 lesions (44.4%). The vascular risk factors for stroke were similar and there were no age or gender differences between the 2 groups. Using CEUS, MES were identified in 2 patients (12.5%) within class 1 (non-neovascularization) as opposed to 15 patients (50.0%) within class 2 (neovascularization) (p = 0.023). CDUS revealed no significant differences in the appearance of the MES between the 2 groups (hyperechoic and hypoechoic) (p = 0.237). This study provides preliminary evidence to suggest that intraplaque neovascularization detected by CEUS is associated with the presence of MESs, where as plaque echogenicity on traditional CDUS does not. These findings argue that CEUS may better identify high-risk plaques

  14. Study of surgical treatment on neovascular glaucoma

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    Xiao-Nü Liu

    2014-05-01

    Full Text Available AIM: To compare the effect of two surgical methods on neovascular glaucoma(NVG. METHODS: The clinical date of 46 cases(57 eyeswith NVG underwent surgical treatment were retrospectively analyzed and followed-up. Patients were divided into Ahmed glaucoma valve(AGVimplantation group(group A, 24 cases, 31 eyesand semiconductor diode laser transscleral ciliary body photocoagulation(TSCPCgroup(group B, 22cases, 26 eyesaccording to the surgical approach. The intraocular pressure, visual acuity and postoperative complications were compared before and after operation. RESULTS: The intraocular pressure postoperative in two groups were significantly lower than those preoperative(P P>0.05. The changes of visual acuity postoperative showed no statistical difference between the two groups(P>0.05. The postoperative complications of group A was significantly lower than that in group B, in which the incidence of eye pain, anterior chamber bleeding were significant differences between two groups(P CONCLUSION: AGV implantation treatment and TSCPC for NVG are both valid, but AGV implantation is filtration surgery, and TSCPC isciliary body destructive surgery, and the latter has higher rate of postoperative complications.

  15. NON-FUNCTIONAL SHOPPING MOTIVES AMONG IRANIAN CONSUMERS

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    Shahriar AZIZI

    2011-01-01

    Full Text Available This study aims to explore the non functional shopping motives among Iranian consumers. In addition, the effects of marital status, gender, age and residential region as an indicator for social class on the non-functional shopping motives are investigated. This paper uses a self-reported and 15 items questionnaire. The analysis is done based on 363 returned and usable questionnaires. Multivariate analysis of variance is applied for this study. MANOVA results show that marital status, gender, age and region have different significant effects on the non-functional shopping motives among Iranian consumers.

  16. Clinical effect of neovascular glaucoma treated by vitrectomy and cyclophotocoagulation

    Directory of Open Access Journals (Sweden)

    Yi-Xuan Jin

    2014-07-01

    Full Text Available AIM: To observe the postoperative intraocular pressure(IOPand operation safety in the eyes of the neovascular glaucoma pateints treated by intraocular cyclophotocoagulation which needed vitrectomy at the same time. METHODS: A total of 12 neovascular glaucoma cases(14 eyessecondary to diabetic retinopathy, retinal detachment surgery and trauma were reviewed in our study. This procedure mainly used intraocular photocoagulation catheter to highlight the ciliary processes until the ciliary became white atrophy or plosion after vitreous surgery treatment. The intraocular photocoagulation catheter was performed at a power of 300-500mW, for a duration of 0.1-0.2ms. Postoperative follow-up was at least for 6mo. The observation of 14 postoperative neovascular glaucoma was performed at 1wk, 1, 6mo observing the IOP and complications. RESULTS: IOP of the 11 eyes was significantly declined and controlled in normal. After cyclophotocoagulation, average IOP at 1wk was 16.7±14.4mmHg, 15.7±8.8mmHg at 1mo and 12.9±4.5mmHg at 6mo, which compared with untreatment(39.6 ±10.0mmHgwas statistically significant different(PCONCLUSION: The intraocular cyclophotocoagulation and vitrectomy simultaneously can deal with the primary disease and secondary neovascular glaucoma. The operation can be accurately performed under direct cyclophotocoagulation and it is a safe and effective way for neovascular glaucoma which needs vitreous surgery.

  17. RETINAL NEOVASCULARIZATION FROM A PATIENT WITH CUTIS MARMORATA TELANGIECTATICA CONGENITA.

    Science.gov (United States)

    Sassalos, Thérèse M; Fields, Taylor S; Levine, Robert; Gao, Hua

    2018-03-14

    To report a rare case of peripheral retinal neovascularization in a patient diagnosed with cutis marmorata telangiectatica congenita (CMTC). Observational case report. A 16-year-old girl was referred to clinic for retinal evaluation. The patient had a clinical diagnosis of CMTC later confirmed by skin biopsy. Examination revealed temporal peripheral retinal sheathing, as well as lattice degeneration in both eyes. Wide-field fluorescein angiogram showed substantive peripheral retinal nonperfusion with evidence of vascular leakage from areas of presumed retinal neovascularization. The patient subsequently had pan retinal photocoagulation laser treatment to each eye without complication. Cutis marmorata telangiectatica congenita is a rare vascular condition known to affect multiple organ systems including the eyes. Although ocular manifestations of CMTC are rare, instances of congenital glaucoma, suprachoroidal hemorrhage, and bilateral total retinal detachments resulting in secondary neovascular glaucoma have been reported. Our patient demonstrates the first reported findings of peripheral nonperfusion and retinal neovascularization related to CMTC in a 16-year-old girl. We propose early retinal examination, wide-field fluorescein angiogram, and early pan retinal photocoagulation laser treatment in patients with peripheral nonperfusion and retinal neovascularization from CMTC.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

  18. Radiation therapy for neovascular age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Robert Petrarca

    2011-01-01

    Full Text Available Robert Petrarca, Timothy L JacksonDepartment of Ophthalmology, King’s College Hospital NHS Foundation Trust, London, UKAbstract: Antivascular endothelial growth factor (anti-VEGF therapies represent the standard of care for most patients presenting with neovascular (wet age-related macular degeneration (neovascular AMD. Anti-VEGF drugs require repeated injections and impose a considerable burden of care, and not all patients respond. Radiation targets the proliferating cells that cause neovascular AMD, including fibroblastic, inflammatory, and endothelial cells. Two new neovascular AMD radiation treatments are being investigated: epimacular brachytherapy and stereotactic radiosurgery. Epimacular brachytherapy uses beta radiation, delivered to the lesion via a pars plana vitrectomy. Stereotactic radiosurgery uses low voltage X-rays in overlapping beams, directed onto the lesion. Feasibility data for epimacular brachytherapy show a greatly reduced need for anti-VEGF therapy, with a mean vision gain of 8.9 ETDRS letters at 12 months. Pivotal trials are underway (MERLOT, CABERNET. Preliminary stereotactic radiosurgery data suggest a mean vision gain of 8 to 10 ETDRS letters at 12 months. A large randomized sham controlled stereotactic radiosurgery feasibility study is underway (CLH002, with pivotal trials to follow. While it is too early to conclude on the safety and efficacy of epimacular brachytherapy and stereotactic radiosurgery, preliminary results are positive, and these suggest that radiation offers a more durable therapeutic effect than intraocular injections.Keywords: wet age-related macular degeneration, neovascular, radiation therapy, epimacular brachytherapy, stereotactic radiosurgery, anti-VEGF

  19. Investigation of the growth patterns of non-functioning pituitary ...

    African Journals Online (AJOL)

    2016-07-28

    Jul 28, 2016 ... Pituitary adenomas are almost always benign (>99.9%), arise from the anterior pituitary and ... Non-functioning pituitary macroadenomas (NFMA) are the most ... pituitary gland, most likely due to alterations in perfusion.

  20. Spontaneous processing of functional and non-functional action sequences

    DEFF Research Database (Denmark)

    Nielbo, Kristoffer Laigaard; Sørensen, Jesper

    2011-01-01

    as sub-categories of non-functional behavior (i.e., actions lacking causal coherence and a necessary integration between subparts). New insights in human action processing can help us explain how cognition might vary depending on the type of behavior processed. Using an event segmentation paradigm, we...... conducted two experiments eliciting differences in participants' response patterns to functional and non-functional actions. Participants consistently segmented non-functional action sequences into smaller units indicating either an attentional shift to the level of gesture analysis or a problem...... of representational integration. Experimental studies of non-functional behavior can strengthen explanations of recurrent features of human action processing, such as ritual and ritualized behavior, as well as indicate potential sources and effects of breakdown of the system....

  1. Ischemic Retinopathy and Neovascular Proliferation Secondary to Severe Head Injury

    Directory of Open Access Journals (Sweden)

    Muge Coban-Karatas

    2014-01-01

    Full Text Available We report a case with severe head trauma and perforating globe injury in one eye and ischemic retinopathy and neovascular proliferation in the other eye. A 37-year-old male was brought to the emergency department after a motor vehicle accident with severe maxillofacial trauma. Ophthalmic examination revealed hematoma of the left eyelids as well as traumatic rupture and disorganization of the left globe. On the right eye, anterior segment and fundoscopic examination were normal. Primary globe repair was performed. At postoperative one-month visit, the right eye revealed no pathology of the optic disc and macula but severe neovascularization in the temporal peripheral retina. The patient was diagnosed as ischemic retinopathy and neovascular proliferation due to head trauma.

  2. The formation of rats' choroidal neovascularization induced by acrolein

    Directory of Open Access Journals (Sweden)

    Guan-Feng Wang

    2016-04-01

    Full Text Available AIM:To investigate the formation of rats' choroidal neovascularization(CNVinduced by acrolein. METHODS:Twelve Sprague-Dawley rats were randomly divided into three groups. Acrolein 200μL(2.5 mg/kg/dwas poured into the rats' stomach for 4wk as acrolein 4wk and for 8wk as acrolein 8wk group. The same volume of fresh water was also done to the rats as the control group. Remove all eye balls and embed into paraffin with HE staining.RESLUTS:The RPE-Bruch membrane was intact with no obvious abnormality in the control group and acrolein 4wk group. Lost in the continuity of RPE and the movement of choroidal neovascularization were found in the acrolein 8wk. CONCLUSION:The long time use of acrolein can induce the formation of choroial neovascularization in rats.

  3. Gemcitabine-induced CXCL8 expression counteracts its actions by inducing tumor neovascularization

    International Nuclear Information System (INIS)

    Song, Yao; Baba, Tomohisa; Li, Ying-Yi; Furukawa, Kaoru; Tanabe, Yamato; Matsugo, Seiichi; Sasaki, Soichiro; Mukaida, Naofumi

    2015-01-01

    Patients with pancreatic ductal adenocarcinoma (PDAC) are frequently complicated with metastatic disease or locally advanced tumors, and consequently need chemotherapy. Gemcitabine is commonly used for PDAC treatment, but with limited efficacy. The capacity of gemcitabine to generate reactive oxygen species (ROS) in human pancreatic cancer cells, prompted us to examine its effects on the expression of pro-inflammatory cytokines and chemokines. We observed that gemcitabine enhanced selectively the expression of CXCL8 in human pancreatic cancer cells through ROS generation and NF-κB activation. In vitro blocking of CXCL8 failed to modulate gemcitabine-mediated inhibition of cell proliferation in human pancreatic cancer cells. Gemcitabine also enhanced CXCL8 expression in pancreatic cancer cells in xenografted tumor tissues. Moreover, anti-CXCL8 antibody treatment in vivo attenuated tumor formation as well as intra-tumoral vascularity in nude mice, which were transplanted with Miapaca-2 cells and treated with gemcitabine. Thus, gemcitabine-induced CXCL8 may counteract the drug through inducing neovascularization. - Highlights: • Gemcitabine induced CXCL8 expression in human pancreatic cancer cells. • CXCL8 expression required ROS generation and NF-κB activation. • CXCL8 did not affect in vitro proliferation of human pancreatic cancer cells. • CXCL8 in vivo counteracted gemcitabine by inducing neovascularization

  4. Gemcitabine-induced CXCL8 expression counteracts its actions by inducing tumor neovascularization

    Energy Technology Data Exchange (ETDEWEB)

    Song, Yao; Baba, Tomohisa [Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa 920-1192 (Japan); Li, Ying-Yi [Cancer Research Institute, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai (China); Furukawa, Kaoru; Tanabe, Yamato [Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa 920-1192 (Japan); School of Natural System Bioengineering Course, College of Science and Engineering, Kanazawa University, Kanazawa, Ishikawa (Japan); Matsugo, Seiichi [School of Natural System Bioengineering Course, College of Science and Engineering, Kanazawa University, Kanazawa, Ishikawa (Japan); Sasaki, Soichiro [Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa 920-1192 (Japan); Mukaida, Naofumi, E-mail: mukaida@staff.kanazawa-u.ac.jp [Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa 920-1192 (Japan)

    2015-03-06

    Patients with pancreatic ductal adenocarcinoma (PDAC) are frequently complicated with metastatic disease or locally advanced tumors, and consequently need chemotherapy. Gemcitabine is commonly used for PDAC treatment, but with limited efficacy. The capacity of gemcitabine to generate reactive oxygen species (ROS) in human pancreatic cancer cells, prompted us to examine its effects on the expression of pro-inflammatory cytokines and chemokines. We observed that gemcitabine enhanced selectively the expression of CXCL8 in human pancreatic cancer cells through ROS generation and NF-κB activation. In vitro blocking of CXCL8 failed to modulate gemcitabine-mediated inhibition of cell proliferation in human pancreatic cancer cells. Gemcitabine also enhanced CXCL8 expression in pancreatic cancer cells in xenografted tumor tissues. Moreover, anti-CXCL8 antibody treatment in vivo attenuated tumor formation as well as intra-tumoral vascularity in nude mice, which were transplanted with Miapaca-2 cells and treated with gemcitabine. Thus, gemcitabine-induced CXCL8 may counteract the drug through inducing neovascularization. - Highlights: • Gemcitabine induced CXCL8 expression in human pancreatic cancer cells. • CXCL8 expression required ROS generation and NF-κB activation. • CXCL8 did not affect in vitro proliferation of human pancreatic cancer cells. • CXCL8 in vivo counteracted gemcitabine by inducing neovascularization.

  5. MR imaging of non-functioning endocrine tumors of the pancreas

    International Nuclear Information System (INIS)

    Irie, Hiroyuki; Honda, Hiroshi; Kuroiwa, Toshiro

    2002-01-01

    The purpose of this study was to clarify the MR imaging characteristics of patients with non-functioning endocrine tumors of the pancreas. Fourteen patients with these tumors underwent MR imaging. The signal characteristics of the tumor on T 1 -, T 2 -, and contrast-enhanced T 1 -weighted images were evaluated. The enhancement pattern of the tumor on dynamic study was also examined. The degree of stromal fibrosis was evaluated on the pathologic specimen, and was then classified as mild, moderate, or marked fibrosis. On T 1 -weighted images, the tumors were hypointense in 12 of 14 cases. The signals of the tumors on T 2 -weighted images were varied. The tumors were hypointense in 1 case, isointense in 2 cases, hyperintense in 6 cases, and very hyperintense in the other 5 cases. On contrast-enhanced T 1 -weighted images, the tumors were hyperintense in 8 cases and very hyperintense in 5 cases. On T 2 - and contrast-enhanced T 1 -weighted images, 4 of 5 malignant tumors were very hyperintense. Dynamic study revealed prolonged enhancement in 10 of 11 cases. Pathologic analysis revealed moderate or marked fibrosis in 10 of 14 cases, and prolonged enhancement was considered to be related stromal fibrosis. In conclusion, MR imaging findings of non-functioning endocrine tumors of the pancreas vary in relation to pathological variety. Prolonged enhancement of the tumor on dynamic study is considered to be one of the characteristic MR imaging findings that corresponds to stromal fibrosis of the tumor. (author)

  6. Establishment of a tumor neovascularization animal model with biomaterials in rabbit corneal pouch.

    Science.gov (United States)

    Chu, Yu-Ping; Li, Hong-Chuan; Ma, Ling; Xia, Yang

    2018-06-01

    The present animal model of tumor neovascularization most often used by researchers is zebrafish. For studies on human breast cancer cell neovascularization, a new animal model was established to enable a more convenient study of tumor neovascularization. A sodium alginate-gelatin blend gel system was used to design the new animal model. The model was established using rabbit corneal pouch implantation. Then, the animal model was validated by human breast cancer cell lines MCF-7-Kindlin-2 and MCF-7-CMV. The experiment intuitively observed the relationship between tumor and neovascularization, and demonstrated the advantages of this animal model in the study of tumor neovascularization. The use of sodium alginate-gelatin blends to establish tumor neovascularization in a rabbit corneal pouch is a novel and ideal method for the study of neovascularization. It may be a better animal model for expanding the research in this area. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. Results of laser treatment for sub-retinal neovascular membranes ...

    African Journals Online (AJOL)

    A retrospective study was carried out to determine the results of laser treatment for choroidal neovascular membranes in age-related macular degeneration in 92 patients in whom fluorescein angiography was performed for this condition over a 7-year period. Twenty-nine of these patients, treated with the argon laser, were ...

  8. Broad spectrum antiangiogenic treatment for ocular neovascular diseases.

    Directory of Open Access Journals (Sweden)

    Ofra Benny

    2010-09-01

    Full Text Available Pathological neovascularization is a hallmark of late stage neovascular (wet age-related macular degeneration (AMD and the leading cause of blindness in people over the age of 50 in the western world. The treatments focus on suppression of choroidal neovascularization (CNV, while current approved therapies are limited to inhibiting vascular endothelial growth factor (VEGF exclusively. However, this treatment does not address the underlying cause of AMD, and the loss of VEGF's neuroprotective can be a potential side effect. Therapy which targets the key processes in AMD, the pathological neovascularization, vessel leakage and inflammation could bring a major shift in the approach to disease treatment and prevention. In this study we have demonstrated the efficacy of such broad spectrum antiangiogenic therapy on mouse model of AMD.Lodamin, a polymeric formulation of TNP-470, is a potent broad-spectrum antiangiogenic drug. Lodamin significantly reduced key processes involved in AMD progression as demonstrated in mice and rats. Its suppressive effects on angiogenesis, vascular leakage and inflammation were studied in a wide array of assays including; a Matrigel, delayed-type hypersensitivity (DTH, Miles assay, laser-induced CNV and corneal micropocket assay. Lodamin significantly suppressed the secretion of various pro-inflammatory cytokines in the CNV lesion including monocyte chemotactic protein-1 (MCP-1/Ccl2. Importantly, Lodamin was found to regress established CNV lesions, unlike soluble fms-like tyrosine kinase-1 (sFlk-1. The drug was found to be safe in mice and have little toxicity as demonstrated by electroretinography (ERG assessing retinal and by histology.Lodamin, a polymer formulation of TNP-470, was identified as a first in its class, broad-spectrum antiangiogenic drug that can be administered orally or locally to treat corneal and retinal neovascularization. Several unique properties make Lodamin especially beneficial for ophthalmic

  9. Early Quantitative Assessment of Non-Functional Requirements

    NARCIS (Netherlands)

    Kassab, M.; Daneva, Maia; Ormandjieva, O.

    2007-01-01

    Non-functional requirements (NFRs) of software systems are a well known source of uncertainty in effort estimation. Yet, quantitatively approaching NFR early in a project is hard. This paper makes a step towards reducing the impact of uncertainty due to NRF. It offers a solution that incorporates

  10. Management of neovascular age-related macular degeneration: current state-of-the-art care for optimizing visual outcomes and therapies in development

    Directory of Open Access Journals (Sweden)

    Agarwal A

    2015-06-01

    Full Text Available Aniruddha Agarwal, William R Rhoades, Mostafa Hanout, Mohamed Kamel Soliman, Salman Sarwar, Mohammad Ali Sadiq, Yasir Jamal Sepah, Diana V Do, Quan Dong Nguyen Stanley M Truhlsen Eye Institute, University of Nebraska Medical Center, Omaha, NE, USA Abstract: Contemporary management of neovascular age-related macular degeneration (AMD has evolved significantly over the last few years. The goal of treatment is shifting from merely salvaging vision to maintaining a high quality of life. There have been significant breakthroughs in the identification of viable drug targets and gene therapies. Imaging tools with near-histological precision have enhanced our knowledge about pathophysiological mechanisms that play a role in vision loss due to AMD. Visual, social, and vocational rehabilitation are all important treatment goals. In this review, evidence from landmark clinical trials is summarized to elucidate the optimum modern-day management of neovascular AMD. Therapeutic strategies currently under development, such as gene therapy and personalized medicine, are also described. Keywords: AMD, neovascular AMD, choroidal neovascular membrane, pharmacogenomics, VEGF, low-vision rehabilitation, gene therapy

  11. Spontaneous and Hierarchical Segmentation of Non-functional Events

    DEFF Research Database (Denmark)

    Nielbo, Kristoffer Laigaard

    2012-01-01

    information associations and, further, that the simulations’ ecological validity can be increased through the use of input based on a motion capture device, while the results still support the main findings. Part 4 is a general discussion, which reviews the empirical findings and the corresponding model...... four main parts that span research history and contemporary theories of perception and cognition (Theory), methodology of the dual approach (Methodology), empirical investigations (Synthesizing and analyzing perception of non-functional events), and a general discussion (General discussion). Part 1...... ritual behavior. Part 1 concludes with five primary theoretical hypotheses: I) non-functional events will increase the human event segmentation rate; II) transitions between events will increase the cognitive prediction error signal independent of event type, but this signal will be chronically high...

  12. NON FUNCTIONAL REQUIREMENT TRACEABILITY AUTOMATION-AN MOBILE MULTIMEDIA APPROACH

    OpenAIRE

    J. Selvakumar; M. Rajaram

    2012-01-01

    Requirements Engineering (RE) is the area of software engineering that deals with the discovery and specification of the objectives for the system under development and the environment in which it is used including the human activities it supports. Requirement Elicitation is process of gathering requirements from stakeholders. Incorporating RE to identify non Functional Requirements (NFR) in early stages of design and implementation avoids ambiguities, conflicting requirement and other defect...

  13. Current and emerging treatment options for myopic choroidal neovascularization

    Directory of Open Access Journals (Sweden)

    El Matri L

    2015-04-01

    Full Text Available Leila El Matri, Ahmed Chebil, Fedra Kort Department B of Ophthalmology, Hedi Rais Institute of Ophthalmology, Faculty of Medicine of Tunis, University of El Manar, Tunis, Tunisia Abstract: Choroidal neovascularization (CNV is the main cause of visual impairment in highly myopic patients younger than 50 years of age. There are different treatments for myopic CNV (mCNV, with 5- to 10-year outcomes currently. Chorioretinal atrophy is still the most important determinant factor for visual outcome. The purpose of this study is to provide an overview of the current treatments for mCNV, including laser, surgical management, verteporfin photodynamic therapy, and mainly anti-vascular endothelial growth factor therapy. Emerging treatment options are also discussed. Keywords: myopia, choroidal neovascularization, current treatment, emerging treatment

  14. PPAR Agonists: Potential as Therapeutics for Neovascular Retinopathies

    Directory of Open Access Journals (Sweden)

    Harrihar A. Pershadsingh

    2008-01-01

    Full Text Available The angiogenic, neovascular proliferative retinopathies, proliferative diabetic retinopathy (PDR, and age-dependent macular degeneration (AMD complicated by choroidal neovascularization (CNV, also termed exudative or “wet” AMD, are common causes of blindness. The antidiabetic thiazolidinediones (TZDs, rosiglitazone, and troglitazone are PPAR agonists with demonstrable antiproliferative, and anti-inflammatory effects, in vivo, were shown to ameliorate PDR and CNV in rodent models, implying the potential efficacy of TZDs for treating proliferative retinopathies in humans. Activation of the angiotensin II type 1 receptor (AT1-R propagates proinflammatory and proliferative pathogenic determinants underlying PDR and CNV. The antihypertensive dual AT1-R blocker (ARB, telmisartan, recently was shown to activate PPAR and improve glucose and lipid metabolism and to clinically improve PDR and CNV in rodent models. Therefore, the TZDs and telmisartan, clinically approved antidiabetic and antihypertensive drugs, respectively, may be efficacious for treating and attenuating PDR and CNV humans. Clinical trials are needed to test these possibilities.

  15. Neovascular glaucoma in a child: an unusual presentation of medulloepithelioma

    Directory of Open Access Journals (Sweden)

    Kassa, Enoch

    2014-04-01

    Full Text Available [english] A healthy 12 month old infant without significant medical history presented with left eye redness for one week. Ophthalmic examination showed elevated intraocular pressure with iris neovascularization in the affected eye with increased optic nerve cupping. Scleral depression revealed a ciliary body mass in the supratemporal quadrant. A large, non-pigmented, vascular mass was noted; biopsy results showed multilayered cords, tubules, and sheets resembling primitive medullary epithelium arising from the ciliary body. The patient was diagnosed with medulloepithelioma. The patient underwent enucleation of the affected eye. Medulloepithelioma is a rare but important cause of neovascular glaucoma in the pediatric population. This case will focus on the characteristics of medulloepthelioma and the differential diagnosis for a non-pigmented ciliary body mass in a child.

  16. Leber congenital amaurosis associated with optic disk neovascularization and vitreous hemorrhage.

    Science.gov (United States)

    Kurz, Daryl; Ciulla, Thomas A

    2003-05-01

    To report an unusual case of optic disk neovascularization and vitreous hemorrhage associated with Leber congenital amaurosis (LCA). Interventional case report. A 16-year-old Caucasian girl with a history of LCA presented with decreased vision in her left eye, diffuse retinal pigmentary abnormalities characteristic of LCA, and hemorrhage over the left optic disk and macula. Six months of follow-up revealed optic disk neovascularization. A small amount of neovascularization was noted in the right eye at 6 months. An extensive systemic evaluation indicated no other cause for the neovascularization. Panretinal photocoagulation was performed in both eyes, and subsequently the neovascularization regressed. Leber congenital amaurosis like retinitis pigmentosa, can rarely be associated with neovascularization of the disk, which is amenable to treatment with peripheral photocoagulation if it does not spontaneously regress.

  17. Trabeculectomy versus Ahmed Glaucoma Valve implantation in neovascular glaucoma

    OpenAIRE

    Netland, Peter; Shen,Chris; Salim,Sarwat; Du,Haiming

    2011-01-01

    Christopher C Shen1, Sarwat Salim2, Haiming Du2, Peter A Netland31Glaucoma Consultants Northwest, Seattle, WA, USA; 2University of Tennessee Health Science Center, Memphis, TN, USA; 3University of Virginia School of Medicine, Charlottesville, VA, USAPurpose: To compare surgical outcomes in neovascular glaucoma patients who underwent trabeculectomy with mitomycin C versus Ahmed Glaucoma Valve implantation. Patients and methods: This was a retrospective comparative case series. We reviewed 40 e...

  18. Treatment of Corneal Neovascularization Using Anti-VEGF Bevacizumab

    Directory of Open Access Journals (Sweden)

    Deli Krizova

    2014-01-01

    Full Text Available Purpose. To evaluate antiangiogenic effect of local use of bevacizumab (anti-VEGF antibody in patients with corneal neovascularization. Methods. Patients were divided into two groups. All patients suffered from some form of corneal neovascularization (NV. Patients in group A received 0.2–0.5 mL of bevacizumab solution subconjunctivally (concentration 25 mg/mL in a single dose. Group A included 28 eyes from 27. Patients in group B applied bevacizumab eye drops twice daily (concentration 2.5 mg/mL for two weeks. Group B included 38 eyes from 35 patients. We evaluated the number of corneal segments affected by NV, CDVA, and the incidence of complications and subjective complaints related to the treatment. The minimum follow-up period was six months. Results. By the 6-month follow-up, in group A the percentage reduction of the affected peripheral segments was 21.6% and of the central segments was 9.6%; in group B the percentage reduction of the central segments was 22.7% and of the central segments was 38.04%. In both groups we noticed a statistically significant reduction in the extent of NV. Conclusion. The use of bevacizumab seems to be an effective and safe method in the treatment of corneal neovascularization, either in the subconjunctival or topical application form.

  19. Topical Ranibizumab as a Treatment of Corneal Neovascularization

    Science.gov (United States)

    Ferrari, Giulio; Dastjerdi, Mohammad H.; Okanobo, Andre; Cheng, Sheng-Fu; Amparo, Francisco; Nallasamy, Nambi; Dana, Reza

    2014-01-01

    Purpose To examine the effect of topical ranibizumab on clinically stable corneal neovascularization (NV). Methods This was a prospective, open-label, monocentric, uncontrolled, non-comparative study. Ten eyes of 9 patients with corneal NV received topical ranibizumab (1%) 4 times a day for 3 weeks with a follow-up of 16 weeks. The main corneal neovascularization outcome measures were: neovascular area (NA), the area occupied by the corneal neovessels; vessel caliber (VC), the mean diameter of the corneal neovessels; and invasion area (IA), the fraction of the total cornea area covered by the vessels. This study was conducted at the Massachusetts Eye and Ear Infirmary, Boston, MA, USA. Results Statistically significant decreases in NA (55.3%, P<0.001), which lasted through 16 weeks, and VC (59%, P<0.001), which continued to improve up to week 16, were observed after treatment. No significant decrease was observed in IA (12.3%, P=0.49). There was no statistically significant change in visual acuity or intraocular pressure. No adverse events ascribed to the treatment were noted. Conclusions Topical application of ranibizumab is effective in reducing the severity of corneal NV in the context of established corneal NV, mostly through decrease in VC rather than IA. PMID:23407316

  20. Trabeculectomy versus Ahmed Glaucoma Valve implantation in neovascular glaucoma

    Science.gov (United States)

    Shen, Christopher C; Salim, Sarwat; Du, Haiming; Netland, Peter A

    2011-01-01

    Purpose: To compare surgical outcomes in neovascular glaucoma patients who underwent trabeculectomy with mitomycin C versus Ahmed Glaucoma Valve implantation. Patients and methods: This was a retrospective comparative case series. We reviewed 40 eyes of 39 patients with underlying diagnosis of neovascular glaucoma, divided into two groups: Ahmed Glaucoma Valve (N = 20) and trabeculectomy with mitomycin C (N = 20). Surgical success was defined as 6 mm Hg ≤ intraocular pressure ≤21 mm Hg, with or without the use of glaucoma medications, with no further glaucoma surgery, and light perception or better vision. Early postoperative hypotony was defined as intraocular pressure Ahmed Glaucoma Valve group and 25 months (6–77 months) for the trabeculectomy group. Although the mean number of postoperative intraocular pressure-lowering medications was significantly higher in the trabeculectomy group compared with the Ahmed Glaucoma Valve group at 3 and 6 month time points, there was no statistically significant difference at any other time point. There was no statistically significant difference between both groups in postoperative visual acuity and intraocular pressure. Success was 70% and 65% at 1 year and 60% and 55% at 2 years after Ahmed Glaucoma Valve and trabeculectomy, respectively. Kaplan–Meier survival curve analysis showed no significant difference in success between the two groups (P = 0.815). Hyphema was the most common complication in both groups. Conclusion: We found similar results after trabeculectomy with mitomycin C and Ahmed Glaucoma Valve implantation in eyes with neovascular glaucoma. PMID:21468334

  1. Effect of Ahmed valve implantation on late neovascular glaucoma

    Directory of Open Access Journals (Sweden)

    Ping-An Mao

    2013-09-01

    Full Text Available AIM: To discuss the effect and safety of Ahmed valve implantation in late neovascular glaucoma. METHODS: The Ahmed glaucoma valve were implanted in 41 eyes(41 caseswith late neovascular glaucoma, the follow-up was 12 months on average, intraocular pressure was recorded at 1 day, 1 week, 1 month, 3, 6, 12 months respectively after operation and compared with that before operation, at the same time, the complications and treatment were analyzed.RESULTS: The mean intraocular pressure before operation, 1 day, 1 week, 1 month, 3, 6, 12 months after operation was 59.83±5.53, 19.27±8.19, 19.69±6.86, 20.67±6.73, 21.05±6.93, 21.49±7.42, 22.14±8.08mmHg, the mean intraocular pressure before operation was higher than that after operation and the difference was obvious in statistics. Major complications included hyphema, low intraocular pressure early postoperation, shallow anterior chamber, obstruction of the tube, the plate wrapped or exposed.CONCLUSION: Ahmed valve implantation is an effective method to treatlate neovascular glaucoma.

  2. Automated detection of neovascularization for proliferative diabetic retinopathy screening.

    Science.gov (United States)

    Roychowdhury, Sohini; Koozekanani, Dara D; Parhi, Keshab K

    2016-08-01

    Neovascularization is the primary manifestation of proliferative diabetic retinopathy (PDR) that can lead to acquired blindness. This paper presents a novel method that classifies neovascularizations in the 1-optic disc (OD) diameter region (NVD) and elsewhere (NVE) separately to achieve low false positive rates of neovascularization classification. First, the OD region and blood vessels are extracted. Next, the major blood vessel segments in the 1-OD diameter region are classified for NVD, and minor blood vessel segments elsewhere are classified for NVE. For NVD and NVE classifications, optimal region-based feature sets of 10 and 6 features, respectively, are used. The proposed method achieves classification sensitivity, specificity and accuracy for NVD and NVE of 74%, 98.2%, 87.6%, and 61%, 97.5%, 92.1%, respectively. Also, the proposed method achieves 86.4% sensitivity and 76% specificity for screening images with PDR from public and local data sets. Thus, the proposed NVD and NVE detection methods can play a key role in automated screening and prioritization of patients with diabetic retinopathy.

  3. Suicide gene reveals the myocardial neovascularization role of mesenchymal stem cells overexpressing CXCR4 (MSC(CXCR4.

    Directory of Open Access Journals (Sweden)

    Jialiang Liang

    Full Text Available BACKGROUND: Our previous studies indicated that MSC(CXCR4 improved cardiac function after myocardial infarction (MI. This study was aimed to investigate the specific role of MSC(CXCR4 in neovascularization of infarcted myocardium using a suicide gene approach. METHODS: MSCs were transduced with either lentivirus-null vector/GFP (MSC(Null as control or vector encoding for overexpressing CXCR4/GFP. The MSC derived-endothelial cell (EC differentiation was assessed by a tube formation assay, Dil-ac-LDL uptake, EC marker expression, and VE-cadherin promoter activity assay. Gene expression was analyzed by quantitative RT-PCR or Western blot. The suicide gene approach was under the control of VE-cadherin promoter. In vivo studies: Cell patches containing MSC(Null or MSC(CXCR4 were transduced with suicide gene and implanted into the myocardium of MI rat. Rats received either ganciclovir (GCV or vehicle after cell implantation. After one month, the cardiac functional changes and neovascularization were assessed by echocardiography, histological analysis, and micro-CT imaging. RESULTS: The expression of VEGF-A and HIF-1α was significantly higher in MSC(CXCR4 as compared to MSC(Null under hypoxia. Additionally, MSC(CXCR4 enhanced new vessel formation and EC differentiation, as well as STAT3 phosphorylation under hypoxia. STAT3 participated in the transcription of VE-cadherin in MSC(CXCR4 under hypoxia, which was inhibited by WP1066 (a STAT3 inhibitor. In addition, GCV specifically induced death of ECs with suicide gene activation. In vivo studies: MSC(CXCR4 implantation promoted cardiac functional restoration, reduced infarct size, improved cardiac remodeling, and enhanced neovascularization in ischemic heart tissue. New vessels derived from MSC(CXCR4 were observed at the injured heart margins and communicated with native coronary arteries. However, the derived vessel networks were reduced by GCV, reversing improvement of cardiac function. CONCLUSION: The

  4. Correlation between clinical and histological features in a pig model of choroidal neovascularization

    DEFF Research Database (Denmark)

    Lassota, Nathan; Kiilgaard, Jens Folke; Prause, Jan Ulrik

    2006-01-01

    To analyse the histological changes in the retina and the choroid in a pig model of choroidal neovascularization (CNV) and to correlate these findings with fundus photographic and fluorescein angiographic features.......To analyse the histological changes in the retina and the choroid in a pig model of choroidal neovascularization (CNV) and to correlate these findings with fundus photographic and fluorescein angiographic features....

  5. Subfoveal fibrosis in eyes with neovascular age-related macular degeneration treated with intravitreal ranibizumab

    DEFF Research Database (Denmark)

    Bloch, Sara Brandi; Lund-Andersen, Henrik; Sander, Birgit

    2013-01-01

    To assess baseline and follow-up characteristics of choroidal neovascularization (CNV) lesions in age-related macular degeneration in relation to the development of subfoveal subretinal fibrosis.......To assess baseline and follow-up characteristics of choroidal neovascularization (CNV) lesions in age-related macular degeneration in relation to the development of subfoveal subretinal fibrosis....

  6. Verteporfin plus ranibizumab for choroidal neovascularization in age-related macular degeneration

    DEFF Research Database (Denmark)

    Larsen, Michael; Schmidt-Erfurth, Ursula; Lanzetta, Paolo

    2012-01-01

    To compare the efficacy and safety of same-day verteporfin photodynamic therapy (PDT) and intravitreal ranibizumab combination treatment versus ranibizumab monotherapy in neovascular age-related macular degeneration.......To compare the efficacy and safety of same-day verteporfin photodynamic therapy (PDT) and intravitreal ranibizumab combination treatment versus ranibizumab monotherapy in neovascular age-related macular degeneration....

  7. The association between Neovascular Age-related Macular Degeneration and Regulatory T cells in peripheral blood

    DEFF Research Database (Denmark)

    Madelung, Christopher Fugl; Falk, Mads; Sørensen, Torben Lykke

    2015-01-01

    PURPOSE: To investigate regulatory T cells (Tregs) and subsets of the Treg population in patients with neovascular age-related macular degeneration (AMD). PATIENTS AND METHODS: Twenty-one neovascular AMD cases and 12 age-matched controls without retinal pathology were selected. Patients were...

  8. Modeling Stem/Progenitor Cell-Induced Neovascularization and Oxygenation Around Solid Implants

    KAUST Repository

    Jain, Harsh Vardhan

    2012-07-01

    Tissue engineering constructs and other solid implants with biomedical applications, such as drug delivery devices or bioartificial organs, need oxygen (O(2)) to function properly. To understand better the vascular integration of such devices, we recently developed a novel model sensor containing O(2)-sensitive crystals, consisting of a polymeric capsule limited by a nanoporous filter. The sensor was implanted in mice with hydrogel alone (control) or hydrogel embedded with mouse CD117/c-kit+ bone marrow progenitor cells in order to stimulate peri-implant neovascularization. The sensor provided local partial O(2) pressure (pO(2)) using noninvasive electron paramagnetic resonance signal measurements. A consistently higher level of peri-implant oxygenation was observed in the cell-treatment case than in the control over a 10-week period. To provide a mechanistic explanation of these experimental observations, we present in this article a mathematical model, formulated as a system of coupled partial differential equations, that simulates peri-implant vascularization. In the control case, vascularization is considered to be the result of a foreign body reaction, while in the cell-treatment case, adipogenesis in response to paracrine stimuli produced by the stem cells is assumed to induce neovascularization. The model is validated by fitting numerical predictions of local pO(2) to measurements from the implanted sensor. The model is then used to investigate further the potential for using stem cell treatment to enhance the vascular integration of biomedical implants. We thus demonstrate how mathematical modeling combined with experimentation can be used to infer how vasculature develops around biomedical implants in control and stem cell-treated cases.

  9. Modeling Stem/Progenitor Cell-Induced Neovascularization and Oxygenation Around Solid Implants

    KAUST Repository

    Jain, Harsh Vardhan; Moldovan, Nicanor I.; Byrne, Helen M.

    2012-01-01

    Tissue engineering constructs and other solid implants with biomedical applications, such as drug delivery devices or bioartificial organs, need oxygen (O(2)) to function properly. To understand better the vascular integration of such devices, we recently developed a novel model sensor containing O(2)-sensitive crystals, consisting of a polymeric capsule limited by a nanoporous filter. The sensor was implanted in mice with hydrogel alone (control) or hydrogel embedded with mouse CD117/c-kit+ bone marrow progenitor cells in order to stimulate peri-implant neovascularization. The sensor provided local partial O(2) pressure (pO(2)) using noninvasive electron paramagnetic resonance signal measurements. A consistently higher level of peri-implant oxygenation was observed in the cell-treatment case than in the control over a 10-week period. To provide a mechanistic explanation of these experimental observations, we present in this article a mathematical model, formulated as a system of coupled partial differential equations, that simulates peri-implant vascularization. In the control case, vascularization is considered to be the result of a foreign body reaction, while in the cell-treatment case, adipogenesis in response to paracrine stimuli produced by the stem cells is assumed to induce neovascularization. The model is validated by fitting numerical predictions of local pO(2) to measurements from the implanted sensor. The model is then used to investigate further the potential for using stem cell treatment to enhance the vascular integration of biomedical implants. We thus demonstrate how mathematical modeling combined with experimentation can be used to infer how vasculature develops around biomedical implants in control and stem cell-treated cases.

  10. Modeling Stem/Progenitor Cell-Induced Neovascularization and Oxygenation Around Solid Implants

    Science.gov (United States)

    Moldovan, Nicanor I.; Byrne, Helen M.

    2012-01-01

    Tissue engineering constructs and other solid implants with biomedical applications, such as drug delivery devices or bioartificial organs, need oxygen (O2) to function properly. To understand better the vascular integration of such devices, we recently developed a novel model sensor containing O2-sensitive crystals, consisting of a polymeric capsule limited by a nanoporous filter. The sensor was implanted in mice with hydrogel alone (control) or hydrogel embedded with mouse CD117/c-kit+ bone marrow progenitor cells in order to stimulate peri-implant neovascularization. The sensor provided local partial O2 pressure (pO2) using noninvasive electron paramagnetic resonance signal measurements. A consistently higher level of peri-implant oxygenation was observed in the cell-treatment case than in the control over a 10-week period. To provide a mechanistic explanation of these experimental observations, we present in this article a mathematical model, formulated as a system of coupled partial differential equations, that simulates peri-implant vascularization. In the control case, vascularization is considered to be the result of a foreign body reaction, while in the cell-treatment case, adipogenesis in response to paracrine stimuli produced by the stem cells is assumed to induce neovascularization. The model is validated by fitting numerical predictions of local pO2 to measurements from the implanted sensor. The model is then used to investigate further the potential for using stem cell treatment to enhance the vascular integration of biomedical implants. We thus demonstrate how mathematical modeling combined with experimentation can be used to infer how vasculature develops around biomedical implants in control and stem cell-treated cases. PMID:22224628

  11. Monozygotic twins with CAPN5 autosomal dominant neovascular inflammatory vitreoretinopathy

    Directory of Open Access Journals (Sweden)

    Rowell HA

    2012-12-01

    Full Text Available Hannah A Rowell,1,2 Alexander G Bassuk,3,4 Vinit B Mahajan1,21Omics Laboratory, 2Department of Ophthalmology and Visual Sciences, 3Department of Pediatrics, 4Department of Neurology, University of Iowa, Iowa City, IA, USABackground: The purpose of this study was to describe the clinical findings in a set of monozygotic twins with autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV over a 23-year period.Methods: A pair of female twins were examined between 26 and 49 years of age. The concordance and discordance of their clinical features were determined. The CAPN5 gene was sequenced using genomic DNA.Results: Both twins of an affected father demonstrated Stage I ADNIV with mild vitreous cells and a negative b-wave on electroretinography. Genetic analysis confirmed a guanine to thymine nucleotide (c.728G>T, pArg243Leu mutation in the CAPN5 gene. Over the course of 23 years, each twin progressed to stage III disease, showing posterior uveitis, cystoid macular edema, intraocular fibrosis, early retinal neovascularization, retinal degeneration, and cataract. Disease progression varied moderately between each twin and was asymmetrical between eyes. Twin A had 20/70 and 20/125 in the right and left eye, respectively, and underwent vitrectomy surgery and intravitreal injections with bevacizumab for recurrent cystoid macular edema. Twin B maintained 20/20 and 20/40 in the right and left eye, respectively without intervention.Conclusion: There was asymmetry between the eyes and some discordance in the rate of disease progression in these monozygotic twins with ADNIV. The overall high disease concordance suggests genetic factors play a major role in clinical manifestations in CAPN5 vitreoretinopathy.Keywords: autosomal dominant neovascular inflammatory vitreoretinopathy, ADNIV, CAPN5, calpain-5, monozygotic twins

  12. Desferrioxamine: a practical method for improving neovascularization of prefabricated flaps.

    Science.gov (United States)

    Li, Bin; Li, Hua; Jin, Rui; Cheng, Chen; Wang, Jing; Zhu, Hainan; Zan, Tao; Li, Qingfeng; Hao, Lijun

    2015-02-01

    Prefabricated flaps are an ideal alternative to repair massive and complex tissue defects. Nevertheless, the risk of necrosis due to unpredictable blood supplies is a major obstacle to the application of prefabricated flaps. The survival of a prefabricated flap depends on the neovascularization between the vascular carrier and the donor tissue. Here, we proposed that the iron chelator, desferrioxamine (DFX), owned therapeutic effects that promoted the neovascularization of prefabricated flaps. An abdominal prefabricated flap model was created in rats via a 2-stage operation. The rats were allocated into 4 groups as follows: 2 groups of rats received DFX treatments during the first or the second stage of the operation, respectively; 1 group of rats received a delay procedure 1 week before the second operation; and the final group was used as a blank control. Flap survival rates and capillary densities were evaluated between groups. The influence of DFX on the dermal fibroblasts was also studied in vitro. Desferrioxamine treatment during the first stage of the operation greatly increased flap survival rate compared to the blank control. The results were similar to those produced by the delay treatment. The vessel count results were consistent with the flap survival rate findings. In vitro, DFX treatment up-regulated the expression levels of several angiogenic factors in the dermal fibroblasts. Nevertheless, DFX treatment during the second stage of the operation was therapeutically detrimental. The application of DFX around the time of vascular carrier implantation greatly promoted neovascularization of prefabricated flaps, but was therapeutically detrimental after the flaps had been elevated.

  13. PATTERNS OF FUNDUS AUTOFLUORESCENCE DEFECTS IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION SUBTYPES.

    Science.gov (United States)

    Ozkok, Ahmet; Sigford, Douglas K; Tezel, Tongalp H

    2016-11-01

    To test define characteristic fundus autofluorescence patterns of different exudative age-related macular degeneration subtypes. Cross-sectional study. Fifty-two patients with choroidal neovascularization because of three different neovascular age-related macular degeneration subtypes were included in the study. Macular and peripheral fundus autofluorescence patterns of study subjects were compared in a masked fashion. Fundus autofluorescence patterns of all three neovascular age-related macular degeneration subtypes revealed similar patterns. However, peripapillary hypo-autofluorescence was more common among patients with polypoidal choroidal vasculopathy (88.2%) compared with patients with retinal angiomatous proliferation (12.5%) and patients without retinal angiomatous proliferation and polypoidal choroidal vasculopathy (21.1%) (P autofluorescence defects in neovascular age-related macular degeneration maybe suggestive of polypoidal choroidal vasculopathy as a variant of neovascular age-related macular degeneration.

  14. Management of neovascular age-related macular degeneration: current state-of-the-art care for optimizing visual outcomes and therapies in development

    Science.gov (United States)

    Agarwal, Aniruddha; Rhoades, William R; Hanout, Mostafa; Soliman, Mohamed Kamel; Sarwar, Salman; Sadiq, Mohammad Ali; Sepah, Yasir Jamal; Do, Diana V; Nguyen, Quan Dong

    2015-01-01

    Contemporary management of neovascular age-related macular degeneration (AMD) has evolved significantly over the last few years. The goal of treatment is shifting from merely salvaging vision to maintaining a high quality of life. There have been significant breakthroughs in the identification of viable drug targets and gene therapies. Imaging tools with near-histological precision have enhanced our knowledge about pathophysiological mechanisms that play a role in vision loss due to AMD. Visual, social, and vocational rehabilitation are all important treatment goals. In this review, evidence from landmark clinical trials is summarized to elucidate the optimum modern-day management of neovascular AMD. Therapeutic strategies currently under development, such as gene therapy and personalized medicine, are also described. PMID:26089632

  15. Nanotechnology in corneal neovascularization therapy--a review.

    Science.gov (United States)

    Gonzalez, Lilian; Loza, Raymond J; Han, Kyu-Yeon; Sunoqrot, Suhair; Cunningham, Christy; Purta, Patryk; Drake, James; Jain, Sandeep; Hong, Seungpyo; Chang, Jin-Hong

    2013-03-01

    Nanotechnology is an up-and-coming branch of science that studies and designs materials with at least one dimension sized from 1-100 nm. These nanomaterials have unique functions at the cellular, atomic, and molecular levels. The term "nanotechnology" was first coined in 1974. Since then, it has evolved dramatically and now consists of distinct and independent scientific fields. Nanotechnology is a highly studied topic of interest, as nanoparticles can be applied to various fields ranging from medicine and pharmacology, to chemistry and agriculture, to environmental science and consumer goods. The rapidly evolving field of nanomedicine incorporates nanotechnology with medical applications, seeking to give rise to new diagnostic means, treatments, and tools. Over the past two decades, numerous studies that underscore the successful fusion of nanotechnology with novel medical applications have emerged. This has given rise to promising new therapies for a variety of diseases, especially cancer. It is becoming abundantly clear that nanotechnology has found a place in the medical field by providing new and more efficient ways to deliver treatment. Ophthalmology can also stand to benefit significantly from the advances in nanotechnology research. As it relates to the eye, research in the nanomedicine field has been particularly focused on developing various treatments to prevent and/or reduce corneal neovascularization among other ophthalmologic disorders. This review article aims to provide an overview of corneal neovascularization, currently available treatments, and where nanotechnology comes into play.

  16. Monozygotic twins with CAPN5 autosomal dominant neovascular inflammatory vitreoretinopathy.

    Science.gov (United States)

    Rowell, Hannah A; Bassuk, Alexander G; Mahajan, Vinit B

    2012-01-01

    The purpose of this study was to describe the clinical findings in a set of monozygotic twins with autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV) over a 23-year period. A pair of female twins were examined between 26 and 49 years of age. The concordance and discordance of their clinical features were determined. The CAPN5 gene was sequenced using genomic DNA. Both twins of an affected father demonstrated Stage I ADNIV with mild vitreous cells and a negative b-wave on electroretinography. Genetic analysis confirmed a guanine to thymine nucleotide (c.728G>T, pArg243Leu) mutation in the CAPN5 gene. Over the course of 23 years, each twin progressed to stage III disease, showing posterior uveitis, cystoid macular edema, intraocular fibrosis, early retinal neovascularization, retinal degeneration, and cataract. Disease progression varied moderately between each twin and was asymmetrical between eyes. Twin A had 20/70 and 20/125 in the right and left eye, respectively, and underwent vitrectomy surgery and intravitreal injections with bevacizumab for recurrent cystoid macular edema. Twin B maintained 20/20 and 20/40 in the right and left eye, respectively without intervention. There was asymmetry between the eyes and some discordance in the rate of disease progression in these monozygotic twins with ADNIV. The overall high disease concordance suggests genetic factors play a major role in clinical manifestations in CAPN5 vitreoretinopathy.

  17. Nanotechnology in Corneal Neovascularization Therapy—A Review

    Science.gov (United States)

    Gonzalez, Lilian; Loza, Raymond J.; Han, Kyu-Yeon; Sunoqrot, Suhair; Cunningham, Christy; Purta, Patryk; Drake, James; Jain, Sandeep; Hong, Seungpyo

    2013-01-01

    Abstract Nanotechnology is an up-and-coming branch of science that studies and designs materials with at least one dimension sized from 1–100 nm. These nanomaterials have unique functions at the cellular, atomic, and molecular levels.1 The term “nanotechnology” was first coined in 1974.2 Since then, it has evolved dramatically and now consists of distinct and independent scientific fields. Nanotechnology is a highly studied topic of interest, as nanoparticles can be applied to various fields ranging from medicine and pharmacology, to chemistry and agriculture, to environmental science and consumer goods.3 The rapidly evolving field of nanomedicine incorporates nanotechnology with medical applications, seeking to give rise to new diagnostic means, treatments, and tools. Over the past two decades, numerous studies that underscore the successful fusion of nanotechnology with novel medical applications have emerged. This has given rise to promising new therapies for a variety of diseases, especially cancer. It is becoming abundantly clear that nanotechnology has found a place in the medical field by providing new and more efficient ways to deliver treatment. Ophthalmology can also stand to benefit significantly from the advances in nanotechnology research. As it relates to the eye, research in the nanomedicine field has been particularly focused on developing various treatments to prevent and/or reduce corneal neovascularization among other ophthalmologic disorders. This review article aims to provide an overview of corneal neovascularization, currently available treatments, and where nanotechnology comes into play. PMID:23425431

  18. Secondary glaucoma in CAPN5-associated neovascular inflammatory vitreoretinopathy

    Directory of Open Access Journals (Sweden)

    Cham A

    2016-06-01

    Full Text Available Abdourahman Cham,1,2 Mayank Bansal,3 Himanshu K Banda,4 Young Kwon,1 Paul S Tlucek,1 Alexander G Bassuk,5 Stephen H Tsang,6,7 Warren M Sobol,8 James C Folk,1 Steven Yeh,4 Vinit B Mahajan1,2 1Department of Ophthalmology and Visual Sciences, 2Omics Laboratory, University of Iowa, Iowa City, IA, USA; 3Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India; 4Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA, 5Department of Pediatrics, University of Iowa, Iowa City, IA, 6Barbara and Donald Jonas Laboratory of Stem Cells and Regenerative Medicine and Bernard and Shirlee Brown Glaucoma Laboratory, Department of Pathology and Cell Biology, Institute of Human Nutrition, College of Physicians and Surgeons, Columbia University, 7Edward S Harkness Eye Institute, New York-Presbyterian Hospital, New York, NY, 8Retina Physicians & Surgeons, Inc., Dayton, OH, USA Objective: The objective of this study was to review the treatment outcomes of patients with secondary glaucoma in cases of autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV, a hereditary autoimmune uveitis due to mutations in CAPN5. Patients and methods: A retrospective, observational case series was assembled from ADNIV patients with secondary glaucoma. The main outcome measures were intraocular pressure (IOP, visual acuity, use of antiglaucoma medications, ocular surgeries, and adverse outcomes. Perimetry and optic disk optical coherence tomography (OCT were also analyzed. Results: Nine eyes of five ADNIV patients with secondary glaucoma were reviewed. Each received a fluocinolone acetonide (FA implant for the management of posterior uveitis. Following implantation, no eyes developed neovascular glaucoma. Five eyes (in patients 1, 2, and 5 required Ahmed glaucoma valve surgery for the management of steroid-responsive glaucoma. Patient 2 also developed angle closure with iris bombe and underwent laser

  19. Non-functioning pituitary adenoma: immunohistochemical analysis of 85 cases.

    Science.gov (United States)

    Mahta, Ali; Haghpanah, Vahid; Lashkari, Anahita; Heshmat, Ramin; Larijani, Bagher; Tavangar, Seyed Mohammad

    2007-01-01

    Pituitary adenomas without clinically active hypersecretion are summarized under the term non-functioning pituitary adenoma (NFPA). Since there are no specific serum markers, the differential diagnosis and treatment imply special difficulties. By using immunohistochemical methods we will have new insight into the nature and pathogenesis of these tumours. Ki-67 is a nuclear antigen detected by the monoclonal antibody MIB-1 and its labelling index (LI) is considered a marker of normal and abnormal cell proliferation. The aim of this study was to investigate the possible role of immunohistochemistry and MIB1-LI determination in NFPAs to predict tumoural behaviour and better management. In this clinicopathological study, 85 cases of NFPAs were analysed immunohistochemically. MIB1-LI was also determined in studied cases. Clinical presentation, treatment and follow-up data were also reviewed and the correlation between clinical and pathologic findings was established. Eighteen adenomas (21.2%) were immunoreactive to one or two adenohypophysial hormones of which 4 GH positive adenomas had aggressive behaviour (2 significant juxtasellar extensions and 2 recurrences). MIB-1 LI was more than 5% in only 5 cases including 2 invasive adenomas but with no evidence of recurrence. No significant statistical difference between clinical presentations in immunoreactive and non-immunoreactive NFPAs was observed except for unilateral temporal hemianopia which was more common in immunoreactive adenomas (P=0.022). NFPAs comprise several pathologically different types of tumours, some of which are potentially hormone producing, but some defects in hormone secretion or production of biologically inactive or insufficient amount of hormone may be the culprit in the lack of evidence of rising serum hormone levels. MIB-1 LI may be indicative of invasiveness but not a predictor of recurrence. Silent somatotropinomas may have more aggressive behaviour in comparison with other NFPAs.

  20. Ultrasonographic demonstration of intraneural neovascularization after penetrating nerve injury.

    Science.gov (United States)

    Arányi, Zsuzsanna; Csillik, Anita; Dévay, Katalin; Rosero, Maja

    2018-06-01

    Hypervascularization of nerves has been shown to be a pathological sign in some peripheral nerve disorders, but has not been investigated in nerve trauma. An observational cohort study was performed of the intraneural blood flow of 30 patients (34 nerves) with penetrating nerve injuries, before or after nerve reconstruction. All patients underwent electrophysiological assessment, and B-mode and color Doppler ultrasonography. Intraneural hypervascularization proximal to the site of injury was found in all nerves, which was typically marked and had a longitudinal extension of several centimeters. In 6 nerves, some blood flow was also present within the injury site or immediately distal to the injury. No correlation was found between the degree of vascularization and age, size of the scar / neuroma, or degree of reinnervation. Neovascularization of nerves proximal to injury sites appears to be an essential element of nerve regeneration after penetrating nerve injuries. Muscle Nerve 57: 994-999, 2018. © 2018 Wiley Periodicals, Inc.

  1. Surgical induction of choroidal neovascularization in a porcine model

    DEFF Research Database (Denmark)

    Lassota, Nathan; Kiilgaard, Jens Folke; Prause, Jan Ulrik

    2007-01-01

    PURPOSE: To develop a reproducible surgical technique for the induction of choroidal neovascularization (CNV) in the subretinal space of porcine eyes and to analyse the resulting CNV clinically and histologically. METHODS: Two different modifications of a surgical technique previously described...... were compared with the original method. In ten porcine eyes retinal pigment epithelial (RPE) cells were removed using a silicone tipped cannula, in ten porcine eyes Bruch's membrane was perforated once with a retinal perforator without prior RPE removal and in ten eyes RPE removal was followed...... by a single perforation of Bruch's membrane. Fifteen of the eyes, five from each group, were enucleated 30 minutes after surgery, while the remaining eyes were enucleated after 14 days. Prior to enucleation, at day 14, fundus photographs and fluorescein angiograms were obtained. Eyes were examined by light...

  2. Helicoid peripapillary chorioretinal degeneration complicated by choroidal neovascularization.

    Science.gov (United States)

    Triantafylla, Magdalini; Panos, Georgios D; Dardabounis, Doukas; Nanos, Panagiotis; Konstantinidis, Aristeidis

    2016-02-15

    Helicoid peripapillary chorioretinal degeneration (HPCD) is a hereditary disease of the fundus that is characterized by atrophic chorioretinal areas that appear early in life and expand gradually from the optic disc towards the macula and the periphery. We describe the case of an elderly man with a known diagnosis of HPCD who developed choroidal neovascular membrane (CNV) in both eyes during the course of the disease. The patient was treated with intravitreal injection of ranibizumab, to which he had excellent response. The CNV subsided with 2 injections in the right eye and 1 in the left. Two years after the initial diagnosis of CNV in the right eye, visual acuity was 5/10 OD and 9/10 OS. Helicoid peripapillary chorioretinal degeneration is rarely complicated by CNV as the fundus lacks the trigger factors that would sustain this process. Although rare, HPCD complicated by CNV can be seen bilaterally, but responds well to few ranibizumab injections.

  3. Radiation Therapy for Neovascular Age-related Macular Degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Kishan, Amar U. [Harvard Medical School, Boston, Massachusetts (United States); Modjtahedi, Bobeck S.; Morse, Lawrence S. [Department of Ophthalmology and Vision Sciences, University of California, Davis, Sacramento, California (United States); Lee, Percy, E-mail: percylee@mednet.ucla.edu [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California (United States)

    2013-03-01

    In the enormity of the public health burden imposed by age-related macular degeneration (ARMD), much effort has been directed toward identifying effective and efficient treatments. Currently, anti-vascular endothelial growth factor (VEGF) injections have demonstrated considerably efficacy in treating neovascular ARMD, but patients require frequent treatment to fully benefit. Here, we review the rationale and evidence for radiation therapy of ARMD. The results of early photon external beam radiation therapy are included to provide a framework for the sequential discussion of evidence for the usage of stereotactic radiation therapy, proton therapy, and brachytherapy. The evidence suggests that these 3 modern modalities can provide a dose-dependent benefit in the treatment of ARMD. Most importantly, preliminary data suggest that all 3 can be used in conjunction with anti-VEGF therapeutics, thereby reducing the frequency of anti-VEGF injections required to maintain visual acuity.

  4. Diospyros kaki Extract Inhibits Alkali Burn-Induced Corneal Neovascularization.

    Science.gov (United States)

    Yang, Sung Jae; Jo, Hyoung; Kim, Kyung-A; Ahn, Hong Ryul; Kang, Suk Woo; Jung, Sang Hoon

    2016-01-01

    The purpose of this study was to evaluate the effect of ethanol extract of Diospyros kaki (EEDK) leaves on corneal neovascularization (CoNV) in rats. One week after the alkali burns in the corneas, the CoNV area coverage in the CoNV-positive control group, 100 mg/kg EEDK group, and 200 mg/kg EEDK group was 43.3% ± 5.5%, 337.7% ± 2.5%, and 27.2% ± 4.3%, respectively. The areas of CoNV in the EEDK-treated groups were significantly different from those of the CoNV group. EEDK significantly attenuated the upregulation of vascular endothelial growth factor, fibroblast growth factor, interleukin-6, and matrix metalloproteinase-2 (MMP-2) protein levels. Orally administrated D. kaki inhibited CoNV development in rats.

  5. Knockdown of the placental growth factor gene inhibits laser induced choroidal neovascularization in a murine model.

    Science.gov (United States)

    Nourinia, Ramin; Soheili, Zahra-Soheila; Ahmadieh, Hamid; Akrami, Hassan; Rezaei Kanavi, Mozhgan; Samiei, Shahram

    2013-01-01

    To evaluate the effect of placental growth factor (PlGF) gene knockdown in a murine model of laser-induced choroidal neovascularization. Choroidal neovascularization was induced in the left eyes of 11 mice by infrared laser. Small interfering RNA (siRNA, 20 picomoles/10 μl) corresponding to PlGF mRNA was administered intravitreally by Hamilton syringe in all subjects. One month later, fluorescein angiography and histolologic examination were performed. No leakage was apparent in the 11 eyes treated with siRNA cognate to PlGF. The results of histological evaluation were consistent with angiographic findings showing absence of choroidal neovascularization. Knockdown of the PlGF gene can inhibit the growth of laser-induced choroidal neovascularization in mice.

  6. Knockdown of the Placental Growth Factor Gene Inhibits Laser Induced Choroidal Neovascularization in a Murine Model

    Directory of Open Access Journals (Sweden)

    Ramin Nourinia

    2013-01-01

    Full Text Available Purpose: To evaluate the effect of placental growth factor (PlGF gene knockdown in a murine model of laser-induced choroidal neovascularization. Methods: Choroidal neovascularization was induced in the left eyes of 11 mice by infrared laser. Small interfering RNA (siRNA, 20 picomoles/10 μl corresponding to PlGF mRNA was administered intravitreally by Hamilton syringe in all subjects. One month later, fluorescein angiography and histolologic examination were performed. Results: No leakage was apparent in the 11 eyes treated with siRNA cognate to PlGF. The results of histological evaluation were consistent with angiographic findings showing absence of choroidal neovascularization. Conclusion: Knockdown of the PlGF gene can inhibit the growth of laser-induced choroidal neovascularization in mice.

  7. Somatostatin receptor 2A expression in choroidal neovascularization secondary to age-related macular degeneration

    NARCIS (Netherlands)

    A.C. Lambooij (Antoinette); R.W.A.M. Kuijpers (Robert); E.G. van Lichtenauer-Kaligis; M. Kliffen (Mike); G.S. Baarsma (Seerp); P.M. van Hagen (Martin); C.M. Mooy (Cornelia)

    2000-01-01

    textabstractPURPOSE: The growth of ocular neovascularization is regulated by a balance between stimulating and inhibiting growth factors. Somatostatin affects angiogenesis by inhibiting the growth hormone-insulin-like growth factor axis and also has a direct

  8. Cataract surgery in patients with neovascular age-related macular degeneration

    DEFF Research Database (Denmark)

    Kessel, Line; Theil, Pernille Koefoed; Sørensen, Torben Lykke

    2016-01-01

    Purpose To examine the outcome after cataract surgery in patients with neovascular age-related macular degeneration (AMD) treated with intravitreal anti-vascular endothelial growth factor (VEGF) injections in routine clinical practice. Methods We extracted information about patients recorded...

  9. A prospective comparative study on neovascular glaucoma and non-neovascular refractory glaucoma following Ahmed glaucoma valve implantation.

    Science.gov (United States)

    Li, Zheng; Zhou, Minwen; Wang, Wei; Huang, Wenbin; Chen, Shida; Li, Xingyi; Gao, Xinbo; Zhang, Xiulan

    2014-01-01

    Neovascular glaucoma is a refractory disease, and difficult to manage. The aim of this study was to evaluate the clinical outcomes of Ahmed glaucoma valve implantation (AGVI) in neovascular glaucoma (NVG) and non-NVG patients. This prospective, non-randomized study included 55 eyes of 55 patients with refractory glaucoma; 27 had NVG (NVG group) and 28 had non-NVG (non-NVG group). All of the patients underwent AGVI. The NVG group was adjunctively injected with intravitreal ranibizumab/bevacizumab (IVR/IVB) before AGVI. Intraocular pressure (IOP) was the primary outcome measure in this study. Surgical success rate, number of antiglaucoma medications used, best corrected visual acuity (BCVA), and postoperative complications were analyzed between the groups. All of the patients completed the study (follow-up of 12 months). Kaplan-Meier survival curve analysis indicated that the qualified success rates in the NVG and non-NVG groups at 12 months were 70.5% and 92.9%, respectively; this difference was significant (P = 0.036). The complete success rates in the NVG and non-NVG groups at 12 months were 66.7% and 89.3%, respectively (P = 0.049). Compared with preoperative examinations, the postoperative mean IOP and use of medications were significantly lower at all follow-up time points in both groups (all P glaucoma, but the success rate of surgery was related to the type of refractory glaucoma. The complete and qualified success rates of NVG patient adjunctive anti-vascular endothelial growth factor treatment are still lower than those of non-NVG patients.

  10. Peripapillary Choroidal Neovascularization Associated with Optic Nerve Head Drusen Treated with Anti-VEGF Agents

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    Norman A. Saffra

    2015-02-01

    Full Text Available Optic nerve head drusen can be associated with peripapillary choroidal neovascularization, in both the pediatric and adult population. These membranes can involve the macula, causing significant visual loss. Herein, we present a case that required treatment with an anti-VEGF agent. The patient failed to respond to the initial agent, but subsequently responded to a change of agent. Adult patients with macular degeneration involving peripapillary choroidal neovascularization associated with optic nerve head drusen may require individualized treatment plans.

  11. Retcam fluorescein gonioangiography: a new modality for early detection of angle neovascularization in diabetic retinopathy.

    Science.gov (United States)

    Azad, Rajvardhan; Arora, Tarun; Sihota, Ramanjit; Chandra, Parijat; Mahajan, Deepankur; Sain, Siddarth; Sharma, Yograj

    2013-10-01

    To evaluate the role of Retcam fluorescein gonioangiography in detecting neovascularization of the angle and correlate the same with gonioscopy in diabetic retinopathy. One hundred and fifty eyes of 150 patients (25 each of mild, moderate, severe, very severe nonproliferative diabetic retinopathy (NPDR) proliferative diabetic retinopathy (PDR); and PDR with high-risk characteristics) were recruited. They underwent complete ocular examination including applanation tonometry, gonioscopy, Retcam fluorescein gonioangiography, and fundus fluorescein angiography. Using Retcam fluorescein gonioangiography, of 150 eyes neovascularization of the angle was detected in 37 eyes (24.66%) compared with 22 eyes (14.66%) on gonioscopy (P = 0.04). Small newly formed vessels were evident only with Retcam fluorescein gonioangiography. In 10 of 50 patients (20%) with severe/very severe NPDR, angle neovascularization was appreciable on Retcam fluorescein angiography compared with 5 patients (10%) on gonioscopy. Similarly, 25 of 50 patients (50%) with PDR/PDR with high-risk characteristics had neovascularization of the angle on Retcam gonioangiography compared with 17 (34%) on gonioscopy. Retcam fluorescein gonioangiography is a novel technique for early detection of angle neovascularization in diabetic retinopathy and hence preventing progression to neovascular glaucoma. The objective nature of this test helps in precise decision making compared with gonioscopy for early intervention especially in cases of pre-PDR.

  12. Spontaneous Regression of Choroidal Neovascularization in a Patient with Pattern Dystrophy

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    Anastasios Anastasakis

    2016-01-01

    Full Text Available Purpose. To present a case of a patient with pattern dystrophy (PD associated choroidal neovascularization (CNV that resolved spontaneously without treatment. Methods. A 69-year-old male patient was referred to our unit, for evaluation of a recent visual loss (metamorphopsias in his left eye. Fundus examination, fundus autofluorescence imaging, and fluorescein angiography showed a choroidal neovascular membrane in his left eye. Since visual acuity was satisfactory the patient elected observation. Clinical examination and OCT testing were repeated at 6 and 12 months after presentation. Results. Visual acuity remained stable at the level of 0.9 (baseline BCVA during the follow-up period (12 months. Repeat OCT testing showed complete spontaneous regression of the choroidal neovascular membrane without evidence of intra- or subretinal fluid in both follow-up visits. Conclusions. Spontaneous regression of choroidal neovascularization can occur in patients with retinal dystrophies and associated choroidal neovascular membranes. The decision to treat or observe these patients relies strongly on the presenting visual acuity, since, in isolated instances, spontaneous resolution of choroidal neovascularization may occur.

  13. Slit2 signaling through Robo1 and Robo2 is required for retinal neovascularization

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    Rama, Nicolas; Dubrac, Alexandre; Mathivet, Thomas; Chárthaigh, Róisín-Ana Ní; Genet, Gael; Cristofaro, Brunella; Pibouin-Fragner, Laurence; Ma, Le; Eichmann, Anne; Chédotal, Alain

    2016-01-01

    Ocular neovascular diseases are a leading cause of blindness. Vascular endothelial growth factor (VEGF) blockade improves vision, but not all individuals respond to anti-VEGF treatment, making additional means to prevent neovascularization necessary. Slit-family proteins (Slits) are ligands of Roundabout (Robo) receptors that repel developing axons in the nervous system. Robo1 expression is altered in ocular neovascular diseases, and previous in vitro studies have reported both pro- and anti-angiogenic effects of Slits. However, genetic evidence supporting a role for Slits in ocular neovascularization is lacking. Here we generated conditional knockout mice deficient in various Slit and Robo proteins and found that Slit2 potently and selectively promoted angiogenesis via Robo1 and Robo2 in mouse postnatal retina and in a model of ocular neovascular disease. Mechanistically, Slit2 acting through Robo1 and Robo2 promoted the migration of endothelial cells. These receptors are required for both Slit2- and VEGF-induced Rac1 activation and lamellipodia formation. Thus, Slit2 blockade could potentially be used therapeutically to inhibit angiogenesis in individuals with ocular neovascular disease. PMID:25894826

  14. Multi-scale osteointegration and neovascularization of biphasic calcium phosphate bone scaffolds

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    Lan, Sheeny K.

    undergoes in vivo modifications involving formation of a biological apatite layer within scaffold micropores and possibly co-precipitation of endogenous osteoinductive proteins. To further investigate the effects of scaffold osteoinductivity, BCP scaffolds were implanted in porcine mandibular defects with rhBMP-2, which was partially sequestered in the micropores. Cell migration into osteoinductive scaffold micropores can be enhanced through the delivery of exogenous rhBMP-2 further promoting multi-scale osteointegration. Finally, endothelial colony forming cells (ECFCs) isolated from human umbilical cord blood (UCB) were evaluated in terms of their in vivo vasculogenic potential in the context of bone formation. This work was completed to determine if ECFCs could be utilized in a bone tissue engineering construct to promote neovascularization. ECFCs were combined with a BCP scaffold and rhBMP-2 and implanted subcutaneously on the abdominal wall of NOD/SCID mice. The result was formation of perfused human vessels within BCP scaffold macropores that were present at 4 weeks. The high density and persistence of human vessels at four weeks indicates that human UCB ECFCs exceed their reported in vivo vasculogenic potential when combined with rhBMP-2 and a BCP scaffold. This shows a dual role for BMP-2 in the context of bone regeneration. Collectively, the thesis demonstrates that (1) the design of synthetic bone scaffolds should include controlled multi-scale porosity to promote multi-scale osteointegration, which may significantly improve scaffold mechanical properties and (2) human umbilical cord blood-derived endothelial colony forming cells have potential for promoting neovascularization in a bone defect when combined with rhBMP-2.

  15. Expansion of microvascular networks in vivo by phthalimide neovascular factor 1 (PNF1).

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    Wieghaus, Kristen A; Nickerson, Meghan M; Petrie Aronin, Caren E; Sefcik, Lauren S; Price, Richard J; Paige, Mikell A; Brown, Milton L; Botchwey, Edward A

    2008-12-01

    Phthalimide neovascular factor (PNF1, formerly SC-3-149) is a potent stimulator of proangiogenic signaling pathways in endothelial cells. In this study, we evaluated the in vivo effects of sustained PNF1 release to promote ingrowth and expansion of microvascular networks surrounding biomaterial implants. The dorsal skinfold window chamber was used to evaluate the structural remodeling response of the local microvasculature. PNF1 was released from poly(lactic-co-glycolic acid) (PLAGA) films, and a transport model was utilized to predict PNF1 penetration into the surrounding tissue. PNF1 significantly expanded microvascular networks within a 2mm radius from implants after 3 and 7 days by increasing microvessel length density and lumenal diameter of local arterioles and venules. Staining of histological sections with CD11b showed enhanced recruitment of circulating white blood cells, including monocytes, which are critical for the process of vessel enlargement through arteriogenesis. As PNF1 has been shown to modulate MT1-MMP, a facilitator of CCL2 dependent leukocyte transmigration, aspects of window chamber experiments were repeated in CCR2(-/-) (CCL2 receptor) mouse chimeras to more fully explore the critical nature of monocyte recruitment on the therapeutic benefits of PNF1 function in vivo.

  16. The Robo4 cytoplasmic domain is dispensable for vascular permeability and neovascularization.

    Science.gov (United States)

    Zhang, Feng; Prahst, Claudia; Mathivet, Thomas; Pibouin-Fragner, Laurence; Zhang, Jiasheng; Genet, Gael; Tong, Raymond; Dubrac, Alexandre; Eichmann, Anne

    2016-11-24

    Vascular permeability and neovascularization are implicated in many diseases including retinopathies and diabetic wound healing. Robo4 is an endothelial-specific transmembrane receptor that stabilizes the vasculature, as shown in Robo4 -/- mice that develop hyperpermeability, but how Robo4 signals remained unclear. Here we show that Robo4 deletion enhances permeability and revascularization in oxygen-induced retinopathy (OIR) and accelerates cutaneous wound healing. To determine Robo4 signalling pathways, we generated transgenic mice expressing a truncated Robo4 lacking the cytoplasmic domain (Robo4ΔCD). Robo4ΔCD expression is sufficient to prevent permeability, and inhibits OIR revascularization and wound healing in Robo4 -/- mice. Mechanistically, Robo4 does not affect Slit2 signalling, but Robo4 and Robo4ΔCD counteract Vegfr2-Y949 (Y951 in human VEGFR2) phosphorylation by signalling through the endothelial UNC5B receptor. We conclude that Robo4 inhibits angiogenesis and vessel permeability independently of its cytoplasmic domain, while activating VEGFR2-Y951 via ROBO4 inhibition might accelerate tissue revascularization in retinopathy of prematurity and in diabetic patients.

  17. Multimodal imaging and diagnosis of myopic choroidal neovascularization in Caucasians

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    Milani P

    2016-09-01

    Full Text Available Paolo Milani,1 Amedeo Massacesi,1 Stefania Moschini,1 Marco Setaccioli,1 Ennio Bulone,1 Gemma Tremolada,1 Stefano Ciaccia,1 Elena Mantovani,1 Daniela Morale,2 Fulvio Bergamini1 1Ophthalmology Department, Istituto Auxologico, 2Institute of Mathematics, Universita’ degli Studi di Milano, Milan, Italy Purpose: To investigate myopic choroidal neovascularization (mCNV by fluorescein angio­graphy (FA, spectral-domain optical coherence tomography (SD-OCT, near-infrared (NIR reflectance, and autofluorescence (AF. Methods: This retrospective study included 65 eyes of 62 Caucasian patients with a mean age of 66.72 years (95% confidence interval [CI] 63–70 years and a mean refraction of -9.72 diopters (95% CI -8.74 to -10.70 diopters. Results: Most of the mCNV cases were foveal-juxtafoveal (60/65, 92.3%, with thickening of the corresponding retina (62/65, 95.3% and leakage on FA (44/65, 67.6%. No retinal fluid was detectable in 32 (49.2% eyes and there was no hemorrhage in 25 (38.4% eyes. Papillary chorio­retinal atrophy was evident in 58 (89.2%, a shadowing effect in 48 (73.8%, and an epiretinal membrane in 38 (58.4% eyes. If an area of macular chorioretinal atrophy was present, mCNV frequently developed adjacent to it and was hyperfluorescent rather than with leakage (P<0.001. In eyes with edema or hemorrhage, hyper-reflective foci were more frequent (P<0.005. NIR and AF features were indeterminable in 19 (29.2% and 27 (41.5% eyes, respectively. The predominant feature was black or grayish on NIR (34/65, 52.3% and patchy (hypo- and hyperfluorescence was observed on AF (25/65, 38.4%. FA and SD-OCT correctly detected mCNV in 49 (75.3% and 48 (73.8% eyes, respectively, whereas NIR and AF exhibited limited diagnostic sensitivity. Doubtful diagnosis was associated with hyperfluorescent mCNV (P<0.001, absence of retinal fluid and epiretinal membrane (P<0.05, and presence of macular chorioretinal atrophy (P<0.01. Conclusion: Tomographic, angiographic, AF

  18. Intravitreal ranibizumab as adjuvant treatment for neovascular glaucoma

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    Flavia Gazze Ticly

    2013-04-01

    Full Text Available The purpose of this study was to describe a prospective case series of 5 eyes treated with intravitreal ranibizumab injection for neovascular glaucoma (NVG. Five patients with clinically uncontrolled NVG secondary to proliferative diabetic retinopathy (4 patients and central retinal vein occlusion (1 patient, non-responsive to maximal tolerable medication and panretinal photocoagulation, received intravitreal ranibizumab injection (0.5 mg. Patients were seen at 1st, 3rd and 7th day after the ranibizumab injection and when it was necessary. Success was defined as intraocular pressure (IOP 21, despite maximal tolerable medication, underwent trabeculectomy with 0.5mg/ml mitomycin C (MMC for 1 minute. Failure was defined as IOP > 21 mmHg, phthisis bulbi, loss of light perception or additional glaucoma surgery. The primary outcome was 6-month IOP control. Mean IOP before the ranibizumab injection was 37 mmHg (7 mmHg SD. Two out of five eyes underwent only ranibizumab injection, having an IOP control after the procedure. Three patients were submitted to trabeculectomy with MMC on the 7th day after the injection. At 6-month follow-up, the mean IOP was 12mmHg (3 mmHg SD. All eyes showed regression of rubeosis iridis and IOP control. Visual acuity improved in 2 eyes worsened in 1 eye, and remained stable in 2 eyes. These data suggest that intravitreal ranibizumab injection may be a useful tool in the treatment of NVG.

  19. Overload and neovascularization of shoulder tendons in volleyball players

    Science.gov (United States)

    2012-01-01

    Background In overhead sports like volleyball, the onset of a rotator cuff tendinopathy due to functional overload is a common observation. An angiofibroblastic etiopathogenesis has been hypothesized, whereby a greater anaerobic metabolism occurs in critical zones of the tendon with a lower degree of vascularization; this would induce collagen and extracellular matrix degradation, that could then trigger a compensatory neovascularization response. We performed a clinical observational study of 80 elite volleyball players, monitoring the perfusion values of the supraspinatus tendons by oximetry. Results No statistically significant differences were found between the oximetry data and age, sex or years of sports activity, nor when comparing the right and left arm or the dominant and non-dominant arm. A statistically significant difference was found for the dominant arm values in relation to the competitive role, higher values being obtained in outside hitters (62.7%) than middle hitters (53.7%) (p = 0.01), opposite hitters (55.5%) (p = 0.02) and libero players (54.4%) (p = 0.008), whereas there were no differences in setters (56.2%) (p > 0.05). Conclusions The different tendon vascularization values found in players with different roles in the team may be attributed to a response to the specific biomechanical demands posed by the different overhead throwing roles. PMID:22853746

  20. Implementation studies of ranibizumab for neovascular age-related macular degeneration.

    Science.gov (United States)

    Bloch, Sara Brandi

    2013-11-01

    The pathogenesis of AMD is associated with age changes plus pathological changes involving oxidative stress and an altered inflammatory response leading to injury of retinal pigment epithelial cells and the adjacent choroidea and photoreceptor cells. AMD is divided into early, intermediate and advanced AMD. The advanced form of AMD is further divided into non-neovascular AMD and neovascular AMD. The diagnosis of neovascular AMD is based on FA and clinical characteristics of the eyes. The CNV lesions are by their growth pattern divided into type 1 CNV lesions, which grow primarily beneath the RPE, and type 2 CNV lesions, which have penetrated the RPE and evolve within the subretinal space. The natural course of neovascular AMD leads to visual disability in a majority of cases within the first years after onset, primarily caused by the development of subfoveal fibrous tissue and atrophy of the RPE. The prognosis of visual acuity in neovascular AMD has been markedly improved by the introduction of an intravitreal administered VEGF inhibitor (ranibizumab) given on a monthly basis. Treatment with ranibizumab for neovascular AMD was introduced in Denmark in 2006 under a fully reimbursed national healthcare plan. Treatment with ranibizumab is given in a variable dosing regimen that varies from the monthly dosing regimen administered in the studies that led to the approval of ranibizumab for neovascular AMD in Europe. The main objectives of this PhD thesis were to evaluate and potentially improve treatment with ranibizumab in a variable OCT guided regimen for neovascular AMD. Another intension of this PhD thesis was to prepare the conditions for future research to further improve the visual prognosis in neovascular AMD treated with anti-VEGF agents. The first study revealed that vision was improved in eyes with active neovascular AMD treated for 1 year in a variable ranibizumab treatment regimen as compared to PDT and the natural course of the disease. We assumed by

  1. The prevalence of neovascularity in patients clinically diagnosed with rotator cuff tendinopathy

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    Raza Syed A

    2009-12-01

    Full Text Available Abstract Background Shoulder dysfunction is common and pathology of the rotator cuff tendons and subacromial bursa are considered to be a major cause of pain and morbidity. Although many hypotheses exist there is no definitive understanding as to the origin of the pain arising from these structures. Research investigations from other tendons have placed intra-tendinous neovascularity as a potential mechanism of pain production. The prevalence of neovascularity in patients with a clinical diagnosis of rotator cuff tendinopathy is unknown. As such the primary aim of this pilot study was to investigate if neovascularity could be identified and to determine the prevalence of neovascularity in the rotator cuff tendons and subacromial bursa in subjects with unilateral shoulder pain clinically assessed to be rotator cuff tendinopathy. The secondary aims were to investigate the association between the presence of neovascularity and pain, duration of symptoms, and, neovascularity and shoulder function. Methods Patients with a clinical diagnosis of unilateral rotator cuff tendinopathy referred for a routine diagnostic ultrasound (US scan in a major London teaching hospital formed the study population. At referral patients were provided with an information document. On the day of the scan (on average, at least one week later the patients agreeing to participate were taken through the consent process and underwent an additional clinical examination prior to undergoing a bilateral grey scale and colour Doppler US examination (symptomatic and asymptomatic shoulder using a Philips HDI 5000 Sono CT US machine. The ultrasound scans were performed by one of two radiologists who recorded their findings and the final assessment was made by a third radiologist blinded both to the clinical examination and the ultrasound examination. The findings of the radiologists who performed the scans and the blinded radiologist were compared and any disagreements were resolved

  2. Neovascular Glaucoma Induced by Peripheral Retinal Ischemia in Neurofibromatosis Type 1: Management and Imaging Features

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    Francesco Pichi

    2013-04-01

    Full Text Available Purpose: To report the case of a young patient affected by neurofibromatosis 1 (NF-1 with peripheral retinal ischemia-induced neovascular glaucoma and the peculiar spectral-domain optical coherence tomography (SD-OCT features. Material and Methods: A 13-year-old boy affected by NF-1, as diagnosed according to established criteria, was referred with a diagnosis of hypertensive uveitis in his left eye. He underwent a complete ophthalmic examination and comprehensive blood work with viral and immunological tests. The case was documented with fluorescein angiography (FA and SD-OCT. When the intraocular pressure (IOP of the left eye decreased and the cornea cleared, FA revealed retinal ischemia and leakage from pathologic retinal vessels. SD-OCT revealed foveal hypoplasia secondary to the complete absence of the retinal nerve fiber layer. Results: Peripheral retinal ischemia-induced neovascular glaucoma was diagnosed. The patient underwent Ahmed valve implantation to control his IOP, and subsequent retinal photocoagulation by argon laser and intravitreal bevacizumab injection were performed to control neovascularization. Discussion: Retinal ischemia in NF-1 might lead to neovascular glaucoma: lowering of the IOP with surgical implantation of an Ahmed valve, regression of neovascularization by argon laser panretinal photocoagulation and intravitreal injection of bevacizumab can be a helpful way to control such a complication.

  3. Evaluation of Corneal Neovascularization Using Optical Coherence Tomography Angiography in Patients With Limbal Stem Cell Deficiency.

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    Oie, Yoshinori; Nishida, Kohji

    2017-11-01

    Detection of the exact area of corneal neovascularization using slit-lamp photography is often difficult. Thus, we evaluated corneal neovascularization in patients with limbal stem cell deficiency using optical coherence tomography angiography (OCTA). Five patients with 5 eyes showing partial or total limbal stem cell deficiency were enrolled. Three eyes had severe corneal scarring. Five 6- × 6-mm images (frontal, upper, lower, nasal, and temporal) were obtained by OCTA. Slit-lamp photography was performed for all patients on the same day. OCTA has 2 advantages over slit-lamp photography for clear demonstration of corneal neovascularization. First, OCTA can show neovascularization in cases with severe corneal opacification. Second, OCTA can detect not only large vessels but also small vessels that cannot be seen by slit-lamp photography. OCTA is a powerful tool for objective evaluation of vascularization in the anterior and posterior segments of the eye. We have demonstrated that OCTA can visualize corneal neovascularization in patients with corneal diseases more clearly than slit-lamp photography.

  4. Anti-vascular endothelial growth factor for neovascular glaucoma.

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    Simha, Arathi; Braganza, Andrew; Abraham, Lekha; Samuel, Prasanna; Lindsley, Kristina

    2013-10-02

    Neovascular glaucoma (NVG) is a potentially blinding secondary glaucoma. It is caused by the formation of abnormal new blood vessels which prevent normal drainage of aqueous from the anterior segment of the eye. Anti-vascular endothelial growth factor (anti-VEGF) agents are specific inhibitors of the primary mediators of neovascularization. Studies have reported the effectiveness of anti-VEGFs for the control of intraocular pressure (IOP) in NVG. To compare the IOP lowering effects of intraocular anti-VEGF agents to no anti-VEGF treatment, as an adjunct to existing modalities for the treatment of NVG. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 12), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE, (January 1950 to January 2013), EMBASE (January 1980 to January 2013), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to January 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov/) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 11 January 2013. We included randomized controlled trials (RCTs) and quasi-RCTs of people treated with anti-VEGF agents for NVG. Two authors independently assessed the search results for trials to be included in the review. Discrepancies were resolved by discussion with a third author. Since no trial met our inclusion criteria, no assessment of risk of bias or meta-analysis was undertaken. No RCTs were found that met the inclusion criteria for this review. Two RCTs of anti-VEGF agents for treating NVG were not included in the review due to the heterogeneity and uncontrolled assignment of adjunct treatments received by the

  5. Celastrol nanoparticles inhibit corneal neovascularization induced by suturing in rats

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    Li ZR

    2012-03-01

    Full Text Available Zhanrong Li1, Lin Yao1, Jingguo Li2, Wenxin Zhang1, Xianghua Wu1, Yi Liu1, Miaoli Lin1, Wenru Su1, Yongping Li1, Dan Liang11State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, 2School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou, People's Republic of ChinaPurpose: Celastrol, a traditional Chinese medicine, is widely used in anti-inflammation and anti-angiogenesis research. However, the poor water solubility of celastrol restricts its further application. This paper aims to study the effect of celastrol nanoparticles (CNPs on corneal neovascularization (CNV and determine the possible mechanism.Methods: To improve the hydrophilicity of celastrol, celastrol-loaded poly(ethylene glycol-block-poly(ε-caprolactone nanopolymeric micelles were developed. The characterization of CNPs was measured by dynamic light scattering and transmission electron microscopy analysis. Celastrol loading content and release were assessed by ultraviolet-visible analysis and high performance liquid chromatography, respectively. In vitro, human umbilical vein endothelial cell proliferation and capillary-like tube formation were assayed. In vivo, suture-induced CNV was chosen to evaluate the effect of CNPs on CNV in rats. Immunohistochemistry for CD68 assessed the macrophage infiltration of the cornea on day 6 after surgery. Real-time quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay were used to evaluate the messenger ribonucleic acid and protein levels, respectively, of vascular endothelial growth factor, matrix metalloproteinase 9, and monocyte chemoattractant protein 1 in the cornea.Results: The mean diameter of CNPs with spherical shape was 48 nm. The celastrol loading content was 7.36%. The release behavior of CNPs in buffered solution (pH 7.4 showed a typical two-phase release profile. CNPs inhibited the proliferation of human umbilical vein endothelial

  6. Clinical observation of two operation methods for neovascular glaucoma

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    Peng Zhang

    2013-11-01

    Full Text Available AIM: To evaluate the clinical effect of two different surgical treatments for neovascular glaucoma(NVG.METHODS: A total of 30 NVG inpatients(30 eyesat our hospital from April 2008 to December 2011 were reviewed. Patients were divided into two groups according to the different surgical treatments. In group A, 12 cases(12 eyeswere treated with Ahmed glaucoma valve(AGVimplantation and in group B, 18 cases(18 eyeswere treated with semiconductor diode laser photocoagulation transscleral cyclophotocoagulation(TSCPC. Intraocular pressure, visual acuity and complications were compared between two groups postoperatively.RESULTS: The postoperative IOP was significantly lower in each group(PPP>0.05in IOP 1 month after surgery. Visual acuity: in group A, the visual acuity was improved in 3 eyes, unchanged in 7 eyes and worsened in 2 eyes.; in group B, the visual acuity was improved in 3 eyes, unchanged in 12 eyes and worsened in 3 eyes. Postoperative complications: in group A, eyeball pain and corneal edema were found in 5 cases(41.7%, shallow anterior chamber in 3 cases(25%, anterior chamber fibroid exudation in 2 cases(16.7%, hyphema in 3 cases(25%; in group B, eyeball pain atearly stage after surgery were found in 10 cases(55.6% , corneal edema in 11 cases(61.1%, anterior chamber fibroid exudation in 5 cases(27.8%, hyphema in 6 cases(33.3%.CONCLUSION: AGV implantation and TSCPC are both effective surgical treatment methods for NVG. AGV implantation is a filtration surgery, which is relatively safe. TSCPC is more economical and suitable for glaucoma of advanced or absolute stage.

  7. THE GOAL OF VALUE-BASED MEDICINE ANALYSES: COMPARABILITY. THE CASE FOR NEOVASCULAR MACULAR DEGENERATION

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    Brown, Gary C.; Brown, Melissa M.; Brown, Heidi C.; Kindermann, Sylvia; Sharma, Sanjay

    2007-01-01

    Purpose To evaluate the comparability of articles in the peer-reviewed literature assessing the (1) patient value and (2) cost-utility (cost-effectiveness) associated with interventions for neovascular age-related macular degeneration (ARMD). Methods A search was performed in the National Library of Medicine database of 16 million peer-reviewed articles using the key words cost-utility, cost-effectiveness, value, verteporfin, pegaptanib, laser photocoagulation, ranibizumab, and therapy. All articles that used an outcome of quality-adjusted life-years (QALYs) were studied in regard to (1) percent improvement in quality of life, (2) utility methodology, (3) utility respondents, (4) types of costs included (eg, direct healthcare, direct nonhealthcare, indirect), (5) cost bases (eg, Medicare, National Health Service in the United Kingdom), and (6) study cost perspective (eg, government, societal, third-party insurer). To qualify as a value-based medicine analysis, the patient value had to be measured using the outcome of the QALYs conferred by respective interventions. As with value-based medicine analyses, patient-based time tradeoff utility analysis had to be utilized, patient utility respondents were necessary, and direct medical costs were used. Results Among 21 cost-utility analyses performed on interventions for neovascular macular degeneration, 15 (71%) met value-based medicine criteria. The 6 others (29%) were not comparable owing to (1) varying utility methodology, (2) varying utility respondents, (3) differing costs utilized, (4) differing cost bases, and (5) varying study perspectives. Among value-based medicine studies, laser photocoagulation confers a 4.4% value gain (improvement in quality of life) for the treatment of classic subfoveal choroidal neovascularization. Intravitreal pegaptanib confers a 5.9% value gain (improvement in quality of life) for classic, minimally classic, and occult subfoveal choroidal neovascularization, and photodynamic therapy

  8. Clinical correlates of common corneal neovascular diseases:a literature review

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    Nizar Saleh Abdelfattah

    2015-02-01

    Full Text Available A large subset of corneal pathologies involves the formation of new blood and lymph vessels (neovascularization, leading to compromised visual acuity. This article aims to review the clinical causes and presentations of corneal neovascularization (CNV by examining the mechanisms behind common CNV-related corneal pathologies, with a particular focus on herpes simplex stromal keratitis, contact lenses-induced keratitis and CNV secondary to keratoplasty. Moreover, we reviewed CNV in the context of different types of corneal transplantation and keratoprosthesis, and summarized the most relevant treatments available so far.

  9. Systemic diffuse large B-cell lymphoma masquerading as neovascular glaucoma.

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    Bawankar, Pritam; Das, Dipankar; Bhattacharjee, Harsha; Tayab, Shahinur; Deori, Nilutparna; Paulbuddhe, Vivek; Dhar, Shriya; Deka, Apurba

    2018-02-01

    We describe a case of spontaneous hyphema associated with anterior uveitis presents in a 69-year old female as the prominent sign of the intraocular spread of systemic diffuse large B-cell lymphoma (DLBCL). She had a history of diabetes and initially misdiagnosed as neovascular glaucoma. Clinical history of systemic lymphoma, characteristic findings on B-scan ultrasonography and magnetic resonance imaging scan, and identification of atypical lymphoid cells in aqueous sample established the diagnosis of intraocular metastasis of systemic DLBCL. Therefore, this report highlights that life-threatening malignant systemic lymphoma may masquerade as anterior segment ocular inflammation or neovascular glaucoma.

  10. The goal of value-based medicine analyses: comparability. The case for neovascular macular degeneration.

    Science.gov (United States)

    Brown, Gary C; Brown, Melissa M; Brown, Heidi C; Kindermann, Sylvia; Sharma, Sanjay

    2007-01-01

    To evaluate the comparability of articles in the peer-reviewed literature assessing the (1) patient value and (2) cost-utility (cost-effectiveness) associated with interventions for neovascular age-related macular degeneration (ARMD). A search was performed in the National Library of Medicine database of 16 million peer-reviewed articles using the key words cost-utility, cost-effectiveness, value, verteporfin, pegaptanib, laser photocoagulation, ranibizumab, and therapy. All articles that used an outcome of quality-adjusted life-years (QALYs) were studied in regard to (1) percent improvement in quality of life, (2) utility methodology, (3) utility respondents, (4) types of costs included (eg, direct healthcare, direct nonhealthcare, indirect), (5) cost bases (eg, Medicare, National Health Service in the United Kingdom), and (6) study cost perspective (eg, government, societal, third-party insurer). To qualify as a value-based medicine analysis, the patient value had to be measured using the outcome of the QALYs conferred by respective interventions. As with value-based medicine analyses, patient-based time tradeoff utility analysis had to be utilized, patient utility respondents were necessary, and direct medical costs were used. Among 21 cost-utility analyses performed on interventions for neovascular macular degeneration, 15 (71%) met value-based medicine criteria. The 6 others (29%) were not comparable owing to (1) varying utility methodology, (2) varying utility respondents, (3) differing costs utilized, (4) differing cost bases, and (5) varying study perspectives. Among value-based medicine studies, laser photocoagulation confers a 4.4% value gain (improvement in quality of life) for the treatment of classic subfoveal choroidal neovascularization. Intravitreal pegaptanib confers a 5.9% value gain (improvement in quality of life) for classic, minimally classic, and occult subfoveal choroidal neovascularization, and photodynamic therapy with verteporfin confers

  11. Radiation therapy for subfoveal chroidal neovascularization complicating age-related macular degeneration

    International Nuclear Information System (INIS)

    Kawabata, Yuko; Ohara, Masae; Ishii, Kentaro

    2004-01-01

    We evaluated the effect of low-dose external beam irradiation on the visual function of 14 eyes with subfoveal chroidal neovascularization complicating age-related macular degeneration. Patient received external beam irradiation at a dose of 20 Gy in 10 fraction of 2 Gy. After treatment the visual function improved in 2 eyes, remained stable in 8 eyes and deteriorated in 4 eyes. At the last examination visual function improved in 1 eyes, remained stable in 2 eyes and deteriorated in 5 eyes. The low-dose irradiation is potentially beneficial for subfoveal chroidal neovascularization complicating age-related macular degeneration. (author)

  12. Application of Ranibizumab at perioperative period of compound trabeculectomy in patients with neovascular glaucoma

    Directory of Open Access Journals (Sweden)

    Su-Ying Qin

    2016-01-01

    Full Text Available AIM:To observe the effect of intravitreal injection of Ranibizumab at perioperative period of compound trabeculectomy on iris neovascularization, intraocular pressure(IOPfor patients with neovascular glaucoma(NVG.METHODS:Intravitreal injection of ranibizumab, compound trabeculectomy and panretinal photocoagulation were given to 38 patients(38 eyeswith neovascular glaucoma, which could not be controlled by drugs, from January 2013 to January 2014 in Anyang Eye Hospital. Iris neovascularization, IOP and changes of visual acuity were observed before and after treatments. The patients were followed up for 6mo after treatments.RESULTS: Seven days after intravitreal injection, 36 cases(94.74%had complete regression of iris neovascularization. Two cases(5.26%had regression of small blood vessels in the iris, a little thick blood vessels were remained. At 1mo after compound trabeculectomy, iris neovascularization in all patients were subsided; at 3mo after treatments, the iris neovascularization in 8 patients(21.05%were performed again, and accepted intravitreal injection of ranibizumab again. Six months after the first treatments, all patients showed no iris neovascularization. The mean IOP before injection was 42.82±10.29mmHg. At 5d after the drug injection was 39.13±9.71mmHg. Before and after the drug injection, change of IOP was not statistically significant(q=2.65, P>0.05. At 1wk,1,3 and 6mo after compound trabeculectomy, IOP was 10.53±1.81mmHg, 10.11±1.73mmHg, 11.29±2.49mmHg, 12.58±3.01mmHg,which decreased significantly(q=23.15,23.46,22.61,21.68, all Pq=20.51,20.81,19.96,19.04, all PCONCLUSION: Intravitreal injection of ranibizumab at perioperative period of compound trabeculectomy can effectively improve the success rate of the surgeries and reduce risk of complications, and the effect is certainly safe.

  13. Multilayered pigment epithelial detachment in neovascular age-related macular degeneration

    DEFF Research Database (Denmark)

    Rahimy, Ehsan; Freund, K Bailey; Larsen, Michael

    2014-01-01

    , hyperreflective bands, termed a "multilayered PED," which is often seen in conjunction with neovascular tissue adherent to the undersurface of the retinal pigment epithelium monolayer. On the basis of previous histopathologic correlations, these bands may represent a fibrous tissue complex with contractile...... properties. An associated hyporeflective space, termed a "pre-choroidal cleft," separates the fusiform complex from the underlying choroid and may be due to contraction, the exudation of fluid, or both. Many of these eyes maintain good visual acuity, presumably because the neovascular and cicatricial process...

  14. Modeling the Non-functional Requirements in the Context of Usability, Performance, Safety and Security

    OpenAIRE

    Sadiq, Mazhar

    2007-01-01

    Requirement engineering is the most significant part of the software development life cycle. Until now great emphasis has been put on the maturity of the functional requirements. But with the passage of time it reveals that the success of software development does not only pertain to the functional requirements rather non-functional requirements should also be taken into consideration. Among the non-functional requirements usability, performance, safety and security are considered important. ...

  15. Intravitreal itraconazole inhibits laser-induced choroidal neovascularization in rats.

    Directory of Open Access Journals (Sweden)

    Jeong Hun Bae

    Full Text Available Choroidal neovascularization (CNV is a major cause of severe visual loss in patients with age-related macular degeneration (AMD. Recently, itraconazole has shown potent and dose-dependent inhibition of tumor-associated angiogenesis. We evaluated the anti-angiogenic effect of itraconazole in a rat model of laser-induced CNV. After laser photocoagulation in each eye to cause CNV, right eyes were administered intravitreal injections of itraconazole; left eyes received balanced salt solution (BSS as controls. On day 14 after laser induction, fluorescein angiography (FA was used to assess abnormal vascular leakage. Flattened retinal pigment epithelium (RPE-choroid tissue complex was stained with Alexa Fluor 594-conjugated isolectin B4 to measure the CNV area and volume. Vascular endothelial growth factor receptor 2 (VEGFR2 mRNA and protein expression was determined 1, 4, 7, and 14 days after intravitreal injection by quantitative RT-PCR or Western blot. VEGF levels were analyzed by enzyme-linked immunosorbent assay (ELISA. Intravitreal itraconazole significantly reduced leakage from CNV as assessed by FA and CNV area and volume on flat mounts compared with intravitreal BSS (p = 0.002 for CNV leakage, p<0.001 for CNV area and volume. Quantitative RT-PCR showed significantly lower expression of VEGFR2 mRNA in the RPE-choroid complexes of itraconazole-injected eyes than those of BSS-injected eyes on days 7 and 14 (p = 0.003 and p = 0.006. Western blots indicated that VEGFR2 was downregulated after itraconazole treatment. ELISA showed a significant difference in VEGF level between itraconazole-injected and BSS-injected eyes on days 7 and 14 (p = 0.04 and p = 0.001. Our study demonstrated that intravitreal itraconazole significantly inhibited the development of laser-induced CNV in rats. Itraconazole had anti-angiogenic activity along with the reduction of VEGFR2 and VEGF levels. Itraconazole may prove beneficial for treating CNV as an alternative or

  16. Psychometrics of Multiple Choice Questions with Non-Functioning Distracters: Implications to Medical Education.

    Science.gov (United States)

    Deepak, Kishore K; Al-Umran, Khalid Umran; AI-Sheikh, Mona H; Dkoli, B V; Al-Rubaish, Abdullah

    2015-01-01

    The functionality of distracters in a multiple choice question plays a very important role. We examined the frequency and impact of functioning and non-functioning distracters on psychometric properties of 5-option items in clinical disciplines. We analyzed item statistics of 1115 multiple choice questions from 15 summative assessments of undergraduate medical students and classified the items into five groups by their number of non-functioning distracters. We analyzed the effect of varying degree of non-functionality ranging from 0 to 4, on test reliability, difficulty index, discrimination index and point biserial correlation. The non-functionality of distracters inversely affected the test reliability and quality of items in a predictable manner. The non-functioning distracters made the items easier and lowered the discrimination index significantly. Three non-functional distracters in a 5-option MCQ significantly affected all psychometric properties (p psychometrically as effective as 5-option items. Our study reveals that a multiple choice question with 3 functional options provides lower most limit of item format that has adequate psychometric property. The test containing items with less number of functioning options have significantly lower reliability. The distracter function analysis and revision of nonfunctioning distracters can serve as important methods to improve the psychometrics and reliability of assessment.

  17. Evaluation of 10 AMD Associated Polymorphisms as a Cause of Choroidal Neovascularization in Highly Myopic Eyes.

    Directory of Open Access Journals (Sweden)

    Alvaro Velazquez-Villoria

    Full Text Available Choroidal neovascularization (CNV commonly occurs in age related macular degeneration and pathological myopia patients. In this study we conducted a case-control prospective study including 431 participants. The aim of this study was to determine the potential association between 10 single nucleotide polymorphisms (SNPs located in 4 different genetic regions (CFI, COL8A1, LIPC, and APOE, and choroidal neovascularization in age-related macular degeneration and the development of choroidal neovascularization in highly myopic eyes of a Caucasian population. Univariate and multivariate logistic regression analysis adjusted for age, sex and hypertension was performed for each allele, genotype and haplotype frequency analysis. We found that in the univariate analysis that both single-nucleotide polymorphisms in COL8A1 gene (rs13095226 and rs669676 together with age, sex and hypertension were significantly associated with myopic CNV development in Spanish patients (p0.05; however, analysis of the axial length between genotypes of rs13095226 revealed an important influence of COL8A1 in the development of CNV in high myopia. Furthermore we conducted a meta-analysis of COL8A1, CFI and LIPC genes SNPs (rs669676, rs10033900 and rs10468017 and found that only rs669676 of these SNPs were associated with high myopia neovascularization.

  18. Inhibition of corneal neovascularization by recombinant adenovirus-mediated sFlk-1 expression

    International Nuclear Information System (INIS)

    Yu Hui; Wu Jihong; Li Huiming; Wang Zhanli; Chen Xiafang; Tian Yuhua; Yi Miaoying; Ji Xunda; Ma Jialie; Huang Qian

    2007-01-01

    The interaction of vascular endothelial growth factor (VEGF) and its receptors (Flt-1, Flk-1/KDR) is correlated with neovascularization in the eyes. Therefore, blocking the binding of VEGF and the corresponding receptor has become critical for inhibiting corneal neovascularization. In this study, we have expressed the cDNA for sFlk-1 under the control of cytomegalovirus immediate-early promoter (CMV) from an E1/partial E3 deleted replication defective recombinant adenovirus, and Ad.sflk-1 expression was determined by Western blotting. We have shown that conditioned media from Ad.sflk-1-infected ARPE-19 cells significantly reduced VEGF-induced human umbilical vein endothelial cells (HUVEC) and murine endothelial cells (SVEC) proliferation in vitro compared with the control vector. In vivo, adenoviral vectors expressing green fluorescent protein alone (Ad.GFP) were utilized to monitor gene transfer to the cornea. Moreover, in the models of corneal neovascularization, the injection of Ad.sflk-1 (10 8 PFU) into the anterior chamber could significantly inhibit angiogenic changes compared with Ad.null-injected and vehicle-injected models. Immunohistochemical analysis showed that corneal endothelial cells and corneal stroma of cauterized rat eyes were efficiently transduced and expressed sFlk-1. These results not only support that adenoviral vectors are capable of high-level transgene expression but also demonstrate that Ad.sflk-1 gene therapy might be a feasible approach for inhibiting the development of corneal neovascularization

  19. Swept-source optical coherence tomography angiography for choroidal neovascularization after bevacizumab and photodynamic therapy

    Directory of Open Access Journals (Sweden)

    Jesse J. Jung

    2016-04-01

    Conclusion: We report the first SS-OCTA images of successfully treated extrafoveal NV after combination PDT and ant-VEGF therapy. Early treatment of extrafoveal NV may improve our ability to treat mixed type 1 and 2 NV before these neovascular complexes mature from repetitive anti-VEGF treatment.

  20. Natural history of choroidal neovascularization after surgical induction in an animal model

    DEFF Research Database (Denmark)

    Lassota, Nathan; Kiilgaard, Jens Folke; la Cour, Morten

    2008-01-01

    PURPOSE: To study an expanded time course of surgically induced choroidal neovascularization (CNV) in a porcine model applying fluorescence angiography and immunohistology. METHODS: Twenty-two porcine eyes underwent vitrectomy, a retinal bleb was raised and the detached retina perforated using en...

  1. Lahore general hospital protocol for treatment of neovascular glaucoma caused by retinal disease

    International Nuclear Information System (INIS)

    Khaqan, H.A.; Haider, S.A.

    2013-01-01

    To evaluate efficacy of LGH (Lahore General Hospital) protocol for treatment of neovascular glaucoma caused by retinal diseases. Material and Methods: This case series was performed on 9 consecutive eyes of nine patients with uncontrolled neovascular glaucoma at Department of Ophthalmology, Unit II, Lahore General Hospital/PGMI, Lahore. All nine patients completed six months follow up. Among them 6 patients were having PDR (proliferative diabetic retinopathy) and 3 patients having CRVO (central retinal vein occlusion). LGH protocol for treatment of neovascular glaucoma was: To give intravitreal injection of avastin and then PRP (Pan Retinal Photocoagulation) or Trabeculectomy with MMC (Mitomycin C), if PRP and intravitreal avastin fails to control the intra ocular-pressure (IOP). Results: Three patients had IOP control after intravitreal injection of avastin and PRP, 5 patients had uncontrolled IOP after intravitreal avastin and two sessions of PRP, so they under went trabeculectomy with MMC. One patient had uncontrolled IOP despite of full treatment protocol. All other 8 patients IOP remained stable for six months. Conclusion: Significant decrease in intraocular pressure was achieved after observing LGH protocol for treatment of NVG (Neovascular Glaucoma) caused by retinal diseases. (author)

  2. Intravitreal bevacizumab as therapy for refractory neovascular glaucoma secondary to iris metastasis of breast carcinoma

    Directory of Open Access Journals (Sweden)

    Stephanie Vale

    2018-03-01

    Conclusions & importance: A single intravitreal bevacizumab injection may be sufficient to achieve palliative control of neovascular glaucoma secondary to iris breast cancer metastasis. To our knowledge, this is the first case report in which a single intravitreal bevacizumab injection was used for the effective management of this condition.

  3. Hedgehog Signaling Components Are Expressed in Choroidal Neovascularization in Laser-induced Retinal Lesion

    International Nuclear Information System (INIS)

    Nochioka, Katsunori; Okuda, Hiroaki; Tatsumi, Kouko; Morita, Shoko; Ogata, Nahoko; Wanaka, Akio

    2016-01-01

    Choroidal neovascularization is one of the major pathological changes in age-related macular degeneration, which causes devastating blindness in the elderly population. The molecular mechanism of choroidal neovascularization has been under extensive investigation, but is still an open question. We focused on sonic hedgehog signaling, which is implicated in angiogenesis in various organs. Laser-induced injuries to the mouse retina were made to cause choroidal neovascularization. We examined gene expression of sonic hedgehog, its receptors (patched1, smoothened, cell adhesion molecule down-regulated by oncogenes (Cdon) and biregional Cdon-binding protein (Boc)) and downstream transcription factors (Gli1-3) using real-time RT-PCR. At seven days after injury, mRNAs for Patched1 and Gli1 were upregulated in response to injury, but displayed no upregulation in control retinas. Immunohistochemistry revealed that Patched1 and Gli1 proteins were localized to CD31-positive endothelial cells that cluster between the wounded retina and the pigment epithelium layer. Treatment with the hedgehog signaling inhibitor cyclopamine did not significantly decrease the size of the neovascularization areas, but the hedgehog agonist purmorphamine made the areas significantly larger than those in untreated retina. These results suggest that the hedgehog-signaling cascade may be a therapeutic target for age-related macular degeneration

  4. Single-Chain Antibody Fragment VEGF Inhibitor RTH258 for Neovascular Age-Related Macular Degeneration

    DEFF Research Database (Denmark)

    Holz, Frank G; Dugel, Pravin U.; Weissgerber, Georges

    2016-01-01

    Purpose To assess the safety and efficacy of different doses of RTH258 applied as single intravitreal administration compared with ranibizumab 0.5 mg in patients with neovascular age-related macular degeneration (AMD). Design Six-month, phase 1/2, prospective, multicenter, double-masked, randomized...

  5. Visual outcomes in relation to time to treatment in neovascular age-related macular degeneration

    DEFF Research Database (Denmark)

    Rasmussen, Annette; Bloch, Sara Brandi; Fuchs, Josefine

    2015-01-01

    PURPOSE: To study the relation between the interval from diagnosis to initiation of intravitreal injection therapy and visual outcome in neovascular age-related macular degeneration (nAMD) and to report changes over time in fellow-eye status. METHODS: Retrospective chart review. The study included...

  6. T-cell differentiation and CD56+ levels in polypoidal choroidal vasculopathy and neovascular age-related macular degeneration.

    Science.gov (United States)

    Subhi, Yousif; Nielsen, Marie Krogh; Molbech, Christopher Rue; Oishi, Akio; Singh, Amardeep; Nissen, Mogens Holst; Sørensen, Torben Lykke

    2017-11-20

    Polypoidal choroidal vasculopathy (PCV) and neovascular age-related macular degeneration (AMD) are prevalent age-related diseases characterized by exudative changes in the macula. Although they share anatomical and clinical similarities, they are also distinctly characterized by their own features, e.g. vascular abnormalities in PCV and drusen-mediated progression in neovascular AMD. PCV remains etiologically uncharacterized, and ongoing discussion is whether PCV and neovascular AMD share the same etiology or constitute two substantially different diseases. In this study, we investigated T-cell differentiation and aging profile in human patients with PCV, patients with neovascular AMD, and age-matched healthy control individuals. Fresh venous blood was prepared for flow cytometry to investigate CD4 + and CD8 + T-cell differentiation (naïve, central memory, effector memory, effector memory CD45ra + ), loss of differentiation markers CD27 and CD28, and expression of aging marker CD56. Patients with PCV were similar to the healthy controls in all aspects. In patients with neovascular AMD we found significantly accelerated T-cell differentiation (more CD28 - CD27 - cells) and aging (more CD56 + cells) in the CD8 + T-cell compartment. These findings suggest that PCV and neovascular AMD are etiologically different in terms of T cell immunity, and that neovascular AMD is associated with T-cell immunosenescence.

  7. The neuroradiological study of craniopharyngiomas; A comparison with non-functioning pituitary macroadenomas

    Energy Technology Data Exchange (ETDEWEB)

    Oikawa, Susumu; Takemae, Toshiki; Kobayashi, Shigeaki (Shinshu Univ., Matsumoto, Nagano (Japan). Faculty of Medicine)

    1992-06-01

    The neuroradiological manifestations of 10 surgically verified craniopharyngiomas are retrospectively studied and compared with those of 8 non-functioning pituitary macroadenomas. The saucer-like appearance of the sella turcica on a craniogram was noted in 2 of the 10 craniopharyngiomas and in 2 of the 8 pituitary adenomas. A ballooning of the sella turcica was observed in one of the 10 craniopharyngiomas and in 5 of the 8 pituitary adenomas. Calcification on CT scan was presented in only 5 craniopharyngiomas. On a plain CT scan, no craniopharyngioma manifested any high-density mass except calcification. Four pituitary adenomas showed a slightly high density, though. A cystic lesion was revealed in all the craniopharyngiomas and in 4 pituitary adenomas. All the craniopharyngiomas except for one intrasellar type and all the pituitary adenomas were enhanced with a contrast medium. The solid portion in one craniopharyngioma and in one pituitary adenoma was high-intensity on T[sub 1]-weighted MRI. The cystic portion in 4 craniopharyngiomas and in 2 pituitary adenomas manifested a high intensity on a T[sub 1]-weighted image. A normal pituitary gland located on the floor of the sella was disclosed in all the craniopharyngiomas on a sagittal T[sub 1]-weighted image; however in all the pituitary adenomas, no normal pituitary gland was found at least not on the floor of the sella. The presence of a normal pituitary gland on the sellar floor on sagittal T[sub 1]-weighted MRI may be a new differential diagnostic point between craniopharyngioma and pituitary macroadenoma. Calcification, cystic formation, and density on a plain CT scan seem to be useful evidence for diagnosis. (author).

  8. Efficacy of intravitreal ranibizumab combined with Ahmed glaucoma valve implantation for the treatment of neovascular glaucoma.

    Science.gov (United States)

    Tang, Min; Fu, Yang; Wang, Ying; Zheng, Zhi; Fan, Ying; Sun, Xiaodong; Xu, Xun

    2016-01-09

    Neovascular glaucoma is a refractive glaucoma. Recently, anti-VEGF factors have been used alone or in combination for the treatment of neovascular glaucoma. However, the medium- and long-term efficacy of such drugs remains to be evaluated. This study was to determine the efficacy of intravitreal ranibizumab combined with Ahmed glaucoma valve implantation for the treatment of neovascular glaucoma. In this prospective non-randomized study, 43 neovascular glaucoma patients (43 eyes) were assigned to receive either 0.5 mg intravitreal ranibizumab for three to 14 days before Ahmed glaucoma valve implantation (injection group, n = 21) or Ahmed glaucoma valve implantation alone (control group, n = 22). The patients were followed up for six to 12 months. Differences in surgical success rate, intraocular pressure, best corrected visual acuity, anti-glaucoma medications and postoperative complications were compared between the two groups. Surgical success was defined as IOP > = 6 mm Hg and glaucoma medications, and without severe complications or reoperation. Of the 43 patients, 40 completed the 6-month follow-up and 37 completed the 1-year follow-up. Success rate was 73.7% vs. 71.4% at six months and 72.2% vs. 68.4% at 12 months in the injection group and the control group respectively. No significant difference was noted between the two groups (six months: P = 0.87, 12 months: P = 1.00). There were no significant differences in the two groups with respect to intraocular pressure, best corrected visual acuity, anti-glaucoma medications or postoperative complications at six months or 12 months. Single intravitreal ranibizumab (0.5 mg) before surgery has no significant effect on the medium- or long-term outcomes of neovascular glaucoma treated with Ahmed glaucoma valve implantation. Chinese Clinical Trial Registry ( ChiCTR-OOC-14005709, Trial registration date: 2014-12-01).

  9. IQGAP1 is involved in post-ischemic neovascularization by regulating angiogenesis and macrophage infiltration.

    Directory of Open Access Journals (Sweden)

    Norifumi Urao

    2010-10-01

    Full Text Available Neovascularization is an important repair mechanism in response to ischemic injury and is dependent on inflammation, angiogenesis and reactive oxygen species (ROS. IQGAP1, an actin-binding scaffold protein, is a key regulator for actin cytoskeleton and motility. We previously demonstrated that IQGAP1 mediates vascular endothelial growth factor (VEGF-induced ROS production and migration of cultured endothelial cells (ECs; however, its role in post-ischemic neovascularization is unknown.Ischemia was induced by left femoral artery ligation, which resulted in increased IQGAP1 expression in Mac3(+ macrophages and CD31(+ capillary-like ECs in ischemic legs. Mice lacking IQGAP1 exhibited a significant reduction in the post-ischemic neovascularization as evaluated by laser Doppler blood flow, capillary density and α-actin positive arterioles. Furthermore, IQGAP1(-/- mice showed a decrease in macrophage infiltration and ROS production in ischemic muscles, leading to impaired muscle regeneration and increased necrosis and fibrosis. The numbers of bone marrow (BM-derived cells in the peripheral blood were not affected in these knockout mice. BM transplantation revealed that IQGAP1 expressed in both BM-derived cells and tissue resident cells, such as ECs, is required for post-ischemic neovascularization. Moreover, thioglycollate-induced peritoneal macrophage recruitment and ROS production were inhibited in IQGAP1(-/- mice. In vitro, IQGAP1(-/- BM-derived macrophages showed inhibition of migration and adhesion capacity, which may explain the defective macrophage recruitment into the ischemic tissue in IQGAP1(-/- mice.IQGAP1 plays a key role in post-ischemic neovascularization by regulating, not only, ECs-mediated angiogenesis but also macrophage infiltration as well as ROS production. Thus, IQGAP1 is a potential therapeutic target for inflammation- and angiogenesis-dependent ischemic cardiovascular diseases.

  10. Intravitreal Bevacizumab injection combined duplex technique in treatment of neovascular glaucoma

    Directory of Open Access Journals (Sweden)

    Zheng-Jun Hu

    2015-05-01

    Full Text Available AIM: To observe the clinical curative effect of intravitreal Bevacizumab injection combined duplex technique in treatment of neovascular glaucoma(NVG.METHODS:Totally 25 eyes of 25 patients with NVG who underwent intravitreal Bevacizumab injection of 1.0mg(0.05mL, after the regression of iris neovascularization, 5 eyes with anterior chamber paracentesis fluid auxiliary controlled intraocular pressure. After 2wk, patients were treated by trabeculectomy and phacomulsification(9 eyes were implanted intraocular lens. The changes and complications of intraocular pressure, visual acuity, corneas and neovessels were observed after surgery, and followed up 12mo.RESULTS:After injection Bevacizumab in 25 eyes, iris neovascularization of 20 eyes subsided in 3~5d, and 5 eyes subsided in 7d. After controlling intraocular pressure, count of the corneal endothelial cell were 1 629±226mm2, and none suffered decompensation of corneal endothelium after two-surgery of trabeculectomy and phacomulsification. After followed up 12mo, intraocular pressure of 20 eyes were controlled in normal range; 2 eyes could control in normal range after treated by a kind of anti-glaucoma medicine and 3 eyes was 34~38mmHg after treated by anti-glaucoma medicine. 9 eyes had improved vision after implanted intraocular lens.CONCLUSION:Intravitreal Bevacizumab injection can subside iris and anterior chamber angle neovascularization effectively in a short time and reduce intraocular pressure. It can also reduce the risk of bleeding during operation or after operation. Intravitreal Bevacizumab injection combined with two-surgery of trabeculectomy and phacomulsification can treat neovascular glaucoma effectively.

  11. Analysis of intravitreal using of anti vegf-medications for diseases of fundus accompanied by exudation and neovascularization

    Directory of Open Access Journals (Sweden)

    N. G. Zavgorodnya

    2013-08-01

    Full Text Available Nowadays, new methods of treatment of choroidal neovascularization are being actively developed and introduced in exudative form of age-related macular degeneration (AMD, complicated myopia, diabetic retinopathy and post-thrombotic retinopathy. Medications that block vascular endothelial growth factor (VEGF, which is the main link in the pathogenesis of retinal neovascularization and hyperfiltration, have become widespread. It is known that damage of endothelial cells of retinal vessels occurs in consequence of oxidative stress that leads to the death of pericytes, hyperfiltration of plasma from the vascular bed, hemorrhages and retinal hypoxia. The intracellular concentration of specific protein that regulates the transcription of genes (HIF-1 increases in response to hypoxic damage in the cells of the retina, which leads to increased transcription of the VEGF gene, which acts directly on the epithelium providing regeneration, stimulating the proliferation and neovascularization. Considering this, anti-VEGF medications have found their application in the treatment of choroidal neovascularization in clinical practice. Today, two preparations that block VEGF: selective (pegaptanib and non-selective (ranibizumab are used mostly common. The purpose of this investigation was to study the effectiveness of anti-VEGF medications in patients with choroidal neovascularization of different genesis. The analysis presents the results of 50 patients (50 eyes treatment with choroidal neovascularization on the background of various diseases of the retina. Pegaptanib ("Macugen" was used for the treatment of 35 patients (35 eyes, the rest (15 eyes - ranibizumab ("Lucentis". According to fluorescein angiography the subretinal neovascular membrane was in the stage of activity in all eyes. The effectiveness of the treatment was assessed by visometry, ophthalmoscopy, optical coherence tomography and fluorescein angiography. Application of intravitreal injection of

  12. Adsorption of chromium (Ⅵ) on functionalized and non-functionalized carbon nanotubes

    International Nuclear Information System (INIS)

    Mubarak, Nabisab Mujawar; Thines, Raj Kogiladas; Sajuni, Noor Rosyidah; Ganesan, Poobalan; Jayakumar, Natesan Subramanian; Abdullah, Ezzat Chan; Sahu, Jaya Narayan

    2014-01-01

    We did a comparative study on the adsorption capacity of Cr (Ⅵ) between functionalized carbon nanotubes (CNTs) and non-functionalized CNTs. The statistical analysis reveals that the optimum conditions for the highest removal of Cr (Ⅵ) are at pH 9, with dosage 0.1 gram, agitation speed and time of 120 rpm and 120 minutes, respectively. For the initial concentration of 1.0mg/l, the removal efficiency of Cr (Ⅵ) using functionalized CNTs was 87.6% and 83% of non-functionalized CNTs. The maximum adsorption capacities of functionalized and non-functionalized CNTs were 2.517 and 2.49 mg/g, respectively. Langmuir and Freundlich models were adopted to study the adsorption isotherm, which provided a K L and K F value of 1.217 L/mg and 18.14 mg 1-n L n /g functionalized CNT, while 2.365 L/mg and 2.307 mg 1-n L n /g for non-functionalized CNTs. This result proves that functionalized CNTs are a better adsorbent with a higher adsorption capacity compared with the non-functionalized CNTs

  13. Adsorption of chromium (Ⅵ) on functionalized and non-functionalized carbon nanotubes

    Energy Technology Data Exchange (ETDEWEB)

    Mubarak, Nabisab Mujawar; Thines, Raj Kogiladas; Sajuni, Noor Rosyidah [UCSI University, Kuala Lumpur (Malaysia); Ganesan, Poobalan; Jayakumar, Natesan Subramanian [University of Malaya, Kuala Lumpur (Malaysia); Abdullah, Ezzat Chan [Universiti Teknologi Malaysia, Kuala Lumpur (Malaysia); Sahu, Jaya Narayan [Institut Teknologi Brunei, Tungku Gadong (Brunei Darussalam)

    2014-09-15

    We did a comparative study on the adsorption capacity of Cr (Ⅵ) between functionalized carbon nanotubes (CNTs) and non-functionalized CNTs. The statistical analysis reveals that the optimum conditions for the highest removal of Cr (Ⅵ) are at pH 9, with dosage 0.1 gram, agitation speed and time of 120 rpm and 120 minutes, respectively. For the initial concentration of 1.0mg/l, the removal efficiency of Cr (Ⅵ) using functionalized CNTs was 87.6% and 83% of non-functionalized CNTs. The maximum adsorption capacities of functionalized and non-functionalized CNTs were 2.517 and 2.49 mg/g, respectively. Langmuir and Freundlich models were adopted to study the adsorption isotherm, which provided a K{sub L} and K{sub F} value of 1.217 L/mg and 18.14 mg{sup 1-n}L{sup n}/g functionalized CNT, while 2.365 L/mg and 2.307 mg{sup 1-n}L{sup n}/g for non-functionalized CNTs. This result proves that functionalized CNTs are a better adsorbent with a higher adsorption capacity compared with the non-functionalized CNTs.

  14. Pathologic contrast enhancement of cerebral lesions: A comparative study using stereotactic CT, stereotactic MR imaging, and stereotactic biopsy

    International Nuclear Information System (INIS)

    Earnest, F. IV; Kelly, P.J.; Scheithauer, B.; Kall, B.; Cascino, T.L.; Ehman, R.L.; Forbes, G.

    1986-01-01

    The author compared the pattern and degree of Gd-DTPA dimeglumine contrast enhancement demonstrated on stereotactic MR images with that seen on stereotactic CT images obtained after conventional iodinated contrast agent enhancement and with histopathologic findings on sequential stereotactic brain biopsies. Stereotactic biopsies of the areas that enhanced on CT or MR imaging revealed tumor tissue with neovascularity. Tumor tissue with no or mild neovascularity did not enhance with contrast agent administration. Isolated tumor cells were frequently found beyond the margins of some primary brain neoplasms defined by contrast agent-enhanced MR imaging and CT. The histopathologic findings associated with pathologic contrast agent enhancement are presented

  15. Kilovoltage radiosurgery with gold nanoparticles for neovascular age-related macular degeneration (AMD): a Monte Carlo evaluation

    Science.gov (United States)

    Brivio, D.; Zygmanski, P.; Arnoldussen, M.; Hanlon, J.; Chell, E.; Sajo, E.; Makrigiorgos, G. M.; Ngwa, W.

    2015-12-01

    This work uses Monte Carlo radiation transport simulation to assess the potential benefits of gold nanoparticles (AuNP) in the treatment of neovascular age-related macular degeneration with stereotactic radiosurgery. Clinically, a 100 kVp x-ray beam of 4 mm diameter is aimed at the macula to deliver an ablative dose in a single fraction. In the transport model, AuNP accumulated at the bottom of the macula are targeted with a source representative of the clinical beam in order to provide enhanced dose to the diseased macular endothelial cells. It is observed that, because of the AuNP, the dose to the endothelial cells can be significantly enhanced, allowing for greater sparing of optic nerve, retina and other neighboring healthy tissue. For 20 nm diameter AuNP concentration of 32 mg g-1, which has been shown to be achievable in vivo, a dose enhancement ratio (DER) of 1.97 was found to be possible, which could potentially be increased through appropriate optimization of beam quality and/or AuNP targeting. A significant enhancement in dose is seen in the vicinity of the AuNP layer within 30 μm, peaked at the AuNP-tissue interface. Different angular tilting of the 4 mm beam results in a similar enhancement. The DER inside and in the penumbra of the 4 mm irradiation-field are almost the same while the actual delivered dose is more than one order of magnitude lower outside the field leading to normal tissue sparing. The prescribed dose to macular endothelial cells can be delivered using almost half of the radiation allowing reduction of dose to the neighboring organs such as retina/optic nerve by 49% when compared to a treatment without AuNP.

  16. Kilovoltage radiosurgery with gold nanoparticles for neovascular age-related macular degeneration (AMD): a Monte Carlo evaluation

    International Nuclear Information System (INIS)

    Brivio, D; Zygmanski, P; Makrigiorgos, G M; Ngwa, W; Arnoldussen, M; Hanlon, J; Chell, E; Sajo, E

    2015-01-01

    This work uses Monte Carlo radiation transport simulation to assess the potential benefits of gold nanoparticles (AuNP) in the treatment of neovascular age-related macular degeneration with stereotactic radiosurgery. Clinically, a 100 kVp x-ray beam of 4 mm diameter is aimed at the macula to deliver an ablative dose in a single fraction. In the transport model, AuNP accumulated at the bottom of the macula are targeted with a source representative of the clinical beam in order to provide enhanced dose to the diseased macular endothelial cells. It is observed that, because of the AuNP, the dose to the endothelial cells can be significantly enhanced, allowing for greater sparing of optic nerve, retina and other neighboring healthy tissue. For 20 nm diameter AuNP concentration of 32 mg g −1 , which has been shown to be achievable in vivo, a dose enhancement ratio (DER) of 1.97 was found to be possible, which could potentially be increased through appropriate optimization of beam quality and/or AuNP targeting. A significant enhancement in dose is seen in the vicinity of the AuNP layer within 30 μm, peaked at the AuNP-tissue interface. Different angular tilting of the 4 mm beam results in a similar enhancement. The DER inside and in the penumbra of the 4 mm irradiation-field are almost the same while the actual delivered dose is more than one order of magnitude lower outside the field leading to normal tissue sparing. The prescribed dose to macular endothelial cells can be delivered using almost half of the radiation allowing reduction of dose to the neighboring organs such as retina/optic nerve by 49% when compared to a treatment without AuNP. (paper)

  17. The Importance of Clinical and Diagnostic Markers of Aggression of Non-Functional Pituitary Adenomas

    Directory of Open Access Journals (Sweden)

    Yu.M. Urmanova

    2015-09-01

    Full Text Available Sixty patients with non-functional pituitary adenomas were observed. Most patients had large-cell chromophobe pituitary adenomas (81.6%. Small-cell chromophobe adenomas occurred in 10 % cases. Only 1 patient (3.3 % had giant carcinoma with regrowth and metastasis into the brain. Markers of aggression of non-functional pituitary adenomas are the young age of a patient, expressed first symptoms of disease manifestation, large size of tumor, asymmetry and deformation of pituitary, invasion of tumor to the neighboring tissues/arteries/cavernous sinus, presence of small cell and dark-cell chromophobe adenoma, panhypopituitarism.

  18. Towards an Early Software Effort Estimation Based on Functional and Non-Functional Requirements

    Science.gov (United States)

    Kassab, Mohamed; Daneva, Maya; Ormandjieva, Olga

    The increased awareness of the non-functional requirements as a key to software project and product success makes explicit the need to include them in any software project effort estimation activity. However, the existing approaches to defining size-based effort relationships still pay insufficient attention to this need. This paper presents a flexible, yet systematic approach to the early requirements-based effort estimation, based on Non-Functional Requirements ontology. It complementarily uses one standard functional size measurement model and a linear regression technique. We report on a case study which illustrates the application of our solution approach in context and also helps evaluate our experiences in using it.

  19. CD34/CD133 enriched bone marrow progenitor cells promote neovascularization of tissue engineered constructs in vivo

    Directory of Open Access Journals (Sweden)

    Marietta Herrmann

    2014-11-01

    We demonstrate that this population of cells, isolated in a clinically relevant manner and cultured with autologous growth factors readily promoted neovascularization in tissue engineered constructs in vivo enabling a potential translation into the clinic.

  20. Efficacy and Safety of Monthly versus Quarterly Ranibizumab Treatment in Neovascular Age-related Macular Degeneration: The EXCITE Study

    NARCIS (Netherlands)

    Schmidt-Erfurth, Ursula; Eldem, Bora; Guymer, Robyn; Korobelnik, Jean-Franc̦ois; Schlingemann, Reinier O.; Axer-Siegel, Ruth; Wiedemann, Peter; Simader, Christian; Gekkieva, Margarita; Weichselberger, Andreas

    2011-01-01

    Objective: To demonstrate noninferiority of a quarterly treatment regimen to a monthly regimen of ranibizumab in patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). Design: A 12-month, multicenter, randomized, double-masked,

  1. Relapse of choroidal neovascularization in Bietti's crystalline retinopathy following anti-vascular endothelial growth factor therapy: A case report

    OpenAIRE

    HUA, RUI; CHEN, KANG; HU, YUEDONG; WANG, XINLING; CHEN, LEI

    2015-01-01

    Choroidal neovascularization secondary to retinitis pigmentosa is rarely observed in clinical practice. The present study describes a case of atypical retinitis pigmentosa, crystalline retinal pigmentary degeneration, complicated by choroidal neovascularization (CNV) in a 26-year-old man presenting with blurred vision in the right eye. Heidelberg multimodality imaging was performed to achieve a confirmed diagnosis. Bevacizumab was injected once intravitreally. The 3-month follow-up included v...

  2. Clinical and histological findings after intravitreal injection of bevacizumab (Avastin) in a porcine model of choroidal neovascularization

    DEFF Research Database (Denmark)

    Lassota, Nathan; Prause, Jan Ulrik; Scherfig, Erik

    2010-01-01

    PURPOSE: To examine the effect of intravitreally injected bevacizumab (Avastin) on the histological and angiographic morphology of choroidal neovascularization (CNV) in a masked and placebo-controlled animal study. METHODS: Choroidal neovascularization was induced surgically in 11 porcine eyes by...... these membranes. After a single injection, bevacizumab did not exhibit a size reducing effect on CNV, but it was still present in the membranes 14 days after intravitreal injection....

  3. A 4-Year Longitudinal Study of 555 Patients Treated with Ranibizumab for Neovascular Age-related Macular Degeneration

    DEFF Research Database (Denmark)

    Rasmussen, Annette; Bloch, Sara B; Fuchs, Josefine

    2013-01-01

    To investigate the visual outcome, pattern of discontinuation, ocular complications, and mortality of patients treated with a variable ranibizumab dosing regimen for neovascular age-related macular degeneration (AMD) for 4 years.......To investigate the visual outcome, pattern of discontinuation, ocular complications, and mortality of patients treated with a variable ranibizumab dosing regimen for neovascular age-related macular degeneration (AMD) for 4 years....

  4. Business Process Quality Computation : Computing Non-Functional Requirements to Improve Business Processes

    NARCIS (Netherlands)

    Heidari, F.

    2015-01-01

    Business process modelling is an important part of system design. When designing or redesigning a business process, stakeholders specify, negotiate, and agree on business requirements to be satisfied, including non-functional requirements that concern the quality of the business process. This thesis

  5. Genetic Fuzzy Prediction of Mass Perception in Non-Functional 3D Shapes

    DEFF Research Database (Denmark)

    Achiche, Sofiane

    2010-01-01

    and it is argued that human attributes originate from three different levels of the brain: the visceral level; the behavioral level and the reflective level. This paper focuses upon the visceral level of reaction by automatically building a link between geometric properties of non-functional 3D shapes...

  6. Pattern-Driven Architectural Partitioning. Balancing Functional and Non-functional Requirements

    NARCIS (Netherlands)

    Harrison, Neil; Avgeriou, Paris

    2007-01-01

    One of the vexing challenges of software architecture is the problem of satisfying the functional specifications of the system to be created while at the same time meeting its non-functional needs. In this work we focus on the early stages of the software architecture process, when initial

  7. Towards an Early Software Effort Estimation Based on Functional and Non-Functional Requirements

    NARCIS (Netherlands)

    Kassab, M.; Daneva, Maia; Ormanjieva, Olga; Abran, A.; Braungarten, R.; Dumke, R.; Cuadrado-Gallego, J.; Brunekreef, J.

    2009-01-01

    The increased awareness of the non-functional requirements as a key to software project and product success makes explicit the need to include them in any software project effort estimation activity. However, the existing approaches to defining size-based effort relationships still pay insufficient

  8. A Meta-model for the Assessment of Non-Functional Requirement Size

    NARCIS (Netherlands)

    Kassab, M.; Daneva, Maia; Ormandjieva, O.; Mirandola, R.

    2008-01-01

    Non-functional requirements (NFRs) pose unique challenges in estimating the effort it would take to implement them. This is mainly because of their unique nature; NFRs are subjective, relative, interactive and tending to have a broad impact on the system as a whole. Nevertheless, it is crucial, when

  9. The NERV Methodology: Non-Functional Requirements Elicitation, Reasoning and Validation in Agile Processes

    Science.gov (United States)

    Domah, Darshan

    2013-01-01

    Agile software development has become very popular around the world in recent years, with methods such as Scrum and Extreme Programming (XP). Literature suggests that functionality is the primary focus in Agile processes while non-functional requirements (NFR) are either ignored or ill-defined. However, for software to be of good quality both…

  10. Intravitreal bevacizumab for treatment of choroidal neovascularization associated with osteogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Pukhraj Rishi

    2012-01-01

    Full Text Available A 12-year-old girl, diagnosed of osteogenesis imperfecta, presented with sudden visual loss in the left eye. Investigations revealed an active choroidal neovascular membrane. She underwent treatment with intravitreal Bevacizumab (1.25 mg/0.05 ml. Follow-up at 1 month revealed the development of lacquer crack running through the macula, underlying the fovea. The patient received two re-treatments at 1-month intervals, following which the choroidal neovascularization (CNV regressed completely. However, further progression of lacquer cracks was noted. At the last follow-up, 6 months following the last injection, the fundus remained stable and vision was maintained at 20/200. Considering the natural history of the disease and the increased risk of rupture of the Bruch′s membrane in such eyes, the possible complication of a lacquer crack developing must be borne in mind, before initiating treatment.

  11. Bilateral choroidal neovascularization response to unilateral intravitreal Ranibizumab injection in a patient with angioid streaks

    Directory of Open Access Journals (Sweden)

    Otacílio de Oliveira Maia Júnior

    2013-08-01

    Full Text Available Report of a 48 year-old male with bilateral decrease in vision due to choroidal neovascularization secondary to angioid streaks. Best corrected visual acuity was 20/80 in the right eye and counting fingers at 2 meters on the left eye. Patient underwent intravitreal injection of Ranibizumab (Lucentis in the eye with worse visual acuity. Fifteen days after treatment patient reported better visual acuity on the fellow eye, which was measured to be 20/25. Treatment result was evaluated with visual acuity and optical coherence tomography. The effect of ranibizumab was observed in the treated eye, but the fellow eye had complete resolution of the choroidal neovascularization complex. This result may be a response to systemic absorption of the medication.

  12. Accelerated oxygen-induced retinopathy is a reliable model of ischemia-induced retinal neovascularization.

    Science.gov (United States)

    Villacampa, Pilar; Menger, Katja E; Abelleira, Laura; Ribeiro, Joana; Duran, Yanai; Smith, Alexander J; Ali, Robin R; Luhmann, Ulrich F; Bainbridge, James W B

    2017-01-01

    Retinal ischemia and pathological angiogenesis cause severe impairment of sight. Oxygen-induced retinopathy (OIR) in young mice is widely used as a model to investigate the underlying pathological mechanisms and develop therapeutic interventions. We compared directly the conventional OIR model (exposure to 75% O2 from postnatal day (P) 7 to P12) with an alternative, accelerated version (85% O2 from P8 to P11). We found that accelerated OIR induces similar pre-retinal neovascularization but greater retinal vascular regression that recovers more rapidly. The extent of retinal gliosis is similar but neuroretinal function, as measured by electroretinography, is better maintained in the accelerated model. We found no systemic or maternal morbidity in either model. Accelerated OIR offers a safe, reliable and more rapid alternative model in which pre-retinal neovascularization is similar but retinal vascular regression is greater.

  13. Quality of optometry referrals to neovascular age-related macular degeneration clinic: a prospective study

    OpenAIRE

    Muen, Wisam J; Hewick, Simon A

    2011-01-01

    Objectives To evaluate the quality of referrals to a neovascular age-related macular degeneration clinic from optometrists using the standard Rapid Access Referral Form (RARF) from the Royal College of Ophthalmologists. Design A prospective study. Prospective data were gathered from all optometry referrals using the RARF, between the periods of December 2006 to August 2009. These were assessed for accuracy of history, clinical signs and final diagnosis as compared to a macula expert. Setting ...

  14. Placental growth factor and its potential role in diabetic retinopathy and other ocular neovascular diseases.

    Science.gov (United States)

    Nguyen, Quan Dong; De Falco, Sandro; Behar-Cohen, Francine; Lam, Wai-Ching; Li, Xuri; Reichhart, Nadine; Ricci, Federico; Pluim, Jennifer; Li, William W

    2018-02-01

    The role of vascular endothelial growth factor (VEGF), including in retinal vascular diseases, has been well studied, and pharmacological blockade of VEGF is the gold standard of treatment for neovascular age-related macular degeneration, retinal vein occlusion and diabetic macular oedema. Placental growth factor (PGF, previously known as PlGF), a homologue of VEGF, is a multifunctional peptide associated with angiogenesis-dependent pathologies in the eye and non-ocular conditions. Animal studies using genetic modification and pharmacological treatment have demonstrated a mechanistic role for PGF in pathological angiogenesis. Inhibition decreases neovascularization and microvascular abnormalities across different models, including oxygen-induced retinopathy, laser-induced choroidal neovascularization and in diabetic mice exhibiting retinopathies. High levels of PGF have been found in the vitreous of patients with diabetic retinopathy. Despite these strong animal data, the exact role of PGF in pathological angiogenesis in retinal vascular diseases remains to be defined, and the benefits of PGF-specific inhibition in humans with retinal neovascular diseases and macular oedema remain controversial. Comparative effectiveness research studies in patients with diabetic retinal disease have shown that treatment that inhibits both VEGF and PGF may provide superior outcomes in certain patients compared with treatment that inhibits only VEGF. This review summarizes current knowledge of PGF, including its relationship to VEGF and its role in pathological angiogenesis in retinal diseases, and identifies some key unanswered questions about PGF that can serve as a pathway for future basic, translational and clinical research. © 2016 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation and European Association for Vision & Eye Research.

  15. Neovascularization Potential of Blood Outgrowth Endothelial Cells From Patients With Stable Ischemic Heart Failure Is Preserved

    OpenAIRE

    Dauwe, Dieter; Pelacho, Beatriz; Wibowo, Arief; Walravens, Ann-Sophie; Verdonck, Kristoff; Gillijns, Hilde; Caluwe, Ellen; Pokreisz, Peter; van Gastel, Nick; Carmeliet, Geert; Depypere, Maarten; Maes, Frederik; Vanden Driessche, Nina; Droogne, Walter; Van Cleemput, Johan

    2016-01-01

    Background Blood outgrowth endothelial cells (BOECs) mediate therapeutic neovascularization in experimental models, but outgrowth characteristics and functionality of BOECs from patients with ischemic cardiomyopathy (ICMP) are unknown. We compared outgrowth efficiency and in?vitro and in?vivo functionality of BOECs derived from ICMP with BOECs from age?matched (ACON) and healthy young (CON) controls. Methods and Results We isolated 3.6?0.6 BOEC colonies/100?106 mononuclear cells (MNCs) from 6...

  16. Characteristics of choroidal neovascularization in the complications of age-related macular degeneration prevention trial.

    Science.gov (United States)

    Maguire, Maureen G; Alexander, Judith; Fine, Stuart L

    2008-09-01

    To describe the characteristics of incident choroidal neovascularization (CNV) in observed and treated eyes in the Complications of Age-related Macular Degeneration Prevention Trial (CAPT). Cross-sectional descriptive study within a multicenter, randomized clinical trial. Patients who developed CNV during CAPT follow-up. Inclusion criteria for CAPT specified bilateral large drusen (>or=10 drusen at least 125 micro), visual acuity >or=20/40 in each eye, and age >or=50. Exclusion criteria included CNV and geographic atrophy >1 Macular Photocoagulation Study (MPS) disc area or within 500 micro of the foveal center. One eye of each person was selected randomly for low-intensity laser treatment and the contralateral eye was observed. Fluorescein angiography was performed at baseline, annually for >or=5 years, and whenever there were symptoms of CNV. Trained readers at the CAPT Photograph Reading Center assessed color stereo photographs and angiogram negatives to identify CNV. Choroidal neovascularization was classified by type (predominantly classic CNV, minimally classic CNV, occult only CNV, or scar), location, and area. Visual acuity was measured by certified examiners. Symmetry of characteristics between eyes of bilaterally affected patients was examined. Choroidal neovascularization developed in 282 eyes of 225 patients. At the time of detection, 192 (68%) of the lesions were occult only, 153 (54%) were subfoveal, and 157 (56%) were or=20/40 in 123 (69%) of 179 eyes with visual acuity measured at the time of detection. Choroidal neovascularization developed in both eyes in 57 patients (25%) during CAPT follow-up. Lesions in eyes of bilaterally affected patients were no more similar to each other than affected eyes in 2 different patients. When patients are monitored closely, many CNV lesions can be detected outside of the fovea and when they are relatively small. Early detection may lead to improved long-term visual acuity.

  17. Clinical research of retinal laser photocoagulation and Ranibizumab on the treatment of neovascular glaucoma

    Directory of Open Access Journals (Sweden)

    Wei-Peng Jiang

    2015-10-01

    Full Text Available AIM: To explore the improvement of visual function and the adverse reactions of retinal laser photocoagulation combined with ranibizumab for the treatment of neovascular glaucoma(NVG, to provide the basis for clinical treatment.METHODS: One hundred patients with 129 eyes in our hospital from January 2012 to June 2014 were selected. They were randomly divided into the observation group and the control group, 50 cases in each one. Patients in the control group(67 eyeswere treated with retinal laser photocoagulation, and those in the observation group(62 eyeswere given retinal laser photocoagulation combined with ranibizumab treatment. After the treatment, the degeneration of iris neovascularization, visual acuity, intraocular pressure, ocular fundus and the adverse reactions were evaluated. Optical coherence tomography(OCTwas used to detect retinal nerve fiber layer(RNFLthickness and visual field defect. RESULTS: The degeneration rate of the iris neovascularization in the observation group was 95.2%(59/62, higher than that of the control group 83.6%(56/67(PPPPPP>0.05.CONCLUSION: The treatment of NVG with laser photocoagulation combined with ranibizumab has good clinical efficacy, and can significantly improve the vision and retinal structure and function of the patients, and is safer.

  18. Inhibition of erythropoietin siRNA on corneal neovascularization of rabbit

    Directory of Open Access Journals (Sweden)

    Yu-Shun Xue

    2017-03-01

    Full Text Available AIM: To observe the expression of erythropoietin(EPOon the corneal of rabbit and evaluate the inhibition effect of EPO siRNA on corneal neovascularization(CNV. METHODS: Totally 22 healthy rabbits were randomly divided into 2 groups, which were experimental group and normal control group. Both eyes of rabbits in experimental group were chosen to establish corneal neovascularization model by alkali burn. The morphologic change of corneal was observed with slit lamp microscope and the area of CNV was calculated every day. After alkali burn, the right eye of the experimental group was accepted EPO siRNA injection under the conjunctiva, and the left eye was assigned to be experimental control group. The corneal with CNV was collected for immunohistochemistry at 3d, 7d, 14d, 21d after alkali burn, and the expression of EPO was measured. RESULTS: CNV began growing at the 3d after alkali burn in experimental group, and it was vigorous growing at 7d-14d period. The result of immunohistochemistry shows that the expression of EPO increased after the operation. Compared with experimental group, the rabbits who were treated by EPO siRNA was found with less neovascularization on their corneal, and the expression of EPO decreased. There were statistical significance between the two group at different time(PCONCLUSION: EPO is likely to play an important role on CNV growth, and EPO siRNA can inhibit the growth of CNV by restraining the expression of EPO.

  19. The relationship between vascular endothelial dysfunction and treatment frequency in neovascular age-related macular degeneration.

    Science.gov (United States)

    Ueda-Consolvo, Tomoko; Hayashi, Atsushi; Ozaki, Mayumi; Nakamura, Tomoko; Yagou, Takaaki; Abe, Shinya

    2017-07-01

    To assess the correlation between endothelial dysfunction and frequency of antivascular endothelial growth factor (anti-VEGF) treatment for neovascular age-related macular degeneration (nAMD). We examined 64 consecutive patients with nAMD who were evaluated for endothelial function by use of peripheral arterial tonometry (EndoPAT 2000; Itamar Medical, Caesarea, Israel) at Toyama University Hospital from January 2015. We tallied the number of anti-VEGF treatments between January 2014 and December 2015 and determined the correlation between the number of anti-VEGF injections and endothelial function expressed as the reactive hyperemia index (RHI). Multiple regression analysis was also performed to identify the independent predictors of a larger number of injections. The mean number of anti-VEGF injections was 8.2 ± 3.3. The mean lnRHI was 0.47 ± 0.17. The lnRHI correlated with the number of anti-VEGF injections (r = -0.56; P = 0.030). The multiple regression analysis revealed that endothelial function, neovascular subtypes, and treatment regimens were associated with the number of injections. Endothelial dysfunction may affect the efficacy of anti-VEGF therapy. Neovascular subtypes may also predict a larger number of injections.

  20. Predictors of Visual Response to Intravitreal Bevacizumab for Treatment of Neovascular Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Kai Fang

    2013-01-01

    Full Text Available Purpose. To identify the predictors of visual response to the bevacizumab treatment of neovascular age-related macular degeneration (AMD. Design. A cohort study within the Neovascular AMD Treatment Trial Using Bevacizumab (NATTB. Methods. This was a multicenter trial including 144 participants from the NATTB study. Visual outcomes measured by change in visual acuity (VA score, proportion gaining ≥15 letters, and change in central retinal thickness (CRT were compared among groups according to the baseline, demographic, and ocular characteristics and genotypes. Results. Mean change in the VA score was 9.2 ± 2.3 SD letters with a total of 46 participants (31.9% gaining ≥15 letters. Change in median CRT was −81.5 μm. Younger age, lower baseline VA score, shorter duration of neovascular AMD, and TT genotype in rs10490924 were significantly associated with greater VA score improvement (P=0.028, P<0.001, P=0.02, and P=0.039, resp.. Lower baseline VA score and TT genotype in rs10490924 were significantly associated with a higher likelihood of gaining ≥15 letters (P=0.028, and P=0.021, resp.. Conclusions. Baseline VA and genotype of rs10490924 were both important predictors for visual response to bevacizumab at 6 months. This trial is registered with the Registration no. NCT01306591.

  1. Therapeutic Effects of Topical Netrin-4 Inhibits Corneal Neovascularization in Alkali-Burn Rats

    Science.gov (United States)

    Han, Yun; Shao, Yi; Liu, Tingting; Qu, Yang-Luowa; Li, Wei; Liu, Zuguo

    2015-01-01

    Netrins are secreted molecules involved in axon guidance and angiogenesis. However, the role of netrins in the vasculature remains unclear. Netrin-4 and netrin-1 have been found to be either pro- or antiangiogenic factors. Previously, we found that netrin-1 acts as an anti-angiogenic factor in rats by inhibiting alkali burn-induced corneal neovascularization. Here, we further investigate the effects of netrin-4, another member of the same netrin family, on neovascularization in vitro and in vivo. We found that netrin-4 functions similarly as netrin-1 in angiogenesis. In vitro angiogenesis assay shows that netrin-4 affected human umbilical vein endothelial cell (HUVEC) tube formation, viability and proliferation, apoptosis, migration, and invasion in a dose-dependent manner. Netrin-4 was topically applied in vivo to alkali-burned rat corneas on day 0 (immediately after injury) and/or day 10 post-injury. Netrin-4 subsequently suppressed and reversed corneal neovascularization. Netrin-4 inhibited corneal epithelial and stromal cell apoptosis, inhibited vascular endothelial growth factor (VEGF), but promoted pigment epithelium-derived factor (PEDF) expression, decreased NK-KB p65 expression, and inhibits neutrophil and macrophage infiltration. These results indicate that netrin-4 shed new light on its potential roles in treatmenting for angiogenic diseases that affect the ocular surface, as well as other tissues. PMID:25853509

  2. The Future of Contrast-Enhanced Mammography.

    Science.gov (United States)

    Covington, Matthew F; Pizzitola, Victor J; Lorans, Roxanne; Pockaj, Barbara A; Northfelt, Donald W; Appleton, Catherine M; Patel, Bhavika K

    2018-02-01

    The purpose of this article is to discuss facilitators of and barriers to future implementation of contrast-enhanced mammography (CEM) in the United States. CEM provides low-energy 2D mammographic images analogous to digital mammography and contrast-enhanced recombined images that allow assessment of neovascularity similar to that offered by MRI. The utilization of CEM in the United States is currently low but could increase rapidly given the many potential indications for its clinical use.

  3. Pegaptanib sodium treatment in neovascular age-related macular degeneration: clinical experience in Germany

    Directory of Open Access Journals (Sweden)

    Nikolaus Feucht

    2008-06-01

    Full Text Available Nikolaus Feucht, Huebner Matthias, Chris P Lohmann, Mathias MaierAugenklinik rechts der Isar, Technical University Munich, GermanyBackground: The VEGF Inhibition Study In Ocular Neovascularisation (VISION reported the efficacy of intravitreal (ITV vascular endothelial growth factor (VEGF inhibition with pegaptanib sodium (Macugen® for the treatment of neovascular age-related macular degeneration (AMD. This paper reports clinical experience with pegaptanib sodium for the treatment of occult or minimally classic choroidal neovascularization (CNV due to AMD.Material and methods: The study included 50 eyes (in 49 patients with either occult CNV or minimally classic CNV secondary to neovascular AMD who were not eligible for photodynamic therapy (PDT. Study data were analyzed retrospectively. During the 6-month study, patients were administered an average 2.74 injections of 0.3 mg ITV pegaptanib sodium. Angiography and optical coherence tomography (OCT examinations were carried out and intraocular pressure (IOP and visual acuity (VA were measured at baseline, at 3 months and at 6 months. An eye examination was performed and VA was measured the 2 days following treatment and then again at weeks 4–6, and at 3 and 6 months. OCT, VA, and IOP were also assessed at 1 month.Results: ITV pegaptanib sodium was well tolerated and no treatment complications arose. Mean VA was measured as: 0.37 ± 0.24 at baseline; 0.37 ± 0.25 at 1 month; 0.37 ± 0.25 at 3 months and 0.40 ± 0.26 at 6 months. VA was stabilized in approximately 90% of eyes treated with pegaptanib sodium. OCT examination showed a minimal change in central retinal thickness (CRT during the course of the study, from 251.19 µm at baseline to 251.63 µm at 6 months. No elevation in IOP was measured during treatment at 4–6 months in patients receiving pegaptanib sodium.Conclusions: ITV therapy with pegaptanib sodium for occult and minimally classic CNV secondary to neovascular AMD offered good

  4. In vivo analysis of the time and spatial activation pattern of microglia in the retina following laser-induced choroidal neovascularization.

    Science.gov (United States)

    Crespo-Garcia, Sergio; Reichhart, Nadine; Hernandez-Matas, Carlos; Zabulis, Xenophon; Kociok, Norbert; Brockmann, Claudia; Joussen, Antonia M; Strauss, Olaf

    2015-10-01

    Microglia play a major role in retinal neovascularization and degeneration and are thus potential targets for therapeutic intervention. In vivo assessment of microglia behavior in disease models can provide important information to understand patho-mechanisms and develop therapeutic strategies. Although scanning laser ophthalmoscope (SLO) permits the monitoring of microglia in transgenic mice with microglia-specific GFP expression, there are fundamental limitations in reliable identification and quantification of activated cells. Therefore, we aimed to improve the SLO-based analysis of microglia using enhanced image processing with subsequent testing in laser-induced neovascularization (CNV). CNV was induced by argon laser in MacGreen mice. Microglia was visualized in vivo by SLO in the fundus auto-fluorescence (FAF) mode and verified ex vivo using retinal preparations. Three image processing algorithms based on different analysis of sequences of images were tested. The amount of recorded frames was limiting the effectiveness of the different algorithms. Best results from short recordings were obtained with a pixel averaging algorithm, further used to quantify spatial and temporal distribution of activated microglia in CNV. Morphologically, different microglia populations were detected in the inner and outer retinal layers. In CNV, the peak of microglia activation occurred in the inner layer at day 4 after laser, lacking an acute reaction. Besides, the spatial distribution of the activation changed by the time over the inner retina. No significant time and spatial changes were observed in the outer layer. An increase in laser power did not increase number of activated microglia. The SLO, in conjunction with enhanced image processing, is suitable for in vivo quantification of microglia activation. This surprisingly revealed that laser damage at the outer retina led to more reactive microglia in the inner retina, shedding light upon a new perspective to approach

  5. Preliminary study of rabbit model with corneal neovascularization after thermal burn under the constant temperature

    Directory of Open Access Journals (Sweden)

    Yong Jia

    2014-07-01

    Full Text Available AIM:To explore the suitable conditions in rapid model of corneal neovascularization(CNVafter thermal burn under different constant temperature in rabbit. METHODS: Total 45 New Zealand white rabbits were divided randomly into five groups(A, B, C, D, E. A groups: 100℃(n=10, B groups: 200℃(n=10, C groups: 300℃(n=10, D groups: 400℃(n=10, and E groups: control group(n=5. All left eyes of rabbits in A,B,C,D groups were induced corneal neovascularization by constant temperature burning device. The growth of CNV was observed by slit lamp microscope and the area of CNV were recorded on 4 th, 7 th, 14th, 30th days postoperatively. SPSS 19.0 statistical package was used for data analysis, and the data was recorded by mean±standard deviation. Comparison by analysis of variance was made by repeated measures in the area of neovascularization at each time point in groups. Statistical tests were considered significantly when P values were less than 0.05. RESULTS: On postoperative 4th, 7th, 14th, 30th days: no neovascularization was found after corneal thermal burn in A group, but only a few nebula left(n=2; the area of CNV were(9.16±1.45mm2,(37.73±5.49mm2,(62.44±7.54mm2,(40.28±7.39mm2 in B group respectively; and(11.45±1.04mm2,(44.51±4.64mm2,(66.13±4.13mm2,(43.04±2.33mm2 in C group respectively; and(13.23±0.86mm2,(47.26±4.59mm2,(67.57±4.56mm2,(45.59±4.44mm2 in D group respectively, and part corneal carbide(n=4was observed as well as corneal perforation(n=6were found on 3d in D group. No neovascularization was found in normal control group. Comparison of the areas of CNV at each time point between groups was statistically different, PPCOCLUSION: In 4 to 7d, the higher the temperature is, the more the neovascularization area of CNV are. It has no significant difference in 14 to 30d. But corneal carbide and corneal perforation are often found in 400℃ group, so its modeling failure rate is high. It is between 200℃ and 300℃ that

  6. Radiation therapy for ocular choroidal neovascularization (phase I/II study): preliminary report

    International Nuclear Information System (INIS)

    Sasai, Keisuke; Murata, Rumi; Mandai, Michiko; Takahashi, Masayo; Ogura, Yuichiro; Ngata, Yasushi; Nishimura, Yasumasa; Hiraoka, Masahiro

    1997-01-01

    Purpose/Objective: Choroidal neovascularization (CNV) is a major cause of severe loss of visual acuity in some ocular diseases such as age-related macular degeneration (ARMD) and angioid streaks. Laser photocoagulation has been used to treat patients with subfoveal neovascular lesions with well-demarcated boundaries. However, the treatment method is usually associated with a large decrease in visual acuity. Therefore, indications for this treatment are very limited. Recently, some investigators reported the effect of low dose irradiation on the sub retinal neovascular membranes in CNV. We conducted a Phase I/II study to determine the toxicity and efficacy of external photon beam radiotherapy in patients with CNV. Methods and Materials: Between April, 1994 and July, 1995, 36 patients with choroidal neovascularization (34 with ARMD and 2 with angioid streaks) were treated with radiation therapy. Treatment planning was performed using a CT simulator that enables real-time treatment planning from multiple CT slices. The clinical target volume that included the macula and optic disc received a dose of 10 Gy/5 fractions/1 week (first 18 eyes) or 20 Gy/10 fractions/2 weeks (last 18 eyes). All eyes were irradiated with a single lateral 6 MV photon beam, angled 10 degrees posteriorly to exclude the ipsilateral lens and the contralateral eye from the radiation field. The ipsilateral lens was irradiated with less than 10% of the total reference dose. The field size averaged 3.0 x 2.5 cm. Records of the 17 eyes with CNV referred to our hospital in 1993, which satisfied the eligibility criteria for this study, were retrospectively analyzed for comparison. Results: There was no significant acute morbidity. All patients were followed regularly by both ophthalmologists and radiation oncologists. Cataract formation after 1 year of the treatment was observed in one patient who had received a dose of 20 Gy. One patient who had received 20 Gy complained of transient dry-eye sensation

  7. Understanding Service Composition with Non-functional Properties Using Declarative Model-to-model Transformations

    Directory of Open Access Journals (Sweden)

    Max Mäuhlhäuser

    2011-01-01

    Full Text Available Developing applications comprising service composition is a complex task. Therefore, to lower the skill barrier for developers, it is important to describe the problem at hand on an abstract level and not to focus on implementation details. This can be done using declarative programming which allows to describe only the result of the problem (which is what the developer wants rather than the description of the implementation. We therefore use purely declarative model-to-model transformations written in a universal model transformation language which is capable of handling even non functional properties using optimization and mathematical programming. This makes it easier to understand and describe service composition and non-functional properties for the developer.

  8. Pancreatic non-functioning neuroendocrine tumor: a new entity genetically related to Lynch syndrome

    OpenAIRE

    Serracant Barrera, Anna; Serra Pla, Sheila; Blázquez Maña, Carmen María; Salas, Rubén Carrera; García Monforte, Neus; Bejarano González, Natalia; Romaguera Monzonis, Andreu; Andreu Navarro, Francisco Javier; Bella Cueto, Maria Rosa; Borobia, Francisco G.

    2017-01-01

    Some pancreatic neuroendocrine tumors (P-NETs) are associated with hereditary syndromes. An association between Lynch syndrome (LS) and P-NETs has been suggested, however it has not been confirmed to date. We describe the first case associating LS and P-NETs. Here we report a 65-year-old woman who in the past 20 years presented two colorectal carcinomas (CRC) endometrial carcinoma (EC), infiltrating ductal breast carcinoma, small intestine adenocarcinoma, two non-functioning P-NETs and seboma...

  9. Extended SOA to Enable Web Service Discovery on Non Functional Parameters

    OpenAIRE

    Vandan Tiwari Dr. Nirmal Dagdee Dr. Aruna Tiwari Divesh Dixit

    2012-01-01

    The current Service Oriented Architecture (SOA) standards, namely the concept of Web services and service registry lacks mechanism for managing the services’ nonfunctional properties of Web Services. Currently there is no standard that is capable of accurately representing quality of service parameters of web services. Such non functional properties are expressed by the term “Quality of Service (QoS)”. QoS for Web services is an important decisive factor for service selection. Therefore it is...

  10. An Architectural Decision Tool Based on Scenarios and Non-functional Requirements

    OpenAIRE

    Mr. Mahesh Parmar; Prof. W.U. Khan; Dr. Binod Kumar

    2011-01-01

    Software architecture design is often based on architects intuition and previous experience. Little methodological support is available, but there are still no effective solutions to guide the architectural design. The most difficult activity is the transformation from non-functional requirement specification into software architecture. To achieve above things proposed “An Architectural Decision Tool Based on Scenarios and Nonfunctional Requirementsâ€. In this proposed tool scenarios are fi...

  11. Assembling Components using SysML with Non-Functional Requirements

    OpenAIRE

    Chouali , Samir; Hammad , Ahmed; Mountassir , Hassan

    2013-01-01

    International audience; Non-functional requirements of component based systems are important as their functional requirements, therefore they must be considered in components assembly. These properties are beforehand specified with SysML requirement diagram. We specify component based system architecture with SysML block definition diagram, and component behaviors with sequence diagrams. We propose to specify formally component interfaces with interface automata, obtained from requirement and...

  12. On Using Ilities of Non-Functional Properties for Subsystems and Components

    Directory of Open Access Journals (Sweden)

    James Y. Lee

    2017-07-01

    Full Text Available The use of ilities for systems engineering of subsystems and components is investigated. Prior work on ilities has emphasized or restricted their application to system level, non-functional properties. The premise of this work is that ilities can be applied with benefit, and in some cases out of necessity, to lower levels of systems as well. The veracity of this premise is established by providing examples that demonstrate how some ilities are passed and used as a non-functional property of electrical and structural subsystems in aircraft. It is further demonstrated that flowing ilities down to the subsystem level is not only a useful practice for systems engineers, it can also be an essential step to ensure that customer needs are actually met by the system under design or service. Systems engineers often lack the detailed knowledge of the subsystems or components required to translate ilities into functional requirements. Thus, the system ilities are passed down and translated from non-functional to functional requirements by subject matter experts. We first discuss the definition, characteristics and scope of ilities. Then, we formulate the application of ilities at a subsystem level. Next, we show aircraft engineering examples for ilities applications. The application process is formalized with diagrams, and ilities’ relation to system architecture engineering is discussed. The work concludes with a summary and suggestions for future work.

  13. Enhanced

    Directory of Open Access Journals (Sweden)

    Martin I. Bayala

    2014-06-01

    Full Text Available Land Surface Temperature (LST is a key parameter in the energy balance model. However, the spatial resolution of the retrieved LST from sensors with high temporal resolution is not accurate enough to be used in local-scale studies. To explore the LST–Normalised Difference Vegetation Index relationship potential and obtain thermal images with high spatial resolution, six enhanced image sharpening techniques were assessed: the disaggregation procedure for radiometric surface temperatures (TsHARP, the Dry Edge Quadratic Function, the Difference of Edges (Ts∗DL and three models supported by the relationship of surface temperature and water stress of vegetation (Normalised Difference Water Index, Normalised Difference Infrared Index and Soil wetness index. Energy Balance Station data and in situ measurements were used to validate the enhanced LST images over a mixed agricultural landscape in the sub-humid Pampean Region of Argentina (PRA, during 2006–2010. Landsat Thematic Mapper (TM and Moderate Resolution Imaging Spectroradiometer (EOS-MODIS thermal datasets were assessed for different spatial resolutions (e.g., 960, 720 and 240 m and the performances were compared with global and local TsHARP procedures. Results suggest that the Ts∗DL technique is the most adequate for simulating LST to high spatial resolution over the heterogeneous landscape of a sub-humid region, showing an average root mean square error of less than 1 K.

  14. Gene Therapy with Endogenous Inhibitors of Angiogenesis for Neovascular Age-Related Macular Degeneration: Beyond Anti-VEGF Therapy

    Directory of Open Access Journals (Sweden)

    Selwyn M. Prea

    2015-01-01

    Full Text Available Age-related macular degeneration (AMD is the leading cause of substantial and irreversible vision loss amongst elderly populations in industrialized countries. The advanced neovascular (or “wet” form of the disease is responsible for severe and aggressive loss of central vision. Current treatments aim to seal off leaky blood vessels via laser therapy or to suppress vessel leakage and neovascular growth through intraocular injections of antibodies that target vascular endothelial growth factor (VEGF. However, the long-term success of anti-VEGF therapy can be hampered by limitations such as low or variable efficacy, high frequency of administration (usually monthly, potentially serious side effects, and, most importantly, loss of efficacy with prolonged treatment. Gene transfer of endogenous antiangiogenic proteins is an alternative approach that has the potential to provide long-term suppression of neovascularization and/or excessive vascular leakage in the eye. Preclinical studies of gene transfer in a large animal model have provided impressive preliminary results with a number of transgenes. In addition, a clinical trial in patients suffering from advanced neovascular AMD has provided proof-of-concept for successful gene transfer. In this mini review, we summarize current theories pertaining to the application of gene therapy for neovascular AMD and the potential benefits when used in conjunction with endogenous antiangiogenic proteins.

  15. Radiation therapy for ocular choroidal neovascularization (phase I/II study)

    International Nuclear Information System (INIS)

    Sasai, Keisuke; Murata, Rumi; Mandai, Michiko; Takahashi, Masayo; Hiraoka, Masahiro

    1996-01-01

    Purpose/Objective: Choroidal neovascularization (CNV) is a major cause of severe loss of visual acuity in some ocular diseases such as age-related macular degeneration (ARMD) and angio-streaks. Laser photocoagulation has been used to treat patients with subfoveal neovascular lesions with well demarcated boundaries. However, the treatment method is usually associated with a large decrease in visual acuity. Therefore, indications for this treatment are very limited. Recently, some investigators reported the effect of low dose irradiation on the subretinal neovascular membranes in CNV. We conducted a phase I/II study to determine the toxicity and efficacy of external photon beam radiotherapy in patients with CNV. Materials and Methods: Between April 1994 and July 1995, 36 patients with choroidal neovascularization (34 with ARMD; 2 with angiostreaks) were treated with radiation therapy. Eligibility criteria for this study were as follows: the eyes had subretinal neovascular membranes in the avascular area of the fovea; the neovascular membranes had grown in size in the last 6 months; the best pretreatment corrected visual acuity was worse than (20(25)); there were no large subretinal hemorrhages causing decrease in visual acuity; patients were 50 years or older and had not received laser photocoagulation nor other treatment for this condition. Written informed consent was obtained from all patients. The patients underwent fluorescein angiographic evaluation and documentation of their neovascular disease prior to irradiation. Fluorescein angiography, measurement of the best corrected visual acuity, ophthalmoscopic and biomicroscopic examinations were performed at 1, 3, 6, and 12 months after treatment. Treatment planning was performed using a CT simulator which enables real-time treatment planning from multiple CT slices. The clinical target volume included the macula and optic disc, which received a dose of 10 Gy/5 fractions/1 week (first 18 eyes) or 20 Gy/10 fractions

  16. Evaluation of the siRNA PF-04523655 versus ranibizumab for the treatment of neovascular age-related macular degeneration (MONET Study)

    DEFF Research Database (Denmark)

    Nguyen, Quan Dong; Schachar, Ronald A; Nduaka, Chudy I

    2012-01-01

    To evaluate the efficacy of different dosing paradigms of PF-04523655 (PF) versus ranibizumab (comparator) in subjects with neovascular age-related macular degeneration (AMD).......To evaluate the efficacy of different dosing paradigms of PF-04523655 (PF) versus ranibizumab (comparator) in subjects with neovascular age-related macular degeneration (AMD)....

  17. Preferential Hyperacuity Perimeter (PreView PHP) for detecting choroidal neovascularization study.

    Science.gov (United States)

    Alster, Yair; Bressler, Neil M; Bressler, Susan B; Brimacombe, Judith A; Crompton, R Michael; Duh, Yi-Jing; Gabel, Veit-Peter; Heier, Jeffrey S; Ip, Michael S; Loewenstein, Anat; Packo, Kirk H; Stur, Michael; Toaff, Techiya

    2005-10-01

    To assess the ability of the Preferential Hyperacuity Perimeter (PreView PHP; Carl Zeiss Meditec, Dublin, CA) to detect recent-onset choroidal neovascularization (CNV) resulting from age-related macular degeneration (AMD) and to differentiate it from an intermediate stage of AMD. Prospective, comparative, concurrent, nonrandomized, multicenter study. Eligible participants' study eyes had a corrected visual acuity of 20/160 or better and either untreated CNV from AMD diagnosed within the last 60 days or an intermediate stage of AMD. After obtaining consent, visual acuity with habitual correction, masked PHP testing, stereoscopic color fundus photography, and fluorescein angiography were performed. Photographs and angiograms were evaluated by graders masked to diagnosis and PHP results. The reading center's diagnosis determined if the patient was categorized as having intermediate AMD or neovascular AMD. A successful study outcome was defined a priori as a sensitivity of at least 80% and a specificity of at least 80%. Of 185 patients who gave consent to be enrolled, 11 (6%) had PHP results judged to be unreliable. An additional 52 were not included because they did not meet all eligibility criteria. Of the remaining 122 patients, 57 had an intermediate stage of AMD and 65 had neovascular AMD. The sensitivity to detect newly diagnosed CNV using PHP testing was 82% (95% confidence interval [CI], 70%-90%). The specificity to differentiate newly diagnosed CNV from the intermediate stage of AMD using PHP testing was 88% (95% CI, 76%-95%). Preferential Hyperacuity Perimeter testing can detect recent-onset CNV resulting from AMD and can differentiate it from an intermediate stage of AMD with high sensitivity and specificity. These data suggest that monitoring with PHP should detect most cases of CNV of recent onset with few false-positive results at a stage when treatment usually would be beneficial. Thus, this monitoring should be considered in the management of the

  18. Progression of retinal pigment epithelial atrophy in antiangiogenic therapy of neovascular age-related macular degeneration.

    Science.gov (United States)

    Schütze, Christopher; Wedl, Manuela; Baumann, Bernhard; Pircher, Michael; Hitzenberger, Christoph K; Schmidt-Erfurth, Ursula

    2015-06-01

    To monitor retinal pigment epithelial (RPE) atrophy progression during antiangiogenic therapy of neovascular age-related macular degeneration (AMD) over 2 years using polarization-sensitive optical coherence tomography (OCT). Prospective interventional case series. setting: Clinical practice. Thirty patients (31 eyes) with treatment-naïve neovascular AMD. Standard intravitreal therapy (0.5 mg ranibizumab) was administered monthly during the first year and pro re nata (PRN; as-needed) during the second year. Spectral-domain (SD) OCT and polarization-sensitive OCT (selectively imaging the RPE) examinations were performed at baseline and at 1, 3, 6, 12, and 24 months using a standardized protocol. RPE-related changes were evaluated using a semi-automated polarization-sensitive OCT segmentation algorithm and correlated with SD OCT and fundus autofluorescence (FAF) findings. RPE response, geographic atrophy (GA) progression. Atrophic RPE changes included RPE thinning, RPE porosity, focal RPE atrophy, and development of GA. Early RPE loss (ie, RPE porosity, focal atrophy) increased progressively during initial monthly treatment and remained stable during subsequent PRN-based therapy. GA developed in 61% of eyes at month 24. Mean GA area increased from 0.77 mm(2) at 12 months to 1.10 mm(2) (standard deviation = 1.09 mm(2)) at 24 months. Reactive accumulation of RPE-related material at the lesion borders increased until month 3 and subsequently decreased. Progressive RPE atrophy and GA developed in the majority of eyes. RPE migration signifies certain RPE plasticity. Polarization-sensitive OCT specifically images RPE-related changes in neovascular AMD, contrary to conventional imaging methods. Polarization-sensitive OCT allows for precisely monitoring the sequence of RPE-related morphologic changes. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  19. A value-based medicine comparison of interventions for subfoveal neovascular macular degeneration.

    Science.gov (United States)

    Brown, Gary C; Brown, Melissa M; Brown, Heidi C; Kindermann, Sylvia; Sharma, Sanjay

    2007-06-01

    To perform a value-based medicine analysis of clinical trials that evaluate the interventions of laser photocoagulation, intravitreal pegaptanib therapy, and photodynamic therapy (PDT) with verteporfin for the treatment of classic subfoveal choroidal neovascularization. Reference case cost-utility analysis using value-based medicine principles, which use patient-based utility values and standardized, input variable criteria. Data from participants in the Macular Photocoagulation Study, Pegaptanib for Neovascular Age-Related Macular Degeneration Study, and the Treatment of Age-Related Macular Degeneration with Photodynamic Therapy Study. Visual data were converted to a value-based format using time tradeoff utility analysis values from patients with macular degeneration. Costs were obtained from 2005 Medicare data. Outcomes (quality-adjusted life-years [QALYs]) and costs were discounted at a 3% annual rate. Interventional QALYs gained, percent improvement in quality of life, and dollars spent per QALY gained. Laser photocoagulation confers a 4.4% (P = 0.03 versus pegaptanib therapy) improvement in quality of life for the reference case, whereas pegaptanib therapy confers a 5.9% improvement and PDT confers an 8.1% (P = 0.0002 versus pegaptanib therapy) improvement. The cost-utility associated with laser photocoagulation is $8179, that for pegaptanib therapy is $66978, and that for PDT is $31544. All sensitivity analyses remain within the conventional standards of cost-effectiveness. Photodynamic therapy confers greater patient value than intravitreal pegaptanib therapy and laser photocoagulation for the treatment of classic subfoveal choroidal neovascularization. Despite the fact that laser photocoagulation is the most cost-effective intervention, both PDT and pegaptanib therapy deliver greater value, and thus are both preferred over laser photocoagulation. Using an economic measure, photodynamic therapy is the preferred treatment among these 3 interventions.

  20. VEGF-production by CCR2-dependent macrophages contributes to laser-induced choroidal neovascularization.

    Directory of Open Access Journals (Sweden)

    Torsten A Krause

    Full Text Available Age-related macular degeneration (AMD is the most prevalent cause of blindness in the elderly, and its exsudative subtype critically depends on local production of vascular endothelial growth factor A (VEGF. Mononuclear phagocytes, such as macrophages and microglia cells, can produce VEGF. Their precursors, for example monocytes, can be recruited to sites of inflammation by the chemokine receptor CCR2, and this has been proposed to be important in AMD. To investigate the role of macrophages and CCR2 in AMD, we studied intracellular VEGF content in a laser-induced murine model of choroidal neovascularisation. To this end, we established a technique to quantify the VEGF content in cell subsets from the laser-treated retina and choroid separately. 3 days after laser, macrophage numbers and their VEGF content were substantially elevated in the choroid. Macrophage accumulation was CCR2-dependent, indicating recruitment from the circulation. In the retina, microglia cells were the main VEGF+ phagocyte type. A greater proportion of microglia cells contained VEGF after laser, and this was CCR2-independent. On day 6, VEGF-expressing macrophage numbers had already declined, whereas numbers of VEGF+ microglia cells remained increased. Other sources of VEGF detectable by flow cytometry included in dendritic cells and endothelial cells in both retina and choroid, and Müller cells/astrocytes in the retina. However, their VEGF content was not increased after laser. When we analyzed flatmounts of laser-treated eyes, CCR2-deficient mice showed reduced neovascular areas after 2 weeks, but this difference was not evident 3 weeks after laser. In summary, CCR2-dependent influx of macrophages causes a transient VEGF increase in the choroid. However, macrophages augmented choroidal neovascularization only initially, presumably because VEGF production by CCR2-independent eye cells prevailed at later time points. These findings identify macrophages as a relevant source

  1. Neovascularity in patellar tendinopathy and the response to eccentric training: a case report using Power Doppler ultrasound.

    Science.gov (United States)

    McCreesh, Karen M; Riley, Sara J; Crotty, James M

    2013-12-01

    This report describes the case of an amateur soccer player with chronic patellar tendinopathy who underwent ultrasound imaging before and after engaging in an 8-week programme of eccentric exercise. On initial assessment, greyscale ultrasound imaging demonstrated tendon thickening and reduced echogenicity, while Power Doppler imaging demonstrated a large amount of neovascularity. After 8 weeks of an eccentric loading programme, the patient reported significantly improved symptoms and functional scores, while follow-up imaging demonstrated improvement in the echo appearance of the tendon and complete resolution of the neovascularity. The association between neovascularity and symptoms in tendinopathy research is conflicting, with a paucity of research in the area of patellar tendinopathy. While further research is needed to clarify the significance of greyscale and Power Doppler ultrasound changes in relation to symptoms in patellar tendinopathy, ultrasound imaging was shown to be a useful adjunct to diagnosis and outcome assessment in this case. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Increased Expression of CD200 on Circulating CD11b+ Monocytes in Patients with Neovascular Age-related Macular Degeneration

    DEFF Research Database (Denmark)

    Singh, Amardeep; Falk, Mads K; Hviid, Thomas V F

    2013-01-01

    OBJECTIVE: Dysregulation of retinal microglial activity has been implicated in the pathogenesis of neovascular age-related macular degeneration. Microglia activity can be regulated through the membrane protein CD200 and its corresponding receptor, the CD200 receptor (CD200R). Because both...... with neovascular age-related macular degeneration (AMD) and 44 age-matched controls without AMD. METHODS: The participants were aged 60 years or older, had no history of immune dysfunction or cancer, and were not receiving immune-modulating therapy. All participants were subjected to a structured interview......: Patients with neovascular AMD had a higher percentage of CD11b+CD200+ monocytes and CD200+ monocytes compared with controls. Multiple regression analysis revealed that the intergroup differences observed were independent of age. Moreover, an age-related increment in CD200 expression on monocytes...

  3. Decellularized matrix from tumorigenic human mesenchymal stem cells promotes neovascularization with galectin-1 dependent endothelial interaction

    DEFF Research Database (Denmark)

    Burns, Jorge S; Kristiansen, Malthe; Kristensen, Lars P

    2011-01-01

    . Histological analysis showed that cells of the most vascularized tumorigenic clone, -BD11 had a pericyte-like alpha smooth muscle actin (ASMA+) and CD146+ positive phenotype. Upon serum withdrawal in culture, -BD11 cells formed cord-like structures mimicking capillary morphogenesis. In contrast, cells...... of the poorly tumorigenic clone, -BC8 did not stain for ASMA, tumours were less vascularized and serum withdrawal in culture led to cell death. By exploring the heterogeneity in hMSC-TERT20 clones we aimed to understand molecular mechanisms by which mesenchymal stem cells may promote neovascularization....

  4. Surgical choroidal neovascular membrane removal in the era of anti-vascular endothelial growth factor agents

    Directory of Open Access Journals (Sweden)

    Nagpal Manish

    2009-01-01

    Full Text Available Intravitreal anti-vascular endothelial growth factor (VEGF agents have obtained acceptance as the mainstay in the management strategy of subfoveal choroidal neovascular membranes (CNVM due to varying etiologies. Few drawbacks include need for repeated intravitreal injections, with its adjunct risks, and the lack of a predefined treatment end point, which can cause doubts and uncertainty in the mind of the patient. Furthermore, it remains a significant financial burden for the patient. Herein we report our data of three patients who were reluctant for further re-injections of anti-VEGF agents and were therefore offered surgical removal of the CNVM by submacular surgery as an alternative treatment plan.

  5. Ranibizumab in neovascular age-related macular degeneration: a 5-year follow-up

    Directory of Open Access Journals (Sweden)

    Cvetkova NP

    2016-06-01

    Full Text Available Nadezhda P Cvetkova, Kristina Hölldobler, Philipp Prahs, Viola Radeck, Horst Helbig, David Märker Department of Ophthalmology, University of Regensburg, Regensburg, Germany Purpose: Our aim was to evaluate an optical coherence tomography (OCT and visual acuity (VA-guided, variable-dosing regimen with intravitreal ranibizumab injection for treating patients with neovascular age-related macular degeneration (AMD from 2007 to 2012. Design: This was a retrospective clinical study of 5 years follow-up in a tertiary eye center. Patients and methods: In this study, 66 patients with neovascular AMD (mean age of 74 years, SD 8.7 years were included. We investigated the development of best-corrected visual acuity (BCVA, the number of intravitreal injections, and the central retinal thickness measured with OCT (OCT Spectralis over 5 years of intravitreal treatment. Results: The mean number of intravitreal ranibizumab injections over 5 years was 8.8. The mean BCVA before therapy was 0.4 logarithm of the minimum angle of resolution (logMAR. After 5 years of therapy, the mean BCVA was 0.6 logMAR. In all, 16% of treated patients had stable VA over 5 years and 10% of study eyes approved their VA. The mean OCT-measured central retinal thickness at the beginning of this study was 295 µm; after 5 years of treatment, the mean central retinal thickness was 315 µm. There was an increase in central retinal thickness in 47.5% of examined eyes. Conclusion: Other studies showed VA improvement in OCT-guided variable-dosing regimens. Our study revealed a moderate decrease in VA after a total mean injection number as low as 8.8 injections over 5 years. In OCT, an increase in central retinal thickness over 5 years could be observed. Probably, this is due to deficient treatment when comparing the total injection number to other treatment regimens. Anti-VEGF therapy helps to keep the VA stable for a period of time, but cannot totally stop the progression of

  6. Treatment of age-related subfoveal choroidal neovascularization by low-dose external radiation. A preliminary study

    Energy Technology Data Exchange (ETDEWEB)

    Harino, Seiyo; Oshima, Yusuke; Tsujikawa, Kaoru; Oh, Ami; Sugimoto, Kiyoshi [Yodogawa Christian Hospital, Osaka (Japan); Murayama, Shigeyuki; Inoue, Toshihiko

    1997-04-01

    We applied low dose external beam radiation (6MV) to 17 eyes of 17 patients (Mean age 70.9 years, range 58-85) who had subfoveal choroidal neovascularization associated with age-related macular degeneration. None of the cases were suitable for photocoagulation according to the Macular Photo-coagulation Study protocol, and no feeding vessels underlying choroidal neovascular membrane could be detected. Corrected visual acuity ranged from 0.02 to 0.6 before treatment. The patients were divided into two groups. One group of 11 eyes was treated with 10 Gy and the other group of 6 eyes with 21 Gy. Mean follow up period was 347{+-}89 (mean{+-}standard deviation) days in the 10 Gy group and 312{+-}100 days in the 21 Gy group. We evaluated the outcome as `effective` if no progression in neovascular membrane was found by ophthalmoscopic and angiographic examination. Only 3 eyes (21%) of patients in the 10 Gy group and 2 eyes (33%) in 21 Gy group showed any effect. Although the rate of progression in choroidal neovascular membrane was significantly smaller in the 10 and 21 Gy group than in the controls, the corrected visual acuity in the treated group was not improved over that of the controls. No serious complications were seen. Only one case showed a stabilized neovascular membrane in the control group of 7 patients. Although the present results seem to be worse than those in previous reports, the efficacy of this treatment still needs to be evaluated because no beneficial strategies in the treatment of subfoveal neovascularization have been established. (author)

  7. Strategies for improving early detection and diagnosis of neovascular age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Keane PA

    2015-02-01

    Full Text Available Pearse A Keane,1 Gabriella de Salvo,2 Dawn A Sim,1 Srini Goverdhan,2 Rupesh Agrawal,1 Adnan Tufail1 1NIHR Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, 2Department of Ophthalmology, University Hospital Southampton NHS Foundation Trust, Southampton, UK Abstract: Treatment of the neovascular form of age-related macular degeneration (AMD has been revolutionized by the introduction of such agents as ranibizumab, bevacizumab, and aflibercept. As a result, the incidence of legal blindness occurring secondary to AMD has fallen dramatically in recent years in many countries. While these agents have undoubtedly been successful in reducing visual impairment and blindness, patients with neovascular AMD typically lose some vision over time, and often lose the ability to read, drive, or perform other important activities of daily living. Efforts are therefore under way to develop strategies that allow for earlier detection and treatment of this disease. In this review, we begin by providing an overview of the rationale for, and the benefits of, early detection and treatment of neovascular AMD. To achieve this, we begin by providing an overview of the pathophysiology and natural history of choroidal neovascularization, before reviewing the evidence from both clinical trials and “real-world” outcome studies. We continue by highlighting an area that is often overlooked: the importance of patient education and awareness for early AMD detection. We conclude the review by reviewing an array of both established and emerging technologies for early detection of choroidal neovascularization, ranging from Amsler chart testing, to hyperacuity testing, to advanced imaging techniques, such as optical coherence tomography. Keywords: Amsler, detection, choroidal neovascularization, hyperacuity, optical coherence tomography

  8. The most common cause of non-functioning kidney nephrectomy: Urolithiasis

    Directory of Open Access Journals (Sweden)

    Şenol Adanur

    2014-09-01

    Full Text Available Objective: Our aim is to evaluate and present the characteristics of patients underwent nephrectomy due to nonfunctional kidney secondary to urolithiasis in our clinic. Methods:Totally 696 patients were anlyzed retrospectively who underwent nephrectomy in our clinic between January 2000 and December 2012. Etiologies and characteristics of nephrectomy applied patients due to nontumoral non-functional kidney related with urinary tract stones are evaluated. Diagnoses of the patients were confirmed by using urinary system ultrasonography, ab dominal computed tomography, intravenous urography and renal scintigraphy. Results:Nephrectomy was performed for 280 (40.2% patients due to tumor formation and for 416 (59.8% patients due to non-functional kidney of totally 696 patients.43.8% (182 of non-funtional kidney cases were resulted by upper urinary tract stones. Mean age of nephrectomy performed urolithiasis patients were 43.7±16.9 years. 53.3% (97 of patients were male and 46.7% (85 patients were female. Preoperative mean creatinine value of patients were detected 2.98±0.47 mg/dl. Renal stone local izatian was ureteropelvic junction in 81.3% (148, ureter in 14.3% (26 and renal+ureter in 4.4% (8 of the patients. 66.8% of reteropelvic junction stones were 10-30 mm in size. Conclusion: Upper urinary tract stones are primer responsible of non-functional kidney development besides forming most of the non-tumor related nephrectomies. Routine urinary system examination should be suggested to patients with a history of urolithiasis in order to prevent later probable organ losses.

  9. Mobile health systems for bipolar disorder: the relevance of non-functional requirements in MONARCA project

    DEFF Research Database (Denmark)

    Mayora, Oscar; Frost, Mads; Arnrich, Bert

    2016-01-01

    This paper presents a series of challenges for developing mobile health solutions for mental health as a result of MONARCA project three-year activities. The lessons learnt on the design, development and evaluation of a mobile health system for supporting the treatment of bipolar disorder....... The findings presented here are the result of over 3 years of activity within the MONARCA EU project. The challenges listed and detailed in this paper may be used in future research as a starting point for identifying important non-functional requirements involved in mobile health provisioning...

  10. Activation of the Small GTPase Rap1 Inhibits Choroidal Neovascularization by Regulating Cell Junctions and ROS Generation in Rats.

    Science.gov (United States)

    Li, Jiajia; Zhang, Rong; Wang, Caixia; Wang, Xin; Xu, Man; Ma, Jingxue; Shang, Qingli

    2018-03-30

    Choroidal neovascularization (CNV) is a common vision-threatening complication associated with many  fundus diseases. The retinal pigment epithelial (RPE) cell junction barrier has critical functions in preventing CNV, and oxidative stress can cause compromise of barrier integrity and induce angiogenesis. Rap1, a small guanosine triphosphatase (GTPase), is involved in regulating endothelial and epithelial cell junctions. In this work, we explored the function and mechanism of Rap1 in CNV in vivo. A laser-induced rat CNV model was developed. Rap1 was activated through intravitreal injection of the Rap1 activator 8CPT-2'-O-Me-cAMP (8CPT). At 14 days after laser treatment, CNV size in RPE/choroid flat mounts was measured by fluorescein isothiocyanate-dextran staining. Expression of vascular endothelial growth factor (VEGF) and cell junction proteins in RPE/choroid tissues were analyzed by western blots and quantitative real-time PCR assays. Reactive oxygen species (ROS) in RPE cells were detectedbydichloro-dihydro-fluorescein diacetate assays. The antioxidant apocynin was intraperitoneally injected into rats. Activating Rap1 by 8CPT significantly reduced CNV size and VEGF expression in the rat CNV model. Rap1 activation enhanced protein and mRNA levels of ZO-1 and occludin, two tight junction proteins in the RPE barrier. In addition, reducing ROS generation by injection of apocynin, a NADPH oxidase inhibitor, inhibited CNV formation. Rap1 activation reduced ROS generation and expression of NADPH oxidase 4. Rap1 activation inhibits CNV through regulating barrier integrity and ROS generation of RPE in vivo, and selectively activating Rap1 may be a way to reduce vision loss from CNV.

  11. Role of optical coherence tomography angiography in myopic choroidal neovascularization after intravitreal injections of Ranibizumab

    Directory of Open Access Journals (Sweden)

    Meng Cai

    2017-10-01

    Full Text Available AIM: To investigate the change of myopic choroidal neovascularization treated by ranibizumab and evaluate their value in monitoring the effect of anti- vascular endothelial growth factor(VEGFtherapy.METHODS: The study enrolled 30 patients(30 eyesdiagnosed with myopic choroidal neovascularization. All affected eyes were treated with intravitreal ranibizumab 0.05mL(10mg/mL. Best corrected visual acuity(BCVA, non-contact tonometer, ophthalmoscope, fundus fluorescein angiograph(FFAand OCTA were evaluated monthly until 6mo. The changes of BCVA and central macular thickness(CMTwere compared at 1, 3 and 6mo after treatment.RESULTS: All patients received an average of 1.70±0.65 injections. BCVA was 0.96±0.17(LogMARbefore therapy, and BCVA 1, 3 and 6mo after treatment respectively improved by 0.23±0.09, 0.34±0.07, 0.38±0.11. The differences were significant(t=5.461, 8.191, 8.894; Pt=12.007, 13.360, 9.531; PCONCLUSION: Intravitreal ranibizumab for CNV secondary to pathologic myopia is effective and safe; OCTA is a noninvasive and time-saving new technology, and it also is a promising tool for clinicians to make preliminary diagnosis and assess treatment efficacy in the follow-up visits.

  12. Posterior capsule opacification and neovascularization treated with intravitreal bevacizumab and Nd:YAG capsulotomy

    Directory of Open Access Journals (Sweden)

    Grimelda Yuriana Sánchez-Castro

    2008-10-01

    Full Text Available Grimelda Yuriana Sánchez-Castro1, Alejandra Hitos-Fájer1, Erick Mendoza-Schuster1, Raul Velez-Montoya2, Cecilio Francisco Velasco-Barona11Asociación para Evitar la Ceguera en México. Hospital “Dr. Luis Sánchez Bulnes”, México, D.F. Ophthalmology Department – Anterior Segment; 2Asociación para Evitar la Ceguera en México. Hospital “Dr. Luis Sánchez Bulnes”, México, D.F. Ophthalmology Department – Retina departmentAbstract: We reported a 75-year-old diabetic man, who developed opacification and neovascularization of the posterior capsule after extracapsular cataract extraction and posterior chamber intraocular lens implantation. The patient was treated with two injections of 2.5 mg of intravitreal bevacizumab. The treatment produced an important regression of the posterior capsular new vessels, allowing us to perform a successful Nd:YAG capsulotomy, clearing the visual axis and improving the visualization of the posterior pole. Even though, best corrected visual acuity was 20/200 due to diabetic macular edema.Keywords: posterior capsule opacification, posterior capsule neovascularization, cataract surgery, postoperative complications, intravitreal bevacizumab

  13. Surgical Outcome of Ahmed Valve Implantation in Mexican Patients with Neovascular Glaucoma.

    Science.gov (United States)

    Hernandez-Oteyza, Alejandra; Lazcano-Gomez, Gabriel; Jimenez-Roman, Jesus; Hernandez-Garciadiego, Carlos

    2014-01-01

    To describe clinical results of Ahmed glaucoma valve implantation in Mexican patients with neovascular glaucoma (NVG). We reviewed records of 60 eyes of 60 patients with NVG who underwent Ahmed valve implantation, with a follow-up period of 1 year. We identified successful and failed cases and compared baseline and follow-up characteristics to identify possible differences between both groups. We classified 36 eyes (60%) as successful and 24 (40%) as failed cases. We found a significant difference in success rate in patients who had a hypertensive phase at any time during the follow-up period (OR = 5.15, CI = 1.49-20.15, p = 0.004). Patients in the success group showed a statistically significant decrease in the number of glaucoma medications 1 year after surgery (p Ahmed valve surgical failure in patients with NVG. How to cite this article: Hernandez-Oteyza A, Lazcano-Gomez G, Jimenez-Roman J, Hernandez-Garciadiego C. Surgical Outcome of Ahmed Valve Implantation in Mexican Patients with Neovascular Glaucoma. J Curr Glaucoma Pract 2014;8(3):86-90.

  14. Therapeutic Effect of Novel Single-Stranded RNAi Agent Targeting Periostin in Eyes with Retinal Neovascularization

    Directory of Open Access Journals (Sweden)

    Takahito Nakama

    2017-03-01

    Full Text Available Retinal neovascularization (NV due to retinal ischemia remains one of the principal causes of vision impairment in patients with ischemic retinal diseases. We recently reported that periostin (POSTN may play a role in the development of preretinal fibrovascular membranes, but its role in retinal NV has not been determined. The purpose of this study was to examine the expression of POSTN in the ischemic retinas of a mouse model of oxygen-induced retinal NV. We also studied the function of POSTN on retinal NV using Postn KO mice and human retinal endothelial cells (HRECs in culture. In addition, we used a novel RNAi agent, NK0144, which targets POSTN to determine its effect on the development of retinal NV. Our results showed that the expression of POSTN was increased in the vascular endothelial cells, pericytes, and M2 macrophages in ischemic retinas. POSTN promoted the ischemia-induced retinal NV by Akt phosphorylation through integrin αvβ3. NK0144 had a greater inhibitory effect than canonical double-stranded siRNA on preretinal pathological NV in vivo and in vitro. These findings suggest a causal relationship between POSTN and retinal NV, and indicate a potential therapeutic role of intravitreal injection of NK0144 for retinal neovascular diseases.

  15. Neocellularization and neovascularization of nanosized bioactive glass-coated decellularized trabecular bone scaffolds

    KAUST Repository

    Gerhardt, Lutz Christian

    2012-09-11

    In this study, the in vivo recellularization and neovascularization of nanosized bioactive glass (n-BG)-coated decellu-larized trabecular bone scaffolds were studied in a rat model and quantified using stereological analyses. Based on the highest amount of vascular endothelial growth factor (VEGF) secreted by human fibroblasts grown on n-BG coatings (0-1.245 mg/cm 2), decellularized trabecular bone samples (porosity: 43-81%) were coated with n-BG particles. Grown on n-BG particles at a coating density of 0.263 mg/cm2, human fibroblasts produced 4.3 times more VEGF than on uncoated controls. After 8 weeks of implantation in Sprague-Dawley rats, both uncoated and n-BG-coated samples were well infiltrated with newly formed tissue (47-48%) and blood vessels (3-4%). No significant differences were found in cellularization and vascularization between uncoated bone scaffolds and n-BG-coated scaffolds. This finding indicates that the decellularized bone itself may exhibit growth-promoting properties induced by the highly interconnected pore microarchitecture and/or proteins left behind on decellularized scaffolds. Even if we did not find proangiogenic effects in n-BG-coated bone scaffolds, a bioactive coating is considered to be beneficial to impart osteoinductive and osteoconductive properties to decellularized bone. n-BG-coated bone grafts have thus high clinical potential for the regeneration of complex tissue defects given their ability for recellularization and neovascularization. © 2012 Wiley Periodicals, Inc.

  16. Inhibitory Effects of Glycyrrhiza glabra and Its Major Constituent Glycyrrhizin on Inflammation-Associated Corneal Neovascularization

    Directory of Open Access Journals (Sweden)

    Syed Luqman Shah

    2018-01-01

    Full Text Available Glycyrrhiza glabra L. (Leguminosae is widely used in folk medicines. Glycyrrhizin, an active compound of G. glabra, possesses anti-inflammatory activity. This study investigates the G. glabra methanol extract and glycyrrhizin for the treatment of corneal neovascularization (CNV. G. glabra was extracted in 70% aqueous methanol. Phytochemical tests, thin layer chromatography (TLC, and high performance liquid chromatography (HPLC were used for the analysis of chemical composition. The topical solution of G. glabra methanol extract (2% w/v and glycyrrhizin (1% w/v was prepared in normal saline. After corneal burn (1 N NaOH, animals were left untreated for a week so that neovascularization appears in all groups. Treatments started on day 7 and continued for next 21 consecutive days. The animals were treated with 3 drops of various topical solutions thrice a day. Digital photograph analysis and histological studies were used for the evaluation of CNV. Phytochemical analysis of the G. glabra methanol extract showed the presence of saponins, phenols, carbohydrates, flavonoids, and proteins. TLC and HPLC confirmed the presence of glycyrrhizin. Photograph analysis of the extract and glycyrrhizin treated group showed a considerable decrease in CNV. Histological study of G. glabra and glycyrrhizin treated groups showed no blood vessels with properly arranged collagen fibers. This study showed that G. glabra and glycyrrhizin can be used for the treatment of CNV. Bioassay guided isolation can lead to preparation of ophthalmic solutions for the treatment of CNV.

  17. Low-dose radiation therapy for choroidal neovascularization in age-related macular degeneration

    International Nuclear Information System (INIS)

    Matsuhashi, Hideaki; Takahashi, Daisuke; Mariya, Yasushi; Tarusawa, Nobuko; Yoshimoto, Hiroshi; Matsuyama, Shuichi; Noda, Yasuko.

    1996-01-01

    The efficacy of low-dose radiation was evaluated in the treatment of eyes with subfoveal or juxtafoveal choroidal neovascularization in age-related macular degeneration. Ten eyes of ten patients received a total dose of 14 Gy of 10 MV X-rays in seven fractions and the mean follow-up time was 12 months (range 9-18 months). Thirteen control eyes of thirteen patients were followed for an average of 18 months (range 12-24 months). Visual acuity was improved in 2 eyes (20%), unchanged in 3 eyes (30%), and deteriorated in 5 eyes (50%) of treated patients, and it was improved in no eyes (0%), unchanged in 5 eyes (32%), and deteriorated in 8 eyes (50%) of the control patients at their last follow-up examinations. Funduscopic and angiographic findings were improved in 3 eyes (30%), unchanged in 2 eyes (20%), and deteriorated in 5 eyes (50%) of treated patients, and they were improved in no eyes (0%), unchanged in 5 eyes (32%), and deteriorated in 8 eyes (50%) of the control patients. These results suggested that low-dose radiation is beneficial for the management of subfoveal or juxtafoveal choroidal neovascularization in age-related macular degeneration. (author)

  18. Radiation therapy for small choroidal neovascularization in age-related macular degeneration

    International Nuclear Information System (INIS)

    Matsuhashi, Hideaki; Noda, Yasuko; Takahashi, Daisuke; Mariya, Yasushi

    2000-01-01

    The purpose of this study was to evaluate the effects of radiation therapy on age-related macular degeneration with subfoveal or juxtafoveal choroidal neovascularization ≤1 disc area. Fourteen patients (14 eyes) received a total radiation dose of 10-20 Gy in 5-10 fractions. The mean follow-up time was 22 months. Ten patients (10 eyes) in a control group were followed up for an average of 16 months without treatment. At a 12-month posttreatment examination, funduscopic and angiographic findings showed improvement in 7 eyes (50%), no change in 1 eye (7%), and deterioration in 6 eyes (43%) among the treated patients. The same findings demonstrated improvement in 1 eye (10%), no change in 2 eyes (20%), and deterioration in 7 eyes (70%) among the control patients. This difference was determined to be statistically significant between the two groups by the Mann-Whitney U-test. Visual acuity had improved in 4 eyes (29%), was unchanged in 6 eyes (43%), and had declined in 4 eyes (29%), among the treated patients. Among the control patients, visual acuity had improved in none of the eyes (0%), was unchanged in 6 eyes (60%), and had declined in 4 eyes (40%). The difference in visual acuity between the two groups was not statistically significant. Radiation therapy inhibited small choroidal neovascularization, as seen by funduscopy and angiography, but its effectiveness in improving visual prognosis was not always evident. (author)

  19. Amlodipine Ameliorates Ischemia-Induced Neovascularization in Diabetic Rats through Endothelial Progenitor Cell Mobilization

    Directory of Open Access Journals (Sweden)

    Jiayin Sun

    2016-01-01

    Full Text Available Objectives. We investigated whether amlodipine could improve angiogenic responses in a diabetic rat model of acute myocardial infarction (AMI through improving bone marrow endothelial progenitor cell (EPC mobilization, in the same way as angiotensin converting enzyme inhibitors. Methods. After induction of AMI by coronary artery ligation, diabetic rats were randomly assigned to receive perindopril (2 mgkg−1 day−1, amlodipine (2.5 mgkg−1 day−1, or vehicle by gavage (n=20 per group. Circulating EPC counts before ligation and on days 1, 3, 5, 7, 14, and 28 after AMI were measured in each group. Microvessel density, cardiac function, and cardiac remodeling were assessed 4 weeks after treatment. The signaling pathway related to EPC mobilization was also measured. Results. Circulating EPC count in amlodipine- and perindopril-treated rats peaked at day 7, to an obvious higher level than the control group peak which was reached earlier (at day 5. Rats treated with amlodipine showed improved postischemia neovascularization and cardiac function, together with reduced cardiac remodeling, decreased interstitial fibrosis, and cardiomyocyte apoptosis. Amlodipine treatment also increased cardiac SDF-1/CXCR4 expression and gave rise to activation of VEGF/Akt/eNOS signaling in bone marrow. Conclusions. Amlodipine promotes neovascularization by improving EPC mobilization from bone marrow in diabetic rats after AMI, and activation of VEGF/Akt/eNOS signaling may in part contribute to this.

  20. Radiation therapy for small choroidal neovascularization in age-related macular degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Matsuhashi, Hideaki; Noda, Yasuko; Takahashi, Daisuke; Mariya, Yasushi [Hirosaki Univ., Aomori (Japan). School of Medicine

    2000-12-01

    The purpose of this study was to evaluate the effects of radiation therapy on age-related macular degeneration with subfoveal or juxtafoveal choroidal neovascularization {<=}1 disc area. Fourteen patients (14 eyes) received a total radiation dose of 10-20 Gy in 5-10 fractions. The mean follow-up time was 22 months. Ten patients (10 eyes) in a control group were followed up for an average of 16 months without treatment. At a 12-month posttreatment examination, funduscopic and angiographic findings showed improvement in 7 eyes (50%), no change in 1 eye (7%), and deterioration in 6 eyes (43%) among the treated patients. The same findings demonstrated improvement in 1 eye (10%), no change in 2 eyes (20%), and deterioration in 7 eyes (70%) among the control patients. This difference was determined to be statistically significant between the two groups by the Mann-Whitney U-test. Visual acuity had improved in 4 eyes (29%), was unchanged in 6 eyes (43%), and had declined in 4 eyes (29%), among the treated patients. Among the control patients, visual acuity had improved in none of the eyes (0%), was unchanged in 6 eyes (60%), and had declined in 4 eyes (40%). The difference in visual acuity between the two groups was not statistically significant. Radiation therapy inhibited small choroidal neovascularization, as seen by funduscopy and angiography, but its effectiveness in improving visual prognosis was not always evident. (author)

  1. Low-dose radiation therapy for choroidal neovascularization in age-related macular degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Matsuhashi, Hideaki; Takahashi, Daisuke; Mariya, Yasushi; Tarusawa, Nobuko; Yoshimoto, Hiroshi; Matsuyama, Shuichi [Hirosaki Univ., Aomori (Japan). School of Medicine; Noda, Yasuko

    1996-10-01

    The efficacy of low-dose radiation was evaluated in the treatment of eyes with subfoveal or juxtafoveal choroidal neovascularization in age-related macular degeneration. Ten eyes of ten patients received a total dose of 14 Gy of 10 MV X-rays in seven fractions and the mean follow-up time was 12 months (range 9-18 months). Thirteen control eyes of thirteen patients were followed for an average of 18 months (range 12-24 months). Visual acuity was improved in 2 eyes (20%), unchanged in 3 eyes (30%), and deteriorated in 5 eyes (50%) of treated patients, and it was improved in no eyes (0%), unchanged in 5 eyes (32%), and deteriorated in 8 eyes (50%) of the control patients at their last follow-up examinations. Funduscopic and angiographic findings were improved in 3 eyes (30%), unchanged in 2 eyes (20%), and deteriorated in 5 eyes (50%) of treated patients, and they were improved in no eyes (0%), unchanged in 5 eyes (32%), and deteriorated in 8 eyes (50%) of the control patients. These results suggested that low-dose radiation is beneficial for the management of subfoveal or juxtafoveal choroidal neovascularization in age-related macular degeneration. (author)

  2. Radiation therapy for small choroidal neovascularization in age-related macular degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Matsuhashi, Hideaki; Noda, Yasuko; Takahashi, Daisuke; Mariya, Yasushi [Hirosaki Univ., Aomori (Japan). School of Medicine

    1999-06-01

    Radiation therapy for age-related macular degeneration with subfoveal or juxtafoveal choroidal neovascularization smaller than or equal to 1 disc area was evaluated. Fourteen eyes received a total radiation dose of 10-20 Gy in 5-10 fractions. The mean follow-up time was 22 months. Ten eyes in a control group were followed for an average of 16 months without any treatment. At a 12-month follow-up examination, funduscopic and angiographic findings had improved in 7 eyes (50%), were unchanged in 1 eye (7%) and, had deteriorated in 6 eyes (43%) among the treated patients. The same findings had improved in 1 eye (10%), were unchanged in 2 eyes (20%), and had deteriorated in 7 eyes (70%) among the control patients. There was a statistically significant difference by Mann-Whitney U test between the two groups. Visual acuity had improved in 4 eyes (29%), was unchanged in 6 eyes (43%), and had declined in 4 eyes (29%) among the treated patients. Among the control patients visual acuity had improved in none of the eyes (0%), was unchanged in 6 eyes (60%), and had declined in 4 eyes (40%). The difference between the two groups was not statistically significant. Of the 7 cases whose fundus had improved by 12 months, 4 cases maintained a favorable status through the following 2 years. Radiation therapy had an inhibitory effect on small choroidal neovascularization when viewed by funduscopy and angiography, but, the efficacy for visual prognosis was not always identified. (author)

  3. RISK FACTORS AND CLINICAL SIGNIFICANCE OF PRECHOROIDAL CLEFT IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

    Science.gov (United States)

    Kim, Jong Min; Kang, Se Woong; Son, Dae Yong; Bae, Kunho

    2017-11-01

    To investigate the risk factors associated with prechoroidal cleft occurrence after treatment for neovascular age-related macular degeneration (nAMD) and to elucidate its clinical significance. Two hundred thirty-four subjects who were treated for neovascular age-related macular degeneration were assessed to identify prechoroidal cleft on optical coherence tomography. Clinical variables were compared between patients manifesting a cleft (cleft group) and patients who did not (control group). Prechoroidal cleft was detected in 29 of 234 patients (8.1%). Although the baseline visual acuity was not different between the 2 groups, logMAR visual acuity at final visit was 0.89 ± 0.74 (with approximate Snellen equivalent of 20/160) in the cleft group and 0.65 ± 0.69 (with approximate Snellen equivalent of 20/100) in controls (P age-related macular degeneration (P age-related macular degeneration, and a submacular hemorrhage treated by pneumatic displacement were the independent risk factors for development of prechoroidal cleft. Eyes with a cleft, especially clefts that develop early, generally had worse prognoses than eyes without clefts.

  4. JNK inhibition reduces apoptosis and neovascularization in a murine model of age-related macular degeneration.

    Science.gov (United States)

    Du, Hongjun; Sun, Xufang; Guma, Monica; Luo, Jing; Ouyang, Hong; Zhang, Xiaohui; Zeng, Jing; Quach, John; Nguyen, Duy H; Shaw, Peter X; Karin, Michael; Zhang, Kang

    2013-02-05

    Age-related macular degeneration (AMD) is the leading cause of registered blindness among the elderly and affects over 30 million people worldwide. It is well established that oxidative stress, inflammation, and apoptosis play critical roles in pathogenesis of AMD. In advanced wet AMD, although, most of the severe vision loss is due to bleeding and exudation of choroidal neovascularization (CNV), and it is well known that vascular endothelial growth factor (VEGF) plays a pivotal role in the growth of the abnormal blood vessels. VEGF suppression therapy improves visual acuity in AMD patients. However, there are unresolved issues, including safety and cost. Here we show that mice lacking c-Jun N-terminal kinase 1 (JNK1) exhibit decreased inflammation, reduced CNV, lower levels of choroidal VEGF, and impaired choroidal macrophage recruitment in a murine model of wet AMD (laser-induced CNV). Interestingly, we also detected a substantial reduction in choroidal apoptosis of JNK1-deficient mice. Intravitreal injection of a pan-caspase inhibitor reduced neovascularization in the laser-induced CNV model, suggesting that apoptosis plays a role in laser-induced pathological angiogenesis. Intravitreal injection of a specific JNK inhibitor decreased choroidal VEGF expression and reduced pathological CNV. These results suggest that JNK1 plays a key role in linking oxidative stress, inflammation, macrophage recruitment apoptosis, and VEGF production in wet AMD and pharmacological JNK inhibition offers a unique and alternative avenue for prevention and treatment of AMD.

  5. Estradiol-induced, endothelial progenitor cell-mediated neovascularization in male mice with hind-limb ischemia

    NARCIS (Netherlands)

    Ruifrok, Willem-Peter T.; de Boer, Rudolf A.; Iwakura, Atsushi; Silver, Marcy; Kusano, Kengo; Tio, Rene A.; Losordo, Douglas W.

    We investigated whether administration of estradiol to male mice augments mobilization of bone marrow-derived endothelial progenitor cells (EPC) and incorporation into foci of neovascularization after hind-limb ischemia, thereby contributing to blood flow restoration. Mice were randomized and

  6. Neovascular age-related macular degeneration without drusen in the fellow eye : clinical spectrum and therapeutic outcome

    NARCIS (Netherlands)

    Chung, Wing H; van Dijk, Elon H C; Mohabati, Danial; Dijkman, Greet; Yzer, Suzanne; de Jong, Eiko K; Fauser, Sascha; Schlingemann, Reinier O; Hoyng, Carel B; Boon, Camiel J F

    2017-01-01

    PURPOSE: To investigate the clinical characteristics and therapeutic outcome of patients with neovascular age-related macular degeneration (nAMD) in 1 eye, without drusen in the fellow eye. PATIENTS AND METHODS: Medical records of 381 patients were analyzed to identify the cases. The main outcomes

  7. Neovascular age-related macular degeneration without drusen in the fellow eye: clinical spectrum and therapeutic outcome

    NARCIS (Netherlands)

    Chung, Wing H.; van Dijk, Elon H. C.; Mohabati, Danial; Dijkman, Greet; Yzer, Suzanne; de Jong, Eiko K.; Fauser, Sascha; Schlingemann, Reinier O.; Hoyng, Carel B.; Boon, Camiel J. F.

    2017-01-01

    Purpose: To investigate the clinical characteristics and therapeutic outcome of patients with neovascular age-related macular degeneration (nAMD) in 1 eye, without drusen in the fellow eye. Patients and methods: Medical records of 381 patients were analyzed to identify the cases. The main outcomes

  8. Safety and Efficacy of a Flexible Dosing Regimen of Ranibizumab in Neovascular Age-Related Macular Degeneration: The SUSTAIN Study

    NARCIS (Netherlands)

    Holz, Frank G.; Amoaku, Winfried; Donate, Juan; Guymer, Robyn H.; Kellner, Ulrich; Schlingemann, Reinier O.; Weichselberger, Andreas; Staurenghi, Giovanni

    2011-01-01

    Objective: To evaluate the safety and efficacy of individualized ranibizumab treatment in patients with neovascular age-related macular degeneration. Design: Twelve-month, phase III, multicenter, open-label, single-arm study. Participants: A total of 513 ranibizumab-naive SUSTAIN patients.

  9. Neovascular age-related macular degeneration treated with ranibizumab or aflibercept in the same large clinical setting

    DEFF Research Database (Denmark)

    Rasmussen, Annette; Sander, Birgit; Larsen, Michael

    2017-01-01

    PURPOSE: To study visual outcome and number of annual injections in treatment-naïve patients with neovascular age-related macular degeneration (nAMD) before and after a change in first-line therapy from ranibizumab to aflibercept in a high-volume clinical practice. METHODS: This was a retrospective...

  10. In patients with neovascular age-related macular degeneration, physical activity may influence C-reactive protein levels

    DEFF Research Database (Denmark)

    Subhi, Yousif; Singh, Amardeep; Falk, Mads Krüger

    2014-01-01

    Association of neovascular age-related macular degeneration (AMD) with C-reactive protein (CRP) was previously reported, indicating a relation to systemic low-grade inflammation. However, visual impairment limits physical activity, and physical activity modulates CRP levels. Here, we investigated...

  11. Long-term longitudinal study of patients treated with ranibizumab for neovascular age-related macular degeneration

    DEFF Research Database (Denmark)

    Rasmussen, Annette; Sander, Birgit

    2014-01-01

    PURPOSE OF REVIEW: To review the current literature regarding long-term treatment beyond 2 years with anti-vascular endothelial growth factor (VEGF) inhibition for neovascular age-related macular degeneration (nv-AMD). RECENT FINDINGS: Only few studies of anti-VEGF treatment for nv-AMD exist beyond...

  12. A Proinflammatory Function of Toll-Like Receptor 2 in the Retinal Pigment Epithelium as a Novel Target for Reducing Choroidal Neovascularization in Age-Related Macular Degeneration.

    Science.gov (United States)

    Feng, Lili; Ju, Meihua; Lee, Kei Ying V; Mackey, Ashley; Evangelista, Mariasilvia; Iwata, Daiju; Adamson, Peter; Lashkari, Kameran; Foxton, Richard; Shima, David; Ng, Yin Shan

    2017-10-01

    Current treatments for choroidal neovascularization, a major cause of blindness for patients with age-related macular degeneration, treat symptoms but not the underlying causes of the disease. Inflammation has been strongly implicated in the pathogenesis of choroidal neovascularization. We examined the inflammatory role of Toll-like receptor 2 (TLR2) in age-related macular degeneration. TLR2 was robustly expressed by the retinal pigment epithelium in mouse and human eyes, both normal and with macular degeneration/choroidal neovascularization. Nuclear localization of NF-κB, a major downstream target of TLR2 signaling, was detected in the retinal pigment epithelium of human eyes, particularly in eyes with advanced stages of age-related macular degeneration. TLR2 antagonism effectively suppressed initiation and growth of spontaneous choroidal neovascularization in a mouse model, and the combination of anti-TLR2 and antivascular endothelial growth factor receptor 2 yielded an additive therapeutic effect on both area and number of spontaneous choroidal neovascularization lesions. Finally, in primary human fetal retinal pigment epithelium cells, ligand binding to TLR2 induced robust expression of proinflammatory cytokines, and end products of lipid oxidation had a synergistic effect on TLR2 activation. Our data illustrate a functional role for TLR2 in the pathogenesis of choroidal neovascularization, likely by promoting inflammation of the retinal pigment epithelium, and validate TLR2 as a novel therapeutic target for reducing choroidal neovascularization. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  13. Ocular neovascularization in eyes with a central retinal artery occlusion or a branch retinal artery occlusion

    Directory of Open Access Journals (Sweden)

    Mason lll JO

    2015-06-01

    Full Text Available John O Mason III,1,2 Shyam A Patel,1 Richard M Feist,1,2 Michael A Albert Jr,1,2 Carrie Huisingh,1 Gerald McGwin Jr,1,3 Martin L Thomley1,2 1Department of Ophthalmology, University of Alabama School of Medicine, Birmingham, AL, USA; 2Retina Consultants of Alabama, Callahan Eye Foundation Hospital, Birmingham, AL, USA; 3Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA Purpose: To investigate the ocular neovascularization (ONV rate in eyes with a branch retinal artery occlusion (BRAO or a central retinal artery occlusion (CRAO, and to study factors that may influence the ONV rate secondary to CRAO.Methods: This was a retrospective case series of consecutive patients (286 total eyes: 83 CRAOs and 203 BRAOs who were diagnosed with a retinal artery occlusion from 1998 to 2013 at the Retina Consultants of Alabama and University of Alabama at Birmingham, Birmingham, AL, USA. Generalized estimating equations were used to evaluate the association between hypothesized risk factors and ONV development.Results: Twelve (14.5% of the 83 eyes with a CRAO developed ONV. Eleven of 12 eyes (91.7% had iris neovascularization, ten of 12 eyes (83.3% had neovascular glaucoma, and two of 12 eyes (16.7% had neovascularization of the optic disc. The average time for ONV development secondary to CRAO was 30.7 days, ranging from the date of presentation to 137 days. Only two (<1.0% of the 203 eyes with a BRAO developed iris neovascularization. Diabetes mellitus type 2 was a risk factor for ONV development following a CRAO with an adjusted odds ratio of 5.2 (95% confidence interval: 1.4–19.8 (P=0.02.Conclusion: ONV is an important complication of CRAO and is a less-frequent complication of BRAO. Patients with a CRAO, especially those with diabetes mellitus type 2, should be closely monitored for the first 6 months for ONV. Keywords: neovascularization, neovascular glaucoma, retinal artery occlusion, central

  14. Semantic Web Service Delivery in Healthcare Based on Functional and Non-Functional Properties.

    Science.gov (United States)

    Schweitzer, Marco; Gorfer, Thilo; Hörbst, Alexander

    2017-01-01

    In the past decades, a lot of endeavor has been made on the trans-institutional exchange of healthcare data through electronic health records (EHR) in order to obtain a lifelong, shared accessible health record of a patient. Besides basic information exchange, there is a growing need for Information and Communication Technology (ICT) to support the use of the collected health data in an individual, case-specific workflow-based manner. This paper presents the results on how workflows can be used to process data from electronic health records, following a semantic web service approach that enables automatic discovery, composition and invocation of suitable web services. Based on this solution, the user (physician) can define its needs from a domain-specific perspective, whereas the ICT-system fulfills those needs with modular web services. By involving also non-functional properties for the service selection, this approach is even more suitable for the dynamic medical domain.

  15. Surgical treatment of non-functioning pituitary macroadenomas by the endoscopic endonasal approach in the elderly

    Directory of Open Access Journals (Sweden)

    Horacio Armando Marenco

    2015-09-01

    Full Text Available Over the past three decades, surgical series of elderly patients treated for pituitary adenomas have been published, all of which used the microscopic transsphenoidal or transcranial approach. The objective of this study was to retrospectively analyze the surgical results of our first 25 elderly patients with non-functioning pituitary macroadenoma (NFPM operated by the endoscopic endonasal approach (EEA. Preoperative visual loss was found in 92.8% of the cases, and 70.8% experienced visual improvement following surgery. Preoperative pituitary dysfunction was found in 69.2% of the cases and postoperative pituitary recovery occurred in 22.2% of them. Mean hospital stay was 6.7 days. The results of this study suggest that surgery remains the first line of treatment for NFPM in the elderly. Because age alone is not a barrier for surgery, patients should be selected for surgical treatment based on their symptoms and clinical condition, as defined by comorbidities.

  16. Gene expression profiling of fast- and slow- growing gonadotroph non-functioning pituitary adenomas

    DEFF Research Database (Denmark)

    Falch, Camilla Maria; Sundaram, Arvind Y M; Øystese, Kristin Astrid

    2018-01-01

    Objective Reliable biomarkers associated with aggressiveness of non-functioning gonadotroph adenomas (GAs) are lacking. As the growth of tumor remnants is highly variable, molecular markers for growth potential prediction are necessary. We hypothesized that fast- and slow - growing GAs present......, GPM6A and six EMT-related genes (SPAG9, SKIL, MTDH, HOOK1, CNOT6L and PRKACB). MTDH, but not EMCN, demonstrated involvement in cell migration and association with EMT-markers. Conclusions Fast- and slow- growing GAs present different gene expression profiles and genes related to EMT have higher...... expression in fast-growing tumors. In addition to MTDH, identified as an important contributor to aggressiveness, the other genes might represent markers for tumor growth potential and possible targets for drug therapy. ....

  17. Therapy for non-functional pituitary adenoma. Residual tumor and radiotherapy

    International Nuclear Information System (INIS)

    Takahashi, Toshio; Ito, Satoshi; Shimamura, Norihito; Sekiya, Tetsuharu; Tanaka, Masahiko; Suzuki, Shigeharu

    1997-01-01

    Effects and complication of radiotherapy after surgery of non-functional pituitary adenoma were evaluated with consideration on findings in recent literatures. On 44 cases of 64 patients (36 males and 28 females), the mean age of 48.9y, with macroadenoma, a comparison was made on their recurrence and complication between irradiated and non-irradiated groups after surgery. The follow-up period was >1 year (5y4m in a mean). The total radiation dose was in the range of 40-60 (average 47.3) Gy. Recurrence was seen in 1/31 cases in irradiated group, and 5/13 in non-irradiated group. Reduction of visual acuity and hypopituitarism were observed in 1 and 2 cases, respectively, in irradiated group. Radiotherapy for residual tumor was confirmed useful for preventing recurrence. (K.H.)

  18. Estimated cases of blindness and visual impairment from neovascular age-related macular degeneration avoided in Australia by ranibizumab treatment.

    Science.gov (United States)

    Mitchell, Paul; Bressler, Neil; Doan, Quan V; Dolan, Chantal; Ferreira, Alberto; Osborne, Aaron; Rochtchina, Elena; Danese, Mark; Colman, Shoshana; Wong, Tien Y

    2014-01-01

    Intravitreal injections of anti-vascular endothelial growth factor agents, such as ranibizumab, have significantly improved the management of neovascular age-related macular degeneration. This study used patient-level simulation modelling to estimate the number of individuals in Australia who would have been likely to avoid legal blindness or visual impairment due to neovascular age-related macular degeneration over a 2-year period as a result of intravitreal ranibizumab injections. The modelling approach used existing data for the incidence of neovascular age-related macular degeneration in Australia and outcomes from ranibizumab trials. Blindness and visual impairment were defined as visual acuity in the better-seeing eye of worse than 6/60 or 6/12, respectively. In 2010, 14,634 individuals in Australia were estimated to develop neovascular age-related macular degeneration who would be eligible for ranibizumab therapy. Without treatment, 2246 individuals would become legally blind over 2 years. Monthly 0.5 mg intravitreal ranibizumab would reduce incident blindness by 72% (95% simulation interval, 70-74%). Ranibizumab given as needed would reduce incident blindness by 68% (64-71%). Without treatment, 4846 individuals would become visually impaired over 2 years; this proportion would be reduced by 37% (34-39%) with monthly intravitreal ranibizumab, and by 28% (23-33%) with ranibizumab given as needed. These data suggest that intravitreal injections of ranibizumab, given either monthly or as needed, can substantially lower the number of cases of blindness and visual impairment over 2 years after the diagnosis of neovascular age-related macular degeneration.

  19. Efficacy of patterned scan laser in treatment of macular edema and retinal neovascularization

    Directory of Open Access Journals (Sweden)

    Dimple Modi

    2009-08-01

    Full Text Available Dimple Modi, Paulpoj Chiranand, Levent AkdumanSaint Louis University School of Medicine, Department of Ophthalmology, Saint Louis University Eye Institute, St. Louis, Missouri, USAPurpose: To analyze the benefits, efficacy, and complications of the PASCAL® photocoagulation laser system (OptiMedica, Santa Clara, CA, USA in patients treated at our institution.Methods: We conducted a retrospective chart review of 19 patients (28 eyes who underwent laser treatment using the PASCAL® photocoagulation system from November 2006 to November 2007. These 28 eyes were divided into two groups; group 1 eyes underwent macular grid laser and group 2 eyes underwent panretinal photocoagulation. Treatment was performed for macular edema or for iris or retinal neovascularization. Outcomes measured included best-corrected visual acuity (BCVA, efficacy of laser treatment, complications, duration of the procedure, and pain perception, which were noted in the charts for panretinal treatments.Results: Follow-up was 5.9 ± 2.6 months for group 1 and 5.9 ± 4.0 months for group 2. In group 1, 9/28 eyes required a second treatment for remaining edema. BCVA was stable or better in 66% (14/21 and average central foveal thickness on ocular coherence tomography improved in 71% (15/21. Time to completion for a number of laser patterns for grid photocoagulation was felt to be too long for completing the total pattern safely, although we have not noted any related complications. In group 2, the neovascularization regressed at least partially in 3/7 patients. Patient-reported pain perception was 3.6 on a scale of 1 to 10 for group 2. Occasional hemorrhages occurred secondary to irregular laser uptake at different spots in the patterns. We observed no visual outcome consequences because of these hemorrhages during follow-up.Conclusions: Retinal photocoagulation by the PASCAL® laser has comparable efficacy to historical results with conventional retinal photocoagulation in short

  20. Zoledronate inhibits ischemia-induced neovascularization by impairing the mobilization and function of endothelial progenitor cells.

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    Shih-Hung Tsai

    Full Text Available BACKGROUND: Bisphosphonates are a class of pharmacologic compounds that are commonly used to treat postmenopausal osteoporosis and malignant osteolytic processes. Studies have shown that bone marrow-derived endothelial progenitor cells (EPCs play a significant role in postnatal neovascularization. Whether the nitrogen-containing bisphosphonate zoledronate inhibits ischemia-induced neovascularization by modulating EPC functions remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: Unilateral hindlimb ischemia was surgically induced in wild-type mice after 2 weeks of treatment with vehicle or zoledronate (low-dose: 30 μg/kg; high-dose: 100 μg/kg. Doppler perfusion imaging demonstrated that the ischemic limb/normal side blood perfusion ratio was significantly lower in wild-type mice treated with low-dose zoledronate and in mice treated with high-dose zoledronate than in controls 4 weeks after ischemic surgery (control vs. low-dose vs. high-dose: 87±7% vs. *61±18% vs. **49±17%, *p<0.01, **p<0.005 compared to control. Capillary densities were also significantly lower in mice treated with low-dose zoledronate and in mice treated with high-dose zoledronate than in control mice. Flow cytometry analysis showed impaired mobilization of EPC-like cells (Sca-1(+/Flk-1(+ after surgical induction of ischemia in mice treated with zoledronate but normal levels of mobilization in mice treated with vehicle. In addition, ischemic tissue from mice that received zoledronate treatment exhibited significantly lower levels of the active form of MMP-9, lower levels of VEGF, and lower levels of phosphorylated eNOS and phosphorylated Akt than ischemic tissue from mice that received vehicle. Results of the in vitro studies showed that incubation with zoledronate inhibited the viability, migration, and tube-forming capacities of EPC. CONCLUSIONS/SIGNIFICANCE: Zoledronate inhibited ischemia-induced neovascularization by impairing EPC mobilization and angiogenic functions

  1. A circulating microrna profile is associated with late-stage neovascular age-related macular degeneration.

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    Felix Grassmann

    Full Text Available Age-related macular degeneration (AMD is the leading cause of severe vision impairment in Western populations over 55 years. A growing number of gene variants have been identified which are strongly associated with an altered risk to develop AMD. Nevertheless, gene-based biomarkers which could be dysregulated at defined stages of AMD may point toward key processes in disease mechanism and thus may support efforts to design novel treatment regimens for this blinding disorder. Circulating microRNAs (cmiRNAs which are carried by nanosized exosomes or microvesicles in blood plasma or serum, have been recognized as valuable indicators for various age-related diseases. We therefore aimed to elucidate the role of cmiRNAs in AMD by genome-wide miRNA expression profiling and replication analyses in 147 controls and 129 neovascular AMD patients. We identified three microRNAs differentially secreted in neovascular (NV AMD (hsa-mir-301-3p, pcorrected = 5.6*10-5, hsa-mir-361-5p, pcorrected = 8.0*10-4 and hsa-mir-424-5p, pcorrected = 9.6*10-3. A combined profile of the three miRNAs revealed an area under the curve (AUC value of 0.727 and was highly associated with NV AMD (p = 1.2*10-8. To evaluate subtype-specificity, an additional 59 AMD cases with pure unilateral or bilateral geographic atrophy (GA were analyzed for microRNAs hsa-mir-301-3p, hsa-mir-361-5p, and hsa-mir-424-5p. While we found no significant differences between GA AMD and controls neither individually nor for a combined microRNAs profile, hsa-mir-424-5p levels remained significantly higher in GA AMD when compared to NV (pcorrected<0.005. Pathway enrichment analysis on genes predicted to be regulated by microRNAs hsa-mir-301-3p, hsa-mir-361-5p, and hsa-mir-424-5p, suggests canonical TGFβ, mTOR and related pathways to be involved in NV AMD. In addition, knockdown of hsa-mir-361-5p resulted in increased neovascularization in an in vitro angiogenesis assay.

  2. Evaluation of radiological prognostic factors of hepatic metastases in patients with non-functional pancreatic neuroendocrine tumors

    Energy Technology Data Exchange (ETDEWEB)

    Denecke, Timm [Klinik für Radiologie, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin (Germany); Baur, Alexander D.J., E-mail: alexander.baur@charite.de [Klinik für Radiologie, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin (Germany); Ihm, Claudia; Steffen, Ingo G. [Klinik für Radiologie, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin (Germany); Tischer, Elisabeth [Medizinische Klinik m.S. Hepatologie Gastroenterologie, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin (Germany); Arsenic, Ruza [Institut für Pathologie, Campus Charité Mitte, Charité - Universitätsmedizin Berlin (Germany); Pascher, Andreas [Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin (Germany); Wiedenmann, Bertram; Pavel, Marianne [Medizinische Klinik m.S. Hepatologie Gastroenterologie, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin (Germany)

    2013-10-01

    Purpose: There are different therapeutic options in non-functional well to moderately differentiated (G1 and G2) pancreatic neuroendocrine tumors (pNET) with unresectable hepatic metastases including systemic chemotherapy and novel molecular targeted therapies. Treatment with somatostatin analogs (SSA) as antiproliferative agents is optional. At initial diagnosis watchful waiting until tumor progression is a well-established approach. Goal of this study was to evaluate imaging features as potential prognostic factors predicting early tumor progression in order to select patients that might benefit from an earlier initiation of medical treatment. Patients and methods: In 44 patients we correlated tumor grade, chromogranin A (CgA) levels, treatment with SSA and imaging features of hepatic metastases on contrast-enhanced multiphase CT and MR imaging with time to tumor progression (TTP) according to RECIST 1.0. Results: In the total patient cohort none of the tested imaging features was found to be a statistically significant prognostic factor for TTP. Since treatment with SSA was associated with an increased TTP we also analyzed a subgroup of 30 patients not treated with SSA. In this subgroup of patients hypoenhancement of hepatic metastases during early contrast phases was found to be a negative prognostic factor for early tumor progression within 12 months (p = 0.039). The other evaluated parameters including hepatic tumor load, number of metastases, and presence of regressive morphological changes did not reveal significant results. Conclusion: Hypovascularization of liver metastases from G1 and G2 pNET reflected by hypoenhancement during the early contrast phases seems to be associated with early tumor progression. In patients with hypoenhancing metastases repeated biopsy for reassessment of grading of these metastases, and early initiation of therapy should be considered.

  3. Regression of peripapillary choroidal neovascular membrane in a patient with sarcoidosis after oral steroid therapy☆

    Science.gov (United States)

    Shoughy, Samir S.; Jaroudi, Mahmoud O.; Tabbara, Khalid F.

    2014-01-01

    Choroidal neovascular membrane (CNV) may occur in patients with posterior uveitis. Treatment of patients with corticosteroids induces regression of the inflammation in the posterior pole with downregulation of many cytokines including vascular endothelial growth factors. We report herewith, a case of biopsy proven sarcoidosis that developed posterior uveitis and peripapillary CNV membrane and subretinal hemorrhage with fluid. The patient was treated with systemic steroids. She demonstrated progressive regression of the CNV membrane and complete resolution of the subretinal hemorrhage and fluids. In conclusion, control of the posterior segment inflammation is crucial in the resolution of the CNV membrane in uveitis and the intravitreal anti-vascular endothelial growth factor may not be always indicated. PMID:24843312

  4. Regression of peripapillary choroidal neovascular membrane in a patient with sarcoidosis after oral steroid therapy.

    Science.gov (United States)

    Shoughy, Samir S; Jaroudi, Mahmoud O; Tabbara, Khalid F

    2014-04-01

    Choroidal neovascular membrane (CNV) may occur in patients with posterior uveitis. Treatment of patients with corticosteroids induces regression of the inflammation in the posterior pole with downregulation of many cytokines including vascular endothelial growth factors. We report herewith, a case of biopsy proven sarcoidosis that developed posterior uveitis and peripapillary CNV membrane and subretinal hemorrhage with fluid. The patient was treated with systemic steroids. She demonstrated progressive regression of the CNV membrane and complete resolution of the subretinal hemorrhage and fluids. In conclusion, control of the posterior segment inflammation is crucial in the resolution of the CNV membrane in uveitis and the intravitreal anti-vascular endothelial growth factor may not be always indicated.

  5. Viability of a jejunal segment after neovascularization by omentoenteropexy Viabilidade de segmento jejunal neovascularizado por omentoenteropexia

    Directory of Open Access Journals (Sweden)

    Mércia Maria Braga Rocha

    2002-01-01

    Full Text Available Omentoenteropexy was developed as an alternative technique to promote neovascularization in an isolated bowel segment. OBJECTIVE: The aim of the present protocol was to study the long-term viability of an isolated jejunal segment following neovascularization by omentoenteropexy. Long-term survival of a neovascularized bowel segment is an indication that the utilization of this segment as an intestinal graft can be successful. METHODS: To test the proposed surgical technique, 13 Wistar rats were subjected to laparotomy, the jejunum was exposed at 20 cm from the angle of Treitz and a pedicle of greater omentum was isolated. An incision of 6 cm was made along the antimesenteric jejunal border, exposing the submucosa. Omentoenteropexy was performed between the incision of the jejunum and the pedicle of the greater omentum. After seven weeks, the mesentery of the jejunal segment subjected to omentoenteropexy was ligated and isolated from the rest of the jejunum by a complete proximal and distal transversal section. Subsequently, an end-to-end anastomosis was performed to restore the continuity of the bowel. RESULTS: At 10 weeks from the first surgical intervention, the isolated jejunal segment subjected to omentoenteropexy was completely neovascularized and viable. CONCLUSION: No evidence of anatomical or functional intestinal obstruction was observed.A omentoenteropexia foi desenvolvida como uma alternativa para técnica de neovascularização em segmentos intestinais isolados, evidenciando algumas vantagens em relação a utilização de órgãos previamente descritos. OBJETIVO: Avaliar a viabilidade de um segmento jejunal neovascularizado por omentoenteropexia. MÉTODOS: Treze ratos Wistar foram submetidos a laparotomia, com exposição do jejuno vinte centímetros após o ligamento de Treitz e obtenção de um pedículo de omento. Na borda antimesentérica do jejuno foi feita uma incisão de seis centímetros com exposição da submucosa intacta

  6. Heparanase-1 activities in the development of laser induced choroidal neovascularization

    Directory of Open Access Journals (Sweden)

    Bao-Ke Hou

    2013-04-01

    Full Text Available AIM:To investigate the role of heparanase-1 in laser-induced choroidal neovascularization (CNV.METHODS:Experimental CNV was induced by krypton laser photocoagulation in 15 male Brown Norway rats. Fundus fluorescein angiography and histopathological examination were performed in observing the CNV development. The expression and distribution of heparanase-1 protein in the laser lesions were determined by immunohistochemistry and western blotting analysis.RESULTS:The success rate of laser induced CNV was approximately 75% on 3-4 weeks after laser photocoagulation. The protein levels of heparanase-1 increased significantly in the retina-choroidal complex of CNV models when compared to normal rat eyes (P<0.01. Immunostaining confirmed strong heparanase-1 expressions in all laser lesions, and it displayed to be highest at the newly formed blood vessels within the fibrovascular complex in the subretinal space.CONCLUSION:Heparanase-1 is closely involved in the development of laser induced CNV.

  7. [Choroidal neovascularization followed in a patient with "Multiple Evanescent White Dot Syndrome" (MEWDS) -- a case report].

    Science.gov (United States)

    Löw, U; Palmowski, A M; Weich, C-M; Ruprecht, K W

    2004-12-01

    Since the description of the "multiple evanescent white dot syndrome" (MEWDS) by Jampol et al, choroiditis has been in the focus of interest. But the classical type of MEWDS was an exceptional case in clinical routine. A 48-year-old female presented to our hospital with a sudden unilateral visual acuity decrease and an extension of the blind spot. Ophthalmoscopy and fluorescein angiography revealed typical multiple grey-white chorioretinal patches of the same stage with lesion areas of about 100 - 200 microm compatible with the diagnose of MEWDS. Although visual acuity increased continuously the patient developed a classical choroidal neovascularization within 4 weeks. She was treated with PDT and visual acuity as well as the ophthalmoscopic diagnosis remained stable. In spite of visual improvement in MEWDS, regular control is recommended. In addition we propose to consider the diagnosis of MEWDS if an enlargement of the blind spot and CNV without lesions of the retinal pigment epithelium are diagnosed.

  8. Evolution of Choroidal Neovascular Membrane in Best Disease after Single Intravitreal Bevacizumab. Case Report.

    Science.gov (United States)

    Celea, Christiana; Pop, Mihai; Avidis-Zamfiroiu, Nicoleta; Celea, Cristian

    2015-03-01

    Best's disease is a hereditary form of macular dystrophy that starts in childhood and progresses until visual symptoms occur. In evolution it can be complicated with choroidal neovascularization, condition very rare in children. We report an important visual improvement in a 8-year-old caucasian girl after successful treatment with one intravitreal bevacizumab injection. There are few cases reported in literature (1-7), and the patient presented here have important particularities: one of the youngest children ever-mentioned with this complication, the third-member of her family with this disease and the first patient who didn't receive a second intravitreal bevacizumab at six weeks after first treatment, even though BCVA was lower than expected. The girl accused decrease of vision in the RE for the past 3-4 months. BCVA at presentation was 1/10. After 6 weeks from the intravitreal treatment, BCVA improved, but not very satisfactory (5/10). Because fundus and OCT aspects were encouraging, we waited another 4 weeks before the second injection. BCVA doubled in this period (8/10). Visual acuity, fundus and OCT aspects stabilized for 18 months of follow-up. We note that choroidal neovascular membrane associated with Best's disease can appear at such young children, this fact being very important in the phase of diagnosis, when the clinician should also take in consideration this possibility. Another important idea underlined here is the long-term efficacy of a single intravitreal anti-VEGF injection and also the no-need for imminent, fast re-treatment when the fundus and OCT aspects are encouraging through the follow-up.

  9. Phthalimide neovascular factor 1 (PNF1) modulates MT1-MMP activity in human microvascular endothelial cells.

    Science.gov (United States)

    Wieghaus, Kristen A; Gianchandani, Erwin P; Neal, Rebekah A; Paige, Mikell A; Brown, Milton L; Papin, Jason A; Botchwey, Edward A

    2009-07-01

    We are creating synthetic pharmaceuticals with angiogenic activity and potential to promote vascular invasion. We previously demonstrated that one of these molecules, phthalimide neovascular factor 1 (PNF1), significantly expands microvascular networks in vivo following sustained release from poly(lactic-co-glycolic acid) (PLAGA) films. In addition, to probe PNF1 mode of action, we recently applied a novel pathway-based compendium analysis to a multi-timepoint, controlled microarray data set of PNF1-treated (vs. control) human microvascular endothelial cells (HMVECs), and we identified induction of tumor necrosis factor-alpha (TNF-alpha) and, subsequently, transforming growth factor-beta (TGF-beta) signaling networks by PNF1. Here we validate this microarray data set with quantitative real-time polymerase chain reaction (RT-PCR) analysis. Subsequently, we probe this data set and identify three specific TGF-beta-induced genes with regulation by PNF1 conserved over multiple timepoints-amyloid beta (A4) precursor protein (APP), early growth response 1 (EGR-1), and matrix metalloproteinase 14 (MMP14 or MT1-MMP)-that are also implicated in angiogenesis. We further focus on MMP14 given its unique role in angiogenesis, and we validate MT1-MMP modulation by PNF1 with an in vitro fluorescence assay that demonstrates the direct effects that PNF1 exerts on functional metalloproteinase activity. We also utilize endothelial cord formation in collagen gels to show that PNF1-induced stimulation of endothelial cord network formation in vitro is in some way MT1-MMP-dependent. Ultimately, this new network analysis of our transcriptional footprint characterizing PNF1 activity 1-48 h post-supplementation in HMVECs coupled with corresponding validating experiments suggests a key set of a few specific targets that are involved in PNF1 mode of action and important for successful promotion of the neovascularization that we have observed by the drug in vivo.

  10. Inhibitory effects of regorafenib, a multiple tyrosine kinase inhibitor, on corneal neovascularization

    Directory of Open Access Journals (Sweden)

    Halil Ibrahim Onder

    2014-04-01

    Full Text Available AIM:To evaluate the inhibitory effects of regorafenib (BAY 73-4506, a multikinase inhibitor, on corneal neovascularization (NV.METHODS:Thirty adult male Sprague-Dawley rats weighing 250-300 g, were used. Corneal NV was induced by NaOH in the left eyes of each rat. Following the establishment of alkali burn, the animals were randomized into five groups according to topical treatment. Group 1 (n = 6 received 0.9% NaCl, Group 2 (n = 6 received dimethyl sulfoxide, Group 3 (n = 6 received regorafenib 1 mg/mL, Group 4 (n =6 received bevacizumab 5 mg/mL and Group 5 (n = 6 received 0.1% dexamethasone phosphate. On the 7d, the corneal surface covered with neovascular vessels was measured on photographs as the percentage of the cornea’s total area using computer-imaging analysis. The corneas obtained from rats were semiquantitatively evaluated for caspase-3 and vascular endothelial growth factor by immunostaining.RESULTS:A statistically significant difference in the percent area of corneal NV was found among the groups (P <0.001. Although the Group 5 had the smallest percent area of corneal NV, there was no difference among Groups 3, 4 and 5 (P >0.005. There was a statistically significant difference among the groups in apoptotic cell density (P = 0.002. The staining intensity of vascular endothelial growth factor in the epithelial and endothelial layers of cornea was significantly different among the groups (P <0.05. The staining intensity of epithelial and endothelial vascular endothelial growth factor was significantly weaker in Groups 3, 4 and 5 than in Groups 1 and 2.CONCLUSION: Topical administration of regorafenib 1 mg/mL is partly effective for preventing alkali-induced corneal NV in rats.

  11. miR-539-5p inhibits experimental choroidal neovascularization by targeting CXCR7.

    Science.gov (United States)

    Feng, Yifan; Wang, Jing; Yuan, Yuanzhi; Zhang, Xi; Shen, Minqian; Yuan, Fei

    2018-03-01

    Stromal cell-derived factor-1 (SDF-1) has been previously confirmed to participate in the formation of choroidal neovascularization (CNV) via its receptor, CXC chemokine receptor (CXCR) 4; CXCR7 is a recently identified receptor for SDF-1. The molecular mechanisms and therapeutic value of CXCR7 in CNV remain undefined. In this study, experimental CNV was induced by laser photocoagulation in Brown-Norway pigmented rats, and aberrant CXCR7 overexpression was detected in the retinal pigment epithelial/choroid/sclera tissues of laser-injured eyes. Blockade of CXCR7 activation via CXCR7 knockdown or neutralizing Ab administration inhibited SDF-1-induced cell survival and the tubular formation of human retinal microvascular endothelial cells (HRMECs) in vitro and reduced CNV leakage and lesion size in vivo. By using microRNA array screening and bioinformatic analyses, we identified miR-539-5p as a regulator of CXCR7. Transfection of HRMECs and choroid-retinal endothelial (RF/6A) cells with the miR-539-5p mimic inhibited their survival and tube formation, whereas CXCR7 overexpression rescued the suppressive effect of miR-539-5p. The antiangiogenic activities of the miR-539-5p mimic were additionally demonstrated in vivo by intravitreal injection. ERK1/2 and AKT signaling downstream of CXCR7 is involved in the miR-539-5p regulation of endothelial cell behaviors. These findings suggest that the manipulation of miR-539-5p/CXCR7 levels may have important therapeutic implications in CNV-associated diseases.-Feng, Y., Wang, J., Yuan, Y., Zhang, X., Shen, M., Yuan, F. miR-539-5p inhibits experimental choroidal neovascularization by targeting CXCR7.

  12. Podoplanin-expressing Cells Derived from Bone Marrow Play a Crucial Role in Postnatal Lymphatic Neovascularization

    Science.gov (United States)

    Lee, Ji Yoon; Park, Changwon; Cho, Yong Pil; Lee, Eugine; Kim, Hyongbum; Kim, Pilhan; Yun, Seok H.; Yoon, Young-sup

    2010-01-01

    Background Emerging evidence has suggested a contribution of bone marrow (BM) cells to lymphatic vessel formation; however, the exact phenotype of the cells with lymphatic endothelial progenitor cell (LEPC) function has yet to be identified. Here we investigate the identity of BM-derived LEPCs and their role in lymphatic neovascularization. Methods and Results Culture of BM-mononuclear cells (MNCs) in the presence of VEGFA, VEGFC and EGF resulted in expression of lymphatic endothelial cell (LEC) markers. Among these cells, podoplanin+ cells were isolated by magnetic-labeled cell separation system (MACS) and characterized by FACS and immunocytochemistry. These podoplanin+ cells highly express markers for LECs, hematopoietic lineages, and stem/progenitor cells, and upon further cultivation, generate LECs. We further confirmed that podoplanin+ cells exist in small numbers in BM and peripheral blood (PB) of normal mice, but are significantly (15 fold) augmented upon lymphangiogenic stimuli such as tumor implantation. Next, to evaluate the potential of podoplanin+ cells for the formation of new lymphatic vessels in vivo, we injected culture-isolated or freshly isolated BM-derived podoplanin+ cells into wound and tumor models. Immunohistochemistry demonstrated that the injected cells were incorporated into the lymphatic vasculature, displayed LEC phenotypes, and increased lymphatic vascular density in tissues, suggesting lymphvasculogenesis. Podoplanin+ cells also expressed high levels of lymphangiogenic cytokines and increased proliferation of LECs during co-culture, suggesting a lymphangiogenic or paracrine role. Conclusions Our results provide compelling evidence that BM-derived podoplanin+ cells, a previously unrecognized cell type, function as LEPCs and participate in postnatal lymphatic neovascularization through both lymphvasculogenesis and lymphangiogenesis. PMID:20855662

  13. Study of krypton laser-induced choroidal neovascularization in a Guinea pig model of high anisometropia.

    Science.gov (United States)

    Wang, Jianghui; Jiang, Wei; Kang, Zefeng; Liang, Lina; Liu, Xiaoman; Tian, Nannan; Zhang, Qing

    2012-06-01

    To investigate the association between high anisometropia and the area of choroidal neovascularization (CNV) induced by krypton laser in guinea pigs and better understand the pathogenesis and prevention of myopic CNV. Nine 3-week old male guinea pigs with anisometropia >6.00D were randomly assigned to three groups according to examination date after laser photocoagulation (7d, 14d and 28d). All animals underwent refraction. The eye with higher myopia was used as the experimental eye, and the other as the control eye. All eyes received repeated multi-wavelength krypton laser photocoagulation treatments (wavelength: 532nm; laser power: 400mW; spot diameter: 50μm; exposure time: 0.1s). Fundus photography and indocyanine green angiography (ICGA) were performed. Afterwards, the animals were sacrificed immediately, and the eyes were enucleated and processed for histopathologic examination and flat mounts. CNV appeared at 7d after laser treatment. The area of CNV peaked at 14d, and decrease in area and the presence of scarring was noted at 28 d. CNV was present in 66.7% of eyes by ICGA at 14 d. CNV could be observed under light microscopy at all three time points. At 14d, flat mount showed the neovascular plexus around the lesion. Semi-quantitative analysis revealed that the area of CNV in treated eyes was greater than that of control eyes. Since the mechanism of CNV in this study resembles that of CNV in pathological myopia, this model can be used to investigate the etiology, pathogenesis and treatment of CNV in pathological myopia.

  14. Decellularized Matrix from Tumorigenic Human Mesenchymal Stem Cells Promotes Neovascularization with Galectin-1 Dependent Endothelial Interaction

    Science.gov (United States)

    Burns, Jorge S.; Kristiansen, Malthe; Kristensen, Lars P.; Larsen, Kenneth H.; Nielsen, Maria O.; Christiansen, Helle; Nehlin, Jan; Andersen, Jens S.; Kassem, Moustapha

    2011-01-01

    Background Acquisition of a blood supply is fundamental for extensive tumor growth. We recently described vascular heterogeneity in tumours derived from cell clones of a human mesenchymal stem cell (hMSC) strain (hMSC-TERT20) immortalized by retroviral vector mediated human telomerase (hTERT) gene expression. Histological analysis showed that cells of the most vascularized tumorigenic clone, -BD11 had a pericyte-like alpha smooth muscle actin (ASMA+) and CD146+ positive phenotype. Upon serum withdrawal in culture, -BD11 cells formed cord-like structures mimicking capillary morphogenesis. In contrast, cells of the poorly tumorigenic clone, -BC8 did not stain for ASMA, tumours were less vascularized and serum withdrawal in culture led to cell death. By exploring the heterogeneity in hMSC-TERT20 clones we aimed to understand molecular mechanisms by which mesenchymal stem cells may promote neovascularization. Methodology/Principal Findings Quantitative qRT-PCR analysis revealed similar mRNA levels for genes encoding the angiogenic cytokines VEGF and Angiopoietin-1 in both clones. However, clone-BD11 produced a denser extracellular matrix that supported stable ex vivo capillary morphogenesis of human endothelial cells and promoted in vivo neovascularization. Proteomic characterization of the -BD11 decellularized matrix identified 50 extracellular angiogenic proteins, including galectin-1. siRNA knock down of galectin-1 expression abrogated the ex vivo interaction between decellularized -BD11 matrix and endothelial cells. More stable shRNA knock down of galectin-1 expression did not prevent -BD11 tumorigenesis, but greatly reduced endothelial migration into -BD11 cell xenografts. Conclusions Decellularized hMSC matrix had significant angiogenic potential with at least 50 angiogenic cell surface and extracellular proteins, implicated in attracting endothelial cells, their adhesion and activation to form tubular structures. hMSC -BD11 surface galectin-1 expression was

  15. External beam radiotherapy for subretinal neovascularization in age-related macular degeneration: is this treatment efficient?

    International Nuclear Information System (INIS)

    Staar, Susanne; Krott, Ralf; Mueller, Rolf-Peter; Bartz-Schmidt, Karl U.; Heimann, Klaus

    1999-01-01

    Purpose: Control of the natural course of sub retinal neovascularization (SRNV) in age-related macular degeneration (AMD) is difficult. Only a subset of patients is suitable for laser coagulation. This prospective study aimed to determine the efficacy and individual benefit of external beam radiotherapy (EBRT). Methods and Materials: The prospective trial included 287 patients with subfoveal neovascularization due to AMD which was verified by fluorescein angiography. Patients have been treated between January 1996 and October 1997. All patients received a total dose of 16 Gy in 2-Gy daily fractions with 5-6 MeV photons based on computerized treatment planning in individual head mask fixation. This first analysis is based on 73 patients (50 women, 23 men, median age 74.3 years), with a median follow-up of 13.3 months and a minimum follow-up of 11 months. Results: All patients completed therapy and tolerability was good. First clinical control with second angiography was performed 6 weeks after irradiation, then in 3-month intervals. Eighteen patients with SRNV refusing radiotherapy served as a control group and were matched with 18 irradiated patients. After 7 months median visual acuity (VA) was 20/160 for the irradiated and 20/400 for the untreated patients. One year after radiotherapy final median VA was 20/400 in both groups. Conclusion: These results suggest that 16 Gy of conventionally fractionated external beam irradiation slows down the visual loss in exudative AMD for only a few months. Patients' reading vision could not be saved for a long-term run

  16. Transscleral sustained vasohibin-1 delivery by a novel device suppressed experimentally-induced choroidal neovascularization.

    Directory of Open Access Journals (Sweden)

    Hideyuki Onami

    Full Text Available We established a sustained vasohibin-1 (a 42-kDa protein, delivery device by a novel method using photopolymerization of a mixture of polyethylene glycol dimethacrylate, triethylene glycol dimethacrylate, and collagen microparticles. We evaluated its effects in a model of rat laser-induced choroidal neovascularization (CNV using a transscleral approach. We used variable concentrations of vasohibin-1 in the devices, and used an enzyme-linked immunosorbent assay and Western blotting to measure the released vasohibin-1 (0.31 nM/day when using the 10 μM vasohibin-1 delivery device [10VDD]. The released vasohibin-1 showed suppression activity comparable to native effects when evaluated using endothelial tube formation. We also used pelletized vasohibin-1 and fluorescein isothiocyanate-labeled 40 kDa dextran as controls. Strong fluorescein staining was observed on the sclera when the device was used for drug delivery, whereas pellet use produced strong staining in the conjunctiva and surrounding tissue, but not on the sclera. Vasohibin-1 was found in the sclera, choroid, retinal pigment epithelium (RPE, and neural retina after device implantation. Stronger immunoreactivity at the RPE and ganglion cell layers was observed than in other retinal regions. Significantly lower fluorescein angiography (FA scores and smaller CNV areas in the flat mounts of RPE-choroid-sclera were observed for the 10VDD, VDD (1 μM vasohibin-1 delivery device, and vasohibin-1 intravitreal direct injection (0.24 μM groups when compared to the pellet, non-vasohibin-1 delivery device, and intravitreal vehicle injection groups. Choroidal neovascularization can be treated with transscleral sustained protein delivery using our novel device. We offer a safer sustained protein release for treatment of retinal disease using the transscleral approach.

  17. Anti-vascular endothelial growth factor therapy for the treatment of myopic choroidal neovascularization

    Directory of Open Access Journals (Sweden)

    Tan CS

    2017-09-01

    Full Text Available Colin S Tan,1,2 SriniVas R Sadda3 1National Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore; 2Fundus Image Reading Center, National Healthcare Group Eye Institute, Singapore; 3Doheny Eye Institute, University of California Los Angeles, CA, USA Abstract: Myopic choroidal neovascularization (CNV is a sight-threatening condition which occurs in eyes with myopia, particularly in those with pathologic myopia. It is the most common cause of CNV among patients younger than 50 years. Hemorrhage and exudation from the CNV lesion may eventually result in scarring or chorioretinal atrophy. While myopic CNV was previously treated with focal laser photocoagulation or photodynamic therapy (PDT, the current treatment of choice is anti-vascular endothelial growth factor (VEGF agents. Many studies have demonstrated the efficacy of intravitreal anti-VEGF agents in the treatment of myopic CNV. The RADIANCE study reported that intravitreal ranibizumab was superior to PDT in eyes with myopic CNV (at 3 months, both groups receiving intravitreal ranibizumab gained 10.5 and 10.6 letters vs 2.2 letters among patients receiving PDT. In addition, the study demonstrated similar visual outcomes in eyes treated on the basis of visual acuity stabilization or disease activity criteria. Other clinical studies have provided evidence for the efficacy of ranibizumab and aflibercept in the treatment of myopic CNV. This review addresses the epidemiology, pathophysiology, and imaging characteristics of myopic CNV, and discusses the evidence for the efficacy of anti-VEGF agents as compared to laser photocoagulation and PDT. Keywords: myopic choroidal neovascularization, ranibizumab, anti-vascular endothelial growth factor

  18. Optical Coherence Tomography and the Development of Antiangiogenic Therapies in Neovascular Age-Related Macular Degeneration

    Science.gov (United States)

    Rosenfeld, Philip J.

    2016-01-01

    Purpose To explain the pivotal role optical coherence tomography (OCT) imaging had in the development of antiangiogenic therapies for the treatment of neovascular age-related macular degeneration (nvAMD). Methods A historical literature review was combined with personal perspectives from the introduction of OCT imaging and the early clinical use of vascular endothelial growth factor (VEGF) inhibitors. Results At the time that OCT emerged, the gold standard for imaging of nvAMD was fluorescein angiography (FA), a time-consuming, dye-based, invasive technique that provided en face images of the retina and was used to characterize leakage, perfusion status, and the types of macular neovascularization (MNV). In comparison, OCT imaging was a fast, safe, noninvasive technique that complemented FA imaging by providing cross-sectional images of the macula. OCT was able to visualize and quantify the macular fluid that was associated with the presence of excess VEGF, which was identified by intraretinal fluid, subretinal fluid, and fluid under the retinal pigment epithelium (RPE). Clinicians quickly appreciated the benefits of OCT imaging for following macular fluid after anti-VEGF therapy. By observing the qualitative and quantitative changes in macular fluid depicted by OCT imaging, clinicians were empowered to compare anti-VEGF drugs and move from fixed-dosing regimens to patient-specific dosing strategies requiring fewer injections. Conclusions Optical coherence tomography imaging was adopted as a VEGF-meter, a method to detect excess VEGF, and evolved to become the gold standard imaging strategy for diagnosing nvAMD, assessing treatment responses to anti-VEGF drugs, deciding when to re-treat, and evaluating disease progression. PMID:27409464

  19. Corneal Neovascularization with Associated Lipid Keratopathy in a Patient with Obstructive Sleep Apnea-Hypopnea Syndrome Using a Continuous Positive Airway Pressure Machine

    Directory of Open Access Journals (Sweden)

    Konstantinos Oikonomakis

    2017-08-01

    Full Text Available Objective: To report a case of corneal neovascularization with secondary lipid keratopathy in a patient treated with continuous positive airway pressure (CPAP for obstructive sleep apnea-hypopnea syndrome (OSAHS. Case Report: A 49-year-old male had been diagnosed with obstructive sleep apnea syndrome 10 years ago and has been treated with the application of a CPAP machine during night sleep ever since. For the past year, the patient had been complaining for ocular irritation and excessive tearing of the left eye on awakening. Slit-lamp biomicroscopy revealed the presence of neovascularization and lipid exudation in the inferior third of the cornea of the left eye. Ocular patching during night sleep resulted in recession of the reported symptoms and shrinkage of the neovascularization, while the area of lipid exudation ceased to enlarge. Conclusion: To the best of our knowledge, this is the first report of corneal neovascularization in a patient using a CPAP machine for OSAHS.

  20. Corneal Neovascularization with Associated Lipid Keratopathy in a Patient with Obstructive Sleep Apnea-Hypopnea Syndrome Using a Continuous Positive Airway Pressure Machine.

    Science.gov (United States)

    Oikonomakis, Konstantinos; Petrelli, Myrsini; Andreanos, Konstantinos; Mouchtouris, Andreas; Petrou, Petros; Georgalas, Ilias; Papaconstantinou, Dimitrios; Kymionis, George

    2017-01-01

    To report a case of corneal neovascularization with secondary lipid keratopathy in a patient treated with continuous positive airway pressure (CPAP) for obstructive sleep apnea-hypopnea syndrome (OSAHS). A 49-year-old male had been diagnosed with obstructive sleep apnea syndrome 10 years ago and has been treated with the application of a CPAP machine during night sleep ever since. For the past year, the patient had been complaining for ocular irritation and excessive tearing of the left eye on awakening. Slit-lamp biomicroscopy revealed the presence of neovascularization and lipid exudation in the inferior third of the cornea of the left eye. Ocular patching during night sleep resulted in recession of the reported symptoms and shrinkage of the neovascularization, while the area of lipid exudation ceased to enlarge. To the best of our knowledge, this is the first report of corneal neovascularization in a patient using a CPAP machine for OSAHS.

  1. Aflibercept: a review of its use in the treatment of choroidal neovascularization due to age-related macular degeneration

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    Balaratnasingam C

    2015-12-01

    Full Text Available Chandrakumar Balaratnasingam,1–3 Elona Dhrami-Gavazi,1,2,4 Jesse T McCann,1,2,4,5 Quraish Ghadiali,1,2 K Bailey Freund1,2,4,5 1Vitreous-Retina-Macula Consultants of New York, NY, USA; 2LuEsther T Mertz Retinal Research Center, Manhattan Eye, Ear and Throat Hospital, New York, NY, USA; 3Centre for Ophthalmology and Visual Sciences, Lions Eye Institute, University of Western Australia, Perth, WA, Australia; 4Department of Ophthalmology, Edward S Harkness Eye Institute, Columbia University College of Physicians and Surgeons, New York, NY, USA; 5Department of Ophthalmology, New York University School of Medicine, New York, NY, USA Abstract: Choroidal neovascularization (CNV due to age-related macular degeneration (AMD is an important cause of visual morbidity globally. Modern treatment strategies for neovascular AMD achieve regression of CNV by suppressing the activity of key growth factors that mediate angiogenesis. Vascular endothelial growth factor (VEGF has been the major target of neovascular AMD therapy for almost two decades, and there have been several intravitreally-administered agents that have enabled anatomical restitution and improvement in visual function with continual dosing. Aflibercept (EYLEA®, initially named VEGF Trap-eye, is the most recent anti-VEGF agent to be granted US Food and Drug Administration approval for the treatment of neovascular AMD. Biologic advantages of aflibercept include its greater binding affinity for VEGF, a longer intravitreal half-life relative to other anti-VEGF agents, and the capacity to antagonize growth factors other than VEGF. This paper provides an up-to-date summary of the molecular mechanisms mediating CNV. The structural, pharmacodynamic, and pharmacokinetic advantages of aflibercept are also reviewed to rationalize the utility of this agent for treating CNV. Results of landmark clinical investigations, including VIEW 1 and 2 trials, and other important studies are then summarized and used to

  2. Non-functioning parathyroid cystic tumour: malignant or not? Report of a case.

    Science.gov (United States)

    Cocorullo, G; Scerrino, G; Melfa, G; Raspanti, C; Rotolo, G; Mannino, V; Richiusa, P; Cabibi, D; Giannone, A G; Porrello, C; Gulotta, G

    2017-01-01

    Parathyroid carcinoma (PC) is a very rare endocrine tumour, usually characterized by symptoms such as a neck mass, dysphonia, severe hypercalcemia exceeding 140 mg/L and elevated serum parathyroid hormone levels, even more than 5 times the upper limit of normal. Non-functioning parathyroid cancer is extremely rare and, in this case, its pre-operative diagnosis is often difficult. A 54-year old female patient, referring dysphagia and dysphonia, underwent neck ultrasound and neck CT. A left thyroid nodule, probably cystic, was found. It presented caudal extent on anterior mediastinum causing compression of the left lateral wall of the trachea. The preoperative calcemia was into the normal range. The patient underwent left thyroid lobectomy. Histological exam showed a cystic lesion, immunohistochemically originating from parathyroid that oriented for carcinoma. The 18 months follow-up did not show a residual-recurrent disease. The parathyroid origin of a neck lesion could not be suspected before surgery when specific laboratory tests are not available and clinical effects of hyperparathyroidism syndrome are not present. Histological features are not always sufficient for the differential diagnosis between the parathyroid adenoma and carcinoma. The immunohistochemistry is an useful tool that can aid to reach the definite diagnosis.

  3. Contribution of molecular analysis to the typification of the non-functioning pituitary adenomas

    Science.gov (United States)

    Sanchez-Ortiga, Ruth; Aranda, Francisco Ignacio

    2017-01-01

    Aim The WHO Classification of Tumours of Endocrine Organs considers the inmunohistochemical characterization of pituitary adenomas (PA) as mandatory for patient diagnosis. Recent advances in the knowledge of the molecular patterns of these tumours could complement this classification with gene expression profiling. Methods Within the context of the Spanish Molecular Registry of Pituitary Adenomas (REMAH), a multicentre clinical-basic research project, we analysed the molecular phenotype of 142 PAs with complete IHC and clinical information. Gene expression levels of all pituitary hormones, type 1 corticotrophin-releasing hormone receptor, dopamine receptors and arginine vasopressin receptor 1b were measured by quantitative real-time polymerase chain reaction. In addition, we used three housekeeping genes for normalization and a pool of nine healthy pituitary glands from autopsies as calibration reference standard. Results Based on the clinically functioning PA (FPA: somatotroph, corticotroph, thyrotroph and lactotroph adenomas), we established the interquartile range of relative expression for all genes studied in each PA subtype. That allowed molecularly the different PA subtypes, including the clinically non-functioning PA (NFPA). Afterwards, we estimated the concordance of the molecular and immunohistochemical classification with clinical diagnosis in FPA and between them in NFPA. The kappa values were higher in molecular than in immunohistochemical classification in FPA and showed a bad concordance in all NFPA subtypes. Conclusions According to these results, the molecular characterization of the PA complements the IHC analysis, allowing a better typification of the NFPA. PMID:28692683

  4. Contribution of molecular analysis to the typification of the non-functioning pituitary adenomas.

    Directory of Open Access Journals (Sweden)

    Laura Sanchez-Tejada

    Full Text Available The WHO Classification of Tumours of Endocrine Organs considers the inmunohistochemical characterization of pituitary adenomas (PA as mandatory for patient diagnosis. Recent advances in the knowledge of the molecular patterns of these tumours could complement this classification with gene expression profiling.Within the context of the Spanish Molecular Registry of Pituitary Adenomas (REMAH, a multicentre clinical-basic research project, we analysed the molecular phenotype of 142 PAs with complete IHC and clinical information. Gene expression levels of all pituitary hormones, type 1 corticotrophin-releasing hormone receptor, dopamine receptors and arginine vasopressin receptor 1b were measured by quantitative real-time polymerase chain reaction. In addition, we used three housekeeping genes for normalization and a pool of nine healthy pituitary glands from autopsies as calibration reference standard.Based on the clinically functioning PA (FPA: somatotroph, corticotroph, thyrotroph and lactotroph adenomas, we established the interquartile range of relative expression for all genes studied in each PA subtype. That allowed molecularly the different PA subtypes, including the clinically non-functioning PA (NFPA. Afterwards, we estimated the concordance of the molecular and immunohistochemical classification with clinical diagnosis in FPA and between them in NFPA. The kappa values were higher in molecular than in immunohistochemical classification in FPA and showed a bad concordance in all NFPA subtypes.According to these results, the molecular characterization of the PA complements the IHC analysis, allowing a better typification of the NFPA.

  5. Hypogonadotropic Hypogonadism in Non-Functioning Pituitary Adenomas: Impact of Intervention.

    Science.gov (United States)

    Monteiro, Diana Margarida; Freitas, Paula; Vieira, Romana; Carvalho, Davide

    2017-06-01

    To determine the prevalence of hypogonadotropic hypogonadism (HH) among patients with non-functioning pituitary adenomas (NFPA) and the post-surgery outcome on pituitary gonadotropins secretion (PGS); to determine the prevalence of erectile dysfunction (ED) on male patients with NFPA, to evaluate the impact of testosterone replacement therapy (TRT) in those with HH. Retrospective evaluation of gonadal function in 109 NFPA patients (45 males), with a mean age of 51.8 years, diagnosed on the last 10 years. ED questionnaire applied to 34 male patients. Male patients with NFPA were significantly older (males 58.1±15.8 vs. females 47.4±16.94; p=0.001). Most patients had macroadenomas (67%; p=0.001) and only a minority were incidentalomas (19%; pmales, 25% on females; pmales, 42% of females; pMales were older, had more HH and surgery. There was no significant improvement of pituitary function with surgery (17%) and 13% became iatrogenic HH. TRT had a low efficacy to improve ED in these patients. © Georg Thieme Verlag KG Stuttgart · New York.

  6. Intraoperative magnetic resonance imaging assessment of non-functioning pituitary adenomas during transsphenoidal surgery.

    Science.gov (United States)

    Patel, Kunal S; Yao, Yong; Wang, Renzhi; Carter, Bob S; Chen, Clark C

    2016-04-01

    To review the utility of intraoperative imaging in facilitating maximal resection of non-functioning pituitary adenomas (NFAs). We performed an exhaustive MEDLINE search, which yielded 5598 articles. Upon careful review of these studies, 31 were pertinent to the issue of interest. Nine studies examined whether intraoperative MRI (iMRI) findings correlated with the presence of residual tumor on MRI taken 3 months after surgical resection. All studies using iMRI of >0.15T showed a ≥90% concordance between iMRI and 3-month post-operative MRI findings. 24 studies (22 iMRI and 2 intraoperative CT) examined whether intraoperative imaging improved the surgeon's ability to achieve a more complete resection. The resections were carried out under microscopic magnification in 17 studies and under endoscopic visualization in 7 studies. All studies support the value of intraoperative imaging in this regard, with improved resection in 15-83% of patients. Two studies examined whether iMRI (≥0.3T) improved visualization of residual NFA when compared to endoscopic visualization. Both studies demonstrated the value of iMRI in this regard, particularly when the tumor is located lateral of the sella, in the cavernous sinus, and in the suprasellar space. The currently available literature supports the utility of intraoperative imaging in facilitating increased NFA resection, without compromising safety.

  7. Long-Term Visual Outcomes for a Treat and Extend Anti-Vascular Endothelial Growth Factor Regimen in Eyes with Neovascular Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Sarah Mrejen

    2015-07-01

    Full Text Available With the advent of anti-vascular endothelial growth factor (VEGF therapy, clinicians are now focused on various treatment strategies to better control neovascular age-related macular degeneration (NVAMD, a leading cause of irreversible blindness. Herein, we retrospectively reviewed consecutive patients with treatment-naïve NVAMD initially classified based on fluorescein angiography (FA alone or with an anatomic classification utilizing both FA and optical coherence tomography (OCT and correlated long-term visual outcomes of these patients treated with an anti-VEGF Treat-and-Extend Regimen (TER with baseline characteristics including neovascular phenotype. Overall, 185 patients (210 eyes were followed over an average of 3.5 years (range 1–6.6 with a retention rate of 62.9%, and visual acuity significantly improved with a TER that required a mean number of 8.3 (±1.6 (± standard deviation intravitreal anti-VEGF injections/year (range 4–13. The number of injections and the anatomic classification were independent predictors of visual acuity at 6 months, 1, 2, 3 and 4 years. Patients with Type 1 neovascularization had better visual outcomes and received more injections than the other neovascular subtypes. There were no serious adverse events. A TER provided sustained long-term visual gains. Eyes with Type 1 neovascularization had better visual outcomes than those with other neovascular subtypes.

  8. Relapse of choroidal neovascularization in Bietti's crystalline retinopathy following anti-vascular endothelial growth factor therapy: A case report.

    Science.gov (United States)

    Hua, Rui; Chen, Kang; Hu, Yuedong; Wang, Xinling; Chen, Lei

    2015-11-01

    Choroidal neovascularization secondary to retinitis pigmentosa is rarely observed in clinical practice. The present study describes a case of atypical retinitis pigmentosa, crystalline retinal pigmentary degeneration, complicated by choroidal neovascularization (CNV) in a 26-year-old man presenting with blurred vision in the right eye. Heidelberg multimodality imaging was performed to achieve a confirmed diagnosis. Bevacizumab was injected once intravitreally. The 3-month follow-up included visualization of the lesion's regression with spectral domain optical coherence tomography (SD-OCT). However, at 3 months after the injection, the CNV reoccurred. To the best of our knowledge, this is the first time that a case of CNV secondary to retinitis pigmentosa, in which the diagnosis was confirmed via multimodality imaging and the therapeutic efficacy was evaluated by SD-OCT, has been reported in China.

  9. Prognostic factors of non-functioning pancreatic neuroendocrine tumor revisited: The value of WHO 2010 classification.

    Science.gov (United States)

    Bu, Jiyoung; Youn, Sangmin; Kwon, Wooil; Jang, Kee Taek; Han, Sanghyup; Han, Sunjong; You, Younghun; Heo, Jin Seok; Choi, Seong Ho; Choi, Dong Wook

    2018-02-01

    Various factors have been reported as prognostic factors of non-functional pancreatic neuroendocrine tumors (NF-pNETs). There remains some controversy as to the factors which might actually serve to successfully prognosticate future manifestation and diagnosis of NF-pNETs. As well, consensus regarding management strategy has never been achieved. The aim of this study is to further investigate potential prognostic factors using a large single-center cohort to help determine the management strategy of NF-pNETs. During the time period 1995 through 2013, 166 patients with NF-pNETs who underwent surgery in Samsung Medical Center were entered in a prospective database, and those factors thought to represent predictors of prognosis were tested in uni- and multivariate models. The median follow-up time was 46.5 months; there was a maximum follow-up period of 217 months. The five-year overall survival and disease-free survival rates were 88.5% and 77.0%, respectively. The 2010 WHO classification was found to be the only prognostic factor which affects overall survival and disease-free survival in multivariate analysis. Also, pathologic tumor size and preoperative image tumor size correlated strongly with the WHO grades ( p <0.001, and p <0.001). Our study demonstrates that 2010 WHO classification represents a valuable prognostic factor of NF-pNETs and tumor size on preoperative image correlated with WHO grade. In view of the foregoing, the preoperative image size is thought to represent a reasonable reference with regard to determination and development of treatment strategy of NF-pNETs.

  10. Effects of nuclear factor κB expression on retinal neovascularization and apoptosis in a diabetic retinopathy rat model

    Institute of Scientific and Technical Information of China (English)

    Ning; Jiang; Xiao-Long; Chen; Hong-Wei; Yang; Yu-Ru; Ma

    2015-01-01

    AIM: To investigate the expression and role of nuclear factor κB(NF-κB) in diabetic retinopathy(DR) and its relationship with neovascularization and retinal cell apoptosis. METHODS: A total of 80 male Wistar rats were randomly assigned to control(4, 8, 12 and 16 wk, n =10 in each group) and diabetes mellitus(DM) groups(4, 8, 12 and 16wk, n =10 in each group). A diabetic rat model was established by intraperitoneal injection of streptozotocin(60 mg/kg). After 4, 8, 12 and 16 wk, rats were sacrificed.Retinal layers and retinal neovascularization growth were stained with hematoxylin-eosin and examined under light microscopy. Cell apoptosis in the retina was detected by Td T-mediated d UTP nick end labeling, and NF-κB distribution and expression in the retina was determined using immunohistochemistry. RESULTS: DM model success rate up to 100%.Diabetes model at each time point after the experimental groupcompared with the control group, the blood glucose was significantly increased, decreased body weight, each time point showed significant differences compared with the control group(P <0.01). After 12 wk other pathological changes in the retina of diabetic rats were observed; after 16 wk, neovascularization were observed. After 1mo, retinal cell apoptosis was observed.Compared with the control group, NF-κB expression in the DM group significantly increased with disease duration.CONCLUSION: With the prolonging of DM progression,the expression NF-κB increases. NF-κB may be related to retinal cell apoptosis and neovascularization.

  11. Short-term outcomes after EX-PRESS implantation versus trabeculectomy alone in patients with neovascular glaucoma

    OpenAIRE

    Shinohara, Yoichiro; Akiyama, Hideo; Magori, Mikiya; Kishi, Shoji

    2017-01-01

    Yoichiro Shinohara, Hideo Akiyama, Mikiya Magori, Shoji Kishi Department of Ophthalmology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan Background: The purpose of this study was to investigate postoperative clinical outcomes in patients with neovascular glaucoma (NVG) who underwent trabeculectomy or EX-PRESS implantation and to identify predictors of successful EX-PRESS implantation. Methods: The study designed as a retrospective observational analysis and was set in...

  12. Worsening anatomic outcomes following aflibercept for neovascular age-related macular degeneration in eyes previously well controlled with ranibizumab

    Directory of Open Access Journals (Sweden)

    Nudleman E

    2016-06-01

    Full Text Available Eric Nudleman,1 Jeremy D Wolfe,2,3 Maria A Woodward,4 Yoshihiro Yonekawa,2,3 George A Williams,2,3 Tarek S Hassan2,3 1Department of Ophthalmology, Shiley Eye Center, University of California, San Diego, La Jolla, CA, 2Beaumont Eye Institute, Oakland University William Beaumont School of Medicine, 3Associated Retinal Consultants, Royal Oak, 4Kellogg Eye Center, University of Michigan Medical School, Ann Arbor, MI, USA Purpose: Antivascular endothelial growth factor injection is the mainstay of treating neovascular age-related macular degeneration (AMD. Previous studies have shown that switching treatment from ranibizumab to aflibercept led to an improvement in eyes with recalcitrant activity. Herein, we identify a unique subset of patients whose eyes with neovascular AMD were previously well controlled with ranibizumab injections were then worsened after being switched to aflibercept. Methods: This is a retrospective interventional case series. Eyes with neovascular AMD, previously well controlled with monthly injections of ranibizumab, which then developed worsening of subretinal fluid after being switched to aflibercept were included. Results: A total of 17 eyes were included. All eyes developed increased subretinal fluid when switched from ranibizumab to aflibercept. Fourteen patients were switched back to ranibizumab after a single injection of aflibercept and had subsequent rapid resolution of subretinal fluid. Three patients continued with monthly aflibercept injections for two subsequent months and demonstrated the persistence of the increased subretinal fluid until they were switched back to treatment with ranibizumab at which time the fluid resolved. No eye had persistent decline in visual acuity. Conclusion: Switching from intravitreal ranibizumab to aflibercept in eyes with well-controlled neovascular AMD may result in worsening in a subset of patients and resolves when therapy is switched back to ranibizumab. Keywords: anti

  13. Intravitreal bevacizumab has initial clinical benefit lasting eight weeks in eyes with neovascular age-related macular degeneration

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    P William Conrad

    2008-06-01

    Full Text Available P William Conrad, David N Zacks, Mark W JohnsonDepartment of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan, USAPurpose: To determine whether the effect of a single initial intravitreal injection of bevacizumab for neovascular age-related macular degeneration (AMD persists for 8 weeks.Methods: We reviewed the records of 25 consecutive patients with neovascular AMD treated with intravitreal bevacizumab. Patients were included (n = 15 if follow up data were available from 4 and 8 week visits after a single initial injection. Additionally, optical coherence tomography (OCT images were graded qualitatively in a masked fashion by a single reader.Results: Baseline mean visual acuity was 20/200, improving to 20/125 at 4 weeks (p = 0.0153 and 20/100 at 8 weeks (p = 0.0027. Mean central retinal thickness was 316 ± 107 µm at baseline and decreased to 223 ± 70 µm and 206 ± 45 µm at 4 and 8 weeks post-injection, respectively (p = 0.0003 and 0.0005. By masked OCT grading, macular fluid was resolved in 10/15 (66.7% and 11/15 (73.3% eyes at 4 and 8 weeks, respectively, and 3/15 (20% eyes had continued reduction in residual macular fluid between 4 and 8 weeks.Conclusions: A single initial bevacizumab injection has persistent clinical benefit lasting 8 weeks in most eyes with neovascular AMD. Results of prospective randomized studies are needed before changes in treatment regimens can be recommended.Keywords: age-related macular degeneration, bevacizumab, choroidal neovascular membrane, optical coherence tomography

  14. Use of Adipose-Derived Mesenchymal Stem Cells to Accelerate Neovascularization in Interpolation Flaps.

    Science.gov (United States)

    Izmirli, Hakki Hayrettin; Alagoz, Murat Sahin; Gercek, Huseyin; Eren, Guler Gamze; Yucel, Ergin; Subasi, Cansu; Isgoren, Serkan; Muezzinoglu, Bahar; Karaoz, Erdal

    2016-01-01

    Interpolation flaps are commonly used in plastic surgery to cover wide and deep defects. The need to, wait for 2 to 3 weeks until the division of the pedicle still, however, poses a serious challenge, not only extending treatment and hospital stay, but also increasing hospital expenses. To solve this problem, we have aimed to use the angiogenic potential of stem cells to selectively accelerate neovascularization with a view to increasing the viability of interpolation flaps and achieving early pedicle removal. A total of 32 rats were allocated to 2 groups as control (N = 16) and experiment (N = 16). The cranial flaps 6 × 5 cm in size located on the back of the rats were raised. Then, a total suspension containing 3 × 10(6) adipose-derived mesenchymal stem cells (ADSC) tagged with a green fluorescent protein (GFP) was injected diffusely into the distal part of the flap, receiving bed, and wound edges. In the control group, only a medium solution was injected into the same sites. After covering the 3 × 5 cm region in the proximal part of the area where the flap was removed, the distal part of the flap was adapted to the uncovered distal area. The pedicles of 4 rats in each group were divided on postoperative days 5, 8, 11, and 14. The areas were photographed 7 days after the pedicles were released. The photographs were processed using Adobe Acrobat 9 Pro software (San Jose, CA) to measure the flap survival area in millimeters and to compare groups. Seven days after the flap pedicle was divided, the rats were injected with 250 mCi Tc-99 mm (methoxy-isobutyl-isonitrie) from the penile vein, and scintigraphic images were obtained. The images obtained from each group were subjected to a numerical evaluation, which was then used in the comparison between groups. The flaps were then examined by histology to numerically compare the number of newly formed vessels. Neovascularization was also assessed by microangiography. In addition, radiographic images were obtained by

  15. Effect of trapping vascular endothelial growth factor-A in a murine model of dry eye with inflammatory neovascularization.

    Science.gov (United States)

    Kwon, Jin Woo; Choi, Jin A; Shin, Eun Young; La, Tae Yoon; Jee, Dong Hyun; Chung, Yeon Woong; Cho, Yang Kyung

    2016-01-01

    To evaluate whether trapping vascular endothelial growth factor A (VEGF-A) would suppress angiogenesis and inflammation in dry eye corneas in a murine corneal suture model. We established two groups of animals, one with non-dry eyes and the other with induced dry eyes. In both groups, a corneal suture model was used to induce inflammation and neovascularization. Each of two groups was again divided into three subgroups according to the treatment; subgroup I (aflibercept), subgroup II (dexamethasone) and subgroup III (phosphate buffered saline, PBS). Corneas were harvested and immunohistochemical staining was performed to compare the extents of neovascularization and CD11b+ cell infiltration. Real-time polymerase chain reaction was performed to quantify the expression of inflammatory cytokines and VEGF-A in the corneas. Trapping VEGF-A with aflibercept resulted in significantly decreased angiogenesis and inflammation compared with the dexamethasone and PBS treatments in the dry eye corneas (all P dry eyes. The anti-inflammatory and anti-angiogenic effects of VEGF-A trapping were stronger than those of dexamethasone in both dry eye and non-dry eye corneas (all P dry eye group. Compared with non-dry eye corneas, dry eye corneas have greater amounts of inflammation and neovascularization and also have a more robust response to anti-inflammatory and anti-angiogenic agents after ocular surface surgery. Trapping VEGF-A is effective in decreasing both angiogenesis and inflammation in dry eye corneas after ocular surface surgery.

  16. The effect of bevacizumab for anterior segment neovascularization after silicone oil removal in eyes with previous vitreoretinal surgery.

    Science.gov (United States)

    Batman, C; Ozdamar, Y

    2010-07-01

    To report the outcomes of the use of intracameral bevacizumab for iris neovascularization occurring after silicone oil (SO) removal in eyes undergoing vitreoretinal surgery (VRS). This study included 12 eyes that had iris neovascularization after SO removal. The clinical outcomes of 12 eyes after intravitreal bevacizumab injection were reviewed. There were eight men and four women with an average age of 41.58+/-12.68 years. All eyes had VRS for various vitreoretinal diseases. After the mean follow-up period of 9.7+/-5.3 months, SO removal was performed. Then, the patients were followed for more than 2 months and detailed retinal examinations and intraocular pressure (IOP) were normal during this period, but rubeosis iridis (RI) developed. RI was treated with 1 dose of 1.25 mg bevacizumab into the anterior chamber. After a mean follow-up period of 4.8+/-2.2 months, the regression of iris neovacularization was detected and IOP was below 21 mmHg in all eyes. Anterior segment neovascularization (ASNV) may develop through various mechanisms in patients with VRS after SO removal, and anterior chamber injection of bevacizumab may lead to regression of ASNV.

  17. Effectiveness of multiple therapeutic strategies in neovascular glaucoma patients: A PRISMA-compliant network meta-analysis.

    Science.gov (United States)

    Dong, Zixian; Gong, Jianyang; Liao, Rongfeng; Xu, Shaojun

    2018-04-01

    Neovascular glaucoma (NVG) is a severe secondary glaucoma with uncontrolled intraocular pressure that leads to serious eye pain and vision loss. Presently, the therapeutic strategies for NVG are diverse, but the therapeutic effects are still not ideal. We performed a network analysis to assess the effect of multiple therapeutic strategies on the treatment of NVG patients. We searched public electronic databases through April 2017 using the following keywords "neovascular glaucoma," "iris neovascularization," "hemorrhagic glaucoma," and "random" without language restrictions. The outcome considered in the present analysis was treatment success rate. A network meta-analysis and multilevel mixed-effects logistic regression were used to compare regimens. We included 27 articles assessing a total of 1884 NVG patients in our analysis. According to the network analysis, interferon and mitomycin plus trabeculectomy (94.9%), glaucoma valve implantation (86.9%), and iris photocoagulation plus trabeculectomy (81.9%) were the most likely to improve treatment success rate in NVG patients. The multilevel logistic regression analysis showed that glaucoma valve, bevacizumab, interferon, cyclophotocoagulation, trabeculectomy, iris photocoagulation, ranibizumab, and mitomycin had advantages in terms of improving treatment success rate in NVG patients. However, the application of retinal photocoagulation and vitrectomy reduced patient treatment success rate. The regimen including mitomycin, interferon, and trabeculectomy was the most likely to improve the treatment success rate in NVG patients. The application of glaucoma valve and bevacizumab were more beneficial for improving patient treatment success rate as a surgery and as an agent, respectively.

  18. Ranibizumab in the treatment of choroidal neovascularization on the border of an inferior staphyloma associated with tilted disc syndrome

    Directory of Open Access Journals (Sweden)

    Luis Arias

    2010-03-01

    Full Text Available Luis Arias1,2, Jordi Monés21Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Barcelona; 2Institut de la Màcula i de la Retina, Centro Médico Teknon, BarcelonaPurpose: To describe a case of choroidal neovascularization (CNV on the border of an inferior staphyloma associated with tilted disc syndrome treated with intravitreal ranibizumab.Patients: Observational case report.Methods: A patient with CNV on the border of an inferior staphyloma associated with tilted disc syndrome was imaged using fluorescein angiography, autofluorescence and spectral domain optical coherence tomography, and treated with intravitreal injections of ranibizumab. Results: The patient received 3 ranibizumab injections during the 9-month follow-up. The visual acuity improved from 20/40 to 20/32 and the foveal thickness reduced from 470 microns to 248 microns. The angiograms showed resolution of leakage associated with CNV. There were no adverse events.Conclusion: Intravitreal ranibizumab is an efficacious and safe treatment in the management of choroidal neovascularization on the border of an inferior staphyloma associated with tilted disc syndrome.Keywords: intravitreal ranibizumab, choroidal neovascularization, tilted disc syndrome, inferior staphyloma

  19. [Krypton laser photocoagulation at low power setting for age-related macular degeneration complicated with subfoveal choroidal neovascularization].

    Science.gov (United States)

    Zhang, Cheng-fen; Jia, Yan; Li, Zhi-qing; Du, Hong; Han, Bao-ling

    2004-12-01

    To evaluate the efficacy of krypton laser photocoagulation for treatment of age-related macular degeneration (AMD) complicated with mainly subfoveal classic choroidal neovascularization (CNV). Seventeen eyes of 17 cases, aged 50 - 74 years (averaged 60.8 years) with mainly subfoveal classic choroidal neovascularization were treated with krypton laser at lower power setting. The treatment was completed in one session. Another course of treatment was given 4 weeks later if there was active leakage demonstrated at the CNV area. Visual acuity, anterior segment and fundus examination, perimetry test, fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) were performed before and after treatment. The follow-up period was 3.5 years on average (1 - 8 years). There was no immediately decrease of visual acuity after treatment. All treated eyes showed absorption of hemorrhages and/or exudates and diminished leakages. Visual acuity was stable in 8 eyes; improved in 6 eyes (>/= 2 lines), and decreased in 3 eyes (Krypton laser photocoagulation at low power setting is an effective treatment for AMD with mainly classic subfoveal choroidal neovascularization.

  20. A PEDF-Derived Peptide Inhibits Retinal Neovascularization and Blocks Mobilization of Bone Marrow-Derived Endothelial Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Richard Longeras

    2012-01-01

    Full Text Available Proliferative diabetic retinopathy is characterized by pathological retinal neovascularization, mediated by both angiogenesis (involving mature endothelial cells and vasculogenesis (involving bone marrow-derived circulating endothelial progenitor cells (EPCs. Pigment epithelium-derived factor (PEDF contains an N-terminal 34-amino acid peptide (PEDF-34 that has antiangiogenic properties. Herein, we present a novel finding that PEDF-34 also possesses antivasculogenic activity. In the oxygen-induced retinopathy (OIR model using transgenic mice that have Tie2 promoter-driven GFP expression, we quantified Tie2GFP+ cells in bone marrow and peripheral blood by fluorescence-activated cell sorting (FACS. OIR significantly increased the number of circulating Tie2-GFP+ at P16, correlating with the peak progression of neovascularization. Daily intraperitoneal injections of PEDF-34 into OIR mice decreased the number of Tie2-GFP+ cells in the circulation at P16 by 65% but did not affect the number of Tie2-GFP+ cells in the bone marrow. These studies suggest that PEDF-34 attenuates EPC mobilization from the bone marrow into the blood circulation during retinal neovascularization.

  1. Treatment of Non-neovascular Idiopathic Macular Telangiectasia Type 2 with Intravitreal Ranibizumab: Results of a Phase II Clinical Trial

    Science.gov (United States)

    Toy, Brian C.; Koo, Euna; Cukras, Catherine; Meyerle, Catherine B.; Chew, Emily Y.; Wong, Wai T.

    2015-01-01

    Purpose To evaluate the safety and preliminary efficacy of intravitreal ranibizumab for non-neovascular idiopathic macular telangiectasia, type 2 (IMT2). Methods Single-center, open-label phase II clinical trial enrolling 5 participants with bilateral non-neovascular IMT2. Intravitreal ranibizumab (0.5mg) was administered every 4 weeks in the study eye for 12 months with the contralateral eye observed. Outcome measures included changes in: best corrected visual acuity (BCVA), area of late-phase leakage on fluorescein angiography (FA), and retinal thickness on optical coherence tomography (OCT). Results The study treatment was well-tolerated and associated with few adverse events. Change in BCVA at 12 months was not significantly different between treated study eyes (0.0±7.5 letters) and control fellow eyes (+2.2±1.9 letters). However, decreases in the area of late-phase FA leakage (−33±20% for study eyes, +1±8% for fellow eyes) and in OCT central subfield retinal thickness (−11.7±7.0% for study eyes and −2.9±3.5% for fellow eyes) were greater in study eyes compared to fellow eyes. Conclusions Despite significant anatomical responses to treatment, functional improvement in visual acuity was not detected. Intravitreal ranibizumab administered monthly over a time course of 12 months is unlikely to provide a general and significant benefit to patients with non-neovascular IMT2. PMID:22266930

  2. Visual outcome of ranibizumab therapy for neovascular age related macular degeneration in the black population: a report of five cases

    Directory of Open Access Journals (Sweden)

    Roopa Vemala

    2010-08-01

    Full Text Available Roopa Vemala, Bhaskar Gupta, Sobha SivaprasadLaser and Retinal Research Unit, King’s College Hospital, London SE5 9RS, UKIntroduction: Neovascular age related macular degeneration (AMD is relatively uncommon in the black population. We report the 12-month outcome of ranibizumab therapy in five black patients with choroidal neovascular membrane (CNV secondary to AMD.Material and methods: Retrospective analysis of a prospective audit database maintained for all patients on ranibizumab therapy in a retinal specialist unit that caters to a multi-ethnic cohort in London, United Kingdom.Results: At 12 months, all the 5 patients maintained stable vision (loss of less than 15 ETDRS letters. However, none of them gained more than 15 ETDRS letters. All eyes showed early subretinal fibrosis while 2 patients showed extended areas of retinal pigment atrophy.Conclusion: Our case studies indicate that ranibizumab stabilizes the vision in black patients with CNV secondary to AMD but they tend to develop early subretinal fibrosis and retinal pigment atrophy.Keywords: choroidal neovascular membrane, Afro-Caribbean, blacks

  3. Increased levels of circulating CD34+ cells in neovascular age-related macular degeneration: relation with clinical and OCT features.

    Science.gov (United States)

    Kara, Caner; Özdal, Pınar Ç; Beyazyıldız, Emrullah; Özcan, Nurgül E; Teke, Mehmet Y; Vural, Gülden; Öztürk, Faruk

    2018-01-01

    To investigate the levels of circulating CD34+ stem cells in patients with neovascular type age-related macular degeneration (AMD) and its relation with clinical and optical coherence tomography (OCT) findings. The study consisted of 55 patients: 28 patients (18 male and 10 female) with neovascular type AMD as a study group and 27 patients (12 male and 15 female) scheduled for cataract surgery as a control group. The level of CD34+ stem cells was measured by flow cytometry. Demographic and clinical data were recorded. The mean ages of patients in the study and control groups were 71 ± 8 and 68 ± 6 years, respectively. There was no statistically significant difference in terms of age, sex, or systemic disease association between study and control groups. However, smoking status was significantly higher in the study group (67.9% vs 37.0%; p = 0.02). Stem cell levels were significantly higher in the study group (1.5 ± 0.9 vs 0.5 ± 0.3; p<0.001), but there was no relation between stem cell levels and clinical and OCT findings. Increased circulating CD34+ stem cell levels were observed in patients with choroidal neovascular membrane associated with AMD, but no significant relation was found between cell levels and clinical and OCT findings.

  4. Bevacizumab treatment reduces retinal neovascularization in a mouse model of retinopathy of prematurity

    Institute of Scientific and Technical Information of China (English)

    Fei; Feng; Yan; Cheng; Qing-Huai; Liu

    2014-01-01

    ·AIM: To evaluate the effect of different bevacizumab concentrations on retinal neovascularization in a retinopathy of prematurity(ROP) mouse model.·METHODS: A total of 60 of C57BL/6 J mice were exposed to 75% ±2% oxygen from postnatal d7 to postnatal d12. Fifteen nonexposed mice served as negative controls(group A). On d12, 30 mice(group C)were injected with 2.5 μg intravitreal bevacizumab(IVB),30 mice(group D) were injected with 1.25 μg IVB in one eye. The contralateral eyes were injected with balanced salt solution(BSS)(control group =group B). The adenosine diphosphatase(ADPase) histochemical technique was used for retinal flat mount to assess the oxygen-induced changes of retinal vessels.Neovascularization was quantified by counting the endothelial cell proliferation on the vitreal side of the inner limiting membrane of the retina. Histological changes were examined by light microscopy. The mRNA levels of vascular endothelial growth factor(VEGF) were quantified by Real-time PCR. Western-blotting analysis was performed to examine the expression of P-VEGFR.· RESULTS: Comparing with the control group B,regular distributions and reduced tortuosity of vessels were observed in our retinal flat mounts in groups C and D. The endothelial cell count per histological section was lower in groups C(P <0.0001) and D(P <0.0001) compared with the control group B. Histological evaluation showed no retinal toxicity in any group. In all oxygen treated groups VEGF mRNA expression was significantly increased as compared to age-matched controls. No significant change in VEGF mRNA expression could be achieved in either of the treatments or the oxygen controls. The results of the Western blot were consistent with that of the Real-time PCR analysis.·CONCLUSION: An intravitreal injection of bevacizumab is able to reduce angioproliferative retinopathy in a mouse model for oxygen-induced retinopathy.

  5. Decellularized matrix from tumorigenic human mesenchymal stem cells promotes neovascularization with galectin-1 dependent endothelial interaction.

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    Jorge S Burns

    Full Text Available BACKGROUND: Acquisition of a blood supply is fundamental for extensive tumor growth. We recently described vascular heterogeneity in tumours derived from cell clones of a human mesenchymal stem cell (hMSC strain (hMSC-TERT20 immortalized by retroviral vector mediated human telomerase (hTERT gene expression. Histological analysis showed that cells of the most vascularized tumorigenic clone, -BD11 had a pericyte-like alpha smooth muscle actin (ASMA+ and CD146+ positive phenotype. Upon serum withdrawal in culture, -BD11 cells formed cord-like structures mimicking capillary morphogenesis. In contrast, cells of the poorly tumorigenic clone, -BC8 did not stain for ASMA, tumours were less vascularized and serum withdrawal in culture led to cell death. By exploring the heterogeneity in hMSC-TERT20 clones we aimed to understand molecular mechanisms by which mesenchymal stem cells may promote neovascularization. METHODOLOGY/PRINCIPAL FINDINGS: Quantitative qRT-PCR analysis revealed similar mRNA levels for genes encoding the angiogenic cytokines VEGF and Angiopoietin-1 in both clones. However, clone-BD11 produced a denser extracellular matrix that supported stable ex vivo capillary morphogenesis of human endothelial cells and promoted in vivo neovascularization. Proteomic characterization of the -BD11 decellularized matrix identified 50 extracellular angiogenic proteins, including galectin-1. siRNA knock down of galectin-1 expression abrogated the ex vivo interaction between decellularized -BD11 matrix and endothelial cells. More stable shRNA knock down of galectin-1 expression did not prevent -BD11 tumorigenesis, but greatly reduced endothelial migration into -BD11 cell xenografts. CONCLUSIONS: Decellularized hMSC matrix had significant angiogenic potential with at least 50 angiogenic cell surface and extracellular proteins, implicated in attracting endothelial cells, their adhesion and activation to form tubular structures. hMSC -BD11 surface galectin-1

  6. Idiopathic polypoidal choroidal vasculopathy in Thai patients with clinical and angiographic choroidal neovascularization

    Directory of Open Access Journals (Sweden)

    Bhoomibunchoo C

    2017-02-01

    Full Text Available Chavakij Bhoomibunchoo,1 Yosanan Yospaiboon,1 Somanus Thoongsuwan,2 Duangnate Rojanaporn,3 Nawat Watanachai,4 Pichai Jirarattanasopa,5 Nattapon Wongcumchang,6 Atchara Amphornphruet,7 Sritatath Vongkulsiri,8 Eakkachai Arayangkoon9 1Department of Ophthalmology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 2Department of Ophthalmology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, 3Department of Ophthalmology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, 4Department of Ophthalmology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 5Department of Ophthalmology, Faculty of Medicine, Prince of Songkla University, Songkhla, 6Department of Ophthalmology, Faculty of Medicine, Thammasat University, Pathum Thani, 7Department of Ophthalmology, Rajavithi Hospital, Bangkok, 8Department of Ophthalmology, Phramongkutklao Hospital, Bangkok, 9Department of Ophthalmology, Mettapracharak Hospital, Nakhon Pathom, Thailand Objective: This study aimed to study the prevalence and characteristics of idiopathic polypoidal choroidal vasculopathy (IPCV in Thai patients with clinical and angiographic choroidal neovascularization (CNV.Patients and methods: A consecutive case study of 140 patients presenting with CNV was conducted in nine large referral eye centers throughout Thailand. The demographic data, fundus photographs, fundus fluorescein angiography and indocyanine green angiography of the patients were analyzed.Results: Of 129 patients with clinical and angiographic CNV, IPCV was diagnosed in 100 patients (77.52%, idiopathic CNVs in 16 patients (12.40% and age-related macular degeneration (AMD in 12 patients (9.30%. Of the 107 eyes with IPCV, 90 eyes (84.11% had both branching venous networks (BVNs and polypoidal lesions. Most IPCV patients (93% had unilateral involvement and were at a younger age than AMD patients. In all, 79 eyes (73.83% had lesions found in the macular area, 14 eyes (13.08% in the

  7. Lentivirus-mediated RNA interference of vascular endothelial growth factor in monkey eyes with iris neovascularization.

    Science.gov (United States)

    Yuan, Meng-Ke; Tao, Yong; Yu, Wen-Zhen; Kai, Wang; Jiang, Yan-Rong

    2010-08-25

    To explore the in vivo anti-angiogenesis effects resulting from lentivirus-mediated RNAi of vascular endothelial growth factor (VEGF) in monkeys with iris neovascularization (INV). Five specific recombinant lentiviral vectors for RNA interference, targeting Macaca mulatta VEGFA, were designed and the one with best knock down efficacy (LV-GFP-VEGFi1) in H1299 cells and RF/6A cells was selected by real-time PCR for in vivo use. A laser-induced retinal vein occlusion model was established in one eye of seven cynomolgus monkeys. In monkeys number 1, 3, and 5 (Group 1), the virus (1x10(8) particles) was intravitreally injected into the preretinal space of the animal's eye immediately after laser coagulation; and in monkeys number 2, 4, and 6 (Group 2), the virus (1x10(8) particles) was injected at 10 days after laser coagulation. In monkey number 7, a blank control injection was performed. In monkeys number 1 and 2, virus without RNAi sequence was used; in monkeys number 3 and 4, virus with nonspecific RNAi sequence was used; and in monkeys 5 and 6, LV-GFP-VEGFi1 was used. In monkey number 5, at 23 days after laser treatment, no obvious INV was observed, while fluorescein angiography of the iris revealed high fluorescence at the margin of pupil and point posterior synechiae. At 50 days after laser treatment, only a slight ectropion uvea was found. However, in the other eyes, obvious INV or hyphema was observed. The densities of new iridic vessels all significantly varied: between monkey number 5 and number 3 (36.01+/-4.49/mm(2) versus 48.68+/-9.30/mm(2), p=0.025), between monkey number 3 and monkey number 7 (48.68+/-9.30/mm(2) versus 74.38+/-9.23/mm(2), p=0.002), and between monkey number 5 and number 7 (36.01+/-4.49/mm(2) versus 74.38+/-9.23/mm(2), p<0.001). Lentivirus-mediated RNAi of VEGF may be a new strategy to treat iris neovascularization, while further studies are needed to investigate the long-term effect.

  8. Brain abnormalities on MRI in non-functioning pituitary adenoma patients treated with or without postoperative radiotherapy

    NARCIS (Netherlands)

    Sattler, Margriet G. A.; Meiners, Linda C.; Sluiter, Wim J.; van den Berg, Gerrit; Langendijk, Johannes A.; Wolffenbuttel, Bruce H. R.; van den Bergh, Alphons C. M.; van Beek, Andre P.

    Background and purpose: To assess and compare brain abnormalities on Magnetic Resonance Imaging (MRI) in non-functioning pituitary macro-adenoma (NFA) patients treated with or without postoperative radiotherapy (RT). Material and methods: In 86 NFA patients, treated between 1987 and 2008 at the

  9. A Case Study of Non-Functional Requirements and Continuous Improvement at a National Communications System Contractor

    Science.gov (United States)

    Douglas, Volney L. R.

    2010-01-01

    National communications systems (NCS) are critical elements of a government's infrastructure. Limited improvements to the non-functional requirements (NFR) of NCS have caused issues during national emergencies such as 9/11 and Hurricane Katrina. The literature indicates that these issues result from a deficiency in understanding the roles NFRs and…

  10. The influence of somatostatin receptor scintigraphy during preoperative staging of non-functioning pancreatic neuroendocrine tumours

    International Nuclear Information System (INIS)

    Jilesen, A.P.J.; Hoefnagel, S.J.M.; Busch, O.R.C.; Bennink, R.J.; Gouma, D.J.; Nieveen van Dijkum, E.J.M.

    2016-01-01

    Aim: To determine whether somatostatin receptor scintigraphy (SRS) influences the preoperative staging and clinical management of non-functioning pancreatic neuroendocrine tumours (NF-pNETs). Materials and methods: All SRS examinations performed between 2002–2013 were selected. Patients with NF-pNET were included if both computed tomography (CT) and SRS was performed during preoperative staging. The diagnostic accuracy of CT and SRS for detecting NF-pNET metastases was analysed. Altered TNM classification and changed clinical management were calculated. Changed management was defined as a change from surgical resection into systemic treatment or vice versa. NF-pNETs were defined as tumours without clinical symptoms of hormonal hypersecretion. Results: Overall, 62 patients with NF-pNET were included with a mean age of 57 years (SD: 12.4) 2 . In 28 patients (45%), CT and SRS were correct and in agreement in the detection of primary tumour/metastases. In 34 patients (55%), one of the techniques was incorrect and therefore, there was no agreement. SRS altered the TNM classification in 14 patients (23%) and clinical management in nine patients (15%). In patients without metastases on CT, SRS detected lymph node metastases in one patient. The sensitivity to detect the primary tumour with CT was 95% and with SRS was 73%. In detecting metastases, the sensitivity and specificity were both 85% for CT versus 80% and 90% for SRS. Conclusion: Overall, CT and SRS were in agreement in the detection of NF-pNET. In NF-pNET without suspicious metastatic lesions on CT, SRS has limited value. SRS may be indicated to confirm lesions suspicious for neuroendocrine tumours metastases. - Highlights: • In 28 patients (45%), CT and SRS were correct and in agreement in the detection of primary tumor/metastases. • In 34 patients (55%) one of the modalities was incorrect and therefore, there was no agreement. • Sensitivity to detect the primary tumor with CT and SRS were 95% versus 73

  11. Antiangiogenic immunotherapy targeting Flk-1, DNA vaccine and adoptive T cell transfer, inhibits ocular neovascularization

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Han [Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582 (Japan); Sonoda, Koh-Hei, E-mail: sonodak@med.kyushu-u.ac.jp [Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582 (Japan); Hijioka, Kuniaki; Qiao, Hong; Oshima, Yuji; Ishibashi, Tatsuro [Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582 (Japan)

    2009-04-17

    Ocular neovascularization (NV) is the primary cause of blindness in a wide range of ocular diseases. The exact mechanism underlying the pathogenesis of ocular NV is not yet well understood, and so there is no satisfactory therapy for ocular NV. Here, we describe a strategy targeting Flk-1, a self-antigen overexpressed on proliferating endothelial cells in ocular NV, by antiangiogenic immunotherapy-DNA vaccine and adoptive T cell therapy. An oral DNA vaccine encoding Flk-1 carried by attenuated Salmonella typhimurium markedly suppressed development of laser-induced choroidal NV. We further demonstrated that adoptive transfer of vaccine-induced CD8{sup +} T cells reduced pathological preretinal NV, with a concomitant facilitation of physiological revascularization after oxygen-induced retinal vessel obliteration. However, physiological retinal vascular development was unaffected in neonatal mice transferred with vaccine-induced CD8{sup +} T cells. These findings suggested that antiangiogenic immunotherapy targeting Flk-1 such as vaccination and adoptive immunotherapy may contribute to future therapies for ocular NV.

  12. HTRA1 variant confers similar risks to geographic atrophy and neovascular age-related macular degeneration.

    Science.gov (United States)

    Cameron, D Joshua; Yang, Zhenglin; Gibbs, Daniel; Chen, Haoyu; Kaminoh, Yuuki; Jorgensen, Adam; Zeng, Jiexi; Luo, Ling; Brinton, Eric; Brinton, Gregory; Brand, John M; Bernstein, Paul S; Zabriskie, Norman A; Tang, Shibo; Constantine, Ryan; Tong, Zongzhong; Zhang, Kang

    2007-05-02

    Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment in the developed world. The two forms of advanced AMD, geographic atrophy (GA) and choroidal neovascularization (wet AMD), represent two types of degenerative processes in the macula that lead to loss of central vision. Soft confluent drusen, characterized by deposits in macula without visual loss are considered a precursor of advanced AMD. A single nucleotide polymorphism, rs11200638, in the promoter of HTRA1 has been shown to increases the risk for wet AMD. However, its impact on soft confluent drusen and GA or the relationship between them is unclear. To better understand the role the HTRA1 polymorphism plays in AMD subtypes, we genotyped an expanded Utah population with 658 patients having advanced AMD or soft confluent drusen and 294 normal controls and found that the rs11200638 was significantly associated with GA. This association remains significant conditional on LOC387715 rs10490924. In addition, rs11200638 was significantly associated with soft confluent drusen, which are strongly immunolabeled with HTRA1 antibody in an AMD eye with GA similar to wet AMD. Two-locus analyses were performed for CFH Y402H variant at 1q31 and the HTRA1 polymorphism. Together CFH and HTRA1 risk variants increase the odds of having AMD by more than 40 times. These findings expand the role of HTRA1 in AMD. Understanding the underlying molecular mechanism will provide an important insight in pathogenesis of AMD.

  13. [Neovascular form of age-related macular degeneration --current management in Poland and in Europe].

    Science.gov (United States)

    Teper, Sławomir; Nowińska, Anna; Lyssek-Boroń, Anita; Wylegała, Edward

    2014-07-01

    Currently in Poland neovascular form of age-related macular degeneration (AMD) is treated with vascular endothelial growth factor (VEGF) inhibitors--ranibizumab, aflibercept and bevacizumab. Photodynamic therapy is still refunded, although it is very rarely used. It can be estimated that only small minority (about 5-10%) of cases are properly treated due to mainly refunding restrictions in Poland. In countries with wider access to treatment 50% reduction in AMD-related blindness incidence was noted. Low-cost off-label anti-VEGF agent bevacizumab is almost inaccessible in Polish public health system because of law regulations. In order to increase availability of anti-VEGF injections vials of all mentioned drugs are divided which raises safety concerns. Despite new potent drug in the market aflibercept, cost of treatment remains very high. The optimal treatment regimen includes three monthly injections, after which is usually used pro re nata therapy based primarily on the outcome of macular optical coherence tomography. Routinely recommended antibiotic prophylaxis of injection-related endophthalmitis probably has no meaning apart from the generation of resistance.

  14. Mobile Laser Indirect Ophthalmoscope: For the Induction of Choroidal Neovascularization in a Mouse Model.

    Science.gov (United States)

    Weinberger, Dov; Bor-Shavit, Elite; Barliya, Tilda; Dahbash, Mor; Kinrot, Opher; Gaton, Dan D; Nisgav, Yael; Livnat, Tami

    2017-11-01

    This study aims to evaluate and standardize the reliability of a mobile laser indirect ophthalmoscope in the induction of choroidal neovascularization (CNV) in a mouse model. A diode laser indirect ophthalmoscope was used to induce CNV in pigmented male C57BL/6J mice. Standardization of spot size and laser intensity was determined using different aspheric lenses with increasing laser intensities applied around the optic disc. Development of CNV was evaluated 1, 5, and 14 days post laser application using fluorescein angiography (FA), histology, and choroidal flat mounts stained for the endothelial marker CD31 and FITC-dextran. Correlation between the number of laser hits to the number and size of developed CNV lesions was determined using flat mount choroid staining. The ability of intravitreally injected anti-human and anti-mouse VEGF antibodies to inhibit CNV induced by the mobile laser was evaluated. Laser parameters were standardized on 350 mW for 100 msec, using the 90 diopter lens to accomplish the highest incidence of Bruch's membrane rupture. CNV lesions' formation was validated on days 5 and 14 post laser injury, though FA showed leakage on as early as day 1. The number of laser hits was significantly correlated with the CNV area. CNV growth was successfully inhibited by both anti-human and mouse VEGF antibodies. The mobile laser indirect ophthalmoscope can serve as a feasible and a reliable alternative method for the CNV induction in a mouse model.

  15. Quantitative evaluation and modeling of two-dimensional neovascular network complexity: the surface fractal dimension

    International Nuclear Information System (INIS)

    Grizzi, Fabio; Russo, Carlo; Colombo, Piergiuseppe; Franceschini, Barbara; Frezza, Eldo E; Cobos, Everardo; Chiriva-Internati, Maurizio

    2005-01-01

    Modeling the complex development and growth of tumor angiogenesis using mathematics and biological data is a burgeoning area of cancer research. Architectural complexity is the main feature of every anatomical system, including organs, tissues, cells and sub-cellular entities. The vascular system is a complex network whose geometrical characteristics cannot be properly defined using the principles of Euclidean geometry, which is only capable of interpreting regular and smooth objects that are almost impossible to find in Nature. However, fractal geometry is a more powerful means of quantifying the spatial complexity of real objects. This paper introduces the surface fractal dimension (D s ) as a numerical index of the two-dimensional (2-D) geometrical complexity of tumor vascular networks, and their behavior during computer-simulated changes in vessel density and distribution. We show that D s significantly depends on the number of vessels and their pattern of distribution. This demonstrates that the quantitative evaluation of the 2-D geometrical complexity of tumor vascular systems can be useful not only to measure its complex architecture, but also to model its development and growth. Studying the fractal properties of neovascularity induces reflections upon the real significance of the complex form of branched anatomical structures, in an attempt to define more appropriate methods of describing them quantitatively. This knowledge can be used to predict the aggressiveness of malignant tumors and design compounds that can halt the process of angiogenesis and influence tumor growth

  16. Time-dependent LXR/RXR pathway modulation characterizes capillary remodeling in inflammatory corneal neovascularization.

    Science.gov (United States)

    Mukwaya, Anthony; Lennikov, Anton; Xeroudaki, Maria; Mirabelli, Pierfrancesco; Lachota, Mieszko; Jensen, Lasse; Peebo, Beatrice; Lagali, Neil

    2018-05-01

    Inflammation in the normally immune-privileged cornea can initiate a pathologic angiogenic response causing vision-threatening corneal neovascularization. Inflammatory pathways, however, are numerous, complex and are activated in a time-dependent manner. Effective resolution of inflammation and associated angiogenesis in the cornea requires knowledge of these pathways and their time dependence, which has, to date, remained largely unexplored. Here, using a model of endogenous resolution of inflammation-induced corneal angiogenesis, we investigate the time dependence of inflammatory genes in effecting capillary regression and the return of corneal transparency. Endogenous capillary regression was characterized by a progressive thinning and remodeling of angiogenic capillaries and inflammatory cell retreat in vivo in the rat cornea. By whole-genome longitudinal microarray analysis, early suppression of VEGF ligand-receptor signaling and inflammatory pathways preceded an unexpected later-phase preferential activation of LXR/RXR, PPARα/RXRα and STAT3 canonical pathways, with a concurrent attenuation of LPS/IL-1 inhibition of RXR function and Wnt/β-catenin signaling pathways. Potent downstream inflammatory cytokines such as Cxcl5, IL-1β, IL-6 and Ccl2 were concomitantly downregulated during the remodeling phase. Upstream regulators of the inflammatory pathways included Socs3, Sparc and ApoE. A complex and coordinated time-dependent interplay between pro- and anti-inflammatory signaling pathways highlights a potential anti-inflammatory role of LXR/RXR, PPARα/RXRα and STAT3 signaling pathways in resolving inflammatory corneal angiogenesis.

  17. Efficacy of intravitreal Ranibizumab injection for choroidal neovascularization secondary to pathologic myopia

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    Li-Hong Cui

    2016-03-01

    Full Text Available AIM:To observe the efficacy and safety of intravitreal Ranibizumab injection in patiens with choroidal neovascularization(CNVsecondary to pathologic myopia.METHODS:In this retrospective and comparative study,24 patients(25 eyeswith CNV secondary to pathologic myopia were enrolled. All patients were assessed by examinations of ETDRS visual acuity chart, preplaced-mirror ophthalmoscopy, fundus fluorescein angiography(FFA, indocyanine green angiography(ICGAand optical coherence tomography(OCT. Patiens received intravitreally injected ranibizumab 0.5mg(0.05mL. Treatments were repeated if the follow-up indicated that it was necessary. The follow-up periods were 4~10mo. Best corrected visual acuity(BCVA, central macular thickness(CMTand leakage of CNV before and after the treatment were compared. RESULTS:No local or systemic complications occurred in any patients during the treatment or follow-up. The average time of injection was 1.52. The mean BCVA was 23.93±12.46 letters before the therapy. In the last follow-up, the mean BCVA was 40.63±7.25 letters, improved by 14.27±9.36 letters and the difference was statically significant(t=5.74, Pt=3.96, PCONCLUSION:Intravitreal ranibizumab injection for CNV secondary to pathologic myopia is safe and effective, and this treatment can improve visual acuity, reduce retina edema and leakage of CNV.

  18. Topical Use of Angiopoietin-like Protein 2 RNAi-loaded Lipid Nanoparticles Suppresses Corneal Neovascularization

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    Yukako Taketani

    2016-01-01

    Full Text Available Corneal neovascularization (CNV is a sight-threatening condition that is encountered in various inflammatory settings including chemical injury. We recently confirmed that angiopoietin-like protein 2 (ANGPTL2 is a potent angiogenic and proinflammatory factor in the cornea, and we have produced a single-stranded proline-modified short hairpin anti-ANGPTL2 RNA interference molecule that is carried in a lipid nanoparticle (ANGPTL2 Li-pshRNA for topical application. In this study, we have further examined the topical delivery and anti-ANGPTL2 activity of this molecule and have found that fluorescence-labeled ANGPTL2 Li-pshRNA eye drops can penetrate all layers of the cornea and that ANGPTL2 mRNA expression was dramatically inhibited in both epithelium and stroma at 12 and 24 hours after administration. We also examined the inhibitory effect of ANGPTL2 Li-pshRNA on CNV in a mouse chemical injury model and found that the area of angiogenesis was significantly decreased in corneas treated with ANGPTL2 Li-pshRNA eye drops compared to controls. Together, these findings indicate that this modified RNA interference agent is clinically viable in a topical formulation for use against CNV.

  19. Association of Neovascular Glaucoma with Risk of Stroke: A Population-Based Cohort Study

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    Cheng-Wen Su

    2017-01-01

    Full Text Available Neovascular glaucoma (NVG, caused by ocular ischemia, is a serious ocular disease complicated by intractably increased intraocular pressure. Cerebrovascular accidents are classified into ischemic and hemorrhagic stroke. Based on the similar pathogenic mechanisms of NVG and ischemic stroke, we investigated the relationship between NVG and stroke by using a nationally representative sample. This study included 416 NVG patients and 4160 controls. Medical comorbidities were also evaluated. The cumulative incidence of ischemic stroke was 15.6% higher in the NVG cohort than in the control cohort (p<0.001; the incidence density rates of stroke were 3.80 and 1.19 per 10,000 person-years in the NVG and control cohorts, respectively. According to the multivariable Cox regression results, the estimated adjusted hazard ratio (aHR of stroke was 2.07 (95% confidence interval (CI = 1.41–3.02 for the NVG cohort. Furthermore, the NVG cohort was 2.24-fold more likely to develop ischemic stroke (95% CI = 1.51–3.32. The risk of ischemic stroke was higher in patients with hypertension (aHR = 2.09, 95% CI = 1.55–2.82 and in patients with diabetic retinopathy (aHR = 1.69, 95% CI = 1.05–2.72. Notably, patients with NVG have a higher risk of ischemic stroke, but not hemorrhagic stroke.

  20. Cerebrovascular accidents in patients treated for choroidal neovascularization with ranibizumab in randomized controlled trials.

    Science.gov (United States)

    Bressler, Neil M; Boyer, David S; Williams, David F; Butler, Steven; Francom, Steven F; Brown, Benton; Di Nucci, Flavia; Cramm, Timothy; Tuomi, Lisa L; Ianchulev, Tsontcho; Rubio, Roman G

    2012-10-01

    To analyze cerebrovascular accidents (CVAs) pooled from large, randomized, controlled clinical trials of ranibizumab treatment for neovascular age-related macular degeneration. Events in five trials (FOCUS, MARINA, ANCHOR, PIER, and SAILOR) were analyzed using a standard safety monitoring process. Exact methods, stratified by study, were used to test for treatment differences based on odds ratios. A stepwise logistic regression model was fit to classify subjects' risk for CVA based on medical history. Treatment differences in CVA rates at 1 year or 2 years were evaluated within risk groups using stratified exact methods. Pooled 2-year CVA rates were <3%; odds ratios (95% confidence intervals) for CVA risk were 1.2 (0.4-4.4) for ranibizumab 0.3-mg versus control, 2.2 (0.8-7.1) for 0.5 mg versus control, and 1.5 (0.8-3.0) for 0.5-mg versus 0.3-mg ranibizumab. No substantial increased risk of CVA for 0.5 mg versus 0.3 mg was identified in pooled analyses or any of the individual trials. In pooled analyses, the difference between 0.5-mg ranibizumab and control was larger (7.7 [1.2-177]) among high-risk CVA patients. This analysis provided some evidence, although not definitive, of a potential increased risk of CVA with ranibizumab versus control or with 0.5-mg versus 0.3-mg ranibizumab. Continued monitoring for CVA within clinical trials seems warrented.

  1. Antiangiogenic immunotherapy targeting Flk-1, DNA vaccine and adoptive T cell transfer, inhibits ocular neovascularization

    International Nuclear Information System (INIS)

    Zhang, Han; Sonoda, Koh-Hei; Hijioka, Kuniaki; Qiao, Hong; Oshima, Yuji; Ishibashi, Tatsuro

    2009-01-01

    Ocular neovascularization (NV) is the primary cause of blindness in a wide range of ocular diseases. The exact mechanism underlying the pathogenesis of ocular NV is not yet well understood, and so there is no satisfactory therapy for ocular NV. Here, we describe a strategy targeting Flk-1, a self-antigen overexpressed on proliferating endothelial cells in ocular NV, by antiangiogenic immunotherapy-DNA vaccine and adoptive T cell therapy. An oral DNA vaccine encoding Flk-1 carried by attenuated Salmonella typhimurium markedly suppressed development of laser-induced choroidal NV. We further demonstrated that adoptive transfer of vaccine-induced CD8 + T cells reduced pathological preretinal NV, with a concomitant facilitation of physiological revascularization after oxygen-induced retinal vessel obliteration. However, physiological retinal vascular development was unaffected in neonatal mice transferred with vaccine-induced CD8 + T cells. These findings suggested that antiangiogenic immunotherapy targeting Flk-1 such as vaccination and adoptive immunotherapy may contribute to future therapies for ocular NV.

  2. Bevacizumab (Avastin and Thermal Laser Combination Therapy for Peripapillary Choroidal Neovascular Membranes

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    Sean D. Adrean

    2017-01-01

    Full Text Available Objective. This is a retrospective interventional case series describing the results of 5 eyes from 5 patients with symptomatic peripapillary choroidal neovascularization (CNVM receiving initial bevacizumab treatment followed by thermal laser and bevacizumab combination therapy. Methods. Patients received intravitreal bevacizumab injections until the lesions were well-defined. Thermal laser ablation was then administered and followed by an additional bevacizumab injection after one week. Visual outcomes, OCT changes, and rates of recurrence were recorded and analyzed. Results. Median visual outcomes improved from 20/50 to 20/30 (p=0.0232. Median central macular thickness decreased from 347 μm to 152 μm (p=0.0253. The mean visual improvement was 3 lines. An average of 3.8 bevacizumab injections per patient were given overall. Patients were followed for an average of 24 months, during which all eyes were absent for recurrence. Conclusion. Symptomatic peripapillary CNVM may be successfully managed with bevacizumab followed by a combination of thermal laser and bevacizumab without the need for frequent retreatment. The area requiring treatment may be better defined using bevacizumab, limiting the ablation of the healthy retina and improving treatment margins. With this treatment regimen, the patients experience improved visual outcomes and have a low rate of recurrence.

  3. Extracellular superoxide dismutase deficiency impairs wound healing in advanced age by reducing neovascularization and fibroblast function.

    Science.gov (United States)

    Fujiwara, Toshihiro; Duscher, Dominik; Rustad, Kristine C; Kosaraju, Revanth; Rodrigues, Melanie; Whittam, Alexander J; Januszyk, Michael; Maan, Zeshaan N; Gurtner, Geoffrey C

    2016-03-01

    Advanced age is characterized by impairments in wound healing, and evidence is accumulating that this may be due in part to a concomitant increase in oxidative stress. Extended exposure to reactive oxygen species (ROS) is thought to lead to cellular dysfunction and organismal death via the destructive oxidation of intra-cellular proteins, lipids and nucleic acids. Extracellular superoxide dismutase (ecSOD/SOD3) is a prime antioxidant enzyme in the extracellular space that eliminates ROS. Here, we demonstrate that reduced SOD3 levels contribute to healing impairments in aged mice. These impairments include delayed wound closure, reduced neovascularization, impaired fibroblast proliferation and increased neutrophil recruitment. We further establish that SOD3 KO and aged fibroblasts both display reduced production of TGF-β1, leading to decreased differentiation of fibroblasts into myofibroblasts. Taken together, these results suggest that wound healing impairments in ageing are associated with increased levels of ROS, decreased SOD3 expression and impaired extracellular oxidative stress regulation. Our results identify SOD3 as a possible target to correct age-related cellular dysfunction in wound healing. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Inhibition of the recombinant human endostatin adenavirus on experimental choroidal neovascularization in rats

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    Li-Juan Chen

    2017-06-01

    Full Text Available AIM: To investigate the inhibition of the recombinant human endostatin adenavirus(Ad-Eson the experimental choroidal neovascularization(CNVmodels by intravitreous injection. METHODS: Experimental CNV models were induced by semiconductor laser in 30 male Brown Norway(BNrats and randomly divided into 3 groups with 10 rats in each group. At 21d after photocoagulation, the single administration group were given intravitreous injection with Ad-Es 0.01mL; the repeated administration group were given intravitreous injection with Ad-Es 0.01mL and a repeated injection 7d later; the saline control group were given intravitreous injection with saline 0.01mL. At 7d after final administration, the leakage of fundus fluorescein angiography(FFAwas observed. Various CNV areas were measured by using laser confocal microscopy of choroidal flatmount method. Pathology and ultrastructure were observed with light microscopy, the expressions of CD105 were measured by immunohistochemistry. RESULTS: The leakage of CNV of the administration group abviously decreased as compared with those in the saline group, the leakage of repeated administration group decreased compared with that of single administration group(PPCONCLUSION: Ad-Es can effectively inhibit semiconductor laser induced CNV in BN rats, and the inhibition effect of repeated administration group is better than that of single administration group. It may be a useful new method in the treatment of CNV.

  5. RECURRENCE OF CHOROIDAL NEOVASCULARIZATION LESION ACTIVITY AFTER AFLIBERCEPT TREATMENT FOR AGE-RELATED MACULAR DEGENERATION.

    Science.gov (United States)

    Wakazono, Tomotaka; Yamashiro, Kenji; Oishi, Akio; Ooto, Sotaro; Tamura, Hiroshi; Akagi-Kurashige, Yumiko; Hata, Masayuki; Takahashi, Ayako; Tsujikawa, Akitaka; Yoshimura, Nagahisa

    2017-11-01

    To examine the recurrence rate of choroidal neovascularization (CNV) lesion activity in age-related macular degeneration (AMD) and associated factors after 1-year aflibercept treatment. Age-related macular degeneration eyes with 1-year aflibercept fixed-regimen treatment and a follow-up period of at least 18 months from the initial aflibercept injection for treatment-naive exudative AMD were retrospectively evaluated. The recurrence rate was examined. Age, gender, visual acuity, AMD subtype, greatest linear dimension, and retinal and choroidal thicknesses at the 12th month examination were compared between eyes with and without recurrence. Presence of remnant polyps and pigment epithelial detachment (PED) morphology were also compared in polypoidal choroidal vasculopathy (PCV) eyes. Of the 98 eyes studied, 69 displayed a dry macula at the 12th month examination; 43.7% exhibited recurrence during the subsequent 12-month period in Kaplan-Meier analysis. Although no factors associated with recurrence were detected in AMD, remnant polyps and pigment epithelial detachment morphology at the 12th month examination were significantly associated with recurrence in polypoidal choroidal vasculopathy (P = 0.018 and 0.048, respectively). Continuous, proactive treatment would be considered overtreatment for more than half of the AMD eyes that achieved a dry macula. Angiography and optical coherence tomography analyses may be useful for predicting recurrence in polypoidal choroidal vasculopathy eyes.

  6. Hypoxia-induced retinal neovascularization in zebrafish embryos: a potential model of retinopathy of prematurity.

    Science.gov (United States)

    Wu, Yu-Ching; Chang, Chao-Yuan; Kao, Alex; Hsi, Brian; Lee, Shwu-Huey; Chen, Yau-Hung; Wang, I-Jong

    2015-01-01

    Retinopathy of prematurity, formerly known as a retrolental fibroplasia, is a leading cause of infantile blindness worldwide. Retinopathy of prematurity is caused by the failure of central retinal vessels to reach the retinal periphery, creating a nonperfused peripheral retina, resulting in retinal hypoxia, neovascularization, vitreous hemorrhage, vitreoretinal fibrosis, and loss of vision. We established a potential retinopathy of prematurity model by using a green fluorescent vascular endothelium zebrafish transgenic line treated with cobalt chloride (a hypoxia-inducing agent), followed by GS4012 (a vascular endothelial growth factor inducer) at 24 hours postfertilization, and observed that the number of vascular branches and sprouts significantly increased in the central retinal vascular trunks 2-4 days after treatment. We created an angiography method by using tetramethylrhodamine dextran, which exhibited severe vascular leakage through the vessel wall into the surrounding retinal tissues. The quantification of mRNA extracted from the heads of the larvae by using real-time quantitative polymerase chain reaction revealed a twofold increase in vegfaa and vegfr2 expression compared with the control group, indicating increased vascular endothelial growth factor signaling in the hypoxic condition. In addition, we demonstrated that the hypoxic insult could be effectively rescued by several antivascular endothelial growth factor agents such as SU5416, bevacizumab, and ranibizumab. In conclusion, we provide a simple, highly reproducible, and clinically relevant retinopathy of prematurity model based on zebrafish embryos; this model may serve as a useful platform for clarifying the mechanisms of human retinopathy of prematurity and its progression.

  7. FIVE-YEAR OUTCOMES OF INTRAVITREAL RANIBIZUMAB FOR CHOROIDAL NEOVASCULARIZATION IN PATIENTS WITH PATHOLOGIC MYOPIA.

    Science.gov (United States)

    Onishi, Yuka; Yokoi, Tae; Kasahara, Kaori; Yoshida, Takeshi; Nagaoka, Natsuko; Shinohara, Kosei; Kaneko, Yuichiro; Suga, Mitsuki; Uramoto, Kengo; Ohno-Tanaka, Akiko; Ohno-Matsui, Kyoko

    2018-05-03

    To determine the 5-year outcome of intravitreal ranibizumab (IVR) for myopic choroidal neovascularization (CNV). We retrospectively analyzed the medical records of 51 eyes of 51 consecutive patients with myopic CNV who had been treated with IVR with a minimum follow-up period of 5 years after the initial IVR injection. The factors that predicted the best-corrected visual acuity (BCVA) at 5 years after IVR were determined by multiple regression analysis. The mean age of the subjects was 63.6 years, and the mean axial length was 29.4 mm. The mean number of IVR was 1.6, and 34 eyes (66.7%) had only a single IVR. At the baseline and at the 1-year, 2-year, 4-year, and 5-year period, the mean BCVAs were 20/49, 20/37, 20/41, 20/45, and 20/42, respectively. Stepwise multiple regression analysis showed that the BCVA at 5-year period was significantly correlated with the baseline BCVA, the number of IVR injections, and the size of the CNV-related macular atrophy. Intravitreal ranibizumab provide a 5-year visual benefit in eyes with myopic CNV compared with the natural course. A lack of enlargement of the CNV-related macular atrophy, a better baseline BCVA, and a minimum number of IVR injections were associated with better visual outcomes.

  8. Effects of ginkgo biloba extract on laser-induced choroidal neovascularization in rats

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    Chao Chen

    2013-11-01

    Full Text Available AIM: To investigate the effects of ginkgo biloba extract(EGb 761on laser-induced choroidal neovascularization(CNVin rats.METHODS: Totally 60 BN rats were randomly divided into 4 groups: normal control group, model group, experimental group, physiological saline group with 15 in each group. All CNV models were made by krypton laser. Rats in experimental group were intraperitoneally injected with 0.35% EGb761(100mg/kgevery day after laser exposure until they were sacrificed. Rats in physiological saline group were intraperitoneally injected physiological saline every day after laser exposure until they were sacrificed. Fundus fluorescein angiography(FFAwas performed on every rat on the 7th day, 14th day and the 21st day after laser exposure, then the rats were sacrificed immediately. The eyes were enucleated and processed for histopathologic examination.RESULTS: There was no choroidal fluorescein leakage staining in normal rats. There were obviously less choroidal fluorescein leakage points in experimental groups than that in the corresponding model groups(PCONCLUSION: EGb761 len inhibit the formation of laser-induced CNV in rats. The longer the time, the better curative effect.

  9. An experimental study on choroidal neovascularization induced by Krypton laser in rat model.

    Science.gov (United States)

    Cui, Jing; Liu, Yuanyuan; Zhang, Jingkai; Yan, Hua

    2014-01-01

    The purpose of this work was to study the efficacy and safety of choroidal neovascularization (CNV) formation induced by Krypton laser in Brown Norway (BN) rats, and observe the trend of the change of CNV after laser photocoagulation. Twenty-five male BN rats were involved in this study. Two eyes of one rat without any laser photocoagulation were randomly selected as the control group, and the other 48 eyes of 24 rats were selected as the experimental group. Eight eyes of four rats were randomly selected to receive the examinations of fundus fluorescein angiography (FFA), histopathology, and transmission electron microscopy 3, 7, 14, 21, 28, and 56 days after laser photocoagulation. After laser photocoagulation, the leakage appeared in burns on day 7 (59%), reached the peak on day 21 (84%), (p0.05). The thickness of CNV increased from day 7 to day 21 (p0.05). The experimental model of CNV can be successfully induced by Krypton laser in rats with a stable, long-lasting, and high success rate. After laser photocoagulation, the leakages appear on day 7, reach the peak on day 21, and remain stable after day 21.

  10. Optical Coherence Tomography Angiography in Retinal Vascular Diseases and Choroidal Neovascularization

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    Rodolfo Mastropasqua

    2015-01-01

    Full Text Available Purpose. To assess the ability of optical coherence tomography-angiography (OCT-A to show and analyze retinal vascular patterns and the choroidal neovascularization (CNV in retinal vascular diseases. Methods. Seven eyes of seven consecutive patients with retinal vascular diseases were examined. Two healthy subjects served as controls. All eyes were scanned with the SD-OCT XR Avanti (Optovue Inc, Fremont CA, USA. Split spectrum amplitude decorrelation angiography algorithm was used to identify the blood flow within the tissue. Fluorescein angiography (FA and indocyanine green angiography (ICGA with Spectralis HRA + OCT (Heidelberg Engineering GmbH were performed. Results. In healthy subjects OCT-A visualized major macular vessels and detailed capillary networks around the foveal avascular zone. Patients were affected with myopic CNV (2 eyes, age-related macular degeneration related (2, branch retinal vein occlusion (BRVO (2, and branch retinal artery occlusion (BRAO (1. OCT-A images provided distinct vascular patterns, distinguishing perfused and nonperfused areas in BRVO and BRAO and recognizing the presence, location, and size of CNV. Conclusions. OCT-A provides detailed images of retinal vascular plexuses and quantitative data of pathologic structures. Further studies are warranted to define the role of OCT-A in the assessment of retinovascular diseases, with respect to conventional FA and ICG-A.

  11. Detection of neovascularization based on fractal and texture analysis with interaction effects in diabetic retinopathy.

    Science.gov (United States)

    Lee, Jack; Zee, Benny Chung Ying; Li, Qing

    2013-01-01

    Diabetic retinopathy is a major cause of blindness. Proliferative diabetic retinopathy is a result of severe vascular complication and is visible as neovascularization of the retina. Automatic detection of such new vessels would be useful for the severity grading of diabetic retinopathy, and it is an important part of screening process to identify those who may require immediate treatment for their diabetic retinopathy. We proposed a novel new vessels detection method including statistical texture analysis (STA), high order spectrum analysis (HOS), fractal analysis (FA), and most importantly we have shown that by incorporating their associated interactions the accuracy of new vessels detection can be greatly improved. To assess its performance, the sensitivity, specificity and accuracy (AUC) are obtained. They are 96.3%, 99.1% and 98.5% (99.3%), respectively. It is found that the proposed method can improve the accuracy of new vessels detection significantly over previous methods. The algorithm can be automated and is valuable to detect relatively severe cases of diabetic retinopathy among diabetes patients.

  12. Detection of neovascularization based on fractal and texture analysis with interaction effects in diabetic retinopathy.

    Directory of Open Access Journals (Sweden)

    Jack Lee

    Full Text Available Diabetic retinopathy is a major cause of blindness. Proliferative diabetic retinopathy is a result of severe vascular complication and is visible as neovascularization of the retina. Automatic detection of such new vessels would be useful for the severity grading of diabetic retinopathy, and it is an important part of screening process to identify those who may require immediate treatment for their diabetic retinopathy. We proposed a novel new vessels detection method including statistical texture analysis (STA, high order spectrum analysis (HOS, fractal analysis (FA, and most importantly we have shown that by incorporating their associated interactions the accuracy of new vessels detection can be greatly improved. To assess its performance, the sensitivity, specificity and accuracy (AUC are obtained. They are 96.3%, 99.1% and 98.5% (99.3%, respectively. It is found that the proposed method can improve the accuracy of new vessels detection significantly over previous methods. The algorithm can be automated and is valuable to detect relatively severe cases of diabetic retinopathy among diabetes patients.

  13. Variability of disease activity in patients treated with ranibizumab for neovascular age-related macular degeneration.

    Science.gov (United States)

    Enders, P; Scholz, P; Muether, P S; Fauser, S

    2016-08-01

    PurposeTo analyze choroidal neovasularization (CNV) activity and recurrence patterns in patients with neovascular age-related macular degeneration (nAMD) treated with ranibizumab, and the correlation with individual intraocular vascular endothelial growth factor (VEGF) suppression time (VST).MethodsPost-hoc analysis of data from a prospective, non-randomized clinical study. Patients with nAMD treated with ranibizumab on a pro re nata regimen. Disease activity was analyzed monthly by spectral-domain optical coherence tomography and correlated with VSTs.ResultsOverall, 73 eyes of 73 patients were included in the study with a mean follow-up of 717 days (range: 412-1239 days). Overall, the mean CNV-activity-free interval was 76.5 days (range: 0-829 days). The individual range of the length of dry intervals was high. A total of 42% of patients had a range of more than 90 days. Overall, 16% of patients showed persistent activity. And 12% stayed dry after the initial ranibizumab treatment. No significant correlation was found between the CNV-recurrence pattern and VST (P=0.12).ConclusionsCNV activity in nAMD is irregular, which is reflected in the range of the duration of dry intervals and late recurrences. The biomarker VST solely seems not to be sufficient to explain recurrence pattern of CNV in all AMD patients.

  14. Caregiver Burden in Patients Receiving Ranibizumab Therapy for Neovascular Age Related Macular Degeneration.

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    Rishma Gohil

    Full Text Available To assess the caregiver burden and factors determining the burden in patients receiving ranibizumab therapy for neovascular AMD (nAMD.This is a cross-sectional questionnaire survey of 250 matched patient caregiver dyads across three large ophthalmic treatment centres in United Kingdom. The primary outcome was the subjective caregiver burden measured using caregiver reaction assessment scale (CRA. Objective caregiver burden was determined by the caregiver tasks and level of care provided. The factors that may predict the caregiver burden such as the patient's visual acuity of the better eye and vision related quality of life, demographics, satisfaction and support provided by the healthcare and the health status of the dyads were also collected and assessed in a hierarchical regression model.The mean CRA score was 3.2±0.5, similar to the score reported by caregivers for atrial fibrillation who require regular hospital appointments for monitoring their thromboprophylaxis. Caregiver tasks including accompanying for hospital appointments for eye treatment and patient's visual acuity in the better eye were the biggest contributors to the caregiver burden hierarchical model explaining 18% and 11% of the variance respectively.Ranibizumab therapy for nAMD is associated with significant caregiver burden. Both disease impact and treatment frequency contributed to the overall burden.

  15. Targeting NCK-Mediated Endothelial Cell Front-Rear Polarity Inhibits Neovascularization.

    Science.gov (United States)

    Dubrac, Alexandre; Genet, Gael; Ola, Roxana; Zhang, Feng; Pibouin-Fragner, Laurence; Han, Jinah; Zhang, Jiasheng; Thomas, Jean-Léon; Chedotal, Alain; Schwartz, Martin A; Eichmann, Anne

    2016-01-26

    Sprouting angiogenesis is a key process driving blood vessel growth in ischemic tissues and an important drug target in a number of diseases, including wet macular degeneration and wound healing. Endothelial cells forming the sprout must develop front-rear polarity to allow sprout extension. The adaptor proteins Nck1 and 2 are known regulators of cytoskeletal dynamics and polarity, but their function in angiogenesis is poorly understood. Here, we show that the Nck adaptors are required for endothelial cell front-rear polarity and migration downstream of the angiogenic growth factors VEGF-A and Slit2. Mice carrying inducible, endothelial-specific Nck1/2 deletions fail to develop front-rear polarized vessel sprouts and exhibit severe angiogenesis defects in the postnatal retina and during embryonic development. Inactivation of NCK1 and 2 inhibits polarity by preventing Cdc42 and Pak2 activation by VEGF-A and Slit2. Mechanistically, NCK binding to ROBO1 is required for both Slit2- and VEGF-induced front-rear polarity. Selective inhibition of polarized endothelial cell migration by targeting Nck1/2 prevents hypersprouting induced by Notch or Bmp signaling inhibition, and pathological ocular neovascularization and wound healing, as well. These data reveal a novel signal integration mechanism involving NCK1/2, ROBO1/2, and VEGFR2 that controls endothelial cell front-rear polarity during sprouting angiogenesis. © 2015 American Heart Association, Inc.

  16. Targeting NCK-Mediated Endothelial Cell Front-Rear Polarity Inhibits Neo-Vascularization

    Science.gov (United States)

    Dubrac, Alexandre; Genet, Gael; Ola, Roxana; Zhang, Feng; Pibouin-Fragner, Laurence; Han, Jinah; Zhang, Jiasheng; Thomas, Jean-Léon; Chedotal, Alain; Schwartz, Martin A.; Eichmann, Anne

    2015-01-01

    Background Sprouting angiogenesis is a key process driving blood vessel growth in ischemic tissues and an important drug target in a number of diseases, including wet macular degeneration and wound healing. Endothelial cells forming the sprout must develop front-rear polarity to allow sprout extension. The adaptor proteins Nck1 and 2 are known regulators of cytoskeletal dynamics and polarity, but their function in angiogenesis is poorly understood. Here we show that the Nck adaptors are required for endothelial cell front-rear polarity and migration downstream of the angiogenic growth factors VEGF-A and Slit2. Methods and Results Mice carrying inducible, endothelial-specific Nck1/2 deletions fail to develop front-rear polarized vessel sprouts and exhibit severe angiogenesis defects in the postnatal retina and during embryonic development. Inactivation of NCK1 and 2 inhibits polarity by preventing Cdc42 and Pak2 activation by VEGF-A and Slit2. Mechanistically, NCK binding to ROBO1 is required for both Slit2 and VEGF induced front-rear polarity. Selective inhibition of polarized endothelial cell migration by targeting Nck1/2 prevents hypersprouting induced by Notch or Bmp signaling inhibition, as well as pathological ocular neovascularization and wound healing. Conclusions These data reveal a novel signal integration mechanism involving NCK1/2, ROBO1/2 and VEGFR2 that controls endothelial cell front-rear polarity during sprouting angiogenesis. PMID:26659946

  17. Role of macular xanthophylls in prevention of common neovascular retinopathies: retinopathy of prematurity and diabetic retinopathy.

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    Gong, Xiaoming; Rubin, Lewis P

    2015-04-15

    Retinopathy of prematurity (ROP) and diabetic retinopathy (DR) are important causes of blindness among children and working-age adults, respectively. The development of both diseases involves retinal microvascular degeneration, vessel loss and consequent hypoxic and inflammatory pathologic retinal neovascularization. Mechanistic studies have shown that oxidative stress and subsequent derangement of cell signaling are important factors in disease progression. In eye and vision research, role of the dietary xanthophyll carotenoids, lutein and zeaxanthin, has been more extensively studied in adult onset macular degeneration than these other retinopathies. These carotenoids also may decrease severity of ROP in preterm infants and of DR in working-age adults. A randomized controlled clinical trial of carotenoid supplementation in preterm infants indicated that lutein has functional effects in the neonatal eye and is anti-inflammatory. Three multicenter clinical trials all showed a trend of decreased ROP severity in the lutein supplemented group. Prospective studies on patients with non-proliferative DR indicate serum levels of lutein and zeaxanthin are significantly lower in these patients compared to normal subjects. The present review describes recent advances in lutein and zeaxanthin modulation of oxidative stress and inflammation related to ROP and DR and discusses potential roles of lutein/zeaxanthin in preventing or lessening the risks of disease initiation or progression. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Effect of combined topical heparin and steroid on corneal neovascularization in children.

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    Michels, Rike; Michels, Stephan; Kaminski, Stephan

    2012-01-01

    To demonstrate the effect of topical heparin combined with topical steroid on corneal neovascularization (CN) in children. Four children (5 eyes) with new-onset progressive CN in at least one eye received topical rimexolone or dexamethasone in combination with heparin until complete regression of CN was obtained. The regression of CN was documented by slit-lamp or anterior segment photography. All 5 eyes showed complete regression of CN within 5 months. An anti-angiogenic effect was found as early as 1 week after starting topical combination treatment. No ocular and systemic side effects were detected and treatment was well tolerated by all children. In the 3 eyes with involvement of the optical axis, symmetrical visual acuity was obtained by amblyopia treatment. Recurrence of the CN was detectable in 2 eyes at 1 and 6 months, respectively, after ending combination therapy. Both eyes responded favorably to re-treatment. Combination of topical heparin and steroid leads to rapid regression and complete inactivity of CN. This therapeutic approach is promising, especially in children with limited therapeutic alternatives and a high risk for amblyopia. Copyright 2012, SLACK Incorporated.

  19. Visual function after strontium-90 plaque irradiation in patients with age-related subfoveal choroidal neovascularization

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    Jaakkola, A.; Tarkkanen, A.; Immonen, I. [Helsinki Univ. Central Hospital, Dept. of Ophthalmology (Finland); Heikkonen, J. [Helsinki Univ. Central Hospital, Dept. of Oncology (Finland)

    1999-05-01

    Purpose: To report 2-year visual and angiographic results in eyes treated with strontium plaque irradiation for subfoveal choroidal neovascular membranes (CNVM) in age-related macular degeneration. Methods: Twenty eyes with recent subfoveal CNVM were treated with local irradiation. The impact of the treatment on visual function was evaluated by visual acuity, contrast sensitivity and reading speed testing. Results: At 12 months visual acuity had improved or remained the same in 9/20 eyes (45%). At 24 months visual acuity was stable in 5/18 eyes (28%). Eyes with signs of CNVM regression (13/18,72%) lost a mean of 3.3 lines, but eyes with recurrent CNVM lost a mean of 5.1 lines of vision. The mean contrast sensitivity was better in the irradiated eyes than in the fellow eyes with late age-related macular degeneration at 24 months. Six of 17 irradiated eyes (35%) could read at least some words at 24 months. Conclusion: Visual function decreases in patients treated with strontium irradiation, but less in eyes showing regression of the CNVM than in eyes with further growth of the CNVM. (au) 20 refs.

  20. Influence of new societal factors on neovascular age-related macular degeneration outcomes.

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    Giocanti-Aurégan, Audrey; Chbat, Elige; Darugar, Adil; Morel, Christophe; Morin, Bruno; Conrath, John; Devin, François

    2018-02-01

    To assess the impact of unstudied societal factors for neovascular age-related macular degeneration (nAMD) on functional outcomes after anti-VEGFs. Charts of 94 nAMD patients treated in the Monticelli-Paradis Centre, Marseille, France, were reviewed. Phone interviews were conducted to assess societal factors, including transportation, living status, daily reading and social security scheme (SSS). Primary outcome was the impact of family support and disease burden on functional improvement in nAMD. Between baseline and month 24 (M24), 42.4% of the variability in best-corrected visual acuity (BCVA) was explained by the cumulative effect of the following societal factors: intermittent out-patient follow-up, marital status, daily reading, transportation type, commuting time. No isolated societal factor significantly correlated with ETDRS BCVA severity at M24. A trend to correlation was observed between the EDTRS score at M24 and the SSS (P = 0.076), economic burden (P = 0.075), time between diagnosis and treatment initiation (P = 0.070). A significant correlation was found for the disease burdensome on the patient (P = 0.034) and low vision rehabilitation (P = 0.014). Societal factors could influence functional outcomes in nAMD patients treated with anti-VEGFs. They could contribute to the healing process or sustain disease progression.

  1. Submacular hemorrhage in neovascular age-related macular degeneration: A synthesis of the literature.

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    Stanescu-Segall, Dinu; Balta, Florian; Jackson, Timothy L

    2016-01-01

    Large submacular hemorrhage, an uncommon manifestation of neovascular age-related macular degeneration, may also occur with idiopathic polypoidal choroidal vasculopathy. Submacular hemorrhage damages photoreceptors owing to iron toxicity, fibrin meshwork contraction, and reduced nutrient flux, with subsequent macular scarring. Clinical and experimental studies support prompt treatment, as tissue damage can occur within 24 hours. Without treatment the natural history is poor, with a mean final visual acuity (VA) of 20/1600. Reported treatments include retinal pigment epithelial patch, macular translocation, pneumatic displacement, intravitreal or subretinal tissue plasminogen activator, intravitreal anti-vascular endothelial growth factor (VEGF) drugs, and combinations thereof. In the absence of comparative studies, we combined eligible studies to assess the VA change before and after each treatment option. The greatest improvement occurred after combined pars plana vitrectomy, subretinal tissue plasminogen activator, intravitreal gas, and anti-vascular endothelial growth factor treatment, with VA improving from 20/1000 to 20/400. The best final VA occurred using combined intravitreal tissue plasminogen activator, gas, and anti-vascular endothelial growth factor therapy, with VA improving from 20/200 to 20/100. Both treatments had an acceptable safety profile, but most studies were small, and larger randomized controlled trials are needed to determine both safety and efficacy. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  2. Fasudil hydrochloride, a potent ROCK inhibitor, inhibits corneal neovascularization after alkali burns in mice

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    Zeng, Peng; Pi, Rong-biao; Li, Peng; Chen, Rong-xin; Lin, Li-mian; He, Hong

    2015-01-01

    Purpose To investigate the effects and mechanisms of fasudil hydrochloride (fasudil) on and in alkali burn-induced corneal neovascularization (CNV) in mice. Methods To observe the effect of fasudil, mice with alkali-burned corneas were treated with either fasudil eye drops or phosphate-buffered saline (PBS) four times per day for 14 consecutive days. After injury, CNV and corneal epithelial defects were measured. The production of reactive oxygen species (ROS) and heme oxygenase-1(HO-1) was measured. The infiltration of polymorphonuclear neutrophils (PMNs) and the mRNA expressions of CNV-related genes were analyzed on day 14. Results The incidence of CNV was significantly lower after treatment with 100 μM and 300 μM fasudil than with PBS, especially with 100 μM fasudil. Meanwhile, the incidences of corneal epithelial defects was lower (n=15, all palkali burn-induced CNV and promote the healing of corneal epithelial defects in mice. These effects are attributed to a decrease in inflammatory cell infiltration, reduction of ROS, and upregulation of HO-1 protein after fasudil treatment. PMID:26120273

  3. Bevacizumab (Avastin® no tratamento da membrana neovascular coroidal secundária à degeneração macular relacionada à idade: relato de caso Bevacizumab (Avastin® in treatment of choroidal neovascularization secondary to age-related macular degeneration: a case report

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    Tiago Eugênio Faria e Arantes

    2007-12-01

    Full Text Available As drogas anti-angiogênicas foram introduzidas recentemente no arsenal terapêutico das membranas neovasculares coroidais. O objetivo deste relato é descrever um caso de membranas neovasculares coroidais oculta com extenso descolamento do epitélio pigmentado da retina, tratada com bevacizumab (Avastin® intravítrea. A eficácia da medicação foi avaliada por meio da acuidade visual e de exames complementares (angiografia fluoresceínica, videoangiografia com indocianina verde e tomografia de coerência óptica. Após três injeções intravítreas de bevacizumab, obteve-se uma resposta anatômica e visual satisfatória, denotando benefícios da droga, apesar do extenso descolamento do epitélio pigmentado da retina associada a membranas neovasculares coroidais oculta.The antiangiogenic drugs have been recently introduced in the therapeutic armamentarium of choroidal neovascularization. The purpose of this report is to describe a case of occult choroidal neovascularization with extensive retinal pigment epithelial detachment treated with intravitreal bevacizumab (Avastin®. The efficacy of the medication was evaluated by means of visual acuity and complementary exams (fluorescein angiography, indocyanine green video angiography and optical coherence tomography. After three intravitreal injections of bevacizumab a satisfactory anatomic and visual response was achieved, showing benefits of the drug, despite the extensive retinal pigment epithelial detachment associated with occult choroidal neovascularization.

  4. An assessment of functioning and non-functioning distractors in multiple-choice questions: a descriptive analysis

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    Mohammed Ahmed M

    2009-07-01

    Full Text Available Abstract Background Four- or five-option multiple choice questions (MCQs are the standard in health-science disciplines, both on certification-level examinations and on in-house developed tests. Previous research has shown, however, that few MCQs have three or four functioning distractors. The purpose of this study was to investigate non-functioning distractors in teacher-developed tests in one nursing program in an English-language university in Hong Kong. Methods Using item-analysis data, we assessed the proportion of non-functioning distractors on a sample of seven test papers administered to undergraduate nursing students. A total of 514 items were reviewed, including 2056 options (1542 distractors and 514 correct responses. Non-functioning options were defined as ones that were chosen by fewer than 5% of examinees and those with a positive option discrimination statistic. Results The proportion of items containing 0, 1, 2, and 3 functioning distractors was 12.3%, 34.8%, 39.1%, and 13.8% respectively. Overall, items contained an average of 1.54 (SD = 0.88 functioning distractors. Only 52.2% (n = 805 of all distractors were functioning effectively and 10.2% (n = 158 had a choice frequency of 0. Items with more functioning distractors were more difficult and more discriminating. Conclusion The low frequency of items with three functioning distractors in the four-option items in this study suggests that teachers have difficulty developing plausible distractors for most MCQs. Test items should consist of as many options as is feasible given the item content and the number of plausible distractors; in most cases this would be three. Item analysis results can be used to identify and remove non-functioning distractors from MCQs that have been used in previous tests.

  5. An assessment of functioning and non-functioning distractors in multiple-choice questions: a descriptive analysis.

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    Tarrant, Marie; Ware, James; Mohammed, Ahmed M

    2009-07-07

    Four- or five-option multiple choice questions (MCQs) are the standard in health-science disciplines, both on certification-level examinations and on in-house developed tests. Previous research has shown, however, that few MCQs have three or four functioning distractors. The purpose of this study was to investigate non-functioning distractors in teacher-developed tests in one nursing program in an English-language university in Hong Kong. Using item-analysis data, we assessed the proportion of non-functioning distractors on a sample of seven test papers administered to undergraduate nursing students. A total of 514 items were reviewed, including 2056 options (1542 distractors and 514 correct responses). Non-functioning options were defined as ones that were chosen by fewer than 5% of examinees and those with a positive option discrimination statistic. The proportion of items containing 0, 1, 2, and 3 functioning distractors was 12.3%, 34.8%, 39.1%, and 13.8% respectively. Overall, items contained an average of 1.54 (SD = 0.88) functioning distractors. Only 52.2% (n = 805) of all distractors were functioning effectively and 10.2% (n = 158) had a choice frequency of 0. Items with more functioning distractors were more difficult and more discriminating. The low frequency of items with three functioning distractors in the four-option items in this study suggests that teachers have difficulty developing plausible distractors for most MCQs. Test items should consist of as many options as is feasible given the item content and the number of plausible distractors; in most cases this would be three. Item analysis results can be used to identify and remove non-functioning distractors from MCQs that have been used in previous tests.

  6. Optimization of an Image-Guided Laser-Induced Choroidal Neovascularization Model in Mice.

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    Yan Gong

    Full Text Available The mouse model of laser-induced choroidal neovascularization (CNV has been used in studies of the exudative form of age-related macular degeneration using both the conventional slit lamp and a new image-guided laser system. A standardized protocol is needed for consistent results using this model, which has been lacking. We optimized details of laser-induced CNV using the image-guided laser photocoagulation system. Four lesions with similar size were consistently applied per eye at approximately double the disc diameter away from the optic nerve, using different laser power levels, and mice of various ages and genders. After 7 days, the mice were sacrificed and retinal pigment epithelium/choroid/sclera was flat-mounted, stained with Isolectin B4, and imaged. Quantification of the area of the laser-induced lesions was performed using an established and constant threshold. Exclusion criteria are described that were necessary for reliable data analysis of the laser-induced CNV lesions. The CNV lesion area was proportional to the laser power levels. Mice at 12-16 weeks of age developed more severe CNV than those at 6-8 weeks of age, and the gender difference was only significant in mice at 12-16 weeks of age, but not in those at 6-8 weeks of age. Dietary intake of omega-3 long-chain polyunsaturated fatty acid reduced laser-induced CNV in mice. Taken together, laser-induced CNV lesions can be easily and consistently applied using the image-guided laser platform. Mice at 6-8 weeks of age are ideal for the laser-induced CNV model.

  7. Theme trends and knowledge structure on choroidal neovascularization: a quantitative and co-word analysis.

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    Zhao, Fangkun; Shi, Bei; Liu, Ruixin; Zhou, Wenkai; Shi, Dong; Zhang, Jinsong

    2018-04-03

    The distribution pattern and knowledge structure of choroidal neovascularization (CNV) was surveyed based on literatures in PubMed. Published scientific papers about CNV were retrieved from Jan 1st, 2012 to May 31st, 2017. Extracted MeSH terms were analyzed quantitatively by using Bibliographic Item Co-Occurrence Matrix Builder (BICOMB) and high-frequency MeSH terms were identified. Hierarchical cluster analysis was conducted by SPSS 19.0 according to the MeSH term-source article matrix. High-frequency MeSH terms co-occurrence matrix was constructed to support strategic diagram and social network analysis (SNA). According to the searching strategy, all together 2366 papers were included, and the number of annual papers changed slightly from Jan 1st, 2012 to May 31st, 2017. Among all the extracted MeSH terms, 44 high-frequency MeSH terms were identified and hotspots were clustered into 6 categories. In the strategic diagram, clinical drug therapy, pathology and diagnosis related researches of CNV were well developed. In contrast, the metabolism, etiology, complications, prevention and control of CNV in animal models, and genetics related researches of CNV were relatively immature, which offers potential research space for future study. As for the SNA result, the position status of each component was described by the centrality values. The studies on CNV are relatively divergent and the 6 research categories concluded from this study could reflect the publication trends on CNV to some extent. By providing a quantitative bibliometric research across a 5-year span, it could help to depict an overall command of the latest topics and provide some hints for researchers when launching new projects.

  8. Expression of hypoxia-inducible factor-1α and erythropoietin at corneal neovascularization in rats

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    Ji-Min Wang

    2014-12-01

    Full Text Available AIM: To describe the expression of hypoxia-inducible factor-1α(HIF-1αand erythropoietin(EPOin rats' corneal and evaluate its potential effect on corneal neovascularization(CNVgrowth. METHODS: The young SD rats(3mowas chosen and randomly divided into 2 groups, which were experimental group and normal control group. CNV model was established by alkali burn, and the length and area of CNV was observed everyday after operation by slit lamp. After that, the expression of HIF-1α and EPO was measured by SABC and RT-PCR methods at 1, 3, 5, 7, and 14d after alkali burn. The data was analyzed by SPSS 20.0. RESULTS: The area of CNV was increasing at 1, 3, 5, 7, and 14d after alkali burn, and the peak point appear at 7d. The growth speed was decreased after 14d. SABC method told us that no HIF-1α and very tiny amount EPO was detected at normal rats' corneal. The expression of the two factors increased at 1d after alkali burn in corneal epithelium and endoderm. The results of RT-PCR showed that a few amounts of HIF-1α and EPO mRNA were detected at normal group. The expression of the two factors was increased at 3d after alkali burn, and the peak value was found at 7d, however, it was decreased at 14d. Statistical difference was found at different time(PCONCLUSION: HIF-1α and EPO is closely related to CNV.

  9. OPTIMAL MANAGEMENT OF PIGMENT EPITHELIAL DETACHMENTS IN EYES WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

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    Khanani, Arshad M; Eichenbaum, David; Schlottmann, Patricio G; Tuomi, Lisa; Sarraf, David

    2018-04-24

    This review aimed to determine the optimal management of retinal pigment epithelial detachments (PEDs) in neovascular age-related macular degeneration (nAMD) based on review of available evidence in the literature. A comprehensive literature review evaluates previous retrospective and prospective studies that assessed the treatment of PEDs in nAMD. Studies illustrated that anti-vascular endothelial growth factor (VEGF) therapy can be effective in eyes with PED secondary to nAMD. Similar visual outcomes are associated with different anti-VEGF treatments. Higher anti-VEGF doses may improve anatomical response, without correlation with vision improvement. Fibrovascular PEDs may be difficult to treat, but even these eyes can gain vision with anti-VEGF therapy. A retinal pigment epithelial tear may develop in 15% to 20% of eyes with PEDs after anti-VEGF therapy, especially in PEDs greater than 500 µm to 600 µm in height; however, vision may stabilize with continued therapy. Atrophy may complicate eyes with PED and nAMD after anti-VEGF therapy, especially in association with complete PED resolution. Available literature suggests that anti-VEGF therapy is safe and efficacious for PED and nAMD. Treatment should focus on vision gains rather than PED resolution because there is no apparent correlation between anatomical and functional improvement in most eyes with PED and nAMD.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

  10. Changes of subfoveal choroidal thickness after treated by Ranibizumab for choroidal neovascularization secondary to pathologic myopia

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    Jian-Shu Yuan

    2016-05-01

    Full Text Available AIM:To observe the change of subfoveal choroidal thickness(SFCTafter intravitreal injections of anti-vascular endothelial growth factor monoclonal antibody Ranibizumab in patients with choroidal neovascularization(CNVsecondary to pathologic myopia(PMand to research the relation between visual acuity and SFCT.METHODS:This was a prospective, contrast, open-label study.Fifty pathologic myopia patients with CNV(50 eyeswere recruited in this study. Before the injection,best-corrected visual acuity detected by visual chart from Early Treatment of Diabetic Retinopathy Study(ETDRS,non-contact tonometer,ophthalmoscope,fundus photography, fundus fluorescein angiograph(FFAand optical coherence tomography(OCTexamination were necessary. All affected eye were treated with intravitreal ranibizumab 0.05mL. Following up for 12mo, the changes of visual acuity and SFCT were compared before and after treatment, also the relation between them. RESULTS:All eyes received an average of 2.47±2.23 injections,the final vision of follow-up increased by 13.62±8.98 letters than that before(t=6.69,Pt=0.95, P>0.05.While after 6 and 12mo,the differences were significant(t=2.34, 2.61; PPP>0.05.There were no serious systemic or local side effects during the follow up.CONCLUSION:Intravitreal ranibizumab for CNV secondary to pathologic myopia is safe and can improve the visual acuity.Intravitreal injections of ranibizumab can induce SFCT reduction for CNV secondary to pathologic myopia.We hypothesized that increase of SFCT may be one of evaluation index for CNV activity.

  11. Intraocular Vascular Endothelial Growth Factor Levels in Pachychoroid Neovasculopathy and Neovascular Age-Related Macular Degeneration.

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    Hata, Masayuki; Yamashiro, Kenji; Ooto, Sotaro; Oishi, Akio; Tamura, Hiroshi; Miyata, Manabu; Ueda-Arakawa, Naoko; Takahashi, Ayako; Tsujikawa, Akitaka; Yoshimura, Nagahisa

    2017-01-01

    To investigate the difference in intraocular vascular endothelial growth factor (VEGF) concentration between pachychoroid neovasculopathy and neovascular age-related macular degeneration (nAMD) and its associations with responses to three monthly anti-VEGF injections as an initial treatment for the two conditions. This study included nine eyes with treatment-naïve pachychoroid neovasculopathy and 21 eyes with treatment-naïve nAMD. Before the initial intravitreal anti-VEGF injection, aqueous humor samples were collected and the concentration of VEGF was measured using enzyme-linked immunosorbent assay. The concentration was compared between the two conditions, and its associations with responses to anti-VEGF therapy were investigated. The mean VEGF concentration in pachychoroid neovasculopathy was significantly lower than that in nAMD (63.4 ± 17.8 pg/ml and 89.8 ± 45.0 pg/ml, respectively; P = 0.035). The VEGF concentration was associated with the presence or absence of drusen (β = 0.503, P = 0.004). After anti-VEGF therapy, 6 (66.7%) of 9 eyes with pachychoroid neovasculopathy and 17 (81.0%) of 21 eyes with nAMD achieved dry macula (P = 0.640). Dry macula at 3 months and 12 months was significantly associated with a low VEGF concentration in pachychoroid neovasculopathy (P = 0.013 and P = 0.042, respectively), but not in nAMD (P = 0.108 and P = 0.219). The mean VEGF concentration in pachychoroid neovasculopathy was lower than that in nAMD, suggesting that the way in which VEGF is involved in angiogenesis may differ between pachychoroid neovasculopathy and nAMD.

  12. The effect of intravitreal bevacizumab injection before Ahmed valve implantation in patients with neovascular glaucoma.

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    Kang, Jung Youb; Nam, Ki Yup; Lee, Sang Joon; Lee, Seung Uk

    2014-08-01

    To evaluate the effect of intravitreal bevacizumab (IVB) before Ahmed valve implantation for treatment of neovascular glaucoma (NVG). This study is a retrospective, comparative, consecutive case series. The study group consisted of 27 eyes of 26 patients with NVG who underwent an Ahmed valve implantation. Thirteen eyes were treated with Ahmed valve implantation alone (control group), and 14 eyes were treated with a combination of preoperative IVB injection and Ahmed valve implantation (IVB group). Visual acuity, intraocular pressure (IOP), number of anti-glaucoma medications, surgical complications, and success rate were compared between the two groups. There were no significant differences in preoperative characteristics between the two groups. Visual acuity at 1, 2 weeks, and 1 month after surgery were significantly better in the IVB group (p = 0.038, 0.034, and 0.032, respectively). Hyphema associated with Ahmed valve implantation occurred significantly less in the IVB group (p = 0.016). On the other hand, the mean IOP and number of anti-glaucoma medications at all follow-up periods were similar between the two groups. Kaplan-Meier survival analysis showed the probability of success 6 months after surgery as 71.4 % in the IVB group and 84.6 % in the control group. No significant difference in success rate was found between the groups (p = 0.422). IVB before Ahmed valve implantation for treatment of NVG reduced the incidence of hyphema. In this retrospective study, IVB provided better visual outcome in the early postoperative periods but did not significantly improve mean IOP, number of anti-glaucoma medications, or success rate.

  13. Clinical efficacy analysis of Ahmed glaucoma valve implantation in neovascular glaucoma and influencing factors

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    He, Ye; Tian, Ying; Song, Weitao; Su, Ting; Jiang, Haibo; Xia, Xiaobo

    2017-01-01

    Abstract This study aimed to evaluate the efficacy of Ahmed glaucoma valve (AGV) implantation in treating neovascular glaucoma (NVG) and to analyze the factors influencing the surgical success rate. This is a retrospective review of 40 eyes of 40 NVG patients who underwent AGV implantation at Xiangya Hospital of Central South University, China, between January 2014 and December 2016. Pre- and postoperative intraocular pressure (IOP), visual acuity, surgical success rate, medications, and complications were observed. Surgical success criteria were defined as IOP ≤21 and >6 mm Hg with or without additional medications. Kaplan–Meier survival curves and Multivariate cox regression analysis were used to examine success rates and risk factors for surgical outcomes. The mean follow-up period was 8.88 ± 3.12 months (range: 3–17). IOP declined at each visit postoperatively and it was statistically significant (P < .001). An average of 3.55 ± 0.86 drugs was applied preoperatively, while an average of 0.64 ± 0.90 drugs was used postoperatively, with the difference being of statistical significance (P < .05). The complete surgical success rate of 3, 6, and 12 months after the operation was 85%, 75%, and 65%, respectively. Meanwhile, the qualified success rate of 3, 6, and 12 months after the operation was 85%, 80%, and 77.5%, respectively. The multivariate cox regression analysis showed that age (hazard ratio: 3.717, 7.246; 95% confidence interval: 1.149–12.048, 1.349–38.461; P = .028, .021) was influencing factors for complete success rate and qualified success rate among all NVG patients. Gender, previous operation history, primary disease, and preoperative IOP were found to be not significant. AGV implantation is an effective and safe surgical method to treat NVG. Age is an important factor influencing the surgical success rate. PMID:29049253

  14. Patchy Chorioretinal Atrophy Changes at the Posterior Pole After Ranibizumab for Myopic Choroidal Neovascularization.

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    Parravano, Mariacristina; Scarinci, Fabio; Gilardi, Marta; Querques, Lea; Varano, Monica; Oddone, Francesco; Bandello, Francesco; Querques, Giuseppe

    2017-12-01

    To investigate the potential role of ranibizumab treatment on the development or enlargement of chorioretinal atrophy (CRA) at the posterior pole in eyes with myopic choroidal neovascularization (mCNV). This observational case series included patients having high myopia spherical equivalent refractive error ≥ -6.00 diopters, axial length (AxL) ≥ 26.0 mm in both eyes, and mCNV treated with ranibizumab 0.5 mg in one eye, who were retrospectively enrolled. Areas of CRA in treated and fellow eyes were measured on fundus autofluorescence images at baseline, 12, and 24 months. The CRA hypoautofluorescent lesions were divided in two groups: perilesional atrophy, corresponding to area around the mCNV, and patchy extralesional atrophy, corresponding to CRA between the temporal vascular arcades. Thirty-six eyes of 18 patients were included. The mean perilesional CRA size significantly increased from baseline to 12 months (3.5 ± 10.6 mm2, P = 0.02) and 24 months (4.4 ± 11.7 mm2, P = 0.038) in the treated eye. In treated and not treated eyes, patchy extralesional CRA at the posterior pole increased significantly from baseline to 12 and 24 months follow-up. None of the fellow eyes developed mCNV. No significant relationship was found between the number of injections, AxL, age, and perilesional and patchy extralesional CRA in the treated and not treated eyes (P > 0.05). In eyes with pathologic myopia and mCNV, intravitreal injections of ranibizumab should not be considered as a contributing risk factor worsening the natural course of CRA, even though the risk of the perilesional CRA enlargement should be taken into account.

  15. En-face optical coherence tomography angiography of neovascularization elsewhere in hemicentral retinal vein occlusion

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    Sogawa K

    2015-10-01

    Full Text Available Kenji Sogawa, Taiji Nagaoka, Akihiro Ishibazawa, Atsushi Takahashi, Tomofumi Tani, Akitoshi Yoshida Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Japan Purpose: To evaluate how the growth of neovascularization elsewhere (NVE was delineated in an eye with hemicentral retinal vein occlusion (CRVO using optical coherence tomography (OCT angiography. Patients and methods: We examined a 64-year-old man diagnosed with hemi-CRVO. The area around the occluded vein was scanned using a spectral-domain OCT device (RTVue XR Avanti. Blood flow was detected using the split-spectrum amplitude-decorrelation angiography (SSADA algorithm. Color fundus photography, fluorescein angiography (FA, and OCT angiography examinations were performed at the first visit and at 3 and 6 months postpresentation. Results: At the first visit, FA revealed delayed retinal venous filling and extensive areas of capillary nonperfusion. The patient underwent a trial of intravitreal ranibizumab injection (0.5 mg/0.05 mL for the treatment of macular edema. At 3 months postpresentation, there was no NVE around the occluded vein in the en-face SSADA image, but at 6 months, NVE appeared on the occluded veins. The en-face SSADA image showed the NVE structure in the fibrovascular membrane on the occluded vein more clearly than FA images. Conclusion: OCT angiography clearly visualized the sprouting of NVE in an eye with hemi-CRVO. New findings of the vascular structure of NVE in hemi-CRVO were revealed using the en-face SSADA algorithm. Keywords: OCT angiography, hemi-CRVO, NVE

  16. Imaging choroidal neovascular membrane using en face swept-source optical coherence tomography angiography

    Directory of Open Access Journals (Sweden)

    Moussa M

    2017-10-01

    Full Text Available Magdy Moussa,1,2 Mahmoud Leila,3 Hagar Khalid1,2 1Ophthalmology Department, Faculty of Medicine, Tanta University, Tanta, Egypt; 2MEDIC Eye Center, Tanta, Egypt; 3Retina Department, Research Institute of Ophthalmology, Giza, Egypt Purpose: The aim of this study was to assess the efficacy of swept-source optical coherence tomography angiography (SS-OCTA in delineating the morphology of choroidal neovascular membrane (CNV. Patients and methods: This was a retrospective observational case series reviewing clinical data and fundus fluorescein angiography (FFA, swept-source optical coherence tomography (SS-OCT, and SS-OCTA images of patients with CNV and comparing the findings. The swept-source technology enables deeper penetration and superior axial resolution. The incorporated blood flow detection algorithm, optical coherence tomography angiography ratio analysis (OCTARA, enables visualization of CNV in vivo without the need for dye injection. Results: The study included 136 eyes of 105 patients. Active lesions on SS-OCTA images showed increased capillary density, extensive arborization, vascular anastomosis and looping, and peri-lesional hollow. Inactive lesions showed decreased capillary density, presence of large linear vessels, and presence of feeder vessels supplying the CNV. We detected positive correlation between SS-OCTA, FFA, and SS-OCT images in 97% of eyes. In the remaining 3%, SS-OCTA confirmed the absence of CNV, whereas FFA and SS-OCT either were inconclusive in the diagnosis of CNV or yielded false-positive results. Conclusion: SS-OCT and SS-OCTA represent a reproducible risk-free analog for FFA in imaging CNV. SS-OCTA is particularly versatile in cases where FFA and SS-OCT are inconclusive. Keywords: swept-source OCT, OCT angiography, imaging of CNV, OCTARA algorithm

  17. Mathematical modeling of atherosclerotic plaque destabilization: Role of neovascularization and intraplaque hemorrhage.

    Science.gov (United States)

    Guo, Muyi; Cai, Yan; Yao, Xinke; Li, Zhiyong

    2018-08-07

    Observational studies have identified angiogenesis from the adventitial vasa vasorum and intraplaque hemorrhage (IPH) as critical factors in atherosclerotic plaque progression and destabilization. Here we propose a mathematical model incorporating intraplaque neovascularization and hemodynamic calculation with plaque destabilization for the quantitative evaluation of the role of neoangiogenesis and IPH in the vulnerable atherosclerotic plaque formation. An angiogenic microvasculature is generated by two-dimensional nine-point discretization of endothelial cell proliferation and migration from the vasa vasorum. Three key cells (endothelial cells, smooth muscle cells and macrophages) and three key chemicals (vascular endothelial growth factors, extracellular matrix and matrix metalloproteinase) are involved in the plaque progression model, and described by the reaction-diffusion partial differential equations. The hemodynamic calculation of the microcirculation on the generated microvessel network is carried out by coupling the intravascular, interstitial and transvascular flow. The plasma concentration in the interstitial domain is defined as the description of IPH area according to the diffusion and convection with the interstitial fluid flow, as well as the extravascular movement across the leaky vessel wall. The simulation results demonstrate a series of pathophysiological phenomena during the vulnerable progression of an atherosclerotic plaque, including the expanding necrotic core, the exacerbated inflammation, the high microvessel density (MVD) region at the shoulder areas, the transvascular flow through the capillary wall and the IPH. The important role of IPH in the plaque destabilization is evidenced by simulations with varied model parameters. It is found that the IPH can significantly speed up the plaque vulnerability by increasing necrotic core and thinning fibrous cap. In addition, the decreased MVD and vessel permeability may slow down the process of

  18. A Pharmacodynamic Analysis of Choroidal Neovascularization in a Porcine Model Using Three Targeted Drugs

    Science.gov (United States)

    Tran, Jeffrey; Craven, Caroline; Wabner, Kathy; Schmit, Jenn; Matter, Brock; Kompella, Uday; Grossniklaus, Hans E.; Olsen, Timothy W.

    2017-01-01

    Purpose To compare the efficacy of microneedle-delivered suprachoroidal (SC) pazopanib to intravitreal (Ivit) delivery of pazopanib, bevacizumab, or a fusion protein hI-con1 versus vehicle controls on choroidal neovascularization (CNV) growth in a pig model. Methods Forty-one pigs were injected on the day of CNV induction (hI-con1 on postinduction day 14) with either 2.5 mg Ivit bevacizumab (n = 9), 1 mg Ivit pazopanib (n = 9), 300 Ivit μg hI-con1 (n = 4), or 1 mg SC pazopanib (n = 9), vs. 10 vehicle controls (3 SC + 7 Ivit = 10). Pigs were euthanized at week 2 (11), 3 (8), 4 (11), and 8 (11), and eyes were fixed for histology. The size of the CNV was determined from histology, and CNV height was the primary outcome measure. Immunostaining for cytotoxic T-cells was performed in the hI-con1 study. Results In 39 of 41 (95%) eyes, type 2 CNV lesions were identified. One CNV lesion was lost during dissection. One animal was euthanized due to surgical complications. For mean CNV size comparisons, Ivit pazopanib had smaller mean height measurements (90 ± 20 μm) versus controls (180 ± 20 μm; P = 0.009), and Ivit pazopanib had smaller maximum CNV height (173 ± 43 μm) compared to SC pazopanib (478 ± 105 μm; P = 0.018). The mean lesion size in hI-con1–treated animals trended smaller than in controls (P = 0.11). Immunostaining did not detect cytotoxic T-cells. Conclusions Intravitreal pazopanib and to a lesser extent hI-con1 reduced the size of CNV lesions. The pig model has nearly a 100% rate of type 2 CNV induction and is a reliable preclinical model with pharmacodynamics similar to humans. PMID:28738417

  19. RETINAL PIGMENT EPITHELIAL TEAR AFTER INTRAVITREAL RANIBIZUMAB TREATMENT FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

    Science.gov (United States)

    Cho, Han Joo; Kim, Hyoung Seok; Yoo, Seul Gi; Han, Jung Il; Lew, Young Ju; Cho, Sung Won; Lee, Tae Gon; Kim, Jong Woo

    2016-10-01

    To evaluate the risk factors for retinal pigment epithelium (RPE) tears after intravitreal ranibizumab injections in neovascular age-related macular degeneration (nAMD) and to determine the efficacy of continued ranibizumab treatment after RPE tears. A total of 407 treatment-naïve eyes (377 patients) with nAMD were retrospectively included. All patients were treated with an initial series of 3 monthly loading injections, followed by further injections as required. Baseline characteristics and pigment epithelial detachment (PED) lesion features were evaluated as potential risk factors for RPE tear. The visual and anatomical outcomes after treatment during 12 months were also evaluated. By 12 months, RPE tears developed in 32 eyes (7.9%). Pigment epithelial detachment height was associated with a higher risk of RPE tear (odds ratio [OR], 1.318; 95% confidence interval [CI], 1.217-2.031, P = 0.018). Fibrovascular PED compared with serous PED had a higher risk of developing tears (OR, 9.129; 95% CI, 6.228-32.124, P = 0.039), and typical nAMD (OR, 4.166; 95% CI, 2.030-14.913, P = 0.031) and retinal angiomatous proliferation (OR, 3.778; 95% CI, 2.185-9.277, P = 0.040) had a higher risk of developing tears compared with polypoidal choroidal vasculopathy. Mean best-corrected visual acuity (BCVA) of RPE tear patients showed no significant improvement after treatment at 12 months; however, patients with RPE tears without foveal involvement (19 eyes) showed significant BCVA improvement at 12 months (P = 0.034). PED type and nAMD subtype are associated with the development of RPE tears after intravitreal ranibizumab injections. Continued ranibizumab therapy after RPE tear development can maintain visual acuity when the fovea is not involved.

  20. Bevacizumab vs ranibizumab for neovascular age-related macular degeneration in Chinese patients

    Directory of Open Access Journals (Sweden)

    Zhe-Li Liu

    2013-04-01

    Full Text Available AIM:To compare the clinical efficacy of intravitreal injections of bevacizumab and ranibizumab for treating Chinese patients with neovascular age-related macular degeneration (AMD. METHODS: Among 60 Chinese patients with exudative AMD (60 eyes, 28 received intravitreal bevacizumab injections (1.25mg and 32 received intravitreal ranibizumab injections (0.5mg, once a month for 3 months and were followed for a total of 6 months. Monthly optical coherence tomography (OCT was used to determine whether the patients received additional treatments during the follow-up. We compared the baseline and 6-month follow-up values of mean best-corrected visual acuity (BCVA and central retinal thickness (CRT in both groups of patients. We also compared the occurrence of adverse events. RESULTS:At the 6-month follow-up, the mean BCVA (logMAR of the bevacizumab and ranibizumab treatment groups improved from the baseline measurements of 0.72±0.23 and 0.73±0.22 to 0.47±0.14 and 0.45±0.20, respectively (P<0.05 for both groups. However, the change was not significantly different between the two groups. As evaluated by OCT, CRT decreased from 366.71±34.72μm and 352±36.9μm at baseline to 250.86±41.51μm and 243.22±41.38μm in the bevacizumab and ranibizumab groups, respectively (P<0.05 for both groups. However, the change was not significantly different between the two groups. There were no severe local adverse reactions or systemic adverse events. CONCLUSION:Intravitreal bevacizumab and ranibizumab have equivalent effects on BCVA and CRT and appeare safe over the short-term.

  1. Neovascular Glaucoma After Stereotactic Radiotherapy for Juxtapapillary Choroidal Melanoma: Histopathologic and Dosimetric Findings

    International Nuclear Information System (INIS)

    Fernandes, Bruno F.; Weisbrod, Daniel; Yuecel, Yeni H.; Follwell, Matthew; Krema, Hatem; Heydarian, Mostafa; Xu Wei; Payne, David; McGowan, Hugh; Simpson, Ernest R.; Laperriere, Normand; Sahgal, Arjun

    2011-01-01

    Purpose: Enucleation after stereotactic radiotherapy (SRT) for juxtapapillary choroidal melanoma may be required because of tumor progression (TP) or the development of intractable radiation-induced neovascular glaucoma (NVG). We compare pathologic changes and dosimetric findings in those eyes enucleated secondary to NVG as opposed to TP to better understand potential mechanisms. Methods and Materials: Patients with juxtapapillary choroidal melanoma treated with SRT (70 Gy in 5 fractions, alternate days over a total of 10 days) at the Princess Margaret Hospital, Toronto, Ontario, Canada, who underwent enucleation between 1998 and 2006 were selected. We correlated dosimetric data based on the patient's original SRT treatment plan with histopathologic findings in the retina, optic nerve head, and anterior chamber. A dedicated ocular pathologist reviewed each case in a blinded fashion. Results: Ten eyes in ten patients were enucleated after SRT. Six were enucleated secondary to NVG and four secondary to because of TP. Aggressive tumor features such as invasion of the sclera and epithelioid cell type were observed predominantly in the TP group. Retinal damage was more predominant in the NVG group, as were findings of radiation-related retinal vascular changes of fibrinoid necrosis and hyalinization. No conclusive radiation-related effects were found in the anterior chamber. The maximum point dose and dose to 0.1 cc were lower for the anterior chamber as compared with the dose to the tumor, retina, and optic nerve head. The mean 0.1-cc doses to the retina were 69.4 Gy and 73.5 Gy and to the anterior chamber were 4.9 Gy and 17.3 Gy for the NVG group and tumor progression group, respectively. Conclusions: Our findings suggest that NVG is due to radiation damage to the posterior chamber of the eye rather than primary radiation damage to the anterior segment.

  2. Targeted decorin gene therapy delivered with adeno-associated virus effectively retards corneal neovascularization in vivo.

    Directory of Open Access Journals (Sweden)

    Rajiv R Mohan

    Full Text Available Decorin, small leucine-rich proteoglycan, has been shown to modulate angiogenesis in nonocular tissues. This study tested a hypothesis that tissue-selective targeted decorin gene therapy delivered to the rabbit stroma with adeno-associated virus serotype 5 (AAV5 impedes corneal neovascularization (CNV in vivo without significant side effects. An established rabbit CNV model was used. Targeted decorin gene therapy in the rabbit stroma was delivered with a single topical AAV5 titer (100 µl; 5×10(12 vg/ml application onto the stroma for two minutes after removing corneal epithelium. The levels of CNV were examined with stereomicroscopy, H&E staining, lectin, collagen type IV, CD31 immunocytochemistry and CD31 immunoblotting. Real-time PCR quantified mRNA expression of pro- and anti-angiogenic genes. Corneal health in live animals was monitored with clinical, slit-lamp and optical coherence tomography biomicroscopic examinations. Selective decorin delivery into stroma showed significant 52% (p<0.05, 66% (p<0.001, and 63% (p<0.01 reduction at early (day 5, mid (day 10, and late (day 14 stages of CNV in decorin-delivered rabbit corneas compared to control (no decorin delivered corneas in morphometric analysis. The H&E staining, lectin, collagen type IV, CD31 immunostaining (57-65, p<0.5, and CD31 immunoblotting (62-67%, p<0.05 supported morphometric findings. Quantitative PCR studies demonstrated decorin gene therapy down-regulated expression of VEGF, MCP1 and angiopoietin (pro-angiogenic and up-regulated PEDF (anti-angiogenic genes. The clinical, biomicroscopy and transmission electron microscopy studies revealed that AAV5-mediated decorin gene therapy is safe for the cornea. Tissue-targeted AAV5-mediated decorin gene therapy decreases CNV with no major side effects, and could potentially be used for treating patients.

  3. Emerging vascular endothelial growth factor antagonists to treat neovascular age-related macular degeneration.

    Science.gov (United States)

    Hussain, Rehan M; Ciulla, Thomas A

    2017-09-01

    Evolving anti-vascular endothelial growth factor (VEGF) treatments for neovascular age-related macular degeneration (nAMD) include long acting agents, combination strategies involving new pathways, topical agents, sustained-release, and genetic therapy strategies. Areas covered: Brolucizumab and abicipar pegol have smaller molecular size, facilitating higher concentrations and potentially longer duration than current anti-VEGF agents. Agents being combined with anti-VEGFs include OPT-302 (to inhibit VEGF-C and VEGF-D); pegpleranib and rinucumab (to inhibit platelet derived growth factor, PDGF - but both failed to show consistently improved visual outcomes compared to anti-VEGF monotherapy); and RG7716, ARP-1536 and nesvacumab (to activate the Tie-2 tyrosine kinase receptor, which reduces permeability). X-82 is an oral anti-VEGF and anti-PDGF being tested in phase 2 studies. Topical anti-VEGF ± anti-PDGF drugs under study include pazopanib, PAN-90806, squalamine lactate, regorafinib, and LHA510. Sustained-release anti-VEGF delivery treatments, such as the ranibizumab Port Delivery System, GB-102, NT-503, hydrogel depot, Durasert, and ENV1305 aim to reduce the burden of frequent injections. Gene therapies with new viral vectors hold the potential to induce sustained expression of anti-angiogenic proteins via the retina's cellular apparatus, and include AVA-101/201, ADVM-202/302, AAV2-sFLT01, RGX314, and Retinostat. Expert opinion: There are many emerging anti-VEGF treatments that aim to improve visual outcomes and reduce the treatment burden of nAMD.

  4. Pegaptanib: choroidal neovascularization in patients with age-related macular degeneration and previous arterial thromboembolic events.

    Science.gov (United States)

    Battaglia Parodi, Maurizio; Di Bartolo, Emanuele; Brue, Claudia; Cappello, Ezio; Furino, Claudio; Giuffrida, Sebastiano; Imparato, Manuela; Reibaldi, Michele

    2018-01-01

    To evaluate the efficacy and the rate of side effects of the pegylated aptamer pegaptanib in the treatment of patients with choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) and a history of previous arterial thromboembolic events (ATEs). Twenty-three eyes of 23 patients with subfoveal CNV due to AMD and cerebrovascular accidents (n = 12) and myocardial infarction (n = 11) in the previous 6 months received intravitreal pegaptanib 0.3 mg according to a pro re nata regimen and were followed for 12 months. The paired Student t test was used to evaluate mean changes in best-corrected visual acuity (BCVA; primary outcome measure) and central foveal thickness (CFT). The mean patient age was 71.5 ± 4.6 years; there were 14 women and 9 men. The CNV was type 1, 2, and 3 in 18, 3, and 2 eyes, respectively. The mean BCVA improved from 0.67 ± 0.23 logMAR at baseline to 0.52 ± 0.31 logMAR at the end of 12-month follow-up (p = 0.044). Thirty-five percent of patients achieved ≥3 Early Treatment Diabetic Retinopathy Study lines improvement at 12 months. Mean CFT at baseline (381 ± 111 µm) decreased to 304 ± 82 µm at 12 months (p = 0.008). Patients received a mean of 4.3 ± 1.3 (range 3-7) injections. No systemic or ocular side effects occurred; no patient experienced further ATEs. Intravitreal pegaptanib can be considered a viable treatment option for patients with AMD-related CNV who are at high risk of ATEs.

  5. Risks of newly onset hemorrhagic stroke in patients with neovascular age-related macular degeneration.

    Science.gov (United States)

    Lee, Wan-Ju Annabelle; Cheng, Ching-Lan; Lee, Cheng-Han; Kao Yang, Yea-Huei; Lin, Swu-Jane; Hsieh, Cheng-Yang

    2017-10-01

    Age-related macular degeneration (AMD) is an eye disease causing blindness in the elderly. It shares many common possible pathogenic mechanisms with cardiovascular diseases. Many studies have discussed the association between AMD and stroke, but the results were inconsistent. Our aim was to determine the associations between neovascular AMD and the risk of stroke in the Taiwanese population. This is a retrospective cohort study. We used claims data from National Health Insurance Research Database. Patients aged more than 45 years without stroke, myocardial infarction, or any AMD were selected from 2001 to 2008 and followed until 2010. The index date was defined as the date of nAMD diagnosis (ICD-9 code, 362.52). The comparison group was patients without an nAMD diagnosis with age- and sex-matched to nAMD subjects at a ratio of up to 10 to 1. Kaplan-Meier survival analysis and Cox regression analysis were used. The incidence of stroke events (ICD-9 codes, 430-434) and their subtypes (hemorrhagic and ischemic) were primary outcomes. Secondary outcomes included acute myocardial infarction (AMI), composite AMI/stroke, and all-cause mortality. Patients with nAMD had a higher risk of developing stroke, with an adjusted HR of 1.30 (95% CI, 1.01-1.68). A higher risk for hemorrhagic stroke (HR, 1.70, 95% CI, 1.03-2.83) was also found. No significant differences were observed in ischemic stroke, the composite of AMI/stroke, and all-cause mortality. Patients with nAMD had a significantly higher risk of developing stroke, which was driven mainly by the increased risk of developing the hemorrhagic subtype. Copyright © 2017 John Wiley & Sons, Ltd.

  6. Functional impact of treatment with ranibizumab under a reactive strategy in patients with neovascular age-related macular degeneration.

    Science.gov (United States)

    Gallego-Pinazo, R; Dolz-Marco, R; Andreu-Fenoll, M; Farrés, J; Monclús, L

    2017-03-01

    To analyse the functional recovery using a pro re nata (PRN) dosing strategy with intravitreal injections of ranibizumab for patients with neovascular age-related macular degeneration (AMD). An observational, retrospective, single-centre study, was conducted on patients with neovascular AMD managed with a PRN strategy with ranibizumab, and were followed-up for a minimum of 18 months. Sociodemographic and clinical data were collected from medical records. The percentage of visual acuity (VA) recovered after losing 5 or more letters was calculated taking into account the previous visit, as well as considering the best VA recorded prior to the retreament. The analysis included 128 patients. The mean (SD) follow-up period was 18.9 (2.3) months. The mean (SD) elapsed days between onset of symptoms and diagnosis, and between prescription and administration of treatment was 50.2 (57.4) and 10.9 (16.0), respectively. Only 108 patients were prescribed ranibizumab after losing 5 or more letters of VA. The mean (SD) VA recovery compared to the previous VA was 70.3% (114.4). On the other hand, the mean (SD) VA recovery when considering the best VA registered before the retreatment was 43.5% (112.9), with 59.4% of re-treatments having a VA recovery below 75%, and with 11.7% not presenting any VA recovery. A PRN dosing strategy with intravitreal ranibizumab for neovascular AMD may not be efficient in preserving and/or recovering VA in the long-term, due to a cumulative irreversible VA loss. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  7. Guidelines for the management of neovascular age-related macular degeneration by the European Society of Retina Specialists (EURETINA).

    Science.gov (United States)

    Schmidt-Erfurth, Ursula; Chong, Victor; Loewenstein, Anat; Larsen, Michael; Souied, Eric; Schlingemann, Reinier; Eldem, Bora; Monés, Jordi; Richard, Gisbert; Bandello, Francesco

    2014-09-01

    Age-related macular degeneration (AMD) is still referred to as the leading cause of severe and irreversible visual loss world-wide. The disease has a profound effect on quality of life of affected individuals and represents a major socioeconomic challenge for societies due to the exponential increase in life expectancy and environmental risks. Advances in medical research have identified vascular endothelial growth factor (VEGF) as an important pathophysiological player in neovascular AMD and intraocular inhibition of VEGF as one of the most efficient therapies in medicine. The wide introduction of anti-VEGF therapy has led to an overwhelming improvement in the prognosis of patients affected by neovascular AMD, allowing recovery and maintenance of visual function in the vast majority of patients. However, the therapeutic benefit is accompanied by significant economic investments, unresolved medicolegal debates about the use of off-label substances and overwhelming problems in large population management. The burden of disease has turned into a burden of care with a dissociation of scientific advances and real-world clinical performance. Simultaneously, ground-breaking innovations in diagnostic technologies, such as optical coherence tomography, allows unprecedented high-resolution visualisation of disease morphology and provides a promising horizon for early disease detection and efficient therapeutic follow-up. However, definite conclusions from morphologic parameters are still lacking, and valid biomarkers have yet to be identified to provide a practical base for disease management. The European Society of Retina Specialists offers expert guidance for diagnostic and therapeutic management of neovascular AMD supporting healthcare givers and doctors in providing the best state-of-the-art care to their patients. NCT01318941. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  8. Density-tunable conjugation of cyclic RGD ligands with polyion complex vesicles for the neovascular imaging of orthotopic glioblastomas

    International Nuclear Information System (INIS)

    Kawamura, Wataru; Nomoto, Takahiro; Sueyoshi, Daiki; Kataoka, Kazunori; Miura, Yutaka; Toh, Kazuko; Yamada, Naoki; Matsumoto, Yu; Liu, Xueying; Kokuryo, Daisuke; Aoki, Ichio; Saga, Tsuneo; Kano, Mitsunobu R; Nishiyama, Nobuhiro; Kishimura, Akihiro

    2015-01-01

    Introduction of ligands into 100 nm scaled hollow capsules has great potential for diagnostic and therapeutic applications in drug delivery systems. Polyethylene glycol-conjugated (PEGylated) polyion complex vesicles (PICsomes) are promising hollow nano-capsules that can survive for long periods in the blood circulation and can be used to deliver water-soluble macromolecules to target tissues. In this study, cyclic RGD (cRGD) peptide, which is specifically recognized by α V β 3 and α v β 5 integrins that are expressed at high levels in the neovascular system, was conjugated onto the distal end of PEG strands on PICsomes for active neovascular targeting. Density-tunable cRGD-conjugation was achieved using PICsomes with definite fraction of end-functionalized PEG, to substitute 20, 40, and 100% of PEG distal end of the PICsomes to cRGD moieties. Compared with control-PICsomes without cRGD, cRGD-PICsomes exhibited increased uptake into human umbilical vein endothelial cells. Intravital confocal laser scanning microscopy revealed that the 40%-cRGD-PICsomes accumulated mainly in the tumor neovasculature and remained in the perivascular region even after 24 h. Furthermore, we prepared superparamagnetic iron oxide (SPIO)-loaded cRGD-PICsomes for magnetic resonance imaging (MRI) and successfully visualized the neovasculature in an orthotopic glioblastoma model, which suggests that SPIO-loaded cRGD-PICsomes might be useful as a MRI contrast reagent for imaging of the tumor microenvironment, including neovascular regions that overexpress α V β 3 integrins. (paper)

  9. Guidelines for the management of neovascular age-related macular degeneration by the European Society of Retina Specialists (EURETINA)

    Science.gov (United States)

    Schmidt-Erfurth, Ursula; Chong, Victor; Loewenstein, Anat; Larsen, Michael; Souied, Eric; Schlingemann, Reinier; Eldem, Bora; Monés, Jordi; Richard, Gisbert; Bandello, Francesco

    2014-01-01

    Age-related macular degeneration (AMD) is still referred to as the leading cause of severe and irreversible visual loss world-wide. The disease has a profound effect on quality of life of affected individuals and represents a major socioeconomic challenge for societies due to the exponential increase in life expectancy and environmental risks. Advances in medical research have identified vascular endothelial growth factor (VEGF) as an important pathophysiological player in neovascular AMD and intraocular inhibition of VEGF as one of the most efficient therapies in medicine. The wide introduction of anti-VEGF therapy has led to an overwhelming improvement in the prognosis of patients affected by neovascular AMD, allowing recovery and maintenance of visual function in the vast majority of patients. However, the therapeutic benefit is accompanied by significant economic investments, unresolved medicolegal debates about the use of off-label substances and overwhelming problems in large population management. The burden of disease has turned into a burden of care with a dissociation of scientific advances and real-world clinical performance. Simultaneously, ground-breaking innovations in diagnostic technologies, such as optical coherence tomography, allows unprecedented high-resolution visualisation of disease morphology and provides a promising horizon for early disease detection and efficient therapeutic follow-up. However, definite conclusions from morphologic parameters are still lacking, and valid biomarkers have yet to be identified to provide a practical base for disease management. The European Society of Retina Specialists offers expert guidance for diagnostic and therapeutic management of neovascular AMD supporting healthcare givers and doctors in providing the best state-of-the-art care to their patients. Trial registration number NCT01318941. PMID:25136079

  10. Fibroblast-Specific Deletion of Hypoxia Inducible Factor-1 Critically Impairs Murine Cutaneous Neovascularization and Wound Healing.

    Science.gov (United States)

    Duscher, Dominik; Maan, Zeshaan N; Whittam, Alexander J; Sorkin, Michael; Hu, Michael S; Walmsley, Graham G; Baker, Hutton; Fischer, Lauren H; Januszyk, Michael; Wong, Victor W; Gurtner, Geoffrey C

    2015-11-01

    Diabetes and aging are known risk factors for impaired neovascularization in response to ischemic insult, resulting in chronic wounds, and poor outcomes following myocardial infarction and cerebrovascular injury. Hypoxia-inducible factor (HIF)-1α, has been identified as a critical regulator of the response to ischemic injury and is dysfunctional in diabetic and elderly patients. To better understand the role of this master hypoxia regulator within cutaneous tissue, the authors generated and evaluated a fibroblast-specific HIF-1α knockout mouse model. The authors generated floxed HIF-1 mice (HIF-1) by introducing loxP sites around exon 1 of the HIF-1 allele in C57BL/6J mice. Fibroblast-restricted HIF-1α knockout (FbKO) mice were generated by breeding our HIF-1 with tamoxifen-inducible Col1a2-Cre mice (Col1a2-CreER). HIF-1α knockout was evaluated on a DNA, RNA, and protein level. Knockout and wild-type mice were subjected to ischemic flap and wound healing models, and CD31 immunohistochemistry was performed to assess vascularity of healed wounds. Quantitative real-time polymerase chain reaction of FbKO skin demonstrated significantly reduced Hif1 and Vegfa expression compared with wild-type. This finding was confirmed at the protein level (p wound closure and vascularity (p wound healing, reduced wound vascularity, and significant impairment in the ischemic neovascular response. These findings provide new insight into the importance of cell-specific responses to hypoxia during cutaneous neovascularization.

  11. Efficacy and safety of intravitreal bevacizumab in eyes with neovascular glaucoma undergoing Ahmed glaucoma valve implantation: 2-year follow-up.

    Science.gov (United States)

    Arcieri, Enyr S; Paula, Jayter S; Jorge, Rodrigo; Barella, Kleyton A; Arcieri, Rafael S; Secches, Danilo J; Costa, Vital P

    2015-02-01

    To evaluate the efficacy and safety of intravitreal bevacizumab (IVB) in eyes with neovascular glaucoma (NVG) undergoing Ahmed glaucoma valve (AGV) implantation. This was a multicentre, prospective, randomized clinical trial that enrolled 40 patients with uncontrolled neovascular glaucoma that had undergone panretinal photocoagulation and required glaucoma drainage device implantation. Patients were randomized to receive IVB (1.25 mg) or not during Ahmed valve implant surgery. Injections were administered intra-operatively, and 4 and 8 weeks after surgery. After a mean follow-up of 2.25 ± 0.67 years (range 1.5-3 years), both groups showed a significant decrease in IOP (p glaucoma undergoing Ahmed glaucoma valve implantation. There is a trend to slightly lower IOPs and number of medications with IVB use during AGV implantation for neovascular glaucoma. © 2014 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  12. CT angiography. Abdominal CT using intravenous aortography for contrast enhancement

    Energy Technology Data Exchange (ETDEWEB)

    Nagai, J; Nakauma, Y; Egawa, J; Kawamura, M [Teikyo Univ., Tokyo (Japan). Faculty of Medicine

    1980-04-01

    To obtain imaging effects close to those of abdominal aortography and investigate a technique with little invasion to patients, intravenous aortography was applied to contrast enhancement (CE) in abdominal CT, and its usefulness was discussed. Intravenous aortography could clearly visualize lesions with rich neovascularity such as hepatocellular carcinoma and renal cell carcinoma. Differing from a drip infusion method, this method has complexities in its technique that contrast medium is injected at once, blood circulation time which is represented by the time between the injection and the time when the patients feel bitterness (10 - 12 seconds) must be measured before CE, and scanning begins 2 seconds before the patients feel bitterness. However, the invasion to patients due to this method is slight, and the capacity of this method to visualize neovascularity is superior to CE by a drip infusion method. Therefore, qualitative diagnosis by CT will be improved by using this method together with a drip infusion method.

  13. Combination therapy of low-fluence photodynamic therapy and intravitreal ranibizumab for choroidal neovascular membrane in choroidal osteoma

    Directory of Open Access Journals (Sweden)

    Rodney J Morris

    2011-01-01

    Full Text Available Choroidal osteoma is an unusual form of intraocular calcification seen in otherwise healthy eyes. It is a benign idiopathic osseous tumor of the choroid, typically seen in young females. Choroidal neovascular membrane (CNVM is a complication seen in one-third of these patients and carries a poor visual outcome. We report a case of a 25-year-old hyperthyroid female with choroidal osteoma and subfoveal CNVM in her left eye which was successfully treated using low-fluence photodynamic therapy (PDT with verteporfin followed by a single injection of intravitreal ranibizumab.

  14. Clinical characteristics of reticular pseudodrusen in the fellow eye of patients with unilateral neovascular age-related macular degeneration.

    Science.gov (United States)

    Hogg, Ruth E; Silva, Rufino; Staurenghi, Giovanni; Murphy, George; Santos, Ana R; Rosina, Chiara; Chakravarthy, Usha

    2014-09-01

    To describe associations between reticular pseudodrusen, individual characteristics, and retinal function. Cohort study. We recruited 105 patients (age range, 52-93 years) who had advanced neovascular age-related macular degeneration (AMD) in only 1 eye from 3 clinical centers in Europe. Minimum follow-up was 12 months. The eye selected for study was the fellow eye without advanced disease. Clinical measures of vision were distance visual acuity, near visual acuity, and results of the Smith-Kettlewell low-luminance acuity test (SKILL). Fundus imaging included color photography, red-free imaging, blue autofluorescence imaging, fluorescein angiography, indocyanine green angiography, and optical coherence tomography using standardized protocols. These were used to detect progression to neovascular AMD in the study eye during follow-up. All imaging outputs were graded for the presence or absence of reticular pseudodrusen (RPD) using a multimodal approach. Choroidal thickness was measured at the foveal center and at 2 other equidistant locations from the fovea (1500 μm) nasally and temporally. Metrics on retinal thickness and volume were obtained from the manufacturer-supplied automated segmentation readouts. Presence of RPD, distance visual acuity, near visual acuity, SKILL score, choroidal thickness, retinal thickness, and retinal volume. Reticular pseudodrusen was found in 43 participants (41%) on 1 or more imaging method. The SKILL score was significantly worse in those with reticular drusen (mean score ± standard deviation [SD, 38±12) versus those without (mean score ± SD, 33±9) (P = 0.034). Parafoveal retinal thickness, parafoveal retinal volume, and all of the choroidal thickness parameters measured were significantly lower in those with reticular drusen than in those without. The presence of RPD was associated with development of neovascular AMD when corrected for age and sex (odds ratio, 5.5; 95% confidence interval, 1.1-28.8; P = 0.042). All participants

  15. Electrophysiological assessment of retinal function during 6 months of bevacizumab treatment in neovascular age-related macular degeneration

    DEFF Research Database (Denmark)

    Pedersen, Karen Bjerg; Møller, Flemming; Sjølie, Anne Katrin

    2010-01-01

    PURPOSE: The purpose of this study was to assess the alteration of retinal function by multifocal electroretinography and full-field electroretinography in patients with age-related macular degeneration treated with bevacizumab. METHODS: We performed a prospective pilot study of 26 eyes of 26...... previously treatment-naïve patients with neovascular age-related macular degeneration receiving intravitreal injections with 1.25 mg bevacizumab. Patients were examined with multifocal electroretinography, full-field electroretinography, optical coherence tomography, and visual acuity. Follow...

  16. Microcystic adenoma of the pancreas associated with non-functioning islet cell tumor: a case report

    International Nuclear Information System (INIS)

    Kong, Keun Young; Lee, Dong Ho; Ko, Young Tae; Kim, Youn Wha

    1997-01-01

    Among cystic tumors arising in the pancreas, microcystic adenoma is relatively uncommon;it is usually benign, and is comprised of cysts that vary in size from microscopic to 2 cm in diameter. It has recently been reported to be associated with other pancreatic tumors with malignant potential; in particular, microcystic adenoma with coexistent islet cell tumor has been reported in von Hippel-Lindau disease. We report a case of microcystic adenoma of the pancreas associated with coexistent surgically-proven islet cell tumor. On spiral CT, the islet cell tumor was seen as a highly enhanced inhomogeneous solid mass in the pancreatic head, and microcystic adenoma as numerous small cysts throughout the pancreas.=20

  17. Suppression of Retinal Neovascularization in vivo by Inhibition of Vascular Endothelial Growth Factor (VEGF) Using Soluble VEGF-Receptor Chimeric Proteins

    Science.gov (United States)

    Aiello, Lloyd Paul; Pierce, Eric A.; Foley, Eliot D.; Takagi, Hitoshi; Chen, Helen; Riddle, Lavon; Ferrara, Napoleone; King, George L.; Smith, Lois E. H.

    1995-11-01

    The majority of severe visual loss in the United States results from complications associated with retinal neovascularization in patients with ischemic ocular diseases such as diabetic retinopathy, retinal vein occlusion, and retinopathy of prematurity. Intraocular expression of the angiogenic protein vascular endothelial growth factor (VEGF) is closely correlated with neovascularization in these human disorders and with ischemia-induced retinal neovascularization in mice. In this study, we evaluated whether in vivo inhibition of VEGF action could suppress retinal neovascularization in a murine model of ischemic retinopathy. VEGF-neutralizing chimeric proteins were constructed by joining the extracellular domain of either human (Flt) or mouse (Flk) high-affinity VEGF receptors with IgG. Control chimeric proteins that did not bind VEGF were also used. VEGF-receptor chimeric proteins eliminated in vitro retinal endothelial cell growth stimulation by either VEGF (P hypoxic conditioned medium (P < 0.005) without affecting growth under nonstimulated conditions. Control proteins had no effect. To assess in vivo response, animals with bilateral retinal ischemia received intravitreal injections of VEGF antagonist in one eye and control protein in the contralateral eye. Retinal neovascularization was quantitated histologically by a masked protocol. Retinal neovascularization in the eye injected with human Flt or murine Flk chimeric protein was reduced in 100% (25/25; P < 0.0001) and 95% (21/22; P < 0.0001) of animals, respectively, compared to the control treated eye. This response was evident after only a single intravitreal injection and was dose dependent with suppression of neovascularization noted after total delivery of 200 ng of protein (P < 0.002). Reduction of histologically evident neovascular nuclei per 6-um section averaged 47% ± 4% (P < 0.001) and 37% ± 2% (P < 0.001) for Flt and Flk chimeric proteins with maximal inhibitory effects of 77% and 66

  18. Everolimus in advanced, progressive, well-differentiated, non-functional neuroendocrine tumors: RADIANT-4 lung subgroup analysis.

    Science.gov (United States)

    Fazio, Nicola; Buzzoni, Roberto; Delle Fave, Gianfranco; Tesselaar, Margot E; Wolin, Edward; Van Cutsem, Eric; Tomassetti, Paola; Strosberg, Jonathan; Voi, Maurizio; Bubuteishvili-Pacaud, Lida; Ridolfi, Antonia; Herbst, Fabian; Tomasek, Jiri; Singh, Simron; Pavel, Marianne; Kulke, Matthew H; Valle, Juan W; Yao, James C

    2018-01-01

    In the phase III RADIANT-4 study, everolimus improved median progression-free survival (PFS) by 7.1 months in patients with advanced, progressive, well-differentiated (grade 1 or grade 2), non-functional lung or gastrointestinal neuroendocrine tumors (NETs) vs placebo (hazard ratio, 0.48; 95% confidence interval [CI], 0.35-0.67; P < .00001). This exploratory analysis reports the outcomes of the subgroup of patients with lung NETs. In RADIANT-4, patients were randomized (2:1) to everolimus 10 mg/d or placebo, both with best supportive care. This is a post hoc analysis of the lung subgroup with PFS, by central radiology review, as the primary endpoint; secondary endpoints included objective response rate and safety measures. Ninety of the 302 patients enrolled in the study had primary lung NET (everolimus, n = 63; placebo, n = 27). Median PFS (95% CI) by central review was 9.2 (6.8-10.9) months in the everolimus arm vs 3.6 (1.9-5.1) months in the placebo arm (hazard ratio, 0.50; 95% CI, 0.28-0.88). More patients who received everolimus (58%) experienced tumor shrinkage compared with placebo (13%). Most frequently reported (≥5% incidence) grade 3-4 drug-related adverse events (everolimus vs. placebo) included stomatitis (11% vs. 0%), hyperglycemia (10% vs. 0%), and any infections (8% vs. 0%). In patients with advanced, progressive, well-differentiated, non-functional lung NET, treatment with everolimus was associated with a median PFS improvement of 5.6 months, with a safety profile similar to that of the overall RADIANT-4 cohort. These results support the use of everolimus in patients with advanced, non-functional lung NET. The trial is registered with ClinicalTrials.gov (no. NCT01524783). © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  19. Small laser spot versus standard laser spot photodynamic therapy for idiopathic choroidal neovascularization: a randomized controlled study.

    Science.gov (United States)

    Li, Xiao-xin; Tao, Yong

    2012-12-01

    Idiopathic choroidal neovascularization (ICNV) affects young patients and thus may have a significant impact on vision and life quality over a patient's lifespan. This study was designed to compare the visual outcome and retinal pigment epithelium (RPE) damage after photodynamic therapy (PDT) with small laser spot and PDT with standard laser spot for idiopathic choroidal neovascularization (ICNV). This was a randomized controlled study. Fifty-two patients with ICNV were enrolled and randomly divided into a study group (small laser spot PDT, n = 27) and a control group (standard laser spot PDT, n = 25). Best corrected visual acuity (BCVA), optic coherence tomography (OCT) and fluorescein angiography (FA) findings were the main measurements. The patients were followed up 1 week, 1, 3, 6, 9 months and 1 year after PDT. BCVA improvement was statistically significantly higher in the study group than the control group at 6-month ((25.53 ± 15.01) letters vs. (14.71 ± 11.66) letters, P = 0.025) and 9-month follow-ups ((27.53 ± 17.78) letters vs. (15.59 ± 12.21) letters, P = 0.039). At 3- and 6-month follow-ups, the quadrants of RPE damage between the two groups varied significantly (P laser spot PDT group than in the standard laser spot PDT group for ICNV.

  20. Efficacy of Intravitreal injection of 2-Methoxyestradiol in regression of neovascularization of a retinopathy of prematurity rat model.

    Science.gov (United States)

    Said, Azza Mohamed Ahmed; Zaki, Rania Gamal Eldin; Salah Eldin, Rania A; Nasr, Maha; Azab, Samar Saad; Elzankalony, Yaser Abdelmageuid

    2017-04-04

    Retinopathy of prematurity (ROP) is one of the targets for early detection and treatment to prevent childhood blindness in world health organization programs. The purpose of study was to evaluate the efficacy of intravitreal injection of 2-Methoxyestradiol (2-ME) nanoemulsion in regressing neovascularization of a ROP rat model. A prospective comparative case - control animal study conducted on 56 eyes of 28 healthy new born Sprague Dawley male albino rat. ROP was induced in 21 rats then two concentrations of 2-ME nanoparticles were injected in right eyes of 14 rats (low dose; study group I, high dose; study group II). A blank nanoemulsion was injected in the right eyes of seven rats (control positive group I). No injections performed in contralateral left eyes (control positive group II). Seven rats (14 eyes) were kept in room air (control negative group). On postnatal day 17, eyeballs were enucleated. Histological structure of the retina was examined using Hematoxylin and eosin staining. Vascular endothelial growth factor (VEGF) and glial fibrillary acidic protein (GFAP) expressions were detected by immunohistochemical studies. Intravitreal injection of 2-ME (in the two concentrations) caused marked regression of the new vascular tufts on the vitreal side with normal organization and thickness of the retina especially in study group II, which also show negative VEGF immunoreaction. Positive GFAP expression was detected in the control positive groups and study group (I). Intravitreal injection of 2-Methoxyestradiol nanoemulsion is a promising effective method in reduction of neovascularization of a ROP rat model.

  1. Laparoscopic ischemic conditioning of the stomach increases neovascularization of the gastric conduit in patients undergoing esophagectomy for cancer.

    Science.gov (United States)

    Pham, Thai H; Melton, Shelby D; McLaren, Patrick J; Mokdad, Ali A; Huerta, Sergio; Wang, David H; Perry, Kyle A; Hardaker, Hope L; Dolan, James P

    2017-09-01

    Gastric ischemic preconditioning has been proposed to improve blood flow and reduce the incidence of anastomotic complications following esophagectomy with gastric pull-up. This study aimed to evaluate the effect of prolonged ischemic preconditioning on the degree of neovascularization in the distal gastric conduit at the time of esophagectomy. A retrospective review of a prospectively maintained database identified 30 patients who underwent esophagectomy. The patients were divided into three groups: control (no preconditioning, n = 9), partial (short gastric vessel ligation only, n = 8), and complete ischemic preconditioning (left and short gastric vessel ligation, n = 13). Microvessel counts were assessed, using immunohistologic analysis to determine the degree of neovascularization at the distal gastric margin. The groups did not differ in age, gender, BMI, pathologic stage, or cancer subtype. Ischemic preconditioning durations were 163 ± 156 days for partial ischemic preconditioning, compared to 95 ± 50 days for complete ischemic preconditioning (P = 0.2). Immunohistologic analysis demonstrated an increase in microvessel counts of 29% following partial ischemic preconditioning (P = 0.3) and 67% after complete ischemic preconditioning (P gastric conduit. © 2017 Wiley Periodicals, Inc.

  2. Long-term outcome after radiation therapy for subfoveal choroidal neovascularization associated with age-related macular degeneration

    International Nuclear Information System (INIS)

    Mandai, Michiko; Takahashi, Masayo; Miyamoto, Hideki; Hiroshiba, Naoko; Kimura, Hideya; Ogura, Yuichiro; Honda, Yoshihito; Sasai, Keisuke

    2000-01-01

    The purpose of this study was to investigate the long-term effect of low-dose radiation therapy on subfoveal choroidal neovascularization associated with age-related macular degeneration. The clinical course and visual outcome were compared retrospectively among two treated groups and a control group; 15 patients (15 eyes) received 10 Gy, another 15 patients (15 eyes) received 20 Gy. The control group consisted of 15 patients (15 eyes) without treatment. All patients were followed up for at least 18 months, and most were followed up for 3 years. The macula was irradiated with either 10 Gy in 5 fractions or with 20 Gy in 10 fractions after computed tomography (CT) simulation enabled real-time treatment planning from multiple CT slices. During the 3 years of follow-up, the lesions became better in 5 eyes, unchanged in 1, and worse in 9 with 10 Gy radiation; better in 7 eyes, unchanged in 1, and worse in 7 eyes with 20 Gy; and better in 1 eye and worse in 14 with no treatment. The difference between the groups treated with radiation and the control was statistically significant (P<.05). Visual acuity was also significantly better in the group receiving 20 Gy than in the control group up to 2 years after radiation (P<.01). Radiation may extend the period of good visual function substantially by reducing subfoveal choroidal neovascularization activity. (author)

  3. Clinical experience with fixed bimonthly aflibercept dosing in treatment-experienced patients with neovascular age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Khanani AM

    2015-07-01

    Full Text Available Arshad M Khanani Sierra Eye Associates, Reno, NV, USA Purpose: To evaluate the durability of fixed bimonthly dosing of intravitreal aflibercept for neovascular age-related macular degeneration.Methods: Records of 16 patients were retrospectively reviewed. Patients received three initial 2.0 mg monthly doses of aflibercept then 8-weekly doses according to the product label. Best-corrected visual acuity (Early Treatment Diabetic Retinopathy Study [ETDRS] letters, central macular thickness, fluid on optical coherence tomography, and pigment epithelial detachment (PED were measured.Results: Prior to starting aflibercept, 13 patients had subretinal fluid (SRF, five had intraretinal fluid (IRF, four had PED, and baseline visual acuity (VA was 62 approximate ETDRS letters. Following the monthly dosing, seven patients had no improvement or decreased VA, ten patients still had SRF/IRF, and PED had worsened in one patient. At Visit 4, an average of 6.8 weeks after Visit 3, VA had decreased in seven patients, SRF/IRF had increased in 12 patients, and PED had returned in all patients who initially responded. Based on the presence of fluid after the initial monthly injections, 12 patients could not be extended to fixed bimonthly dosing.Conclusion: This case series adds to the growing body of evidence on the need for flexible dosing schedules for the personalized treatment of neovascular age-related macular degeneration. Keywords: age-related macular degeneration, AMD, bimonthly, regimen, aflibercept, case studies, retinal fluid

  4. Long-term outcome after radiation therapy for subfoveal choroidal neovascularization associated with age-related macular degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Mandai, Michiko; Takahashi, Masayo; Miyamoto, Hideki; Hiroshiba, Naoko; Kimura, Hideya; Ogura, Yuichiro; Honda, Yoshihito; Sasai, Keisuke [Kyoto Univ. (Japan). Graduate School of Medicine

    2000-10-01

    The purpose of this study was to investigate the long-term effect of low-dose radiation therapy on subfoveal choroidal neovascularization associated with age-related macular degeneration. The clinical course and visual outcome were compared retrospectively among two treated groups and a control group; 15 patients (15 eyes) received 10 Gy, another 15 patients (15 eyes) received 20 Gy. The control group consisted of 15 patients (15 eyes) without treatment. All patients were followed up for at least 18 months, and most were followed up for 3 years. The macula was irradiated with either 10 Gy in 5 fractions or with 20 Gy in 10 fractions after computed tomography (CT) simulation enabled real-time treatment planning from multiple CT slices. During the 3 years of follow-up, the lesions became better in 5 eyes, unchanged in 1, and worse in 9 with 10 Gy radiation; better in 7 eyes, unchanged in 1, and worse in 7 eyes with 20 Gy; and better in 1 eye and worse in 14 with no treatment. The difference between the groups treated with radiation and the control was statistically significant (P<.05). Visual acuity was also significantly better in the group receiving 20 Gy than in the control group up to 2 years after radiation (P<.01). Radiation may extend the period of good visual function substantially by reducing subfoveal choroidal neovascularization activity. (author)

  5. Treatment of age-related subfoveal neovascular membranes by teletherapy. Results of a non-randomized study

    Energy Technology Data Exchange (ETDEWEB)

    Subasi, M.; Akmansu, M.; Or, M. [Gazi Univ., Ankara (Turkey). Medical Faculty

    1999-03-01

    This investigation was designed to determine whether low-dose radiation to the macular region could influence the natural course of age-related subfoveal neovascularization. Thirty-one patients with subfoveal membranes due to age-related macular degeneration (ARMD) were treated with 12 Gy of 6 MV X-rays, and 72 patients who were untreated served as a control group. Both groups were followed-up. At six months of follow-up visual acuity was maintained in 54.8% and improved 25.8% of patients treated by radiotherapy. In the control group, visual acuity showed deterioration in 55.5%. There was a significant difference between the treated and untreated groups (p<0.01). Significant neovascular membrane regression or stabilization was recorded in 61.3% of treated patients at six months post-radiation, whereas the membranes in all. 72 control patients showed progressive enlargement. This non-randomized study suggested that low doses of radiation may be an alternative treatment for ARMD without an immediate drop in visual acuity or significant radiation morbidity. (author)

  6. The inhibitory effect of different concentrations of KH902 eye drops on corneal neovascularization induced by alkali burn

    Directory of Open Access Journals (Sweden)

    Yan Wu

    2017-01-01

    Full Text Available Purpose: The aim of this study was to evaluate the inhibitory effect of different concentrations of KH902 eye drops on rabbit corneal neovascularization (CNV induced by alkali burn. Methods: Forty-eight adult rabbits were randomized into four groups after alkali burning: Group A (2.5 mg/ml, Group B (5 mg/ml, and Group C (10 mg/ml by different concentrations of KH902 eye drops and Group D by saline solution as control with three times a day for 2 weeks. At days 7, 14, and 28, the anterior segment photographs, confocal microscopy, and histopathology were performed to evaluate corneal opacity, neovascularization, inflammatory cell density, vessel size, and edema. Immunohistochemistry was applied to analyze the vascular endothelial growth factor (VEGF level. Results: (1 The CNV in the medicine-treated groups showed a reduction without obvious corneal side effects histologically. (2 Compared to the control group, the three medicine-treated groups showed a reduction in the VEGF levels and CNV areas on days 7, 14, and 28 and in the inflammatory cell density on days 14 and 28 (P 0.05. Conclusion: KH902 eye drops in lower concentration showed an obvious reduction of the CNV growing for rabbit corneal alkali burn without side effects.

  7. MUC1-specific CTLs are non-functional within a pancreatic tumor microenvironment.

    Science.gov (United States)

    Mukherjee, P; Ginardi, A R; Madsen, C S; Tinder, T L; Jacobs, F; Parker, J; Agrawal, B; Longenecker, B M; Gendler, S J

    2001-01-01

    Pancreatic cancer is a highly aggressive, treatment refractory disease and is the fourth leading cause of death in the United States. In humans, 90% of pancreatic adenocarcinomas over-express altered forms of a tumor-associated antigen, MUC1 (an epithelial mucin glycoprotein), which is a target for immunotherapy. Using a clinically relevant mouse model of pancreas cancer that demonstrates peripheral and central tolerance to human MUC1 and develops spontaneous tumors of the pancreas, we have previously reported the presence of functionally active, low affinity, MUC1-specific precursor cytotoxic T cells (pCTLs). Hypothesis for this study is that MUC1-based immunization may enhance the low level MUC1-specific immunity that may lead to an effective anti-tumor response. Data demonstrate that MUC1 peptide-based immunization elicits mature MUC1-specific CTLs in the peripheral lymphoid organs. The mature CTLs secrete IFN-gamma and are cytolytic against MUC1-expressing tumor cells in vitro. However, active CTLs that infiltrate the pancreas tumor microenvironment become cytolytically anergic and are tolerized to MUC1 antigen, allowing the tumor to grow. We demonstrate that the CTL tolerance could be reversed at least in vitro with the use of anti-CD40 co-stimulation. The pancreas tumor cells secrete immunosuppressive cytokines, including IL-10 and TGF-beta that are partly responsible for the down-regulation of CTL activity. In addition, they down-regulate their MHC class I molecules to avoid immune recognition. CD4+ CD25+ T regulatory cells, which secrete IL-10, were also found in the tumor environment. Together these data indicate the use of several immune evasion mechanisms by tumor cells to evade CTL killing. Thus altering the tumor microenvironment to make it more conducive to CTL killing may be key in developing a successful anti-cancer immunotherapy.

  8. Evolution of Geographic Atrophy in Participants Treated with Ranibizumab for Neovascular Age-related Macular Degeneration.

    Science.gov (United States)

    Thavikulwat, Alisa T; Jacobs-El, Naima; Kim, Jane S; Agrón, Elvira; Hasan, Jesia; Meyerle, Catherine B; Valent, David; Cukras, Catherine A; Wiley, Henry E; Wong, Wai T; Chew, Emily Y

    2017-01-01

    To evaluate the risk factors, incidence, and rate of progression of geographic atrophy (GA) in eyes with neovascular age-related macular degeneration (nAMD) treated with ranibizumab. Post-hoc analysis of a prospective clinical study. 69 participants with nAMD in at least one eye. Participants were prospectively treated in the study eye with 0.5 mg intravitreal ranibizumab. Study eyes received 4 monthly injections followed by pro re nata injections until a fluid-free macula was achieved on optical coherence tomography. Risk factors assessed included baseline demographics, treatment, and ocular characteristics on imaging. Eyes were evaluated on fundus autofluorescence (FAF) for GA. The rate of GA area growth in study and fellow eyes was analyzed by linear regression of square-root transformed areas. Development of new-onset GA and rate of GA area growth measured on ocular imaging, including FAF images of the study eyes. Sixty-nine participants (mean age 78.8±7.8 years) with an average of 40.0±13.6 months of follow-up were analyzed. Twenty-two of 69 study eyes (32%) were treatment naïve. During their first year of the study, participants received an average of 9.2±3.3 injections in the study eye. Of 63 study eyes with quality baseline images, 22 (35%) had pre-existing GA. Of the remaining 41 eyes, 7 (17%) developed new-onset GA during study follow-up. Those who developed new GA were older (all ≥79 years old) and had received fewer study injections on average (6.9 vs. 10.4 injections at 1 year) compared to those who did not develop new GA. Of the 12 treatment naïve study eyes without GA at baseline, 1 (8.3%) developed new GA during the study. In 21 study eyes with quantifiable GA area, eyes with GA present at baseline (16/21) enlarged by 0.34±0.26 mm/year, compared to 0.19±0.12 mm/year in eyes developing new-onset GA (5/21). While 17% of study eyes without GA present at baseline receiving ranibizumab developed new GA, the role of ranibizumab in the development

  9. [Economic Short-Term Cost Model for Stereotactic Radiotherapy of Neovascular AMD].

    Science.gov (United States)

    Neubauer, A S; Reznicek, L; Minartz, C; Ziemssen, F

    2016-08-01

    Stereotactic radiation therapy (Oraya, OT) is available as a second line therapy for patients who, despite intensive anti-VEGF therapy for neovascular AMD, do not show an improvement in CNV. As OT is expensive (5,308 €), the short term economics for starting this therapy were investigated. A short-term cost model was set up in MS Excel with a two year time horizon. On the basis of the data of the randomised, controlled INTREPID pivotal trial and current treatment practice in Germany, the costs were compared of conventional anti-VEGF therapy, with or without a single OT treatment. Patients with an active lesion after initial anti-VEGF therapy and a maximum lesion diameter ≤ 4 mm were included. Modeled cost components/aspects were direct savings from injection number, control follow-up examinations and aids, as well as anti-VEGF switches. Costs for Germany were employed and a univariate sensitivity analysis was performed to address the existing uncertainty. For the patients with a maximum AMD lesion diameter ≤ 4 mm and a macula volume > 7.4 mm(3), the INTREPID trial showed a mean reduction of 3.68 intravitreal injections for 16 Gy radiation versus sham over a time period of 2 years. These 3.68 IVM result in ~ 4,500 € direct cost savings. Moreover, due to the higher response rate with 16 Gy radiation, the number of follow-up visits and aids can be reduced, which results in savings between 207 € and 1,224 € over 2 years. After radiation, fewer anti-VEGF switches for low or non-responders are expected, which is modeled to result in ~ 1.7 fewer injections over 2 years. Due to overall fewer injections, fewer endophthalmitis cases would be expected. However, endophthalmitis and microvascular abnormalities, which can be observed in a few cases, are associated with low or non-quantifiable costs in this cost-cost comparison model. In summary, cost reductions of between 6,400 and 8,500 € are predicted in the model over two years

  10. Comparison of intravitreal bevacizumab treatment between phakic and pseudophakic neovascular age-related macular degeneration.

    Science.gov (United States)

    Ozkaya, Abdullah; Alkin, Zeynep; Perente, Irfan; Yuksel, Kemal; Baz, Okkes; Alagoz, Cengiz; Yazici, Ahmet Taylan; Demirok, Ahmet

    2014-01-01

    Before the era of intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment, only prevention for visual loss might have been achieved in a limited number of neovascular age-related macular generation (nAMD) patients with different treatment options. To compare the efficacy of intravitreal bevacizumab (IVB) for the treatment of nAMD between phakic and pseudophakic eyes. The newly diagnosed nAMD patients were included in this retrospective study. The patients were divided into the phakic and pseudophakic groups. Initially, the patients received three consecutive, monthly, IVB injections, and then the treatment was continued on an as-needed regimen. The patients were examined monthly, and the data at the baseline, at 3, 6, 9, and 12 months and at the last follow-up were evaluated. The changes in the visual acuity (VA), central retinal thickness (CRT) and the number of injections were compared between the two groups. The study included 62 eyes of 62 patients (39 phakic, and 23 pseudophakic patients). The mean follow-up time was 19.7 and 17.2 months in the phakic and pseudophakic groups, respectively (p=0.06). The mean Log MAR VA at the baseline, 12 months and the last follow-up was 0.82, 0.72 and 0.75 in the phakic group and 0.77, 0.67, and 0.68 in the pseudophakic group, respectively. The change in the mean BCVA from the baseline to 12 months and at the last follow-up was not statistically different between the two groups (p=0.9 and p=0.7, respectively). The mean injection number at 12 months was 4.5 and 4.9 in the phakic and pseudophakic group, respectively (p=0.2). The beneficial effect of IVB is equal in both the phakic and pseudophakic group of nAMD patients. The functional and anatomical outcomes of the treatment and the number of injections were similar in the two groups. © NEPjOPH.

  11. Clinical polyomavirus BK variants with agnogene deletion are non-functional but rescued by trans-complementation

    International Nuclear Information System (INIS)

    Myhre, Marit Renee; Olsen, Gunn-Hege; Gosert, Rainer; Hirsch, Hans H.; Rinaldo, Christine Hanssen

    2010-01-01

    High-level replication of polyomavirus BK (BKV) in kidney transplant recipients is associated with the emergence of BKV variants with rearranged (rr) non-coding control region (NCCR) increasing viral early gene expression and cytopathology. Cloning and sequencing revealed the presence of a BKV quasispecies which included non-functional variants when assayed in a recombinant virus assay. Here we report that the rr-NCCR of BKV variants RH-3 and RH-12, both bearing a NCCR deletion including the 5' end of the agnoprotein coding sequence, mediated early and late viral reporter gene expression in kidney cells. However, in a recombinant virus they failed to produce infectious progeny despite large T-antigen and VP1 expression and the formation of nuclear virus-like particles. Infectious progeny was generated when the agnogene was reconstructed in cis or agnoprotein provided in trans from a co-existing BKV rr-NCCR variant. We conclude that complementation can rescue non-functional BKV variants in vitro and possibly in vivo.

  12. Effect of sonication on particle dispersion, administered dose and metal release of non-functionalized, non-inert metal nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Pradhan, Sulena; Hedberg, Jonas, E-mail: jhed@kth.se; Blomberg, Eva [KTH Royal Institute of Technology, Division of Surface and Corrosion Science, Department of Chemistry (Sweden); Wold, Susanna [KTH Royal Institute of Technology, Division of Applied Physical Chemistry, Department of Chemistry (Sweden); Odnevall Wallinder, Inger [KTH Royal Institute of Technology, Division of Surface and Corrosion Science, Department of Chemistry (Sweden)

    2016-09-15

    In this study, we elucidate the effect of different sonication techniques to efficiently prepare particle dispersions from selected non-functionalized NPs (Cu, Al, Mn, ZnO), and corresponding consequences on the particle dose, surface charge and release of metals. Probe sonication was shown to be the preferred method for dispersing non-inert, non-functionalized metal NPs (Cu, Mn, Al). However, rapid sedimentation during sonication resulted in differences between the real and the administered doses in the order of 30–80 % when sonicating in 1 and 2.56 g/L NP stock solutions. After sonication, extensive agglomeration of the metal NPs resulted in rapid sedimentation of all particles. DLVO calculations supported these findings, showing the strong van der Waals forces of the metal NPs to result in significant NP agglomeration. Metal release from the metal NPs was slightly increased by increased sonication. The addition of a stabilizing agent (bovine serum albumin) had an accelerating effect on the release of metals in sonicated solutions. For Cu and Mn NPs, the extent of particle dissolution increased from <1.6 to ~5 % after sonication for 15 min. A prolonged sonication time (3–15 min) had negligible effects on the zeta potential of the studied NPs. In all, it is shown that it is of utmost importance to carefully investigate how sonication influences the physico-chemical properties of dispersed metal NPs. This should be considered in nanotoxicology investigations of metal NPs.Graphical Abstract.

  13. Intracameral air injection during Ahmed glaucoma valve implantation in neovascular glaucoma for the prevention of tube obstruction with blood clot: Case Report.

    Science.gov (United States)

    Hwang, Sung Ha; Yoo, Chungkwon; Kim, Yong Yeon; Lee, Dae Young; Nam, Dong Heun; Lee, Jong Yeon

    2017-12-01

    Glaucoma drainage implant surgery is a treatment option for the management of neovascular glaucoma. However, tube obstruction by blood clot after Ahmed glaucoma valve (AGV) implantation is an unpredictable clinically challenging situation. We report 4 cases using intracameral air injection for the prevention of the tube obstruction of AGV by blood clot. The first case was a 57-year-old female suffering from ocular pain because of a tube obstruction with blood clot after AGV implantation in neovascular glaucoma. Surgical blood clot removal was performed. However, intractable bleeding was noted during the removal of the blood clot, and so intracameral air injection was performed to prevent a recurrent tube obstruction. After the procedure, although blood clots formed around the tube, the tube opening where air could touch remained patent. In 3 cases of neovascular glaucoma with preoperative severe intraocular hemorrhages, intracameral air injection and AGV implantation were performed simultaneously. In all 3 cases, tube openings were patent. It appears that air impeded the blood clots formation in front of the tube opening. Intracameral air injection could be a feasible option to prevent tube obstruction of AGV implant with a blood clot in neovascular glaucoma with high risk of tube obstruction. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  14. Neurotrophin p75 receptor (p75NTR) promotes endothelial cell apoptosis and inhibits angiogenesis: implications for diabetes-induced impaired neovascularization in ischemic limb muscles

    NARCIS (Netherlands)

    Caporali, Andrea; Pani, Elisabetta; Horrevoets, Anton J. G.; Kraenkel, Nicolle; Oikawa, Atsuhiko; Sala-Newby, Graciela B.; Meloni, Marco; Cristofaro, Brunella; Graiani, Gallia; Leroyer, Aurelie S.; Boulanger, Chantal M.; Spinetti, Gaia; Yoon, Sung Ok; Madeddu, Paolo; Emanueli, Costanza

    2008-01-01

    Diabetes impairs endothelial function and reparative neovascularization. The p75 receptor of neurotrophins (p75(NTR)), which is scarcely present in healthy endothelial cells (ECs), becomes strongly expressed by capillary ECs after induction of peripheral ischemia in type-1 diabetic mice. Here, we

  15. Fixation stability and implication for multifocal electroretinography in patients with neovascular age-related macular degeneration after anti-VEGF treatment

    DEFF Research Database (Denmark)

    Pedersen, Karen Bjerg; Sjølie, Anne Katrin; Vestergaard, Anders Højslet

    2016-01-01

    Purpose: To quantify fixation stability in patients with neovascular age-related macular degeneration (nAMD) at baseline, 3 and 6 months after anti-vascular endothelial growth factor (anti-VEGF) treatment and furthermore asses the implications of an unsteady fixation for multifocal...

  16. A prospective, observational, open-label, multicentre study to investigate the daily treatment practice of ranibizumab in patients with neovascular age-related macular degeneration

    NARCIS (Netherlands)

    Asten, F. van; Evers-Birkenkamp, K.U.; Lith-Verhoeven, J.J. van; Jong-Hesse, Y. de; Hoppenreijs, V.P.T.; Hommersom, R.F.; Scholten, A.M.; Hoyng, C.B.; Klaver, J.H.

    2015-01-01

    PURPOSE: The HELIOS (Health Economics with Lucentis in Observational Settings) study was designed on request of the Dutch Health Authority for an observational study to assess the effectiveness and safety of ranibizumab for neovascular age-related macular degeneration (wet AMD) in daily practice.

  17. A prospective, observational, open-label, multicentre study to investigate the daily treatment practice of ranibizumab in patients with neovascular age-related macular degeneration

    NARCIS (Netherlands)

    van Asten, Freekje; Evers-Birkenkamp, Kim U.; van Lith-Verhoeven, Janneke J. C.; de Jong-Hesse, Yvonne; Hoppenreijs, Vincent P. T.; Hommersom, Richard F.; Scholten, Agnes M.; Hoyng, Carel B.; Klaver, Johannes H. J.; Klaver, J. H. J.; Hoyng, C. B.; Raijmakers, A. J.; van Lith-Verhoeven, J. J. C.; Rulo, A. H. F.; Verbraak, F. D.; Schlingemann, R. O.; Hommersom, C. F.; de Jong-Hesse, Y.; Bosch-Driessen, E. H.; Smeets, M. H.; Gonçalves, A.; Klomp, H. J.; Hoppenreijs, V. P. T.; Dito, J. J.

    2015-01-01

    The HELIOS (Health Economics with Lucentis in Observational Settings) study was designed on request of the Dutch Health Authority for an observational study to assess the effectiveness and safety of ranibizumab for neovascular age-related macular degeneration (wet AMD) in daily practice. The HELIOS

  18. HL-217, a new topical anti-angiogenic agent, inhibits retinal vascular leakage and pathogenic subretinal neovascularization in Vldlr{sup −/−} mice

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Junghyun; Kim, Chan-Sik; Jo, Kyuhyung [Korean Medicine Based Herbal Drug Development Group, Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon (Korea, Republic of); Cho, Yun-Seok; Kim, Hyun-Gyu; Lee, Geun-Hyeog [Research and Development Center, Hanlim Pharm. Co. Ltd., 1656-10, Seocho-dong, Seocho-gu, Seoul (Korea, Republic of); Lee, Yun Mi; Sohn, Eunjin [Korean Medicine Based Herbal Drug Development Group, Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon (Korea, Republic of); Kim, Jin Sook, E-mail: jskim@kiom.re.kr [Korean Medicine Based Herbal Drug Development Group, Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon (Korea, Republic of)

    2015-01-02

    Highlights: • HL-217 is a new synthetic topical anti-angiogenic agent. • HL-217 attenuated subretinal neovascularization in Vldlr{sup −/−} mice. • HL-217 blocked the binding of PDGF-BB to PDGFRβ. - Abstract: HL-217 is a new synthetic angiogenesis inhibitor. Platelet derived growth factor (PDGF) is a vasoactive factor and has been implicated in proliferative retinopathies. In this study, we examined the mechanism of action and efficacy of topical application of HL-217 on subretinal neovascularization in very low-density lipoprotein receptor knockout (Vldlr{sup −/−}) mice. In three-week-old male Vldlr{sup −/−} mice, HL-217 (1.5 or 3 mg/ml) was administered twice per day for 4 weeks by topical eye drop instillation. Neovascular areas were then measured. We used a protein array to evaluate the expression levels of angiogenic factors. The inhibitory effect of HL-217 on the PDGF-BB/PDGFRβ interaction was evaluated in vitro. The neovascular area in the Vldlr{sup −/−} mice was significantly reduced by HL-217. Additionally, HL-217 decreased the expression levels of PDGF-BB protein and VEGF mRNA. Moreover, HL-217 dose-dependently inhibited the PDGF-BB/PDGFRβ interaction (IC{sub 50} = 38.9 ± 0.7 μM). These results suggest that HL-217 is a potent inhibitor of PDGF-BB. HL-217, when applied topically, is an effective inhibitor of subretinal neovascularization due to its ability to inhibit the pro-angiogenic effects of PDGF-BB.

  19. HL-217, a new topical anti-angiogenic agent, inhibits retinal vascular leakage and pathogenic subretinal neovascularization in Vldlr−/− mice

    International Nuclear Information System (INIS)

    Kim, Junghyun; Kim, Chan-Sik; Jo, Kyuhyung; Cho, Yun-Seok; Kim, Hyun-Gyu; Lee, Geun-Hyeog; Lee, Yun Mi; Sohn, Eunjin; Kim, Jin Sook

    2015-01-01

    Highlights: • HL-217 is a new synthetic topical anti-angiogenic agent. • HL-217 attenuated subretinal neovascularization in Vldlr −/− mice. • HL-217 blocked the binding of PDGF-BB to PDGFRβ. - Abstract: HL-217 is a new synthetic angiogenesis inhibitor. Platelet derived growth factor (PDGF) is a vasoactive factor and has been implicated in proliferative retinopathies. In this study, we examined the mechanism of action and efficacy of topical application of HL-217 on subretinal neovascularization in very low-density lipoprotein receptor knockout (Vldlr −/− ) mice. In three-week-old male Vldlr −/− mice, HL-217 (1.5 or 3 mg/ml) was administered twice per day for 4 weeks by topical eye drop instillation. Neovascular areas were then measured. We used a protein array to evaluate the expression levels of angiogenic factors. The inhibitory effect of HL-217 on the PDGF-BB/PDGFRβ interaction was evaluated in vitro. The neovascular area in the Vldlr −/− mice was significantly reduced by HL-217. Additionally, HL-217 decreased the expression levels of PDGF-BB protein and VEGF mRNA. Moreover, HL-217 dose-dependently inhibited the PDGF-BB/PDGFRβ interaction (IC 50 = 38.9 ± 0.7 μM). These results suggest that HL-217 is a potent inhibitor of PDGF-BB. HL-217, when applied topically, is an effective inhibitor of subretinal neovascularization due to its ability to inhibit the pro-angiogenic effects of PDGF-BB

  20. IGF-1R Regulates the Extracellular Level of Active MMP-2, Pathological Neovascularization, and Functionality in Retinas of OIR Mouse Model.

    Science.gov (United States)

    Lorenc, Valeria E; Subirada Caldarone, Paula V; Paz, María C; Ferrer, Darío G; Luna, José D; Chiabrando, Gustavo A; Sánchez, María C

    2018-02-01

    In ischemic proliferative diseases such as retinopathies, persistent hypoxia leads to the release of numerous neovascular factors that participate in the formation of abnormal vessels and eventually cause blindness. The upregulation and activation of metalloproteinases (MMP-2 and MMP-9) represent a final common pathway in this process. Although many regulators of the neovascular process have been identified, the complete role of the insulin-like growth factor 1 (IGF-1) and its receptor (IGF-1R) appears to be significantly more complex. In this study, we used an oxygen-induced retinopathy (OIR) mouse model as well as an in vitro model of hypoxia to study the role of MMP-2 derived from Müller glial cells (MGCs) and its relation with the IGF-1/IGF-1R system. We demonstrated that MMP-2 protein expression increased in P17 OIR mice, which coincided with the active phase of the neovascular process. Also, glutamine synthetase (GS)-positive cells were also positive for MMP-2, whereas IGF-1R was expressed by GFAP-positive cells, indicating that both proteins were expressed in MGCs. In addition, in the OIR model a single intravitreal injection of the IGF-1R blocking antibody (αIR3) administered at P12 effectively prevented pathologic neovascularization, accelerated physiological revascularization, and improved retinal functionality at P17. Finally, in MGC supernatants, the blocking antibody abolished the IGF-1 effect on active MMP-2 under normoxic and hypoxic conditions without affecting the extracellular levels of pro-MMP-2. These results demonstrate, for the first time, that the IGF-1/IGF-1R system regulates active MMP-2 levels in MGCs, thus contributing to MEC remodeling during the retinal neovascular process.

  1. Effect of Factor XIII-A G185T Polymorphism on Visual Prognosis after Photodynamic Therapy for Neovascular Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Francesco Parmeggiani

    2015-08-01

    Full Text Available Macular degenerations represent leading causes of central blindness or low vision in developed countries. Most of these severe visual disabilities are due to age-related macular degeneration (AMD and pathologic myopia (PM, both of which are frequently complicated by subfoveal choroidal neovascularization (CNV. Photodynamic therapy with verteporfin (PDT-V is still employed for CNV treatment in selected cases or in combined regimen. In Caucasian patients, the common polymorphism G185T of factor XIII-A gene (FXIII-A-G185T; rs5985 has been described as predictor of poor angiographic CNV responsiveness to PDT-V. Nevertheless, the prognostic implications of this pharmacogenetic determinant on long-term visual outcome after a PDT-V regimen have not been evaluated. We retrospectively selected Caucasian patients presenting with treatment-naive CNV and receiving standardized PDT-V protocol for two years. The study population included patients affected by subfoveal CNV secondary to AMD or PM. We assessed the correlations between the polymorphic allele T of FXIII-A-G185T and: (1 total number of photodynamic treatments; and (2 change in visual acuity from baseline to the end of the follow-up period. Considering a total study population of 412 patients with neovascular AMD or PM, the carriers of 185 T-allele of FXIII-A (GT or TT genotype received a higher number of photodynamic treatments than patients without it (GG wild-type genotype (p < 0.01; mean number of PDT-V: 5.51 vs. 3.76, respectively. Moreover, patients with 185 T-allele of FXIII-A had a more marked worsening of visual acuity at 24 months than those with the GG-185 wild genotype (p < 0.01; mean difference in logMAR visual acuity: 0.22 vs. 0.08, respectively. The present findings show that the G185T polymorphism of the FXIII-A gene is associated with significant differences in the long-term therapeutic outcomes of patients treated with standardized PDT-V protocol. The comprehensive appraisal of

  2. Injection frequency and anatomic outcomes 1 year following conversion to aflibercept in patients with neovascular age-related macular degeneration.

    Science.gov (United States)

    Messenger, Wyatt B; Campbell, J Peter; Faridi, Ambar; Shippey, Loton; Bailey, Steven T; Lauer, Andreas K; Flaxel, Christina J; Hwang, Thomas S

    2014-09-01

    To evaluate the clinical, anatomic and functional effects of conversion to aflibercept following ranibizumab and/or bevacizumab in patients with neovascular age-related macular degeneration (AMD). A retrospective review of patients with neovascular AMD treated with intravitreal ranibizumab and/or bevacizumab who were switched to aflibercept was performed. The primary outcome was change in injection frequency in the year following the change. Secondary outcomes included change in central macular thickness (CMT) at 6 months and 1 year, presence of intraretinal and subretinal fluid at 6 months and visual acuity at 1 year. A total of 109 eyes with neovascular AMD were switched to aflibercept and met inclusion criteria. Overall, aflibercept injection frequency was unchanged with patients receiving 7.4 antivascular endothelial growth factor (VEGF) injections the year prior to conversion compared with 7.2 aflibercept injections in the year following (p=0.47). However, the change to aflibercept was associated with improvement in CMT from 324 to 295 μm (p=0.0001) at 6 months and 299 μm (p=0.0047) at 1 year. There was no effect on visual acuity at 1 year. In a subgroup analysis, patients who had received ≥10 anti-VEGF injections in the year prior had fewer injections (11.1 to 8.4, p<0.0001) and clinic visits (13.9 to 9.6, p<0.0001) as well as a significant decrease in CMT (-35 μm, p=0.02). In our population, switching to aflibercept therapy was not associated with a change in injection frequency nor improved visual acuity, but was associated with improved CMT at 6 months and 1 year. In patients who received at least 10 anti-VEGF injections in the year prior, transitioning to aflibercept was associated with a reduced injection frequency and CMT, suggesting potential cost savings in this population. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  3. Polarisation-sensitive OCT is useful for evaluating retinal pigment epithelial lesions in patients with neovascular AMD.

    Science.gov (United States)

    Schütze, Christopher; Teleky, Katharina; Baumann, Bernhard; Pircher, Michael; Götzinger, Erich; Hitzenberger, Christoph K; Schmidt-Erfurth, Ursula

    2016-03-01

    To examine the reproducibility of lesion dimensions of the retinal pigment epithelium (RPE) in neovascular age-related macular degeneration (AMD) with polarisation-sensitive optical coherence tomography (PS-OCT), specifically imaging the RPE. Twenty-six patients (28 eyes) with neovascular AMD were included in this study, and examined by a PS-OCT prototype. Each patient was scanned five times at a 1-day visit. The PS-OCT B-scan located closest to the macular centre presenting with RPE atrophy was identified, and the longitudinal diameter of the lesion was quantified manually using AutoCAD 2008. This procedure was followed for the identical B-scan position in all five scans per eye and patient. Reproducibility of qualitative changes in PS-OCT was evaluated. Interobserver variability was assessed. Results were compared with intensity-based spectral-domain OCT (SD-OCT) imaging. Mean variability of all atrophy lesion dimensions was 0.10 mm (SD±=0.06 mm). Coefficient of variation (SD±/mean) was 0.06 on average (SD±=0.03). Interobserver variability assessment showed a mean difference of 0.02 mm across all patients regarding RPE lesion size evaluation (paired t test: p=0.38). Spearman correlation coefficient was r=0.98, p<0.001. Results revealed a good overall reproducibility of ∼90%. PS-OCT specifically detected the RPE in all eyes compared with conventional intensity-based SD-OCT that was not capable to clearly identify RPE atrophy in 25 eyes (89.3%, p<0.01). PS-OCT offers good reproducibility of RPE atrophy assessment in neovascular AMD, and may be suitable for precise RPE evaluation in clinical practice. PS-OCT unambiguously identifies RPE changes in choroidal neovascularisation compared with intensity-based SD-OCT that does not identify the RPE status reliably. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  4. A Value-Based Medicine cost-utility analysis of genetic testing for neovascular macular degeneration.

    Science.gov (United States)

    Brown, Gary C; Brown, Melissa M; Lieske, Heidi B; Lieske, Philip A; Brown, Kathryn S

    2015-01-01

    There is a dearth of patient, preference-based cost-effectiveness analyses evaluating genetic testing for neovascular age-related macular degeneration (NVAMD). A Value-Based Medicine, 12-year, combined-eye model, cost-utility analysis evaluated genetic testing of Category 3 AMD patients at age 65 for progression to NVAMD. The benefit of genetic testing was predicated upon the fact that early-treatment ranibizumab therapy (baseline vision 20/40-20/80) for NVAMD confers greater patient value than late-treatment (baseline vision ≤20/160). Published genetic data and MARINA Study ranibizumab therapy data were utilized in the analysis. Patient value (quality-of-life gain) and financial value (2012 US real dollar) outcomes were discounted at 3 % annually. Genetic testing-enabled, early-treatment ranibizumab therapy per patient conferred mean 20/40 -1 vision, a 0.845 QALY gain and 14.1 % quality-of-life gain over sham therapy. Late-treatment ranibizumab therapy conferred mean 20/160 +2 vision, a 0.250 QALY gain and 4.2 % quality-of-life gain over sham therapy. The gain from early-treatment over late-treatment was 0.595 QALY (10.0 % quality-of-life gain). The per-patient cost for genetic testing/closer monitoring was $2205 per screened person, $2.082 billion for the 944,000 estimated new Category 3 AMD patients annually. Genetic testing/monitoring costs per early-treatment patient totaled $66,180. Costs per early-treatment patient included: genetic testing costs: $66,180 + direct non-ophthalmic medical costs: -$40,914 + caregiver costs: -$172,443 + employment costs: -$14,098 = a net societal cost saving of $160,582 per early treatment patient. When genetic screening facilitated an incremental 12,965 (8.0 %) of the 161,754, new annual NVAMD patients aged ≥65 in the US to undergo early-treatment ranibizumab therapy, each additional patient treated accrued an overall, net financial gain for society of $160,582. Genetic screening was cost-effective, using World

  5. Comorbidity and cardiovascular risk factors in adult GH deficiency following treatment for Cushing's disease or non-functioning pituitary adenomas during childhood

    DEFF Research Database (Denmark)

    Ragnarsson, Oskar; Höybye, Charlotte; Jönsson, Peter J

    2012-01-01

    Cushing's disease (CD) and non-functioning pituitary adenoma (NFPA) are rare in paediatric patients. The aim of this study was to describe long-term consequences in adults with GH deficiency (GHD) treated for CD or NFPA during childhood.......Cushing's disease (CD) and non-functioning pituitary adenoma (NFPA) are rare in paediatric patients. The aim of this study was to describe long-term consequences in adults with GH deficiency (GHD) treated for CD or NFPA during childhood....

  6. Reproductive Function in Patients with Non-functioning Pituitary Adenoma According to the Register of the Republic of Uzbekistan

    Directory of Open Access Journals (Sweden)

    Dinara A. Alieva

    2016-06-01

    Full Text Available The main aim of our study was to evaluate the reproductive system status and gonadotropic pituitary function in patients with non-functioning pituitary adenoma (NFPA according to the register data. Depending on the state of the reproductive system at the time of NFPA diagnosis, men and women can be classified into three groups: secondary hypogonadism (40.7%; normal state of the sexual system (22.0%; and PCOS in women (36.5% and reduced testicular size in men (11.2%. Menstrual irregularities took place in 77.8% NFPA women of reproductive age (41.3% of them had galactorea-oligo/amenorrhea combined with moderate hyperprolactinemia, and sexual dysfunction occurred in 42.0% of male patients with NFPA.

  7. Impact of non-functionalized and amino-functionalized multiwall carbon nanotubes on pesticide uptake by lettuce (Lactuca sativa L.).

    Science.gov (United States)

    Hamdi, Helmi; De La Torre-Roche, Roberto; Hawthorne, Joseph; White, Jason C

    2015-03-01

    The effect of non-functionalized and amino-functionalized multiwall carbon nanotube (CNT) exposure, as well as the impact of CNT presence on coexistent pesticide accumulation, was investigated in lettuce (Lactuca sativa L.). Lettuce seeds were sown directly into CNT-amended vermiculite (1000 mg L(-1)) to monitor phytotoxicity during germination and growth. During growth, lettuce seedlings were subsequently exposed to chlordane (cis-chlordane [CS], trans-chlordane [TC] and trans-nonachlor [TN]) and p,p'-DDE (all at 100 ng/L) in the irrigation solution for a 19-d growth period. CNT exposure did not significantly influence seed germination (82-96%) or plant growth. Similarly, pesticide exposure had no impact on plant growth, total pigment production or tissue lipid peroxidation. After 19 d, the root content of total chlordane and p,p'-DDE was 390 and 73.8 µg g(-1), respectively; in plants not exposed to CNTs, the shoot levels were 1.58 and 0.40 µg g(-1), respectively. The presence and type of CNT significantly influenced pesticide availability to lettuce seedlings. Non-functionalized CNT decreased the root and shoot pesticide content by 88% and 78%, respectively, but amino-functionalized CNT effects were significantly more modest, with decreases of 57% in the roots and 23% in the shoots, respectively. The presence of humic acid completely reversed the reduced accumulation of pesticides induced by amino-functionalized CNT, likely due to strong competition over adsorption sites on the nanomaterial (NM). These findings have implications for food safety and for the use of engineered NMs in agriculture, especially with leafy vegetables.

  8. The effect of pore size on tissue ingrowth and neovascularization in porous bioceramics of controlled architecture in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Bai Feng; Zhang Jinkang; Wang Zhen; Liu Jian; Meng Guolin; Dong Xin [Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China); Lu Jianxi; Chang Jiang, E-mail: baifeng_fmmu@126.com [Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050 (China)

    2011-02-15

    The purpose of this study was to investigate the role of pore size on tissue ingrowth and neovascularization in porous bioceramics under the accurate control of the pore parameters. For that purpose, {beta}-tricalcium phosphate ({beta}-TCP) cylinders with four different macropore sizes (300-400, 400-500, 500-600 and 600-700 {mu}m) but the same interconnection size (120 {mu}m) and unchangeable porosity were implanted into fascia lumbodorsalis in rabbits. The fibrous tissues and blood vessels formed in scaffolds were observed histologically and histomorphometrically. The vascularization of the porous bioceramics was analyzed by single-photon emission computed tomography (SPECT). It is found that pore size as an important parameter of a porous structure plays an important role in tissue infiltration into porous biomaterial scaffolds. The amount of fibrous tissue ingrowth increases with the decrease of the pore size. In four kinds of scaffolds with different macropore sizes (300-400, 400-500, 500-600 and 600-700 {mu}m) and a constant interconnection size of 120 {mu}m, the areas of fibrous tissue (%) were 60.5%, 52.2%, 41.3% and 37.3%, respectively, representing a significant decrease at 4 weeks (P < 0.01). The pore size of a scaffold is closely related to neovascularization of macroporous biomaterials implanted in vivo. A large pore size is beneficial for the growth of blood vessels, and the diameter of a pore smaller than 400 {mu}m limits the growth of blood vessels and results in a smaller blood vessel diameter.

  9. Low-dose fractionated percutaneous teletherapy in age-related macular degeneration with subfoveolar neovascularization - 3 year results

    International Nuclear Information System (INIS)

    Schittkowski, M.; Schneider, H.; Guthoff, R.; Grueschow, K.; Ziegler, P.G.; Fietkau, R.

    2001-01-01

    The effect of low dose fractionated percutaneous teletherapy to visual acuity and the changes in subfoveolar neovascular membranes in age-related macular degeneration were investigated. Patients and Method: 126 eyes of 118 patients (age 55-89 years; mean 74 ys.) were treated. Best distal and near visual acuity was assessed prior to (= initial visual acuity [IVA]) and 3, 6, 12, 18, 24, and 36 months after teletherapy. Fluorescein angiography was performed prior to and 6, 12, 24 and 36 months after radiation therapy. For analysis patients were divided into different groups by IVA and membrane size. Maximal duration of observation was 36 months. Teletherapy was done by a 9-MeV photon linear accelerator through a lateral port in half-beam technique with a single dose of 2 Gy up to a total dose of 20 Gy within 12 days. Results: No severe negative side effects have been observed. Eight patients reported of epiphora and four patients complained of transient sicca syndrome. Visual acuity decreased more than one line in the group IVA 0.05-0.2. The group IVA 0.3-0.5 remained unchanged for 1 year. We found a tendency for increased visual acuity in group IVA ≥ 0.6 for 18 months. After that time both groups showed decreased visual acuity, but all these patients reported of reduced metamorphopsia and increased color and contrast perception. Conclusions: There is an influence of low dose fractionated percutaneous teletherapy on visual acuity, subfoveal neovascular membranes and metamorphopsia. IVA and duration of anamnesis play an important role. There seems to be no persistent effect; possibly increased dosage will bring a benefit. (orig.) [de

  10. Short-term outcomes after EX-PRESS implantation versus trabeculectomy alone in patients with neovascular glaucoma

    Directory of Open Access Journals (Sweden)

    Shinohara Y

    2017-12-01

    Full Text Available Yoichiro Shinohara, Hideo Akiyama, Mikiya Magori, Shoji Kishi Department of Ophthalmology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan Background: The purpose of this study was to investigate postoperative clinical outcomes in patients with neovascular glaucoma (NVG who underwent trabeculectomy or EX-PRESS implantation and to identify predictors of successful EX-PRESS implantation. Methods: The study designed as a retrospective observational analysis and was set in a single tertiary center. Eighty-nine patients (89 eyes with NVG, were treated using trabeculectomy alone (Trab group; n=39 or EX-PRESS implantation (EX group; n=50. All patients with a history of glaucoma surgery were excluded. The main outcome measures were postoperative intraocular pressure (IOP, visual acuity (VA, number of medications, complications, additional therapy, and success rate. Results: The mean follow-up duration was 4.6 months in the Trab group and 4.2 months in the EX group. There was no significant difference in IOP between the groups except at 1-month follow-up (P=0.045. The number of patients with early postoperative hypotony, a shallow anterior chamber, hyphema, or anterior chamber irrigation was significantly lower in the EX group than in the Trab group (P=0.016, 0.008, 0.019, and 0.014, respectively. The other outcomes, ie, VA, number of medications, and success rate, were similar between the two groups. In the EX group, the success rate was significantly lower in 15 patients with a history of vitrectomy compared to that in 35 patients without a history of vitrectomy (P=0.047. Conclusion: Implantation of an EX-PRESS device may be more effective and safer than trabeculectomy alone in patients with NVG. However, a history of vitrectomy may affect the surgical success rate when using EX-PRESS. Keywords: trabeculectomy, EX-PRESS, neovascular glaucoma, surgery, tube shunt

  11. Real-Time Demonstration of Split Skin Graft Inosculation and Integra Dermal Matrix Neovascularization Using Confocal Laser Scanning Microscopy

    Science.gov (United States)

    Greenwood, John; Amjadi, Mahyar; Dearman, Bronwyn; Mackie, Ian

    2009-01-01

    Objectives: During the first 48 hours after placement, an autograft “drinks” nutrients and dissolved oxygen from fluid exuding from the underlying recipient bed (“plasmatic imbibition”). The theory of inosculation (that skin grafts subsequently obtain nourishment via blood vessel “anastomosis” between new vessels invading from the wound bed and existing graft vessels) was hotly debated from the late 19th to mid-20th century. This study aimed to noninvasively observe blood flow in split skin grafts and Integra™ dermal regeneration matrix to provide further proof of inosculation and to contrast the structure of vascularization in both materials, reflecting mechanism. Methods: Observations were made both clinically and using confocal microscopy on normal skin, split skin graft, and Integra™. The VivaScope™ allows noninvasive, real-time, in vivo images of tissue to be obtained. Results: Observations of blood flow and tissue architecture in autologous skin graft and Integra™ suggest that 2 very different processes are occurring in the establishment of circulation in each case. Inosculation provides rapid circulatory return to skin grafts whereas slower neovascularization creates an unusual initial Integra™ circulation. Conclusions: The advent of confocal laser microscopy like the VivaScope 1500™, together with “virtual” journals such as ePlasty, enables us to provide exciting images and distribute them widely to a “reading” audience. The development of the early Integra™ vasculature by neovascularization results in a large-vessel, high-volume, rapid flow circulation contrasting markedly from the inosculatory process in skin grafts and the capillary circulation in normal skin and merits further (planned) investigation. PMID:19787028

  12. Relationship of retinal morphology and retinal sensitivity in the treatment of neovascular age-related macular degeneration using aflibercept.

    Science.gov (United States)

    Sulzbacher, Florian; Roberts, Philipp; Munk, Marion R; Kaider, Alexandra; Kroh, Maria Elisabeth; Sacu, Stefan; Schmidt-Erfurth, Ursula

    2014-12-11

    To relate the functional response to distinct morphological features of the retina during aflibercept treatment for neovascular AMD (nAMD). A total of 726 retinal locations in 22 consecutive eyes presenting with treatment-naive nAMD underwent a standardized examination with spectral-domain optical coherence tomography (SD-OCT) and topographic microperimetry (MP) at baseline, after 3 and 12 months of continuous intravitreal aflibercept therapy. The retinal sensitivity at each stimulus location was registered to the corresponding location on SD-OCT morphology. Subsequently, the microperimetric responses were evaluated with respect to the following underlying SD-OCT features: neovascular complex (NVC), subretinal fluid (SRF), intraretinal fluid (IRF), intraretinal cystoid space (IRC), serous pigment epithelium detachment (sPED), and fibrovascular pigment epithelium detachment (fPED). Baseline sensitivity was reduced to mean values of 1.8 dB in NVC, 2.2 dB in IRC, 2.8 dB in IRF, 2.6 dB in sPED, 3.6 dB in SRF, and 4.6 dB in fPED. Improvements in retinal sensitivity were most pronounced during the initial 3-month interval, when significant recovery was documented for SRF and sPED with +4.0/5.5 dB (P 0.05 for each category). Significant functional benefits following intravitreal aflibercept treatment could be detected over all defined morphological pathologies. The level of improvement varied dependent on the associated feature with the best prognosis for visual improvement in SRF and sPED and least with intraretinal fluid and particularly intraretinal cysts. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

  13. Ranibizumab for choroidal neovascularization secondary to pseudoxanthoma elasticum: 4-year results from the PIXEL study in France.

    Science.gov (United States)

    Mimoun, Gérard; Ebran, Jean-Marc; Grenet, Typhaine; Donati, Alain; Cohen, Salomon-Yves; Ponthieux, Anne

    2017-08-01

    To evaluate the long-term effectiveness and safety of ranibizumab 0.5 mg in patients with choroidal neovascularization (CNV) secondary to pseudoxanthoma elasticum (PXE) in a real-world setting. A descriptive, observational, multicenter study in a retrospective and prospective cohort was conducted in France that included patients who had received at least one injection of ranibizumab 0.5 mg during the period October 2011 to October 2014, for CNV secondary to PXE. Eligible patients were identified by review of medical records or during routine consultations. The main objectives were to describe patient characteristics, assess changes in best-corrected visual acuity [VA, Early Treatment Diabetic Retinopathy Study (ETDRS) letters] over time, the number and reasons for ranibizumab treatment and overall safety. Of the 72 enrolled patients (98 eyes) from 23 centers, 39 (54.2%) were male and mean [±standard deviation (SD)] age was 59.6 (±8.3) years. The mean VA was 64.6 letters at the first ranibizumab injection, which was maintained at the 1-year follow-up (64.7 letters). Thereafter, the mean VA was stable until the 4-year follow-up. At 4 years, the proportion of eyes with VA gain of ≥15 letters was 3/19 (15.8%) and stable VA (change between -15 and +15 letters) was 10/19 (52.6%). Mean (±SD) annual number of ranibizumab injections was 4.1 (±4.0), lower in the second versus first year. The most common reason for ranibizumab treatment was progression of neovascular activity (42.9%). No deaths or new safety findings were reported. In patients with CNV secondary to PXE, ranibizumab 0.5 mg resulted in stable VA over 4 years with a limited number of injections. Safety findings were consistent with the established safety profile of ranibizumab.

  14. Evaluation of the thrombus of abdominal aortic aneurysms using contrast enhanced ultrasound - preliminary results

    Science.gov (United States)

    Łukasiewicz, Adam; Garkowski, Adam; Rutka, Katarzyna; Janica, Jacek; Łebkowska, Urszula

    2016-09-01

    It is hypothesized that the degree of vascularization of the thrombus may have a significant impact on the rupture of aortic aneurysms. The presence of neovascularization of the vessel wall and mural thrombus has been confirmed only in histopathological studies. However, no non-invasive imaging technique of qualitative assessment of thrombus and neovascularization has been implemented so far. Contrast-enhanced ultrasound (CEUS) has been proposed as a feasible and minimally invasive technique for in vivo visualization of neovascularization in the evaluation of tumors and atherosclerotic plaques. The aim of this study was the evaluation of mural thrombus and AAAs wall with CEUS. CEUS was performed in a group of seventeen patients with AAAs. The mural thrombus enhancement was recognized in 12 cases, yet no significant correlation between the degree of contrast enhancement and AAAs diameter, thrombus width, and thrombus echogenicity was found. We observed a rise in AAAs thrombus heterogeneity with the increase in the aneurysm diameter (r = 0.62, p = 0.017). In conclusion CEUS can visualize small channels within AAAs thrombus, which could be a result of an ongoing angiogenesis. There is a need for further research to find out whether the degree of vascularization of the thrombus may have a significant impact on the rupture of aneurysms.

  15. Improved Adherence to Vision Self-monitoring with the Vision and Memory Stimulating (VMS) Journal for Non-neovascular Age-related Macular Degeneration during a Randomized Controlled Trial

    OpenAIRE

    Bittner, Ava K; Torr-Brown, Sheryl; Arnold, Ellen; Nwankwo, Antonia; Beaton, Patricia; Rampat, Radhika; Dagnelie, Gislin; Roser, Mark

    2014-01-01

    Objective An educational, interactive journal [Vision and Memory Stimulating (VMS) journal] was developed to boost patient confidence and promote long-term adherence with weekly vision self-monitoring in age-related macular degeneration (AMD) patients at risk for vision loss from new-onset neovascularization. Methods In a multicenter randomized controlled trial, 198 subjects with intermediate stage, non-neovascular AMD received the VMS journal or followed usual care (e.g. their doctor’s instr...

  16. Optimizing Anti-VEGF Treatment Outcomes for Patients with Neovascular Age-Related Macular Degeneration.

    Science.gov (United States)

    Wykoff, Charles C; Clark, W Lloyd; Nielsen, Jared S; Brill, Joel V; Greene, Laurence S; Heggen, Cherilyn L

    2018-02-01

    The introduction of anti-vascular endothelial growth factor (anti-VEGF) drugs to ophthalmology has revolutionized the treatment of neovascular age-related macular degeneration (nAMD). Despite this significant progress, gaps and challenges persist in the diagnosis of nAMD, initiation of treatment, and management of frequent intravitreal injections. Thus, nAMD remains a leading cause of blindness in the United States. To present current knowledge, evidence, and expert perspectives on anti-VEGF therapies in nAMD to support managed care professionals and providers in decision making and collaborative strategies to overcome barriers to optimize anti-VEGF treatment outcomes among nAMD patients. Three anti-VEGF therapies currently form the mainstay of treatment for nAMD, including 2 therapies approved by the FDA for treatment of nAMD (aflibercept and ranibizumab) and 1 therapy approved by the FDA for oncology indications and used off-label for treatment of nAMD (bevacizumab). In clinical trials, each of the 3 agents maintained visual acuity (VA) in approximately 90% or more of nAMD patients over 2 years. However, in long-term and real-world settings, significant gaps and challenges in diagnosis, treatment, and management pose barriers to achieving optimal outcomes for patients with nAMD. Many considerations, including individual patient characteristics, on-label versus off-label treatment, repackaging, and financial considerations, add to the complexity of nAMD decision making and management. Many factors may contribute to additional challenges leading to suboptimal long-term outcomes among nAMD patients, such as delays in diagnosis and/or treatment approval and initiation, individual patient response to different anti-VEGF therapies, lapses in physician regimentation of anti-VEGF injection and monitoring, and inadequate patient adherence to treatment and monitoring. These latter factors highlight the considerable logistical, emotional, and financial burdens of long

  17. Identification of novel CYP2D7-2D6 hybrids: non-functional and functional variants

    Directory of Open Access Journals (Sweden)

    Andrea Gaedigk

    2010-10-01

    Full Text Available Polymorphic expression of CYP2D6 contributes to the wide range of activity observed for this clinically important drug metabolizing enzyme. In this report we describe novel CYP2D7/2D6 hybrid genes encoding non-functional and functional CYP2D6 protein and a CYP2D7 variant that mimics a CYP2D7/2D6 hybrid gene. Five kb long PCR products encompassing the novel genes were entirely sequenced. A quantitative assay probing in different gene regions was employed to determine CYP2D6 and 2D7 copy number variations and the relative position of the hybrid genes within the locus was assessed by long-range PCR. In addition to the previously known CYP2D6*13 and *66 hybrids, we describe three novel non-functional CYP2D7-2D6 hybrids with gene switching in exon 2 (CYP2D6*79, intron 2 (CYP2D6*80 and intron 5 (CYP2D6*67. A CYP2D7-specific T-ins in exon 1 causes a detrimental frame shift. One subject revealed a CYP2D7 conversion in the 5’-flanking region of a CYP2D6*35 allele, was otherwise unaffected (designated CYP2D6*35B. Finally, three DNAs revealed a CYP2D7 gene with a CYP2D6-like region downstream of exon 9 (designated CYP2D7[REP6]. Quantitative copy number determination, sequence analyses and long-range PCR mapping were in agreement and excluded the presence of additional gene units. Undetected hybrid genes may cause over-estimation of CYP2D6 activity (CYP2D6*1/*1 vs *1/hybrid, etc, but may also cause results that may interfere with the genotype determination. Detection of hybrid events, ‘single’ and tandem, will contribute to more accurate phenotype prediction from genotype data.

  18. Comparison of intravitreal aflibercept and ranibizumab injections on subfoveal and peripapillary choroidal thickness in eyes with neovascular age-related macular degeneration.

    Science.gov (United States)

    Yun, Cheolmin; Oh, Jaeryung; Ahn, Jaemoon; Hwang, Soon-Young; Lee, Boram; Kim, Seong-Woo; Huh, Kuhl

    2016-09-01

    We aimed to compare changes in subfoveal and peripapillary choroidal thickness (CT) after intravitreal aflibercept or ranibizumab injections for neovascular age-related macular degeneration (AMD). Medical records of 54 treatment-naïve, consecutive patients (54 eyes) who were diagnosed with neovascular AMD and received three monthly injections of aflibercept (21 eyes) or ranibizumab (33 eyes) were reviewed. Subfoveal and peripapillary CT were measured with images obtained using spectral domain optical coherence tomography at baseline and at three months. Subfoveal CT decreased from 232.2 ± 94.4 μm at baseline to 207.1 ± 89.3 μm at three months in the aflibercept group (p macula as well.

  19. Early Changes of Retinal Morphology in Therapy of Neovascular Age-Related Macular Degeneration with Three Commonly Used Anti-VEGF Agents.

    Science.gov (United States)

    Enders, Philip; Sitnilska, Vasilena; Altay, Lebriz; Fauser, Sascha

    2018-01-01

    To compare changes of retinal morphology in the first weeks following injection of anti-VEGF agents for neovascular age-related macular degeneration (nAMD). In a prospective study 50 patients with active choroidal neovascularization secondary to nAMD were monitored weekly by spectral-domain optical coherence tomography for 3 weeks after treatment. Twenty-two patients received bevacizumab, 15 ranibizumab, and 13 aflibercept. Morphological parameters of retinal compartments were compared. Mean central retinal thickness (391.22 ± 123.41 µm) was reduced by -26.15 µm (p treatment. This information could be clinically helpful to evaluate early non-response. © 2017 S. Karger AG, Basel.

  20. INTRAVITREAL DEXAMETHASONE IMPLANT AS ADJUVANT TREATMENT FOR BEVACIZUMAB- AND RANIBIZUMAB-RESISTANT NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: A Prospective Pilot Study.

    Science.gov (United States)

    Barikian, Anita; Salti, Haytham; Safar, Ammar; Mahfoud, Ziyad R; Bashshur, Ziad F

    2017-07-01

    To study the benefit of intravitreal dexamethasone implant in the management of neovascular age-related macular degeneration resistant to bevacizumab and ranibizumab. Patients with persistent macular fluid on optical coherence tomography despite monthly treatment with at least three consecutive bevacizumab injections followed by at least three ranibizumab injections were prospectively enrolled. A single dexamethasone implant was administered followed by intravitreal ranibizumab 1 week later. Ranibizumab was continued afterward on an as-needed basis. Main outcomes were improvement in central retinal thickness and best-corrected visual acuity. Nineteen patients (19 eyes) were enrolled. There was no significant change in best-corrected visual acuity over 6 months. Greatest reduction in mean central retinal thickness, from 295.2 μm to 236.2 μm, occurred 1 month after dexamethasone implant (P macular intraretinal fluid in eyes with neovascular age-related macular degeneration resistant to bevacizumab and ranibizumab. However, this treatment had a limited duration.

  1. Fibroblast growth factor-2-induced host stroma reaction during initial tumor growth promotes progression of mouse melanoma via vascular endothelial growth factor A-dependent neovascularization.

    Science.gov (United States)

    Tsunoda, Satoshi; Nakamura, Toshiyuki; Sakurai, Hiroaki; Saiki, Ikuo

    2007-04-01

    Fibroblast growth factor (FGF)-2 has been considered to play a critical role in neovascularization in several tumors; however, its precise role in tumor progression is not fully understood. In the present study, we have characterized the role of FGF-2 in B16-BL6 mouse melanoma cells, focusing on effects during the initial phase of tumor growth. FGF-2 was injected at the tumor inoculation site of dorsal skin during the initial phase. FGF-2 induced marked tumor growth and lymph node metastasis. This was well correlated with an increase in neovascularization in the host stroma. FGF-2 also recruited inflammatory and mesenchymal cells in host stroma. Marked tumor growth, pulmonary metastasis and intensive neovascularization in tumor parenchyma were also observed after a single injection of FGF-2 into the footpad inoculation site. In contrast, repeated injections of FGF-2 at a site remote from the footpad tumor were ineffective in promoting tumor growth and metastasis. These promoting activities of FGF-2 were blocked by local injections of a glucocorticoid hormone, suggesting that host inflammatory responses induced by FGF-2 are associated with FGF-2-induced tumor progression. In addition, although FGF-2 did not promote cellular proliferation and vascular endothelial growth factor A (VEGFA) mRNA expression in B16-BL6 cells in vitro, FGF-2 induced VEGFA expression in host stroma rather than tumor tissue, and local injections of a neutralizing antibody against VEGFA inhibited these activities of FGF-2 in vivo. These results indicate that abundant FGF-2 during the initial phase of tumor growth induces VEGFA-dependent intensive neovascularization in host stroma, and supports marked tumor growth and metastasis.

  2. Contrast Enhanced Spectral Mammography: A Review.

    Science.gov (United States)

    Patel, Bhavika K; Lobbes, M B I; Lewin, John

    2018-02-01

    Contrast-enhanced spectral mammography (CESM) provides low-energy 2D mammographic images comparable to standard digital mammography and a post-contrast recombined image to assess tumor neovascularity similar to magnetic resonance imaging (MRI). The utilization of CESM in the United States is currently low but could increase rapidly given many potential indications for clinical use. This article discusses historical background and literature review of indications and diagnostic accuracy of CESM to date. CESM is a growing technique for breast cancer detection and diagnosis that has levels of sensitivity and specificity on par with contrast-enhanced breast MRI. Because of its similar performance and ease of implementation, CESM is being adopted for multiple indications previously reserved for MRI, such as problem-solving, disease extent in newly diagnosed patients, and evaluating the treatment response of neoadjuvant chemotherapy. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. Comparison of polypropylene and silicone Ahmed® glaucoma valves in the treatment of neovascular glaucoma: A 2-year follow-up.

    Science.gov (United States)

    Lubiński, Wojciech; Krzystolik, Karol; Gosławski, Wojciech; Kuprjanowicz, Leszek; Mularczyk, Maciej

    2018-01-01

    Inflammation associated with biomaterials of Ahmed® glaucoma drainage devices may cause the formation of a capsule around the device and can thus have a significant influence on the level of intraocular pressure reduction. The objective of this study was to compare the clinical outcomes after the implantation of a polypropylene or silicone Ahmed® glaucoma valve in patients with neovascular glaucoma. In the study, 27 eyes with neovascular glaucoma (group 1) received silicon Ahmed® valves and 23 eyes (group 2) received polypropylene valves. The best corrected distance visual acuity (BCDVA), intraocular pressure (IOP) and number of anti-glaucomatous drugs were recorded preoperatively and during a follow-up period of 24 months after surgery. Success was defined by the following criteria: 1) intraocular pressure in the rage of 6-21 mm Hg; 2) IOP reduction of at least 30% relative to preoperative values. All complications were registered. One month postoperatively, the mean BCDVA increased significantly in both groups compared to preoperative values (p glaucoma, the implantation of a silicone valve is associated with a significantly higher probability of long-term reduction of IOP below 21 mm Hg and with a lower risk of valve encapsulation in comparison to polypropylene valves. The obtained results suggest that silicone Ahmed® valves are more effective in the treatment of patients with neovascular glaucoma.

  4. COMPARING THE OUTCOME OF SINGLE VERSUS MULTIPLE SESSION LASER PHOTOABLATION OF FLAT NEOVASCULARIZATION IN ZONE 1 AGGRESSIVE POSTERIOR RETINOPATHY OF PREMATURITY: A Prospective Randomized Study.

    Science.gov (United States)

    Vinekar, Anand; Jayadev, Chaitra; Mangalesh, Shwetha; Kumar, Anupama Kiran; Bauer, Noel; Capone, Antonio; Trese, Michael; Shetty, Bhujang

    2015-10-01

    To compare single versus 2-session laser photoablation for flat neovascularization in cases with Zone 1 aggressive posterior retinopathy of prematurity. Twenty-nine Asian Indian infants with aggressive posterior retinopathy of prematurity were randomized; each eye received 1 of 2 methods (29 each in Group A or B) proposed by the PHOTO-ROP group. Group A underwent single session laser to the avascular retina underlying the flat neovascularization by direct laser over the fronds. Group B underwent laser in 2 sessions; first, laser was delivered to the avascular periphery up to the flat neovascularization and 7 days later to the avascular bed exposed by the retraction of the fronds. Outcome and complications between the two groups were compared. Mean birthweight and gestational ages were 1,276 g and 30.1 weeks, respectively. All eyes showed favorable outcome at a minimum 12-month follow-up. Hemorrhages after laser (41.4% vs. 17.2%, P Large hemorrhages (>1 disk diameter) seen in Group A took longer than 8 weeks to resolve and developed focal fibrosis. This study demonstrates that the two-staged laser procedure produces fewer and smaller hemorrhages and no fibrosis compared with a single session. Both methods have comparable favorable outcomes in Asian Indian infants.

  5. In vivo secretory potential and the effect of combination therapy with octreotide and cabergoline in patients with clinically non-functioning pituitary adenomas

    DEFF Research Database (Denmark)

    Andersen, M; Bjerre, P; Schrøder, H D

    2001-01-01

    The secretory capacity, in vivo, of clinically non-functioning pituitary adenomas may possibly predict tumour volume reduction during intensive medical therapy. Ten patients (mean (range) 53 years (26-73)) with clinically non-functioning macroadenomas, > or = 10 mm were studied. The secretory...... capacity of the adenomas was examined using basal, NaCl and TRH-stimulated LH, FSH and alpha-subunit levels. The effect on tumour volume of 6 months' therapy with the combination of a somatostatin analogue, octreotide 200 microg x 3/day and a dopamine-D2-agonist, cabergoline 0.5 mg x 1/day was studied...... therapy in all of our patients with non-functioning pituitary adenomas....

  6. Topical ocular delivery to laser-induced choroidal neovascularization by dual internalizing RGD and TAT peptide-modified nanoparticles

    Directory of Open Access Journals (Sweden)

    Chu YC

    2017-02-01

    Full Text Available Yongchao Chu,1,* Ning Chen,2,* Huajun Yu,2,* Hongjie Mu,1 Bin He,1 Hongchen Hua,1 Aiping Wang,1 Kaoxiang Sun1 1School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Yantai University, Yantai, Shandong, People’s Republic of China; 2Department of Ophthalmology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, People’s Republic of China *These authors contributed equally to this work Abstract: A nanoparticle (NP was developed to target choroidal neovascularization (CNV via topical ocular administration. The NPs were prepared through conjugation of internalizing arginine-glycine-aspartic acid RGD (iRGD; Ac-CCRGDKGPDC and transactivated transcription (TAT (RKKRRQRRRC peptide to polymerized ethylene glycol and lactic-co-glycolic acid. The iRGD sequence can specifically bind with integrin αvβ3, while TAT facilitates penetration through the ocular barrier. 1H nuclear magnetic resonance and high-performance liquid chromatography demonstrated that up to 80% of iRGD and TAT were conjugated to poly(ethylene glycol–poly(lactic-co-glycolic acid. The resulting particle size was 67.0±1.7 nm, and the zeta potential of the particles was −6.63±0.43 mV. The corneal permeation of iRGD and TAT NPs increased by 5.50- and 4.56-fold compared to that of bare and iRGD-modified NPs, respectively. Cellular uptake showed that the red fluorescence intensity of iRGD and TAT NPs was highest among primary NPs and iRGD- or TAT-modified NPs. CNV was fully formed 14 days after photocoagulation in Brown Norway (BN rats as shown by optical coherence tomography and fundus fluorescein angiography analyses. Choroidal flat mounts in BN rats showed that the red fluorescence intensity of NPs followed the order of iRGD and TAT NPs > TAT-modified NPs > iRGD-modified NPs

  7. Neovascular age-related macular degeneration without drusen in the fellow eye: clinical spectrum and therapeutic outcome

    Directory of Open Access Journals (Sweden)

    Chung WH

    2016-12-01

    Full Text Available Wing H Chung,1 Elon H C van Dijk,1 Danial Mohabati,1 Greet Dijkman,1 Suzanne Yzer,2 Eiko K de Jong,3 Sascha Fauser,4 Reinier O Schlingemann,5–7 Carel B Hoyng,3 Camiel J F Boon1,5 1Department of Ophthalmology, Leiden University Medical Center, Leiden, 2Rotterdam Eye Hospital, Rotterdam, 3Department of Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands; 4Department of Ophthalmology, University Hospital of Cologne, Cologne, Germany; 5Department of Ophthalmology, 6Ocular Angiogenesis Group, Departments of Ophthalmology and Cell Biology and Histology, Academic Medical Center, 7Netherlands Institute for Neuroscience, Amsterdam, the Netherlands Purpose: To investigate the clinical characteristics and therapeutic outcome of patients with neovascular age-related macular degeneration (nAMD in 1 eye, without drusen in the fellow eye. Patients and methods: Medical records of 381 patients were analyzed to identify the cases. The main outcomes included Early Treatment Diabetic Retinopathy Study (ETDRS best-corrected visual acuity (BCVA and change in central retinal thickness (CRT. These parameters were reviewed at baseline, first follow-up visit, and after 6, 12, and 24 months. Results: Out of 381 patients, 29 cases (8% were included (of whom 3 had polypoidal choroidal vasculopathy [PCV] who were treated with anti-vascular endothelial growth factor (anti-VEGF therapy which was supplemented by photodynamic therapy (PDT in the PCV patients. Overall, no statistically significant change in mean BCVA was observed during follow-up. BCVA improved or remained stable (defined as a gain in BCVA, a stable BCVA, or a loss of <5 ETDRS letters in 22 patients (76%, and 7 patients (23% had lost ≥5 ETDRS letters at final follow-up. A gain of ≥15 ETDRS letters at final follow-up was seen in 5 patients (17%. Mean CRT had decreased significantly with 99 µm (P<0.001 at 24 months after the

  8. Intravitreal ranibizumab injection combined trabeculectomy versus Ahmed valve surgery in the treatment of neovascular glaucoma: assessment of efficacy and complications.

    Science.gov (United States)

    Liu, Lan; Xu, Yongfeng; Huang, Zhu; Wang, Xiaoyu

    2016-05-26

    Researches have shown anti-vascular endothelial growth factor (VEGF) agent is effective in treating neovascular eye diseases. The purpose of this study is to evaluate the efficacy and safety of intravitreal ranibizumab (IVR) injection combined trabeculectomy in the treatment of neovascular glaucoma (NVG), and compared it with Ahmed valve surgery. Thirty-six NVG patients (37 eyes) from the First Affiliated Hospital of Zhejiang medical college, between January 1, 2014 and January 31, 2015, were included in this prospective, interventional clinical study. Eighteen NVG eyes were given IVR injection one week before trabeculectomy. Ahmed valve implantation surgery was performed in nineteen eyes. Ocular pain, best corrected visual acuity (BCVA), intraocular pressure (IOP) and surgical complications were evaluated before and after the surgery. IOP was significantly decreased following IVR injection combined trabeculectomy treatment (baseline 57.1 ± 8.9 mmHg; week 1, 15.2 ± 4.3 mmHg p = 0.000; month 1, 16.9 ± 2.1 mmHg p = 0.000; month 3, 20.3 ± 7.7 mmHg p = 0.000; month 6, 19.7 ± 7.3 mmHg p = 0.000). There was a significant, though modest, BCVA improvement in sighted eyes of IVR group (baseline 2.42 ± 0.68, W1 1.80 ± 0.91, P = 0.013; M1 1.77 ± 0.93, p = 0.011). IVR injection combined trabeculectomy had less postoperative complications and lower failure ratio than Ahmed surgery (IVR 5.6 %, Ahmed 31.6 %). The study revealed that IVR injection combined trabeculectomy was an effective and safe treatment for NVG. Compared with Ahmed surgery, IVR injection combined trabeculectomy had less complications and higher success ratio. (Chinese Clinical Registry, TRN ChiCTR-OPN-16008147, 3/24/2016, retrospectively registered).

  9. Successful single treatment with ziv-aflibercept for existing corneal neovascularization following ocular chemical insult in the rabbit model.

    Science.gov (United States)

    Gore, Ariel; Horwitz, Vered; Cohen, Maayan; Gutman, Hila; Cohen, Liat; Gez, Rellie; Kadar, Tamar; Dachir, Shlomit

    2018-03-13

    To evaluate the efficacy of ziv-aflibercept as a treatment for established corneal neovascularization (NV) and to compare its efficacy to that of bevacizumab following ocular chemical insult of sulfur mustard (SM) in the rabbit model. Chemical SM burn was induced in the right eye of NZW rabbits by vapor exposure. Ziv-aflibercept (2 mg) was applied once to neovascularized eyes by subconjunctival injection while subconjunctival bevacizumab (5 mg) was administered twice a week, for 3 weeks. Non-treated exposed eyes served as a control. A clinical follow-up employed by slit-lamp microscope, was performed up to 12 weeks following exposure and digital photographs of the cornea were taken for measurement of blood vessels length using the image analysis software. Eyes were taken for histological evaluation 2, 4 and 8 weeks following treatment for general morphology and for visualization of NV, using H&E and Masson Trichrome stainings, while conjunctival goblet cell density was determined by PAS staining. Corneal NV developed, starting as early as two weeks after exposure. A single subconjunctival treatment of ziv-aflibercept at 4 weeks post exposure, significantly reduced the extent of existing NV already one week following injection, an effect which lasted for at least 8 weeks following treatment, while NV in the non-treated exposed eyes continued to advance. The extensive reduction in corneal NV in the ziv-aflibercept treated group was confirmed by histological evaluation. Bevacizumab multiple treatment showed a benefit in NV reduction, but to a lesser extent compared to the ziv-aflibercept treatment. Finally, ziv-aflibercept increased the density of conjunctival goblet cells as compared to the exposed non-treated group. Subconjunctival ziv-aflibercept single treatment presented a highly efficient long-term therapeutic benefit in reducing existing corneal NV, following ocular sulfur mustard exposure. These findings show the robust anti-angiogenic efficacy of ziv

  10. Investigation of the growth patterns of non-functioning pituitary macroadenomas using volumetric assessments on serial MRI investigations

    Directory of Open Access Journals (Sweden)

    Jaco Pieterse

    2016-07-01

    Full Text Available Background: Benign non-functioning pituitary macroadenomas (NFMA often cause mass effect on the optic chiasm necessitating transsphenoidal surgery to prevent blindness.However, surgery is complicated and there is a high tumour recurrence rate. Currently, very little is known about the natural (and residual post-surgical growth patterns of these NFMA. Conflicting data describe decreased growth to exponential growth over various time periods.Due to lack of information on growth dynamics of these NFMA, suitable follow-up imaging protocols have not been described to date. Objective: To determine if NFMA grow or stay quiescent over a time period using serial MRI investigations and a stereo logical method to determine tumour volume. In addition, to evaluate if NFMA adhere to a certain growth pattern or grow at random. Method: Thirteen patients with NFMA had serial MRI investigations over a 73-month period at the Universitas Academic Hospital. Six of the selected patients had undergone previous surgery, while seven patients had received no medical or surgical intervention. By using astereological method, tumour volumes were calculated and plotted over time to demonstrate growth curves. The data were then fitted to tumour growth models already described in literature in order to obtain the best fit by calculating the r2 value. Results: Positive tumour growth was demonstrated in all cases. Tumour growth patterns of nine patients best fitted the exponential growth curve while the growth patterns of three patients best fitted the logistic growth curve. The remaining patient demonstrated a linear growth pattern. Conclusion: A specific growth model best described tumour growth observed in non-surgical and surgical cases. If follow-up imaging confirms positive growth, future growth can be predicted by extrapolation. This information can then be used to determine the relevant follow-up-imaging interval in each individual patient.

  11. Primary non-function is frequently associated with fatty liver allografts and high mortality after re-transplantation.

    Science.gov (United States)

    Kulik, Ulf; Lehner, Frank; Klempnauer, Jürgen; Borlak, Jürgen

    2017-08-01

    The shortage of liver donations demands the use of suboptimal grafts with steatosis being a frequent finding. Although ≤30% macrovesicular steatosis is considered to be safe the risk for primary non-function (PNF) and outcome after re-transplantation (re-OLT) is unknown. Among 1205 orthotopic liver transplantations performed at our institution the frequency, survival and reason of re-OLT were evaluated. PNF (group A) cases and those with initial transplant function but subsequent need for re-OLT (group B) were analysed. Histopathology and clinical judgement determined the cause of PNF and included an assessment of hepatic steatosis. Additionally, survival of fatty liver allografts (group C) not requiring re-OLT was considered in Kaplan-Meier and multivariate regression analysis. A total of 77 high urgency re-OLTs were identified and included 39 PNF cases. Nearly 70% of PNF cases were due to primary fatty liver allografts. The 3-month in-hospital mortality for PNF cases after re-OLT was 46% and the mean survival after re-OLT was 0.5 years as compared to 5.2 and 5.1 years for group B, C, respectively, (Phepatic steatosis was associated with an inferior survival (HR 4.272, P=.002). The MELD score, donor BMI, age, cold ischaemic time, ICU stay, serum sodium and transaminases did not influence overall survival. Our study highlights fatty liver allografts to be a major cause for PNF with excessive mortality after re-transplantation. The findings demand the development of new methods to predict risk for PNF of fatty liver allografts. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. An evaluation of the effects of somatostatin analogue therapy in non-functioning pituitary adenomas in comparison to acromegaly.

    Science.gov (United States)

    Zawada, Natalia Bożena; Kunert-Radek, Jolanta; Pawlikowski, Marek; Pisarek, Hanna; Radek, Maciej

    2016-01-01

    Non-functioning pituitary adenomas (NFPA) are often diagnosed late as invasive macroadenomas. The surgical resection is usually incomplete and about 50% of patients require additional surgery. Recent data suggest that somatostatin analogues (SSA), so important in the pharmacotherapy of acromegaly, can also be effective in the management of NFPA. We analysed data of patients who had been treated up to 10 years previously with SSA: 40 with acromegaly (23 - primary, 17 - recurrent tumours) and 22 with NFPA (4 - primary, 18 - recurrent tumours). Hormonal profile, dynamics of tumour size change, ophthalmic syndromes, somatostatin receptor (SSTR) scintigraphy, and immunohistochemistry of SSTR subtypes of operated tumours as well as side effects were investigated. Biochemical cure of acromegaly was achieved in 57.5% of patients, while reduction of tumour size was observed in 37% of patients and it was more frequent in not-operated cases. Regarding NFPA, stabilisation of tumour size was noticed in 68% of patients. Tumour shrinkage was reported in 9% of cases, but in 23% of the study group the adenoma size increased with indication for reoperation. The efficacy of SSA in NFPA is much lower in comparison to their well-established effects in the treatment of acromegaly. Stabilisation of tumour size, which is observed in the majority of NFPA, is significantly more frequent in comparison to the natural history of untreated NFPA and our previous studies as well. Analysis of SSTR subtypes is an argument in favour of introduction of novel broad-spectrum SSA that may be more effective in the treatment of NFPA. Referring to acromegaly, adenoma size decrease was reported more frequently in primary therapy. Considering recurrent tumours better outcomes were achieved in patients who were pre-treated with SSA before planned surgery. (Endokrynol Pol 2016; 67 (3): 292-298).

  13. Pigment epithelial detachment followed by retinal cystoid degeneration leads to vision loss in treatment of neovascular age-related macular degeneration.

    Science.gov (United States)

    Schmidt-Erfurth, Ursula; Waldstein, Sebastian M; Deak, Gabor-Gyoergy; Kundi, Michael; Simader, Christian

    2015-04-01

    Intravitreal antiangiogenic therapy is the major therapeutic breakthrough in neovascular age-related macular degeneration (AMD). Optical coherence tomography (OCT) is the leading diagnostic tool, but solid criteria for optimal therapeutic outcomes are lacking. A comprehensive analysis of structure/function correlations using Food and Drug Administration- and European Medicines Agency-approved substances and fixed and flexible regimens was performed. Post hoc analysis of a prospective, randomized multicenter clinical trial including 189 study sites. A total of 1240 patients with active neovascular AMD. Participants received intravitreal ranibizumab or aflibercept. A fixed regimen was used for 48 weeks followed by a flexible regimen until week 96. At monthly intervals, best-corrected visual acuity (BCVA) was measured and retinal morphology was assessed by standardized OCT, including intraretinal cysts (IRCs), subretinal fluid (SRF), and pigment epithelial detachment (PED), presenting with a width ≥400 μm or a height of ≥200 μm. Results were correlated for each regimen, feature, and time. The BCVA outcomes in relation to retinal pathomorphology based on noninferiority for all treatment arms. In neovascular AMD, only IRC at baseline and persistent through week 12 had a negative impact on BCVA. With therapeutic intervention, exudative features such as IRC and SRF resolved rapidly in 74% of eyes, whereas PED responded only slowly with 38%. Independent of the type of regimen, fixed or flexible, retinal morphology correlated tightly with visual function. Intraretinal cysts consistently showed the lowest BCVA gains with either regimen or substance. With the switch from a fixed to a flexible pro re nata (PRN) regimen, progressive visual loss occurred exclusively in the group with primary PED presenting as the hallmark of neovascular activity and was induced by secondary formation of IRC in the neurosensory retina. The efficacy of antiangiogenic therapy in neovascular

  14. The ARMOUR Study: Anti-VEGF in Neovascular AMD--Our Understanding in a Real-World Indian Setting.

    Science.gov (United States)

    Jain, Nimesh; Yadav, Naresh Kumar; Jayadev, Chaitra; Srinivasan, Priya; Mohan, Ashwin; Shetty, Bhujang K

    2017-01-01

    The aim of our study was to share our experience with anti-vascular endothelial growth factor (anti-VEGF) injections in the treatment of neovascular age-related macular degeneration (nAMD) in a real-world setting. A retrospective, observational study. Patients of Indian origin with nAMD receiving anti-VEGF with a minimum follow-up of 12 months were enrolled in this study. In group 1, patients were treated on a pro re nata (PRN) basis; in group 2, patients received a loading dose (3 injecti Results: Overall, we observed that 77.31% (92/119 eyes) of patients either maintained or had improved visual acuity at 12 months' follow-up. Similar visual outcome was observed in both groups. The average number of injections given in group 1 was 4.98 and in group 2 was 3.7. CDVA at 12 months was significantly correlated with type of drug molecule, CSFT at 3 and 12 months, baseline visual acuity, and CDVA at 3 months. PRN treatment with significantly fewer injections achieved similar anatomical and functional outcomes when compared with the loading dose group. The results of this study need to be validated with a larger study group and a longer follow-up. Copyright 2017 Asia-Pacific Academy of Ophthalmology.

  15. Edaravone is a free radical scavenger that protects against laser-induced choroidal neovascularization in mice and common marmosets.

    Science.gov (United States)

    Masuda, Tomomi; Shimazawa, Masamitsu; Takata, Shinsuke; Nakamura, Shinsuke; Tsuruma, Kazuhiro; Hara, Hideaki

    2016-05-01

    Choroidal neovascularization (CNV) is a main characteristic in exudative type of age-related macular degeneration (AMD). Our study aimed to evaluate the effects of edaravone, a free radical scavenger on laser-induced CNV. CNV was induced by laser photocoagulation to the subretinal choroidal area of mice and common marmosets. Edaravone was administered either intraperitoneally twice a day for 2 weeks or intravenously just once after laser photocoagulation. The effects of edaravone on laser-induced CNV were evaluated by fundus fluorescein angiography, CNV area measurements, and the expression of 4-hydroxy-2-nonenal (4-HNE) modified proteins, a marker of oxidative stress. Furthermore, the effects of edaravone on the production of H2O2-induced reactive oxygen species (ROS) and vascular endothelial growth factor (VEGF)-induced cell proliferation were evaluated using human retinal pigment epithelium cells (ARPE-19) and human retinal microvascular endothelial cells, respectively. CNV areas in the edaravone-treated group were significantly smaller in mice and common marmosets. The expression of 4-HNE modified proteins was upregulated 3 h after laser photocoagulation, and intravenously administered edaravone decreased it. In in vitro studies, edaravone inhibited H2O2-induced ROS production and VEGF-induced cell proliferation. These findings suggest that edaravone may protect against laser-induced CNV by inhibiting oxidative stress and endothelial cell proliferation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Impact of Lycium Barbarum Polysaccharide and Danshensu on vascular endothelial growth factor in the process of retinal neovascularization of rabbit

    Directory of Open Access Journals (Sweden)

    Xue-Min Tian

    2013-02-01

    Full Text Available AIM:To discuss the impact of Lycium Barbarum Polysaccharide (LBP and Danshensu purified from Traditional Chinese Medicine (TCM on vascular endothelial growth factor (VEGF of rabbits with retinal neovascularization.METHODS:Forty rabbits were divided into normal control group, model control group, LBP group and Danshensu group. Animals in the normal control group were fed in the normal oxygen environment. Animals in the other three groups were put into the environment with 70% oxygen for 5 days in order to build the model of oxygen-induced vascular proliferation retinopathy. And then different TCM extract was injected into the abdominal cavities of these annimals. After 7 days, the VEGF content of in the serum of rabbit was measured by double antibody sandwich method.RESULTS:Data analysis indicated that VEGF content was as follows:Danshensu group was lower than model control group (12.92±3.84ng/L vs 19.32±4.15ng/L, Pvs 19.32±4.15ng/L, P<0.01; total blood viscosity, plasma viscosity, cholesterol content, fibrinogen content and triacylglycerol content after peritoneal injection of LBP and Danshensu were obviously lower than before injection.CONCLUSION:TCM extract-LBP and Danshensu can prominently reduce the content of VEGF in the process of vascular proliferative retinopathy of rabbit; can prevent the occurrence of retinal microvascular disease by improving partial oxygen-deficient environment or affecting all kinds of new growth factor.

  17. Quantitative evaluation of experimental choroidal neovascularization by confocal scanning laser ophthalmoscopy: fluorescein angiogram parallels heparan sulfate proteoglycan expression

    Directory of Open Access Journals (Sweden)

    C.V. Regatieri

    2010-07-01

    Full Text Available The objective of the present study was to develop a quantitative method to evaluate laser-induced choroidal neovascularization (CNV in a rat model using Heidelberg Retina Angiograph 2 (HRA2 imaging. The expression of two heparan sulfate proteoglycans (HSPG related to inflammation and angiogenesis was also investigated. CNV lesions were induced with argon laser in 21 heterozygous Zucker rats and after three weeks a fluorescein angiogram and autofluorescence exams were performed using HRA2. The area and greatest linear dimension were measured by two observers not aware of the protocol. Bland-Altman plots showed agreement between the observers, suggesting that the technique was reproducible. After fluorescein angiogram, HSPG (perlecan and syndecan-4 were analyzed by real-time RT-PCR and immunohistochemistry. There was a significant increase in the expression of perlecan and syndecan-4 (P < 0.0001 in retinas bearing CNV lesions compared to control retinas. The expression of these two HSPG increased with increasing CNV area. Immunohistochemistry demonstrated that the rat retina damaged with laser shots presented increased expression of perlecan and syndecan-4. Moreover, we observed that the overexpression occurred in the outer layer of the retina, which is related to choroidal damage. It was possible to develop a standardized quantitative method to evaluate CNV in a rat model using HRA2. In addition, we presented data indicating that the expression of HSPG parallels the area of CNV lesion. The understanding of these events offers opportunities for studies of new therapeutic interventions targeting these HSPG.

  18. Anti-vascular endothelial growth factors for choroidal neovascularization secondary to choroidal osteoma: Long-term results

    Directory of Open Access Journals (Sweden)

    T Lekha

    2015-01-01

    Full Text Available Choroidal osteoma is an uncommon benign osseous intraocular tumor typically seen unilaterally in young women. Visual loss can occur due to choroidal neovascularization (CNV complicating osteoma. We report a rare case of bilateral choroidal osteoma with secondary CNV in a young male and the long-term results following anti-vascular endothelial growth factor (VEGF therapy. A 30-year-old male with history of defective vision in both eyes since several years and recent worsening in the right eye (RE since 2 months was found to have bilateral macular osteoma with CNV in the RE based on clinical evaluation, fluorescein angiography, optical coherence tomography, and ultrasonography. Intravitreal injection of ranibizumab at monthly intervals for three doses resulted in resolution of CNV and remained stable for 5 years. Recurrent CNV detected 6 years later responded to an injection of intravitreal bevacizumab and has remained stable till date. Anti-VEGF therapy stabilized the secondary CNV in our patient for 7 years with satisfactory structural and functional outcome, demonstrating the long-term efficacy of this modality of treatment.

  19. A Delphi Study to Detect Deficiencies and Propose Actions in Real Life Treatment of Neovascular Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Alfredo García-Layana

    2014-01-01

    Full Text Available Purpose. Spanish retina specialists were surveyed in order to propose actions to decrease deficiencies in real-life neovascular age macular degeneration treatment (nv-AMD. Methods. One hundred experts, members of the Spanish Vitreoretinal Society (SERV, were invited to complete an online survey of 52 statements about nv-AMD management with a modified Delphi methodology. Four rounds were performed using a 5-point Linkert scale. Recommendations were developed after analyzing the differences between the results and the SERV guidelines recommendations. Results. Eighty-seven specialists completed all the Delphi rounds. Once major potential deficiencies in real-life nv-AMD treatment were identified, 15 recommendations were developed with a high level of agreement. Consensus statements to reduce the burden of the disease included the use of treat and extend regimen and to reduce the amount of diagnostic tests during the loading phase and training technical staff to perform these tests and reduce the time between relapse detection and reinjection, as well as establishing patient referral protocols to outside general ophthalmology clinics. Conclusion. The level of agreement with the final recommendations for nv-AMD treatment among Spanish retinal specialist was high indicating that some actions could be applied in order to reduce the deficiencies in real-life nv-AMD treatment.

  20. Photodynamic monotherapy or combination treatment with intravitreal triamcinolone acetonide, bevacizumab or ranibizumab for choroidal neovascularization associated with pathological myopia

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    Pukhraj Rishi

    2011-01-01

    Full Text Available This retrospective, interventional case series analyses treatment outcomes in eyes with choroidal neovascularization (CNV secondary to pathological myopia, managed with photodynamic therapy, (PDT, (Group 1, N = 11, PDT and intravitreal triamcinolone acetonide (4 mg/0.1ml (Group 2, N = 3, PDT and intravitreal anti-vascular endothelial growth factor (anti-VEGF bevacizumab 1.25 mg/0.05 ml, ranibizumab 0.5 mg/0.05 ml and reduced-fluence PDT and intravitreal ranibizumab 0.5 mg/0.05 ml (Group 3, N=12. All the patients underwent PDT. Intravitreal injections were repeated as required. SPSS 14 software was used to evaluate the data. Wilcoxon signed ranks test was used to evaluate pre- and post-treatment vision. The Kruskal-Wallis test was used for comparison between the groups. All the groups were statistically comparable. All the eyes showed complete regression of CNV, with a minimum follow-up of six months. All groups had visual improvement; significantly in Group 3 ( p = 0.003. Combination PDT with anti-VEGF agents appeared to be efficacious in eyes with myopic CNV. However, a larger study with a longer follow-up is required to validate these results.

  1. Intravitreal Ranibizumab Injection as an Adjuvant in the Treatment of Neovascular Glaucoma Accompanied by Vitreous Hemorrhage after Diabetic Vitrectomy

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    Xi Shen

    2016-01-01

    Full Text Available Purpose. To determine the efficacy of intravitreal ranibizumab injection as adjuvant therapy in the treatment of neovascular glaucoma (NVG accompanied by postvitrectomy diabetic vitreous hemorrhage (PDVH. Methods. Eighteen NVG patients (18 eyes accompanied by PDVH were enrolled in this prospective, monocenter, 12-month, interventional case series. The consecutive 18 patients with an IOP ≥ 25 mmHg despite being treated with the maximum medical therapy were treated with intravitreal ranibizumab injections. Vitreous surgery or/with Ahmed valve implantation were indicated if no clinical improvement in vitreous haemorrhage and uncontrolled IOP was shown. Results. Ten patients got clear vitreous and controlled IOP only with 2.7±1.8 injections of ranibizumab without additional surgery. Vitrectomy or/with Ahmed valve implantation was administered in the other 8 eyes due to uncontrolled VH and IOP. At follow-up month 12, all the 18 eyes gained clear vitreous. At month 12 BCVA improved significantly compared to baseline. The baseline and follow-up at month 12 IOP/medication usage were 36.7±8.1 mmHg on 3.4±0.7 medications and 16.2±4.9 mmHg on 0.67±0.77 medications, respectively. Conclusions. The findings suggest that intravitreal ranibizumab injection as adjuvant therapy for treatment of NVG accompanied by PDVH may be safe and potentially effective. This clinical trial is registered with NCT02647515.

  2. Evolution of Choroidal Neovascularization due to Presumed Ocular Histoplasmosis Syndrome on Multimodal Imaging including Optical Coherence Tomography Angiography

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    T. Y. Alvin Liu

    2018-01-01

    Full Text Available A 37-year-old Caucasian woman presented with acute decrease in central vision in her right eye and was found to have subfoveal choroidal neovascularization (CNV due to presumed ocular histoplasmosis syndrome (POHS. Her visual acuity improved from 20/70 to 20/20 at her 6-month follow-up, after 3 consecutive monthly intravitreal bevacizumab injections were initiated at her first visit. Although no CNV activity was seen on fluorescein angiography (FA or spectral-domain optical coherence tomography (SD-OCT at her 2-month, 4-month, and 6-month follow-up visits, persistent flow in the CNV lesion was detected on optical coherence tomography angiography (OCTA. OCTA shows persistent vascular flow as well as changes in vascular flow in CNV lesions associated with POHS, indicating the continued presence of patent vessels and changes in these CNV lesions, even when traditional imaging of the lesion with OCT and FA indicates stability of the lesion with no disease activity. Additional cases with longitudinal follow-up are needed to assess how OCTA should be incorporated into clinical practice.

  3. Modulating release of ranibizumab and aflibercept from thiolated chitosan-based hydrogels for potential treatment of ocular neovascularization.

    Science.gov (United States)

    Moreno, Miguel; Pow, Poh Yih; Tabitha, Tan Su Teng; Nirmal, Sonali; Larsson, Andreas; Radhakrishnan, Krishna; Nirmal, Jayabalan; Quah, Soo Tng; Geifman Shochat, Susana; Agrawal, Rupesh; Venkatraman, Subbu

    2017-08-01

    This paper describes the synthesis of thiolated chitosan-based hydrogels with varying degrees of crosslinking that has been utilized to modulate release kinetics of two clinically relevant FDA-approved anti-VEGF protein drugs, ranibizumab and aflibercept. These hydrogels have been fabricated into disc shaped structures for potential use as patches on ocular surface. Protein conformational changes and aggregation after loading and release was evaluated by circular dichroism (CD), steady-state tryptophan fluorescence spectroscopy, electrophoresis and size-exclusion chromatography (SEC). Finally, the capacity of both released proteins to bind to VEGF was tested by ELISA and surface plasmon resonance (SPR) technology. The study demonstrates the versatility of thiolated chitosan-based hydrogels for delivering proteins. The effect of various parameters of the hydrogel on protein release kinetics and mechanism of protein release was studied using the Korsmeyer-Peppas release model. Furthermore, we have studied the stability of released proteins in detail while comparing it with non-entrapped proteins under physiological conditions to understand the effect of formulation conditions on protein stability. The disc-shaped thiolated chitosan-based hydrogels provide a potentially useful platform to deliver ranibizumab and aflibercept for the treatments of ocular diseases such as wet AMD, DME and corneal neovascularization.

  4. Repeatability of swept-source optical coherence tomography retinal and choroidal thickness measurements in neovascular age-related macular degeneration

    DEFF Research Database (Denmark)

    Hanumunthadu, Daren; Ilginis, Tomas; Restori, Marie

    2017-01-01

    BACKGROUND: The aim was to determine the intrasession repeatability of swept-source optical coherence tomography (SS-OCT)-derived retinal and choroidal thickness measurements in eyes with neovascular age-related macular degeneration (nAMD). METHODS: A prospective study consisting of patients...... with active nAMD enrolled in the Distance of Choroid Study at Moorfields Eye Hospital, London. Patients underwent three 12×9 mm macular raster scans using the deep range imaging (DRI) OCT-1 SS-OCT (Topcon) device in a single imaging session. Retinal and choroidal thicknesses were calculated for the ETDRS...... macular subfields. Repeatability was calculated according to methods described by Bland and Altman. RESULTS: 39 eyes of 39 patients with nAMD were included with a mean (±SD) age of 73.9 (±7.2) years. The mean (±SD) retinal thickness of the central macular subfield was 225.7 μm (±12.4 μm...

  5. Epidemiological and Clinical Baseline Characteristics as Predictive Biomarkers of Response to Anti-VEGF Treatment in Patients with Neovascular AMD

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    Miltiadis K. Tsilimbaris

    2016-01-01

    Full Text Available Purpose. To review the current literature investigating patient response to antivascular endothelial growth factor-A (VEGF therapy in the treatment of neovascular age-related macular degeneration (nAMD and to identify baseline characteristics that might predict response. Method. A literature search of the PubMed database was performed, using the keywords: AMD, anti-VEGF, biomarker, optical coherence tomography, treatment outcome, and predictor. The search was limited to articles published from 2006 to date. Exclusion criteria included phase 1 trials, case reports, studies focusing on indications other than nAMD, and oncology. Results. A total of 1467 articles were identified, of which 845 were excluded. Of the 622 remaining references, 47 met all the search criteria and were included in this review. Conclusion. Several baseline characteristics correlated with anti-VEGF treatment response, including best-corrected visual acuity, age, lesion size, and retinal thickness. The majority of factors were associated with disease duration, suggesting that longer disease duration before treatment results in worse treatment outcomes. This highlights the need for early treatment for patients with nAMD to gain optimal treatment outcomes. Many of the identified baseline characteristics are interconnected and cannot be evaluated in isolation; therefore multivariate analyses will be required to determine any specific relationship with treatment response.

  6. Monitoring performance, pituitary-adrenal hormones and mood profiles : how to diagnose non-functional over-reaching in male elite junior soccer players

    NARCIS (Netherlands)

    Schmikli, Sandor L.; de Vries, Wouter R.; Brink, Michel S.; Backx, Frank J. G.

    2012-01-01

    Objective To verify if in male elite junior soccer players a minimum 1-month performance decrease is accompanied by a mood profile and hormone levels typical of non-functional over-reaching (NFOR). Design A prospective case-control study using a monthly performance monitor with a standardised field

  7. Can we detect non-functional overreaching in young elite soccer players and middle-long distance runners using field performance tests?

    NARCIS (Netherlands)

    Schmikli, S. L.; Brink, M. S.; de Vries, W. R.; Backx, F. J. G.

    Objective To study whether field performance tests can make a valid distinction between non-functionally overreaching (NFO) athletes and control athletes. Design Monthly field performance tests were used to determine a performance decrement (PD) throughout a season. Athletes with a minimum of 1

  8. Aflibercept treatment for neovascular AMD beyond the first year: consensus recommendations by a UK expert roundtable panel, 2017 update

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    Patel PJ

    2017-11-01

    Full Text Available Praveen J Patel,1 Helen Devonport,2 Sobha Sivaprasad,1 Adam H Ross,3 Gavin Walters,4 Richard P Gale,5 Andrew J Lotery,6 Sajjad Mahmood,7 James S Talks,8 Jackie Napier9 1National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK; 2The Ophthalmology Department, Bradford Royal Infirmary, Bradford, UK; 3The Ophthalmology Department, Bristol Eye Hospital, Bristol, UK; 4Department of Ophthalmology, Harrogate District Hospital, Harrogate, UK; 5The Ophthalmology Department, The York Hospital and Department of Health Sciences, University of York, York, UK; 6Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK; 7Manchester Royal Eye Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK; 8Newcastle Eye Centre, Royal Victoria Infirmary, Newcastle upon Tyne, UK; 9Medical Affairs, Bayer plc, Reading, Berkshire, UK Abstract: National recommendations on continued administration of aflibercept solution for injection after the first year of treatment for neovascular age-related macular degeneration (nAMD have been developed by an expert panel of UK retina specialists, based on clinician experience and treatment outcomes seen in year 2. The 2017 update reiterates that the treatment goal is to maintain or improve the macular structural and functional gains achieved in year 1 while attempting to reduce or minimize the treatment burden, recognizing the need for ongoing treatment. At the end of year 1 (ie, the decision visit at month 11, two treatment options should be considered: do not extend the treatment interval and maintain fixed 8-weekly dosing, or extend the treatment interval using a treat-and-extend regimen up to a maximum 12 weeks. Criteria for considering not extending the treatment interval are persistent macular fluid with stable

  9. A phytomodulatory hydrogel with enhanced healing effects.

    Science.gov (United States)

    Vasconcelos, Mirele S; Souza, Tamiris F G; Figueiredo, Ingrid S; Sousa, Emília T; Sousa, Felipe D; Moreira, Renato A; Alencar, Nylane M N; Lima-Filho, José V; Ramos, Márcio V

    2018-04-01

    The healing performance of a hydrogel composed of hemicelluloses extracted from seeds of Caesalpinia pulcherrima (Fabaceae) and mixed with phytomodulatory proteins obtained from the latex of Calotropis procera was characterized on excisional wounds. The hydrogel did not induce dermal irritability. When topically used on excisional wounds, the hydrogel enhanced healing by wound contraction. Histology and the measurement of inflammatory mediators (myeloperoxidase, interleukin-1β, and interleukin-6) suggested that the inflammatory phase of the healing process was intensified, stimulating fibroplasia and neovascularization (proliferative phase) and tissue remodeling by increasing new collagen fiber deposition. In addition, reduction on levels of malondialdehyde in the groups that the hydrogel was applied suggested that the oxidative stress was reduced. The hydrogel performed better than the reference drug used, as revealed by the extended thickness of the remodeled epithelium. Copyright © 2018 John Wiley & Sons, Ltd.

  10. R102G polymorphism of the complement component 3 gene in Malaysian subjects with neovascular age-related macular degeneration

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    Nur Afiqah Mohamad

    2018-04-01

    Full Text Available Background: Genetic and environmental factors are known to be risk factors in development of neovascular age-related macular degeneration (nAMD. Genetic factors such as polymorphisms in the complement component pathway genes might play a role in pathogenesis of nAMD and has been studied in various populations excluding Malaysia. Aim of the study: To determine the association of the R102G polymorphism of the complement component (C3 gene in nAMD subjects. Patients and methods: A total of 301 Malaysian subjects (149 case and 152 controls were recruited and genotyped for the R102G (rs2230199 variant of the C3 gene. Genotyping was conducted using the PCR-RFLP method and association analysis was conducted using appropriate statistical tests. Results: From our findings, no significant association was observed in the allele distribution of C3 R102G between nAMD and controls (OR = 1.42, 95% CI = 0.77–2.62, P = 0.268. A further analysis that compared three genetic models (dominant, recessive and co-dominant also recorded no significant difference (P > 0.05. These findings could be due to the low frequency of the GG variant in the case (4.7% and control (1.3% groups, compared to the normal variant CC, which is present in 91.3% of case and 92.8% of control alleles. Conclusion: The present study showed no evidence of association between C3 R102G polymorphism and nAMD in Malaysian subjects. Keywords: Age-related macular degeneration, Complement component 3, C3 gene, R102G gene polymorphism

  11. Metallothionein polymorphisms in a Northern Spanish population with neovascular and dry forms of age-related macular degeneration.

    Science.gov (United States)

    García, Montserrat; Álvarez, Lydia; Fernández, Ángela; González-Iglesias, Héctor; Escribano, Julio; Fernández-Vega, Beatriz; Villota, Eva; Fernández-Vega Cueto, Luis; Fernández-Vega, Álvaro; Coca-Prados, Miguel

    2017-01-01

    To elucidate the potential role of single nucleotide polymorphisms (SNPs) in the metallothionein (MT) genes in Northern Spanish patients with age-related macular degeneration (AMD). A total of 130 unrelated Northern Spanish natives diagnosed with AMD (46 dry, 35 neovascular, and 49 mixed) and 96 healthy controls, matched by age and ethnicity, were enrolled in a case-control study. DNA was isolated from peripheral blood and genotyped for 14 SNPs located at 5 MT genes (MT1A: rs11076161, rs 11640851, rs8052394, and rs7196890; MT1B: rs8052334, rs964372, and rs7191779; MT1M: rs2270836 and rs9936741; MT2A: rs28366003, rs1610216, rs10636, and rs1580833; MT3: rs45570941) using TaqMan probes. The association study was performed using the HaploView 4.0 software. The allelic and genotypic frequencies analysis revealed that rs28366003 at MT2A gene is significantly associated with dry AMD. The frequency of genotype AG was significantly higher in dry AMD than in control cases (p = 2.65 × 10 -4 ; AG vs. AA) conferring more than ninefold increased risk to dry AMD (OR = 9.39, 95% CI: 2.11-41.72), whereas the genotype AA confers disease protection (OR = 0.82, 95% CI: 0.71-0.95). No statistically significant differences were observed between AMD subjects and controls in the rest of the 14 SNPs analyzed. The present study is the first to investigate the potential association of SNPs at MT genes with susceptibility to AMD. We found a significant association of SNP rs28366003 at MT2A gene with susceptibility to the dry form of AMD in a Northern Spanish population.

  12. Treatment satisfaction of patients undergoing ranibizumab therapy for neovascular age-related macular degeneration in a real-life setting

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    Gohil R

    2016-05-01

    Full Text Available Rishma Gohil,1,2 Roxanne Crosby-Nwaobi,1,2 Angus Forbes,2 Ben J Burton,3 Philip Hykin,1 Sobha Sivaprasad1,4 1National Institute for Health Research Moorfields Biomedical Research Centre, London, 2Diabetes Nursing, King’s College London, London, 3Ophthalmology Department, James Paget University Hospital, Great Yarmouth, 4Laser and Retinal Research Unit, King’s College Hospital, London, UK Context: Treatment satisfaction with a loading phase of monthly injections for 3 months followed by a pro-re-nata regimen of ranibizumab in neovascular age-related macular degeneration (nAMD remains unclear.Aims: The aim was to evaluate the treatment satisfaction of persons with nAMD treated with ranibizumab in a real-life setting.Settings and design: A cross-sectional study was conducted across three eye clinics within the National Health Service in the UK, where treatment is provided free at point of contact.Materials and methods: A total of 250 patients were selected randomly for the study. Treatment satisfaction was assessed using the Macular Treatment Satisfaction Questionnaire. Data were collected on satisfaction of the service provided (Client Service Questionnaire-8 and the patients’ demographic and quality of life and treatment history. Factors governing treatment questionnaire were determined.Results: The most important factors that determined the satisfaction were the service provided at the clinic (Client Service Questionnaire-8, health-related quality of life (EQ-5D-3L, and duration of AMD. Visual acuity changes were rated as less important than one would have expected.Conclusion: The study result suggested that treatment satisfaction for nAMD was governed by the perception of being reviewed and injected regularly over a long period of time than the actual change in visual acuity from the treatment. Keyword: macular treatment satisfaction questionnaire, patient related outcome measure, treatment history, quality of life 

  13. Anterior Segment Optical Coherence Tomography Angiography for Identification of Iris Vasculature and Staging of Iris Neovascularization: A Pilot Study.

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    Roberts, Philipp K; Goldstein, Debra A; Fawzi, Amani A

    2017-08-01

    Purpose/Aim of the study: To assess the ability of optical coherence tomographic angiography (OCTA) to visualize the normal iris vasculature as well as neovascularization of the iris (NVI). Study participants with healthy eyes, patients at risk of NVI development and patients with active or regressed NVI were consecutively included in this cross-sectional observational study. Imaging was performed using a commercially available OCTA system (RTVue- XR Avanti, Optovue Inc., Fremont, CA, USA). Abnormal iris vessels were graded on OCTA according to a modified clinical staging system and compared to slitlamp and gonioscopic findings. Fifty eyes of 26 study participants (16 healthy eyes, 19 eyes at risk, 15 eyes with different stages of NVI) were imaged using OCTA. In 11 out of 16 healthy eyes (69%) with light or moderately dark iris pigmentation, we observed physiological, radially aligned iris vasculature on OCTA imaging, which could not be visualized in five eyes (31%) with darkly pigmented irides. One eye in the "eyes at risk" group was diagnosed with NVI based on OCTA, which was not observed clinically. Fifteen eyes with clinically active or regressed NVI were imaged. Different stages of NVI could be differentiated by OCTA, corresponding well to an established clinical grading system. Four eyes showed regressed NVI by OCTA, not seen clinically, and were graded as a newly defined stage 4. This pilot clinical study showed that OCTA for imaging of the iris vasculature in health and disease is highly dependent on iris pigmentation. Fine, clinically invisible iris vessels can be visualized by OCTA in the very early stages as well as in the regressed stage of NVI.

  14. Adeno-Associated Viral Vector-Mediated mTOR Inhibition by Short Hairpin RNA Suppresses Laser-Induced Choroidal Neovascularization

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    Tae Kwann Park

    2017-09-01

    Full Text Available Choroidal neovascularization (CNV is the defining characteristic feature of the wet subtype of age-related macular degeneration (AMD and may result in irreversible blindness. Based on anti-vascular endothelial growth factor (anti-VEGF, the current therapeutic approaches to CNV are fraught with difficulties, and mammalian target of rapamycin (mTOR has recently been proposed as a possible therapeutic target, although few studies have been conducted. Here, we show that a recombinant adeno-associated virus-delivered mTOR-inhibiting short hairpin RNA (rAAV-mTOR shRNA, which blocks the activity of both mTOR complex 1 and 2, represents a promising therapeutic approach for the treatment of CNV. Eight-week-old male C57/B6 mice were treated with the short hairpin RNA (shRNA after generating CNV lesions in the eyes via laser photocoagulation. The recombinant adeno-associated virus (rAAV delivery vehicle was able to effectively transduce cells in the inner retina, and significantly fewer inflammatory cells and less extensive CNV were observed in the animals treated with rAAV-mTOR shRNA when compared with control- and rAAV-scrambled shRNA-treated groups. Presumably related to the reduction of CNV, increased autophagy was detected in CNV lesions treated with rAAV-mTOR shRNA, whereas significantly fewer apoptotic cells detected in the outer nuclear layer around the CNV indicate that mTOR inhibition may also have neuroprotective effects. Taken together, these results demonstrate the therapeutic potential of mTOR inhibition, resulting from rAAV-mTOR shRNA activity, in the treatment of AMD-related CNV. Keywords: retinal neovascularization, choroidal neovascularization, adeno-associated virus, mTOR, RNA interference, mTOR shRNA, autophagy

  15. Effect of ranibizumab on high-speed indocyanine green angiography and minimum intensity projection optical coherence tomography findings in neovascular age-related macular degeneration.

    Science.gov (United States)

    Nicholson, Benjamin P; Nigam, Divya; Toy, Brian; Stetson, Paul F; Agrón, Elvira; Jacobs-El, Naima; Cunningham, Denise; Cukras, Catherine; Wong, Wai; Wiley, Henry; Chew, Emily; Ferris, Frederick; Meyerle, Catherine B

    2015-01-01

    The purpose of this 1-year prospective study was to investigate how induction/pro re nata ranibizumab intravitreal treatment of eyes with neovascular age-related macular degeneration affects the anatomy of choroidal neovascularization (CNV) and the overlying outer retinal tissue. High-speed indocyanine green (HS-ICG) angiography measurements provided quantification of the CNV size in 60 patients followed for 1 year. Minimum intensity projection optical coherence tomography (MinIP OCT), a novel algorithm assessing minimum optical intensity between the internal limiting membrane and retinal pigment epithelium, measured the area of outer retinal disruption overlying the CNV. Fluorescein angiography was also assessed to evaluate late retinal leakage. After 1 year, the mean area of CNV measured with indocyanine green angiography decreased by 5.8%. The mean area of MinIP OCT of outer retinal disruption overlying the CNV decreased by 4.2%. Mean area of fluorescein angiography leakage decreased by 6.3%. Both the area of outer retinal disruption measured with MinIP OCT and the area of leakage on fluorescein angiography typically exceeded the area of CNV on indocyanine green angiography at baseline and 1 year. Choroidal neovascularization treated with induction/pro re nata intravitreal ranibizumab for 1 year essentially remained static. Minimum intensity projection optical coherence tomography suggests that the area of outer retinal disruption overlying the CNV may be greater than the CNV itself and often correlates with the leakage area on fluorescein angiography. Additionally, there was minimal change in the area of outer retinal disruption on MinIP OCT even when fluid resolved. Measurements of the extent of CNV lesions based on indocyanine green angiography and MinIP OCT may provide useful outcome variables to help assess the CNV complex longitudinally and warrant further validation.

  16. Efficacy of treat-and-extend regimen with aflibercept for pachychoroid neovasculopathy and Type 1 neovascular age-related macular degeneration.

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    Matsumoto, Hidetaka; Hiroe, Takashi; Morimoto, Masahiro; Mimura, Kensuke; Ito, Arisa; Akiyama, Hideo

    2018-03-01

    To evaluate the efficacy of intravitreal aflibercept therapy using a treat-and-extend regimen on treatment-naïve pachychoroid neovasculopathy (PNV) and Type 1 neovascular age-related macular degeneration (AMD). We retrospectively studied 42 eyes with PNV and 60 eyes with Type 1 neovascular AMD. We assessed best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), and total number of injections over 2 years. The BCVA and CMT improvements during the 2-year treatment period did not differ significantly between PNV and AMD; however, CCT decreased significantly in PNV than in AMD (P<0.05). Management of PNV required significantly fewer injections than AMD during the 2-year period (P<0.05). There were no significant differences in BCVA, CMT and CCT changes between PNV with and without polypoidal lesions (28 vs. 14 eyes) during the 2 year period. Significantly fewer injections were needed for PNV with polypoidal lesions than for PNV without (P<0.01). There were no significant differences in BCVA, CMT and CCT changes, or in the number of injections during the 2-year treatment period, between AMD with and without polypoidal lesions (30 vs. 30 eyes). Treat-and-extend regimen of intravitreal aflibercept injection may be equally effective in terms of improvement of BCVA and exudative changes both in eyes with PNV and those with Type 1 neovascular AMD requiring fewer injections for the former. Among eyes with PNV, those with polypoidal lesions needed fewer injections than those without polypoidal lesions.

  17. Epigalloccatechin-3-gallate Inhibits Ocular Neovascularization and Vascular Permeability in Human Retinal Pigment Epithelial and Human Retinal Microvascular Endothelial Cells via Suppression of MMP-9 and VEGF Activation

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    Hak Sung Lee

    2014-08-01

    Full Text Available Epigalloccatechin-3-gallate (EGCG is the main polyphenol component of green tea (leaves of Camellia sinensis. EGCG is known for its antioxidant, anti-inflammatory, antiviral, and anti-carcinogenic properties. Here, we identify EGCG as a new inhibitor of ocular angiogenesis and its vascular permeability. Matrix metalloproteinases (MMPs and vascular endothelial growth factor (VEGF play a key role in the processes of extracellular matrix (ECM remodeling and microvascular permeability during angiogenesis. We investigated the inhibitory effects of EGCG on ocular neovascularization and vascular permeability using the retina oriented cells and animal models induced by VEGF and alkaline burn. EGCG treatment significantly decreased mRNA and protein expression levels of MMP-9 in the presence of 12-O-tetradecanoylphorbol-13-acetate (TPA and tumor necrosis factor alpha (TNF-α in human retinal pigment epithelial cells (HRPECs. EGCG also effectively protected ARPE-19 cells from cell death and attenuated mRNA expressions of key angiogenic factors (MMP-9, VEGF, VEGF Receptor-2 by inhibiting generation of reactive oxygen species (ROS. EGCG significantly inhibited proliferation, vascular permeability, and tube formation in VEGF-induced human retinal microvascular endothelial cells (HRMECs. Furthermore, EGCG significantly reduced vascular leakage and permeability by blood-retinal barrier breakdown in VEGF-induced animal models. In addition, EGCG effectively limited upregulation of MMP-9 and platelet endothelial cell adhesion molecule (PECAM/CD31 on corneal neovascularization (CNV induced by alkaline burn. Our data suggest that MMP-9 and VEGF are key therapeutic targets of EGCG for treatment and prevention of ocular angiogenic diseases such as age-related macular degeneration, diabetic retinopathy, and corneal neovascularization.

  18. Choroidal neovascularization associated with sympathetic ophthalmia: case report Neovascularização coroidiana associada à oftalmia simpática: relato de caso

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    Raul Nunes Galvarro Vianna

    2005-06-01

    Full Text Available A 7-year-old boy with sympathetic ophthalmia secondary to penetrating ocular trauma developed choroidal neovascularization in the macular region of the sympathizing eye. Posterior segment biomicroscopy disclosed a single, round, small, slightly elevated yellow-white lesion temporal to the fovea, linked to the temporal edge of the optic disc by a fibrotic band. On fluorescein angiography the round lesion showed a gradual hyperfluorescence, with late staining and leakage, and was interpreted as a fibrovascular scar from previous choroidal neovascularization. Despite intense immunosuppressive therapy, the patient's final visual acuity was 20/400. Although rarely associated with sympathetic ophthalmia, choroidal neovascularization and its cicatricial stages can occur and compromise the visual prognosis of an already debilitated eye. The best course of treatment for choroidal neovascularization in these types of cases has not yet been determined.Paciente com oftalmia simpática (OS desenvolveu neovascularização coroidiana (NVC na região macular do olho simpatizado. A biomicroscopia do segmento posterior do olho afetado revelou uma pequena lesão branco-amarelada, discretamente elevada, localizada na região temporal à fóvea. Uma banda fibrosa ligava o disco óptico à lesão foveal. À angiografia fluoresceínica, a lesão revelou hiperfluorescência progressiva, com impregnação e extravazamento tardio do corante, achados esses característicos de uma cicatriz fibrovascular. Apesar de intenso tratamento com medicação imunossupressora, a acuidade visual final do paciente foi de 20/400. Embora raramente associada à oftalmia simpática a neovascularização coroidiana pode ocorrer e comprometer o prognóstico visual de um olho já debilitado. A melhor opção para o tratamento da neovascularização coroidiana em casos de oftalmia simpática ainda não está determinada.

  19. Efficacy and safety of intravitreal ranibizumab with panretinal photocoagulation followed by trabeculectomy compared with Ahmed glaucoma valve implantation in neovascular glaucoma

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    Jin-Tao Sun

    2017-03-01

    Full Text Available AIM: To evaluate the efficacy and safety of intravitreal ranibizumab (IVR with panretinal photocoagulation (PRP followed by trabeculectomy compared with Ahmed glaucoma valve (AGV implantation in neovascular glaucoma (NVG. METHODS: This was a retrospective comparative study. We reviewed the cases of a total of 45 eyes from 45 NVG patients among which 23 eyes underwent AGV implantation and the other 22 underwent trabeculectomy. The causes of neovascular glaucoma included: diabetic retinopathy (25 eyes, and retinal vein occlusion (20 eyes. All patients received preoperative IVR combined with postoperative PRP. The mean best-corrected visual acuities (BCVA were converted to the logarithms of the minimum angle of resolution (logMAR for the statisitical analyses. Intraocular pressure (IOP, the logMAR BCVA and surgical complications were evaluated before and after surgery. The follow-up period was 12mo. RESULTS: A total of 39 cases showed complete regression of iris neovascularization at 7d after injection, and 6 cases showed a small amount of residual iris neovascularization. The success rates were 81.8% and 82.6% at 12mo after trabeculectomy and AGV implantation, respectively. In the trabeculectomy group, the logMAR BCVA improved at the last follow-up in 14 eyes, remained stable in 6 eyes and decreased in 2 eyes. In 4 cases, slight hyphemas developed after trabeculectomy. A shallow anterior chamber developed in 2 cases and 2 vitreous hemorrhages. In the AGV group, the logMAR BCVA improved in 14 eyes, remained stable in 5 eyes and decreased in 4 eyes. Slight hyphemas developed in 3 cases, and a shallow anterior chamber in 3 cases. The mean postoperative IOP was significantly lower in both groups after surgery (F=545.468, P<0.05, and the mean postoperative logMAR BCVA was also significantly improved (F=10.964, P<0.05 with no significant difference between two groups. CONCLUSION: It is safe and effective to treat NVG with this combined procedure, and we

  20. Krypton laser treatment of neovascularization in retinal vein occlusion%氪激光治疗视网膜静脉阻塞的新生血管

    Institute of Scientific and Technical Information of China (English)

    吴又凯; 武志峰; 张清

    2001-01-01

    Objective To investigate the method and effect of krypton laser photocoagulation for neovascularization in retinal vein occlusion. Methods Tweenty eight eyes of 27 patients with retinal vein occlusion with neovascularization were photocoagulated by krypton-green and-red laser.The fundus changes were observed by fundus fluorescein angiography after photocoagulation. Results The neovascularization disappeared completely in 20 eyes and became smaller in 6 eyes,remained no-change in 2 eyes,and the visual acuity improved in 17 eyes (60.7%) after 6 monthes to 2.5 years of follow-up. Conclusion Krypton laser photocoagulation is obviously effective on regression of neovascularization and prevenion of vitreous hemorrhage in retinal vein occlusion.%目的探讨氪激光治疗视网膜静脉阻塞新生血管的方法和疗效。方法对27例视网膜静脉阻塞伴有新生血管的28只患眼采用氪绿、氪红激光进行光凝治疗。光凝后经6个月~2.5年随访,对比分析光凝前后的荧光素眼底血管造影及视力变化情况。结果新生血管萎缩20只眼,占71.4%,好转6只眼,占21.4%,无效2只眼,占7.2%。视力进步17只眼,占60.7%。结论氪激光光凝术对视网膜静脉阻塞新生血管的消退及预防其玻璃体积血具有显著疗效。

  1. Surgical Outcome of Endoscopic Endonasal Surgery for Non-Functional Pituitary Adenoma by a Team of Neurosurgeons and Otolaryngologists Adenoma by a Team of Neurosurgeons and Otolaryngologists.

    Science.gov (United States)

    Kikuchi, Ryogo; Toda, Masahiro; Tomita, Toshiki; Ogawa, Kaoru; Yoshida, Kazunari

    2017-01-01

    This study aimed to assess the efficacy of endoscopic endonasal surgery, conducted by a team of neurosurgeons and otolaryngologists. We studied 40 patients who were undergoing surgery for primary non-functional pituitary adenomas with Knosp grades 1 to 3, at Keio University Hospital between 2005 and 2012. We compared the endoscopic endonasal transsphenoidal approach (team-eTSS; T-eTSS), with a microscopic transsphenoidal approach (mTSS). Analyses were conducted for differences between the two groups in tumor resection rates, operating durations, and complications from the non-functional pituitary adenomas. We also compared the heminostril and binostril approaches for T-eTSS. Tumor resection rates were higher when the surgeries were conducted by T-eTSS than mTSS. In particular, when the maximum tumor diameter was more than 25 mm, resection rates were significantly higher for T-eTSS than for mTSS. There were no unexpected complications in either group. There was no significant difference in resection rates between the heminostril and binostril approaches when T-eTSS was performed. T-eTSS is an efficacious surgical option for non-functional pituitary adenomas, particularly when the adenoma is of large size. Benefits of the heminostril approach are evident.

  2. A novel platelet lysate hydrogel for endothelial cell and mesenchymal stem cell-directed neovascularization.

    Science.gov (United States)

    Robinson, Scott T; Douglas, Alison M; Chadid, Tatiana; Kuo, Katie; Rajabalan, Ajai; Li, Haiyan; Copland, Ian B; Barker, Thomas H; Galipeau, Jacques; Brewster, Luke P

    2016-05-01

    Mesenchymal stem cells (MSC) hold promise in promoting vascular regeneration of ischemic tissue in conditions like critical limb ischemia of the leg. However, this approach has been limited in part by poor cell retention and survival after delivery. New biomaterials offer an opportunity to localize cells to the desired tissue after delivery, but also to improve cell survival after delivery. Here we characterize the mechanical and microstructural properties of a novel hydrogel composed of pooled human platelet lysate (PL) and test its ability to promote MSC angiogenic activity using clinically relevant in vitro and in vivo models. This PL hydrogel had comparable storage and loss modulus and behaved as a viscoelastic solid similar to fibrin hydrogels despite having 1/4-1/10th the fibrin content of standard fibrin gels. Additionally, PL hydrogels enabled sustained release of endogenous PDGF-BB for up to 20days and were resistant to protease degradation. PL hydrogel stimulated pro-angiogenic activity by promoting human MSC growth and invasion in a 3D environment, and enhancing endothelial cell sprouting alone and in co-culture with MSCs. When delivered in vivo, the combination of PL and human MSCs improved local tissue perfusion after 8days compared to controls when assessed with laser Doppler perfusion imaging in a murine model of hind limb ischemia. These results support the use of a PL hydrogel as a scaffold for MSC delivery to promote vascular regeneration. Innovative strategies for improved retention and viability of mesenchymal stem cells (MSCs) are needed for cellular therapies. Human platelet lysate is a potent serum supplement that improves the expansion of MSCs. Here we characterize our novel PL hydrogel's desirable structural and biologic properties for human MSCs and endothelial cells. PL hydrogel can localize cells for retention in the desired tissue, improves cell viability, and augments MSCs' angiogenic activity. As a result of these unique traits, PL

  3. Transcriptome Profiling of Neovascularized Corneas Reveals miR-204 as a Multi-target Biotherapy Deliverable by rAAVs

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    Yi Lu

    2018-03-01

    Full Text Available Corneal neovascularization (NV is the major sight-threatening pathology caused by angiogenic stimuli. Current drugs that directly target pro-angiogenic factors to inhibit or reverse the disease require multiple rounds of administration and have limited efficacies. Here, we identify potential anti-angiogenic corneal microRNAs (miRNAs and demonstrate a framework that employs discovered miRNAs as biotherapies deliverable by recombinant adeno-associated viruses (rAAVs. By querying differentially expressed miRNAs in neovascularized mouse corneas induced by alkali burn, we have revealed 39 miRNAs that are predicted to target more than 5,500 differentially expressed corneal mRNAs. Among these, we selected miR-204 and assessed its efficacy and therapeutic benefit for treating injured corneas. Our results show that delivery of miR-204 by rAAV normalizes multiple novel target genes and biological pathways to attenuate vascularization of injured mouse cornea. Importantly, this gene therapy treatment alternative is efficacious and safe for mitigating corneal NV. Overall, our work demonstrates the discovery of potential therapeutic miRNAs in corneal disorders and their translation into viable treatment alternatives.

  4. Intravitreal injection of (99)Tc-MDP inhibits the development of laser-induced choroidal neovascularization in rhesus monkeys.

    Science.gov (United States)

    Lai, Kunbei; Jin, Chenjin; Tu, Shu; Xiong, Yunfan; Huang, Rui; Ge, Jian

    2014-07-01

    The aim of this study was to investigate the safety and efficacy of intravitreal injection of (99)Tc-MDP, a decay product of (99m)Tc-MDP, on the development of laser-induced choroidal neovascularization (CNV) in rhesus monkeys. Experimental CNV was induced by argon laser with a small high-energy laser spot. Monkeys were given 50 μL of (99)Tc-MDP at a concentration of 0.005 μg/mL (n = 6) or 0.01 μg/mL (n = 6) by intravitreal injection once a week immediately after laser injury for a period of 56 days. Control animals were treated with the same volume of PBS (n = 6) in the same way. Eyes were monitored by ophthalmic examination, color fundus photography, fluorescence fundus angiography (FFA), optical coherence tomography (OCT) and histology. Incidences of grade 4 CNV lesions as well as the leakage areas of grade 4 CNVs on the late-phase of fluorescein angiograms were measured in a standardized, randomized and masked fashion fortnightly. The maximum widths and heights of grade 4 CNVs were also calculated by histology at the end of the experiment. Toxicity of (99)Tc-MDP on the retina was evaluated by electroretinogram (ERG) and histologic analysis. (99)Tc-MDP reduced the incidences of grade 4 CNVs by 33.33 % and 39.40 % in the 0.005 μg/mL and 0.01 μg/mL groups, respectively, compared with the PBS group on day 28 (P 99)Tc-MDP treated groups than those in the PBS group. Although intravitreal injection of (99)Tc-MDP led to mild inflammatory reaction in the anterior chamber, histology and ERG findings demonstrated that (99)Tc-MDP did not cause any change in histological structure or function of the retina (p>0.05). Intravitreal injection of (99)Tc-MDP can inhibit the development of laser-induced CNV without toxic effect on retina, suggesting that (99)Tc-MDP has therapeutic potential for CNV related diseases.

  5. A Quantitative and Standardized Method for the Evaluation of Choroidal Neovascularization Using MICRON III Fluorescein Angiograms in Rats.

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    Jonathan P Wigg

    Full Text Available In-vivo imaging of choroidal neovascularization (CNV has been increasingly recognized as a valuable tool in the investigation of age-related macular degeneration (AMD in both clinical and basic research applications. Arguably the most widely utilised model replicating AMD is laser generated CNV by rupture of Bruch's membrane in rodents. Heretofore CNV evaluation via in-vivo imaging techniques has been hamstrung by a lack of appropriate rodent fundus camera and a non-standardised analysis method. The aim of this study was to establish a simple, quantifiable method of fluorescein fundus angiogram (FFA image analysis for CNV lesions.Laser was applied to 32 Brown Norway Rats; FFA images were taken using a rodent specific fundus camera (Micron III, Phoenix Laboratories over 3 weeks and compared to conventional ex-vivo CNV assessment. FFA images acquired with fluorescein administered by intraperitoneal injection and intravenous injection were compared and shown to greatly influence lesion properties. Utilising commonly used software packages, FFA images were assessed for CNV and chorioretinal burns lesion area by manually outlining the maximum border of each lesion and normalising against the optic nerve head. Net fluorescence above background and derived value of area corrected lesion intensity were calculated.CNV lesions of rats treated with anti-VEGF antibody were significantly smaller in normalised lesion area (p < 0.001 and fluorescent intensity (p < 0.001 than the PBS treated control two weeks post laser. The calculated area corrected lesion intensity was significantly smaller (p < 0.001 in anti-VEGF treated animals at 2 and 3 weeks post laser. The results obtained using FFA correlated with, and were confirmed by conventional lesion area measurements from isolectin stained choroidal flatmounts, where lesions of anti-VEGF treated rats were significantly smaller at 2 weeks (p = 0.049 and 3 weeks (p < 0.001 post laser.The presented method of in

  6. Subthreshold transpupillary thermotherapy reduces experimental choroidal neovascularization in the mouse without collateral damage to the neural retina.

    Science.gov (United States)

    Ming, Yue; Algvere, Peep V; Odergren, Anne; Berglin, Lennart; van der Ploeg, Ingeborg; Seregard, Stefan; Kvanta, Anders

    2004-06-01

    Transpupillary thermotherapy (TTT) is currently being evaluated for treatment of choroidal neovascularization (CNV) in age-related macular degeneration. To optimize TTT for CNV, the effect was analyzed of invisible (subthreshold) or visible (threshold) doses of TTT on the normal mouse retina and on experimental CNV. TTT was delivered to the normal retina of 42 mice with a diode laser at increasing power settings (50, 60, 70, or 80 mW), to obtain thermal lesions ranging from invisible (subthreshold) to visible (threshold) burns. CNV was induced in 53 mice by krypton laser photocoagulation of the fundus, after which the CNV lesions were treated with TTT (50, 60, or 80 mW). Eyes were enucleated 7 days after TTT and prepared for histology, and the CNV complex was evaluated on hematoxylin-eosin stained serial sections by measuring the maximum height of the CNV lesions. Ultrastructural changes were examined by transmission electron microscopy. Increasing the TTT laser power yielded gradually more visible effects. At 50 mW, which induced subthreshold burns, no damage was seen in the neural retina, retinal pigment epithelium (RPE), or choroid at any time point. By contrast, eyes treated with higher power exhibited progressively more damage to the neural retina, including a complete disruption of the outer nuclear layer. When TTT was applied to the laser-induced CNV lesions, the height of lesions was significantly reduced (P response to all three power settings at 7 days after treatment. The mean relative thickness of the CNV lesion was 3.29 +/- 0.89 in untreated mice, whereas in TTT-treated mice it was 1.69 +/- 0.35, 1.69 +/- 0.41 and 1.70 +/- 0.17 at power settings of 50, 60, and 80 mW, respectively. The overlying neural retina showed no apparent damage with the 50- or 60-mW settings, whereas outer nuclear layer disruption occurred with a power of 80 mW. Electron microscopy confirmed the presence of vascular occlusion at 1 day and a fibrotic scar at 7 days after TTT

  7. Incidence of choroidal neovascularization in the fellow eye in the comparison of age-related macular degeneration treatments trials.

    Science.gov (United States)

    Maguire, Maureen G; Daniel, Ebenezer; Shah, Ankoor R; Grunwald, Juan E; Hagstrom, Stephanie A; Avery, Robert L; Huang, Jiayan; Martin, Revell W; Roth, Daniel B; Castellarin, Alessandro A; Bakri, Sophie J; Fine, Stuart L; Martin, Daniel F

    2013-10-01

    To assess the influence of drug; dosing regimen; and traditional, nontraditional, and genetic risk factors on the incidence of choroidal neovascularization (CNV) in the fellow eye of patients treated for CNV with ranibizumab or bevacizumab. Cohort study of patients enrolled in a multicenter, randomized clinical trial. Patients with no CNV in the fellow eye at the time of enrollment in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT). Eligibility criteria for the clinical trial required that study eyes have evidence on fluorescein angiography and optical coherence tomography of CNV secondary to age-related macular degeneration (AMD) and visual acuity between 20/25 and 20/320. Treatment for the study eye was assigned randomly to either ranibizumab or bevacizumab and to 3 different regimens for dosing over a 2-year period. The genotypes for 4 single nucleotide polymorphisms (SNPs) associated with risk of AMD were determined. Only patients without CNV in the fellow eye at baseline were considered at risk. The CATT ophthalmologists examined patients every 4 weeks through 2 years and recorded treatment for CNV in the fellow eye. Development of CNV in the fellow eye. Among 1185 CATT participants, 727 (61%) had no CNV in the fellow eye at enrollment. At 2 years, CNV had developed in 75 (20.6%) of 365 patients treated with ranibizumab and in 60 (16.6%) of 362 patients treated with bevacizumab (absolute difference, 4.0%; 95% confidence interval [CI], -1.7% to 9.6%; P = 0.17). The risk ratio for pro re nata dosing relative to monthly dosing was 1.1 (95% CI, 0.8-1.6). Greater elevation of the retinal pigment epithelium and fluid in the foveal center of the study eye were associated with increased incidence of CNV in the fellow eye. Incidence was not associated with genotype on rs1061170 (CFH), rs10490924 (ARMS2), rs11200638 (HTRA1), and rs2230199 (C3; P>0.35). Through 2 years, there was no statistically significant difference between ranibizumab and

  8. Treatment for neovascular age-related macular degeneration in Sweden: outcomes at seven years in the Swedish Macula Register.

    Science.gov (United States)

    Westborg, Inger; Granstam, Elisabet; Rosso, Aldana; Albrecht, Susanne; Karlsson, Niklas; Lövestam-Adrian, Monica

    2017-12-01

    To present Swedish Macula Register (SMR) data regarding treatment of neovascular age-related macular degeneration (AMD) in clinical practice since 2008. A retrospective register-based study was conducted. Evaluation of baseline demographics, visual outcome and number of injections during this period is presented. Mean age at diagnosis was 79 ± (SD) 8 years; 65% were female. The proportion of patients with <2 months' duration of symptoms increased from 26% in 2008 to 41% in 2014 (p = 0.001). Mean visual acuity (VA) at baseline increased from 54.3 ± 15.0 early treatment diabetic retinopathy study (ETDRS) letters in 2008 to 57.8 ± 15.6 letters in 2014 (CI 95 2.6; 4.3; p < 0.001). Mean VA after 1 year of treatment increased from 57.8 ± 17.7 ETDRS letters for patients who started the treatment in 2008 to 62.8 ± 16.4 ETDRS letters in patients starting treatment in 2014 (CI 95 2.67; 4.64; p < 0.001). During all study years, the proportion of patients with an improvement in VA of between 5 and 15 letters was around 30%, while 14% had VA improvement of more than 15 letters. The mean number of injections during the first treatment year increased from 4.3 ± 1.9 in 2008 to 5.9 ± 2.9 in 2014 (CI 95 1.40; 1.67; p < 0.001). Seven-year follow-up of 322 eyes showed a mean change of -1 letters from baseline, with a mean of 21 injections for the entire period. The duration of symptoms before treatment decreased, while VA at baseline and after 1 year of treatment increased over the years and so did the number of injections. Long-term follow-up demonstrated stable VA. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  9. Enhanced adhesion of early endothelial progenitor cells to radiation-induced senescence-like vascular endothelial cells in vitro

    International Nuclear Information System (INIS)

    Sermsathanasawadi, N.; Inoue, Yoshinori; Iwai, Takehisa; Ishii, Hideto; Yoshida, Masayuki; Igarashi, Kaori; Miura, Masahiko

    2009-01-01

    The effects of ionizing radiation (IR) on tumor neovascularization are still unclear. We previously reported that vascular endothelial cells (ECs) expressing the IR-induced senescence-like (IRSL) phenotype exhibit a significant decrease in angiogenic activity in vitro. In this study, we examined the effects of the IRSL phenotype on adhesion to early endothelial progenitor cells (early EPCs). Adhesion of human peripheral blood-derived early EPCs to human umbilical vein endothelial cells (HUVECs) expressing the IRSL phenotype was evaluated by an adhesion assay under static conditions. It was revealed that the IRSL HUVECs supported significantly more adhesion of early EPCs than normal HUVECs. Expressions of ICAM-1, VCAM-1 and E-selectin were up-regulated in IRSL HUVECs. Pre-treatment of IRSL HUVECs with adhesion-blocking monoclonal antibodies against E-selectin and VCAM-1 significantly reduced early EPC adhesion to IRSL HUVECs, suggesting a potential role for the E-selectin and VCAM-1 in the adhesion between IRSL ECs and early EPCs. Therefore, the IRSL phenotype expressed in ECs may enhance neovascularization via increased homing of early EPCs. Our findings are first to implicate the complex effects of this phenotype on tumor neovascularization following irradiation. (author)

  10. Cytomegalovirus and BK-Virus co-infection of a clinically non-functioning adrenal adenoma: innocent bystanders or new pathogenetic agents?

    Science.gov (United States)

    Pomara, G; Cappello, F; Barzon, L; Morelli, G; Rappa, F; Benvegna, L; Giannarini, G; Palù, G; Selli, C

    2006-01-01

    We report a case of a 64-year-old woman who underwent left adrenalectomy with removal of a 8,5 cm clinically non-functioning adrenocortical adenoma and a 4-cm myelolipoma. Molecular testing for viral infection demonstrated the presence of cytomegalovirus (CMV) DNA sequences in the adrenal adenoma, but not in the myelolipoma (confirmed by immunohistochemistry). Moreover, the adrenal adenoma was also positive for parvovirus B19, and both adrenal tumor samples were positive for polyomavirus BK (BKV) and adenovirus DNA sequences. This is the first report of co-infection of an adrenocortical adenoma by CMV and BKV. The role of these viruses in adrenal tumorigenesis was postulated.

  11. Candida albicans endophthalmitis in a patient with a non-functioning pituitary adenoma evolving into Cushing׳s disease: A case report

    Directory of Open Access Journals (Sweden)

    Eun Kyoung Lee

    2014-10-01

    Full Text Available A 53-year-old woman presented with complaints of blurred vision in the left eye. She had been treated for recurrent non-functioning pituitary adenoma (NFPA. A vitreous biopsy followed by histopathologic examination showed the presence of Candida albicans. Meanwhile, Cushing׳s disease was diagnosed and gamma knife surgery was performed. Vitrectomy and antifungal treatment improved ocular infection and inflammation. Herein, we describe the first case of C. albicans endophthalmitis in a patient with NFPA evolving into Cushing׳s disease.

  12. Myopic Choroidal Neovascularization

    DEFF Research Database (Denmark)

    Cheung, Chui Ming Gemmy; Arnold, Jennifer J; Holz, Frank G

    2017-01-01

    ) therapies have had a major impact on the management of patients with myopic CNV, there remain significant gaps in our understanding of this condition and how to best administer treatment. Additionally, the long-term safety and efficacy of these treatments are largely unknown. METHODS: We carried out...

  13. Monitoring performance, pituitary-adrenal hormones and mood profiles: how to diagnose non-functional over-reaching in male elite junior soccer players.

    Science.gov (United States)

    Schmikli, Sándor L; de Vries, Wouter R; Brink, Michel S; Backx, Frank Jg

    2012-11-01

    To verify if in male elite junior soccer players a minimum 1-month performance decrease is accompanied by a mood profile and hormone levels typical of non-functional over-reaching (NFOR). A prospective case-control study using a monthly performance monitor with a standardised field test to detect the performance changes. Players with a performance decrease lasting at least 1 month were compared with control players without a performance decrease on mood scores and pre-exercise and postexercise levels of stress hormones. Sporting field and sports medical laboratory. Ninety-four young elite soccer players were monitored during the 2006-2008 seasons. Twenty-one players were invited to the laboratory, seven of whom showed a significant performance decrease. Performance change over time, scores on the profile of mood states and premaximal and postmaximal exercise serum levels of adrenocorticotropic hormone (ACTH), growth hormone (GH) and cortisol. Players with a performance decrease showed psychological and hormonal changes typical of the non-functional state of over-reaching. Scores were higher on depression and anger, whereas the resting GH levels and ACTH levels after maximal exercise were reduced. ACTH and GH were capable of classifying all but one player correctly as either NFOR or control. Performance-related criteria in field tests are capable of identifying players with worsened mood and adaptations of the endocrine system that fit the definition of NFOR. Performance, mood and hormone levels may therefore be considered as valid instruments to diagnose NFOR in young elite soccer players.

  14. Indium-111 labelled platelet scintigraphy can predict the immunological origin of fever in patients on dialysis carrying a non-functioning renal allograft

    International Nuclear Information System (INIS)

    Fuster, D.; Lomena, F.; Piera, C.; Setoain, F.J.; Laterza, C.; Herranz, R.; Setoain, J.; Torregrosa, J.V.; Oppenheimer, F.

    2000-01-01

    The purpose of this study was to evaluate the usefulness of labelled platelet scintigraphy in the differential diagnosis of a prolonged febrile syndrome (PFS) in patients on dialysis carrying a non-functioning renal allograft. We prospectively performed an indium-111 mercaptopyridine-labelled platelet scan on 91 patients (54 men, 37 women; mean age 39.6±12 years). The mean duration of PFS was 35 days (range 7-122). Forty-six of the 91 patients underwent steroid therapy (2- 10 mg/day). Platelet labelling was carried out following Thakur's method. Platelet scans were performed 48 h after reinjection of labelled platelets. The platelet uptake index (PUI) was calculated by dividing the cpm/pixel in the allograft ROI by cpm/pixel in a mirror background ROI. The final diagnosis of PFS was established depending on the outcome after treatment. In 61/91 patients the fever had an immunological origin because it disappeared after graft embolisation or transplantectomy. In 30/91 patients the PFS disappeared after antibiotic therapy (non-immunological origin). The PUI in patients with immunological PFS was 1.80±0.7, while in patients with non-immunological PFS it was 1.12±0.1 (P 111 In-labelled platelet scintigraphy can accurately predict an immunological PFS in patients on dialysis carrying a non-functioning renal allograft. Therapy with steroids could reduce the sensitivity of 111 In-labelled platelet scintigraphy in detecting immunological PFS. (orig.)

  15. Atomic layer deposited highly dispersed platinum nanoparticles supported on non-functionalized multiwalled carbon nanotubes for the hydrogenation of xylose to xylitol

    Science.gov (United States)

    Liang, Xinhua; Jiang, Chengjun

    2013-09-01

    Highly dispersed platinum nanoparticles were deposited on gram quantities of non-functionalized multiwalled carbon nanotubes (MWCNTs) by atomic layer deposition (ALD) in a fluidized bed reactor at 300 °C. (Methylcyclopentadienyl) trimethylplatinum and oxygen were used as precursors. The results of TEM analysis showed that 1.3 nm Pt nanoparticles were highly dispersed on non-functionalized MWCNTs. The porous structures of MWCNTs did not change with the deposition of Pt nanoparticles. For comparison, the commercial 3 wt% Pt/C catalyst was also characterized. The ALD-prepared Pt/MWCNT was used for the hydrogenation of xylose to xylitol. The ALD-prepared Pt/MWCNT showed the best catalytic performance with 100 % conversion of xylose and 99.3 % selectivity to xylitol, compared to commercially available Pt/C, Ru/C, and Raney Ni catalysts. The stability of ALD produced Pt/MWCNT catalyst was higher than that of the commercial Pt/C, due to the presence of surface defects on the MWCNTs and the strong metal-support interaction for the ALD-prepared Pt/MWCNT catalyst.

  16. Atomic layer deposited highly dispersed platinum nanoparticles supported on non-functionalized multiwalled carbon nanotubes for the hydrogenation of xylose to xylitol

    Energy Technology Data Exchange (ETDEWEB)

    Liang, Xinhua, E-mail: liangxin@mst.edu [Missouri University of Science and Technology, Department of Chemical and Biochemical Engineering (United States); Jiang, Chengjun [Zhejiang University of Science and Technology, Department of Chemical and Biological Engineering (China)

    2013-09-15

    Highly dispersed platinum nanoparticles were deposited on gram quantities of non-functionalized multiwalled carbon nanotubes (MWCNTs) by atomic layer deposition (ALD) in a fluidized bed reactor at 300 Degree-Sign C. (Methylcyclopentadienyl) trimethylplatinum and oxygen were used as precursors. The results of TEM analysis showed that {approx}1.3 nm Pt nanoparticles were highly dispersed on non-functionalized MWCNTs. The porous structures of MWCNTs did not change with the deposition of Pt nanoparticles. For comparison, the commercial 3 wt% Pt/C catalyst was also characterized. The ALD-prepared Pt/MWCNT was used for the hydrogenation of xylose to xylitol. The ALD-prepared Pt/MWCNT showed the best catalytic performance with 100 % conversion of xylose and 99.3 % selectivity to xylitol, compared to commercially available Pt/C, Ru/C, and Raney Ni catalysts. The stability of ALD produced Pt/MWCNT catalyst was higher than that of the commercial Pt/C, due to the presence of surface defects on the MWCNTs and the strong metal-support interaction for the ALD-prepared Pt/MWCNT catalyst.

  17. Middle-preserving pancreatectomy for advanced transverse colon cancer invading the duodenun and non-functioning endocrine tumor in the pancreatic tail.

    Science.gov (United States)

    Noda, Hiroshi; Kato, Takaharu; Kamiyama, Hidenori; Toyama, Nobuyuki; Konishi, Fumio

    2011-02-01

    A 73-year-old female was referred to our hospital with a diagnosis of advanced transverse colon cancer with severe anemia and body weight loss. Preoperative evaluations, including colonoscopy, gastroduodenoscopy, and computed tomography, revealed not only a transverse colon cancer massively invading the duodenum, but also a non-functioning endocrine tumor in the pancreatic tail. We performed middle-preserving pancreatectomy (MPP) with right hemicolectomy for these tumors with a curative intent. After the resection, about 6 cm of the body of the pancreas was preserved, and signs of diabetes mellitus have not appeared. The postoperative course was complicated by a grade B pancreatic fistula, but this was successfully treated with conservative management. After a 33-day hospital stay, the patient returned to daily life without signs of pancreatic exocrine insufficiency. Although the long-term follow-up of the patient is indispensable, in this case, MPP might be able to lead to the curative resection of transverse colon cancer massively invading the duodenum and non-functioning endocrine tumor in the pancreatic tail with preservation of pancreatic function.

  18. TNF-α mediates choroidal neovascularization by upregulating VEGF expression in RPE through ROS-dependent β-catenin activation.

    Science.gov (United States)

    Wang, Haibo; Han, Xiaokun; Wittchen, Erika S; Hartnett, M Elizabeth

    2016-01-01

    Inflammation, oxidative stress, and angiogenesis have been proposed to interact in age-related macular degeneration. It has been postulated that external stimuli that cause oxidative stress can increase production of vascular endothelial growth factor (VEGF) in retinal pigment epithelial (RPE) cells. In this study, we tested the hypothesis that the inflammatory cytokine, tumor necrosis factor alpha (TNF-α), contributed to choroidal neovascularization (CNV) by upregulating VEGF in RPE through intracellular reactive oxygen species (ROS)-dependent signaling and sought to understand the mechanisms involved. In a murine laser-induced CNV model, 7 days after laser treatment and intravitreal neutralizing mouse TNF-α antibody or isotype immunoglobulin G (IgG) control, the following measurements were made: 1) TNF-α protein and VEGF protein in RPE/choroids with western blot, 2) CNV volume in RPE/choroidal flatmounts, and 3) semiquantification of oxidized phospholipids stained with E06 antibody within CNV with immunohistochemistry (IHC). In cultured human RPE cells treated with TNF-α or PBS control, 1) ROS generation was measured using the 2',7'-dichlorodihydrofluorescein diacetate (DCFDA) fluorescence assay, and 2) NOX4 protein and VEGF protein or mRNA were measured with western blot or quantitative real-time PCR in cells pretreated with apocynin or nicotinamide adenine dinucleotide phosphate-oxidase (NADPH) inhibitor, VAS 2870, or transfected with p22phox siRNA, and each was compared to its appropriate control. Western blots of phosphorylated p65 (p-p65), total p65 and β-actin, and quantitative real-time PCR of VEGF mRNA were measured in human RPE cells treated with TNF-α and pretreatment with the nuclear factor kappa B inhibitor, Bay 11-7082 or control. Western blots of β-catenin, VEGF, and p22phox and coimmunoprecipitation of β-catenin and T-cell transcriptional factor were performed in human RPE cells treated with TNF-α following pretreatment with

  19. Combined Transpupillary Thermotherapy with Subtenon Triamcinolone Injection in Treatment of Choroidal Neovascularization Secondary to Exudative Age Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    M Naseripour

    2008-04-01

    Full Text Available ABSTRACT: Introduction & Objective: In spite of several treatment methods which are being used to treat exudative age-related macular degeneration (ARMD like laser therapy, Intravitreal steroids injections or anti-vascular endothelial growth factors (VEGF, no method has been yet presented as the best treatment way. This study aimed to assess the effectiveness of combined transpupillary thermotherapy (TTT with subtenon triamcinolone acetonide (TA injection in treatment of choroidal neovascularization (CNV in patients with ARMD. Materials & Methods: In this clinical trial, 63 eyes of 57 patients with CNV secondary to exudative age-related macular degeneration (ARMD were studied. All CNVs (including 20 predominantly classic and 43 predominantly occult lesions were treated with diode laser (810nm. In 20 eyes with predominantly classic CNVs, 20 mg and 40 mg subtenon triamcinolone was injected in 12 and 8 eyes respectively. The patients were followed for a mean of 9.1 months (ranging from 5.5 to 16 months. The average number of treatment sessions was 1.25. In 43 eyes with occult CNV, 20 mg and 40 mg subtenon triamcinolone was injected in 31 eyes and in 12 eyes respectively. Mean follow up time was 12 months (4.5 to 23 months. Mean treatment times was 1.17. A variable spot size of 0.8, 1.2, 2 and 3 mm was used depending on the size of CNV and treatment was given in one area for 1 minute. Thermotherapy was adminstered through a contact lens at a power range between 120-560 mw. At the end of treatment, each patient randomly received 20 mg or 40 mg subtenon triamcinolone acetonide injection in superotemporal quadrant. Outcome was assessed with clinical and angiographic examination.collected data were analyzed by one-sample and paired –sample T test, using SPSS software. Results: At the end of the study in first group, visual acuity remained stable (0 to ± one line in 14 out of 20 (70 % of eyes, improved (> one line in 2 of 20 (10 % eyes and showed a

  20. Effect of integrin α5β1 inhibition on SDF-l/CXCR4- mediated choroidal neovascularization

    Directory of Open Access Journals (Sweden)

    Yang Lyu

    2018-05-01

    Full Text Available AIM: To investigate the roles of integrins in choroidal neovascularization (CNV and their associations with the stromal cell-derived factor-1 (SDF-1/CXCR4 axis. METHODS: CNV lesions were induced in mice using laser photocoagulation. After CNV induction, all animals were randomly assigned to: control, SDF-1, SDF-1+age-related macular degeneration (AMD 3100 (CXCR4 inhibitor, and SDF-1+ATN161 (integrin α5β1 inhibitor groups; their effects on CNV progression were observed using hematoxylin eosin (HE staining, fundus fluorescein angiography (FFA grading and optical coherence tomography (OCT, and their effects on CXCR4/integrin α5 expression were evaluated using Western blot and double immunofluorescence staining. Hypoxia-exposed endothelial cells (ECs were used to simulate CNV in vitro, they were treated with SDF-1, combined with CXCR4 siRNA/AMD3100 or ATN161, and expression of integrin α5, cell migration and tube formation were analyzed. RESULTS: Integrin subunit α5 increased at 3rd and 7th day and decreased at 14th day in CNV mice, with no significant change of β1-integrin. CXCR4 expression in CNV mice had persistent increase within 14d after induction. SDF-1 treatment significantly promoted the CNV progression during 3-14d. The mean CNV length in AMD3100 and ATN161 group at day 7 was 270.13 and 264.23 μm in HE images, significantly lower than the mean length in SDF-1 (345.70 μm group. AMD3100 and ATN161 also significantly reduced thickness and leakage of CNV induced by SDF-1. Mean integrin α5 positive area in SDF-1 group reached 2.31×104 μm2, significantly higher than control (1.25×104 μm2, which decreased to 1.78×104 μm2 after AMD3100 treatment. About 61.36% of ECs in CNV lesions expressed α5 in SDF-1 group, which significantly decreased to 43.12% after AMD3100 treatment. In vitro, integrin α5 peaked by 6 folds after 6h of hypoxia exposure and CXCR4 gradually increased by up to 2.3 folds after 24h of hypoxia. Approximately 25

  1. Intravitreous injection of AAV2-sFLT01 in patients with advanced neovascular age-related macular degeneration: a phase 1, open-label trial.

    Science.gov (United States)

    Heier, Jeffrey S; Kherani, Saleema; Desai, Shilpa; Dugel, Pravin; Kaushal, Shalesh; Cheng, Seng H; Delacono, Cheryl; Purvis, Annie; Richards, Susan; Le-Halpere, Annaig; Connelly, John; Wadsworth, Samuel C; Varona, Rafael; Buggage, Ronald; Scaria, Abraham; Campochiaro, Peter A

    2017-07-01

    Long-term intraocular injections of vascular endothelial growth factor (VEGF)-neutralising proteins can preserve central vision in many patients with neovascular age-related macular degeneration. We tested the safety and tolerability of a single intravitreous injection of an AAV2 vector expressing the VEGF-neutralising protein sFLT01 in patients with advanced neovascular age-related macular degeneration. This was a phase 1, open-label, dose-escalating study done at four outpatient retina clinics in the USA. Patients were assigned to each cohort in order of enrolment, with the first three patients being assigned to and completing the first cohort before filling positions in the following treatment groups. Patients aged 50 years or older with neovascular age-related macular degeneration and a baseline best-corrected visual acuity score of 20/100 or less in the study eye were enrolled in four dose-ranging cohorts (cohort 1, 2 × 10 8 vector genomes (vg); cohort 2, 2 × 10 9 vg; cohort 3, 6 × 10 9 vg; and cohort 4, 2 × 10 10 vg, n=3 per cohort) and one maximum tolerated dose cohort (cohort 5, 2 × 10 10 vg, n=7) and followed up for 52 weeks. The primary objective of the study was to assess the safety and tolerability of a single intravitreous injection of AAV2-sFLT01, through the measurement of eye-related adverse events. This trial is registered with ClinicalTrials.gov, number NCT01024998. 19 patients with advanced neovascular age-related macular degeneration were enrolled in the study between May 18, 2010, and July 14, 2014. All patients completed the 52-week trial period. Two patients in cohort 4 (2 × 10 10 vg) experienced adverse events that were possibly study-drug related: pyrexia and intraocular inflammation that resolved with a topical steroid. Five of ten patients who received 2 × 10 10 vg had aqueous humour concentrations of sFLT01 that peaked at 32·7-112·0 ng/mL (mean 73·7 ng/mL, SD 30·5) by week 26 with a slight decrease to

  2. Local partial depletion of CD11b+ cells and their influence on choroidal neovascularization using the CD11b-HSVTK mouse model.

    Science.gov (United States)

    Brockmann, Claudia; Kociok, Norbert; Dege, Sabrina; Davids, Anja-Maria; Brockmann, Tobias; Miller, Kelly R; Joussen, Antonia M

    2018-03-14

    To assess the influence of retinal macrophages and microglia on the formation of choroidal neovascularization (CNV). Therefore, we used a transgenic mouse (CD11b-HSVTK) in which the application of ganciclovir (GCV) results in a depletion of CD11b + cells. We first investigated if a local depletion of CD11b + macrophages and microglia in the retina is feasible. In a second step, the influence of CD11b + cell depletion on CNV formation was analysed. One eye of each CD11b-HSVTK mouse was injected with GCV, and the fellow eye received sodium chloride solution (NaCl). Cell counting was performed at day 3 and 7 (one injection) or at day 14 and 21 (two injections). Choroidal neovascularization (CNV) was induced by argon laser and analysed at day 14. The most effective CD11b + cell depletion was achieved 7 days after a single injection and 14 days after two injections of GCV. After two injections of GCV, we found a significant reduction of CD11b + cells in central (52 ± 23.9 cells/mm 2 ) and peripheral retina (53 ± 20.6 cells/mm 2 ); compared to eyes received NaCl (216 ± 49.0 and 210 ± 50.5 cells/mm 2 , p depletion of CD11b + cells in the retina. Nevertheless, only a partial depletion of CD11b + cells could be achieved compared to baseline data without any intravitreal injections. Our results did not reveal a significant reduction in CNV areas. In the light of previous knowledge, the potential influence of systemic immune cells on CNV formation might be more relevant than expected. © 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  3. Is Spectral-Domain Optical Coherence Tomography Essential for Flexible Treatment Regimens with Ranibizumab for Neovascular Age-Related Macular Degeneration?

    Directory of Open Access Journals (Sweden)

    Abdullah Ozkaya

    2013-01-01

    Full Text Available Purpose. To evaluate the ability of spectral-domain optical coherence tomography to detect subtle amounts of retinal fluid when the choroidal neovascularization is detected as inactive via time-domain optical coherence tomography and clinical examination in neovascular age-related macular degeneration (nAMD patients. Methods. Forty-nine eyes of 49 patients with nAMD after ranibizumab treatment were included in this cross-sectional, prospective study. All patients were imaged with TD-OCT and SD-OCT at the same visit one month after a ranibizumab injection. The presence of subretinal, intraretinal, and subretinal pigment epithelium fluid (subRPE in SD-OCT was evaluated; also mean central retinal thickness (CRT and the rate of vitreoretinal surface disorders detected via the two devices were evaluated. Results. The mean CRT via TD-OCT and SD-OCT was 218.1±51.3 and 325.7±78.8 microns. Sixteen patients (32.6% showed any kind of retinal fluid via SD-OCT. In detail, 8 patients (16.3% showed subretinal fluid, 10 patients (20.4% showed intraretinal fluid, and 3 patients (6.1% showed SubRPE fluid. The ability of detecting vitreoretinal surface disorders was comparable between the two devices, except vitreomacular traction. Conclusion. SD-OCT is essential for the nAMD patients who are on an as-needed treatment regimen with ranibizumab. Only TD-OCT and clinical examination may cause insufficient treatment in this group of patients.

  4. Insulin Like Growth Factor-1 (IGF-1 Causes Overproduction of IL-8, an Angiogenic Cytokine and Stimulates Neovascularization in Isoproterenol-Induced Myocardial Infarction in Rats

    Directory of Open Access Journals (Sweden)

    Nagaraja Haleagrahara

    2011-11-01

    Full Text Available Angiogenesis factors are produced in response to hypoxic or ischemic insult at the site of pathology, which will cause neovascularization. Insulin like growth factor-1 (IGF-1 exerts potent proliferative, angiogenic and anti-apoptotic effects in target tissues. The present study was aimed to evaluate the effects of IGF-1 on circulating level of angiogenic cytokine interleukin-8 (IL-8, in experimentally-induced myocardial ischemia in rats. Male Sprague-Dawley rats were divided into control, IGF-1 treated (2 µg/kg/day subcutaneously, for 5 and 10 days, isoproterenol (ISO treated (85 mg/kg, subcutaneously for two days and ISO with IGF-1 treated (for 5 and 10 days. Heart weight, serum IGF-1, IL-8 and cardiac marker enzymes (CK-MB and LDH were recorded after 5 and 10 days of treatment. Histopathological analyses of the myocardium were also done. There was a significant increase in serum cardiac markers with ISO treatment indicating myocardial infarction in rats. IGF-1 level increased significantly in ISO treated groups and the level of IGF-1 was significantly higher after 10 days of treatment. IL-8 level increased significantly after ISO treatment after 5 and 10 days and IGF-1 concurrent treatment to ISO rats had significantly increased IL-8 levels. Histopathologically, myocyte necrosis and nuclear pyknosis were reduced significantly in IGF-1 treated group and there were numerous areas of capillary sprouting suggestive of neovascularization in the myocardium. Thus, IGF-1 protects the ischemic myocardium with increased production of circulating angiogenic cytokine, IL-8 and increased angiogenesis.

  5. Neovascular age-related macular degeneration is not associated with coronary heart disease in a Chinese Population: a population-based study.

    Science.gov (United States)

    Hu, Chao-Chien; Lin, Herng-Ching; Sheu, Jau-Jiuan; Kao, Li-Ting

    2017-11-01

    This case-control study aimed to explore the association between prior coronary heart disease (CHD) and neovascular age-related macular degeneration (AMD) using a population-based data set in Taiwan. We analysed data sourced from the Taiwan Longitudinal Health Insurance Database 2005. The study consisted of 1970 patients with neovascular AMD as cases and 5910 age- and sex-matched controls. We performed a conditional logistic regression to examine the odds ratio (OR) and its corresponding 95% confidence interval (CI) for previously diagnosed CHD between cases and controls. Of the 7880 sampled patients, 24.5% had a prior history of CHD; CHD was found in 25.7% of cases and in 22.7% of controls (p = 0.008). The conditional logistic regression analysis indicated that the OR for prior CHD for cases was 1.17 [95% confidence interval (CI): 1.04-1.32] compared to the controls. However, after adjusting for patient's monthly income, geographic location, urbanization level, age, hyperlipidaemia, diabetes and hypertension, we failed to observe an association between prior CHD and AMD (OR = 1.03, 95% CI = 0.91-1.17). Additionally, the medical comorbidities of hyperlipidaemia (adjusted OR = 1.29, 95% CI = 1.15-1.45), hypertension (adjusted OR = 1.20, 95% CI = 1.05-1.37) and diabetes (adjusted OR = 1.47, 95% CI = 1.32-1.65) were significantly associated with AMD. This study presented no significant difference in the odds of prior CHD between patients with AMD and those without AMD after adjusting for comorbidities and sociodemographic characteristics in a Chinese population. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  6. EFFECT OF INTRAVITREAL RANIBIZUMAB ON GANGLION CELL COMPLEX AND PERIPAPILLARY RETINAL NERVE FIBER LAYER IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION USING SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY.

    Science.gov (United States)

    Zucchiatti, Ilaria; Cicinelli, Maria V; Parodi, Maurizio Battaglia; Pierro, Luisa; Gagliardi, Marco; Accardo, Agostino; Bandello, Francesco

    2017-07-01

    To analyze the changes in ganglion cell complex and peripapillary retinal nerve fiber layer thickness, in central macular thickness and choroidal thickness on spectral domain optical coherence tomography in patients with neovascular age-related macular degeneration treated with intravitreal ranibizumab injections. All consecutive patients with untreated neovascular age-related macular degeneration received loading phase of three monthly intravitreal ranibizumab, followed by retreatments on a pro re nata protocol for 12 months. changes in ganglion cell complex and retinal nerve fiber layer at the end of follow-up. Secondary outcome: changes in best-corrected visual acuity, central macular thickness, and choroidal thickness at the end of follow-up. Choroidal thickness was measured at 500 μm, 1000 μm, and 1,500 μm intervals nasally, temporally, superiorly, and inferiorly to the fovea, respectively, on horizontal and vertical line scans centered on the fovea. Twenty-four eyes were included. Ganglion cell complex and peripapillary retinal nerve fiber layer thickness did not show statistically significant changes through 12 months (55.6 ± 18.5 and 81.9 ± 9.9 μm at baseline, 52.7 ± 19.3 and 84.6 ± 15.5 μm at month 12, P > 0.05). Central macular thickness showed progressive decrease from baseline to month 12, with maximum reduction at month 3 (P macular thickness was significantly reduced at the end of treatment. Further studies, with larger sample, longer follow-up, and greater number of injections, are warranted.

  7. Long-Term Outcomes in Patients with Neovascular Age-Related Macular Degeneration Who Maintain Dry Macula after Three Monthly Ranibizumab Injections.

    Science.gov (United States)

    Kim, Kyung Min; Kim, Jae Hui; Chang, Young Suk; Kim, Jong Woo; Kim, Chul Gu

    2018-01-01

    To evaluate long-term changes in visual acuity and retinal microstructure in patients with neovascular age-related macular degeneration (AMD) who had maintained dry macula after initial treatment. This retrospective observational study included 55 eyes that were diagnosed with neovascular AMD, were treated with three monthly ranibizumab injections, and maintained dry macula during a two-year follow-up. Best-corrected visual acuity (BCVA) at three months and at the final follow-up were compared, and the degree of visual improvement was compared between eyes with and without improvement of the ellipsoid zone. In addition, the incidence of improvement of the ellipsoid zone was compared between eyes with different extents of disruption. The mean follow-up period was 30.3 ± 4.1 months. BCVA at three months and at the final follow-up was 0.51 ± 0.46 and 0.45 ± 0.49 (P200 μm of disruption of the ellipsoid zone, 15 (42.9%) showed improvement of the ellipsoid zone, and the improvement in BCVA was greater in these eyes than that in the remaining 20 eyes (P=0.021). A higher incidence of improvement of the ellipsoid zone was noted in eyes with 200 to 800 μm of disruption than in eyes with >800 μm of disruption (P<0.001). Long-term improvement in visual acuity was noted in eyes that had maintained dry macula after three ranibizumab injections. The status of the ellipsoid zone at three months was closely associated with visual improvement.

  8. Cytomegalovirus and BK-Virus co-infection of a clinically non-functioning adrenal adenoma: innocent bystanders or new pathogenetic agents?

    Directory of Open Access Journals (Sweden)

    G Pomara

    2009-06-01

    Full Text Available We report a case of a 64-year-old woman who underwent left adrenalectomy with removal of a 8,5 cm clinically non-functioning adrenocortical adenoma and a 4-cm myelolipoma. Molecular testing for viral infection demonstrated the presence of cytomegalovirus (CMV DNA sequences in the adrenal adenoma, but not in the myelolipoma (confirmed by immunohistochemistry. Moreover, the adrenal adenoma was also positive for parvovirus B19, and both adrenal tumor samples were positive for polyomavirus BK (BKV and adenovirus DNA sequences. This is the first report of co-infection of an adrenocortical adenoma by CMV and BKV. The role of these viruses in adrenal tumorigenesis was postulated.

  9. Creation of Functional Viruses from Non-Functional cDNA Clones Obtained from an RNA Virus Population by the Use of Ancestral Reconstruction

    DEFF Research Database (Denmark)

    Fahnøe, Ulrik; Pedersen, Anders Gorm; Dräger, Carolin

    2015-01-01

    necessarily be the descendant of a functional ancestor, we hypothesized that it should be possible to produce functional clones by reconstructing ancestral sequences. To test this we used phylogenetic methods to infer two ancestral sequences, which were then reconstructed as cDNA clones. Viruses rescued from...... the reconstructed cDNAs were tested in cell culture and pigs. Both reconstructed ancestral genomes proved functional, and displayed distinct phenotypes in vitro and in vivo. We suggest that reconstruction of ancestral viruses is a useful tool for experimental and computational investigations of virulence and viral...... evolution. Importantly, ancestral reconstruction can be done even on the basis of a set of sequences that all correspond to non-functional variants....

  10. Enhanced mesenchymal cell engraftment by IGF-1 improves left ventricular function in rats undergoing myocardial infarction.

    Science.gov (United States)

    Enoki, Chiharu; Otani, Hajime; Sato, Daisuke; Okada, Takayuki; Hattori, Reiji; Imamura, Hiroji

    2010-01-07

    We hypothesized that enhanced mesenchymal cell (MC) engraftment with insulin-like growth factor-1 (IGF-1) improves left ventricular (LV) function and survival. IGF-1 (10 microg/ml) increased adhesion and inhibited apoptosis under hypoxia in vitro through activation of phosphatidylinositol 3-kinase (PI3K) in bone marrow-derived MCs obtained from transgenic rats expressing green fluorescence protein. Myocardial infarction (MI) in rats was produced by ligature of the left coronary artery. One month after MI, rat hearts were injected with MCs in the presence or absence of 10 microg/ml IGF-1 with or without PI3K inhibitor, 5 microM LY294002. IGF-1 significantly increased engraftment of MCs between 6 h and 3 days after transplantation associated with the increase in stromal cell-derived factor-1alpha in the infracted LV. The transplanted MCs had disappeared 1 month after transplantation in all groups. MC transplantation with IGF-1 significantly increased neovascularization and inhibited cardiomyocyte apoptosis 3 days and 1 month after MC transplantation. This was associated with improved LV function 1 month after MC transplantation and eventually survival. LY294002 abrogated all of the beneficial effects of MC transplantation with IGF-1. IGF-1 alone had no effect on neovascularization and did not improve LV function and/or survival. These results suggest that IGF-1 improves engraftment of MCs at the time of transplantation via activation of PI3K and this improved engraftment of MCs may be attributed to an increased neovascularization and inhibition of cardiomyocyte death, leading to improvement of LV function and prolongation of survival despite the eventual loss of the transplanted MCs.

  11. Heat enhances radiation inhibition of wound healing

    International Nuclear Information System (INIS)

    Twomey, P.; Hill, S.; Joiner, M.; Hobson, B.; Denekamp, J.

    1987-01-01

    To study the effect of hyperthermia on the inhibition of healing by radiation, the authors used 2 models of wound tensile strength in mice. In one, tensile strength of 1 cm strips of wounded skin was measured. In the other, strength was measured on 2 by 1 by .3 cm surgical prosthetic sponges of polyvinyl alcohol which has been cut, resutured, and implanted subcutaneously. Granulation tissue grows into the pores of the sponges which gradually fill with collagen. Tensile strength in both models was measured on day 14 using a constant strain extensiometer. The wounds were given graduated doses of ortho-voltage radiation with or without hyperthermia. Maximum radiation sensitivity occurred during the period of rapid neovascularization in the first 5 days after wounding, when a loss of 80% in wound strength occurred with doses less than 20 gray. For single radiation doses given 48 hours after wounding, the authors found a steep dose-response curve with half maximum reduction in strength occurring in both models at approximately 10 gray. Hyperthermia was produced in two ways. Skin wounds were heated in a circulating water bath. In the sponge model, more uniform heating occurs with an RF generator scaled to the mouse. At a dose of 43 C for 30 minutes, no inhibition of healing by heat alone was found. However the combination of heat and radiation produced definite enhancement of radiation damage, with thermal enhancement ratios of up to 1.9 being observed

  12. The role of contrast-enhanced ultrasound in risk assessment of carotid atheroma

    Directory of Open Access Journals (Sweden)

    Silviu Stanciu

    2016-07-01

    Full Text Available Background and objective: Contrast-enhanced ultrasound, used to assess atherosclerotic carotid plaques, improves visualization of vessel wall irregularities and depicts intraplaque neovascularization. This article illustrates the use of contrast-enhanced ultrasound in the risk assessment of carotid atherosclerotic lesions, especially in challenging plaques evaluation. Materials and methods: For 23 patients with difficult duplex ultrasound examination due to carotid tortuosity or calcifications we assessed plaque morphology (contour, echogenicity and stenosis degree using contrast substance (Sonovue, Braco with dedicated vascular low mechanical index CPC software. Conclusion: Contrast-enhanced ultrasound is a new, noninvasive, and safe procedure for imaging carotid atherosclerotic lesions. It is a valuable tool for evaluating the vulnerable plaque at risk for rupture and for the diagnostic of the development and severity of systemic atherosclerotic disease

  13. Age-related macular degeneration with choroidal neovascularization in the setting of pre-existing geographic atrophy and ranibizumab treatment. Analysis of a case series and revision paper

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    Miguel Hage Amaro

    2012-12-01

    Full Text Available PURPOSE: To report the response of choroidal neovascularization (CNV to intravitreal ranibizumab treatment in the setting of age-related macular degeneration (AMD with extensive pre-existing geographic atrophy (GA and a revision paper. METHODS: This is a revision paper and a retrospective case series of 10 eyes in nine consecutive patients from a photographic database. The patients were actively treated with ranibizumab for neovascular AMD with extensive pre-existing GA. Patients were included if they had GA at or adjacent to the foveal center that was present before the development of CNV. The best corrected visual acuity and optical coherence tomography (OCT analysis of the central macular thickness were recorded for each visit. Serial injections of ranibizumab were administered until there was resolution of any subretinal fluid clinically or on OCT. Data over the entire follow-up period were analyzed for overall visual and OCT changes. All patients had been followed for at least 2 years since diagnosis. RESULTS: The patients received an average of 6 ± 3 intravitreal injections over the treatment period. Eight eyes had reduced retinal thickening on OCT. On average, the central macular thickness was reduced by 94 ± 101 µm. Eight eyes had improvement of one or more lines of vision, where as one eye had dramatic vision loss and one had no change. The average treatment outcome for all patients was -0.07 ± 4.25 logMAR units, which corresponded to a gain of 0.6 ± 4.4 lines of Snellen acuity. The treatment resulted in a good anatomic response with the disappearance of the subretinal fluid, improved visual acuity, and stabilized final visual results. CONCLUSION: The results of this case series suggest that the use of an intravitreal anti-vascular endothelial growth factor (VEGF agent (ranibizumab for CNV in AMD with extensive pre-existing GA is effective. Our results are not as striking as published results from large-scale trials of anti

  14. Preliminary in vitro and in vivo assessment of a new targeted inhibitor for choroidal neovascularization in age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Li W

    2016-10-01

    Full Text Available Wenbo Li,1,* Lijie Dong,1,* Minwang Ma,2,* Bojie Hu,1 Zhenyu Lu,3 Xun Liu,1 Juping Liu,1 Xiaorong Li1 1Tianjin Medical University Eye Hospital, Tianjin, People’s Republic of China; 2Affiliated Hospital of Medical College of Chinese People’s Armed Police Forces (CapF, Tianjin, People’s Republic of China; 3Tianjin Precision Cell Biotechnology Co. Ltd., Tianjin, People’s Republic of China *These authors contributed equally to this work Abstract: Choroidal neovascularization (CNV in age-related macular degeneration usually causes blindness. We established a novel targeted inhibitor for CNV in age-related macular degeneration. The inhibitor CR2-sFlt 1 comprises a CR2-targeting fragment and an anti-vascular endothelial growth factor (VEGF domain (sFlt 1. The targeting of CR2-sFlt 1 was studied using the transwell assay in vitro and frozen sections in vivo using green fluorescent labeling. Trans­well assay results showed that CR2-sFlt 1 migrated to the interface of complement activation products and was present in the retinal tissue of the CR2-sFlt 1-treated CNV mice. Treatment effects were assessed by investigating the VEGF concentration in retinal pigmented epithelial cell medium and the thickness of the CNV complex in the mice treated with CR2-sFlt 1. CR2-sFlt 1 significantly reduced the VEGF secretion from retinal pigmented epithelial cells in vitro and retarded CNV progress in a mouse model. Expression analysis of VEGF and VEGFRs after CR2-sFlt 1 intervention indicated the existence of feedback mechanisms in exogenous CR2-sFlt 1, endogenous VEGF, and VEGFR interaction. In summary, we demonstrated for the first time that using CR2-sFlt 1 could inhibit CNV with clear targeting and high selectivity. Keywords: choroidal neovascularization, macular degeneration, complement activation, vascular endothelial growth factor

  15. Bilateral visual outcomes and service utilization of patients treated for 3 years with ranibizumab for neovascular age-related macular degeneration

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    Chavan R

    2014-04-01

    Full Text Available Randhir Chavan,1,* Swati Panneerselvam,1,* Parul Adhana,1 Nirodhini Narendran,1 Yit Yang1,2 1Eye Infirmary, New Cross Hospital, Royal Wolverhampton Hospitals NHS Trust Wolverhampton, West Midlands, UK; 2Faculty of Life and Health Sciences, Aston University, Birmingham, UK *These authors contributed equally to this paper Background: The aim of this study was to describe bilateral visual outcomes and the effect of incomplete follow-up after 3 years of ranibizumab therapy for neovascular age-related macular degeneration. Secondarily, the demands on service provision over a 3-year period were described. Methods: Data on visual acuity, hospital visits, and injections were collected over 36 months on consecutive patients commencing treatment over a 9-month period. Visual outcome was determined for 1 all patients, using last observation carried forward for missed visits due to early discontinuation and 2 only those patients completing full 36-month follow-up. Results: Over 3 years, 120 patients cumulatively attended hospital for 1,823 noninjection visits and 1,365 injection visits. A visual acuity loss of <15 letters (L was experienced by 78.2% of patients. For all patients (n=120, there was a mean loss of 1.68 L using last observation carried forward for missing values. Excluding five patients who died and 30 who discontinued follow-up, mean gain was 1.47 L. In bilateral cases, final acuity was on average 9 L better in second eyes compared to first eyes. Also, 91% of better-seeing eyes continued to be the better-seeing eye. Conclusion: We have demonstrated our approach to describing the long-term service provision and visual outcomes of ranibizumab therapy for neovascular age-related macular degeneration in a consecutive cohort of patients. Although there was a heavy burden with very frequent injections and clinic visits, patients can expect a good level of visual stability and a very high chance of maintaining their better

  16. Changes in Fundus Autofluorescence after Anti-vascular Endothelial Growth Factor According to the Type of Choroidal Neovascularization in Age-related Macular Degeneration.

    Science.gov (United States)

    Lee, Ji Young; Chung, Hyewon; Kim, Hyung Chan

    2016-02-01

    To describe the changes of fundus autofluorescence (FAF) in patients with age-related macular degeneration before and after intravitreal injection of anti-vascular endothelial growth factor according to the type of choroidal neovascularization (CNV) and to evaluate the correlation of FAF with spectral domain optical coherence tomography (SD-OCT) parameters and vi