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Sample records for degeneration choroidal neovascularization

  1. Subfoveal choroidal thickness changes after intravitreal bevacizumab therapy for neovascular age-related macular degeneration

    Institute of Scientific and Technical Information of China (English)

    Cihan; ünlü; Gurkan; Erdogan; Betul; Onal; Gunay; Betul; Ilkay; Sezgin; Akcay; Esra; Kardes

    2015-01-01

    <正>Dear Sir,Iam Dr.Cihanünlü,from the Department of Opthalmology,ümraniye Training and Research Hospital,Istanbul,Turkey.I write to present our study findings on subfoveal choroidal thickness(SFCT)changes after intravitreal bevacizumab(IVB)therapy for neovascular age-related macular degeneration(AMD).AMD is the leading cause of severe visual loss in adults older than 60y[1].Visual loss in late stages of AMD may be the result of one of the two processes:geographic atrophy(GA)or choroidal neovascularization(CNV).Many types of

  2. Early detection of choroidal neovascularization in age related macular degeneration

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    Tural Galbinur

    2012-01-01

    Full Text Available Purpose: to identify factors associated with early detection of choroidal neovascularization CNV in clinical practice.Methods: Seventy six AMD patients who had history of CNV in one eye and presented with CNV in the second eye and evaluated for association with visual acuity (VA at time of presentation. Demographics, clinical data and lesion characteristics were retrospectively collected.Results: Better VA was associated with history of CNV in the fellow eye (p<0.0001, adherence to follow-up every four-months (p=0.015, younger age (p=0.03, smaller lesion (p<0.0001, and non-subfoveal localization (p=0.048. VA of the fellow eye did not correlate with VA at presentation with CNV.Conclusion: these data suggest that experience of CNV, regardless of VA, facilitates early diagnosis in the fellow eye. Adherence to follow-up in the routine clinic setting also facilitates early detection of CNV.

  3. Transpupillary thermotherapy in subfoveal choroidal neovascular membrane secondary to age-related macular degeneration

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    Verma Lalit

    2004-01-01

    Full Text Available Purpose: To report our initial experience in the treatment of subfoveal choroidal neovascular membrane, secondary to age-related macular degeneration (AMD by transpupillary thermotherapy (TTT. Methods: Fifty consecutive patients with subfoveal choroidal neovascularisation (CNV secondary to AMD, were included in the study. The parameters assessed before the TTT were visual acuity by ETDRS chart, scotoma score by Amsler grid chart, reading speed, fundus examination by direct and indirect ophthalmoscope as well as +90 Diopter lens followed by digital fundus photography and fluorescein angiography (FA. Results: The letter visual acuity improved or stabilized in 72% cases up to 12 weeks after TTT. Mean scotoma score decreased from a mean of 47.56, to 43.56 at 6 weeks and to 37 at 12 weeks. Mean reading speed increased from 27.04 words/minute at pretreatment to 34.52 words/minute at 6 weeks and 37.33 words/minute 12 weeks after TTT. Conclusion: TTT is not only a cheaper alternative to photodynamic therapy (PDT, but also is an efficacious tool in stabilisation or improvement of visual acuity in the management of subfoveal choroidal neovascular membrane due to AMD.

  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...

  5. Identification of Chlamydia pneumoniae within human choroidal neovascular membranes secondary to age-related macular degeneration.

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    Kalayoglu, Murat V; Bula, Deisy; Arroyo, Jorge; Gragoudas, Evangelos S; D'Amico, Donald; Miller, Joan W

    2005-11-01

    Age-related macular degeneration (AMD) is a leading cause of blindness in the United States, and increasing evidence suggests that it is an inflammatory disease. The prokaryotic obligate intracellular pathogen Chlamydia pneumoniae is emerging as a novel risk factor in cardiovascular disease, and recent sero-epidemiological data suggest that C. pneumoniae infection is also associated with AMD. In this study, we examined choroidal neovascular membrane (CNV) tissue from patients with neovascular AMD for the presence of C. pneumoniae and determined whether the pathogen can dysregulate the function of key cell types in ways that can cause neovascular AMD. Nine CNV removed from patients with neovascular AMD were examined for the presence of C. pneumoniae by immunohistochemistry (IHC) and polymerase chain reaction (PCR); in addition, we performed PCR on nine non-AMD eyes, and IHC on five non-AMD CNV, seven non-AMD eyes, and one internal limiting membrane specimen. Finally, human monocyte-derived macrophages and retinal pigment epithelial (RPE) cells were exposed to C. pneumoniae and assayed in vitro for the production of pro-angiogenic immunomodulators (VEGF, IL-8, and MCP-1). C. pneumoniae was detected in four of nine AMD CNV by IHC and two of nine AMD CNV by PCR, induced VEGF production by human macrophages, and increased production of IL-8 and MCP-1 by RPE cells. In contrast, none of the 22 non-AMD specimens showed evidence for C. pneumoniae. These data indicate that a pathogen capable of inducing chronic inflammation and pro-angiogenic cytokines can be detected in some AMD CNV, and suggest that infection may contribute to the pathogenesis of AMD.

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

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    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....

  7. Intravitreal ranibizumab for symptomatic drusenoid pigment epithelial detachment without choroidal neovascularization in age-related macular degeneration

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    Roberto Gallego-Pinazo

    2011-02-01

    Full Text Available Roberto Gallego-Pinazo1,2, Ana Marina Suelves-Cogollos1, Ester Francés-Muñoz1, J María Millán2,3, J Fernando Arevalo4, J Luis Mullor5, Manuel Díaz-Llopis1,2,61Department of Ophthalmology, Hospital Universitario La Fe, Valencia, Spain; 2Centro de Investigación Biomédica en Red de Enfermedades Raras, Valencia, Spain; 3Department of Genetics, Hospital Universitario La Fe, Valencia, Spain; 4Retina and Vitreous Service, Clínica Oftalmológica Centro Caracas, Caracas, Venezuela; 5Unit of Experimental Ophthalmology, Fundación para la Investigación del Hospital Universitario La Fe, Valencia, Spain; 6University of Valencia, Faculty of Medicine, Valencia, SpainBackground: The aim of our study was to evaluate the functional and anatomic outcomes of intravitreal ranibizumab for the treatment of symptomatic drusenoid pigment epithelial detachment without choroidal neovascularization in age-related macular degeneration.Methods: This was a prospective, single-center, uncontrolled, interventional pilot study. Six consecutive eyes (six patients with drusenoid pigment epithelial detachment with a visual acuity of 20/63 to 20/100 and no evidence of choroidal neovascularization in age-related macular degeneration participated. Patients were given at least one intravitreal ranibizumab injection and were followed for a mean of 66.67 ± 10.3 weeks. Main outcome measures included best-corrected visual acuity (BCVA measured by Early Treatment Diabetic Retinopathy Study charts and optical coherence tomography, and central macular thickness measured by optical coherence tomography.Results: The mean number of intravitreal ranibizumab injections was 3.0 at the end of follow-up. Regarding BCVA and optical coherence tomography, 33.3% of eyes gained between 19 and 21 letters of BCVA, with a median decrease in central macular thickness of 21 µm. There was a statistically significant difference between baseline and final BCVA (P = 0.046. There was a positive

  8. Matrix Metalloproteinases Expression in Choroidal Neovascular Membranes

    Institute of Scientific and Technical Information of China (English)

    Jun Zeng; Deyong Jiang; Xiangping Liu; Xiaohua Zhu; Luosheng Tang

    2004-01-01

    Purpose: To investigate the expression of matrix metalloproteinases (MMPs) in choroidal neovascular membranes with age-related macular degeneration (AMD).Methods: Seventeen choroidal neovascular membranes surgically removed from AMD patients with pars plana vitrectomy and subretinal membranes peeling were investigated.The expression of MMP-2 and MMP-9 was determined with immunohistochemical technique.Results: Immunohistochemistry staining in choroidal neovascular membranes for MMP2 and MMP-9 was observed in 17 specimens. There was no detective of MMP-2 and MMP-9 in normal retinas.Conclusions: MMP-2 and MMP-9 were found in choroidal neovascular membranes, may degrade the Bruch membrane and be associated with the perforation of new vessels into Bruch membrane, involving a basic pathogenic process of AMD.

  9. 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

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

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    Balaratnasingam, Chandrakumar; Dhrami-Gavazi, Elona; McCann, Jesse T; Ghadiali, Quraish; Freund, K Bailey

    2015-01-01

    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 illustrate the efficacy of aflibercept for managing treatment-naïve CNV, recalcitrant CNV, and CNV due to polypoidal choroidal vasculopathy. Safety profile, patient tolerability, and quality of life measures related to aflibercept are also provided. The evidence provided in this paper suggests aflibercept to be a promising agent that can be used to reduce the treatment burden of neovascular AMD.

  11. Choroid, Haller's, and Sattler's layer thickness in intermediate age-related macular degeneration with and without fellow neovascular eyes.

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    Esmaeelpour, Marieh; Ansari-Shahrezaei, Siamak; Glittenberg, Carl; Nemetz, Susanne; Kraus, Martin F; Hornegger, Joachim; Fujimoto, James G; Drexler, Wolfgang; Binder, Susanne

    2014-07-22

    To analyze choroidal, Sattler's, and Haller's layer thickness maps in age-related macular degeneration (AMD) patients having eyes with bilateral large drusen and pigment changes (intermediate AMD), in patients having intermediate AMD eyes with neovascular fellow eyes (nAMD), and in healthy subjects using three-dimensional (3D) 1060-nm optical coherence tomography (OCT). Automatically generated choroidal thickness (ChT), retinal thickness, and Sattler's and Haller's layer thickness maps were statistically analyzed in 67 subjects consisting of intermediate AMD (n = 21), intermediate AMD (n = 22) with fellow nAMD eyes (n = 22), and healthy eyes (n = 24) with no age and axial eye length difference between groups of eyes (P > 0.05, ANOVA). Eyes were imaged by a prototype high-speed (60,000 A-scans/s) spectral-domain 3D 1060-nm OCT over a 36° × 36° field of view. The mean ± SD (μm) subfoveal ChT for healthy subjects and for bilateral intermediate AMD, unilateral intermediate AMD, and their nAMD fellow eyes was 259 ± 95 and 222 ± 98, 149 ± 60, and 171 ± 78, respectively. Choroidal thickness maps demonstrated significant submacular thinning in unilateral intermediate AMD in comparison to healthy and bilateral intermediate AMD eyes (P choroid and its sublayers, there was no difference between the intermediate AMD eyes and their fellow nAMD eyes (paired testing, P choroidal imaging visualized significant changes in choroidal, Sattler's, and Haller's layer thickness in relation to the progression of AMD. This may be important for understanding the choroidopathy in the pathophysiology of AMD. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  12. Repeatability of swept-source optical coherence tomography retinal and choroidal thickness measurements in neovascular age-related macular degeneration.

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    Hanumunthadu, Daren; Ilginis, Tomas; Restori, Marie; Sagoo, Mandeep S; Tufail, Adnan; Balaggan, Kamaljit S; Patel, Praveen J

    2017-05-01

    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). 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. 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). The repeatability this subfield, expressed as a percentage of the mean central macular subfield thickness, was 23.2%. The percentage repeatability of the other macular subfields ranged from 13.2% to 28.7%. The intrasession coefficient of repeatability of choroidal thickness of the central macular subfield was 57.2 μm with a mean choroidal thickness (±SD) of 181 μm (±15.8 μm). This study suggests that a change >23.2% of retinal thickness and 57.2 μm choroidal thickness in the central macular subfield is required to distinguish true clinical change from measurement variability when using the DRI OCT-1 device to manage patients with nAMD. 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/.

  13. Inflammatory choroidal neovascularization

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    Neri Piergiorgio

    2009-01-01

    Full Text Available Purpose and Methods: Choroidal neovascularization (CNV can be a severe sight-threatening sequela, which can be secondary to both infectious and noninfectious uveitis. This review summarizes the different diseases associated with CNV, highlighting new treatment modalities and the possible strategies, which could be applied for the therapy of this occurrence. Results: Since CNV can often originate from posterior pole lesions and can be hard to identify, an accurate examination is mandatory in order to identify the correct diagnosis. In the majority of cases, fluorescein angiography (FA, indocyanine green angiography (ICGA and optical coherence tomography (OCT enable the determination of the clinical characteristics of the CNV. An infectious disease should be looked for to include a suitable therapy when available. The treatment strategy for CNV secondary to noninfectious uveal inflammations should be directed at controlling the inflammatory process. Systemic corticosteroids with or without immunosuppressive agents are indicated even when the CNV occurs with apparently inactive uveitis: Chronic subclinical inflammation can be the basis for the pathogenesis of CNV. Additional therapies aimed directly at the neovascular process, such as the intravitreal anti-Vascular Endothelial Growth Factor (VEGF agents, are recommended particularly when the therapy shows an insufficient response. Conclusion: CNV secondary to uveitis is a severe sequela leading to significant visual impairment. ICGA is mandatory in order to obtain relevant information about the choroidal status. Several therapeutic options have been considered, but no guidelines are provided at the moment. Moreover, the current data are still only based on case reports or small series. For such reasons, further trials are mandatory to validate the preliminary available results.

  14. Transpupillary thermotherapy for choroidal neovascular membrane in age related macular degeneration

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    Agarwal Manisha

    2004-01-01

    Full Text Available Purpose: To evaluate the efficacy of transpupillary thermotherapy (TTT in choroidal neovasularisation (CNVM secondary to age related macular degeneration ( AMD. Material and methods: Retrospective, non-randomized study of 28 eyes of 28 patients with subfoveal CNVM (classic, occult or mixed secondary to AMD. Results: Fifteen patients (53.57% maintained their pre-treatment vision, 2 (7.14% patients showed improvement of more than 2 lines and 11(39.28% patients showed deterioration of vision by> 2 lines. Angiographic and clinical regression of CNVM was noted in 19 patients (67.8% on an average follow up of 15.32 ± 3.31 months. Conclusion: TTT leads to stabilisation of vision in 60% of treated eyes with CNVM due to AMD.

  15. Choroidal neovascularization secondary to choroidal nevus simulating an inflammatory lesion

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    Samuray Tuncer

    2013-01-01

    Full Text Available Choroidal nevi are the most common benign pigmented lesions of the fundus. Choroidal neovascularization is a rare complication of choroidal nevi. We report herein a young patient managed successfully with intravitreal bevacizumab injections for juxtapapillary choroidal neovascularization secondary to choroidal nevus simulating an inflammatory lesion.

  16. Topical application of PPADS inhibits complement activation and choroidal neovascularization in a model of age-related macular degeneration.

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    Kerstin Birke

    Full Text Available Age-related macular degeneration (AMD is the most common cause of blindness among the elderly. AMD patients have elevated levels of membrane attack complex (MAC in their choroidal blood vessels and retinal pigment epithelium (RPE. MAC forms pores in cell membranes. Low levels of MAC result in an elevation of cytokine release such as vascular endothelial growth factor (VEGF that promotes the formation of choroidal neovascularization (CNV. High levels of MAC result in cell lysis and RPE degeneration is a hallmark of advanced AMD. The current standard of care for CNV associated with wet AMD is intravitreal injection of anti-VEGF molecules every 4 to 12 weeks. Such injections have significant side effects. Recently, it has been found that membrane pore-forming proteins such as α-haemolysin can mediate their toxic effects through auto- and paracrine signaling and that complement-induced lysis is amplified through ATP release followed by P2X receptor activation. We hypothesized that attenuation of P2X receptor activation may lead to a reduction in MAC deposition and consequent formation of CNV. Hence, in this study we investigated topical application of the purinergic P2X antagonist Pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS as a potential treatment for AMD. We found that 4.17 µM PPADS inhibited formation of HUVEC master junctions and master segments by 74.7%. In a human complement mediated cell lysis assay, 104 µM PPADS enabled almost complete protection of Hepa1c1c7 cells from 1% normal human serum mediated cell lysis. Daily topical application of 4.17 mM PPADS for 3 days attenuated the progression of laser induced CNV in mice by 41.8% and attenuated the deposition of MAC at the site of the laser injury by 19.7%. Our data have implications for the future treatment of AMD and potentially other ocular disorders involving CNV such as angioid streaks, choroidal rupture and high myopia.

  17. Choroidal thickness after intravitreal ranibizumab injections for choroidal neovascularization

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    Ellabban AA

    2012-05-01

    Full Text Available Abdallah A Ellabban, Akitaka Tsujikawa, Ken Ogino, Sotaro Ooto, Kenji Yamashiro, Akio Oishi, Nagahisa YoshimuraDepartment of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, JapanPurpose: To study changes in choroidal thickness with ranibizumab treatment for choroidal neovascularization (CNV.Design: Prospective case series.Methods: This prospective study consisted of 60 CNV-affected eyes of 60 patients treated with intravitreal injections of ranibizumab using an on-demand protocol after an initial loading phase. The eyes studied included 20 with age-related macular degeneration (AMD, 20 with polypoidal choroidal vasculopathy (PCV, and 20 with myopic CNV. In the eyes with AMD and PCV, choroidal thickness at the fovea was measured with optical coherence tomography using enhanced depth imaging. In eyes with myopic CNV, the choroidal thickness was measured using standard optical coherence tomography without the enhanced depth imaging technique.Results: With ranibizumab treatment, central retinal thickness decreased significantly (P < 0.001 and visual acuity improved significantly (P < 0.001. However, central choroidal thickness (167.2 ± 108.3 µm showed no significant change at 1 month after the loading phase (165.2 ± 107.8 µm, P = 0.120 or at final examination (164.8 ± 107.7 µm, P = 0.115. At baseline, central retinal thickness in eyes with AMD was significantly greater that those with PCV (P = 0.005 or high myopia (P = 0.029. However, central choroidal thickness in eyes with myopic CNV was significantly thinner than in eyes with AMD (P < 0.001 or PCV (P < 0.001. In each type of disease, there was no significant change in central choroidal thickness with ranibizumab treatment.Conclusion: The effect of ranibizumab on the choroidal thickness is minimal, if any.Keywords: choroidal thickness, ranibizumab, optical coherence tomography

  18. New approaches in the management of choroidal neovascular membrane in age-related macular degeneration.

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    Verma Lalit

    2000-01-01

    Full Text Available Age-related macular degeneration (AMD is a leading cause of blindness in the elderly population. The prevalence is reported to be 1.2-1.4% in several population-based epidemiological studies. Currently 25-30 million people worldwide are blind due to AMD. With the aging world population it is bound to increase significantly, and could become a significant public health problem in next two decades, with serious socio-economic implications. Several strategies are today available to treat the wet form of AMD, which is responsible for significant visual loss. These were until recently confined to laser photocoagulation, and subretinal surgery, but today two other modalities, namely, radiation and photodynamic therapy, are available. These treatment modalities however, are aimed at preservation of vision only, and not at reversing the process of the disease. Further research on antiangiogenic drugs and gene therapy could significantly help AMD patients.

  19. Intravitreal Ranibizumab for Subfoveal Choroidal Neovascularization from Age-Related Macular Degeneration with Combined Severe Diabetic Retinopathy

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    So Young Han

    2015-02-01

    Full Text Available BackgroundTo evaluate the efficacy of intravitreal ranibizumab for subfoveal choroidal neovascularization (CNV from age-related macular degeneration (AMD with combined severe diabetic retinopathy (DR.MethodsThis retrospective, interventional case series included eleven patients (mean age, 70.09 years; range, 54 to 83 years with at least severe non-proliferative DR and subfoveal CNV secondary to AMD. Each subject was treated with intravitreal injections of 0.5 mg ranibizumab. The primary outcomes included change in best-corrected visual acuity and central subfield thickness (CST on optical coherence tomography (OCT.ResultsThe mean follow-up time was 16.7±14 months (range, 6 to 31 months. Mean visual acuity improved from 1.21±0.80 logarithm of the minimum angle of resolution (logMAR to 1.0±0.6 logMAR (P=0.107, 0.95±0.62 logMAR (P=0.044, 1.10±0.68 logMAR (P=0.296, and 1.13±0.66 logMAR (P=0.838 at 1, 3, 6, and 12 months after injection, respectively. Eight patients (72.7% gained or maintained vision (mean 0.32 logMAR, whereas three patients (27.3% lost more than one line of vision (mean 0.51 logMAR. The mean OCT CST was 343.9±134.6 µm at baseline, and the mean CST at 1, 3, 6, 12 months after the injection was 367.8±172.1 (P=0.864, 346.2±246.2 (P=0.857, 342±194.1 (P=0.551, and 294.2±108.3 µm (P=0.621, respectively.ConclusionIntravitreal ranibizumab injection can be considered to be a therapy for the stabilization of subfoveal CNV secondary to AMD with combined severe DR. However, these patients might exhibit limited visual improvement after treatment.

  20. Combined Transpupillary Thermotherapy with Subtenon Triamcinolone Injection in Treatment of Choroidal Neovascularization Secondary to Exudative Age Related Macular Degeneration

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    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

  1. Two Different Doses of Intravitreal Bevacizumab for Treatment of Choroidal Neovascularization Associated with Age-related Macular Degeneration

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    Mehdi Modarreszadeh

    2008-12-01

    Full Text Available

    PURPOSE: To compare the efficacy and safety of 1.25 mg versus 2.5 mg intravitreal bevacizumab (IVB for treatment of choroidal neovascularization (CNV associated with age-related macular degeneration (AMD. METHODS: In this randomized clinical trial, consecutive patients with active CNV associated with AMD received 1.25 mg or 2.5 mg IVB. Best corrected visual acuity (BCVA, foveal thickness and side effects of therapy were evaluated one and three months after intervention. RESULTS: Overall 86 subjects were enrolled and completed the scheduled follow-up. Forty seven and 39 patients received 1.25 and 2.5 mg IVB respectively. The study groups were balanced in terms of baseline characteristics such as age, BCVA and foveal thickness. Mean improvement in BCVA was 0.06±0.3 logMAR in the 1.25 mg group and 0.07±0.34 logMAR in the 2.5 mg group (P=0.9. Mean decrease in foveal thickness was 49±36 µm in the 1.25 mg group and 65±31µm in the 2.5 mg group (P=0.6. Three cases of vitreous reaction and one case of massive subretinal hemorrhage were observed in the 2.5 mg group. CONCLUSION: Double dose (2.5 mg IVB does not seem to be more effective than regular dose (1.25 mg injections for treatment of CNV due to AMD and may lead to more complications.

  1. Bilateral choroidal osteoma with choroidal neovascular membrane treated with bevacizumab in a child.

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    Agarwal, Manisha; Kantha, Meha; Mayor, Rahul; Venkatesh, Ramesh; Shroff, Cyrus M

    2014-01-01

    Choroidal osteoma is a rare benign tumor. We report a male child diagnosed with bilateral choroidal osteoma, high myopia and secondary choroidal neovascularization (CNV) membrane in one eye. Co-existence of posterior staphyloma made the clinical diagnosis of choroidal osteoma difficult due to the osteoma filling the depression of the posterior staphyloma. Typical findings on fundus fluorescein angiography, optical coherence tomography, B-scan and indocyanine green angiography confirmed the diagnosis. A review of literature was performed. CNV secondary to choroidal osteoma was treated with intravitreal bevacizumab and it responded well. Regular follow-up is essential for recurrence of CNV and decalcification of the osteoma.

  2. Choroidal neovascularization associated with coloboma of the choroid: A series of three cases

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    Bhende Muna

    2011-01-01

    Full Text Available Choroidal neovascularization (CNV is a rare complication associated with coloboma of the choroid. We describe three cases of coloboma choroid where there was loss of vision due to CNV development at the edge of the coloboma. One was managed by photodynamic therapy alone and two were managed by a combination of reduced fluence PDT and intravitreal bevacizumab. Significantly we noted that one treatment session was sufficient to achieve regression of the CNV and improvement in visual acuity.

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

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    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. PMID:27239075

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

    Science.gov (United States)

    Anter, Jaouad; Bezunartea, Jaione; Hernandez-Sanchez, Maria; García-García, Laura; Alonso, Elena; Ruiz-Moreno, Jose María; Araiz-Iribarren, Javier; Fernandez-Robredo, Patricia; García-Layana, Alfredo

    2016-01-01

    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. PMID:27643879

  5. 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....

  6. Fluorocoxib A enables targeted detection of cyclooxygenase-2 in laser-induced choroidal neovascularization

    Science.gov (United States)

    Uddin, Md. Jashim; Moore, Chauca E.; Crews, Brenda C.; Daniel, Cristina K.; Ghebreselasie, Kebreab; McIntyre, J. Oliver; Marnett, Lawrence J.; Jayagopal, Ashwath

    2016-09-01

    Ocular angiogenesis is a blinding complication of age-related macular degeneration and other retinal vascular diseases. Clinical imaging approaches to detect inflammation prior to the onset of neovascularization in these diseases may enable early detection and timely therapeutic intervention. We demonstrate the feasibility of a previously developed cyclooxygenase-2 (COX-2) targeted molecular imaging probe, fluorocoxib A, for imaging retinal inflammation in a mouse model of laser-induced choroidal neovascularization. This imaging probe exhibited focal accumulation within laser-induced neovascular lesions, with minimal detection in proximal healthy tissue. The selectivity of the probe for COX-2 was validated in vitro and by in vivo retinal imaging with nontargeted 5-carboxy-X-rhodamine dye, and by blockade of the COX-2 active site with nonfluorescent celecoxib prior to injection of fluorocoxib A. Fluorocoxib A can be utilized for imaging COX-2 expression in vivo for further validation as an imaging biomarker in retinal diseases.

  7. 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

  8. Prevalence of outer retinal tubulation in eyes with choroidal neovascularization

    OpenAIRE

    Giachetti Filho, Richard Geraldo; Zacharias,Leandro Cabral; Monteiro,Thaís Vera; Preti, Rony Carlos; Pimentel, Sérgio Gianoti

    2016-01-01

    Background Outer retinal tubulations (ORTs) are branching tubular structures located in the outer nuclear layer of the retina. The goal of this study is to determine the prevalence of ORTs observed in eyes with choroidal neovascularization (CNV) undergoing treatment with anti-angiogenic intravitreous injection (IVI) with anti-VEGF (vascular endothelial growth factor) at the Ophthalmology Department of a tertiary hospital in São Paulo, Brazil. Methods This is a descriptive study based on medic...

  9. Treatment of neovascular age-related macular degeneration: Current therapies

    Directory of Open Access Journals (Sweden)

    Albert J Augustin

    2009-01-01

    Full Text Available Albert J Augustin, Stefan Scholl, Janna KirchhofDepartment of Ophthalmology, Klinikum Karlsruhe, GermanyAbstract: Choroidal neovascularization (CNV secondary to age-related macular degeneration (AMD is now the leading cause of blindness and severe vision loss among people over the age of 40 in the Western world. Its prevalence is certain to increase substantially as the population ages. Treatments currently available for the disease include laser photocoagulation, verteporfin photodynamic therapy, and intravitreal injections of corticosteroids and anti-angiogenic agents. Many studies have reported the benefits of each of these treatments, although none is without its risks. No intervention actually cures AMD, nor the neovascularization associated with it. However, its symptoms are treated with varying degrees of success. Some treatments stabilize or arrest the progress of the disease. Others have been shown to reverse some of the damage that has already been done. These treatments can even lead to visual improvement. This paper will review the major classes of drugs and therapies designed to treat this condition.Keywords: wet AMD, neovascularization, PDT, steroids, anti-angiogenesis

  10. Optical Coherence Tomography Angiography for Detecting Choroidal Neovascularization Secondary to Choroidal Osteoma.

    Science.gov (United States)

    Szelog, Jason T; Bonini Filho, Marco A; Lally, David R; de Carlo, Talisa E; Duker, Jay S

    2016-01-01

    Choroidal osteoma is an ossifying tumor that is found predominantly in the peripapillary and macular areas. It typically affects otherwise healthy females. Vision loss may occur secondary to the development of choroidal neovascularization (CNV). Fluorescein angiography (FA) remains the gold standard for diagnosing CNV; however, the use of optical coherence tomography angiography (OCTA) as an adjunct to FA is growing. In this report, a 16-year-old female with a large, unilateral peripapillary choroidal osteoma presented with blurred vision. Exam revealed scattered intraretinal hemorrhage, but FA was unable to detect CNV overlying the tumor. OCTA detected abnormal flow in the outer retina corresponding to a type 2 CNV. Following intravitreal anti-vascular endothelial growth factor therapy, the CNV regressed, the hemorrhage resolved, and there was less fluid. OCTA may be helpful in detecting CNV noninvasively in eyes in which FA is equivocal, such as those with choroidal osteoma.

  11. Resistance to anti-VEGF therapy in neovascular age-related macular degeneration: a comprehensive review

    Directory of Open Access Journals (Sweden)

    Yang S

    2016-06-01

    Full Text Available Shiqi Yang,1 Jingke Zhao,1 Xiaodong Sun1–3 1Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 2Eye Research Institute of Shanghai Jiao Tong University, 3Shanghai Key Laboratory of Fundus Disease, Shanghai, People’s Republic of China Abstract: As a progressive chronic disease, age-related macular degeneration (AMD is the leading cause of irreversible vision impairment worldwide. Experimental and clinical evidence has demonstrated that vascular endothelial growth factor (VEGF plays a vital role in the formation of choroidal neovascularization. Intravitreal injections of anti-VEGF agents have been recommended as a first-line treatment for neovascular AMD. However, persistent fluid or recurrent exudation still occurs despite standardized anti-VEGF therapy. Patients suffering from refractory or recurrent neovascular AMD may develop mechanisms of resistance to anti-VEGF therapy, which results in a diminished therapeutic effect. Until now, there has been no consensus on the definitions of refractory neovascular AMD and recurrent neovascular AMD. This article aims at clarifying these concepts to evaluate the efficacy of switching drugs, which contributes to making clinical decision more scientifically. Furthermore, insight into the causes of resistance to anti-VEGF therapy would be helpful for developing possible therapeutic approaches, such as combination therapy and multi-target treatment that can overcome this resistance. Keywords: age-related macular degeneration, vascular endothelial growth factor, choroidal neovascularization, resistance

  12. OCT Angiography Identification of Choroidal Neovascularization Secondary to Acute Zonal Occult Outer Retinopathy.

    Science.gov (United States)

    Levison, Ashleigh L; Baynes, Kimberly; Lowder, Careen Y; Srivastava, Sunil K

    2016-01-01

    A 74-year-old female with acute zonal occult outer retinopathy presented with a new lesion suspicious for choroidal neovascularization (CNV) in her right eye. Optical coherence tomography angiography (OCTA) confirmed the presence of CNV. OCTA is a new imaging technique that may help guide diagnosis and management of choroidal neovascular membranes in uveitic diseases.

  13. Ranibizumab: the evidence of its therapeutic value in neovascular age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Peter K. Kaiser

    2008-07-01

    Full Text Available Peter K. KaiserCole Eye Institute, The Cleveland Clinic Foundation, Cleveland, Ohio, USAIntroduction: Neovascular age-related macular degeneration (AMD is the leading cause of severe, irreversible visual impairment in people over 60 years of age. Neovascular AMD is characterized by abnormal growth of blood vessels under the retina, specifically the macula. These vessels leak blood and fluids, damaging the retina and its photoreceptors, resulting in permanent loss of central vision. Vascular endothelial growth factor-A (VEGF-A has been shown to play a critical role in the pathogenesis of neovascular AMD. In the US, ranibizumab, a VEGF-A blocker, is approved and indicated for the treatment of patients with neovascular AMD.Aims: To review the clinical evidence for ranibizumab in the treatment of neovascular AMD.Evidence review: Phase III clinical trial data have established ranibizumab as a safe and well-tolerated treatment for neovascular AMD. Monthly intravitreal injections of ranibizumab result in a statistically significantly greater proportion of patients losing <15 letters of visual acuity (VA and statistically significant increases in the mean number of letters gained compared with controls. Anatomically, ranibizumab results in stabilization in the mean area of choroidal neovascularization (CNV and statistically significant reductions in the mean area of leakage compared with controls. Although there is limited economic evidence available, ranibizumab therapy for neovascular AMD appears to deliver a significant degree of value gain in terms of quality of life when compared with other neovascular AMD interventions.Place in therapy: Clinical evidence establishes ranibizumab as a first-line therapy option for virtually all treatable neovascular AMD patients. Updating neovascular AMD treatment guidelines to reflect the evidence base for ranibizumab as a preferred first-line therapy would be beneficial for physicians in making informed treatment

  14. Combination verteporfin photodynamic therapy ranibizumab-dexamethasone in choroidal neovascularization due to age-related macular degeneration: results of a phase II randomized trial

    Science.gov (United States)

    Gallemore, Ron P; Wallsh, Josh; Hudson, Henry L; Ho, Allen C; Chace, Richard; Pearlman, Joel

    2017-01-01

    Purpose To assess whether combination therapy (CT) reduces retreatments when compared to ranibizumab monotherapy (RM), while safely maintaining similar vision outcomes. Methods In this 24-month trial, patients with age-related macular degeneration (AMD) were randomized to 1) quarter-fluence or 2) half-fluence triple therapy (verteporfin photodynamic therapy [vPDT] + ranibizumab + dexamethasone), 3) half-fluence double therapy (vPDT + ranibizumab), or 4) RM. The primary outcomes were number of retreatment visits and change from baseline in visual acuity (VA) at 12 months. Results One hundred sixty-two subjects enrolled. There were 4.0 (P=0.02), 3.2 (P<0.001), 4.1 (P=0.03), and 5.7 retreatment visits through month 12, and 5.9 (P=0.03), 4.3 (P<0.001), 5.9 (P=0.02) and 8.7 through month 24, in groups 1, 2, 3, and 4, respectively (P-value comparing with RM). Month 12 VA score change from baseline (95% confidence interval) was +3.6 (−0.9 to +8.1), +6.8 (+2.4 to +11.1), +5.0 (+0.6 to +9.3), and +6.5 (+1.7 to +11.4), respectively. Conclusion CT resulted in significantly fewer retreatment visits than a RM regimen at months 12 and 24. VA results appeared similar although wide confidence intervals preclude conclusions regarding vision outcomes. PMID:28182161

  15. Inflammatory Mediators and Angiogenic Factors in Choroidal Neovascularization: Pathogenetic Interactions and Therapeutic Implications

    Directory of Open Access Journals (Sweden)

    Claudio Campa

    2010-01-01

    Full Text Available Choroidal neovascularization (CNV is a common and severe complication in heterogeneous diseases affecting the posterior segment of the eye, the most frequent being represented by age-related macular degeneration. Although the term may suggest just a vascular pathological condition, CNV is more properly definable as an aberrant tissue invasion of endothelial and inflammatory cells, in which both angiogenesis and inflammation are involved. Experimental and clinical evidences show that vascular endothelial growth factor is a key signal in promoting angiogenesis. However, many other molecules, distinctive of the inflammatory response, act as neovascular activators in CNV. These include fibroblast growth factor, transforming growth factor, tumor necrosis factor, interleukins, and complement. This paper reviews the role of inflammatory mediators and angiogenic factors in the development of CNV, proposing pathogenetic assumptions of mutual interaction. As an extension of this concept, new therapeutic approaches geared to have an effect on both the vascular and the extravascular components of CNV are discussed.

  16. Photodynamic therapy of choroidal neovascularization with enlargement of the spot size to include the feeding complex

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    Ilias Georgalas

    2008-12-01

    Full Text Available Ilias Georgalas, Alexandros A Rouvas, Dimitrios A Karagiannis, Athanasios I Kotsolis, Ioannis D LadasDepartment of Ophthalmology, Medical School of Athens University, Athens, GreeceAbstract: This is a case report of a 83-year-old man with choroidal neovascularization (CNV, due to age-related macular degeneration (AMD in his right eye. Digital fluorescein (FA and indocyanine green angiography (ICG were performed, which disclosed predominantly classic subfoveal CNV and a dilated and tortuous feeding complex. The visual acuity was 20/800. Anti-vascular endothelial growth factor (anti-VEGF treatment was suggested, however, the patient was not keen to receive an intraocular injection. Modified photodynamic therapy (PDT with spot size enlarged, to include not only the CNV lesion but the feeding complex as well, was performed. Ten days after one session of PDT, ICG showed absence of leakage from the CNV and complete occlusion of the feeding complex. The visual acuity gradually improved to 20/100 and remained stable during the following 23 months. No evidence of CNV leakage was seen in the FA and ICG during the follow up period. Adjustment of the PDT spot size to include the detectable by ICG feeding complex might be an additional option in order to close the subfoveal CNV and might be considered as an alternative to intravitreal injection of anti-VEGF in selected cases where anti-VEGF treatment is not available.Keywords: age-related macular degeneration, choroidal neovascularization, photodynamic treatment, feeder vessel

  17. CCR3 is a therapeutic and diagnostic target for neovascular age-related macular degeneration

    OpenAIRE

    2009-01-01

    Age-related macular degeneration (AMD), a leading cause of blindness worldwide, is as prevalent as cancer in industrialized nations. Most blindness in AMD results from invasion of the retina by choroidal neovascularization (CNV). We report that the eosinophil/mast cell chemokine receptor CCR3 is specifically expressed in CNV endothelial cells in humans with AMD, and that, despite the expression of its ligands eotaxin-1, -2, and -3, neither eosinophils nor mast cells are present in human CNV. ...

  18. Effect of vascular endothelial growth factor inhibitors on choroid in patients with macular choroid neovascular membrane and degenerative myopia . Preliminary report

    Directory of Open Access Journals (Sweden)

    V. A. Solomin

    2012-01-01

    Full Text Available Purpose: to assess the effect of vascular endothelial growth factor inhibitors on choroid in patients with myopic macular choroid neovascular membrane.Methods: 12 eyes (12 patients aged 19-47 years with myopia and macular choroid neovascular membrane (mCNV were enrolled in a study group. A control group included fellow eyes with early «dry» form age-related macular degeneration. Eyes with mCNV under- went one intravitreal injection of vascular endothelial growth factor inhibitor Ranibizumab 0.5 mg. Retina and choroid examination was performed with SPECtRALIS HRA+OCt (Heidelberg Engineering. Eyes were examined before treatment, in 1 month and in 3 months after treatment.Results: Mean best corrected visual acuity in 1 moth after ranibizumab 0.5 mg injection improved from 0.37±0.18 to 0.47±0.24. In 3 months after treatment best corrected visual acuity was 0.53±0.24. Mean foveal retinal thickness before treatment was 311.4±57.2 μm; 1 month and 3 months after treatment mean foveal retinal thickness decreased to 229.1±41.8 μm and 221.8±29.3 μm, respec- tively. Mean choroid thickness in 1 moth decreased from 54.4±23.7 μm to 37.4±17.0 μm, in 3 moths mean choroid thickness was 48.9±20.1 μm. In the control group best corrected visual acuity was 0.79±0.18, mean foveal retinal thickness and mean choroid thick- ness were 187.1±10.5 μm and 93.7±24.5 μm, respectively.Conclusion: Injection of vascular endothelial growth factor inhibitor allowed transient choroid thinning.

  19. Metabolic syndrome triggered by high-fructose diet favors choroidal neovascularization and impairs retinal light sensitivity in the rat.

    Science.gov (United States)

    Thierry, Magalie; Pasquis, Bruno; Acar, Niyazi; Grégoire, Stéphane; Febvret, Valérie; Buteau, Bénédicte; Gambert-Nicot, Ségolène; Bron, Alain M; Creuzot-Garcher, Catherine P; Bretillon, Lionel

    2014-01-01

    Diabetic retinopathy and age-related macular degeneration are the leading causes of blindness in Western populations. Although it is a matter of controversy, large-scale population-based studies have reported increased prevalence of age-related macular degeneration in patients with diabetes or diabetic retinopathy. We hypothesized that metabolic syndrome, one of the major risk factors for type 2 diabetes, would represent a favorable environment for the development of choroidal neovascularization, the main complication of age-related macular degeneration. The fructose-fed rat was used as a model for metabolic syndrome in which choroidal neovascularization was induced by laser photocoagulation. Male Brown Norway rats were fed for 1, 3, and 6 months with a standard equilibrated chow diet or a 60%-rich fructose diet (n = 24 per time point). The animals expectedly developed significant body adiposity (+17%), liver steatosis at 3 and 6 months, hyperleptinemia at 1 and 3 months (two-fold increase) and hyperinsulinemia at 3 and 6 months (up to two-fold increase), but remained normoglycemic and normolipemic. The fructose-fed animals exhibited partial loss of rod sensitivity to light stimulus and reduced amplitude of oscillatory potentials at 6 months. Fructose-fed rats developed significantly more choroidal neovascularization at 14 and 21 days post-laser photocoagulation after 1 and 3 months of diet compared to animals fed the control diet. These results were consistent with infiltration/activation of phagocytic cells and up-regulation of pro-angiogenic gene expression such as Vegf and Leptin in the retina. Our data therefore suggested that metabolic syndrome would exacerbate the development of choroidal neovascularization in our experimental model.

  20. Choroidal Thickness Changes After Intravitreal Ranibizumab for Exudative Age-Related Macular Degeneration.

    Science.gov (United States)

    Minnella, Angelo Maria; Federici, Matteo; Falsini, Benedetto; Barbano, Lucilla; Gambini, Gloria; Lanza, Angela; Caporossi, Aldo; Savastano, Maria Cristina

    2016-08-01

    The results regarding changes of choroidal thickness following intravitreal ranibizumab injections in the literature are controversial. Vascular endothelial growth factor A is implicated in pathogenesis of neovascular age-related macular degeneration (AMD). The suspected unchanged choroidal layer thickness after intravitreal injections of ranibizumab suggests a possible protection of the outer blood-retinal barrier in the human eye. The aim was to evaluate choroidal thickness following the first administration of the study drug ranibizumab into the eyes of naïve wet AMD patients (nAMD). In this open label, 3-month, prospective, single-center, interventional, single-arm pilot study, 20 nAMD eyes were included and underwent three consecutive monthly injections of ranibizumab (0.5 mg/0.05 ml). Vital signs (i.e., blood pressure and pulse), ophthalmic examinations, intraocular pressure, best correct visual acuity and subfoveal choroidal thickness as examined with optical coherence tomography using enhanced depth imaging (OCT-EDI) were assessed at each visit. All patients were evaluated at baseline and at 15, 30 60 and 90 days after intravitreal injection. Ten eyes with fibrotic AMD lesions were evaluated as the control group. In all eyes, the choroidal thicknesses (µm) exhibited no significant changes from the baseline visit to the visits at 15, 30, 60 and 90 days post-injection (P > 0.05). The intravitreal treatment with ranibizumab was well tolerated, and no adverse events were registered. Choroidal thickness appeared to be unmodified following the intravitreal injection of ranibizumab into nAMD eyes. Intravitreal ranibizumab injections probably elicit a pharmacologic effect only in the choroidal neovascularization and not in the choroid circulation under neovascular lesions. Clinical Trials Eudract Registration #: 2013-005091-17.

  1. 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

    2015-01-01

    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 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. PMID:26640540

  2. Choroidal Neovascularization in a Patient with Crohn's Disease

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    Giuseppe Casalino

    2014-08-01

    Full Text Available Purpose: To report a case of subfoveal choroidal neovascularization (CNV in a patient with Crohn's disease (CD and to discuss a possible association between these two conditions. Methods: This is an observational case report. Results: A 69-year-old male affected by CD was referred to our department because of sudden visual acuity drop in the left eye. A subfoveal CNV was diagnosed based on slit-lamp fundus biomicroscopy and fluorescein angiography. Color fundus photography, infrared autofluorescence and spectral-domain optical coherence tomography imaging of both eyes were also performed. Following six intravitreal ranibizumab injections, visual improvement was obtained with no related adverse events. Conclusion: We report a case of CNV as a possible rare extraintestinal manifestation of CD. The use of ranibizumab successfully impacted on CNV, while not affecting CD, which remained quiescent.

  3. Rap1 GTPase activation and barrier enhancement in rpe inhibits choroidal neovascularization in vivo.

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    Erika S Wittchen

    Full Text Available Loss of barrier integrity precedes the development of pathologies such as metastasis, inflammatory disorders, and blood-retinal barrier breakdown present in neovascular age-related macular degeneration. Rap1 GTPase is involved in regulating both endothelial and epithelial cell junctions; the specific role of Rap1A vs. Rap1B isoforms is less clear. Compromise of retinal pigment epithelium barrier function is a contributing factor to the development of AMD. We utilized shRNA of Rap1 isoforms in cultured human retinal pigment epithelial cells, along with knockout mouse models to test the role of Rap1 on promoting RPE barrier properties, with emphasis on the dynamic junctional regulation that is triggered when the adhesion between cells is challenged. In vitro, Rap1A shRNA reduced steady-state barrier integrity, whereas Rap1B shRNA affected dynamic junctional responses. In a laser-induced choroidal neovascularization (CNV model of macular degeneration, Rap1b(-/- mice exhibited larger CNV volumes compared to wild-type or Rap1a(-/- . In vivo, intravitreal injection of a cAMP analog (8CPT-2'-O-Me-cAMP that is a known Rap1 activator significantly reduced laser-induced CNV volume, which correlated with the inhibition of CEC transmigration across 8CPT-2'O-Me-cAMP-treated RPE monolayers in vitro. Rap1 activation by 8CPT-2'-O-Me-cAMP treatment increased recruitment of junctional proteins and F-actin to cell-cell contacts, increasing both the linearity of junctions in vitro and in cells surrounding laser-induced lesions in vivo. We conclude that in vitro, Rap1A may be important for steady state barrier integrity, while Rap1B is involved more in dynamic junctional responses such as resistance to junctional disassembly induced by EGTA and reassembly of cell junctions following disruption. Furthermore, activation of Rap1 in vivo inhibited development of choroidal neovascular lesions in a laser-injury model. Our data suggest that targeting Rap1 isoforms in vivo

  4. Combination therapy of low-fluence photodynamic therapy and intravitreal ranibizumab for choroidal neovascular membrane in choroidal osteoma

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    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.

  5. MFGE8 does not influence chorio-retinal homeostasis or choroidal neovascularization in vivo.

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    William Raoul

    Full Text Available PURPOSE: Milk fat globule-epidermal growth factor-factor VIII (MFGE8 is necessary for diurnal outer segment phagocytosis and promotes VEGF-dependent neovascularization. The prevalence of two single nucleotide polymorphisms (SNP in MFGE8 was studied in two exsudative or "wet" Age-related Macular Degeneration (AMD groups and two corresponding control groups. We studied the effect of MFGE8 deficiency on retinal homeostasis with age and on choroidal neovascularization (CNV in mice. METHODS: The distribution of the SNP (rs4945 and rs1878326 of MFGE8 was analyzed in two groups of patients with "wet" AMD and their age-matched controls from Germany and France. MFGE8-expressing cells were identified in Mfge8(+/- mice expressing ß-galactosidase. Aged Mfge8(+/- and Mfge8(-/- mice were studied by funduscopy, histology, electron microscopy, scanning electron microscopy of vascular corrosion casts of the choroid, and after laser-induced CNV. RESULTS: rs1878326 was associated with AMD in the French and German group. The Mfge8 promoter is highly active in photoreceptors but not in retinal pigment epithelium cells. Mfge8(-/- mice did not differ from controls in terms of fundus appearance, photoreceptor cell layers, choroidal architecture or laser-induced CNV. In contrast, the Bruch's membrane (BM was slightly but significantly thicker in Mfge8(-/- mice as compared to controls. CONCLUSIONS: Despite a reproducible minor increase of rs1878326 in AMD patients and a very modest increase in BM in Mfge8(-/- mice, our data suggests that MFGE8 dysfunction does not play a critical role in the pathogenesis of AMD.

  6. Macrophage activation associated with chronic murine cytomegalovirus infection results in more severe experimental choroidal neovascularization.

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    Scott W Cousins

    Full Text Available The neovascular (wet form of age-related macular degeneration (AMD leads to vision loss due to choroidal neovascularization (CNV. Since macrophages are important in CNV development, and cytomegalovirus (CMV-specific IgG serum titers in patients with wet AMD are elevated, we hypothesized that chronic CMV infection contributes to wet AMD, possibly by pro-angiogenic macrophage activation. This hypothesis was tested using an established mouse model of experimental CNV. At 6 days, 6 weeks, or 12 weeks after infection with murine CMV (MCMV, laser-induced CNV was performed, and CNV severity was determined 4 weeks later by analysis of choroidal flatmounts. Although all MCMV-infected mice exhibited more severe CNV when compared with control mice, the most severe CNV developed in mice with chronic infection, a time when MCMV-specific gene sequences could not be detected within choroidal tissues. Splenic macrophages collected from mice with chronic MCMV infection, however, expressed significantly greater levels of TNF-α, COX-2, MMP-9, and, most significantly, VEGF transcripts by quantitative RT-PCR assay when compared to splenic macrophages from control mice. Direct MCMV infection of monolayers of IC-21 mouse macrophages confirmed significant stimulation of VEGF mRNA and VEGF protein as determined by quantitative RT-PCR assay, ELISA, and immunostaining. Stimulation of VEGF production in vivo and in vitro was sensitive to the antiviral ganciclovir. These studies suggest that chronic CMV infection may serve as a heretofore unrecognized risk factor in the pathogenesis of wet AMD. One mechanism by which chronic CMV infection might promote increased CNV severity is via stimulation of macrophages to make pro-angiogenic factors (VEGF, an outcome that requires active virus replication.

  7. Management of Myopic Choroidal Neovascularization: Focus on Anti-VEGF Therapy.

    Science.gov (United States)

    Teo, Kelvin Yi Chong; Ng, Wei Yan; Lee, Shu Yen; Cheung, Chui Ming Gemmy

    2016-07-01

    Myopic choroidal neovascularization (mCNV) is the second most common form of CNV after age-related macular degeneration (AMD). It is a sight-threatening complication of pathologic myopia (PM) and often affects patients in their working years causing significant impact on quality of life. Previous therapies such as photodynamic therapy with verteporfin have shown limited success. Due to the similarities in pathogenesis of mCNV and AMD CNV, anti-vascular endothelial growth factor therapy (anti-VEGF), which has so far been the mainstay of treatment for AMD CNV, has been shown to be effective in the treatment of mCNV and has become the first-line treatment of choice. This article aims to examine briefly the epidemiology and pathophysiology of mCNV, as well as review the evidence for efficacy, safety, and clinical use of anti-VEGF treatment for mCNV.

  8. Long-Term Follow-Up of Intravitreal Ranibizumab for the Treatment of Choroidal Neovascularization due to Choroidal Osteoma

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    Zenith H.Y. Wu

    2012-06-01

    Full Text Available Choroidal osteoma is an uncommon benign osseous intraocular tumor that typically affects young adult women. Choroidal neovascularization (CNV is one of the complications that can develop in eyes with choroidal osteoma. We present a case of CNV secondary to choroidal osteoma treated with intravitreal ranibizumab. A 57-year-old lady presented with painless loss of vision with a right-eye visual acuity of 20/800. Fundus examination showed a well-demarcated yellowish peripapillary choroidal osteoma with associated retinal and subretinal hemorrhage due to CNV. Three intravitreal ranibizumab injections at monthly intervals were given and her visual acuity improved to 20/30 following treatment. After 1.2 years of follow-up, the right eye visual acuity was maintained at 20/30 with no evidence of CNV recurrence. Our findings suggest that intravitreal ranibizumab may be an effective therapeutic option for treating CNV secondary to choroidal osteoma.

  9. Stereotactic radiotherapy in neovascular age-related macular degeneration

    Science.gov (United States)

    Ranjbar, Mahdy; Kurz, Maximilian; Holzhey, Annekatrin; Melchert, Corinna; Rades, Dirk; Grisanti, Salvatore

    2016-01-01

    Abstract Stereotactic radiotherapy (SRT) is a new approach to treat neovascular age-related macular degeneration (nAMD). The INTREPID trial suggested that SRT could reduce the frequency of regular intravitreal injections (IVIs) with antivascular endothelial growth factor drugs, which are necessary to control disease activity. However, the efficacy of SRT in nAMD and resulting morphological changes have not been validated under real-life circumstances, an issue, which we would like to address in this retrospective analysis. Patients who met the INTREPID criteria for best responders were eligible for SRT. A total of 32 eyes of 32 patients were treated. Thereafter, patients were examined monthly for 12 months and received pro re nata IVI of aflibercept or ranibizumab. Outcome measures were: mean number of injections, best-corrected visual acuity, and morphological changes of the outer retina-choroid complex as well as patient safety. Mean number of IVI decreased by almost 50% during the 12 months after SRT compared to the year before, whereas visual acuity increased by one line (logMAR). Morphological evaluation showed that most changes affect outer retinal layers. Stereotactic radiotherapy significantly reduced IVI retreatment in nAMD patients under real-life circumstances. Therefore, SRT might be the first step to stop visual loss as a result of IVI undertreatment, which is a major risk. PMID:28033280

  10. Pegaptanib sodium for neovascular age-related macular degeneration: clinical experience in the UK

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    Sobha Sivaprasad

    2008-06-01

    Full Text Available Sobha Sivaprasad, Nachiketa Acharya, Phil HykinMoorfields Eye Hospital, London, UKAbstract: The pathogenesis of age-related macular degeneration (AMD is unclear, but it can take either a neovascular/exudative/wet form, characterized by choroidal neovascularization (CNV, or a dry form. No treatments are available for the dry form, but there are a number of pharmacological interventions that inhibit vascular endothelial growth factor (VEGF, which is central to the pathogenesis of CNV and neovascular AMD. Available anti-VEGF agents either target all active VEGF isoforms (eg, ranibizumab, or take a more selective approach and inhibit only VEGF165 (eg, pegaptantib sodium. Current guidance on their use is equivocal and restrictive at best, resulting in associated difficulties in securing adequate, timely funding for treatment. The Moorfields Eye Hospital undertook an audit of 70 patients receiving intravitreal (ITV pegaptanib sodium on a pro re nata (prn dosing schedule. Despite initial funding delays, the audit recorded superior treatment outcomes compared with those reported in the VISION trials at 12 weeks: 88% of audit patients maintained stable vision, 29% gained vision and 6% experienced severe vision loss compared with 70%, ≥6% and ≤10% of patients in VISION at 54 weeks, respectively. The audit indicates a positive correlation between patients with better baseline visual acuity (VA and improved therapeutic benefits, including a greater likelihood of both vision gain and vision preservation. Experience at Moorfields also suggests that pegaptanib sodium is more useful in occult lesions than minimally classic lesions, and clinical experience suggests that combination therapies may offer the best approach with anti-VEGF therapies. Further randomized clinical trials will help better determine the optimal treatment strategies with pegaptanib sodium in neovascular AMD.Keywords: age-related macular degeneration, choroidal neovascularization

  11. Retinal Inhibition of CCR3 Induces Retinal Cell Death in a Murine Model of Choroidal Neovascularization.

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    Haibo Wang

    Full Text Available Inhibition of chemokine C-C motif receptor 3 (CCR3 signaling has been considered as treatment for neovascular age-related macular degeneration (AMD. However, CCR3 is expressed in neural retina from aged human donor eyes. Therefore, broad CCR3 inhibition may be harmful to the retina. We assessed the effects of CCR3 inhibition on retina and choroidal endothelial cells (CECs that develop into choroidal neovascularization (CNV. In adult murine eyes, CCR3 colocalized with glutamine-synthetase labeled Műller cells. In a murine laser-induced CNV model, CCR3 immunolocalized not only to lectin-stained cells in CNV lesions but also to the retina. Compared to non-lasered controls, CCR3 mRNA was significantly increased in laser-treated retina. An intravitreal injection of a CCR3 inhibitor (CCR3i significantly reduced CNV compared to DMSO or PBS controls. Both CCR3i and a neutralizing antibody to CCR3 increased TUNEL+ retinal cells overlying CNV, compared to controls. There was no difference in cleaved caspase-3 in laser-induced CNV lesions or in overlying retina between CCR3i- or control-treated eyes. Following CCR3i, apoptotic inducible factor (AIF was significantly increased and anti-apoptotic factor BCL2 decreased in the retina; there were no differences in retinal vascular endothelial growth factor (VEGF. In cultured human Műller cells exposed to eotaxin (CCL11 and VEGF, CCR3i significantly increased TUNEL+ cells and AIF but decreased BCL2 and brain derived neurotrophic factor, without affecting caspase-3 activity or VEGF. CCR3i significantly decreased AIF in RPE/choroids and immunostaining of phosphorylated VEGF receptor 2 (p-VEGFR2 in CNV with a trend toward reduced VEGF. In cultured CECs treated with CCL11 and/or VEGF, CCR3i decreased p-VEGFR2 and increased BCL2 without increasing TUNEL+ cells and AIF. These findings suggest that inhibition of retinal CCR3 causes retinal cell death and that targeted inhibition of CCR3 in CECs may be a safer if CCR3

  12. Diagnosis and Follow-Up of Nonexudative Choroidal Neovascularization With Multiple Optical Coherence Tomography Angiography Devices: A Case Report

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    Lane, Mark; Ferrara, Daniela; Louzada, Ricardo Noguera; Fujimoto, James G.; Seddon, Johanna M.

    2017-01-01

    Nonexudative choroidal neovascularization (CNV) is a new phenomenon that has only recently been described in the literature with the advent of optical coherence tomography angiography (OCTA) imaging. The authors present a 1-year longitudinal follow-up of a nonexudative CNV lesion secondary to age-related macular degeneration. This report describes the appearance of the lesion on two commercially available spectral-domain OCTA devices and one prototype swept-source OCTA device. Management of these cases is still debatable. Watchful waiting with regular follow-up using serial OCTA to monitor disease progression has been valuable in this case. PMID:27548457

  13. Inflammatory choroidal neovascular membrane in posterior uveitis-pathogenesis and treatment

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    Dhingra Narendra

    2010-01-01

    Full Text Available Choroidal neovascular membrane (CNVM formation is a well-documented sight-threatening complication of posterior segment intraocular inflammation (PSII. The aim of this article is to review the basic and clinical science literature on the pathogenesis of CNVM formation in PSII and to present results of a case series. We searched the literature using the mesh terms- inflammation, CNVM, age-related macular degeneration, immunosuppression, photodynamic therapy, steroids, vascular endothelial growth factors and posterior uveitis. Additionally, we evaluated the visual outcome of and clinical response to our standard treatment protocol involving a combination treatment for young patients with inflammatory CNVM. The development of CNVM in PSII is promulgated by infiltrating myeloid cells as well as choroidal and retinal myeloid cell activation, subsequent vascular endothelial growth factors, cytokine and chemokine production and complement activation acting in consort to mediate angiogenic responses. No clear standard of care currently exists for the treatment of inflammatory CNVM and various combinations have been tried. Using our combination treatment, visual acuity improved in four, stabilized in one and worsened in four patients. Though significant advances have occurred in the understanding of the pathogenesis and management of this condition, optimizing therapeutic regimens will require further well-constructed prospective cohort series.

  14. Resistance to anti-VEGF therapy in neovascular age-related macular degeneration: a comprehensive review.

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    Yang, Shiqi; Zhao, Jingke; Sun, Xiaodong

    2016-01-01

    As a progressive chronic disease, age-related macular degeneration (AMD) is the leading cause of irreversible vision impairment worldwide. Experimental and clinical evidence has demonstrated that vascular endothelial growth factor (VEGF) plays a vital role in the formation of choroidal neovascularization. Intravitreal injections of anti-VEGF agents have been recommended as a first-line treatment for neovascular AMD. However, persistent fluid or recurrent exudation still occurs despite standardized anti-VEGF therapy. Patients suffering from refractory or recurrent neovascular AMD may develop mechanisms of resistance to anti-VEGF therapy, which results in a diminished therapeutic effect. Until now, there has been no consensus on the definitions of refractory neovascular AMD and recurrent neovascular AMD. This article aims at clarifying these concepts to evaluate the efficacy of switching drugs, which contributes to making clinical decision more scientifically. Furthermore, insight into the causes of resistance to anti-VEGF therapy would be helpful for developing possible therapeutic approaches, such as combination therapy and multi-target treatment that can overcome this resistance.

  15. 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

  16. Modifying Choroidal Neovascularization Development with a Nutritional Supplement in Mice

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    Alina Adriana Ivanescu

    2015-07-01

    Full Text Available We examined the effect of nutritional supplements (modified Age Related Eye Disease Study (AREDS-II formulation containing vitamins, minerals, lutein, resveratrol, and omega-3 fatty acids on choroidal neovascularization (CNV. Supplements were administered alone and combined with intravitreal anti-VEGF in an early-CNV (diode laser-induced murine model. Sixty mice were evenly divided into group V (oral vehicle, intravitreal saline, group S (oral supplement, intravitreal saline, group V + aVEGF (oral vehicle, intravitreal anti-VEGF, and group S + aVEGF (oral supplement, intravitreal anti-VEGF. Vehicle and nutritional supplements were administered daily for 38 days beginning 10 days before laser. Intravitreal injections were administered 48 h after laser. Fluorescein angiography (FA and flat-mount CD31 staining evaluated leakage and CNV lesion area. Expression of VEGF, MMP-2 and MMP-9 activity, and NLRP3 were evaluated with RT-PCR, zymography, and western-blot. Leakage, CNV size, VEGF gene and protein expression were lower in groups V + aVEGF, S + aVEGF, and S than in V (all p < 0.05. Additionally, MMP-9 gene expression differed between groups S + aVEGF and V (p < 0.05 and MMP-9 activity was lower in S + aVEGF than in V and S (both p < 0.01. Levels of MMP-2 and NLRP3 were not significantly different between groups. Nutritional supplements either alone or combined with anti-VEGF may mitigate CNV development and inhibit retinal disease involving VEGF overexpression and CNV.

  17. Breaking barriers: insight into the pathogenesis of neovascular age-related macular degeneration

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    Hartnett ME

    2011-09-01

    Full Text Available Haibo Wang1, Erika S Wittchen2, M Elizabeth Hartnett11Department of Ophthalmology, John A Moran Eye Center, University of Utah, Salt Lake City, UT; 2Department of Cell and Developmental Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USAAbstract: Neovascular age-related macular degeneration (AMD is a leading cause of central visual acuity loss in a growing segment of the population, those over the age of 60 years. Treatment has improved over the last decade, with the availability of agents that inhibit the bioactivity of vascular endothelial growth factor (VEGF, but it is still limited, because of tachyphylaxis and potential risk and toxicity of anti-VEGF agents. The authors have sought to understand the mechanisms of choroidal endothelial cell (CEC activation and transmigration of the retinal pigment epithelium (RPE and of RPE barrier dysfunction, events preceding vision-threatening neovascular AMD. The authors developed physiologically relevant human RPE and CEC coculture and transmigration models that have been important in helping to understand causes of events in human neovascular AMD. The authors can control for interactions between these cells and can separately assess activation of signaling pathways in each cell type relevant during CEC transmigration. Using these models, it was found that VEGF, particularly the cell-associated VEGF splice variant VEGF189, accounts for about 40% of CEC transmigration across the RPE. This percentage is in the range of similar reports following clinical inhibition of VEGF in neovascular AMD. RPE VEGF189 working through CEC VEGF receptor 2 activates the small guanosine triphosphatase (GTPase of the Rho family, Rac1, in CECs, which in turn facilitates CEC transmigration. Conversely, inhibition of Rac1 activity prevents CEC transmigration. Once activated, Rac1 aggregates with subunits of nicotinamide adenine dinucleotide phosphate (NADPH oxidase, resulting in the generation of reactive

  18. Intravitreal dobesilate in the treatment of choroidal neovascularisation associated with age-related macular degeneration: report of two cases.

    Science.gov (United States)

    Cuevas, Pedro; Outeiriño, Luis; Azanza, Carlos; Giménez-Gallego, Guillermo

    2012-09-03

    This case report presents the effectiveness of intravitreal administration of dobesilate, a synthetic fibroblast growth factor inhibitor, in two patients showing neovascular age-related macular degeneration of the classic, and of the occult choroidal neovascularisation types, respectively. Our study demonstrates that the treatment induces the regression of both forms of this pathology, as assessed by spectral optical coherence tomography. Improvement of the lesions was accompanied of visual acuity improvement.

  19. Antivascular Endothelial Growth Factor Agents for Neovascular Age-Related Macular Degeneration

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    Ilias Zampros

    2012-01-01

    Full Text Available Age-related macular degeneration (AMD is the leading cause of severe visual loss and blindness over the age of 50 in developed countries. Vascular endothelial growth factor (VEGF is considered as a critical molecule in the pathogenesis of choroidal neovascularization (CNV, which characterizes the neovascular AMD. Anti-VEGF agents are considered the most promising way of effectively inhibition of the neovascular AMD process. VEGF is a heparin-binding glycoprotein with potent angiogenic, mitogenic and vascular permeability-enhancing activities specific for endothelial cells. Two anti-VEGF agents have been approved by the US Food and Drug Administration (FDA for the treatment of neovascular AMD. Pegaptanib sodium, which is an aptamer and ranibizumab, which is a monoclonal antibody fragment. Another humanized monoclonal antibody is currently off-label used, bevacizumab. This paper aims to discuss in details the effectiveness, the efficacy and safety of these three anti-VEGF agents. New anti-VEGF compounds which are recently investigated for their clinical usage (VEGF-trap, small interfering RNA are also discussed for their promising outcomes.

  20. Radiation therapy for neovascular age-related macular degeneration

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    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

  1. Simple, reliable and fast spectrofluorometric method for determination of plasma Verteporfin (Visudyne) levels during photodynamic therapy for choroidal neovascularization.

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    Aquaron, R; Forzano, O; Murati, J L; Fayet, G; Aquaron, C; Ridings, B

    2002-12-01

    Photodynamic therapy with Verteporfin, a potent photosensitizer dye, is a very effective treatment for age related macular degeneration due to choroidal neovascularization. Photodynamic therapy offers the potential for selective tissue injury in part attributable to preferential localization of Verteporfin, administrated by intravenous infusion, to the choroidal neovascularization complex and irradiation of the complex with non-laser thermal light at 690 nm resulting in at least temporary thrombosis and vessel closure. Verteporfin is a benzoporphyrin derivative monoacid ring A formulated as a unilamellar liposome. In the blood Verteporfin is associated with lipoprotein fractions and is rapidly cleared via a receptor-mediated uptake mechanism due the high expression of LDL receptors in neovascular tissues. Verteporfin was undetectable in plasma 24 hr after infusion of the recommended dose: 6 mg/m2 of body surface area. The main side effect is photosensitivity of skin which is usually short-lived (24-48 hr) with a low incidence (2.3%). As skin photosensitivity depends on circulating rather than tissue drug levels, we investigate the possibility of developing a simple, fast and reliable spectrofluorometric method to measure plasma Verteporfin levels. Fluorescence emission spectrum (550-750 nm) of 1:10 saline diluted plasma with lambda exc=430 nm showed a characteristic emission peak at 692 nm, the height being proportional to the Verteporfin levels. The sensitivity is around 100 ng/ml and the pharmacokinetics of Verteporfin has been studied from 0 to 5 hr after infusion in six patients older than 65 years with age-related macular degeneration.

  2. 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.

  3. Breaking barriers: insight into the pathogenesis of neovascular age-related macular degeneration

    Science.gov (United States)

    Wang, Haibo; Wittchen, Erika S; Hartnett, M Elizabeth

    2011-01-01

    Neovascular age-related macular degeneration (AMD) is a leading cause of central visual acuity loss in a growing segment of the population, those over the age of 60 years. Treatment has improved over the last decade, with the availability of agents that inhibit the bioactivity of vascular endothelial growth factor (VEGF), but it is still limited, because of tachyphylaxis and potential risk and toxicity of anti-VEGF agents. The authors have sought to understand the mechanisms of choroidal endothelial cell (CEC) activation and transmigration of the retinal pigment epithelium (RPE) and of RPE barrier dysfunction, events preceding vision-threatening neovascular AMD. The authors developed physiologically relevant human RPE and CEC coculture and transmigration models that have been important in helping to understand causes of events in human neovascular AMD. The authors can control for interactions between these cells and can separately assess activation of signaling pathways in each cell type relevant during CEC transmigration. Using these models, it was found that VEGF, particularly the cell-associated VEGF splice variant VEGF189, accounts for about 40% of CEC transmigration across the RPE. This percentage is in the range of similar reports following clinical inhibition of VEGF in neovascular AMD. RPE VEGF189 working through CEC VEGF receptor 2 activates the small guanosine triphosphatase (GTPase) of the Rho family, Rac1, in CECs, which in turn facilitates CEC transmigration. Conversely, inhibition of Rac1 activity prevents CEC transmigration. Once activated, Rac1 aggregates with subunits of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, resulting in the generation of reactive oxygen species. Activated NADPH oxidase increases choroidal neovascularization in animal models of laser-induced injury. Rac1 is also downstream of the eotaxin-CCR3 pathway, another pathway important in human neovascular AMD. Studies also suggest that active Ras-related protein 1

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

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    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

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

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    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

  6. Comparison of the original Amsler grid with the preferential hyperacuity perimeter for detecting choroidal neovascularization in age-related macular degeneration Comparação entre a tela de Amsler original e o perímetro de hiperacuidade preferencial para a detecção de neovascularização de coróide secundária à degeneração macular relacionada à idade

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    David Leonardo Cruvinel Isaac

    2007-10-01

    Full Text Available PURPOSE: To compare the preferential hyperacuity perimeter (Preview PHP; Carl Zeiss Meditec, Dublin, CA with the original Amsler grid in the detection of choroidal neovascularization (CNV in patients with age-related macular degeneration (AMD. METHODS: Patients were classified into groups, based on the severity of the age-related macular degeneration and underwent preferential hyperacuity perimeter and Amsler grid testing. High sensitivity and or high specificity of a method were defined as the observation of at least 80% of each one the parameters. RESULTS: Sixty-five patients (65 eyes were analyzed statistically. The sensitivity of detection of choroidal neovascularization was 70% by the Amsler grid and 90% by the preferential hyperacuity perimeter and the specificity of the Amsler grid was 85.5% and that of the preferential hyperacuity perimeter 81.8%. CONCLUSIONS: The preferential hyperacuity perimeter has greater sensitivity than the Amsler grid in the detection of choroidal neovascularization among patients over 50 years of age and is a promising method for monitoring patients with age-related macular degeneration. Although the original Amsler grid is less sensitive, it is a portable method, not expensive, accessible and presents reasonable sensitivity and high specificity in the diagnosis of choroidal neovascularization. Its use can be recommended for self-monitoring in patients with age-related macular degeneration as an alternative to preferential hyperacuity perimeter and when this method is not available.OBJETIVO: Comparar o perímetro de hiperacuidade preferencial (Preview PHP; Carl Zeiss Meditec, Dublin, Califórnia - EUA com a tela de Amsler original na detecção de neovascularização de coróide (NVC em pacientes com degeneração macular relacionada à idade (DMRI. MÉTODOS: Os pacientes foram classificados em grupos baseados no grau de gravidade da degeneração macular relacionada à idade e foram submetidos aos testes do per

  7. Stereotactic radiotherapy in neovascular age-related macular degeneration

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    Ranjbar, Mahdy; Kurz, Maximilian; Holzhey, Annekatrin; Melchert, Corinna; Rades, Dirk; Grisanti, Salvatore

    2016-01-01

    Abstract Stereotactic radiotherapy (SRT) is a new approach to treat neovascular age-related macular degeneration (nAMD). The INTREPID trial suggested that SRT could reduce the frequency of regular intravitreal injections (IVIs) with antivascular endothelial growth factor drugs, which are necessary to control disease activity. However, the efficacy of SRT in nAMD and resulting morphological changes have not been validated under real-life circumstances, an issue, which we would like to address ...

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

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    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.

  9. Circulating monocytes and B-lymphocytes in neovascular age-related macular degeneration

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    Hector SM

    2017-01-01

    imbalance in the recruitment of macrophages into the retina during disease development. Keywords: macular degeneration, choroidal neovascularization, flow cytometry

  10. Possible vitreous involvement in a case with rapidly progressing choroidal neovascularization

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    Masayuki Hata

    2012-01-01

    Full Text Available A 65-year-old man with subfoveal choroidal neovascularization (CNV underwent photodynamic therapy (PDT. Despite the sequential treatments, the CNV grew larger and finally penetrated the retina. Vitreous adhesion was observed at the edge of the supraretinal fibrotic tissue. The case highlighted the possible unexpected side-effect of PDT. The upregulation of the vascular endothelial growth factor or the enhanced vitreous traction was considered to be responsible for the event.

  11. Intravitreal ranibizumab for the treatment of choroidal neovascularization secondary to ocular toxoplasmosis

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    Nikunj J Shah

    2011-01-01

    Full Text Available The purpose of the study was to report a case of choroidal neovascularization (CNV secondary to ocular toxoplasmosis in an 18-year-old female patient. She was treated with a single intravitreal injection of ranibizumab. The CNV resolved as confirmed by fluorescein angiography and optical coherence tomography (OCT. The visual acuity improved to 20/30, which was maintained till the last follow-up visit at two years, without requisition of a repeat injection.

  12. Effect of photodynamic therapy combined with intravitreal injection of Lucentis therapy on choroidal neovascularization

    Institute of Scientific and Technical Information of China (English)

    Yan-Mei Su

    2016-01-01

    Objective:To analyze the efficacy of photodynamic therapy combined with intravitreal injection of Lucentis therapy for choroidal neovascularization.Methods: A total of 82 cases with choroidal neovascularization receiving inpatient therapy in our hospital from August 2013 to August 2014 were selected as research subjects, and according to random number table method, all enrolled patients were divided into control group (received photodynamic therapy) and observation group (received photodynamic therapy combined with intravitreal injection of Lucentis therapy), each group with 41 cases. Differences in best corrected visual acuity, intraocular pressure and central macular thickness, mean sensitivity of visual field and so on of two groups were compared.Results:After treatment, visual acuity improvement ratio of observation group was significantly higher than that of control group and visual acuity decrease ratio was lower than that of control group (P<0.05); intraocular pressure and central macular thickness were significantly less than those of control group (P<0.05); mean sensitivity of 10o and 30o visual field was higher than that of control group (P<0.05).Conclusions:Photodynamic therapy combined with intravitreal injection of Lucentis therapy can effectively improve vision and visual acuity of patients with choroidal neovascularization and reduce intraocular pressure and central macular thickness; it is an ideal treatment method.

  13. The Application of OCTA in Assessment of Anti-VEGF Therapy for Idiopathic Choroidal Neovascularization

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    Qin Chen

    2016-01-01

    Full Text Available Purpose. To assess the morphology of idiopathic choroidal neovascularization (ICNV by optical coherence tomography angiography (OCTA and determine the therapeutic effects of intravitreal antivascular endothelial growth factor (anti-VEGF. Method. Patients with naive ICNV were assessed by spectral domain optical coherence tomography (SD-OCT and OCTA in this observational study. The timing of observation was before treatment, 1 day after treatment with intravitreal anti-VEGF injection, and 1 month after the treatment. The central retina thickness (CRT on SD-OCT, selected CNV area, and flow area on OCTA were measured. Results. A total of 17 eyes from 17 patients with ICNV were included in this study. OCTA showed visible irregular choroidal neovascularization with “tree-in-bud” form on outer retinal layer. After treatment, as well as in the 1-day follow-up, CNV decreased in size from the periphery, and the vessel density was reduced. As shown on OCTA, the selected CNV area and flow area were significantly reduced compared to pretreatment. The rate of CNV vessel area changes was higher on OCTA than the changes in CRT on SD-OCT at 1-day and 1-month follow-up. Conclusion. Intravitreal injection of anti-VEGF is effective for idiopathic choroidal neovascularization, and the treatment outcomes are observable after 1 day. OCTA provides a useful approach for monitoring and evaluating the treatment of intravitreal anti-VEGF for CNV.

  14. The complement regulatory protein CD59: insights into attenuation of choroidal neovascularization.

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    Schnabolk, Gloriane; Tomlinson, Stephen; Rohrer, Bärbel

    2014-01-01

    Complement activation is associated with age-related macular degeneration (AMD), with the retinal pigment epithelium (RPE) being one of the main target tissues. In AMD, disease severity is correlated with the formation of the membrane attack complex (MAC), the terminal step in the complement cascade, as well as diminished RPE expression of CD59, a membrane-bound regulatory protein of MAC formation. This has prompted the search for therapeutic strategies based on MAC inhibition, and soluble forms of CD59 (sCD59) have been investigated in mouse laser-induced choroidal neovascularization, a model for "wet" AMD. Unlike membrane-bound CD59, sCD59 provides relatively poor cell protection from complement, and different strategies to increase sCD59 activity at the cell membrane level have been investigated. These include increasing the circulatory half-life of sCD59 by the addition of an Fc moiety; increasing the half-life of sCD59 in target tissues by modifying CD59 with a (non-specific) membrane-targeting domain; and by locally overexpressing sCD59 via adenoviral vectors. Finally, a different strategy currently under investigation employs complement receptor (CR)2-mediated targeting of CD59 exclusively to membranes under complement attack. CR2 recognizes long-lasting membrane-bound breakdown activation fragments of complement C3. CR2-CD59 may have greater therapeutic potential than other complement inhibitory approaches, since it can be administered either systemically or locally, it will bind specifically to membranes containing activated complement activation fragments, and dosing can be regulated. Hence, this strategy might offer opportunities for site-specific inhibition of complement in diseases with restricted sites of inflammation such as AMD.

  15. Oscillatory Photodynamic Therapy for Choroidal Neovascularization and Central Serous Retinopathy; a Pilot Study

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    Gholam A Peyman

    2011-01-01

    Full Text Available Purpose: To report the preliminary results of oscillatory photodynamic therapy (OPDT for choroidal neovascularization (CNV and central serous retinopathy (CSR. Methods: This study included 7 eyes of 6 patients with CSR (2 eyes, idiopathic CNV (2 eyes, CNV due to age-related macular degeneration (AMD (2 eyes, and peripapillary CNV secondary to presumed ocular histoplasmosis syndrome (1 eye. Intravenous verteporfin (6 mg/m2 body surface area was infused over 10 minutes followed by oscillating laser (wavelength 689 nm covering slightly beyond the entire lesion. An Area Centralis lens was applied and laser was delivered (600 mW/cm2 fluence rate and 50 J/cm2 dose. Intravitreal bevacizumab and dexamethasone combination therapy was used with OPDT in 4 eyes with CNV; intravitreal dexamethasone and triamcinolone acetonide were injected in the other eye with CNV. Clinical examination, funduscopy, fluorescein angiography, and optical coherence tomography (OCT were performed at baseline and after treatment. Results: After mean follow-up of 7.1±5.1 months, visual acuity improved from 0.87±0.69 logMAR (20/160 to 0.60±0.65 logMAR (20/80 (P = 0.027; central foveal thickness decreased from 322±62.1 to 240.7±34.8 microns as measured by OCT (P = 0.018. Fluorescein angiography and OCT demonstrated cessation of vascular leakage, and resolution of hemorrhage and subretinal fluid in all eyes. No adverse events or recurrence were noted. Conclusion: OPDT was effective in treating CNV lesions and CSR. OPDT may be an improvement on standard PDT due to reduced side effects, thermal damage and scarring.

  16. IKK2 inhibition using TPCA-1-loaded PLGA microparticles attenuates laser-induced choroidal neovascularization and macrophage recruitment.

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    Subhash Gaddipati

    Full Text Available The inhibition of NF-κB by genetic deletion or pharmacological inhibition of IKK2 significantly reduces laser-induced choroid neovascularization (CNV. To achieve a sustained and controlled intraocular release of a selective and potent IKK2 inhibitor, 2-[(aminocarbonylamino]-5-(4-fluorophenyl-3-thiophenecarboxamide (TPCA-1 (MW: 279.29, we developed a biodegradable poly-lactide-co-glycolide (PLGA polymer-delivery system to further investigate the anti-neovascularization effects of IKK2 inhibition and in vivo biosafety using laser-induced CNV mouse model. The solvent-evaporation method produced spherical TPCA-1-loaded PLGA microparticles characterized with a mean diameter of 2.4 ¼m and loading efficiency of 80%. Retrobulbar administration of the TPCA-1-loaded PLGA microparticles maintained a sustained drug level in the retina during the study period. No detectable TPCA-1 level was observed in the untreated contralateral eye. The anti-CNV effect of retrobulbarly administrated TPCA-1-loaded PLGA microparticles was assessed by retinal fluorescein leakage and isolectin staining methods, showing significantly reduced CNV development on day 7 after laser injury. Macrophage infiltration into the laser lesion was attenuated as assayed by choroid/RPE flat-mount staining with anti-F4/80 antibody. Consistently, laser induced expressions of Vegfa and Ccl2 were inhibited by the TPCA-1-loaded PLGA treatment. This TPCA-1 delivery system did not cause any noticeable cellular or functional toxicity to the treated eyes as evaluated by histology and optokinetic reflex (OKR tests; and no systemic toxicity was observed. We conclude that retrobulbar injection of the small-molecule IKK2 inhibitor TPCA-1, delivered by biodegradable PLGA microparticles, can achieve a sustained and controllable drug release into choroid/retina and attenuate laser-induced CNV development without causing apparent systemic toxicity. Our results suggest a potential clinical application of

  17. Anti-vascular endothelial growth factors for choroidal neovascularization secondary to choroidal osteoma: Long-term results

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    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.

  18. VEGF Mediates ApoE4-Induced Neovascularization and Synaptic Pathology in the Choroid and Retina.

    Science.gov (United States)

    Antes, Ran; Salomon-Zimri, Shiran; Beck, Susanne C; Garcia Garrido, Marina; Livnat, Tami; Maharshak, Idit; Kadar, Tamar; Seeliger, Mathias; Weinberger, Dov; Michaelson, Daniel M

    2015-01-01

    Apolipoprotein E4 (apoE4), the most prevalent genetic risk factor for Alzheimer's disease (AD), is associated with neuronal and vascular impairments. Recent findings suggest that retina of apoE4 mice have synaptic and functional impairments. We presently investigated the effects of apoE4 on retinal and choroidal vasculature and the possible role of VEGF in these effects. There were no histological differences between the retinal and choroidal vasculatures of naïve apoE3 and apoE4 mice. In contrast, laserdriven choroidal injury induced higher levels of choroidal neovascularization (CNV) in apoE4 than in apoE3 mice. These effects were associated with an inflammatory response and with activation of the Muller cells and asrocytic markers gluthatione synthetase and GFAP, all of which were more pronounced in the apoE4 mice. CNV also induced a transient increase in the levels of the synaptic markers synaptophysin and PSD95 which were however similar in the apoE4 and apoE3 naive mice. Retinal and choroidal VEGF and apoE levels were lower in naïve apoE4 than in corresponding apoE3 mice. In contrast, VEGF and apoE levels rose more pronouncedly following laser injury in the apoE4 than in apoE3 mice. Taken together, these findings suggest that the apoE4-induced retinal impairments, under basal conditions, may be related to reduced VEGF levels in the eyes of these mice. The hyper-neovascularization in the apoE4 mice might be driven by increased inflammation and the associated surge in VEGF following injury. Retinal and choroidal VEGF and apoE levels were lower in naïve apoE4 than in corresponding apoE3 mice. In contrast, VEGF and apoE levels rose more pronouncedly following laser injury in the apoE4 than in apoE3 mice. Taken together, these findings suggest that the apoE4-induced retinal impairments, under basal conditions, may be related to reduced VEGF levels in the eyes of these mice. The hyper-neovascularization in the apoE4 mice might be driven by increased inflammation

  19. Cytokines in neovascular age-related macular degeneration: fundamentals of targeted combination therapy.

    Science.gov (United States)

    de Oliveira Dias, João Rafael; Rodrigues, Eduardo Büchele; Maia, Mauricio; Magalhães, Octaviano; Penha, Fernando Marcondes; Farah, Michel Eid

    2011-12-01

    The neovascular form of age-related macular degeneration (AMD), called wet-AMD or choroidal neovascularisation, begins with damage to the outer retinal cells and retinal pigment epithelium (RPE), which elicits a cascade of inflammatory and angiogenic responses leading to neovascularisation under the macula. Studies showed that oxidative damage, chronic inflammation of the RPE and complement misregulation work at different steps of this disease. After established neovascularisation, several pro- and antiangiogenic agents start to play an important role. Vascular endothelial growth factors (VEGFs) are the most specific and potent regulators of angiogenesis, which are inhibited by intravitreal injections of ranibizumab, bevacizumab, VEGF Trap, pegaptanib sodium and other agents under investigation. Pigment epithelium-derived factor, on the other hand, shows neuroprotective and antiangiogenic activities. Hepatocyte growth factor (HGF) has a mitogenic effect on a wide range of epithelial and endothelial cells, and it is inhibited by an anti-HGF monoclonal antibody. Platelet-derived growth factor is a potent chemoattractant and mitogen for both fibroblasts and retinal RPE cells, which has been inhibited experimentally by VEGF Trap and human anti-platelet-derived growth factor-D monoclonal antibody. Fibroblast growth factor-2 has pleiotropic effects in different cell and organ systems, and it is blocked by anti-FGF antibodies, with a greater benefit regarding antiangiogenesis when combined treatment with anti-VEGF is performed. Tumour necrosis factor alpha is expressed in the retina and the choroid, and its blockade in choroidal neovascularisation includes the use of monoclonals such as infliximab. This paper reviews the most important cytokines involved in the pathogenesis of wet-AMD, with emphasis on potential combined therapies for disease control.

  20. Quantification of choroidal neovascularization vessel length using optical coherence tomography angiography

    Science.gov (United States)

    Gao, Simon S.; Liu, Li; Bailey, Steven T.; Flaxel, Christina J.; Huang, David; Li, Dengwang; Jia, Yali

    2016-07-01

    Quantification of choroidal neovascularization (CNV) as visualized by optical coherence tomography angiography (OCTA) may have importance clinically when diagnosing or tracking disease. Here, we present an automated algorithm to quantify the vessel skeleton of CNV as vessel length. Initial segmentation of the CNV on en face angiograms was achieved using saliency-based detection and thresholding. A level set method was then used to refine vessel edges. Finally, a skeleton algorithm was applied to identify vessel centerlines. The algorithm was tested on nine OCTA scans from participants with CNV and comparisons of the algorithm's output to manual delineation showed good agreement.

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

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    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.

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

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    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.

  3. Intravitreal ranibizumab therapy versus photodynamic therapy for idiopathic choroidal neovascularization: a comparative study on visual acuity, retinal and choroidal thickness

    Institute of Scientific and Technical Information of China (English)

    Shi Xuehui; Wei Wenbin; Zhang Cong

    2014-01-01

    Background Photodynamic therapy (PDT) has been recommended as a main treatment for idiopathic choroidal neovascularization (I-CNV).But the visual results of PDT were inconsistent and variable,and PDT may bring severe damage to the retinal pigment epithelium and choriocapillaries.In recent years,intravitreal ranibizumab therapy,showing favorable visual outcomes,has developed as an advanced treatment for choroidal neovascularization (CNV).Although both methods have been reported to be effective in treating I-CNV,there is no detailed comparative report between the two methods.This study aimed to compare visual outcomes,retinal and choroidal thickness between intravitreal ranibizumab therapy and PDT in the treatment of I-CNV,and investigate the correlation of visual outcomes with retinal and choroidal thickness in each of the two groups.Methods Thirty-seven eyes of 37 patients with I-CNV were involved in this study; 19 eyes were treated with intravitreal ranibizumab therapy and 18 eyes were treated with PDT.The best corrected visual acuity (BCVA) was recorded before and at each follow-up visit after treatments (IogMAR).Enhanced-depth imaging optical coherence tomography (EDI-OCT) was used to evaluate the retinal structural changes,and to measure central retinal thickness (CRT) and central choroidal thickness (CCT).Results Mean BCVA was 0.64±0.27 in PDT group and 0.69±0.22 in ranibizumab group at baseline (P=0.55).When compared with the baseline,mean BCVA in PDT group was improved significantly at 3-month after PDT (0.41±0.16,P=0.002),then changed little (0.42±0.25 at 12-month,P=0.88).Whereas mean BCVA in Ranibizumab group was improved significantly at each follow-up visit.It improved much more obviously in the first month and then remained stable.The mean BCVA in the ranibizumab group was significantly better at each follow-up visit than that in PDT (P <0.05).When compared with the baseline,mean CRT in PDT group decreased significantly since 3-month visit

  4. Role of Intravitreal Antivascular Endothelial Growth Factor Injections for Choroidal Neovascularization due to Choroidal Osteoma.

    Science.gov (United States)

    Mansour, Ahmad M; Arevalo, J Fernando; Al Kahtani, Eman; Zegarra, Hernando; Abboud, Emad; Anand, Rajiv; Ahmadieh, Hamid; Sisk, Robert A; Mirza, Salman; Tuncer, Samuray; Navea Tejerina, Amparo; Mataix, Jorge; Ascaso, Francisco J; Pulido, Jose S; Guthoff, Rainer; Goebel, Winfried; Roh, Young Jung; Banker, Alay S; Gentile, Ronald C; Martinez, Isabel Alonso; Morris, Rodney; Panday, Neeraj; Min, Park Jung; Mercé, Emilie; Lai, Timothy Y Y; Massoud, Vicky; Ghazi, Nicola G

    2014-01-01

    We treated 26 eyes of 25 young patients having a mean age of 30 years with intravitreal vascular endothelial growth factor (VEGF) inhibitor for choroidal new vessel (CNV) formation overlying choroidal osteoma over a mean follow-up of 26 months. Mean number of injections was 2.4 at 6 months, 3.2 at 12 months, and 5.5 at 24 months. CNV was subfoveal in 14 eyes, juxtafoveal in 5, extrafoveal in 5, and peripapillary in 2. By paired comparison, mean decrease from baseline was 119.7 microns at 6 months (n = 15; P = 0.001), 105.3 microns at 1 year (n = 10; P = 0.03), and 157.6 microns at 2 years (n = 7; P = 0.08). BCVA improved by 3.3 lines at 6 months after therapy (n = 26; P < 0.001), 2.8 lines (n = 20; P = 0.01) at 1 year, and 3.1 lines (n = 13; P = 0.049) at 2 years. We conclude that intravitreal anti-VEGF injections improve vision in majority of eyes with CNV from choroidal osteoma.

  5. Role of Intravitreal Antivascular Endothelial Growth Factor Injections for Choroidal Neovascularization due to Choroidal Osteoma

    Science.gov (United States)

    Mansour, Ahmad M.; Al Kahtani, Eman; Zegarra, Hernando; Anand, Rajiv; Ahmadieh, Hamid; Sisk, Robert A.; Mirza, Salman; Tuncer, Samuray; Navea Tejerina, Amparo; Mataix, Jorge; Ascaso, Francisco J.; Pulido, Jose S.; Guthoff, Rainer; Goebel, Winfried; Roh, Young Jung; Banker, Alay S.; Gentile, Ronald C.; Martinez, Isabel Alonso; Morris, Rodney; Panday, Neeraj; Min, Park Jung; Mercé, Emilie; Lai, Timothy Y. Y.; Massoud, Vicky; Ghazi, Nicola G.

    2014-01-01

    We treated 26 eyes of 25 young patients having a mean age of 30 years with intravitreal vascular endothelial growth factor (VEGF) inhibitor for choroidal new vessel (CNV) formation overlying choroidal osteoma over a mean follow-up of 26 months. Mean number of injections was 2.4 at 6 months, 3.2 at 12 months, and 5.5 at 24 months. CNV was subfoveal in 14 eyes, juxtafoveal in 5, extrafoveal in 5, and peripapillary in 2. By paired comparison, mean decrease from baseline was 119.7 microns at 6 months (n = 15; P = 0.001), 105.3 microns at 1 year (n = 10; P = 0.03), and 157.6 microns at 2 years (n = 7; P = 0.08). BCVA improved by 3.3 lines at 6 months after therapy (n = 26; P < 0.001), 2.8 lines (n = 20; P = 0.01) at 1 year, and 3.1 lines (n = 13; P = 0.049) at 2 years. We conclude that intravitreal anti-VEGF injections improve vision in majority of eyes with CNV from choroidal osteoma. PMID:25147732

  6. Role of Intravitreal Antivascular Endothelial Growth Factor Injections for Choroidal Neovascularization due to Choroidal Osteoma

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    Ahmad M. Mansour

    2014-01-01

    Full Text Available We treated 26 eyes of 25 young patients having a mean age of 30 years with intravitreal vascular endothelial growth factor (VEGF inhibitor for choroidal new vessel (CNV formation overlying choroidal osteoma over a mean follow-up of 26 months. Mean number of injections was 2.4 at 6 months, 3.2 at 12 months, and 5.5 at 24 months. CNV was subfoveal in 14 eyes, juxtafoveal in 5, extrafoveal in 5, and peripapillary in 2. By paired comparison, mean decrease from baseline was 119.7 microns at 6 months (n=15; P=0.001, 105.3 microns at 1 year (n=10; P=0.03, and 157.6 microns at 2 years (n=7; P=0.08. BCVA improved by 3.3 lines at 6 months after therapy (n=26; P<0.001, 2.8 lines (n=20; P=0.01 at 1 year, and 3.1 lines (n=13; P=0.049 at 2 years. We conclude that intravitreal anti-VEGF injections improve vision in majority of eyes with CNV from choroidal osteoma.

  7. Prostate-specific membrane antigen is undetectable in choroidal neovascular membrane

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    Godeiro Katyanne

    2006-01-01

    Full Text Available Abstract Background Choroidal neovascular membrane (CNVM is one of the leading causes of severe visual loss and is often associated with age-related macular degeneration (AMD. Various modalities of treatment, including photocoagulation and surgery, are being considered as options, but with limited success. Prostate-specific membrane antigen (PSMA is a type II membrane glycoprotein expressed in benign and malignant prostatic tissues, in some non-prostatic tissues, and in the endothelium of tumor-associated neovasculature of non-prostatic neoplasm. Some studies have suggested that the expression of PSMA is restricted to endothelium from tumor-associated neovasculature and might be stimulated by some tumor-secreted angiogenic factors. However, no previous study demonstrating PSMA expression in non-related tumor neovasculature, such as CNVM, has been performed to date. Furthermore, demonstration of PSMA expression in CNVM in AMD patients could reveal a novel target for antineovascular therapy. The purpose of this study was to evaluate the immunohistochemical expression of PSMA in CNVM from AMD. Methods Immunohistochemical analysis, with a standard avidin-biotin complex technique, was performed using an anti-PSMA mouse monoclonal antibody in 30 specimens of surgically excised CNVM from AMD patients. Antibody to an endothelial cell specific marker, factor VIII, was used to confirm the location of the endothelial cells. Results The angiogenic microvessels of the 30 cases demonstrated negative staining to PSMA while factor VIII was expressed in all cases. Seventy-five percent of the secretory-acinar epithelium of the prostatic hyperplasia specimen stained positive, confirming that the immunohistochemical technique was correctly performed. Conclusion The absence of PSMA expression in non-tumoral neovasculature supports the theory, previously suggested, that endothelial cell PSMA expression may be stimulated by one or more tumor-secreted angiogenic

  8. Clinical efficacy of intravitreal Ranibizumab in idiopathic choroid neovascularization type Ⅰand type Ⅱ

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    Yue-Ming Sun

    2015-07-01

    Full Text Available AIM: To evaluate the efficacy of intravitreal ranibizumab in idiopathic choroid neovascularization(ICNV, compare the difference of the curative effect between type Ⅰand Ⅱof ICNV by optical coherence tomography(OCT, further provide evidence of the to effectiveness of ranibizumab in the treatment of choroidal neovascularization to guide clinical treatment. METHODS: A retrospective analysis on the clinical data who were diagnosed as ICNV between October 2013 and June 2014 in our hospital were carried out. Totally 31 cases(9 cases of type Ⅰ and 22 cases of type Ⅱaccepted ranibizumab injection voluntarily.All of the patients were evaluated by ophthalmic examination, funduscopy and OCT before and after the injection, classificated according to OCT results. The best-corrected visual acuity(BCVAand maximum of edema thickness after ranibizumab treatment at 3mo follow-up were compared. RESULTS: After statistically analyzed, BCVA and maximum thickness of the retinal lesions of 31 patients(type Ⅰ9 cases, type Ⅱ 22 casesbefore and 1, 3mo after treatment had statistical significance. In different types of retinal ICNV patients, BCVA and maximum thickness of the retinal lesions before and after treatment had no statistical significance. It was said that ranibizumab intravitreal injection had effectiveness for ICNV, however, there were no significant effectiveness for typeⅠ andⅡ ICNV. CONCLUSION: Ranibizumab intravitreal injection has obvious effectiveness for ICNV. However, it has no effect on typeⅠ andⅡ ICNV. Its safety and long-term complications need for further study.

  9. The Use of Intravitreal Ranibizumab for Choroidal Neovascularization Associated with Vogt-Koyanagi-Harada Syndrome

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    A. M. Kolomeyer

    2011-01-01

    Full Text Available Purpose. To describe the use of intravitreal ranibizumab for choroidal neovascular membrane (CNVM secondary to Vogt-Koyanagi-Harada (VKH syndrome. Methods. Interventional case report. Results. A 50-year-old woman presented with conjunctival injection and bilateral eye pain. Vision was 20/400 and 20/80 in the right and left eyes, respectively. Bilateral iritis, vitritis, and choroidal thickening were evident. Exudative retinal detachment was present in the left eye. Corticosteroid treatment improved vision to 20/40 bilaterally. Methotrexate (MTX was initiated and vision remained stable for 3 months. After a 5-month loss to follow-up, vision in the left eye decreased to finger counting (CF and a parafoveal CNVM was identified. After 3 intravitreal ranibizumab injections, vision improved to 20/40. Twelve months later, despite inflammation control, vision decrease to CF due to recurrent CNVM. A fourth ranibizumab injection was given. Twenty months later, best-corrected vision was 20/400, and an inactive CNVM was present in the left eye. Conclusion. After initial CNVM regression and visual acuity improvement due to ranibizumab, the CNVM recurred and became refractory to treatment. Despite control of inflammation and neovascularization, VKH chronicity lead to permanent vision loss in our patient. A combinational treatment approach may be required in such patients.

  10. Ranibizumab for choroidal neovascular membrane in a rare case of Bietti′s crystalline dystrophy: A case report

    OpenAIRE

    Kasinathan Nachiappan; Tandava Krishnan; Jagadeesan Madhavan

    2012-01-01

    We report a rare case of Bietti's crystalline dystrophy presenting with choroidal neovascular membrane (CNVM) which was treated with three injections of intravitreal ranibizumab. The CNVM underwent scarring after the injections with stabilization of visual acuity at a follow-up period of 12 months suggesting that intravitreal ranibizumab may have a role in the management of CNVM in these rare cases.

  11. Correlation of In Vivo and In Vitro Methods in Measuring Choroidal Vascularization Volumes Using a Subretinal Injection Induced Choroidal Neovascularization Model

    Institute of Scientific and Technical Information of China (English)

    Chuang Nie; Mao-Nian Zhang; Hong-Wei Zhao; Thomas D Olsen; Kyle Jackman; Lian-Na Hu; Wen-Ping Ma

    2015-01-01

    Background:In vivo quantification of choroidal neovascularization (CNV) based on noninvasive optical coherence tomography (OCT) examination and in vitro choroidal flatmount immunohistochemistry stained of CNV currently were used to evaluate the process and severity of age-related macular degeneration (AMD) both in human and animal studies.This study aimed to investigate the correlation between these two methods in murine CNV models induced by subretinal injection.Methods:CNV was developed in 20 C57BL6/j mice by subretinal injection of adeno-associated viral delivery of a short hairpin RNA targeting sFLT-1 (AAV.shRNA.sFLT-1),as reported previously.After 4 weeks,CNV was imaged by OCT and fluorescence angiography.The scaling factors for each dimension,x,y,and z (μm/pixel) were recorded,and the corneal curvature standard was adjusted from human (7.7) to mice (1.4).The volume of each OCT image stack was calculated and then normalized by multiplying the number of voxels by the scaling factors for each dimension in Seg3D software (University of Utah Scientific Computing and Imaging Institute,available at http://www.sci.utah.edu/cibc-software/seg3d.html).Eighteen mice were prepared for choroidal flatmounts and stained by CD31.The CNV volumes were calculated using scanning laser confocal microscopy after immunohistochemistry staining.Two mice were stained by Hematoxylin and Eosin for observing the CNV morphology.Results:The CNV volume calculated using OCT was,on average,2.6 times larger than the volume calculated using the laser confocal microscopy.The correlation statistical analysis showed OCT measuring of CNV correlated significantly with the in vitro method (R2 =0.448,P=0.001,n =18).The correlation coefficient for CNV quantification using OCT and confocal microscopy was 0.693 (n =18,P =0.001).Conclusions:There is a fair linear correlation on CNV volumes between in vivo and in vitro methods in CNV models induced by subretinal injection.The result might provide a useful

  12. Correlation of In Vivo and In Vitro Methods in Measuring Choroidal Vascularization Volumes Using a Subretinal Injection Induced Choroidal Neovascularization Model

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    Chuang Nie

    2015-01-01

    Full Text Available Background: In vivo quantification of choroidal neovascularization (CNV based on noninvasive optical coherence tomography (OCT examination and in vitro choroidal flatmount immunohistochemistry stained of CNV currently were used to evaluate the process and severity of age-related macular degeneration (AMD both in human and animal studies. This study aimed to investigate the correlation between these two methods in murine CNV models induced by subretinal injection. Methods: CNV was developed in 20 C57BL6/j mice by subretinal injection of adeno-associated viral delivery of a short hairpin RNA targeting sFLT-1 (AAV.shRNA.sFLT-1, as reported previously. After 4 weeks, CNV was imaged by OCT and fluorescence angiography. The scaling factors for each dimension, x, y, and z (μm/pixel were recorded, and the corneal curvature standard was adjusted from human (7.7 to mice (1.4. The volume of each OCT image stack was calculated and then normalized by multiplying the number of voxels by the scaling factors for each dimension in Seg3D software (University of Utah Scientific Computing and Imaging Institute, available at http://www.sci.utah.edu/cibc-software/seg3d.html. Eighteen mice were prepared for choroidal flatmounts and stained by CD31. The CNV volumes were calculated using scanning laser confocal microscopy after immunohistochemistry staining. Two mice were stained by Hematoxylin and Eosin for observing the CNV morphology. Results: The CNV volume calculated using OCT was, on average, 2.6 times larger than the volume calculated using the laser confocal microscopy. The correlation statistical analysis showed OCT measuring of CNV correlated significantly with the in vitro method (R 2 =0.448, P = 0.001, n = 18. The correlation coefficient for CNV quantification using OCT and confocal microscopy was 0.693 (n = 18, P = 0.001. Conclusions: There is a fair linear correlation on CNV volumes between in vivo and in vitro methods in CNV models induced by subretinal

  13. Intravitreal ranibizumab and bevacizumab for the treatment of nonsubfoveal choroidal neovascularization in age-related macular degeneration Ranibizumab e bevacizumab intravítreo no tratamento da neovascularização de coróide extrafoveal da degeneração macular relacionada à idade

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    Aaron Brock Roller

    2009-10-01

    Full Text Available PURPOSE: To investigate the efficacy of vascular endothelial growth factor-specific (VEGF monoclonal antibodies in the treatment of choroidal neovascularization secondary to age-related macular degeneration (AMD that does not extend beneath the foveal center (nonsubfoveal CNV. METHODS: The study design was a retrospective chart review of consecutive patients over a two-month period under active treatment with bevacizumab and/or ranibizumab for neovascular AMD. Patients with neovascularization within the macula that did not extend beneath the center of the foveal avascular zone, along with at least one large drusen (>125 µ or many intermediate size (63-124 µ drusen were included. Best corrected Snellen visual acuity and optical coherence tomography (OCT analysis of the central macular thickness was recorded for each visit. Serial injections of bevacizumab and/or ranibizumab were administered until there was resolution of subretinal fluid clinically or by OCT. Data over the entire follow-up period were analyzed for overall visual acuity and OCT changes. All patients had follow-up since diagnosis of at least 6 months (mean=9.6 months. RESULTS: Of the thirteen included patients, eleven had reduction of retinal thickening in the area involved by the CNV. The remaining two patients did not have OCT data available but had no fluid or activity on clinical examination at last follow-up. One patient (8% lost one line of vision; one (8% remained stable, and eleven (84% gained one or more lines of visual acuity. Three patients (23% gained three or more lines. The average treatment outcome for all patients was a gain of 1.7 ± 1.3 lines of Snellen acuity. Both therapeutic agents were effective, with an average gain of 1.6 ± 0.6 lines for patients treated with bevacizumab, 1.5 ± 1.9 lines gained for patients treated with ranibizumab and 2.5 ± 0.7 lines gained in the two patients who received both agents over the course of their treatment. CONCLUSIONS

  14. Correlation of CD105 and Vascular Endothelial Growth Factor in Laser-induced Choroidal Neovascularization in Rats

    Institute of Scientific and Technical Information of China (English)

    Jianfeng Xu; Yusheng Wang; Xiumei Yang; Peng Zhang; Lijun Chen

    2006-01-01

    Purpose: Choroidal neovascularization (CNV) plays an important role in pathogenesis of age-related macular degeneration (AMD), ocular histoplasmosis syndrome (OHS) and so on. However, mechanisms of CNV formation are not fully understood. The aim of this study is to investigate the correlation between expressions of CD105 and vascular endothelial growth factor (VEGF) in experimental laserinduced CNV in rats.Methods: CNV model was established by 532 nm laser photocoagulation in BrownNorway rats. The expression of CD105 and VEGF in CNV was observed by immunohistochemistry at 3, 7, 14, 21, 28 and 56 days after laser photocoagulation.The image analysis was performed with the professional software of Image-Pro Plus.Results: Fluorescein angiography showed fluorescein leakage in CNV from days 7 to 56 after photocoagulation. VEGF expression was mainly observed in vascular endothelial cells, ganglion cells, inner nuclear layers and retinal pigment epithelial cells in normal retina and vascular endothelial cells in normal choroid of the rats. On day 3 after photocoagulation, VEGF began to express in laser-induced lesions. VEGF was strongly expressed in CNV after 7 days (P<0.05) and decreased after 14 days (P>0.05). CD105 was initially presented in CNV at 7 days and obviously expressed at 14 days after photocoagulation (P<0.05). Four weeks later, when angiogenesis tended toward inactive status, expression of CD 105 was markedly decreased (P>0.05).There was notablely direct correlation between CD105-positive-microvessel density and positively semiquantitative scoring of VEGF in the CNV(r=0.989, P<0.01).Conclusions: There is direct correlation between the expression of CD105 and VEGF in the laser-induced CNV in rat. It suggests that CD105 and VEGF might participate in the new blood vessel formation and promote the growth of CNV.

  15. Predictors of anti-VEGF treatment response in neovascular age-related macular degeneration.

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    Finger, Robert P; Wickremasinghe, Sanjeewa S; Baird, Paul N; Guymer, Robyn H

    2014-01-01

    Currently available evidence on predictors of anti-vascular endothelial growth factor (VEGF) treatment response in neovascular age-related macular degeneration was reviewed. No meta-analysis of results is possible because of a lack of controlled and randomized trials, varying treatment regimes and outcome measures used, as well as suboptimal reporting. For genetic factors, most evidence to date has been generated for single nucleotide polymorphisms (SNPs) in the complement factor H (CFH), and VEGF-A genes. Just under half of the SNPs assessed in the CFH gene and 15% of the SNPs assessed in the VEGF gene were found to be associated with visual outcomes or the number of injections required during follow-up. Some evidence suggests association of worse treatment outcomes as well as a younger age at treatment onset with an increasing number of risk alleles in known risk genes (CFH and ARMS2/HTRA1) and polymorphisms in the VEGF-A gene. Clinical factors such as higher age, a better visual acuity (VA), a larger choroidal neovascularization (CNV) lesion at baseline, and a delay between symptom onset and initiation of treatment of more than 3 weeks also impact outcomes. Conversely, a worse acuity at baseline predicted more gain in vision. Overall, patients presenting with good acuity at baseline were more likely to have good VA at follow up, but the gain afforded by treatment was impacted by a ceiling effect. Most available evidence suggests a strong association of clinical factors such as age, baseline VA, and CNV lesion size with anti-VEGF treatment outcomes. No behavioral factors such as smoking influence treatment outcomes. Based on the studies conducted so far, the evidence suggests that underlying genotype of known AMD risk associated genes or of the VEGF-A gene have a limited effect, whereas presenting clinical factors appear to be more important in determining treatment outcomes.

  16. Lipopolysaccharide Promotes Choroidal Neovascularization by Up-Regulation of CXCR4 and CXCR7 Expression in Choroid Endothelial Cell.

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    Yi-fan Feng

    Full Text Available Stromal cell-derived factor-1 (SDF-1 has been confirmed to participate in the formation of choroidal neovascularization (CNV via its two receptors: CXC chemokine receptors 4 (CXCR4 and CXCR7. Previous studies have indicated that the activation of Toll-like receptors (TLRs by lipopolysaccharide (LPS might elevate CXCR4 and/or CXCR7 expression in tumor cells, enhancing the response to SDF-1 to promote invasion and cell dissemination. However, the impact of LPS on the CXCR4 and CXCR7 expression in endothelial cells and subsequent pathological angiogenesis formation remains to be elucidated. The present study shows that LPS enhanced the CXCR4 and CXCR7 expression via activation of the TLR4 pathway in choroid-retinal endothelial (RF/6A cells. In addition, the transcriptional regulation of CXCR4 and CXCR7 by LPS was found to be mediated by phosphorylation of the extracellular signal-related kinase (ERK 1/2 and activation of nuclear factor kappa B (NF-κB signaling pathways, which were blocked by ERK- or NF-κB-specific inhibitors. Furthermore, the increased CXCR4 and CXCR7 expression resulted in increased SDF-1-induced RF/6A cells proliferation, migration and tube formation. In vivo, LPS-treated rat had significantly higher mRNA levels of CXCR4 and CXCR7 expression and lager laser-induced CNV area than vehicle-treated rat. SDF-1 blockade with a neutralizing antibody attenuated the progression of CNV in LPS-treated rat after a single intravitreal injection. Altogether, these results demonstrated that LPS might influence CNV formation by enhancing CXCR7 and CXCR7 expression in endothelial cells, possibly providing a new perspective for the treatment of CNV-associated diseases.

  17. Benzoporphyrin (verteporfin photodynamic therapy for choroidal neovascularization in age-related macular degeneration Terapia fotodinâmica de neovascularização de coróide por degeneração macular relacionada à idade com benzoporfirina (verteporfirina

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    Evandro G. Lucena

    2000-12-01

    Full Text Available Purpose: To review and discuss the available treatments for choroidal neovascularization (CNV due to age-related macular degeneration (AMD emphasizing to photodynamic therapy (PDT. Methods: Published papers from 1974 until 1999 related to AMD, its available treatments and PDT were reviewed. Results: The most used effective treatment for CNV is laser photocoagulation which does not have a major impact on the blindness due to AMD. Alternative techniques of prevention and treatment are under investigation including surgery, pharmacological antiangiogenic treatment and prevention with photocoagulation. PDT using verteporfin demonstrated effectiveness in closing CNV membranes in an experimental model. A clinical trial showed that a single course treatment could stabilize the area and extent of leakage from subfoveal CNV with classic component in the majority of patients for up to 3 months (Phase I/II. A 12-month data for quaterly treatments was recently reported and showed that vision stabilization, meaning vision improvement, no change, or loss of Objetivo: Rever e discutir os tratamentos disponíveis para neovascularização subrretiniana (CNV secundária a degeneração macular relacionada a idade (DMRI com ênfase especial a terapia fotodinâmica (PDT. Métodos: Revisamos artigos publicados a partir de 1974 até 1999 relacionados a DMRI, seus tratamentos dispo- níveis e PDT. Resultados: O tratamento provadamente efetivo mais utilizado para CNV é fotocoagulação com laser o qual não apresenta um impacto expressivo na deficiência visual causada pela DMRI. Técnicas alternativas de prevenção e tratamento estão sob investigação incluindo cirurgias, tratamento farmacológico antiangiogênico e prevenção com fotocoagulação. PDT com Verteporfina demonstrou ser efetiva no fechamento de CNV em nosso modelo experimental. Um estudo clínico inicial demonstrou que uma aplicação única poderia estabilizar a área de CNV subfoveal com

  18. 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

  19. 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.

  20. Combined choroidal neovascularization and hypopituitarism in a patient with homozygous mutation in methylenetetrahydrofolate reductase gene

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    Aydogan Aydogdu

    2014-01-01

    Full Text Available We report a case of choroidal neovascularization (CNV secondary to methylenetetrahydrofolate reductase (MTHFR gene mutation in a 20-year-old male patient with hypopituitarism. Treatment with three consecutive injections of intravitreal ranibizumab (anti-vascular endothelial growth factor resulted in significant improvement of the patient′s vision and the appearance of the macula. A search of the literature produced no previously reported case of MTHFR gene mutation associated both CNV and possibly hypopituitarism. With hormone replacement therapy of hypopituitarism, acetyl salicylic acid 100 mg/day also was started. The patient was clinically stable both for CNV and other thromboembolic disorders over a 6-month follow-up and also 1-year follow-up period.

  1. 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...... endodiathermy. Bruch's membrane was perforated with a retinal perforator at a site where the overlying neuroretina was normal. Eyes were enucleated in a time interval between 30 min and 42 days after the perforation, and the pigs were subsequently killed. Immediately prior to enucleation, fundus photographs...... and fluorescein angiograms were obtained. Sections of paraffin-embedded eyes were immunohistochemically stained. RESULTS: On fluorescein angiography, membranes aged 14 days or less exhibited leakage in 10/11 cases while the remaining showed persistent staining. The propensity to leak diminished with time and only...

  2. Bilateral choroidal neovascularization associated with optic nerve head drusen treated by antivascular endothelial growth factor therapy

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    Carreras A

    2012-02-01

    Full Text Available Barbara Delas, Lorena Almudí, Anabel Carreras, Mouafk AsaadOphthalmology Service, Hospital de Terrassa, Barcelona, SpainObjective: To report a good clinical outcome in a patient with bilateral choroidal neovascularization (CNV associated with optic nerve head drusen (ONHD treated with intravitreal ranibizumab injection.Methods: A 12-year-old girl was referred for loss of right eye vision detected in a routine check-up. Best-corrected visual acuity (BCVA was hand movements in the right eye and 0.9 in the left eye. Funduscopy revealed the presence of superficial and buried bilateral ONHD, which was confirmed by ultrasonography and computed tomography, and the study was completed with perimetry. The presence of bilateral CNV, active in the right eye, was observed and subsequently confirmed using fluorescein angiography and optical coherence tomography.Results: Treatment with two consecutive injections of intravitreal ranibizumab resulted in inactivation of the neovascular membrane with subretinal fluid reabsorption and improved right eye BCVA. After 12 months’ follow-up, this was 20/60 and stable.Conclusion: Although there are no published studies of safety in children, antiangiogenic therapy for CNV secondary to ONHD may be useful and safe. A search of the literature produced only one previously reported case of ONHD-associated CNV treated with antivascular endothelial growth factor alone.Keywords: optic nerve head drusen, anti-vegf, children, neovascularisation

  3. 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.

  4. Tissue inhibitor of metalloproteinases-3 peptides inhibit angiogenesis and choroidal neovascularization in mice.

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    Jian Hua Qi

    Full Text Available Tissue inhibitors of metalloproteinases (TIMPs while originally characterized as inhibitors of matrix metalloproteinases (MMPs have recently been shown to have a wide range of functions that are independent of their MMP inhibitory properties. Tissue inhibitor of metalloproteinases-3 (TIMP-3 is a potent inhibitor of VEGF-mediated angiogenesis and neovascularization through its ability to block the binding of VEGF to its receptor VEGFR-2. To identify and characterize the anti-angiogenic domain of TIMP-3, structure function analyses and synthetic peptide studies were performed using VEGF-mediated receptor binding, signaling, migration and proliferation. In addition, the ability of TIMP-3 peptides to inhibit CNV in a mouse model was evaluated. We demonstrate that the anti-angiogenic property resides in the COOH-terminal domain of TIMP-3 protein which can block the binding of VEGF specifically to its receptor VEGFR-2, but not to VEGFR-1 similar to the full-length wild-type protein. Synthetic peptides corresponding to putative loop 6 and tail region of TIMP-3 have anti-angiogenic properties as determined by inhibition of VEGF binding to VEGFR-2, VEGF-induced phosphorylation of VEGFR-2 and downstream signaling pathways as well as endothelial cell proliferation and migration in response to VEGF. In addition, we show that intravitreal administration of TIMP-3 peptide could inhibit the size of laser-induced choroidal neovascularization lesions in mice. Thus, we have identified TIMP-3 peptides to be efficient inhibitors of angiogenesis and have a potential to be used therapeutically in diseases with increased neovascularization.

  5. Melissa officinalis extract inhibits laser-induced choroidal neovascularization in a rat model.

    Science.gov (United States)

    Lee, Eun Kyoung; Kim, Young Joo; Kim, Jin Young; Song, Hyun Beom; Yu, Hyeong Gon

    2014-01-01

    This study investigated the effect of Melissa officinalis extract on laser-induced choroidal neovascularization (CNV) in a rat model. The mechanism by which M. officinalis extract acted was also investigated. Experimental CNV was induced by laser photocoagulation in Brown Norway rats. An active fraction of the Melissa leaf extract was orally administered (50 or 100 mg/kg/day) beginning 3 days before laser photocoagulation and ending 14 days after laser photocoagulation. Optical coherence tomography and fluorescein angiography were performed in vivo to evaluate the thickness and leakage of CNV. Choroidal flat mount and histological analysis were conducted to observe the CNV in vitro. Vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2, and MMP-9 expression were measured in retinal and choroidal-scleral lysates 7 days after laser injury. Moreover, the effect of M. officinalis extract on tertiary-butylhydroperoxide (t-BH)-induced VEGF secretion and mRNA levels of VEGF, MMP-2, and MMP-9 were evaluated in human retinal epithelial cells (ARPE-19) as well as in human umbilical vein endothelial cells (HUVECs). The CNV thickness in M. officinalis-treated rats was significantly lower than in vehicle-treated rats by histological analysis. The CNV thickness was 33.93±7.64 µm in the high-dose group (Pofficinalis, which was significantly lower than in control rats (53.4%, Pofficinalis extract suppressed t-BH-induced transcription of VEGF and MMP-9 in ARPE-19 cells and HUVECs. Systemic administration of M. officinalis extract suppressed laser-induced CNV formation in rats. Inhibition of VEGF and MMP-9 via anti-oxidative activity may underlie this effect.

  6. Enhanced depth imaging optical coherence tomography of choroidal osteoma with secondary neovascular membranes: report of two cases

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    Patrícia Correa de Mello

    2016-06-01

    Full Text Available ABSTRACT We report enhanced depth imaging optical coherence tomography (EDI-OCT features based on clinical and imaging data from two newly diagnosed cases of choroidal osteoma presenting with recent visual loss secondary to choroidal neovascular membranes. The features described in the two cases, compression of the choriocapillaris and disorganization of the medium and large vessel layers, are consistent with those of previous reports. We noticed a sponge-like pattern previously reported, but it was subtle. Both lesions had multiple intralesional layers and a typical intrinsic transparency with visibility of the sclerochoroidal junction.

  7. 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

  8. Intravitreal Expansile Gas and Bevacizumab Injection for Submacular Hemorrhage Due to Neovascular Age-related Macular Degeneration

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    Ramin Nourinia

    2010-01-01

    Full Text Available Purpose: To evaluate the results of intravitreal expansile gas injection, with or without recombinant tissue plasminogen activator (rtPA, followed by intravitreal bevacizumab injection for treatment of submacular hemorrhage (SMH secondary to neovascular age-related macular degeneration (AMD. Methods: In this interventional case series, 5 eyes of 5 patients with SMH secondary to choroidal neovascularization (CNV due to neovascular AMD were treated with 0.3 cc intravitreal SF6 (and 50 μg of rtPA in two eyes, followed by face-down positioning; 24 hours later, 1.25 mg of bevacizumab was injected intravitreally. Main outcome measures included displacement of SMH and best corrected visual acuity (BCVA. Results: Mean patient age was 75.6±9.2 (range, 60-83 years, mean duration of symptoms was 6.4±3.2 (range, 3-10 days, and mean number of bevacizumab injections was 1.8 (range, 1-3. Mean preoperative BCVA was 1.28±0.27 logMAR which improved significantly to 0.57±0.33 logMAR at 12 months (P=0.042. SMH displacement occurred in all eyes, and visual acuity improved and remained stable during the follow-up period of 12 months. Conclusion: Intravitreal expansile gas injection, with or without rtPA, followed by intravitreal bevacizumab injection, seems to be an effective modality for SMH displacement and treatment of the underlying CNV in neovascular AMD.

  9. 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

    was identified immunohistochemically in the inner limiting membrane (ILM) and to a lesser degree in the remaining retina. Strong staining was also detected in both retinal blood vessels and entire CNV membranes with no cellular predisposition. Vascular endothelial growth factor expression was found in the CNV...... membranes, in the ILM, in the ganglion cell layer, in Müller cells throughout the neuroretina and in retinal blood vessels. CONCLUSIONS: Bevacizumab significantly reduced the proliferation of vascular endothelial cells in CNV membranes and showed a strong trend towards a reduction of leakage from......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...

  10. Ranibizumab for choroidal neovascular membrane in a rare case of Bietti′s crystalline dystrophy: A case report

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    Kasinathan Nachiappan

    2012-01-01

    Full Text Available We report a rare case of Bietti′s crystalline dystrophy presenting with choroidal neovascular membrane (CNVM which was treated with three injections of intravitreal ranibizumab. The CNVM underwent scarring after the injections with stabilization of visual acuity at a follow-up period of 12 months suggesting that intravitreal ranibizumab may have a role in the management of CNVM in these rare cases.

  11. Management of neovascular Age-related macular degeneration: A review on landmark randomized controlled trials

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    Aniruddha Agarwal; Kanika Aggarwal; Vishali Gupta

    2016-01-01

    In the last decade, a number of prospective clinical trials with carefully designed study protocols have been conducted for the treatment of neovascular age-related macular degeneration (AMD). These landmark clinical trials such as ANCHOR and MARINA and, more recently, the Comparison of AMD Treatment Trials and VIEW studies have revolutionized the management of neovascular AMD. While AMD continues to remain a leading cause of severe visual loss worldwide, advances in pharmacotherapeutics have...

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

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    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 recr...... were found in the percentages of CD4(+) lymphocytes, CD25(high)CD127(low) Tregs, CD45RA(+) naïve Tregs, or CD31(+) recent thymic emigrant Tregs. CONCLUSION: Our data does not indicate an altered state of systemic Treg cells in neovascular AMD....

  13. The Relationship between Neovascular Age-Related Macular Degeneration and Erectile Dysfunction

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    Harun Çakmak

    2013-01-01

    Full Text Available Purpose. To evaluate association between erectile dysfunction (ED and neovascular age-related macular degeneration (AMD. Methods. 195 men enrolled in this cross-sectional study. 90 of them had neovascular AMD and 105 of them were healthy volunteers. The International Index of Erectile Function (IIEF questionnaire’s erectile function (EF domain was used to assess ED. The patients in the study and control groups were statistically compared according to visual acuity, EF score, and body mass index. Results. The mean ages were 62 (54.5–73 and 60 (54–68, in the neovascular AMD and control groups, respectively. The total EF scores were 9 (6–16 in neovascular AMD and 18 (9.5–27 in control group. The results of IIEF questionnaire on neovascular AMD patients revealed that 85 men (94.4% had some degree of ED, whereas 68 men (64.8% had some degree of ED on control group. Patients with neovascular AMD had a significantly higher incidence of ED than control patients (. There was a significant association between ED and neovascular AMD (. Conclusions. Our results suggested that neovascular AMD has a high association with ED.

  14. Anti-VEGF treatment for myopic choroid neovascularization: from molecular characterization to update on clinical application

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    Zhang Y

    2015-07-01

    Full Text Available Yan Zhang,1 Qian Han,2 Yusha Ru,1 Qiyu Bo,1 Rui Hua Wei1 1Tianjin Medical University Eye Hospital, Tianjin Medical University Eye Institute, College of Optometry and Ophthalmology, Tianjin Medical University, Tianjin, 2Tangshan Eye Hospital, Tangshan, Hebei Province, People’s Republic of China Abstract: Choroidal neovascularization (CNV secondary to pathologic myopia has a very high incidence in global, especially in Asian, populations. It is a common cause of irreversible central vision loss, and severely affects the quality of life in the patients with pathologic myopia. The traditional therapeutic modalities for CNV secondary to pathologic myopia include thermal laser photocoagulation, surgical management, transpupillary thermotherapy, and photodynamic therapy with verteporfin. However, the long-term outcomes of these modalities are disappointing. Recently, intravitreal administration of anti-VEGF biological agents, including bevacizumab, ranibizumab, pegaptanib, aflibercept, and conbercept, has demonstrated promising outcomes for this ocular disease. The anti-VEGF regimens are more effective on improving visual acuity, reducing central fundus thickness and central retina thickness than the traditional modalities. These anti-VEGF agents thus hold the potential to become the first-line medicine for treatment of CNV secondary to pathologic myopia. This review follows the trend of “from bench to bedside”, initially discussing the pathogenesis of myopic CNV, delineating the molecular structures and mechanisms of action of the currently available anti-VEGF drugs, and then systematically comparing the up to date clinical applications as well as the efficacy and safety of the anti-VEGF drugs to the CNV secondary to pathologic myopia. Keywords: formation of new vessels, choroid membrane, pathologic myopia, vascular endothelial growth factor, molecular mechanisms, clinical trials

  15. 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

  16. The Use of Microperimetry to Detect Functional Progression in Non-Neovascular Age-Related Macular Degeneration: A Systematic Review.

    Science.gov (United States)

    Wong, Evan N; Chew, Avenell L; Morgan, William H; Patel, Praveen J; Chen, Fred K

    2017-01-01

    We reviewed the current literature on the ability of microperimetry to detect non-neovascular age-related macular degeneration (AMD) disease progression. The index test was retinal sensitivity measurement assessed by microperimetry and comparators were other functional measures (best-corrected and low-luminance visual acuities, and fixation stability) and structural parameters [retinal thickness, choroidal thickness, and area of geographic atrophy (GA) determined by color fundus photographs, short-wave or near-infrared fundus autofluorescence]. The reference standard was area of GA. The literature search was conducted in January 2016 and included MEDLINE, EMBASE, the Cochrane Library, Biosis, Science Citation Index, ProQuest Health and Medicine, CINAHL, and Highwire Press. We included 6 studies that enrolled 41 eyes with intermediate AMD (from a single study) and 80 eyes with GA secondary to AMD. Retinal sensitivity measured by microperimetry was the only functional measure that consistently detected progression in each cohort. Insufficient reported data precluded meta-analysis. Various microperimetry parameters were used to assess cohort-level change in retinal sensitivity, but the methods of analysis have yet to mature in complexity in comparison with established glaucoma field progression analysis. Microperimetry-assessed retinal sensitivity measurement may be more sensitive in detecting progression than other functional measures in non-neovascular AMD. However, the lack of standardized testing protocol and methods of progression analysis hindered comparison. Harmonization of testing protocol and development of more robust methods of analyzing raw microperimetric data will facilitate clinical implementation of this valuable retinal assessment tool.

  17. Anti-vascular endothelial growth factor for neovascular age-related macular degeneration.

    Science.gov (United States)

    Solomon, Sharon D; Lindsley, Kristina; Vedula, Satyanarayana S; Krzystolik, Magdalena G; Hawkins, Barbara S

    2014-08-29

    Age-related macular degeneration (AMD) is the most common cause of uncorrectable severe vision loss in people aged 55 years and older in the developed world. Choroidal neovascularization (CNV) secondary to neovascular AMD accounts for most AMD-related severe vision loss. Anti-vascular endothelial growth factor (anti-VEGF) agents, injected intravitreally, aim to block the growth of abnormal blood vessels in the eye to prevent vision loss and, in some instances, improve vision. To investigate: (1) the ocular and systemic effects of, and quality of life associated with, intravitreally injected anti-VEGF agents (pegaptanib, ranibizumab, and bevacizumab) for the treatment of neovascular AMD compared with no anti-VEGF treatment; and (2) the relative effects of one anti-VEGF agent compared with another when administered in comparable dosages and regimens. We searched Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 3), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to March 2014), EMBASE (January 1980 to March 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to March 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We used no date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 27 March 2014. We included randomized controlled trials (RCTs) that evaluated pegaptanib, ranibizumab, or bevacizumab versus each other or a control treatment (e.g., sham treatment or photodynamic therapy). All trials followed participants for at least one year. Two review authors independently screened records, extracted data, and

  18. Melissa officinalis extract inhibits laser-induced choroidal neovascularization in a rat model.

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    Eun Kyoung Lee

    Full Text Available PURPOSE: This study investigated the effect of Melissa officinalis extract on laser-induced choroidal neovascularization (CNV in a rat model. The mechanism by which M. officinalis extract acted was also investigated. METHODS: Experimental CNV was induced by laser photocoagulation in Brown Norway rats. An active fraction of the Melissa leaf extract was orally administered (50 or 100 mg/kg/day beginning 3 days before laser photocoagulation and ending 14 days after laser photocoagulation. Optical coherence tomography and fluorescein angiography were performed in vivo to evaluate the thickness and leakage of CNV. Choroidal flat mount and histological analysis were conducted to observe the CNV in vitro. Vascular endothelial growth factor (VEGF, matrix metalloproteinase (MMP-2, and MMP-9 expression were measured in retinal and choroidal-scleral lysates 7 days after laser injury. Moreover, the effect of M. officinalis extract on tertiary-butylhydroperoxide (t-BH-induced VEGF secretion and mRNA levels of VEGF, MMP-2, and MMP-9 were evaluated in human retinal epithelial cells (ARPE-19 as well as in human umbilical vein endothelial cells (HUVECs. RESULTS: The CNV thickness in M. officinalis-treated rats was significantly lower than in vehicle-treated rats by histological analysis. The CNV thickness was 33.93±7.64 µm in the high-dose group (P<0.001, 44.09±12.01 µm in the low-dose group (P = 0.016, and 51.00±12.37 µm in the control group. The proportion of CNV lesions with clinically significant fluorescein leakage was 9.2% in rats treated with high-dose M. officinalis, which was significantly lower than in control rats (53.4%, P<0.001. The levels of VEGF, MMP-2, and MMP-9 were significantly lower in the high-dose group than in the control group. Meanwhile, M. officinalis extract suppressed t-BH-induced transcription of VEGF and MMP-9 in ARPE-19 cells and HUVECs. CONCLUSIONS: Systemic administration of M. officinalis extract suppressed laser

  19. Choroidal neovascularization in pathologic myopia: intravitreal ranibizumab versus bevacizumab--a randomized controlled trial.

    Science.gov (United States)

    Gharbiya, Magda; Giustolisi, Rosalia; Allievi, Francesca; Fantozzi, Nicoletta; Mazzeo, Luigi; Scavella, Vittorio; Gabrieli, Corrado Balacco

    2010-03-01

    To compare the short-term efficacy and safety of intravitreal ranibizumab versus bevacizumab in treating myopic choroidal neovascularization (CNV). Prospective, comparative, randomized, interventional study. Thirty-two eyes from 32 patients with myopic CNV were consecutively enrolled and randomly treated, in a 1:1 ratio, with intravitreal ranibizumab (0.5 mg) or bevacizumab (1.25 mg) as needed, after the first injection. ETDRS best-corrected visual acuity (BCVA), foveal center thickness (FCT) on optical coherence tomography (OCT), and fluorescein angiographic findings were examined before and after treatment. Patients were followed up for 6 months. No statistically significant difference in the BCVA improvement, as well as in the FCT reduction, was found between groups during follow-up (P value at 1, 3, 6 months > .05). Complete resolution of fluorescein leakage was observed in all 16 bevacizumab-treated eyes and in 15 out of 16 (93.7%) ranibizumab-treated eyes. No ocular or systemic adverse effects from treatment were encountered. This randomized clinical study cannot determine a statistically significant difference in anti-VEGF treatment effect between ranibizumab and bevacizumab for the treatment of CNV secondary to pathologic myopia. A larger study is required to determine the relative efficacy and duration of action of these drugs. (c) 2010 Elsevier Inc. All rights reserved.

  20. Evaluation of Idiopathic Choroidal Neovascularization with Indocyanine Green Angiography in Patients Undergoing Bevacizumab Therapy

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    Ryan B. Rush

    2015-01-01

    Full Text Available Purpose. To examine the clinical implications of change in choroidal neovascularization (CNV size on indocyanine green (ICG angiography in subjects with idiopathic CNV undergoing bevacizumab therapy. Methods. The charts of subjects with an idiopathic CNV treated by a modified PRN regimen with intravitreal bevacizumab over a 12-month period were retrospectively reviewed. Results. There were 34 subjects included in the analysis. Baseline CNV sizes of less than 1.0 mm2 on ICG angiography correlated with complete CNV resolution (P=0.0404, fewer injections delivered (P=0.0002, and better Snellen visual acuity (P=0.0098 at 12 months. Subjects that experienced a 33% or more reduction in CNV size on ICG angiography at 2 months had complete CNV resolution (P=0.0047 and fewer injections (P<0.0001 at 12 months compared to subjects that did not experience a 33% or more reduction in CNV size on ICG angiography at 2 months. Conclusions. Smaller baseline CNV size on ICG angiography resulted in better visual acuity and fewer injections at 12 months, and a reduction of 33% or more in CNV size after 2 months may predict a better clinical course in subjects with idiopathic CNV undergoing bevacizumab therapy.

  1. Choroidal neovascularization induced by immunogenic alteration of the retinal pigment epithelium in dengue Fever.

    Science.gov (United States)

    Veloso, Carlos Eduardo; Schmidt-Erfurth, Ursula; Nehemy, Márcio B

    2015-01-01

    To report the first case of choroidal neovascularization (CNV) secondary to dengue fever. A 54-year-old female was referred to our department with blurred vision and metamorphopsia in her left eye. Two weeks earlier, she had presented all of the classic symptoms of dengue fever including a positive serology. Her best-corrected visual acuity (BCVA) was 20/150 in the left eye. She underwent a fundus examination, fluorescein angiography (FA) and spectral domain optical coherence tomography. All findings were consistent with CNV secondary to dengue fever. FA revealed a classic CNV associated with focal retinal pigment epithelium (RPE) destruction and detachment. Three consecutive monthly injections of intravitreal ranibizumab resulted in functional and anatomical improvement for as long as 6 months with a BCVA of 20/25. However, CNV recurred 2 years later, again with an improvement after ranibizumab therapy, but with persistence of a fibrovascular RPE detachment, highlighting the pathomechanism of a classic CNV formation. Maculopathy in dengue fever may be followed by CNV as a result of the immunologic alteration of the RPE. Physicians should be aware of this manifestation to be able to initiate adequate treatment with excellent functional and anatomical results.

  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. 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.

  4. Activation of Rap1 inhibits NADPH oxidase-dependent ROS generation in retinal pigment epithelium and reduces choroidal neovascularization

    Science.gov (United States)

    Wang, Haibo; Jiang, Yanchao; Shi, Dallas; Quilliam, Lawrence A.; Chrzanowska-Wodnicka, Magdalena; Wittchen, Erika S.; Li, Dean Y.; Hartnett, M. Elizabeth

    2014-01-01

    Activation of Rap1 GTPase can improve the integrity of the barrier of the retina pigment epithelium (RPE) and reduce choroidal neovascularization (CNV). Inhibition of NADPH oxidase activation also reduces CNV. We hypothesize that Rap1 inhibits NADPH oxidase-generated ROS and thereby reduces CNV formation. Using a murine model of laser-induced CNV, we determined that reduced Rap1 activity in RPE/choroid occurred with CNV formation and that activation of Rap1 by 2′-O-Me-cAMP (8CPT)-reduced laser-induced CNV via inhibiting NADPH oxidase-generated ROS. In RPE, inhibition of Rap1 by Rap1 GTPase-activating protein (Rap1GAP) increased ROS generation, whereas activation of Rap1 by 8CPT reduced ROS by interfering with the assembly of NADPH oxidase membrane subunit p22phox with NOX4 or cytoplasmic subunit p47phox. Activation of NADPH oxidase with Rap1GAP reduced RPE barrier integrity via cadherin phosphorylation and facilitated choroidal EC migration across the RPE monolayer. Rap1GAP-induced ROS generation was inhibited by active Rap1a, but not Rap1b, and activation of Rap1a by 8CPT in Rap1b−/− mice reduced laser-induced CNV, in correlation with decreased ROS generation in RPE/choroid. These findings provide evidence that active Rap1 reduces CNV by interfering with the assembly of NADPH oxidase subunits and increasing the integrity of the RPE barrier.—Wang, H., Jiang, Y., Shi, D., Quilliam, L. A., Chrzanowska-Wodnicka, M., Wittchen, E. S., Li, D. Y., Hartnett, M. E. Activation of Rap1 inhibits NADPH oxidase-dependent ROS generation in retinal pigment epithelium and reduces choroidal neovascularization. PMID:24043260

  5. 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, random...

  6. Predicting Non-response to Ranibizumab in Patients with Neovascular Age-related Macular Degeneration

    NARCIS (Netherlands)

    Asten, F. van; Rovers, M.M.; Lechanteur, Y.T.E.; Smailhodzic, D.; Muether, P.S.; Chen, J.; Hollander, A.I. den; Fauser, S.; Hoyng, C.B.; Wilt, G.J. van der; Klevering, B.J.

    2014-01-01

    Abstract Purpose: To validate known and determine new predictors of non-response to ranibizumab in patients with neovascular age-related macular degeneration (AMD) and to incorporate these factors into a prediction rule. METHODS: This multicenter, observational cohort study included 391 patients tre

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

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    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

  8. Treatment of neovascular age-related macular degeneration with anti-VEGF agents: retrospective analysis of 5-year outcomes

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    Pedrosa AC

    2016-03-01

    Full Text Available Ana Catarina Pedrosa,1 Adriana Reis-Silva,2 João Pinheiro-Costa,1,3 João Beato,1 Paulo Freitas-da-Costa,1,3 Manuel S Falcão,1,2 Fernando Falcão-Reis,1,2 Ângela Carneiro1,2 1Department of Ophthalmology, Hospital de São João, 2Department of Sense Organs, 3Department of Anatomy, Faculty of Medicine, University of Porto, Porto, Portugal Purpose: To evaluate the 5-year results obtained in clinical practice in the treatment of neovascular age-related macular degeneration (nAMD with anti-VEGF agents.  Materials and methods: We retrospectively analyzed all patients with nAMD who initiated anti-VEGF treatment before October 2009. We collected data regarding visual and anatomical outcomes.  Results: A total of 278 patients met the selection criteria. The mean number of intravitreal injections was 5.7 in the first year and 3.7 in the fifth year. A positive mean visual acuity variation of +3.7 Early Treatment Diabetic Retinopathy Study letters occurred in the first year, but no significant differences relative to baseline were observed thereafter. The majority of patients (71% maintained stable visual acuity throughout follow-up. At 5 years, mean central macular thickness remained substantially inferior to baseline (-96.6 µm, and 56% of patients maintained dry retinas.  Conclusion: Anti-VEGF therapy leads to long-term visual stabilization in the great majority of patients. Keywords: age-related macular degeneration, choroidal neovascularization, vascular endothelial growth factor, visual acuity

  9. Effect of Factor XIII-A G185T Polymorphism on Visual Prognosis after Photodynamic Therapy for Neovascular Macular Degeneration

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    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

  10. Long-term follow-up of patients with choroidal neovascularization due to angioid streaks

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    Martinez-Serrano MG

    2016-12-01

    Full Text Available Maria Guadalupe Martinez-Serrano,1 Abelardo Rodriguez-Reyes,2 Jose Luis Guerrero-Naranjo,1,3 Guillermo Salcedo-Villanueva,1 Jans Fromow-Guerra,1,3 Gerardo García-Aguirre,1,3 Virgilio Morales-Canton,1 Raul Velez-Montoya1,3 1Retina Department, 2Pathology Department, Asociación para Evitar la Ceguera en Mexico, Hospital “Dr Luis Sanchez Bulnes” IAP, 3Macula Retina Consultants, Mexico City, Mexico Background: The following case series describes the long-term anatomical and functional outcome of a group of seven patients with choroidal neovascularization (CNV, secondary to angioid streaks (AS, who were treated with antiangiogenic drugs in a pro re nata (PRN regimen. After the 4-year mark, visual acuity tends to return to pretreatment level. Treatment delays and lack of aware­ness and self-referral by the patients are believed to be the cause of the PRN regimen failure. Purpose: To assess the long-term outcomes (>4 years of patients with CNV due to AS treated with a PRN regimen of antiangiogenic. Methods: This was a retrospective, case series, single-center study. We reviewed the electronic medical records from patients with CNV due to AS. From each record, we noted general demographic data and relevant medical history; clinical presentation, changes in best-corrected visual acuity (BCVA over time, optical coherent tomography parameters, treatment and retreatment details, and systemic associations. Changes in BCVA and central macular thickness were assessed with a Wilcoxon two-sample test, with an alpha value of ≤0.05 for statistical significance. Results: The mean follow-up time was 53.8±26.8 months. BCVA at baseline was: 1.001±0.62 logMAR; at the end of follow-up: 0.996±0.56 logMAR (P=0.9. Central macular thickness at baseline was: 360.85±173.82 µm; at the end of follow-up: 323.85±100.34 µm (P=0.6. Mean number of intravitreal angiogenic drugs: 6±4.16 injections (range 4–15. Mean time between injections was 3.8±2.7 months (range

  11. Forty-two-month outcome of intravitreal bevacizumab in myopic choroidal neovascularization.

    Science.gov (United States)

    Traversi, Claudio; Nuti, Elisabetta; Marigliani, Davide; Cevenini, Gabriele; Balestrazzi, Angelo; Martone, Gianluca; Caporossi, Tomaso; Tosi, Gian Marco

    2015-04-01

    To evaluate the long-term efficacy of bevacizumab in the treatment of choroidal neovascularization (CNV) secondary to pathological myopia. In this retrospective single-center non-comparative study the medical records of 29 eyes from 29 patients with naïve CNV secondary to high myopia and at least 42 months of follow up were reviewed. All eyes received a loading dose of one intravitreal injection per month for two consecutive months and were retreated on an as-needed basis during the course of follow up. The main outcome measures were post-treatment ETDRS best-corrected visual acuity (BCVA) and visual stabilization over time. Stepwise linear regression analysis was performed to identify prognostic factors for visual acuity gain and final visual acuity outcome at 42 months. At 42 months of follow-up bevacizumab was associated with the maintenance of significant benefits in visual acuity compared to baseline. No adverse ocular or systemic effects from treatment were encountered. No statistically significant correlations were found between BCVA change and any of the quantitative variables. However, when final BCVA was taken as a dependent variable and CNV size and pre-treatment VA were included as predictors, a bivariate model was identified by stepwise regression which gave a 75 % of explained variance. Bevacizumab treatment was found to be efficacious in the treatment of myopic CNV, resulting in stable gains in visual acuity lasting at least 42 months, without any adverse ocular or general events. Myopic CNV size was identified as a significant prognostic factor.

  12. Functional characterization and multimodal imaging of treatment-naive "quiescent" choroidal neovascularization.

    Science.gov (United States)

    Querques, Giuseppe; Srour, Mayer; Massamba, Nathalie; Georges, Anouk; Ben Moussa, Naima; Rafaeli, Omer; Souied, Eric H

    2013-10-21

    To investigate the multimodal morphological and functional characteristics of treatment-naïve "quiescent" choroidal neovascularization (CNV) secondary to AMD. Eleven patients with treatment-naïve "quiescent" CNV that consecutively presented over a 6-month period, underwent multimodal morphological and functional assessment (including indocyanine green angiography [ICGA], spectral-domain optical coherence tomography [SD-OCT], microperimetry, and preferential hyperacuity perimeter [PHP]). For the purpose of this study, asymptomatic previously untreated CNVs showing absence of intraretinal/subretinal exudation in two consecutive visits (at least 6 months apart) were defined as treatment-naïve "quiescent" CNV. Eleven eyes of 11 patients (9 females; mean age 76.5 ± 8.5 years) were included. On fluorescein angiography (FA), "quiescent" CNVs appeared as late speckled hyperfluorescent lesions lacking well-demarcated borders. Mid-late phase ICGA allowed visualizing the hyperfluorescent "quiescent" CNV network and delineating the plaque. Mean lesion area (mid-late phase ICGA) appeared larger compared with earliest previous examination performed 23.8 ± 16.0 months before (3.24 ± 2.51 mm(2) vs. 3.52 ± 2.46 mm(2), respectively; P = 0.01). SD-OCT revealed, at the site of "quiescent" CNV, an irregularly slightly elevated RPE, without hyporeflective intraretinal/subretinal fluid, showing a major axis in the horizontal plane, which was characterized by collections of moderately reflective material in the sub-RPE space and clear visualization of the hyperreflective Bruch's membrane. Hypergeometric distribution revealed a significant correlation between microperimetry and PHP with respect to locations of "affected areas" (P = 0.001). "Quiescent" CNVs are sub-RPE CNVs secondary to AMD, showing absence of intraretinal/subretinal exudation on repeated OCT. "Quiescent" CNVs enlarge over time and may contribute to local reduced retinal sensitivity and metamorphopsia.

  13. Imaging polarimetry in patients with neovascular age-related macular degeneration

    Science.gov (United States)

    Elsner, Ann E.; Weber, Anke; Cheney, Michael C.; VanNasdale, Dean A.; Miura, Masahiro

    2007-01-01

    Imaging polarimetry was used to examine different components of neovascular membranes in age-related macular degeneration. Retinal images were acquired with a scanning laser polarimeter. An innovative pseudo-color scale, based on cardinal directions of color, displayed two types of image information: relative phases and magnitudes of birefringence. Membranes had relative phase changes that did not correspond to anatomical structures in reflectance images. Further, membrane borders in depolarized light images had significantly higher contrasts than those in reflectance images. The retinal birefringence in neovascular membranes indicates optical activity consistent with molecular changes rather than merely geometrical changes. PMID:17429494

  14. Emerging therapies for the treatment of neovascular age-related macular degeneration and diabetic macular edema.

    Science.gov (United States)

    Emerson, M Vaughn; Lauer, Andreas K

    2007-01-01

    Diabetic macular edema (DME) and choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD) are the leading causes of vision loss in the industrialized world. The mainstay of treatment for both conditions has been thermal laser photocoagulation, while there have been recent advances in the treatment of CNV using photodynamic therapy with verteporfin. While both of these treatments have prevented further vision loss in a subset of patients, vision improvement is rare. Anti-vascular endothelial growth factor (VEGF)-A therapy has revolutionized the treatment of both conditions. Pegaptanib, an anti-VEGF aptamer, prevents vision loss in CNV, although the performance is similar to that of photodynamic therapy. Ranibizumab, an antibody fragment, and bevacizumab, a full-length humanized monoclonal antibody against VEGF, have both shown promising results, with improvements in visual acuity in the treatment of both diseases. VEGF trap, a modified soluble VEGF receptor analog, binds VEGF more tightly than all other anti-VEGF therapies, and has also shown promising results in early trials. Other treatment strategies to decrease the effect of VEGF have used small interfering RNA to inhibit VEGF production and VEGF receptor production. Corticosteroids have shown efficacy in controlled trials, including anacortave acetate in the treatment and prevention of CNV, and intravitreal triamcinolone acetonide and the fluocinolone acetonide implant in the treatment of DME. Receptor tyrosine kinase inhibitors, such as vatalanib, inhibit downstream effects of VEGF, and have been effective in the treatment of CNV in early studies. Squalamine lactate inhibits plasma membrane ion channels with downstream effects on VEGF, and has shown promising results with systemic administration. Initial results are also encouraging for other growth factors, including pigment epithelium-derived factor administered via an adenoviral vector. Ruboxistaurin, which decreases protein

  15. SEMIAUTOMATED QUANTITATIVE APPROACH TO CHARACTERIZE TREATMENT RESPONSE IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: A Real-World Study.

    Science.gov (United States)

    Roberts, Philipp K; Nesper, Peter L; Gill, Manjot K; Fawzi, Amani A

    2017-08-01

    To perform a quantitative study of the vascular microstructure in actively treated choroidal neovascularization by optical coherence tomographic angiography. Patients undergoing individualized anti-vascular endothelial growth factor therapy of minimum 12 months duration were included in this cross-sectional observational study and imaged using optical coherence tomographic angiography. En face optical coherence tomographic angiography images were analyzed for quantitative features, such as junction density, vessel length, and lacunarity using validated software (Angiotool). Patients were divided into 2 groups depending on their individualized treatment interval: "good responders, treated less frequently than 6 weeks" versus "poor responders, treated every 6 weeks or more frequently." Nonparametric testing was used to assess differences between these groups. Twenty-five eyes of 23 consecutive patients with a median 58-month history of choroidal neovascularization, treated by median of 34 anti-vascular endothelial growth factor injections, were included in the analysis. There was no significant difference between any of the microvascular choroidal neovascularization features between the 2 groups (P > 0.05). The semiautomated vessel segmentation software provides an objective and quantitative approach for choroidal neovascularization characterization. The consistently nonsignificant outcomes between the groups may provide evidence to support the "normalization hypothesis." This would suggest that regardless of treatment interval, individualized therapy in these eyes established vessel stability.

  16. CD105与脉络膜新生血管%CD105 and choroidal neovascularization

    Institute of Scientific and Technical Information of China (English)

    徐建锋; 王雨生

    2008-01-01

    CD105(endoglin)为一种同型二聚体的膜结合性糖蛋白,是转化生长因子-β(transforming growth factor, TGF-β)受体超家族的成员之一.它参与TGF-β受体的信号转导,调节细胞对TGF-β的反应,在新生血管组织及肿瘤组织边缘部分血管起源的内皮细胞中高度表达,是新生血管的标志物之一.脉络膜新生血管(choroidal neovascularization, CNV)的生成是年龄相关性黄斑变性(age-related macular degeneration, AMD)、眼拟组织胞浆菌病综合征(presumed ocular histoplasmosis syndrome, POHS)和病理性近视黄斑变性等CNV相关疾病的的主要病理特征.近年研究表明,CD105与CNV密切相关,可能成为治疗CNV重要的靶分子之一.

  17. Inflammatory choroidal neovascularization in Indian eyes: Etiology, clinical features, and outcomes to anti-vascular endothelial growth factor

    Directory of Open Access Journals (Sweden)

    Rupak Roy

    2017-01-01

    Full Text Available Background and Objectives: The aim was to study the clinical profile of inflammatory choroidal neovascularization (CNV and its treatment response to intravitreal bevacizumab or ranibizumab on pro re nata (PRN basis in Indian eyes. Materials and Methods: This was a retrospective case series of consecutive patients with inflammatory CNV treated with anti-vascular endothelial growth factor (anti-VEGF in a tertiary eye care center in Eastern India between 2009 and 2014. The data about clinical features, investigations, treatment, and outcomes were obtained from the medical records. We included patients with active inflammatory CNV but with no evidence of inflammation and were treated with anti-VEGF alone, with a minimum follow-up of 6 months. Main outcome measures were a clinical and etiological profile of inflammatory CNV in Indian eyes and their response to treatment. Results: Thirty eyes of 28 patients were included in the study. The mean follow-up was 17.93 ± 14.28 months (range 6–53 months. In our cohort, seven (23.33% eyes had inflammatory CNV secondary to idiopathic choroiditis, four (13.33% eyes had toxoplasmosis, idiopathic panuveitis, and Vogt Koyanaki Harada's disease each. Three (10% eyes had geographic helicoid peripapillary choroidopathy and tubercular choroiditis each. Remaining two (6.66% eyes had punctate inner choroidopathy, while multifocal choroiditis with panuveitis, resolved endogenous endophthalmitis and Hansen's diseases were the etiology in one (3.33% case of inflammatory CNV each. The mean number of injections were 2.76 (range 1–5. Among thirty eyes of inflammatory CNV, 16 (53.3% eyes showed improvement, eight (26.6% maintained the same vision, whereas six (20% eyes showed deterioration of vision. Interpretations and Conclusion: Idiopathic choroiditis was the most common cause of inflammatory CNV and PRN intravitreal anti-VEGF (ranibizumab or bevacizumab appears to have effective treatment response.

  18. 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....

  19. Evaluation of visual functional and morphology change in young patients with idiopathic choroidal neovascularization

    Institute of Scientific and Technical Information of China (English)

    WANG Wen-qiu; WANG Feng-hua; SUN Xiao-dong; LIU Hai-yun; LU Feng-qing; HU Wei-ting; GONG Yuan-yuan; WU Ying; XU Shan; WANG Wei-jun; XU Xun

    2011-01-01

    Background Idiopathic choroidal neovascularization (ICNV) is an uncommon disorder affecting primarily individuals younger than the age of 50 years. In CNV patients, no apparent cause can be determined. This study aimed to evaluate the functional and morphological change of the retina with ICNV in young adults.Methods In this retrospective study, 32 eyes of 32 patients with subfoveal or juxta/extra foveal ICNV had been admitted into the Shanghai First People's Hospital from January 2009 to July 2010. The functional changes were evaluated using the best corrected visual acuity (BCVA) and the microperimetry in the macular area. The morphology changes were evaluated using optical coherence tomography (OCT), the color fundus photography and the fluorescein angiography.Results Seventeen patients with juxta/extra foveal and 15 subfoveal CNV were investigated. The mean logarithm of the minimum angle of resolution (LogMAR) BCVA was 0.39, the mean central retinal thickness (CRT) was 334 urn, and the mean sensitivity (MS) was 11.8 decibels (dB). In the subfoveal group, there was a strong correlation between CRT and BCVA (r=-0.675, F=2.167, P<0.01); as well as that between CRT and MS (r=-0.681, F=22.91, P<0.01). While in the juxta/extra foveal CNV group, the correlation of CRT and BCVA was not significant (r=-0.071, P=1.018, P >0.05); neither was the correlation of CRT and MS (r=-0.142, F=36.54, P>0.05). The microperimetry (MP-1) test revealed 17 (53%) patients with stable fixation, 9 (28%) with relatively unstable and 6 (19%) with unstable fixation. Fixation stability correlated positively with sensitivity in the central 2° diameter area (r=0.380, F=3.213, P <0.05) and the duration of symptoms (r=0.401, F=7.933, P<0.05).Conclusions ICNV was associated with reduced total MS, unstable fixation and eccentric fixation. These findings emphasized functional change in ICNV is beyond the BCVA and regular morphology change, which provided additional information of

  20. Intravitreal bevacizumab treatment for choroidal neovascularization in pathologic myopia: 12-month results.

    Science.gov (United States)

    Gharbiya, Magda; Allievi, Francesca; Mazzeo, Luigi; Gabrieli, Corrado Balacco

    2009-01-01

    To evaluate the short-term efficacy and safety of intravitreal bevacizumab for the treatment of myopic choroidal neovascularization (CNV). Prospective, nonrandomized, interventional case series. Twenty eyes from 20 patients with CNV secondary to pathologic myopia participated in this prospective nonrandomized interventional case series. All patients were scheduled for three monthly intravitreal bevacizumab 1.25 mg injections. Early Treatment Diabetic Retinopathy Study best-corrected visual acuity (BCVA), foveal center thickness (FCT) on optical coherence tomography (OCT), and fluorescein angiographic findings were examined before and after treatment. Patients were followed up for 12 months. The mean BCVA (+/- standard deviation [SD]) at baseline was 24.8 (+/- 11.86) letters (Snellen equivalent: 20/80). At 12 months after treatment, the mean BCVA (+/- SD) improved significantly (P = .000001) to 43 (+/- 12.38) letters (Snellen equivalent: 20/35). At 12 month follow-up, BCVA improved 10 letters or more in 18 (90%) out of 20 treated eyes and improved 15 letters or more in 14 (70%) out of 20 treated eyes. No treated eyes experienced a worsening of BCVA from baseline. The mean FCT (+/- SD) at baseline was 223 (+/- 47.43) microns. At 12 months after treatment, the mean FCT (+/- SD) reduced to 206 (+/- 50.87) microns. This reduction in FCT after treatment was not statistically significant (P = .11). At 12 months follow-up, absence of fluorescein leakage from the CNV was demonstrated in 19 (95%) out of 20 treated eyes and persistent leakage in one eye (5%). None of the 19 eyes that had CNV closure experienced recurrence at 12-month follow-up. No ocular or systemic adverse effects from treatment were encountered. These results of intravitreal bevacizumab in myopic CNV are very promising with no apparent short-term safety concerns. At 12 months, treated eyes had a significant improvement in visual acuity (VA). OCT findings, as well, showed a trend consistent with the

  1. Long-term follow-up of patients with choroidal neovascularization due to angioid streaks

    Science.gov (United States)

    Martinez-Serrano, Maria Guadalupe; Rodriguez-Reyes, Abelardo; Guerrero-Naranjo, Jose Luis; Salcedo-Villanueva, Guillermo; Fromow-Guerra, Jans; García-Aguirre, Gerardo; Morales-Canton, Virgilio; Velez-Montoya, Raul

    2017-01-01

    Background The following case series describes the long-term anatomical and functional outcome of a group of seven patients with choroidal neovascularization (CNV), secondary to angioid streaks (AS), who were treated with antiangiogenic drugs in a pro re nata (PRN) regimen. After the 4-year mark, visual acuity tends to return to pretreatment level. Treatment delays and lack of awareness and self-referral by the patients are believed to be the cause of the PRN regimen failure. Purpose To assess the long-term outcomes (>4 years) of patients with CNV due to AS treated with a PRN regimen of antiangiogenic. Methods This was a retrospective, case series, single-center study. We reviewed the electronic medical records from patients with CNV due to AS. From each record, we noted general demographic data and relevant medical history; clinical presentation, changes in best-corrected visual acuity (BCVA) over time, optical coherent tomography parameters, treatment and retreatment details, and systemic associations. Changes in BCVA and central macular thickness were assessed with a Wilcoxon two-sample test, with an alpha value of ≤0.05 for statistical significance. Results The mean follow-up time was 53.8±26.8 months. BCVA at baseline was: 1.001±0.62 logMAR; at the end of follow-up: 0.996±0.56 logMAR (P=0.9). Central macular thickness at baseline was: 360.85±173.82 μm; at the end of follow-up: 323.85±100.34 μm (P=0.6). Mean number of intravitreal angiogenic drugs: 6±4.16 injections (range 4–15). Mean time between injections was 3.8±2.7 months (range 1.9–5.8 months). Conclusion Despite initial anatomical and functional improvement, patients at the end of the follow-up had no visual improvement after a pro re nata regimen of antiangiogenic drugs. The amount of retreatments, number of recurrences, and time between intravitreal injections were similar to previous reports with shorter follow-up. PMID:28031699

  2. The anti-angiogenic role of discoidin domain receptor 2 (DDR2) in laser-induced choroidal neovascularization.

    Science.gov (United States)

    Zhu, Tong; Zhu, Jie; Bu, Xin; Zhao, Hu; Zhang, Shuya; Chang, Yuan; Li, Rong; Yao, Libo; Wang, Yusheng; Su, Jin

    2015-02-01

    Choroidal neovascularization (CNV), an aberrant growth of blood vessels in the choroid layer of the eye, is a major cause of vision loss. In view of our recent finding that discoidin domain receptor 2 (DDR2), a collagen-binding receptor tyrosine kinase, is involved in control of vascular endothelial activity and tumor angiogenesis, the present study aims to investigate whether and how DDR2 affects the pathogenesis of CNV. We initially found that a spontaneous DDR2 mutant mouse colony (slie) exhibited enhanced amplitude of laser-induced CNV. The inhibitory role of DDR2 in CNV development was further confirmed by experiments through intravitreous injection of DDR2 small interference RNA (siRNA) or DDR2-expressing adenovirus. Quantitative real-time polymerase chain reaction (qPCR) and immunoblot analysis showed that DDR2 regulates the expression of several major pro-angiogenic factors in the laser-injured choroid as well as in retinal pigment epithelium (RPE) cells. In addition, it was demonstrated that the CNV-induced increases in the phosphorylation levels of Akt and mTOR were affected by the upregulation or downregulation of DDR2. Thus, the data from this study for the first time revealed that DDR2 negatively regulates the development of experimental CNV in vivo, which may provide a novel target for preventing human pathological ocular neovascularization. Key messages: DDR2 does not affect retinal development. DDR2 inhibits laser-induced CNV. DDR2 regulates angiogenic factor expression in CNV lesion as well as in RPE cells. DDR2 is involved in modulation of CNV-induced activation of PI3K pathway.

  3. Economic Burden of Bilateral Neovascular Age-Related Macular Degeneration: Multi-Country Observational Study

    OpenAIRE

    Alan F. Cruess; Gergana Zlateva; Xiao Xu; Gisele Soubrane; Daniel Pauleikhoff; Andrew Lotery; Jordi Mones; Ronald Buggage; Caroline Schaefer; Tyler Knight; Goss, Thomas F

    2008-01-01

    Background: There is limited previous research examining the healthcare costs of neovascular age-related macular degeneration (NV-AMD), which constrains our understanding of the economic impact of this condition. With aging populations, this leading cause of rapid vision loss in Western countries is expected to become a pressing health predicament, requiring decision makers to evaluate alternative treatment strategies for AMD. Objective: To document the economic burden of bilateral NV-AMD, th...

  4. Treatment of neovascular age-related macular degeneration in patients with diabetes

    Directory of Open Access Journals (Sweden)

    Michael Cummings

    2008-06-01

    Full Text Available Michael Cummings1, José Cunha-Vaz21Academic Department of Diabetes and Endocrinology, Queen Alexandra Hospital, Portsmouth, UK; 2Department of Ophthalmology, University Hospital of Coimbra, Centre of Ophthalmology, Institute of Biomedical Research on Light and Image, Faculty of Medicine, University of Coimbra, and Association for Innovation and Biomedical Research on Light and Image, Coimbra, PortugalAbstract: The number of patients with type 2 diabetes continues to rise; an anticipated 300 million people will be affected by 2025. The immense social and economic burden of the condition is exacerbated by the initial asymptomatic nature of type 2 diabetes, resulting in a high prevalence of micro- and macrovascular complications at presentation. Diabetic retinopathy, one of the potential microvascular complications associated with diabetes, and neovascular age-related macular degeneration (AMD are the two most frequent retinal degenerative diseases, and are responsible for the majority of blindness due to retinal disease. Both conditions predominantly affect the central macula, and are associated with the presence of retinal edema and an aggressive inflammatory repair process that accelerates disease progression. The associated retinal edema and the inflammatory repair process are directly involved in the breakdown of the blood-retinal barrier (BRB. Yet, the underlying alterations to the BRB caused by the diseases are very different. The coexistence of the two conditions appears to be relatively uncommon, suggesting that diabetes may even protect patients from developing neovascular AMD. However, it is thought that the inflammatory repair responses associated with diabetic retinopathy and neovascular AMD may be cumulative and, in patients affected by both, could result in chronic diffuse cystoid edema. Treatment considerations in such patients should, therefore, include the role of retinal edema and the increased susceptibility of patients with

  5. Regulation of signaling events involved in the pathophysiology of neovascular AMD

    OpenAIRE

    Wang, Haibo; Hartnett, M. Elizabeth

    2016-01-01

    Neovascular age-related macular degeneration (AMD) is a complex disease in which an individual’s genetic predisposition is affected by aging and environmental stresses, which trigger signaling pathways involving inflammation, oxidation, and/or angiogenesis in the RPE cells and choroidal endothelial cells (CECs), to lead to vision loss from choroidal neovascularization. Antiangiogenic therapies have greatly improved clinical outcomes in the last decade; however, vision improves in less than ha...

  6. Anti-angiogenic effects of a mutant endostatin: a new prospect for treating retinal and choroidal neovascularization.

    Directory of Open Access Journals (Sweden)

    Yujing Bai

    Full Text Available Pathological fundus angiogenesis is a major cause of vision loss in retina diseases. Endostatin, a C-terminal fragment of collagen XVIII, is an endogenous anti-angiogenic protein. The present study aimed to investigate the in vitro and in vivo anti-angiogenic properties of two proteins: an N-terminal H1D/H3D mutant endostatin (M-ES and a polyethylene glycol propionaldehyde (PEG covalent M-ES (PEG-M-ES.M-ES and PEG-M-ES properties were characterized in vitro using a zinc ion binding assay and a stability test. Activity assays, including migration, proliferation, and tube formation assays, were performed with human retinal microvascular endothelial cells (HRMECs and human umbilical vein endothelial cells (HUVECs. Mouse oxygen-induced retinopathy (OIR and choroidal neovascularization (CNV models were used to evaluate in vivo anti-angiogenic effects. In addition, a rabbit model was used to study the retinal pharmacokinetic profile following an intravitreal injection.The results indicated that the H1D/H3D mutations of endostatin reduced the zinc binding capacity of M-ES and facilitated PEG covalent binding. PEG-M-ES was more stable and persisted longer in the retina compared with M-ES. The in vitro studies demonstrated that M-ES and PEG-M-ES inhibited HRMEC and HUVEC proliferation, migration, and tube formation more efficiently than ES. In vivo, a single intravitreal injection of M-ES and PEG-M-ES significantly decreased neovascularization in both the OIR and CNV animal models.The present study demonstrated for the first time that PEG-M-ES exhibits a long-term inhibitory effect on neovascularization in vitro and in vivo. These data suggest that PEG-M-ES may represent an innovative therapeutic strategy to prevent fundus neovascularization.

  7. Retinal pigment epithelial cell expression of active Rap 1a by scAAV2 inhibits choroidal neovascularization

    Directory of Open Access Journals (Sweden)

    Haibo Wang

    2016-01-01

    Full Text Available To test the hypothesis that increased Rap1a activity specifically in retinal pigment epithelial cells resists choroidal neovascularization (CNV, self-complementary adeno-associated virus 2 (scAAV2 with RPE65-promoter-driven GFP vectors were generated and introduced subretinally into Rap1b-deficient mice. Six-week-old mice that received subretinal control (scAAV2-Con or constitutively active Rap1a (scAAV2-CARap1a showed strong GFP at the 5 × 108 viral particle/μl dose 5 weeks later without altering retinal morphology or function. Compared to scAAV2-Con- or phosphate-buffered saline (PBS-injected, eyes injected with scAAV2-CARap1a had increased Rap1 in retinal pigment epithelial (RPE/choroidal lysates and a significant reduction in CNV volume 7 days after laser, comparable to eyes that received intravitreal anti-VEGF versus IgG control. scAAV2-CARap1a-, but not anti-VEGF-, injected eyes had increased pan-cadherin in RPE/choroids. In cultured RPE cells, increased active Rap1a inhibited TNFα-induced disassociation of junctional pan-cadherin/β-catenin complexes, increased transepithelial electrical resistance through an interaction of β-catenin with phosphorylated scaffold protein, IQGAP1, and inhibited choroidal endothelial cell (CEC transmigration of an RPE monolayer. This evidence shows that increased Rap1a activity specifically in RPE cells is sufficient to reduce CEC transmigration and CNV and involves IQGAP1-mediated protection of RPE junctional complexes.

  8. Retinal pigment epithelial cell expression of active Rap 1a by scAAV2 inhibits choroidal neovascularization.

    Science.gov (United States)

    Wang, Haibo; Han, Xiaokun; Bretz, Colin A; Becker, Silke; Gambhir, Deeksha; Smith, George W; Samulski, R Jude; Wittchen, Erika S; Quilliam, Lawrence A; Chrzanowska-Wodnicka, Magdalena; Hartnett, M Elizabeth

    2016-01-01

    To test the hypothesis that increased Rap1a activity specifically in retinal pigment epithelial cells resists choroidal neovascularization (CNV), self-complementary adeno-associated virus 2 (scAAV2) with RPE65-promoter-driven GFP vectors were generated and introduced subretinally into Rap1b-deficient mice. Six-week-old mice that received subretinal control (scAAV2-Con) or constitutively active Rap1a (scAAV2-CARap1a) showed strong GFP at the 5 × 10(8) viral particle/µl dose 5 weeks later without altering retinal morphology or function. Compared to scAAV2-Con- or phosphate-buffered saline (PBS)-injected, eyes injected with scAAV2-CARap1a had increased Rap1 in retinal pigment epithelial (RPE)/choroidal lysates and a significant reduction in CNV volume 7 days after laser, comparable to eyes that received intravitreal anti-VEGF versus IgG control. scAAV2-CARap1a-, but not anti-VEGF-, injected eyes had increased pan-cadherin in RPE/choroids. In cultured RPE cells, increased active Rap1a inhibited TNFα-induced disassociation of junctional pan-cadherin/β-catenin complexes, increased transepithelial electrical resistance through an interaction of β-catenin with phosphorylated scaffold protein, IQGAP1, and inhibited choroidal endothelial cell (CEC) transmigration of an RPE monolayer. This evidence shows that increased Rap1a activity specifically in RPE cells is sufficient to reduce CEC transmigration and CNV and involves IQGAP1-mediated protection of RPE junctional complexes.

  9. Small laser spot versus standard laser spot photodynamic therapy for idiopathic choroidal neovascularization: a randomized controlled study

    Institute of Scientific and Technical Information of China (English)

    LI Xiao-xin; TAO Yong

    2012-01-01

    Backcround 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).Methods 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.Results 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 <0.001 and P=0.023,respectively).In each follow-up,the number of cases with decreased or unchanged leakage of choroidal neovascularization by FA and reduced subretinal fluid by OCT did not vary significantly between the two groups.Ten cases (37.0%) in the study group and eight cases (32.0%) in the control group suffered from recurrent CNV (P=0.703).Conclusions Better visual improvements,less RPE damage,a similar recurrent rate of CNV and change of subretinal fluid were observed in the small laser spot PDT group than in the standard laser spot PDT group for ICNV.

  10. Macular atrophy in patients with long-term anti-VEGF treatment for neovascular age-related macular degeneration.

    Science.gov (United States)

    Munk, Marion R; Ceklic, Lala; Ebneter, Andreas; Huf, Wolfgang; Wolf, Sebastian; Zinkernagel, Martin S

    2016-12-01

    To identify the prevalence and progression of macular atrophy (MA) in neovascular age-related macular degeneration (AMD) patients under long-term anti-vascular endothelial growth factor (VEGF) therapy and to determine risk factors. This retrospective study included patients with neovascular AMD and ≥30 anti-VEGF injections. Macular atrophy (MA) was measured using near infrared and spectral-domain optical coherence tomography (SD-OCT). Yearly growth rate was estimated using square-root transformation to adjust for baseline area and allow for linearization of growth rate. Multiple regression with Akaike information criterion (AIC) as model selection criterion was used to estimate the influence of various parameters on MA area. Forty-nine eyes (47 patients, mean age 77 ± 14) were included with a mean of 48 ± 13 intravitreal anti-VEGF injections (ranibizumab:37 ± 11, aflibercept:11 ± 6, mean number of injections/year 8 ± 2.1) over a mean treatment period of 6.2 ± 1.3 years (range 4-8.5). Mean best-corrected visual acuity improved from 57 ± 17 letters at baseline (= treatment start) to 60 ± 16 letters at last follow-up. The MA prevalence within and outside the choroidal neovascularization (CNV) border at initial measurement was 45% and increased to 74%. Mean MA area increased from 1.8 ± 2.7 mm(2) within and 0.5 ± 0.98 mm(2) outside the CNV boundary to 2.7 ± 3.4 mm(2) and 1.7 ± 1.8 mm(2) , respectively. Multivariate regression determined posterior vitreous detachment (PVD) and presence/development of intraretinal cysts (IRCs) as significant factors for total MA size (R(2) = 0.16, p = 0.02). Macular atrophy (MA) area outside the CNV border was best explained by the presence of reticular pseudodrusen (RPD) and IRC (R(2) = 0.24, p = 0.02). A majority of patients show MA after long-term anti-VEGF treatment. Reticular pseudodrusen (RPD), IRC and PVD but not number of injections or treatment duration seem to be associated with the

  11. Pneumatic displacement and intravitreal bevacizumab: A new approach for management of submacular hemorrhage in choroidal neovascular membrane

    Directory of Open Access Journals (Sweden)

    Chawla Shobhit

    2009-01-01

    Full Text Available Choroidal neovascular membrane (CNVM is one of the most common causes of submacular hemorrhage (SMH. Conventional treatment involves management of the SMH with pneumatic displacement with or without tissue plasminogen activator (TPA followed by intravitreal injection of bevacizumab in a second sitting. We decided to assess the efficacy of treating SMH secondary to CNVM with pneumatic displacement using sulphur hexafluoride (SF6 gas and intravitreal bevacizumab. Four patients with SMH secondary to CNVM were included in this study. Intravitreal bevacizumab, 0.05 ml, along with 0.5 ml of SF6 was injected through the pars plana into the vitreous cavity. Postoperative best corrected visual acuity improved in all eyes with complete or partial displacement of SMH out of the foveal area.

  12. [Combined hamartoma of the retina and retinal pigment epithelium. Anti-VEGF treatment of the associated choroidal neovascular membranes].

    Science.gov (United States)

    Echevarría, L; Villena, O; Nievas, T; Bellido, R

    2015-02-01

    A 58 year-old female was diagnosed with a juxtapapillary combined hamartoma of the retina and retinal pigment epithelium (CHR-RPE) in her left eye 14 years ago. Her visual acuity in that eye was 20/20. Recently, she came to our department with a sudden visual loss and metamorphopsis in her left eye. After performing funduscopy, angiography and OCT, she was diagnosed with choroidal neovascular membrane (CNVM) at lesion border, and started on antiangiogenic therapy. CHR-RPE, despite being a benign condition, may become complicated with severe visual impairment. Antiangiogenic therapy provides a good alternative to photodynamic therapy or laser photocoagulation for treatment of CNVM, avoiding adding iatrogenesis from these treatment to the complications associated with this pathology. Copyright © 2014 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  13. Intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration in treatment-naive patients

    DEFF Research Database (Denmark)

    Pedersen, Karen Bjerg; Sjølie, Anne Katrin; Møller, Flemming

    2008-01-01

    , pilot study of 26 eyes of 26 patients, all previously treatment-naive to photodynamic therapy, argon laser or anti-vascular endothelial growth factor (VEGF), were treated with one or more intravitreal injections of 1.25 mg bevacizumab. Of the 26 patients, 15 (57.7%) had occult choroidal...... neovascularization (CNV), 6 (23.1%) had predominantly classic CNV and 5 (19.2%) had minimally classic CNV. Ophthalmic outcome measures included changes in standardized Early Treatment Diabetic Research Study (ETDRS) VA, contrast sensitivity and OCT. The patients were examined at baseline and 1 week, 6 weeks, 3...... months and 6 months after the first injection. Re-treatment was given on an 'as needed' basis. Results: Twenty-four eyes of 24 patients completed 6 months of follow-up. Two patients chose to discontinue the study. Mean ETDRS VA score improved from 55 letters at baseline to 60 letters at 1 week (P

  14. Structural and molecular changes in the aging choroid: implications for age-related macular degeneration.

    Science.gov (United States)

    Chirco, K R; Sohn, E H; Stone, E M; Tucker, B A; Mullins, R F

    2017-01-01

    Age-related macular degeneration (AMD) is a devastating disease-causing vision loss in millions of people around the world. In advanced stages of disease, death of photoreceptor cells, retinal pigment epithelial cells, and choroidal endothelial cells (CECs) are common. Loss of endothelial cells of the choriocapillaris is one of the earliest detectable events in AMD, and, because the outer retina relies on the choriocapillaris for metabolic support, this loss may be the trigger for progression to more advanced stages. Here we highlight evidence for loss of CECs, including changes to vascular density within the choriocapillaris, altered abundance of CEC markers, and changes to overall thickness of the choroid. Furthermore, we review the key components and functions of the choroid, as well as Bruch's membrane, both of which are vital for healthy vision. We discuss changes to the structure and molecular composition of these tissues, many of which develop with age and may contribute to AMD pathogenesis. For example, a crucial event that occurs in the aging choriocapillaris is accumulation of the membrane attack complex, which may result in complement-mediated CEC lysis, and may be a primary cause for AMD-associated choriocapillaris degeneration. The actions of elevated monomeric C-reactive protein in the choriocapillaris in at-risk individuals may also contribute to the inflammatory environment in the choroid and promote disease progression. Finally, we discuss the progress that has been made in the development of AMD therapies, with a focus on cell replacement.

  15. Circulating monocytes and B-lymphocytes in neovascular age-related macular degeneration

    Science.gov (United States)

    Hector, Sven Magnus; Sørensen, Torben Lykke

    2017-01-01

    Background Individuals with neovascular age-related macular degeneration (AMD) have altered number and distribution of retinal macrophages and show changes in circulating antibodies. We wanted to investigate the corresponding precursors, with subpopulations. We therefore measured monocyte and B-lymphocyte populations in individuals with neovascular AMD. Design This was an observational case–control study. Participants or samples A total of 31 individuals with neovascular AMD and 30 healthy age-matched controls were included. Methods Patients and controls were interviewed, and ophthalmological examination included visual acuity assessment using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart, spectral domain optical coherence tomography (SD-OCT), slit-lamp examination and fundus photography. Moreover, venous blood was drawn and prepared for flow cytometry. Cells were gated and measured for surface markers. Main outcome measures Relative amounts of monocytes and B-lymphocytes with subsets, as well as selected surface markers, were measured. Results The two groups did not significantly differ in age, smoking history, body mass index, physical activity or C-reactive protein (CRP). Total monocytes (percentage of all leukocytes) were lower in the neovascular AMD group (median 5.5%) compared with the level in the control group (6.5%; P-value: 0.028). The percentage of intermediate monocytes positive for cluster of differentiation 11b (CD11b) was lower for AMD patients (99.4%) compared with 100% for the control group (P-value: 0.032). Conclusion We observed lower numbers of monocytes, which show a potentially impaired ability to migrate across the endothelial wall in patients with neovascular AMD. These subtle changes could potentially lead to an imbalance in the recruitment of macrophages into the retina during disease development. PMID:28176950

  16. 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

  17. Incidence of outer retinal tubulation in eyes with choroidal neovascularization under intravitreal anti-vascular endothelial growth factor therapy in a Japanese population

    Directory of Open Access Journals (Sweden)

    Takagi S

    2017-06-01

    Full Text Available Seiji Takagi,1–3 Michiko Mandai,1,4 Noriko Miyamoto,1,2 Akihiro Nishida,1,2 Yasuhiko Hirami,1,2 Hirofumi Uyama,1,2 Midori Yamamoto,1,2 Masayo Takahashi,1,2,4 Goji Tomita,3 Yasuo Kurimoto1,2 1Department of Ophthalmology, Kobe City Medical Center General Hospital, 2Department of Translational Research, Division of Ophthalmology, Institute of Biomedical Research and Innovation, Kobe, Hyogo, 3Department of Ophthalmology, Toho University Ohashi Medical Center, Meguro-ku, Tokyo, 4RIKEN Center for Developmental Biology, Kobe, Hyogo, Japan Purpose: The purpose of this study was to investigate the occurrence of outer retinal tubulation (ORT among patients with different types of choroidal neovascularization (CNV over time. Materials and methods: In this retrospective chart review, disease type was classified as typical age-related macular degeneration (t-AMD, polypoidal choroidal vasculopathy (PCV, retinal angiomatous proliferation (RAP, or myopic CNV (mCNV. Spectral domain-optical coherence tomography (SD-OCT images were evaluated for the appearance of ORT and subretinal fibrosis and fluid. Furthermore, the association of the presence of ORT with clinical data and OCT findings was investigated. Results: Among the 136 eyes studied, the overall rates of occurrence of ORT were 7.8%, 18.8%, and 31.6% after 12, 24, and 36 months from baseline, respectively. Among patients with t-AMD, RAP, and mCNV, the occurrence of ORT increased soon after the initial visit. In contrast, among patients with PCV, the occurrence of ORT increased slowly over time. Patients with and without ORT – ORT(+ and ORT(- groups, respectively – differed significantly in terms of sex ratio and presence of intraretinal fluid at the initial visit and presence of subretinal fibrosis at 3 years from baseline. The ORT(+ group exhibited lower visual acuity (VA; 0.67±0.43 than that of the ORT(- group (0.41±0.36; P<0.001.Conclusion: The occurrence of ORT tended to increase more slowly

  18. Management of Neovascular Age-related Macular Degeneration: A Review on Landmark Randomized Controlled Trials.

    Science.gov (United States)

    Agarwal, Aniruddha; Aggarwal, Kanika; Gupta, Vishali

    2016-01-01

    In the last decade, a number of prospective clinical trials with carefully designed study protocols have been conducted for the treatment of neovascular age-related macular degeneration (AMD). These landmark clinical trials such as ANCHOR and MARINA and, more recently, the Comparison of AMD Treatment Trials and VIEW studies have revolutionized the management of neovascular AMD. While AMD continues to remain a leading cause of severe visual loss worldwide, advances in pharmacotherapeutics have led to substantial improvements in the outcome of these patients. The introduction of anti-vascular endothelial growth factor agents has resulted in improvement of visual outcomes and has had a positive impact on the quality of life among elderly population. While the contemporary management of neovascular AMD has been successful in tremendously reducing the visual morbidity, the financial burden of therapy has increased exponentially. To overcome these challenges, newer pharmacologic agents are evaluated for their efficacy and safety in AMD. Ground-breaking advances in bench to bedside research have led to discovery of new pathways that appear to be viable targets for preventing visual loss in AMD. In this review, study designs and results of landmark clinical trials in AMD from the past decade have been summarized.

  19. Management of neovascular Age-related macular degeneration: A review on landmark randomized controlled trials

    Directory of Open Access Journals (Sweden)

    Aniruddha Agarwal

    2016-01-01

    Full Text Available In the last decade, a number of prospective clinical trials with carefully designed study protocols have been conducted for the treatment of neovascular age.related macular degeneration (AMD. These landmark clinical trials such as ANCHOR and MARINA and, more recently, the Comparison of AMD Treatment Trials and VIEW studies have revolutionized the management of neovascular AMD. While AMD continues to remain a leading cause of severe visual loss worldwide, advances in pharmacotherapeutics have led to substantial improvements in the outcome of these patients. The introduction of anti.vascular endothelial growth factor agents has resulted in improvement of visual outcomes and has had a positive impact on the quality of life among elderly population. While the contemporary management of neovascular AMD has been successful in tremendously reducing the visual morbidity, the financial burden of therapy has increased exponentially. To overcome these challenges, newer pharmacologic agents are evaluated for their efficacy and safety in AMD. Ground.breaking advances in bench to bedside research have led to discovery of new pathways that appear to be viable targets for preventing visual loss in AMD. In this review, study designs and results of landmark clinical trials in AMD from the past decade have been summarized.

  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. Verteporfin photodynamic therapy combined with intravitreal ranibizumab in neovascular age-related macular degeneration: 24-month follow-up

    Directory of Open Access Journals (Sweden)

    Rosalia Giustolisi

    2014-09-01

    Full Text Available Purpose: to evaluate the efficacy and safety of combined therapy with Photodynamic Therapy with Verteporfin (PDT-V and intravitreal ranibizumab same-day compared with monotherapy with ranibizumab (three monthly injections for the treatment of the choroidal neovascularization (CNV due to age-related macular degeneration (AMD. Type of study : open-label, randomized controlled trial (RCT. Materials and Methods: 17 eyes of 17 patients were consecutively enrolled and randomly assigned to ranibizumab intravitreal injection + PDT compared with a control group of 30 eyes of 30 patients treated with only ranibizumab 0.5mg in three monthly injections. Best corrected visual acuity (BCVA, central macular thickness (CMT on optical coherence tomography were examined before and after treatment. Patients were followed-up for twelve months. Results: in the combined therapy group, the mean baseline BCVA is 32.6 letters, at 24-months after treatment it’s 31.4 letters with a loss of 1.2 letters. The mean central thickness at baseline is 314.6 µm. After twenty four months the mean CMT is 222.5 µm, with mean CMT reduction of 92.1µm. In the ranibizumab-alone group, the mean baseline BCVA is 29.1 letters at 24-months it’s 28.6 letters with a little loss of 0.5 letters. The mean baseline CMT is 297.6 µm, at 24-months it is 235.9 µm, with mean CMT reduction of 61,7µm. Conclusions: the two treatments showed the same efficacy from a functional and anatomic point of view with a less number of retreatments in the combined therapy group. There were no serious ocular adverse events such as retinal detachment, endophthalmitis or ocular hypertone.

  2. 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

    2017-09-27

    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 < 0.001) after 1 week, by -12.54 µm (p < 0.001) after 2 weeks, and by -3.52 µm (p = 0.09) after 3 weeks. Mean intraretinal layer thickness changed only significantly between baseline and week 1 (p < 0.001). Mean subretinal thickness also decreased between weeks 1 and 2 (p = 0.01). Early morphological changes occur primarily in the first 14 days after treatment. This information could be clinically helpful to evaluate early non-response. © 2017 S. Karger AG, Basel.

  3. Role of intravitreal Bevacizumab Injection for Management of Neovascular Age Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Neha K Desai

    2016-06-01

    Full Text Available Background: Age related macular degeneration ( ARMD is the major cause of severe visual loss in older adults. Different treatment modalities are available such as: Laser photocoagulation, photodynamic therapy,transpupillary thermotherapy,submacular surgery and anti-veg. Aims and Objectives: The aim of our study was to evaluate the efficacy and safety of intravitreally administered Bevacizumab a humanized monoclonal anti and ndash;VEGF in Neovascular Age related Macular Degeneration. Methodology: This non randomized, prospective study was carried out on 75 eyes of 75 patients attending the OPD at M and J Institute Of Ophthalmology and diagnosed as having Neovascular ARMD confirmed on FFA and SD-OCT . After taking written informed consent all patients were injected with intravitreal Bevacizumab 1.25 mg/0.05 ml. Follow up visits were scheduled one week, one month post procedure and every monthly thereafter. Results: 75 eyes of 75 patients were included in this non randomized prospective study. and 29.33% patients required 2 injections. Visual acuity is improved more than 3 lines from baseline in 21.33% patient, 64% patient have 2-3 lines gain and 6.66% patients showed 0-1 line gain in snellen's visual acuity. 5.33% patients have a loss of 1 line from baseline and 2.66% patients showed loss of 2-3 lines. Central foveal thickness decreased more than 200 microns from baseline in 52% patients, 28% patients have decreased of 100-200 microns and 20% patients have decreased of less than 100 microns. Discussion: Approximately 10 % of ARMD patients manifest the neovascular form of the disease. 12 weeks. Our study showed that 80% patients had decrease in central foveal thickness more than 100 microns from baseline at the end of one year. 85% patients had gain of 2 or more lines on Snellen's visual acuity chart from baseline.No patient had any serious local or systemic adverse reactions.Limitations of our study is small number of patients,ICG not done

  4. 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)....

  5. Combination treatment of low fluence photodynamic therapy and intravitreal ranibizumab for choroidal neovascular membrane secondary to angioid streaks in Paget′s disease - 12 month results

    Directory of Open Access Journals (Sweden)

    Varsha V Prabhu

    2011-01-01

    Full Text Available Angioid streaks also called Knapp striae are small breaks in the Bruch′s membrane and have been reported with a host of systemic diseases. Rupture of streaks or development of secondary choroidal neovascular membrane (CNVM carries a dismal visual prognosis. We report the successful treatment of CNVM secondary to Paget′s disease using low fluence photodynamic therapy (PDT and intravitreal ranibizumab.

  6. En-face optical coherence tomography in the diagnosis and management of age-related macular degeneration and polypoidal choroidal vasculopathy

    Directory of Open Access Journals (Sweden)

    Tiffany Lau

    2015-01-01

    Full Text Available Optical coherence tomography (OCT is a noninvasive imaging modality providing high-resolution images of the central retina that has completely transformed the field of ophthalmology. While traditional OCT has produced longitudinal cross-sectional images, advancements in data processing have led to the development of en-face OCT, which produces transverse images of retinal and choroidal layers at any specified depth. This offers additional benefit on top of longitudinal cross-sections because it provides an extensive overview of pathological structures in a single image. The aim of this review was to discuss the utility of en-face OCT in the diagnosis and management of age-related macular degeneration (AMD and polypoidal choroidal vasculopathy (PCV. En-face imaging of the inner segment/outer segment junction of retinal photoreceptors has been shown to be a useful indicator of visual acuity and a predictor of the extent of progression of geographic atrophy. En-face OCT has also enabled high-resolution analysis and quantification of pathological structures such as reticular pseudodrusen (RPD and choroidal neovascularization, which have the potential to become useful markers for disease monitoring. En-face Doppler OCT enables subtle changes in the choroidal vasculature to be detected in eyes with RPD and AMD, which has significantly advanced our understanding of their pathogenesis. En-face Doppler OCT has also been shown to be useful for detecting the polypoid lesions and branching vascular networks diagnostic of PCV. It may therefore serve as a noninvasive alternative to fluorescein and indocyanine green angiography for the diagnosis of PCV and other forms of the exudative macular disease.

  7. Topical ocular delivery to laser-induced choroidal neovascularization by dual internalizing RGD and TAT peptide-modified nanoparticles

    Science.gov (United States)

    Chu, Yongchao; Chen, Ning; Yu, Huajun; Mu, Hongjie; He, Bin; Hua, Hongchen; Wang, Aiping; Sun, Kaoxiang

    2017-01-01

    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 > primary NPs. iRGD and TAT dual-modified NPs thus displayed significant targeting and penetration ability both in vitro and in vivo, indicating that it is a promising drug delivery system for managing CNV via topical ocular administration. PMID:28260884

  8. OPTICAL COHERENCE TOMOGRAPHY–BASED CORRELATION BETWEEN CHOROIDAL THICKNESS AND DRUSEN LOAD IN DRY AGE-RELATED MACULAR DEGENERATION

    Science.gov (United States)

    KO, ASHLEY; CAO, SIJIA; PAKZAD-VAEZI, KAIVON; BRASHER, PENELOPE M.; MERKUR, ANDREW B.; ALBIANI, DAVID A.; KIRKER, ANDREW W.; CUI, JING; MATSUBARA, JOANNE; FOROOGHIAN, FARZIN

    2014-01-01

    Purpose Spectral domain optical coherence tomography can be used to measure both choroidal thickness and drusen load. The authors conducted an exploratory study using spectral domain optical coherence tomography to determine if a correlation between choroidal thickness and drusen load exists in patients with dry age-related macular degeneration. Methods Forty-four patients with dry age-related macular degeneration were recruited. The drusen area and volume were determined using the automated software algorithm of the spectral domain optical coherence tomography device, and choroidal thickness was measured using enhanced depth imaging. Correlations were determined using multivariable and univariable analyses. Results The authors found an inverse correlation between choroidal thickness and drusen load (r = −0.35, P = 0.04). Drusen load was also correlated with visual acuity (r = 0.32, P = 0.04). A correlation between choroidal thickness and visual acuity was suggested (r = −0.22, P = 0.21). Conclusion Spectral domain optical coherence tomography can be used to assess the correlation between drusen load and choroidal thickness, both of which show a relationship with visual acuity. The measurement of these outcomes may serve as important outcome parameters in routine clinical care and in clinical trials for patients with dry age-related macular degeneration. PMID:23474546

  9. The SECURE study: long-term safety of ranibizumab 0.5 mg in neovascular age-related macular degeneration

    NARCIS (Netherlands)

    Silva, R. de; Axer-Siegel, R.; Eldem, B.; Guymer, R.; Kirchhof, B.; Papp, A.; Seres, A.; Gekkieva, M.; Nieweg, A.; Pilz, S.; Hoyng, C.B.

    2013-01-01

    OBJECTIVE: To evaluate long-term safety of intravitreal ranibizumab 0.5-mg injections in neovascular age-related macular degeneration (nAMD). DESIGN: Twenty-four-month, open-label, multicenter, phase IV extension study. PARTICIPANTS: Two hundred thirty-four patients previously treated with ranibizum

  10. Year 2 efficacy results of 2 randomized controlled clinical trials of pegaptanib for neovascular age-related macular degeneration.

    NARCIS (Netherlands)

    Chakravarthy, U.; Adamis, A.P.; Cunningham Jr, E.T.; Goldbaum, M.; Guyer, D.R.; Katz, B.; Patel, M.

    2006-01-01

    OBJECTIVE: To evaluate the efficacy of a second year of pegaptanib sodium therapy in patients with neovascular age-related macular degeneration (AMD). DESIGN: Two concurrent, multicenter, randomized, double-masked, sham-controlled studies (V.I.S.I.O.N. [Vascular Endothelial Growth Factor Inhibition

  11. Phacoemulsification Surgery in Eyes with Neovascular Age-Related Macular Degeneration

    Science.gov (United States)

    Papavasileiou, Evangelia; Kumar, Balakrishna Vineeth; Prasad, Som

    2014-01-01

    Purpose. To evaluate the visual outcomes and effect of phacoemulsification surgery on the progression of neovascular age-related macular degeneration (AMD). Methods. Retrospective, noncomparative, and interventional case series. Thirty eyes from 29 subjects with neovascular AMD treated with intravitreal antivascular endothelial growth factor (VEGF) injections who underwent phacoemulsification and had a postsurgery follow-up of 6 months were included. LogMAR best corrected visual acuity (BCVA) was assessed preoperatively; 1 month, 3 months, and 6 months postoperatively; and finally at the last visit. The frequency of anti-VEGF therapy, calculated as the number of intravitreal injections per month, and central macular thickness (CMT) before and after cataract surgery were determined. Results. Median (range) logMAR BCVA was 0.69 (0.16 to 1.32) preoperatively; 0.55 (−0.04 to 1.32) at 1 month, 0.52 (−0.1 to 1.32) at 3 months, and 0.50 (0.0 to 1.32) at 6 months postoperatively; and 0.6 (0.0 to 1.4) at final visit (P = 0.0011). There was no difference in the frequency of anti-VEGF injections between the immediate 6 months before and after phacoemulsification, which was equal to 0.1667 injections per month (P = 0.6377). Median CMT measured 203 μm preoperatively, which temporarily increased to 238 μm at 1 month after surgery (P = 0.0093) and then spontaneously returned to baseline, measuring 212.5 μm at 3 months postoperatively (P = 0.3811). Conclusion. Phacoemulsification surgery significantly improved vision in patients with neovascular AMD, with no increased need for anti-VEGF injections to keep the macula dry postoperatively. PMID:24719771

  12. Long-Term Results of Photodynamic Therapy for Choroidal Neovascularization in Pediatric Patients with Best Vitelliform Macular Dystrophy.

    Science.gov (United States)

    Sodi, Andrea; Murro, Vittoria; Caporossi, Orsola; Passerini, Ilaria; Bacci, Giacomo Maria; Caputo, Roberto; Menchini, Ugo

    2015-06-01

    To report long-term results of photodynamic therapy (PDT) in young patients affected by Best vitelliform macular dystrophy (VMD) complicated by choroidal neovascularization (CNV). We evaluated a group of 30 VMD patients with confirmed mutations in the BEST1 gene. Five of these patients had been diagnosed with CNV when younger than 15 years of age and three of them were treated by PDT. After the treatment they were followed for an average period of 77 months (range 62-99). In all the treated eyes visual acuity was stable during the first year of follow-up and then slowly improved even some years after the treatment. The improvement in visual acuity was associated with the development of fibrous tissue in the macula. PDT was a safe procedure in our series of pediatric patients with VMD complicated by CNV. It was followed by a CNV regression and a consequent improvement in visual acuity which continued to progress even several years after the treatment.

  13. Photodynamic monotherapy or combination treatment with intravitreal triamcinolone acetonide, bevacizumab or ranibizumab for choroidal neovascularization associated with pathological myopia

    Directory of Open Access Journals (Sweden)

    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.

  14. EXPRESSION OF PEDF mRNA AND PROTEIN IN NORMAL MOUSE RETINA AND EXPERIMENTAL CHOROIDAL NEO-VASCULARIZATION TISSUES

    Institute of Scientific and Technical Information of China (English)

    张雷; 王康孙; 王玲; 张士胜; 石海云

    2004-01-01

    Objective To study the expression of pigment epithelium derived factor ( PEDF) in normal mouse retina and experimental choroidal neovascularization (CNV) tissues. Methods CNV mouse models were induced by diode laser. The expression of PEDF mRNA and protein in normal mouse retina and CNV tissues were detected by in situ hybridization and immunohistochemical study. Results In normal mouse retina,PEDF mRNA was observed in the ganglion cell layer, inner nuclear layer and RPE cell layer, and PEDF protein was observed mainly in the nerve fiber layer, ganglion cell layer, photoreceptor cell layer and RPE cell layer, and lower level expression of PEDF protein was also observed in the inner plexiform layer and outer plexiform layer. In CNV tissues,the expression of PEDF mRNA and protein was also observed. 3d and 1 week after photocoagulation, the expression level of PEDF was relatively lower, and increased following the development of CNV. The level was the highest 2 weeks after photocoagulation, then decreased at 3 weeks. Conclusion PEDF was expressed in different layers of retina and was obviously expressed in the CNV tissues induced by laser photocoagulation. These findings suggest that PEDF may participate and modulate the development of CNV.

  15. Different treatment modalities for choroidal neovascularization in two eyes of one patient with bilateral type 2A parafoveal telangiectasia

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    Vivek Dave

    2013-01-01

    Full Text Available A 60-year-old diabetic man presented with a history of decrease in vision in both eyes since 2 weeks. At presentation, best corrected visual acuity (BCVA in the right eye (RE was 20/30 and that in the left eye (LE was 20/80. The right fundus revealed a grayish reflex, yellowish crystalline deposits and retinal pigment epithelial hyperplasia at the macula. The left fundus showed subretinal fluid and temporal subretinal hemorrhage near a grayish reflex at the macula. A diagnosis in both eyes of idiopathic macular telangiectasia (IMT type 2A with RE stage 4 and LE stage 5, choroidal neovascularization (CNVM was made. The patient was treated with photodynamic therapy (PDT in LE. The visual acuity improved to 20/40 over the next 6 months. At a 4-year follow-up, he developed decreased vision in RE diagnosed as IMT with CNV and was treated with intravitreal ranibizumab. At 6-month follow-up post injection, the vision was 20/40p.

  16. Genetic and functional dissection of ARMS2 in age-related macular degeneration and polypoidal choroidal vasculopathy.

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    Yong Cheng

    Full Text Available Age-related maculopathy susceptibility 2(ARMS2 was suggested to be associated with neovascular age-related macular degeneration (nAMD and polypoidal choroidal vasculopathy (PCV in multiple genetic studies in Caucasians and Japanese. To date, no biological properties have been attributed to the putative protein in nAMD and PCV. The complete genes of ARMS2 and HTRA1 including all exons and the promoter region were assessed using direct sequencing technology in 284 unrelated mainland northern Chinese individuals: 96 nAMD patients, 92 PCV patients and 96 controls. Significant associations with both nAMD and PCV were observed in 2 polymorphisms of ARMS2 and HTRA1 rs11200638, with different genotypic distributions between nAMD and PCV (p<0.001. After adjusting for rs11200638, ARMS2 rs10490924 remained significantly associated with nAMD and PCV (p<0.001. Then we overexpressed wild-type ARMS2 and ARMS2 A69S mutation (rs10490924 in RF/6A cells and RPE cells as in vitro study model. Cell proliferation, attachment, migration and tube formation were analyzed for the first time. Compare with wild-type ARMS2, A69S mutation resulted in a significant increase in proliferation and attachment but inhibited cell migration. Moreover, neither wild-type ARMS2 nor A69S mutation affected tube formation of RF/6A cells. There is a strong and consistent association of the ARMS2/HTRA1 locus with both nAMD and PCV, suggesting the two disorders share, at least partially, similar molecular mechanisms. Neither wild-type ARMS2 nor A69S mutation had direct association with neovascularisation in the pathogenesis of AMD.

  17. 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

    1185 eyes in 1099 patients who began vascular endothelial growth factor inhibitor treatment for nAMD during four separate periods in 2007, 2009, 2011 and 2012 using a fixed loading-dose regimen of three ranibizumab injections. RESULTS: Mean best-corrected visual acuity (BCVA) at presentation remained......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....... CONCLUSION: In this study, 2-week-earlier injection was associated with the equivalent of a 5-Early Treatment Diabetic Retinopathy Study letter-gain in mean visual acuity at 3 months after presentation. The difference is larger than expected from the 2-week-longer duration of disease at the study end...

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

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    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

  19. Successful long-term management of choroidal neovascularization secondary to angioid streaks in a patient with pseudoxanthoma elasticum: a case report.

    Science.gov (United States)

    Savastano, Maria Cristina; Minnella, Angelo Maria; Zinzanella, Gaetano; Falsini, Benedetto; Caporossi, Aldo

    2014-12-22

    We describe the long-term effectiveness and tolerability of intravitreal vascular endothelial growth factor inhibitor ranibizumab in a patient with pseudoxanthoma elasticum with bilateral macular choroidal neovascularization secondary to angioid streaks. A 54-year-old Caucasian man with history of heart disease presented with visual loss in his right eye. An examination revealed choroidal neovascularization and reduced visual acuity, while no abnormalities were seen in his left eye. He was diagnosed with angioid streaks associated with pseudoxanthoma elasticum. Off-label treatment with intravitreal bevacizumab once a month initiated in December 2007 was discontinued after 3 months due to lack of efficacy. In September 2008, the patient reported reduced visual acuity in his left eye and an examination revealed changes. Left eye treatment was initiated in October 2008 with a loading dose (three consecutive monthly intravitreal injections of ranibizumab 0.5mg/50 μL) followed by 0.5mg/50 μL followed by treatment as needed until May 2014. After 21 ranibizumab injections, an examination revealed angioid streaks and choroidal neovascularization in both eyes. His right eye showed retinal layer deterioration with outer limiting membrane and photoreceptor inner/outer segment junction involvement. His left eye had a smaller foveal scar, with other areas preserved. Visual acuity was stable in his treated left eye, but had deteriorated in his right eye. Ranibizumab treatment was well tolerated with no adverse events reported. In the present case, an as-needed regimen of ranibizumab after an initial loading dose, achieved maintenance of visual function and was well tolerated over a period of almost 6 years in a patient with pseudoxanthoma elasticum and high cardiovascular risk. As anti-vascular endothelial growth factor agents are associated with increased risk of systemic effects, particularly arterial thromboembolic events, following intravenous administration, the absence

  20. Retinal injury thresholds for 532, 578, and 630 nm lasers in connection to photodynamic therapy for choroidal neovascularization.

    Science.gov (United States)

    Chen, Hongxia; Yang, Zaifu; Zou, Xianbiao; Wang, Jiarui; Zhu, Jianguo; Gu, Ying

    2014-01-01

    The purpose of this study was to explore the retinal injury thresholds in rabbits and evaluate the influence of retinal pigmentation on threshold irradiance at laser wavelengths of 532, 578, and 630 nm which might be involved in hypocrellin B (HB) and hematoporphyrin monomethyl ether (HMME) photodynamic therapy (PDT) for choroidal neovascularization (CNV). The eyes of pigmented and non-pigmented rabbits were exposed to 532, 578, and 630 nm lasers coupled to a slit lamp biological microscope. The exposure duration was 100 seconds and the retinal spot size was 2 mm throughout the experiment. The minimum visible lesions were detected by funduscopy at 1 and 24 hours post exposure. Bliss probit analysis was performed to determine the ED50 thresholds, fiducial limits and probit slope. In pigmented rabbits, the 24-hour retinal threshold irradiances at 532, 578, and 630 nm were 1,003, 1,475, and 1,720 mW/cm(2) , respectively. In non-pigmented rabbits, the 24-hour threshold irradiances were 1,657, 1,865, and 15,360 mW/cm(2) , respectively. The ED50 for 24-hour observation differed very little from the ED50 for 1-hour observation. The non-pigmented rabbits required a ninefold increase in threshold irradiance at 630 nm comparing to the pigmented rabbits. This study will contribute to the knowledge base for the limits of laser irradiance in application of HB or HMME PDT for CNV. © 2013 Wiley Periodicals, Inc.

  1. Autologous Translocation of the Retinal Pigment Epithelium and Choroid in the Treatment of Exudative Age-related Macular Degeneration

    NARCIS (Netherlands)

    K.J.M. Maaijwee (Kristel Johanna Maria)

    2008-01-01

    textabstractAge-related macular degeneration (AMD) is the most important cause of irreversible legal blindness in elderly persons in industrialized countries. AMD has two forms: atrophic (dry) and exudative (wet). In the wet form, abnormal blood vessels, arising from the choriocapillaris (choroidal

  2. The stereotypical molecular cascade in neovascular age-related macular degeneration: the role of dynamic reciprocity.

    Science.gov (United States)

    Kent, D

    2015-11-01

    This review summarises our current understanding of the molecular basis of subretinal neovascularisation (SRNV) in age-related macular degeneration (AMD). The term neovascular AMD (NVAMD) is derived from the dominant early clinical features of haemorrhage, fluid, and lipid in the subretinal space (SRS) and the historical role of fluorescein angiography in detecting the presence of NV tissue. However, at the cellular level, SRNV resembles an aberrant but stereotypical tissue repair response that incorporates both an early inflammatory phase and a late fibrotic phase in addition to the neovascular (NV) component that dominates the early clinical presentation. This review will seek not only to highlight the important molecules involved in each of these components but to demonstrate that the development of SRNV has its origins in the earliest events in non-NV AMD pathogenesis. Current evidence suggests that this early-stage pathogenesis is characterised by complement-mediated immune dysregulation, leading to a state of chronic inflammation in the retinal pigment epithelium/Bruch's membrane/choriocapillaris complex. These initial events can be seamlessly and inextricably linked to late-stage development of SRNV in AMD by the process of dynamic reciprocity (DyR), the ongoing bidirectional communication between cells, and their surrounding matrix. Moreover, this correlation between disease onset and eventual outcome is reflected in the temporal and spatial correlation between chronic inflammation, NV, and fibrosis within the reparative microenvironment of the SRS. In summary, the downstream consequences of the earliest dysfunctional molecular events in AMD can result in the late-stage entity we recognize clinically as SRNV and is characterized by a spectrum of predictable, related, and stereotypical processes referred to as DyR.

  3. Six-year outcomes in neovascular age-related macular degeneration with ranibizumab

    Science.gov (United States)

    Jacob, Julie; Brié, Heidi; Leys, Anita; Levecq, Laurent; Mergaerts, Filip; Denhaerynck, Kris; Vancayzeele, Stefaan; Van Craeyveld, Eline; Abraham, Ivo; MacDonald, Karen

    2017-01-01

    AIM To evaluate the outcomes of ≥6y ranibizumab therapy in neovascular age-related macular degeneration (AMD). METHODS HELIX was a retrospective, observational effectiveness study using medical records of patients treated in three clinics in Belgium. Patients had neovascular AMD and were initially treated with intravitreal ranibizumab (0.5 mg) between November 1, 2007 and October 31, 2008, had ≥6y of data available, and were treated on an ongoing, as-needed basis. Outcomes included best-corrected visual acuity (BCVA) and central retinal thickness (CRT). RESULTS The sample consisted of 88 eyes from 69 patients. Mean age was 76.4±6.5y, most patients were female (62.3%). Most eyes (62.5%) were treatment-naive, 33 previously treated eyes had received predominantly other anti-vascular endothelial growth factor agents and verteporfin. Mean baseline BCVA was 57.4±12.7 ETDRS letters and CRT was 291.5±86.1 μm. On average, patients received 20.6±11.9 ranibizumab injections over the ≥6y. Intervals between injections were on average 12.7±16.1wk. Mean change in BCVA from baseline to last observation for the sample was less than one letter (-0.9±17.3 letters), with an average loss of -3.2±15.6 letters in previously treated eyes versus a gain of 0.6±18.4 letters in treatment-naïve eyes. When considering a loss of AMD patients treated for ≥6y with ranibizumab demonstrates long-term visual stabilization. In light of the natural evolution of the disease, these data confirm that ranibizumab is effective long-term under real-world conditions of heterogeneity of patients, clinicians, and centers. PMID:28149782

  4. 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.

  5. Assessment of Choroidal Microstructure and Subfoveal Thickness Change in Eyes With Different Stages of Age-Related Macular Degeneration.

    Science.gov (United States)

    Lu, Linna; Xu, Shiqiong; He, Fangling; Liu, Yan; Zhang, Yidan; Wang, Jing; Wang, Zhiliang; Fan, Xianqun

    2016-03-01

    Age-related macular degeneration (AMD) is a major cause of irreversible blindness. Choroidal structural changes seem to be inevitable in AMD pathogenesis. Our study revealed associated choroidal microstructural changes in AMD eyes.The aim of the study was to compare choroidal microstructural changes in eyes with AMD of different stages.The study was a retrospective, cross-sectional case series.The participants comprised of 32 age-matched normal eyes as controls, and 26 fellow uninvolved eyes of intermediate/late AMD, 29 of early AMD, 28 of intermediate AMD, and 39 of late AMD.All subjects underwent comprehensive ophthalmologic examination. The choroid images, including subfoveal choroidal thickness, percentage of Sattler layer area, and en face images of the choroid, were obtained using spectral-domain optical coherence tomography.The main outcome measures were subfoveal choroidal thickness changes, percentage of Sattler layer area changes, and en face images of the choroid in AMD eyes.One hundred fifty-four eyes of 96 individuals with mean age of 67.1±9.2 years were included. The mean subfoveal choroidal thickness was 295.4 ± 56.8 μm in age-matched normal eyes, 306.7 ± 68.4 μm in fellow uninvolved eyes with AMD, 293.8 ± 80.4 μm in early AMD, 215.6 ± 80.4 μm in intermediate AMD, and 200.4 ± 66.6 μm in late AMD (F = 14.2, all P Choroidal thickness was greater in early AMD eyes than in intermediate/late AMD eyes (P choroid showed reduced vascular density of Sattler layer areas in late AMD eyes compared with normal eyes.Decreasing subfoveal choroidal thickness and percentage of Sattler layer area were demonstrated in the progression of AMD. The choroidal change was related to atrophy of the microstructural changes of underlying capillaries and medium-sized vessels.

  6. 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.

  7. 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.

  8. Visual Function and Its Relationship with Severity of Early, and Activity of Neovascular, Age-Related Macular Degeneration

    OpenAIRE

    Loughman, James; Sabour-Pickett, Sarah; Nolan, John M.; Klein, Barbara; Klein, Ron; Beatty, Stephen

    2015-01-01

    Purpose: To investigate the relationship between visual function and severity of early age-related macular degeneration (AMD) and activity of neovascular (nv-) AMD. Methods: The following data was collected from 66 eyes of 66 subjects with early AMD and 47 eyes of 47 subjects with active nv-AMD: corrected distance visual acuity (CDVA); contrast sensitivity (CS); glare disability (GD); and retinotopic ocular sensitivity (ROS) of the central 5° of the retina, by microperimetry. Fundus photog...

  9. Assessment of effect of intravitreal ranibizumab injection on the ocular blood flow in patients with neovascular age-related macular degeneration

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    V. V. Neroev

    2014-07-01

    Full Text Available Purpose: To evaluate the effect of intravitreal ranibizumab injection on the ocular blood flow in patients with neovascular agerelatedmacular degeneration (AMD.Methods: 35 patients with wet AMD undergone intravitreal 0.5 mg ranibizumab injection. Color Doppler Imaging (CDI and dopplerographywere used to measure hemodynamic parameters including the peak systolic velocity (Vsyst, cm / s, end-diastolic velocity (V diast, cm / s, and resistance index (RI of blood flow in the central retinal artery (CRA, the short posterior ciliary arteries (PCA, and the ophthalmic artery (OA. All patients were examined before and after injection on day 1‑7 and 30 day during the 3‑month follow up period.Results: Before intravitreal injection Vsyst was decreased in short PCA (p<0.05, RI in CRA and in short PCA significantly increased in comparison with normal index in same vessels. The peak systolic velocity in OA, in CRA and in short PCA was not significantly changed. After second injection resistance index in CRA and in short PCA was normalized.Conclusion: There was not impairment of ocular blood flow in retinal and choroidal after monthly intravitreal injection of ranibizumab during the 3‑month follow up period.

  10. Assessment of effect of intravitreal ranibizumab injection on the ocular blood flow in patients with neovascular age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    V. V. Neroev

    2013-01-01

    Full Text Available Purpose: To evaluate the effect of intravitreal ranibizumab injection on the ocular blood flow in patients with neovascular agerelatedmacular degeneration (AMD.Methods: 35 patients with wet AMD undergone intravitreal 0.5 mg ranibizumab injection. Color Doppler Imaging (CDI and dopplerographywere used to measure hemodynamic parameters including the peak systolic velocity (Vsyst, cm / s, end-diastolic velocity (V diast, cm / s, and resistance index (RI of blood flow in the central retinal artery (CRA, the short posterior ciliary arteries (PCA, and the ophthalmic artery (OA. All patients were examined before and after injection on day 1‑7 and 30 day during the 3‑month follow up period.Results: Before intravitreal injection Vsyst was decreased in short PCA (p<0.05, RI in CRA and in short PCA significantly increased in comparison with normal index in same vessels. The peak systolic velocity in OA, in CRA and in short PCA was not significantly changed. After second injection resistance index in CRA and in short PCA was normalized.Conclusion: There was not impairment of ocular blood flow in retinal and choroidal after monthly intravitreal injection of ranibizumab during the 3‑month follow up period.

  11. Abundance of infiltrating CD163+ cells in the retina of postmortem eyes with dry and neovascular age-related macular degeneration.

    Science.gov (United States)

    Lad, Eleonora M; Cousins, Scott W; Van Arnam, John S; Proia, Alan D

    2015-11-01

    Prior research in animal models has suggested that retinal macrophages play an important role in age-related macular degeneration (AMD), but studies have insufficiently characterized the distribution of retinal macrophages in various stages of human AMD. In this case series, we analyzed H&E, periodic acid-Schiff, and CD163 and CD68 immunostained slides from 56 formaldehyde-fixed, paraffin-embedded autopsy eyes of patients over age 75: 11 age-matched, normal eyes, and 45 AMD eyes. Qualitative analysis of the macula and retinal periphery revealed that all eyes contained a significant number of CD163+ cells but a negligible number of CD68+ cells. In normal eyes and eyes with thin or infrequent basal laminar deposits, CD163+ cells were restricted to the inner retina. In contrast, in AMD eyes with thick basal deposits, choroidal neovascular membranes, and geographic atrophy, qualitatively there was a marked increase in the number and size of the CD163+ cells in the outer retina, sub-retinal, and sub-retinal pigment epithelium space in the macula. The changes in number and localization of retinal CD163+ cells in eyes with intermediate-severe AMD support a key role for macrophages in the pathogenesis and progression of the disease. A larger, quantitative study evaluating the distribution of macrophage subpopulations in postmortem AMD eyes is warranted.

  12. Peripheral Reticular Pigmentary Degeneration and Choroidal Vascular Insufficiency, Studied by Ultra Wide-Field Fluorescein Angiography

    Science.gov (United States)

    Bae, Kunho; Cho, Kyuyeon; Kang, Se Woong; Kim, Sang Jin; Kim, Jong Min

    2017-01-01

    Purpose To explore the pathogenesis of peripheral reticular pigmentary degeneration (PRPD) and its clinical significance. Methods This cross-sectional, observational study (conducted between January 2010 and May 2015) enrolled 441 eyes of 229 subjects, including 35 eyes with PRPD and 406 eyes without PRPD, which was identified by ultra-wide-field fluorescein angiography (UWFA). The distribution and angiographic circulation time of PRPD were assessed by UWFA. The frequencies of systemic and ophthalmologic comorbidities were compared between groups. Univariate and multivariate generalized estimation equation methods were used to determine the risk factors for PRPD. Results The patients with PRPD had a mean age of 75.7 ± 8.5 years (range, 59–93 years), whereas the patients without PRPD had a mean age of 60.1 ± 14.9 years (range, 9–92 years). All eyes with PRPD manifested the lesion in the superior nasal periphery with or without circumferential extension. Among those, only 16 eyes (45.7%) in the PRPD group showed distinctive features in the same location on fundus photographs. There was significant choroidal filling delay in the PRPD group when compared with the control group (1.42±1.22 vs. -0.02±1.05 seconds, P < 0.001). Multivariate regression analysis revealed that older age (P < 0.001), stroke (P = 0.018), ischemic optic neuropathy (P < 0.001), and age-related macular degeneration (P = 0.022) were significantly associated with PRPD. Conclusions UWFA may enhance the diagnostic sensitivity of PRPD. Choroidal vascular insufficiency with compromised systemic circulation in the elderly was related to the manifestation of PRPD. These results help to better understand the pathophysiology of PRPD. Co-existence of systemic and ophthalmic circulatory disorders should be considered in patients with PRPD. PMID:28114409

  13. Visual Performance in Patients with Neovascular Age-Related Macular Degeneration Undergoing Treatment with Intravitreal Ranibizumab

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    Sarah Sabour-Pickett

    2013-01-01

    Full Text Available Purpose. To assess visual function and its response to serial intravitreal ranibizumab (Lucentis, Genentech in patients with neovascular age-related macular degeneration (nv-AMD. Methods. Forty-seven eyes of 47 patients with nv-AMD, and corrected distance visual acuity (CDVA logMAR 0.7 or better, undergoing intravitreal injections of ranibizumab, were enrolled into this prospective study. Visual function was assessed using a range of psychophysical tests, while mean foveal thickness (MFT was determined by optical coherence tomography (OCT. Results. Group mean (±sd MFT reduced significantly from baseline (233 (±59 to exit (205 (±40 (P=0.001. CDVA exhibited no change between baseline and exit visits (P=0.48 and P=0.31, resp.. Measures of visual function that did exhibit statistically significant improvements (P<0.05 for all included reading acuity, reading speed, mesopic and photopic contrast sensitivity (CS, mesopic and photopic glare disability (GD, and retinotopic ocular sensitivity (ROS at all eccentricities. Conclusion. Eyes with nv-AMD undergoing intravitreal ranibizumab injections exhibit improvements in many parameters of visual function. Outcome measures other than CDVA, such as CS, GD, and ROS, should not only be considered in the design of studies investigating nv-AMD, but also in treatment and retreatment strategies for patients with the condition.

  14. Visual performance in patients with neovascular age-related macular degeneration undergoing treatment with intravitreal ranibizumab.

    Science.gov (United States)

    Sabour-Pickett, Sarah; Loughman, James; Nolan, John M; Stack, Jim; Pesudovs, Konrad; Meagher, Katherine A; Beatty, Stephen

    2013-01-01

    Purpose. To assess visual function and its response to serial intravitreal ranibizumab (Lucentis, Genentech) in patients with neovascular age-related macular degeneration (nv-AMD). Methods. Forty-seven eyes of 47 patients with nv-AMD, and corrected distance visual acuity (CDVA) logMAR 0.7 or better, undergoing intravitreal injections of ranibizumab, were enrolled into this prospective study. Visual function was assessed using a range of psychophysical tests, while mean foveal thickness (MFT) was determined by optical coherence tomography (OCT). Results. Group mean (±sd) MFT reduced significantly from baseline (233 (±59)) to exit (205 (±40)) (P = 0.001). CDVA exhibited no change between baseline and exit visits (P = 0.48 and P = 0.31, resp.). Measures of visual function that did exhibit statistically significant improvements (P disability (GD), and retinotopic ocular sensitivity (ROS) at all eccentricities. Conclusion. Eyes with nv-AMD undergoing intravitreal ranibizumab injections exhibit improvements in many parameters of visual function. Outcome measures other than CDVA, such as CS, GD, and ROS, should not only be considered in the design of studies investigating nv-AMD, but also in treatment and retreatment strategies for patients with the condition.

  15. Oxidative Stress, Hypoxia, and Autophagy in the Neovascular Processes of Age-Related Macular Degeneration

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    Janusz Blasiak

    2014-01-01

    Full Text Available Age-related macular degeneration (AMD is the leading cause of severe and irreversible loss of vision in the elderly in developed countries. AMD is a complex chronic neurodegenerative disease associated with many environmental, lifestyle, and genetic factors. Oxidative stress and the production of reactive oxygen species (ROS seem to play a pivotal role in AMD pathogenesis. It is known that the macula receives the highest blood flow of any tissue in the body when related to size, and anything that can reduce the rich blood supply can cause hypoxia, malfunction, or disease. Oxidative stress can affect both the lipid rich retinal outer segment structure and the light processing in the macula. The response to oxidative stress involves several cellular defense reactions, for example, increases in antioxidant production and proteolysis of damaged proteins. The imbalance between production of damaged cellular components and degradation leads to the accumulation of detrimental products, for example, intracellular lipofuscin and extracellular drusen. Autophagy is a central lysosomal clearance system that may play an important role in AMD development. There are many anatomical changes in retinal pigment epithelium (RPE, Bruch’s membrane, and choriocapillaris in response to chronic oxidative stress, hypoxia, and disturbed autophagy and these are estimated to be crucial components in the pathology of neovascular processes in AMD.

  16. Oxidative stress, hypoxia, and autophagy in the neovascular processes of age-related macular degeneration.

    Science.gov (United States)

    Blasiak, Janusz; Petrovski, Goran; Veréb, Zoltán; Facskó, Andrea; Kaarniranta, Kai

    2014-01-01

    Age-related macular degeneration (AMD) is the leading cause of severe and irreversible loss of vision in the elderly in developed countries. AMD is a complex chronic neurodegenerative disease associated with many environmental, lifestyle, and genetic factors. Oxidative stress and the production of reactive oxygen species (ROS) seem to play a pivotal role in AMD pathogenesis. It is known that the macula receives the highest blood flow of any tissue in the body when related to size, and anything that can reduce the rich blood supply can cause hypoxia, malfunction, or disease. Oxidative stress can affect both the lipid rich retinal outer segment structure and the light processing in the macula. The response to oxidative stress involves several cellular defense reactions, for example, increases in antioxidant production and proteolysis of damaged proteins. The imbalance between production of damaged cellular components and degradation leads to the accumulation of detrimental products, for example, intracellular lipofuscin and extracellular drusen. Autophagy is a central lysosomal clearance system that may play an important role in AMD development. There are many anatomical changes in retinal pigment epithelium (RPE), Bruch's membrane, and choriocapillaris in response to chronic oxidative stress, hypoxia, and disturbed autophagy and these are estimated to be crucial components in the pathology of neovascular processes in AMD.

  17. Alterations in Circulating Immune Cells in Neovascular Age-Related Macular Degeneration.

    Science.gov (United States)

    Lechner, Judith; Chen, Mei; Hogg, Ruth E; Toth, Levente; Silvestri, Giuliana; Chakravarthy, Usha; Xu, Heping

    2015-11-17

    Neovascular age-related macular degeneration (nAMD) is the leading cause of irreversible blindness in developed countries. Recent advances have highlighted the essential role of inflammation in the development of the disease. In addition to local retinal chronic inflammatory response, systemic immune alterations have also been observed in AMD patients. In this study we investigated the association between the frequency of circulating leukocyte populations and the prevalence as well as clinical presentations of nAMD. Leukocyte subsets of 103 nAMD patients (most of them were receiving anti-VEGF therapy prior to enrolment) and 26 controls were analysed by flow cytometry by relative cell size, granularity and surface markers. Circulating CD11b(+) cells and CD16(hi)HLA-DR(-) neutrophils were significantly increased (P = 0.015 and 0.009 respectively) in nAMD when compared to controls. The percentage of circulating CD4(+) T-cells was reduced in nAMD patients without subretinal fibrosis (P = 0.026) compared to patients with subretinal fibrosis. There was no correlation between the percentage of circulating leukocytes and the responsiveness to anti-VEGF therapy in nAMD patients. Our results suggest that higher levels of circulating CD11b(+) cells and neutrophils are associated with nAMD and that reduced levels of CD4(+) T-cells are associated with the absence of subretinal fibrosis in nAMD.

  18. Ultrasound-mediated microbubble delivery of pigment epithelium-derived factor gene into retina inhibits choroidal neovascularization

    Institute of Scientific and Technical Information of China (English)

    ZHOU Xi-yuan; LIAO Qing; PU Yi-min; TANG Yong-qiang; GONG Xiao; LI Jia; XU Yan; WANG Zhi-gang

    2009-01-01

    Background Many studies have suggested that the imbalance of angiogenic factor and anti-angiogenic factor expression contributes significantly to the development of choroidal neovascularization (CNV), and ultrasound microbubble combination system can increase the gene transfection efficiency successfully. This study was designed to investigate whether ultrasound-mediated microbubble destruction could effectively deliver therapeutic plasmid into the retina of rat, and whether gene transfer of pigment epithelium-derived factor (PEDF) could inhibit CNV.Methods Human retinal pigment epithelial cells were isolated and treated either with ultrasound or plasmid alone, or with a combination of plasmid, ultrasound and microbubbles to approach feasibility of microbubble-enhanced ultrasound enhance PEDFgene expression; For in vivo animal studies, CNV was induced by argon lasgon laser in rats. These rats were randomly assigned to five groups and were treated by infusing microbubbles attached with the naked plasmid DNA of PEDF into the vitreous of rats followed by immediate ultrasound exposure (intravitreal injection); infusing liposomes with the naked plasmid DNA of PEDF into the vitreous (lipofectamine + PEDF); infusing microbubbles attached with PEDF into the orbit of rats with ultrasound irradiation immediately (retrobular injection); infusing microbubbles attached with PEDF into the femoral vein of rats with exposed to ultrasound immediately (vein injection). The CNV rats without any treatment served as control. Rats were sacrificed and eyes were enucleated at 7, 14, and 28 days after treatment. Gene and protein expression of PEDF was detected by quantitative real-time RT-PCR, Western blotting and immunofluorescence staining, respectively. The effect of PEDF gene transfer on CNV was examined by fluorescein fundus angiography.Results In vitro cell experiments showed that microbubbles with ultrasound irradiation could significantly enhance PEDF delivery as compared with

  19. Influence of Dll4 via HIF-1α-VEGF signaling on the angiogenesis of choroidal neovascularization under hypoxic conditions.

    Directory of Open Access Journals (Sweden)

    Xiao Dong

    Full Text Available Choroidal neovascularization (CNV is the common pathological basis of irreversible visual impairment encountered in a variety of chorioretinal diseases; the pathogenesis of its development is complicated and still imperfectly understood. Recent studies indicated that delta-like ligand 4 (Dll4, one of the Notch family ligands might participate in the HIF-1α-VEGF pathway to regulate CNV angiogenesis. But little is known about the influence and potential mechanism of Dll4/Notch signals on CNV angiogenesis. Real-time RT-PCR, Western blotting were used to analyze the expression alteration of Dll4, VEGF and HIF-1α in hypoxic RF/6A cells. Immunofluorescence staining, a laser-induced rat CNV model and intravitreal injection techniques were used to confirm the relationships among these molecules in vitro and in vivo. RPE-RF/6A cell co-culture systems were used to investigate the effects of Dll4/Notch signals on CNV angiogenesis. We found that the Dll4 was involved in hypoxia signaling in CNV angiogenesis. Results from the co-culture system showed that the enhancement of Dll4 expression in RF/6A cells led to the significantly faster proliferation and stronger tube forming ability, but inhibited cells migration and invasion across a monolayer of RPE cells in hypoxic environment, while siRNA-mediated Dll4 silencing caused the opposite effects. Pharmacological disruption of Notch signaling using gamma-secretase inhibitor (GSI produced similar, but not identical effects, to that caused by the Dll4 siRNA. In addition, the expression of several key molecules involved in the angiogenesis of CNV was altered in RF/6A cells showing constitutively active Dll4 expression. These results suggest that Dll4 play an important role in CNV angiogenesis, which appears to be regulated by HIF-1α and VEGF during the progression of CNV under hypoxic conditions. Targeting Dll4/Notch signaling may facilitate further understanding of the mechanisms that underlie CNV angiogenesis.

  20. Individualized Treatment of Neovascular Age-Related Macular Degeneration: What are Patients Gaining? Or Losing?

    Directory of Open Access Journals (Sweden)

    Michael W. Stewart

    2015-05-01

    Full Text Available The widespread use of drugs that bind diffusible vascular endothelial growth factor (VEGF has revolutionized the treatment of neovascular age-related macular degeneration (AMD. The pivotal ranibizumab and aflibercept registration trials featured monthly intravitreal injections for 12 months, during which visual acuities and macular edema rapidly improved for the first 3 months and modest gains or stabilization continued until the primary endpoint. In many subsequent trials, patients were evaluated monthly and treated as-needed (PRN according to the results of visual acuity (VA testing, fundus examinations and optical coherence tomography scans. Compared to monthly-treated control groups, PRN treated patients require fewer injections during the first year but they also experience smaller VA gains (1–3 letters. A small number of prospective trials that directly compared monthly with PRN therapy showed that VA gains with discontinuous therapy lag slightly behind those achieved with monthly injections. Physicians recognize that monthly office visits with frequent intraocular injections challenge patients’ compliance, accrue high drug and professional service costs, and clog office schedules with frequently returning patients. To decrease the numbers of both office visits and anti-VEGF injections without sacrificing VA gains, physicians have embraced the treat-and-extend strategy. Treat-and-extend has not been studied as rigorously as PRN but it has become popular among both vitreoretinal specialists and patients. Despite the possible risks associated with discontinuous therapy (decreased VA and increased macular fluid, most physicians individualize treatment (PRN or treat-and-extend for the majority of their patients. This review chapter explores the many advantages of individualized therapy, while balancing these against suboptimal responses due to the decreased frequency of anti-VEGF injections.

  1. Association of neovascular age-related macular degeneration with month and season of birth in Italy

    Science.gov (United States)

    Longo, Antonio; Casuccio, Alessandra; Pani, Luca; Avitabile, Teresio; Cillino, Salvatore; Uva, Maurizio G.; Bonfiglio, Vincenza; Russo, Andrea; Parisi, Guglielmo; Cennamo, Gilda; Furino, Claudio; Parravano, Mariacristina; Xoxi, Entela; Reibaldi, Michele

    2017-01-01

    In order to investigate the influence of season and month of birth on the risk of neovascular age-related macular degeneration (n-AMD) in Italy, we evaluated the month birth and sex of all patients, recorded in the anti-vascular endothelial growth factor (VEGF) monitoring registry of the Italian Medicines Agency, born between 1925–1944, who received intravitreal anti-VEGF injections for n-AMD between January 1, 2013 and July 29, 2015. The numbers of all births in Italy in the same years, extracted from the Italian National Institute of Statistics, were used to calculate the expected number of n-AMD cases. Overall, 45,845 patients (19,207 men, 26,638 women) received intravitreal anti-VEGF for n-AMD; in the same years, 20,140,426 people (10,334,262 male, 9,806,164 female) were born in Italy. Comparing the observed number of n-AMD cases with the expected number of n- AMD cases in each season, we found that the season-specific risk for n-AMD was 2.5% higher for those born in summer (OR=1.03, Bonferroni-corrected P=0.008) and 3% lower for those born in winter (OR=0.96, Bonferroni-corrected P=0.0004). When considering the month of birth, the risk of n-AMD was 5.9% lower for people born in January (OR=0.93, Bonferroni-corrected P=0.0012). The factors causing such differences should be determined. PMID:27997361

  2. 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.

  3. Rate of vision loss in neovascular age-related macular degeneration explored.

    Science.gov (United States)

    Real, Juan P; Granero, Gladys E; De Santis, Mariana O; Juarez, Claudio P; Palma, Santiago D; Kelly, Simon P; Luna, José D

    2015-11-01

    To explore decline in visual acuity in patients with neovascular age-related macular degeneration (n-AMD) awaiting intravitreal bevacizumab or ranibizumab treatment following initial diagnosis and after disease reactivation. Retrospective analysis of 74 treatment-naïve patients (84 eyes) in two centers in Córdoba, Argentina. The time between treatment indication and intravitreal injection, and the changes in BCVA produced during this delay were studied in both periods. A linear regression model to search the impact of time on progression visual impairment was conducted. In both periods, a significant reduction in vision occurred awaiting intravitreal injection. The longer the delay, the greater the vision loss (R2 = 0.55 p < 0.01) and the less improvement following treatment (Pearson coefficient -0.26). The result of the model shows that the change in vision as a function of initial delay were best described by a polynomic model with a mean loss of 5 letters in the first 3 weeks, a slowdown in the rate of change of VA, and a dependence of visual acuity at the moment of diagnosis . The loss of visual acuity after reactivation shows the same behavior as at the onset of the disease but independent of visual acuity prior to reactivation. Visual loss awaiting injection intravitreal anti-VEGF is clinically significant and with an asymptotic pattern, with early rapid loss of vision in both the onset of the disease and the reactivation. Initiation of anti-VEGF treatment must be undertaken urgently, as should retreatment of disease activation to reduce visual loss.

  4. Cost-effectiveness of ranibizumab for neovascular age-related macular degeneration

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    Matthews Jane P

    2008-06-01

    Full Text Available Abstract Background Intravitreal ranibizumab prevents vision loss and improves visual acuity in patients with neovascular age-related macular degeneration, but it is expensive, and efficacy beyond 2 years is uncertain. Methods We assessed the cost-effectiveness of ranibizumab compared with no ranibizumab over 10 years, using randomized trial efficacy data for the first 2 years, post-trial efficacy assumptions, and ranibizumab acquisition costs ranging from the wholesale price ($1,950 per dose to the price of bevazicumab ($50, a similar molecule which may be equally efficacious. We used a computer simulation model to estimate the probability of blindness, the number of quality-adjusted life-years (QALYs, direct costs (in 2004 U.S. dollars, and cost-effectiveness ratios for a 67-year old woman. Costs and QALYs were discounted at 3% per year. Results The probability of blindness over 10 years was reduced from 56% to 34% if ranibizumab was efficacious for only 2 years, 27% if efficacy was maintained for a further 2 years only (base-case scenario, and 17% if visual acuity at 4 years was then sustained. It was cost-saving under all price assumptions, when caregiver costs were included. When caregiver costs were excluded, the cost per QALY for the base-case ranged from $5,600, assuming the bevazicumab price, to $91,900 assuming the wholesale ranibizumab price. The cost per QALY was Conclusion From a societal perspective, ranibizumab was cost-saving. From a health care funder's perspective, ranibizumab was an efficient treatment when it cost less than $1000 per dose.

  5. Clinical experience with fixed bimonthly aflibercept dosing in treatment-experienced patients with neovascular age-related macular degeneration

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    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

  6. A prospective pilot study comparing combined intravitreal ranibizumab and half-fluence photodynamic therapy with ranibizumab monotherapy in the treatment of neovascular age-related macular degeneration

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    Williams PD

    2012-09-01

    -tailed t-test (P = 0.2. Due to the presence of outliers in each group, a Mann–Whitney U test was performed to confirm the results (U = 325; P = 0.28. The mean optical coherence tomography foveal thickness improved 92.5 microns and 106.7 microns in the ranibizumab alone and the combined group, respectively. The difference was not significant based on a two-tailed t-test (P = 0.6. The ranibizumab alone group received an average of 6.8 injections, while the combined group received an average of three injections. This difference was not significant based on a chi-square test (P = 0.11.Conclusion: The groups appeared similar based on statistical analysis, but larger studies are needed to determine possible small differences between combination therapy and monotherapy.Keywords: ranibizumab, macular degeneration, photodynamic therapy, verteporfin, choroidal neovascularization, anti-vegf

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

    DEFF Research Database (Denmark)

    Bloch, Sara Brandi

    2013-01-01

    , 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 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...

  8. Choroidal Neovascular Membrane Formation and Retinochoroidopathy in a Patient with Systemic Langerhans Cell Histiocytosis: A Case Report and Review of the Literature

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    Aristomenis Thanos

    2012-04-01

    Full Text Available We report a case of bilateral atrophic retinochoroidopathy with choroidal neovascular membrane (CNVM formation in a patient with systemic Langerhans cell histiocytosis (LCH. A 35-year-old female, diagnosed with LCH at the age of 3, experienced an episode of acute vision loss in her right eye. Visual acuity was counting fingers. Dilated fundus exam and fluorescein angiography revealed the presence of CNVM along with bilateral widespread areas of chorioretinal atrophy. The patient underwent removal of CNVM with excellent postoperative visual acuity (20/25; however, indolent progression of her disease led to gradual deterioration of visual acuity (20/80 in the right eye and 20/320 in the left. This case shows that in contrast to previous reports, intraocular involvement of LCH does not need to be dramatic and clinically evident but it can acquire a chronic degenerative form. This report aims to raise awareness among ophthalmologists concerning the potential intraocular sequelae of LCH.

  9. 经瞳孔温热疗法治疗脉络膜新生血管%Transpupillary thermotherapy of choroidal neovascularization

    Institute of Scientific and Technical Information of China (English)

    高玲; 胡蓉; 唐罗生; 朱小华; 唐朝珍; 王涛

    2005-01-01

    目的初步观察TTT激光治疗脉络膜新生血管的疗效.方法23例24眼CNV行TTT(transpupillary thermotherapy,TTT)治疗,根据CNV(choroidal neovascularization,CNV)的大小选择不同的光斑大小和能量,照射时间为1分钟.结果24眼CNV经TTT治疗后,大部分患者黄斑出血、渗出、水肿减轻或吸收,FFA显示大多数CNV渗漏减少或停止,原CNV瘢痕化,但视力无明显提高.结论TTT治疗脉络膜新生血管有效,但还需要更多的病例来评价治疗效果.

  10. Bevacizumab versus ranibizumab for neovascular agerelated macular degeneration: a Meta-analysis

    Institute of Scientific and Technical Information of China (English)

    Wen-Jie; Wang; Jian; Chen; Xiao-Ling; Zhang; Min; Yao; Xiao-Yong; Liu; Qing; Zhou; Yi-Xin; Qu

    2015-01-01

    AIM: To systematically compare the efficacy and safety of off-label bevacizumab versus licensed ranibizumab intravitreal injections as well as monthly regimen versus pro re nata [PRN(as needed)] regimen in the treatment of neovascular age-related macular degeneration(n AMD).METHODS: Relevant publications were identified through automatically retrieve of database and manually retrieving. The methodological quality of studies included was assessed using the Jadad score and the risk-of-bias assessment. The efficacy estimates were measured by the weight mean difference(WMD) for the improvement of best-corrected visual acuity(BCVA) and central retinal thickness(CRT) reduction. The safety estimates were measured by odds ratios(OR) for adverse events rates. Statistical analysis was conducted by Revman 5.2.7.RESULTS: Seven studies were included in the Metaanalysis. There were no statistically significant differences between bevacizumab and ranibizumab in BCVA at 1 and 2y(P =0.37, P =0.18, respectively),However, both drugs has better BCVA given monthly than given as needed at 1 and 2y(P <0.05). The results demonstrated the mean decrease in CRT was less in bevacizumab group than ranibizumab group at 1y(P <0.05),while the difference was not significant at 2y(P =0.24).Treatment monthly gained much more decrease in CRT at 1 and 2y(P <0.005).There were no differences between drugs in the rates of death, arterial thrombotic events and venous thrombotic events(P =0.41, P =0.55, P =0.10,respectively), while the rates of medical dictionary for regulatory activities(Med DAR) system organ class events and ≥1 systemic serious adverse events were higher in bevacizumab group than ranibizumab group(P <0.05).But the incidences of death, arterial thrombotic events,venous thrombotic events, Med DAR system organ class events as well as ≥1 systemic serious adverse events were not statistically different between both treatment regimens of monthly and as needed(P =0.14, P =0.76,P =0.73, P =0

  11. The Sustained Delivery of Resveratrol or a Defined Grape Powder Inhibits New Blood Vessel Formation in a Mouse Model of Choroidal Neovascularization

    Science.gov (United States)

    Kanavi, Mozhgan Rezaie; Darjatmoko, Soesiawati; Wang, Shoujian; Azari, Amir A.; Farnoodian, Mitra; Kenealey, Jason D.; van Ginkel, Paul R.; Albert, Daniel M.; Sheibani, Nader; Polans, Arthur S.

    2015-01-01

    The objective of this study was to determine whether resveratrol or a defined, reconstituted grape powder can attenuate the formation of new blood vessels in a mouse model of choroidal neovascularization (CNV). To accomplish this objective, C57BL/6J mice were randomized into control or treatment groups which received either resveratrol or grape powder by daily oral gavage, resveratrol or grape powder delivered ad libitum through the drinking water, or resveratrol by slow release via implanted osmotic pumps. A laser was used to rupture Bruch’s membrane to induce CNV which was then detected in sclerochoroidal eyecups stained with antibodies against intercellular adhesion molecule-2. CNV area was measured using fluorescence microscopy and Image J software. Ad libitum delivery of both resveratrol and grape powder was shown to significantly reduce the extent of CNV by 68% and 57%, respectively. Parallel experiments conducted in vitro demonstrated that resveratrol activates p53 and inactivates Akt/protein kinase B in choroidal endothelial cells, contributing to its anti-proliferative and anti-migratory properties. In addition resveratrol was shown to inhibit the formation of endothelial cell networks, augmenting its overall anti-angiogenic effects. The non-toxic nature of resveratrol makes it an especially attractive candidate for the prevention and/or treatment of CNV. PMID:25361423

  12. The Sustained Delivery of Resveratrol or a Defined Grape Powder Inhibits New Blood Vessel Formation in a Mouse Model of Choroidal Neovascularization

    Directory of Open Access Journals (Sweden)

    Mozhgan Rezaie Kanavi

    2014-10-01

    Full Text Available The objective of this study was to determine whether resveratrol or a defined, reconstituted grape powder can attenuate the formation of new blood vessels in a mouse model of choroidal neovascularization (CNV. To accomplish this objective, C57BL/6J mice were randomized into control or treatment groups which received either resveratrol or grape powder by daily oral gavage, resveratrol or grape powder delivered ad libitum through the drinking water, or resveratrol by slow release via implanted osmotic pumps. A laser was used to rupture Bruch’s membrane to induce CNV which was then detected in sclerochoroidal eyecups stained with antibodies against intercellular adhesion molecule-2. CNV area was measured using fluorescence microscopy and Image J software. Ad libitum delivery of both resveratrol and grape powder was shown to significantly reduce the extent of CNV by 68% and 57%, respectively. Parallel experiments conducted in vitro demonstrated that resveratrol activates p53 and inactivates Akt/protein kinase B in choroidal endothelial cells, contributing to its anti-proliferative and anti-migratory properties. In addition resveratrol was shown to inhibit the formation of endothelial cell networks, augmenting its overall anti-angiogenic effects. The non-toxic nature of resveratrol makes it an especially attractive candidate for the prevention and/or treatment of CNV.

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

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    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

  14. Optical coherence tomography and multifocal electroretinography of patients with advanced neovascular age-related macular degeneration before, during, and after treatment with ranibizumab

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    Izabela Negrão Frota de Almeida

    2015-04-01

    Full Text Available Purpose: To evaluate retinal morphology and function of patients with advanced neovascular age-related macular degeneration (AMD before, during, and after treatment with ranibizumab. Methods: Twenty-one eyes diagnosed with advanced AMD were studied with optical coherence tomography (OCT and multifocal electroretinography (mfERG. Three intravitreal injections of ranibizumab were administered at 1-month intervals. Evaluations were performed before the first injection (D0 and at 30 (D30, 60 (D60, and 90 days (D90 after the first injection and compared to an age-matched control group (n=21 eyes. Results: The thickness of macular retinal layers increased before treatment due to the presence of intraretinal fluid. A thick retinal pigment epithelium-choriocapillaris complex (RPE-CC suggested the presence of choroidal neovascular membrane. Intraretinal edema decreased after treatment (P<0.01, but persisting RPE-CC thickness resulted in a subretinal scar. Three different annular retinal areas were studied with mfERG (from center to periphery: rings R1, R2, and R3. The amplitude of the first negative component (N1 decreased in R1, R2, and R3 at D30, D60, and D90 when compared with that in controls (P<0.05; the N1 implicit time was delayed in R3 at D30 (P<0.05. The amplitude of the first positive component (P1 was reduced in R1 and R2 at D30, D60, and D90 when compared with that in controls (P<0.01; the P1 implicit time was delayed in R1 at D0 and D60 (P<0.05, in R2 at D0, D30, and D90 (P<0.01, and in R3 at D30 and D60 (P<0.05. Conclusion: Ranibizumab reduces intraretinal edema, even in advanced cases. Central macular activity appeared to increase after the initiation of treatment, improving over time.

  15. 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

  16. Choroidal OCT

    Science.gov (United States)

    Esmaeelpour, Marieh; Drexler, Wolfgang

    Novel imaging devices, imaging strategies and automated image analysis with optical coherence tomography have improved our understanding of the choroid in health and pathology. Non-invasive in-vivo high resolution choroidal imaging has had its highest impact in the investigation of macular diseases such as diabetes macular edema and age-related macular degeneration. Choroidal thickness may provide a clinically feasible measure of disease stage and treatment success. It will even support disease diagnosis and phenotyping as is demonstrated in this chapter. Utilizing color coded thickness mapping of the choroid and its Sattler's and Haller's layer may further strengthen the sensitivity of the investigation findings.

  17. Tratamento da forma neovascular de degeneração macular relacionada à idade com drogas antiangiogênicas Treatment of neovascular age-related macular degeneration with antiangiogenic drugs

    Directory of Open Access Journals (Sweden)

    Eduardo Büchele Rodrigues

    2006-10-01

    Full Text Available Degeneração macular relacionada à idade (DRMI é a principal causa de cegueira no mundo ocidental. Várias formas clínicas foram reconhecidas, e membrana neovascular coroideana (MNSR representa manifestação importante passível de tratamento. O tratamento de MNSR tem sido um foco importante de pesquisa nas últimas décadas e a primeira terapia estabelecida baseada em evidência foi a fotocoagulação a laser, que reduziu o risco de perda visual em lesões extrafoveais. No fim da década de 90 a terapia fotodinâmica foi estabelecida como método eficiente de tratamento de MNSR predominantemente clássicas e ocultas. Terapias adicionais como a translocação macular, cirurgia submacular, e protrombose mediada por indocianina verde estão atualmente em investigação em ensaios clínicos em larga escala. A biologia molecular permitiu recentemente uma melhor compreensão da patogênese da DMRI e o fator de crescimento vascular endotelial foi reconhecido como um mediador-chave na angiogênese da formação de MNSR. Portanto, a abordagem farmacológica surge como opção terapêutica no tratamento da MNSR. O primeiro agente terapêutico aprovado pelo FDA é o aptâmero pegaptanib sódio (Macugen®, que inativa a isoforma fundamental para a angiogênese intra-ocular: VEGF165. Outros inativadores de VEGF como ranibizumab RhuFab V2 (Lucentis® e bevacizumab (Avastin® estão em avaliação em estudos clínicos. Resultados impressionantes de bevacizumab intravítreo foram liberados recentemente. Adicionalmente, o derivado de esteróides acetato de anecortave, assim como o corticosteróide acetato de triancinolona têm sido propostos como métodos no tratamento de DMRI-neovascular. Este artigo apresenta os princípios e resultados iniciais na terapia antiangiogênica farmacológica da MNSR na DMRI.Age-related macular degeneration (ARMD remains a leading cause of blindness in the western world. Several clinical forms of the disease are recognized

  18. Is monthly retreatment with intravitreal bevacizumab (Avastin® necessary in neovascular age-related macular degeneration?

    Directory of Open Access Journals (Sweden)

    Nicola G Ghazi

    2010-04-01

    Full Text Available Nicola G Ghazi, Tyler Q Kirk, Robert M Knape, James S Tiedeman, Brian P ConwayDepartment of Ophthalmology, University of Virginia Health System, Charlottesville, VA, USAPurpose: To report our short-term experience with bevacizumab in neovascular age-related macular degeneration (AMD and recommend a new treatment strategy.Methods: Retrospective chart review of 29 consecutive patients receiving 1.25 mg of intravitreal bevacizumab for AMD and completing 12 weeks of follow up. Outcome measures were best corrected visual acuity (BCVA and optical coherence tomography (OCT central macular thickness. Injections were repeated if no further improvement was observed.Results: Twenty-nine eyes of 29 patients were included. The average BCVA improved from 20/148 at baseline to 20/106 at twelve weeks (P = 0.041. Of the 29 eyes, 25 (86.2% had stable or improved BCVA. Average mean central macular thickness measured by OCT improved from 351 μm at baseline to 278 μm at 12 weeks (P = 0.003. Stabilization of vision and improved OCT central macular thickness were maintained for at least eight weeks following only a single injection in the majority of eyes. During the three months of follow up, only five eyes (17.2% required repeat injections, with only three (10.3% requiring retreatment at eight weeks and none at four weeks. No significant ocular or systemic side effects were observed. Conclusion: This short-term data suggests that bevacizumab appears to be a safe and effective treatment for neovascular AMD. Injections as frequent as every month do not appear to be necessary since initial treatment effect appears to be maintained for at least eight weeks in almost all of our patients.Keywords: retina, Avastin®, bevacizumab, neovascular age-related macular degeneration, AMD

  19. 丙烯醛诱导大鼠脉络膜新生血管的形成%The formation of rats’ choroidal neovascularization induced by acrolein

    Institute of Scientific and Technical Information of China (English)

    王观峰; 邹秀兰; 李东豪; 王琛; 李文立; 皮荣标

    2016-01-01

    目的::探讨丙烯醛( AC)诱导大鼠脉络膜新生血管( CNV)的形成。方法:选取远交群大鼠( SD)12只,随机将大鼠分为三组,即空白组,AC诱导4wk组和AC诱导8wk组,其中空白对照组每日200μL新鲜自来水灌胃,实验组为200μL AC溶液(2.5 mg/kg/d)每日灌胃,分为诱导4wk组和8wk组,取材后视网膜组织石蜡包埋,切片及HE染色。结果:空白对照组及AC诱导4 wk组均见RPE-Bruch膜连续性完整,未见明显异常;AC 诱导8 wk 组发现 RPE-Bruch膜连续性缺失,脉络膜新生血管长入视网膜神经上皮层内。结论:长期使用AC可以诱导大鼠脉络膜新生血管形成。%AlM:To investigate the formation of rats′ choroidal neovascularization ( CNV) induced by acrolein.METHODS:Twelve Sprague-Dawley rats were randomly divided into three groups. Acrolein 200μL (2. 5 mg/kg/d) was 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.CONCLUSlON:The long time use of acrolein can induce the formation of choroial neovascularization in rats.

  20. Translocation of the retinal pigment epithelium and choroidal neovascularization induced by injecting Matrigel to subretinal space of rats%大鼠视网膜下注射Matrigel诱导视网膜色素上皮易位和脉络膜新生血管形成

    Institute of Scientific and Technical Information of China (English)

    汪振芳; 万鹏霞; 何丽文; 袁钊辉; 温容

    2007-01-01

    Objective To establish an animal model of sub-retinal pigment epithelium (sub-RPE)deposits,and to explore the pathological process of the transloeation of retinal pigment epithelium, choroidal neovascularization and the pathogenesis of age-related macular degeneration (AMD). Methods Matrigel was injected to the subretinal space of rats to create an amorphous deposit. Translocation of retinal pigment epithelium and choroidal neovascularization were observed. Results The subretinal deposit of Matrigel induced RPE translocation and therefore it became a sub-RPE deposit. The RPE mobilization required the presence of photoreceptors. Bruch's membrane devoid of RPE attachment became vulnerable to the invasion of new blood vessels from the choroid. Conclusions A novel model of sub-RPE deposit formation is established successfully. The presence of sub-RPE deposit is sufficient to induce choroidal neovascularization to penetrate Bruch's membrane and may cause the exudative form of AMD.%目的 制备视网膜色素上皮(RPE)下沉积物形成动物模型,并探讨其诱导视网膜色素上皮易位和脉络膜新牛血管(CNV)形成的病理过程以及年龄相关性黄斑变性(AMD)的发病机制.方法 将Matrigel基质胶注射于大鼠视网膜下形成视网膜下沉积物,观察视网膜色素上皮的迁移和脉络膜新生血管的形成.结果 Matrigel形成视网膜下沉积物后诱导RPE易位,而沉积物换位成为视网膜色素上皮层下沉积物.REP细胞的动员需要光感受器细胞的参与.缺乏色素上皮细胞贴附的Bruch膜易受脉络膜新生血管的侵袭.结论 建立了一个新的视网膜色素上皮层下沉积物形成的AMD动物模型.视网膜色素上皮层下沉积物足以导致CNV穿透Bruch膜,可能导致湿性AMD发生.

  1. 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. ME

  2. 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.

  3. A prospective study of treatment patterns and 1-year outcome of Asian age-related macular degeneration and polypoidal choroidal vasculopathy.

    Directory of Open Access Journals (Sweden)

    Chui Ming Gemmy Cheung

    Full Text Available OBJECTIVE: To study the treatment patterns and visual outcome over one year in Asian patients with choroidal neovascular membrane secondary to age-related macular degeneration (AMD-CNV and polypoidal choroidal vasculopathy (PCV. DESIGN: Prospective cohort, non-interventional study. METHODS: 132 treatment-naïve patients who received treatment for AMD-CNV and PCV were included. All patients underwent standardized examination procedures including retinal imaging at baseline and follow-up. AMD-CNV and PCV were defined on fundus fluorescein angiography and indocyanine green angiography at baseline. Patients were treated according to standard of care.We report the visual acuity (VA and optical coherence tomography (OCT measurements at baseline, month 3 and month 12 The factors influencing month 12 outcomes were analyzed. MAIN OUTCOME MEASURE: Type of treatment, number of Anti-vascular endothelial growth factor (VEGF treatments, visual outcome over one year. RESULTS: Anti-VEGF monotherapy was the initial treatment in 89.1% of AMD-CNV, but only 15.1% of PCV. The mean number of anti-VEGF injections up to month 12 was 3.97 (4.51 AMD-CNV, 3.43 PCV, p = 0.021. Baseline OCT, month 3 OCT and month 3 VA were significant in determining continuation of treatment after month 3. At month 12, mean VA improved from 0.82 (∼20/132 at baseline to 0.68 (∼20/96 at month 12 (mean gain 6.5 ETDRS letters, p = 0.002. 34.2% of eyes (38/113 eyes gained ≥15 ETDRS letters and 14.4% (16/113 eyes lost ≥15 ETDRS letters. There were no significant differences in visual outcome between AMD-CNV and PCV (p = 0.51. Factors predictive of month 12 visual outcome were baseline VA, baseline OCT central macular thickness, month 3 VA and age. CONCLUSIONS: There is significant variation in treatment patterns in Asian eyes with exudative maculopathy. There is significant visual improvement in all treatment groups at one year. These data highlight the need for high quality

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    PURPOSE: To describe the spectral domain optical coherence tomography findings in eyes with chronic fibrovascular pigment epithelial detachment (PED) receiving intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy. METHODS: Retrospective observational case series of patients...... over a mean of 36.9 months (median, 37.5; range, 6-84). A fusiform, or spindle-shaped, complex of highly organized layered hyperreflective bands was noted within each PED. Nineteen eyes demonstrated heterogenous, dilated, irregular neovascular tissue adherent to the undersurface of the retinal pigment......, 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...

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

    OpenAIRE

    Rishma Gohil; Roxanne Crosby-Nwaobi; Angus Forbes; Ben Burton; Phil Hykin; Sobha Sivaprasad

    2015-01-01

    Purpose To assess the caregiver burden and factors determining the burden in patients receiving ranibizumab therapy for neovascular AMD (nAMD). Methods 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 ...

  6. Dysregulation of CXCR3 expression on peripheral blood leukocytes in patients with neovascular age-related macular degeneration

    DEFF Research Database (Denmark)

    Falk, Mads Krüger; Singh, Amardeep; Faber, Carsten;

    2014-01-01

    Purpose: The chemokine receptor CXCR3 has been strongly related to inhibition of angiogenesis. The purpose of this study was to investigate the association between expression of CXCR3 on peripheral blood leukocytes and Age-related Wet Macular Degeneration (AMD). Furthermore, we measured the plasma...... concentration of the chemokines CXCL9-11. Methods: The study group consisted of patients with AMD attending our department. Patients referred for other reasons than AMD were enrolled as control persons. The expression of CXCR3 on T-cells and the plasma concentration of CXCL9-11 were measured using flow...... cytometry. Results: We looked at all CD8+ T-cells expressing CXCR3 and found a significant lower percentage of these cells in the neovascular AMD group compared to the age-matched control group (p=0.05). When dividing the CD8+ cells in functional groups according to their expression of CXCR3, we found...

  7. The rs2071559 AA VEGFR-2 Genotype Frequency Is Significantly Lower in Neovascular Age-Related Macular Degeneration Patients

    Directory of Open Access Journals (Sweden)

    Stefano Lazzeri

    2012-01-01

    Full Text Available In this prospective, case-control genetic study, 120 consecutive neovascular age-related macular degeneration (AMD cases and 78 controls were enrolled. Two SNPs (rs2071559 and rs1870377 of VEGF-A receptor-2 (VEGFR-2 gene were analyzed with the technique of Real-Time PCR to investigate a genetic link between AMD and VEGFR-2 gene polymorphisms in Italian patients. The frequency of the VEGFR-2 genotype rs2071559 AA was significantly lower (18.33% in patients with AMD than in the control subjects (34.62%; P=0.0095, chi-square test; Pcorr=0.038; OR=0.42, 95% CI 0.22 to 0.82. In conclusion, although with the limitations of a small sample size and the few SNPs studied, this study demonstrates a lower frequency of VEGFR-2 rs2071559 AA genotype in an AMD patient population, suggesting future studies on the role VEGFR-2 SNPs.

  8. The rs2071559 AA VEGFR-2 genotype frequency is significantly lower in neovascular age-related macular degeneration patients.

    Science.gov (United States)

    Lazzeri, Stefano; Orlandi, Paola; Figus, Michele; Fioravanti, Anna; Cascio, Elisa; Di Desidero, Teresa; Agosta, Elisa; Canu, Bastianina; Sartini, Maria Sole; Danesi, Romano; Nardi, Marco; Bocci, Guido

    2012-01-01

    In this prospective, case-control genetic study, 120 consecutive neovascular age-related macular degeneration (AMD) cases and 78 controls were enrolled. Two SNPs (rs2071559 and rs1870377) of VEGF-A receptor-2 (VEGFR-2) gene were analyzed with the technique of Real-Time PCR to investigate a genetic link between AMD and VEGFR-2 gene polymorphisms in Italian patients. The frequency of the VEGFR-2 genotype rs2071559 AA was significantly lower (18.33%) in patients with AMD than in the control subjects (34.62%; P = 0.0095, chi-square test; P(corr) = 0.038; OR = 0.42, 95% CI 0.22 to 0.82). In conclusion, although with the limitations of a small sample size and the few SNPs studied, this study demonstrates a lower frequency of VEGFR-2 rs2071559 AA genotype in an AMD patient population, suggesting future studies on the role VEGFR-2 SNPs.

  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...... treatment regimen used in both periods. RESULTS: Snellen best-corrected visual acuity (BCVA) at baseline and after one year was 0.23 and 0.31 (p ... forward. The share of patients (73%) still in treatment with ranibizumab at year 1 had a baseline BCVA of 0.26 but 0.40 at year 1 (p visual gains...

  10. Anti-angiogenic effect of ALS-L1023, an extract of Melissa officinalis L., on experimental choroidal neovascularization in mice.

    Science.gov (United States)

    Roh, Young-Jung; Jee, Donghyun; Rho, Chang-Rae; Cho, Won-Kyung; Kang, Seungbum

    2016-01-01

    The effect of ALS-L1023, an extract of Melissa officinalis L. (Labiatae; lemon balm) leaves, on experimental choroidal neovascularization (CNV) in mice was evaluated. C57BL/6 mice were given either vehicle or ALS-L1023 daily via oral gavage for 3 weeks (days 0-21). CNV was induced by rupturing Bruch's membrane using laser photocoagulation (day 7). Two weeks after laser injury (day 21), the CNV lesions were evaluated by an examination of choroidal flat mounts using fluorescein-labelled dextran, immunofluorescence staining with isolectin B4 and fluorescence angiography. The effects of ALS-L1023 on endothelial cell tube formation and the expression of phosphorylated extracellular signal-regulated kinase 1/2 were evaluated using human umbilical vein endothelial cells. The extent of CNV was reduced by ALS-L1023. Mice treated with 100 and 200 mg/kg/day of the material exhibited 44.3 and 68.1% reductions in the extent of CNV lesions, respectively, compared to the vehicle group (P < 0.001). The size of the isolectin B4-labelled area was also significantly decreased in the ALS-L1023-treated groups (P < 0.001). On fluorescein angiography, ALS-L1023-treated mice exhibited significantly less leakage of fluorescent material than did vehicle-treated mice. ALS-L1023 decreased vascular endothelial growth factor-induced human umbilical vein endothelial cell tube formation in a dose-dependent manner. The expression of phosphorylated extracellular signal-regulated kinase 1/2 was suppressed by ALS-L1023. The laser-induced CNV in mice can be inhibited by ALS-L1023. Therefore, it may have therapeutic potential for the treatment of diseases involving CNV. © 2015 Royal Australian and New Zealand College of Ophthalmologists.

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

    Science.gov (United States)

    Mrejen, Sarah; Jung, Jesse J; Chen, Christine; Patel, Samir N; Gallego-Pinazo, Roberto; Yannuzzi, Nicolas; Xu, Luna; Marsiglia, Marcela; Boddu, Sucharita; Freund, K Bailey

    2015-07-08

    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.

  12. 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.

  13. Recurrence of Macular Hole Retinal Detachment after Intravitreal Ranibizumab Injection for the Treatment of Choroidal Neovascularization from the Remaining Macular Hole Edge

    Directory of Open Access Journals (Sweden)

    Keiko Otsuka

    2012-12-01

    Full Text Available Purpose: To report a case who had recurrence of macular hole retinal detachment (MHRD after intravitreal ranibizumab injection (IVR for the treatment of choroidal neovascularization (CNV that arose from the damaged retinal pigment epithelium of the remaining macular hole (MH edge, which had been successfully treated by pars plana vitrectomy (PPV 15 years previously. Case Report: A 67-year-old man with previous PPV for MHRD secondary to high myopia in the right eye had been under observation for 15 years after surgery. The retina had been successfully attached, but the MH remained open. He had CNV which arose from the remaining MH edge. IVR was performed for the treatment of CNV. One month after the injection, CNV was contracted but recurrence of MHRD occurred. PPV with an additional internal limiting membrane peeling, removal of the CNV membrane and 20% SF6 gas tamponade was performed. One year after the last surgery, his right retina was attached and the MH was closed successfully. Conclusion: We propose that patients who undergo IVR should be carefully maintained and followed up for possible complications including the recurrence of MHRD.

  14. Choroidal Thickness and Choroidal Vessel Density in Nonexudative Age-Related Macular Degeneration Using Swept-Source Optical Coherence Tomography Imaging.

    Science.gov (United States)

    Zheng, Fang; Gregori, Giovanni; Schaal, Karen B; Legarreta, Andrew D; Miller, Andrew R; Roisman, Luiz; Feuer, William J; Rosenfeld, Philip J

    2016-11-01

    To analyze the relationship between choroidal thickness and the distribution of choroidal blood vessels in eyes with nonexudative AMD. Eyes with a diagnosis of nonexudative AMD were imaged using a prototype 100-kHz swept-source (SS) optical coherence tomography (OCT) instrument (Carl Zeiss Meditec, Dublin, CA, USA) with a central wavelength of 1050 nm. We used an OCT cube scan pattern consisting of 512 × 512 A-scans over a 12 × 12 mm retinal area. The eyes were partitioned into two groups based on the presence or absence of reticular pseudodrusen (RPD). All scans were segmented using an automated algorithm. In addition, five eyes from each of the two groups were randomly chosen for manual segmentation. Binary choroidal vessels maps were generated from suitable OCT choroidal slabs, and the relationship between the density of large choroidal vessels and choroidal thickness was analyzed using an Early Treatment Diabetic Retinopathy Study-like target centered on the fovea. Twenty-five eyes were enrolled in each group. The automated algorithm produced accurate choroidal thickness maps with an average difference between the manual and automated segmentations of 13.7 μm. There was a significant and stable correlation between choroidal thickness and choroidal vessel density across the two groups. Both average choroidal thickness and vessel density were significantly lower in eyes with RPD. Our fully automated choroidal segmentation algorithm was able to capture the different patterns of choroidal thickness over a wide area. Choroidal thickness has a clear relationship with the density of large choroid vessels in our sample, irrespective of the presence or absence of RPD.

  15. Joint Effect of CFH and ARMS2/HTRA1 Polymorphisms on Neovascular Age-Related Macular Degeneration in Chinese Population

    Directory of Open Access Journals (Sweden)

    Kai Fang

    2015-01-01

    Full Text Available Purpose. The etiology of neovascular age-related macular degeneration (nAMD cannot be completely explained by identified environmental risk factors or single-locus gene variants. This study was to explore the potential interactions among gene variants on nAMD in Chinese population. Methods. 43 SNPs located in different genes were genotyped in 932 Chinese individuals (464 nAMD patients and 468 controls. We explored the potential interactions among gene variants using generalized multifactor dimensionality reduction (GMDR algorithm and the method to measure the departure from the additivity model. Results. The joint effect that involved CFH rs1061170 and HTRA1 rs3793917 was shown statistically significant (P < 0.001 with the highest cross-validation consistency (10/10 and the best testing balanced accuracy (64.50%. In addition, based on the method to measure the departure from the additivity model, the synergy index (S was 2.63 (1.09–6.38 and the attributable proportion due to interaction (AP was 55.7% (21.4%–89.9%, which suggested that a common pathway may exist for these genes for nAMD. Those who carried CC for rs3793917 and TC/CC for rs1061170 were at the highest risk of nAMD (OR: 9.76, 95% CI: 4.65–20.51. Conclusions. Evidence that the joint effect that involved CFH and ARMS2/HTRA1 may contribute to the risk of neovascular AMD in Chinese population was obtained.

  16. Joint Effect of CFH and ARMS2/HTRA1 Polymorphisms on Neovascular Age-Related Macular Degeneration in Chinese Population

    Science.gov (United States)

    Gao, Pei; Tian, Jun; Yu, Wenzhen; Li, Juan; Chen, Qing; Huang, Lvzhen; Chen, Dafang; Hu, Yonghua; Li, Xiaoxin

    2015-01-01

    Purpose. The etiology of neovascular age-related macular degeneration (nAMD) cannot be completely explained by identified environmental risk factors or single-locus gene variants. This study was to explore the potential interactions among gene variants on nAMD in Chinese population. Methods. 43 SNPs located in different genes were genotyped in 932 Chinese individuals (464 nAMD patients and 468 controls). We explored the potential interactions among gene variants using generalized multifactor dimensionality reduction (GMDR) algorithm and the method to measure the departure from the additivity model. Results. The joint effect that involved CFH rs1061170 and HTRA1 rs3793917 was shown statistically significant (P < 0.001) with the highest cross-validation consistency (10/10) and the best testing balanced accuracy (64.50%). In addition, based on the method to measure the departure from the additivity model, the synergy index (S) was 2.63 (1.09–6.38) and the attributable proportion due to interaction (AP) was 55.7% (21.4%–89.9%), which suggested that a common pathway may exist for these genes for nAMD. Those who carried CC for rs3793917 and TC/CC for rs1061170 were at the highest risk of nAMD (OR: 9.76, 95% CI: 4.65–20.51). Conclusions. Evidence that the joint effect that involved CFH and ARMS2/HTRA1 may contribute to the risk of neovascular AMD in Chinese population was obtained. PMID:25883802

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    being treated with a median of 10 (range 3-36) anti-VEGF injections for neovascular AMD. Visual acuity improved by a mean of 7.1 [95% confidence interval (CI) 4.6-9.6] ETDRS letters in the first 6 months after cataract surgery. The need of anti-VEGF injections did not change after cataract surgery...... in electronic databases managing anti-VEGF injections and cataract surgery. We compared Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity and frequency of anti-VEGF injections before and after cataract surgery. RESULTS: We identified 89 eyes from 89 patients who had cataract surgery after...... AMD. Cataract surgery was not associated with an increased need for anti-VEGF treatment and patients who were in active anti-VEGF treatment had better visual outcomes than patients who had cataract surgery after long injection-free periods....

  18. Terapia fotodinâmica com verteporfirina em neovascularização coroidiana subfoveal secundária a coriorretinopatia serosa central: relato de caso Photodynamic therapy with verteporfin for subfoveal choroidal neovascularization in central serous chorioretinopathy: case report

    Directory of Open Access Journals (Sweden)

    Hugo Soares Maia

    2005-08-01

    Full Text Available Relatamos o uso da terapia fotodinâmica com verteporfirina em neovascularização coroidiana subfoveal secundária a coriorretinopatia serosa central. O paciente apresentou melhora da acuidade visual (0,5 para 1,0 30 dias após a primeira sessão. Depois de 141 dias, apresentou reativação da membrana, sendo submetido a nova sessão, obtendo melhora da acuidade visual (0,5 para 1,0 após 30 dias. O quadro mantém-se inalterado há 20 meses. A terapia fotodinâmica pode ser eficiente no tratamento de neovascularização coroidiana secundária a coriorretinopatia serosa central.We report the use of photodynamic therapy with verteporfin for subfoveal choroidal neovacularization in central serous chorioretinopathy. Visual acuity improved (0.5 to 1.0 30 days after the first session. After 141 days, the choroidal neovascularization reactivated and the patient was retreated. Again, visual acuity improved (0.5 to 1.0 30 days afterwards. It remains stable after 20 months. Photodynamic therapy can be efficient in the treatment of choroidal neovascularization in central serous chorioretinopathy.

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

    OpenAIRE

    Agarwal A; Rhoades WR; Hanout M; Soliman MK; Sarwar S.; Sadiq MA; Sepah YJ; Do DV; Nguyen QD

    2015-01-01

    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 ...

  20. Oxidative Stress, Hypoxia, and Autophagy in the Neovascular Processes of Age-Related Macular Degeneration

    OpenAIRE

    Blasiak, Janusz; Petrovski, Goran; Veréb, Zoltán; Facskó, Andrea; Kaarniranta, Kai

    2014-01-01

    Age-related macular degeneration (AMD) is the leading cause of severe and irreversible loss of vision in the elderly in developed countries. AMD is a complex chronic neurodegenerative disease associated with many environmental, lifestyle, and genetic factors. Oxidative stress and the production of reactive oxygen species (ROS) seem to play a pivotal role in AMD pathogenesis. It is known that the macula receives the highest blood flow of any tissue in the body when related to size, and anythin...

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Anti-vascular endothelial growth factor treatment for choroidal neovascularization secondary to angioid streaks in pseudoxanthoma elasticum:a case report and systemic review

    Institute of Scientific and Technical Information of China (English)

    Aiyi Zhou; Chenjing Zhou; Ziyao Liu; Yanlong Quan

    2016-01-01

    The present study reports a case of a patient with choroidal neovascularization (CNV) associated with pseudoxanthoma elasticum (PXE). We observed the functional and anatomical improvement of the patient treated with intravitreal vascular endothelial growth factor (VEGF) inhibitor bevacizumab. The study also systematically searched the database for similar cases to provide a literature review. Data concerning the clinical features, treatment strategies and outcomes were extracted and analyzed. Retrospective interventional case report and systematic literature review. A 56-year-old healthy Chinese woman with CNV secondary to PXE was reported. Examinations included best corrected visual acuity (BCVA), biomicroscopy, optical coherence tomography (OCT), lfuorescein and indocyanine green angiography and digital fundus photography. The patient managed with intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections (bevacizumab 1.25 mg/0.05 mL). The Cochrane Library, PubMed, OVID, and UpToDate databases were searched using the term pseudoxanthoma elasticum or Grönblad-Strandberg syndrome with the limits English. Articles that predated the databases were gathered from current references. Fundus examination revealed angioid streaks bilaterally and CNV in left eye (LE). After the patient underwent three intravitreal injections of bevacizumab, the LE showed absorption of the subretinal lfuid and shrinkage of the CNV. Visual acuity (VA) was improved in her treated LE. Bevacizumab treatment was well tolerated with no adverse events reported. Approximately ten articles about 45 patients (49 eyes) describing CNV secondary to angioid streaks in PXE treated with anti-VEGF were found in the literature search. In the present case, bevacizumab of an initial three injection loading dose, achieved maintenance of visual function in the treatment of CNV associated with angioid streaks in PXE. Literature articles concluded that the intravitreal application of anti-VEGF is

  3. Detailed functional and structural phenotype of Bietti crystalline dystrophy associated with mutations in CYP4V2 complicated by choroidal neovascularization.

    Science.gov (United States)

    Fuerst, Nicole M; Serrano, Leona; Han, Grace; Morgan, Jessica I W; Maguire, Albert M; Leroy, Bart P; Kim, Benjamin J; Aleman, Tomas S

    2016-12-01

    To describe in detail the phenotype of a patient with Bietti crystalline dystrophy (BCD) complicated by choroidal neovascularization (CNV) and the response to intravitreal Bevacizumab (Avastin(®); Genentech/Roche). A 34-year-old woman with BCD and mutations in CYP4V2 (c.802-8_806del13/p.H331P:c992A>C) underwent a complete ophthalmic examination, full-field flash electroretinography (ERG), kinetic and two-color dark-adapted perimetry, and dark-adaptometry. Imaging was performed with spectral domain optical coherence tomography (SD-OCT), near infrared (NIR) and short wavelength (SW) fundus autofluorescence (FAF), and fluorescein angiography (FA). Best-corrected visual acuity (BCVA) was 20/20 and 20/60 for the right and left eye, respectively. There were corneal paralimbal crystal-like deposits. Kinetic fields were normal in the peripheral extent. Retinal crystals were most obvious on NIR-reflectance and corresponded with hyperreflectivities within the RPE on SD-OCT. There was parafoveal/perifoveal hypofluorescence on SW-FAF and NIR-FAF. Rod > cone sensitivity loss surrounded fixation and extended to ~10° of eccentricity corresponding to regions of photoreceptor outer segment-retinal pigmented epithelium (RPE) interdigitation abnormalities. The outer nuclear layer was normal in thickness. Recovery of sensitivity following a ~76% rhodopsin bleach was normal. ERGs were normal. A subretinal hemorrhage in the left eye co-localized with elevation of the RPE on SD-OCT and leakage on FA, suggestive of CNV. Three monthly intravitreal injections of Bevacizumab led to restoration of BCVA to baseline (20/25). crystals in BCD were predominantly located within the RPE. Photoreceptor outer segment and apical RPE abnormalities underlie the relatively extensive retinal dysfunction observed in relatively early-stage BCD. Intravitreal Bevacizumab was effective in treating CNV in this setting.

  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. Inhibition of Ocular Neovascularization by Co-Inhibition of VEGF-A and PLGF

    OpenAIRE

    Xiaochuan Huo; Youxiang Li; Yuhua Jiang; Xiaoyun Sun; Lixue Gu; Wenshi Guo; Dapeng Sun

    2015-01-01

    Background/Aims: Age-related macular degeneration (AMD) appears to be a disease with increasing incidence in Western countries and may develop into acquired blindness. Choroidal neovascularization (CNV) is the most frequent cause for AMD, and is commonly induced by regional inflammation. Past studies have highlighted vascular endothelial growth factor A (VEGF-A) as a major trigger for CNV. However, studies on the associated angiogenic factors other than VEGF-A are lacking. Methods: Here, we u...

  6. Genetic predictive biomarkers of anti-VEGF treatment response in patients with neovascular age-related macular degeneration.

    Science.gov (United States)

    Fauser, Sascha; Lambrou, George N

    2015-01-01

    Anti-vascular endothelial growth factor (anti-VEGF) therapies for neovascular age-related macular degeneration (nAMD) have proven efficacy at a study-population level, although individual patient responses vary, with most of the patients responding well to anti-VEGF therapies, while a few respond poorly. The pathogenesis of AMD is known to have a genetic component, but it is unclear if any particular genotype can predict response to anti-VEGF therapy. With the advent of less expensive genotyping technology, there have been numerous studies within this area. Here we analyze potential biomarker candidates identified that could be used in a clinical setting to predict response to anti-VEGF treatment of nAMD. We analyze single nucleotide polymorphisms (SNPs) identified from 39 publications. The SNPs that appeared to be of most importance fell into two main groups: those previously associated with AMD pathogenesis and those within the signaling pathway targeted by anti-VEGF therapies. A number of small studies found evidence supporting an association between anti-VEGF treatment response and two SNPs, CFH rs1061170 and VEGFA rs699947, but results from randomized controlled trials found no such association. It is possible that, in the future, the cumulative effect of several high-risk SNPs may prove useful in a clinical setting and that other genetic biomarkers may emerge.

  7. The direct, indirect and intangible costs of visual impairment caused by neovascular age-related macular degeneration.

    Science.gov (United States)

    Ke, Kathleen Melissa

    2010-12-01

    Neovascular age-related macular degeneration (nvAMD) is a chronic, progressive disease of the central retina, and its prevalence is expected to rise with the ageing population. Using a bottom-up approach based on retrospective data, this cross-sectional study estimated average annual direct costs of nvAMD to be £4,047, and average annual indirect costs to be £449. An attempt to measure intangible costs through willingness-to-pay yielded a lower response rate and estimated intangible costs to be 11.5% of monthly income. Direct costs were significantly higher for male participants, for those who have mild or moderate visual impairment in both eyes, and for those who have been diagnosed for a shorter time. The findings of this study suggest that the availability of early diagnosis, effective treatment, support services, and sustained research into the management of nvAMD may reduce the burden of visual impairment caused by nvAMD to affected individuals and the state.

  8. 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.

  9. The Potential Importance of Detection of Neovascular Age-Related Macular Degeneration When Visual Acuity Is Relatively Good.

    Science.gov (United States)

    Ho, Allen C; Albini, Thomas A; Brown, David M; Boyer, David S; Regillo, Carl D; Heier, Jeffrey S

    2017-03-01

    The advent of anti-vascular endothelial growth factor treatment has changed the prognosis for patients with neovascular age-related macular degeneration (nvAMD). The ability to stabilize or improve vision with these treatments is a major step in enabling patients to continue to function at the highest possible level. Many studies have demonstrated that the better the visual acuity (VA) is at the time of treatment initiation, the higher the likelihood that VA will be better during at least the following 2 years; as such, detection of nvAMD when VA is relatively good is important. Data on the VA of patients with intermediate AMD and VA at the time of nvAMD diagnosis suggest that patients are typically losing an average of 3 to 5 lines of vision and possibly more between the time that intermediate AMD progresses to nvAMD and the diagnosis of nvAMD is made. The average patient may have nvAMD for 6 to 12 months before diagnosis and treatment initiation. Current efforts in management of nvAMD are primarily aimed at optimizing anti-vascular endothelial growth factor treatments that have the potential to improve VA outcomes by a magnitude of letters. Additional tools or other efforts to identify patients with nvAMD before substantial vision loss has occurred may reduce the amount of visual loss sustained with anti-vascular endothelial growth factor therapy, and have the potential to improve VA outcomes substantially.

  10. Spectral domain optical coherence tomography for quantitative evaluation of drusen and associated structural changes in non-neovascular age-related macular degeneration.

    Science.gov (United States)

    Yi, K; Mujat, M; Park, B H; Sun, W; Miller, J W; Seddon, J M; Young, L H; de Boer, J F; Chen, T C

    2009-02-01

    To demonstrate how spectral domain optical coherence tomography (SDOCT) can better evaluate drusen and associated anatomical changes in eyes with non-neovascular age-related macular degeneration (AMD) compared with time domain optical coherence tomography (TDOCT). Images were obtained from three eyes of three patients with AMD using an experimental SDOCT system. Both a titanium-sapphire (Ti:sapphire) laser and a superluminescent diode (SLD) were used as a broadband light source to achieve cross-sectional images of the retina. A qualitative and quantitative analysis was performed for structural changes associated with non-neovascular AMD. An automated algorithm was developed to analyse drusen area and volume from SDOCT images. TDOCT was performed using the fast macular scan (StratusOCT, Carl Zeiss Meditec, Dublin, California). SDOCT images can demonstrate structural changes associated with non-neovascular AMD. A new SDOCT algorithm can determine drusen area, drusen volume and proportion of drusen. With new algorithms to determine drusen area and volume and its unprecedented simultaneous ultra-high speed ultra-high resolution imaging, SDOCT can improve the evaluation of structural abnormalities in non-neovascular AMD.

  11. Association of the Intestinal Microbiome with the Development of Neovascular Age-Related Macular Degeneration

    Science.gov (United States)

    Zinkernagel, Martin S.; Zysset-Burri, Denise C.; Keller, Irene; Berger, Lieselotte E.; Leichtle, Alexander B.; Largiadèr, Carlo R.; Fiedler, Georg M.; Wolf, Sebastian

    2017-01-01

    Age-related macular degeneration (AMD) is the most frequent cause of blindness in the elderly. There is evidence that nutrition, inflammation and genetic risk factors play an important role in the development of AMD. Recent studies suggest that the composition of the intestinal microbiome is associated with metabolic diseases through modulation of inflammation and host metabolism. To investigate whether compositional and functional alterations of the intestinal microbiome are associated with AMD, we sequenced the gut metagenomes of patients with AMD and controls. The genera Anaerotruncus and Oscillibacter as well as Ruminococcus torques and Eubacterium ventriosum were relatively enriched in patients with AMD, whereas Bacteroides eggerthii was enriched in controls. Patient’s intestinal microbiomes were enriched in genes of the L-alanine fermentation, glutamate degradation and arginine biosynthesis pathways and decreased in genes of the fatty acid elongation pathway. These findings suggest that modifications in the intestinal microbiome are associated with AMD, inferring that this common sight threatening disease may be targeted by microbiome-altering interventions. PMID:28094305

  12. Comparative effectiveness of aflibercept for the treatment of patients with neovascular age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Thomas M

    2013-03-01

    Full Text Available Michael Thomas,1 Shaymaa S Mousa,2 Shaker A Mousa1 1Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, NY, USA; 2The Johns Hopkins University, Baltimore, MD, USA Abstract: Wet age-related macular degeneration (AMD is the most common reason for vision loss in the United States. Many treatments, such as laser therapy and photodynamic therapies, have been used but their efficacy is limited. Emerging anti-vascular endothelial growth factor (VEGF therapies are now considered the standard of care. Anti-VEGF agents inhibit angiogenesis in the eye by suppressing abnormal blood vessel growth, leading to vision improvement. Ranibizumab and bevacizumab are two examples of anti-VEGF drugs that have been approved; both showed promise based on the visual acuity scale. Aflibercept, another new therapy known to trap VEGF and inhibit multiple growth factors, is promising not only because it can be taken bimonthly based on year 1 of the VIEW trials, but it can also be extended, as demonstrated in year 2 of the VIEW trials. Based on a cost–effect analysis, aflibercept is comparable to other leading therapies. This is a review of relevant clinical trials that have proven the non-inferiority and safety of aflibercept compared to the standard of care and its unique role in the current management of wet AMD. Keywords: aflibercept, VEGF, anti-VEGF, pegatanib, bevacizumab, ranibizumab, VIEW trials

  13. Intravitreal Bevacizumab Versus Ranibizumab for Treatment of Neovascular Age-Related Macular Degeneration: Findings from a Cochrane Systematic Review

    Science.gov (United States)

    Solomon, Sharon D.; Lindsley, Kristina B.; Krzystolik, Magdalena G.; Vedula, Satyanarayana S.; Hawkins, Barbara S.

    2015-01-01

    Topic To summarize the relative effects of bevacizumab (Avastin®, Genentech, Inc.) and ranibizumab (Lucentis®, Genentech, Inc.), using findings from a Cochrane Eyes and Vision Group systematic review . Clinical relevance Neovascular age-related macular degeneration (NVAMD) is the most common cause of uncorrectable vision loss in the elderly in developed countries. Bevacizumab and ranibizumab are the most frequently-used anti-VEGF agents injected intravitreally to treat NVAMD Methods We included only randomized controlled trials (RCTs) in which the two anti-VEGF agents had been compared directly. The primary outcome was 1-year gain in best-corrected visual acuity (BCVA) of 15 or more logMAR letters. We followed Cochrane methods for trial selection, data extraction, and data analyses. Relative effects of bevacizumab versus ranibizumab are presented as estimated risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs). Results We identified 6 eligible RCTs with 2809 participants. The proportion of eyes that gained 15 or more letters of BCVA by 1 year was similar for the two agents when the same regimens were compared: RR=0.90, 95% CI: 0.73 to 1.11. The mean change in BCVA from baseline also was similar: MD=−0.5 letter; 95% CI: −1.6 to +0.6. Other BCVA and quality-of-life outcomes were similar for the two agents. One-year treatment cost with ranibizumab was 5.1 and 25.5 times the cost for bevacizumab in the two largest trials. Ocular adverse events were uncommon (<1%); rates were similar for the two agents. Conclusions We found no important difference in effectiveness or safety between bevacizumab and ranibizumab for NVAMD treatment but a large cost difference. PMID:26477843

  14. Treatment satisfaction of patients undergoing ranibizumab therapy for neovascular age-related macular degeneration in a real-life setting

    Directory of Open Access Journals (Sweden)

    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 

  15. Experiences of patients undergoing anti-VEGF treatment for neovascular age-related macular degeneration: a systematic review.

    Science.gov (United States)

    Boyle, Jessica; Vukicevic, Meri; Koklanis, Konstandina; Itsiopoulos, Catherine

    2015-01-01

    Current therapy to slow disease progression in patients with neovascular age-related macular degeneration (AMD) often entails intra-vitreal injection of an anti-vascular endothelial growth factor (VEGF) agent, that begins with a three-month loading phase of four weekly injections followed by regular monthly visits with clinician-determined re-treatment. The effects of AMD on quality of life and visual function have been extensively reported in the literature, however, less is known about the burden imposed on patients by the arduous and often indefinite treatment schedule which habitually follows a diagnosis of wet AMD. To date, no systematic review has been conducted of research investigating patients' experiences of anti-VEGF treatment for AMD. A systematic search of the Embase, Medline, PsycINFO and PubMed electronic databases was undertaken to identify all studies between January 2004 and December 2013, published in the English language and involving human participants. A hand-search of an additional four journals was conducted. Ten articles were identified for inclusion in this review. A critical appraisal was undertaken using the Critical Appraisal Skills Programme Qualitative Research Checklist and the results synthesised to form a narrative review. Few studies to date have investigated patients' experiences of treatment for AMD. These studies have focused primarily on patients' experiences of the injection procedure with respect to pain and anxiety. Anticipated discomfort is often greater than actual discomfort experienced during intra-vitreal injection. However, different stages of the treatment procedure produce varying levels of patient discomfort. No one method of anaesthesia has consistently been shown to be more effective in reducing discomfort associated with treatment. Common reasons underlying patient apprehension surrounding treatment include the thought of having an injection, fear of losing eyesight and fear of the unknown. Whilst these studies

  16. 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.

  17. Transforming Growth Factor-Beta Inhibition Reduces Progression of Early Choroidal Neovascularization Lesions in Rats: P17 and P144 Peptides

    Science.gov (United States)

    Zarranz-Ventura, Javier; Fernández-Robredo, Patricia; Recalde, Sergio; Salinas-Alamán, Angel; Borrás-Cuesta, Francisco; Dotor, Javier; García-Layana, Alfredo

    2013-01-01

    The purpose of this study was to assess the effects of transforming growth factor beta (TGF-β) inhibitor peptides (P17 & P144) on early laser-induced choroidal neovascularization (LI-CNV) lesions in rats, two weeks after laser CNV induction. Seventy-one Long Evans rats underwent diode laser application in an established LI-CNV model. Baseline fluorescein angiography (FA) was performed 14 days following laser procedure, and treatments were administered 16 days post-laser application via different administration routes. Intravenous groups included control (IV-Control), P17 (IV-17), and P144 (IV-144) groups, whereas intravitreal groups included P17 (IVT-17), P144 (IVT-144), and a mixture of both peptides (IVT-17+144) (with fellow eyes receiving vehicle alone). CNV evolution was assessed using FA performed weekly for four weeks after treatment. Following sacrifice, VEGF, TGF-β, COX-2, IGF-1, PAI-1, IL-6, MMP-2, MMP-9, and TNF-α gene expression was assessed using RT-PCR. VEGF and p-SMAD2 protein levels were also assessed by western-blot, while MMP-2 activity was assessed with gelatin zymography. Regarding the FA analysis, the mean CNV area was lower from the 3rd week in IVT-17 and IVT-144 groups, and also from the 2nd week in IVT-17+144. Biochemical analysis revealed that gene expression was lower for VEGF and COX-2 genes in IV-17 and IV-144 groups, VEGF gene in IVT-17+144 group and MMP-2 gene in IVT-17 and IVT-144 groups. VEGF protein expression was also decreased in IV-17, IV-144, IVT-17 and IVT-144, whereas pSMAD-2 levels were lower in IV-17, IV-144 and IVT-17+144 groups. Zymogram analysis revealed decreased MMP-2 activity in IV-17, IV-144, IVT-17 and IVT-144 groups. These data suggest that the use of TGF-β inhibitor peptides (P17 & P144) decrease the development of early CNV lesions by targeting different mediators than those typically affected using current anti-angiogenic therapies. Its potential role in the treatment of early CNV appears promising as a single

  18. Transforming growth factor-beta inhibition reduces progression of early choroidal neovascularization lesions in rats: P17 and P144 peptides.

    Directory of Open Access Journals (Sweden)

    Javier Zarranz-Ventura

    Full Text Available The purpose of this study was to assess the effects of transforming growth factor beta (TGF-β inhibitor peptides (P17 & P144 on early laser-induced choroidal neovascularization (LI-CNV lesions in rats, two weeks after laser CNV induction. Seventy-one Long Evans rats underwent diode laser application in an established LI-CNV model. Baseline fluorescein angiography (FA was performed 14 days following laser procedure, and treatments were administered 16 days post-laser application via different administration routes. Intravenous groups included control (IV-Control, P17 (IV-17, and P144 (IV-144 groups, whereas intravitreal groups included P17 (IVT-17, P144 (IVT-144, and a mixture of both peptides (IVT-17+144 (with fellow eyes receiving vehicle alone. CNV evolution was assessed using FA performed weekly for four weeks after treatment. Following sacrifice, VEGF, TGF-β, COX-2, IGF-1, PAI-1, IL-6, MMP-2, MMP-9, and TNF-α gene expression was assessed using RT-PCR. VEGF and p-SMAD2 protein levels were also assessed by western-blot, while MMP-2 activity was assessed with gelatin zymography. Regarding the FA analysis, the mean CNV area was lower from the 3(rd week in IVT-17 and IVT-144 groups, and also from the 2(nd week in IVT-17+144. Biochemical analysis revealed that gene expression was lower for VEGF and COX-2 genes in IV-17 and IV-144 groups, VEGF gene in IVT-17+144 group and MMP-2 gene in IVT-17 and IVT-144 groups. VEGF protein expression was also decreased in IV-17, IV-144, IVT-17 and IVT-144, whereas pSMAD-2 levels were lower in IV-17, IV-144 and IVT-17+144 groups. Zymogram analysis revealed decreased MMP-2 activity in IV-17, IV-144, IVT-17 and IVT-144 groups. These data suggest that the use of TGF-β inhibitor peptides (P17 & P144 decrease the development of early CNV lesions by targeting different mediators than those typically affected using current anti-angiogenic therapies. Its potential role in the treatment of early CNV appears promising

  19. 黄斑部脉络膜新生血管的OCT图像特征及与视力的相关性%Correlation between optical coherence tomography image characteristics of macular choroidal neovascularization and visual acuity

    Institute of Scientific and Technical Information of China (English)

    张敏芳; 孟晓红; 陈军; 冉黎

    2011-01-01

    目的 观察黄斑部脉络膜新生血管(choroidal neovascularization,CNV)的光学相干断层扫描(optical coherence tomography,OCT)图像特征,评估其与最佳矫正视力的相关性. 方法 收集在我院经眼底荧光血管造影(fundus fluorescein angiography,FFA)及吲哚氰绿血管造影(indocyanine green angiography,ICGA)检查确诊为黄斑部典型性CNV高度近视(high myopia,HM)、年龄相关性黄斑变性(age-related macular degeneration,AMD)及中心性渗出性脉络膜视网膜病变(central exudative chorioretinopathy,CEC)患者共34例36眼,经验光检查得到最佳矫正视力(best corrected visual acuity,BCVA);采用OCT仪检查并分析CNV的图像特征,并测量CNV突破RPE/脉络膜毛细血管复合层的基底部宽度、高度、离中心凹的距离及中心处视网膜神经上皮层组织厚度,分别评估其与视力改变的相关性. 结果 CNV的OCT图像特征:RPE/脉络膜毛细血管层下见大小不等局限性增强隆起反射带;合并病灶周围视网膜神经上皮层组织下局限性无反射暗区或组织内反射增厚.AMD所引起的CNV基底部宽度、高度及中心处神经上皮层组织厚度值均最大.经直线相关分析统计显示:AMD和CEC所引起CNV的基底部宽度及中心处视网膜神经上皮层组织厚度均与BCVA具有负相关性(均为P<0.05),而HM所引起的CNV仅中心处视网膜神经上皮层组织厚度与BCVA具有负相关性(P<0.05). 结论 OCT能有效测量CNV的长度及黄斑水肿程度,在有效评估其与BCVA的相关性中具有重要作用.%Objective To investigate the optical coherence tomography (OCT) image characteristics of macular choroidal neovascularization (CNV) and evaluate their correlation with visual acuity. Methods Thirty-six eyes of 34 cases with high myopia, age-related macular degeneration ( AMD) and center exudation chorioretinopathy, which were diagnosed as typical macular CNV using fundus fluorescein angiography and indocyanine

  20. Amyloid beta deposition and phosphorylated tau accumulation are key features in aged choroidal vessels in the complement factor H knock out model of retinal degeneration.

    Science.gov (United States)

    Aboelnour, Asmaa; Kam, Jaimie Hoh; Elnasharty, M A; Sayed-Ahmed, Ahmed; Jeffery, Glen

    2016-06-01

    Extra-cellular deposition including amyloid beta (Aβ) is a feature of retinal ageing. It has been documented for Bruch's membrane (BM) where Aβ is elevated in complement factor H knockout mice (Cfh(-/-)) proposed as a model for age related macular degeneration. However, arterial deposition in choroidal vessels prior to perfusion across BM has not been examined. Aβ is associated with tau phosphorylation and these are linked in blood vessels in Alzheimers Disease where they can drive perivascular pathology. Here we ask if Aβ, tau and phosphorylated tau are features of ageing in choroidal vessels in 12 month C57 BL/6 and Cfh(-/-) mice, using immune staining and Western blot analysis. Greater levels of Aβ and phosphorylated tau are found in choroidal vessels in Cfh(-/-) mice. Western blot revealed a 40% increase in Aβ in Cfh(-/-) over C57 BL/6 mice. Aβ deposits coat around 55% of the luminal wall in Cfh(-/-) compared to only about 40% in C57 BL/6. Total tau was similar in both groups, but phosphorylated tau increased by >100% in Cfh(-/-) compared to C57 BL/6 and covered >75% of the luminal wall compared to 50% in C57 BL/6. Hence, phosphorylated tau is a marked choroidal feature in this mouse model. Aβ deposition was clumped in Cfh(-/-) mice and likely to influence blood flow dynamics. Disturbed flow is associated with atherogenesis and may be related to the accumulation of membrane attack complex recently identified between choroidal vessels in those at high risk of macular degeneration due to complement factor H polymorphisms.

  1. Visual function 5 years or more after macular translocation surgery for myopic choroidal neovascularisation and age-related macular degeneration

    Science.gov (United States)

    Takeuchi, K; Kachi, S; Iwata, E; Ishikawa, K; Terasaki, H

    2012-01-01

    Purpose To evaluate the changes in the best-corrected visual acuity (BCVA) after 1 year and after ≥5 years after macular translocation for age-related macular degeneration (AMD) or myopic choroidal neovascularisation (mCNV). Methods The medical records of 61 consecutive patients who underwent macular translocation with 360° retinotomy for AMD (35 eyes) or mCNV (26 eyes) were reviewed. Overall, 40 patients, 17 mCNV and 23 AMD, were followed for at least 5 years. BCVA and area of the Goldmann visual field (VF) measured before, 12 months after surgery, and at the final visit. Results In the 23 AMD eyes followed for ≥5 years, the mean preoperative BCVA was 1.149±0.105 logMAR units, which significantly improved to 0.69±0.06 logMAR units at 1 year (P142 logMAR units on their final examination. The area of the VF was significantly decreased at 12 months and did not change significantly thereafter. Conclusions Our results show that macular translocation surgery significantly improves the BCVA and significantly decreases the VF area of eyes with mCNV or AMD after first 1 year. The BCVA and VF area do not change significantly from the values at 1 year for at least 5 years. PMID:22173070

  2. Intravitreal ranibizumab for symptomatic drusenoid pigment epithelial detachment without choroidal neovascularization in age-related macular degeneration

    OpenAIRE

    Roberto Gallego-Pinazo; Ana Marina Suelves-Cogollos; Ester Francés-Muñoz; et. al.

    2011-01-01

    Roberto Gallego-Pinazo1,2, Ana Marina Suelves-Cogollos1, Ester Francés-Muñoz1, J María Millán2,3, J Fernando Arevalo4, J Luis Mullor5, Manuel Díaz-Llopis1,2,61Department of Ophthalmology, Hospital Universitario La Fe, Valencia, Spain; 2Centro de Investigación Biomédica en Red de Enfermedades Raras, Valencia, Spain; 3Department of Genetics, Hospital Universitario La Fe, Valencia, Spain; 4Retina and Vitreous Service, C...

  3. Intravitreal ranibizumab for symptomatic drusenoid pigment epithelial detachment without choroidal neovascularization in age-related macular degeneration

    OpenAIRE

    Diaz-Llopis,Manuel; Suelves-Cogollos,; Frances-Munoz,E; Millan, J.M.; Mullor ,Jose; Gallego-Pinazo, Roberto; Arevalo, J Fernando

    2011-01-01

    Roberto Gallego-Pinazo,1,2 Ana Marina Suelves-Cogollos1, Ester Francés-Muñoz,1 J María Millán,2,3 J Fernando Arevalo,4 J Luis Mullor,5 Manuel Díaz-Llopis,1,2,61Department of Ophthalmology, Hospital Universitario La Fe, Valencia, Spain; 2Centro de Investigación Biomédica en Red de Enfermedades Raras, Valencia, Spain; 3Department of Genetics, Hospital Universitario La Fe, Valencia, Spain; 4Retina and Vitreous Service, ...

  4. Intravitreal aflibercept (A-IVI) for the treatment of neovascular age-related macular degeneration (nv-AMD): one year experience

    OpenAIRE

    Papavasileiou, Evangelia; Zygoura, V; Richardson, T.; Cortis, D; Eleftheriadis, Haralabos; Jackson, Timothy Llewwllyn

    2015-01-01

    OBJECTIVE: To report the anatomical and functional results of intravitreal injections of aflibercept (Eylea) (A-IVI) for the treatment of naïve eyes with neovascular age-related macular degeneration (nv-AMD). SUBJECTS AND METHODS: This retrospective, one-center, non-comparative chart review included 26 treatment naïve eyes with nv-AMD of 26 patients (14 male) with a mean age of 80.5 (range 63-91) who had a complete follow-up of 14 months. The morphological analysis included spectral domain op...

  5. Early detection of age related macular degeneration: current status

    OpenAIRE

    Schwartz, Roy; Loewenstein, Anat

    2015-01-01

    Early diagnosis and treatment of choroidal neovascularization (CNV), a main cause of severe vision loss in age related macular degeneration (AMD), is crucial in order to preserve vision and the quality of life of patients. This review summarizes current literature on the subject of early detection of CNV, both in the clinic setting and mainly in the patient’s home. New technologies are evolving to allow for earlier detection and thus vision preservation in AMD patients.

  6. Early detection of age related macular degeneration: current status.

    Science.gov (United States)

    Schwartz, Roy; Loewenstein, Anat

    2015-01-01

    Early diagnosis and treatment of choroidal neovascularization (CNV), a main cause of severe vision loss in age related macular degeneration (AMD), is crucial in order to preserve vision and the quality of life of patients. This review summarizes current literature on the subject of early detection of CNV, both in the clinic setting and mainly in the patient's home. New technologies are evolving to allow for earlier detection and thus vision preservation in AMD patients.

  7. Results of submacular surgery in age-related macula degeneration

    OpenAIRE

    Laue, Jessica

    2010-01-01

    Due to a disruption of barrier function of the membrane Bruch and a change of the phagocities retinal pigment epithelial (rpe), exists possibility for progress of pathologist invasion of new vessels from the choroidea under the retina. On the position of the macula it will cause quick loss of central visual acuity. The most frequent cause for a choroidal neovascular membrane (CNV) is age-related macula degeneration (AMD); further causes are based on idiopathic or postinflammable reasons. ...

  8. CFH Y402H and ARMS2 A69S Polymorphisms and Oral Supplementation with Docosahexaenoic Acid in Neovascular Age-Related Macular Degeneration Patients: The NAT2 Study.

    Directory of Open Access Journals (Sweden)

    Bénédicte M J Merle

    Full Text Available Genetic susceptibility could be modified by environmental factors and may also influence differential responses to treatments for age-related macular degeneration (AMD. We investigated whether genotype could influence response to docosahexaenoic acid (DHA-supplementation in the occurrence of choroidal new vessels (CNV.The Nutritional AMD Treatment 2 (NAT2 study was a randomized, placebo-controlled, double-blind, parallel, comparative study, including 250 patients aged 55 to 85 years with early lesions of age-related maculopathy, visual acuity better than 0.4 Logarithm of Minimum Angle of Resolution units in the study eye and neovascular AMD in the fellow eye. Patients were randomized at baseline to receive either 3 daily fish-oil capsules, each containing 280 mg DHA, 90 mg EPA and 2 mg Vitamin E, or placebo.Patients carrying the risk allele (C for CFH Y402H had no statistically significant increased risk for developing CNV in the study eye (Hazard Ratio (HR=0.97; 95% Confidence Interval (CI: 0.54-1.76 for heterozygous and HR=1.29; 95%CI: 0.69-2.40 for homozygous. Patients carrying the risk allele (T for ARMS2 A69S had no statistically significant increased risk for developing CNV in the study eye (HR=1.68; 95%CI: 0.91-3.12 for heterozygous and HR=1.78; 95%CI: 0.90-3.52 for homozygous. A significant interaction was observed between CFH Y402H and DHA-supplementation (p=0.01. We showed a protective effect of DHA-supplementation among homozygous non-risk patients. Among these patients, occurrence of CNV was 38.2% in placebo group versus 16.7% in DHA group (p=0.008.These results suggest that a genetic predisposition to AMD conferred by the CFH Y402H variant limits the benefit provided by DHA supplementation.ISRCTN registry 98246501.

  9. CD36 deficiency leads to choroidal involution via COX2 down-regulation in rodents.

    Directory of Open Access Journals (Sweden)

    Marianne Houssier

    2008-02-01

    Full Text Available BACKGROUND: In the Western world, a major cause of blindness is age-related macular degeneration (AMD. Recent research in angiogenesis has furthered the understanding of choroidal neovascularization, which occurs in the "wet" form of AMD. In contrast, very little is known about the mechanisms of the predominant, "dry" form of AMD, which is characterized by retinal atrophy and choroidal involution. The aim of this study is to elucidate the possible implication of the scavenger receptor CD36 in retinal degeneration and choroidal involution, the cardinal features of the dry form of AMD. METHODS AND FINDINGS: We here show that deficiency of CD36, which participates in outer segment (OS phagocytosis by the retinal pigment epithelium (RPE in vitro, leads to significant progressive age-related photoreceptor degeneration evaluated histologically at different ages in two rodent models of CD36 invalidation in vivo (Spontaneous hypertensive rats (SHR and CD36-/- mice. Furthermore, these animals developed significant age related choroidal involution reflected in a 100%-300% increase in the avascular area of the choriocapillaries measured on vascular corrosion casts of aged animals. We also show that proangiogenic COX2 expression in RPE is stimulated by CD36 activating antibody and that CD36-deficient RPE cells from SHR rats fail to induce COX2 and subsequent vascular endothelial growth factor (VEGF expression upon OS or antibody stimulation in vitro. CD36-/- mice express reduced levels of COX2 and VEGF in vivo, and COX2-/- mice develop progressive choroidal degeneration similar to what is seen in CD36 deficiency. CONCLUSIONS: CD36 deficiency leads to choroidal involution via COX2 down-regulation in the RPE. These results show a novel molecular mechanism of choroidal degeneration, a key feature of dry AMD. These findings unveil a pathogenic process, to our knowledge previously undescribed, with important implications for the development of new therapies.

  10. Toxoplasmosis retinochoroiditis after photodynamic therapy and intravitreal triamcinolone for a supposed choroidal neovascularization: a case report Retinocoroidite toxoplásmica após terapia fotodinâmica e triancinolona intravítrea em suposta neovascularização de coróide: relato de um caso

    Directory of Open Access Journals (Sweden)

    Mário Junqueira Nóbrega

    2007-02-01

    Full Text Available The purpose is to report a complication after photodynamic therapy (PDT and intravitreal triamcinolone for a presumed choroidal neovascularization in age-related macular degeneration. Photodynamic therapy and intravitreal triamcinolone were used in an 84-year-old man with choroidal neovascularization in the left eye. Forty-five days after therapy, the patient returned with a severe necrotizing uveitis in the posterior pole and vitritis. Laboratory investigation disclosed a high anti-Toxoplasma IgG titer. Therapy with pyrimethamine, sulfadiazine and folinic acid resulted in total lesion healing although central vision was lost. Intravitreal triamcinolone may have had an influence on the exacerbation of retinochoroiditis in the posterior pole of the patient. Although rare, this complication may not be disregarded in the cases that require intraocular corticosteroids for treatment of several conditions, especially in patients who had previously suffered from toxoplasmosis infection.O objetivo é relatar complicação após terapia fotodinâmica (PDT e triancinolona intravítrea para presumida neovascularização de coróide em degeneração macular relacionada à idade. A terapia fotodinâmica e triancinolona intravítrea foram utilizados em paciente de 84 anos, do sexo masculino, com neovascularização de coróide no olho esquerdo. Quarenta e cinco dias após o tratamento, o paciente retornou com grave retinite necrosante do pólo posterior e vitreíte. Investigação laboratorial indicou alto título de IgG anti-Toxoplasma. Tratamento com pirimetamina, sulfadiazina e ácido folínico levaram à total cicatrização da lesão embora a visão central tenha sido comprometida. Conclui-se que a triancinolona intravítrea pode ter influenciado na exacerbação da retinocoroidite no pólo posterior do paciente. Embora rara, esta complicação não pode ser descartada nos casos que necessitem corticóide intra-ocular para tratamento de várias doen

  11. 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

    , and detailed retinal imaging was performed: fundus autofluorescence imaging, digital color fundoscopy, and spectral-domain optical coherence tomography. Fluorescein and indocyanine green angiography were performed in patients with suspected neovascular AMD. Visual acuity was measured in both eyes. Fresh venous...... was observed in controls with healthy eyes, but not in patients with neovascular AMD. We did not find any differences in CD200 and CD200R expression between patients with subretinal fibrosis and patients without subretinal fibrosis. CONCLUSIONS: The surface expression of CD200 on circulating CD11b+ monocytes...... was found to be increased in patients with neovascular AMD compared with controls with healthy eyes. This novel finding supports the notion that altered regulation of the inflammatory response plays an integral role in the pathogenesis of AMD. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary...

  12. Structural and Biochemical Analyses of Choroidal Thickness in Human Donor Eyes

    Science.gov (United States)

    Sohn, Elliott H.; Khanna, Aditi; Tucker, Budd A.; Abràmoff, Michael D.; Stone, Edwin M.; Mullins, Robert F.

    2014-01-01

    Purpose. The choroid plays a vital role in the health of the outer retina. While measurements of choroid using optical coherence tomography show altered thickness in aging and macular disease, detailed histopathologic and proteomic analyses are lacking. In this study we sought to evaluate biochemical differences in human donor eyes between very thin and thick choroids. Methods. One hundred forty-one eyes from 104 donors (mean age ± standard deviation, 81.5 ± 12.2) were studied. Macular sections were collected, and the distance between Bruch's membrane and the inner surface of the sclera was measured in control, early/dry age-related macular degeneration (AMD), neovascular AMD, and geographic atrophy eyes. Proteins from the RPE-choroid of eyes with thick and thin choroids were analyzed using two-dimensional electrophoresis and/or mass spectrometry. Two proteins with altered abundance were confirmed using Western blot analysis. Results. Donor eyes showed a normal distribution of thicknesses. Eyes with geographic atrophy had significantly thinner choroids than age-matched controls or early AMD eyes. Proteomic analysis showed higher levels of the serine protease SERPINA3 in thick choroids and increased levels of tissue inhibitor of metalloproteinases-3 (TIMP3) in thin choroids. Conclusions. Consistent with clinical imaging observations, geographic atrophy was associated with choroidal thinning. Biochemical data suggest an alteration in the balance between proteases and protease inhibitors in eyes that lie at the extremes of choroidal thickness. An improved understanding of the basic mechanisms associated with choroidal thinning may guide the development of new therapies for AMD. PMID:24519422

  13. Guidelines for the management of neovascular age-related macular degeneration by the European Society of Retina Specialists (EURETINA)

    DEFF Research Database (Denmark)

    Schmidt-Erfurth, Ursula; Chong, Victor; Loewenstein, Anat

    2014-01-01

    , 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...

  14. Foveal morphology affects self-perceived visual function and treatment response in neovascular age-related macular degeneration: a cohort study.

    Directory of Open Access Journals (Sweden)

    Yousif Subhi

    Full Text Available OBJECTIVES: To investigate the relationship between foveal morphology and self-perceived visual function in patients with neovascular age-related macular degeneration (AMD and whether foveal characteristics are associated with Ranibizumab treatment response on the self-perceived visual function. METHODS: This prospective cohort study included patients with newly diagnosed neovascular AMD found eligible for treatment with Ranibizumab. Foveal morphology of both eyes was assessed using spectral-domain optical coherence tomography and all patients were interviewed using the 39-item National Eye Institute Visual Function Questionnaire (VFQ. Patients were re-interviewed 3 and 12 months after initiation of treatment with Ranibizumab. We evaluated foveal morphology at baseline in relation to VFQ scores at baseline and clinically meaningful changes in VFQ after 3 and 12 months. RESULTS: VFQ scores correlated with central foveal thickness, central foveal thickness of neuroretina (CFN, foveal RPE elevation, foveal integrity of the photoreceptor inner segment/outer segment junction (IS/OS, and external limiting membrane. In a multiple linear regression model, only best-corrected visual acuity of the better eye (p<0.001 and the IS/OS status in the better eye (p = 0.012 remained significant (Adjusted R(2 = 0.418. Lower baseline VFQ and a baseline CFN within 170-270 µm in the better eye were both associated with a clinically meaningful increase in the VFQ scores after 3 and 12 months. An absent foveal IS/OS band in the better eye was associated with a clinically meaningful decrease in the VFQ scores at 12 months. CONCLUSIONS: Foveal morphology in the better eye influences the self-perceived visual function in patients with neovascular AMD and possesses a predictive value for change in the self-perceived visual function at 3 and 12 months after initiation of treatment. These findings may help clinicians provide patients more individualized information of their

  15. Joint Assessment of Intended and Unintended Effects of Medications: An Example Using Vascular Endothelial Growth Factor Inhibitors for Neovascular Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Adrian R. Levy

    2009-01-01

    Full Text Available Objective. To estimate the net health benefits of pegaptanib and ranibizumab by considering the impact of visual acuity and unintended effects (cardiovascular and hemorrhagic events on quality-of-life among persons with neovascular age-related macular degeneration. Methods. We designed a probabilistic decision-analytic model using published data. It employed 17 visual health states and three for unintended effects. We calculated incremental net health benefits by subtracting the harms of each medication from the benefit using the quality-adjusted life year (QALY. Results. In a hypothetical cohort of 1,000 75-year olds with new-onset bilateral age-related macular degeneration followed for ten years, the mean QALYs per patient is 3.7 for usual care, 4.2 for pegaptanib, and 4.3 for ranibizumab. Net benefits decline with increasing baseline rates of unintended effects. Interpretation. Net health benefits present a quantitative, potentially useful tool to assist patients and ophthalmologists in balancing the benefits and harms of interventions for age-related macular degeneration.

  16. CHOROIDAL MORPHOLOGY IN EYES WITH POLYPOIDAL CHOROIDAL VASCULOPATHY AND NORMAL OR SUBNORMAL SUBFOVEAL CHOROIDAL THICKNESS.

    Science.gov (United States)

    Lee, Won Ki; Baek, Jiwon; Dansingani, Kunal K; Lee, Jae Hyung; Freund, K Bailey

    2016-12-01

    To subsegment the choroid in patients with polypoidal choroidal vasculopathy and to determine whether the ratio of choriocapillaris/Sattler layer thickness to total choroidal thickness is decreased at sites of polypoidal pathology. Retrospective, observational, cross-sectional study. A total of 320 eyes of 305 patients with polypoidal choroidal vasculopathy were studied with optical coherence tomography and dye angiography. The ratio of choriocapillaris/Sattler layer thickness to total choroidal thickness was calculated at polypoidal lesion sites in eyes with subfoveal choroidal thickness (SFCT) ≤200 μm. Mean SFCT was 267.7 ± 118.5 μm for the entire cohort. Mean SFCT was 151.2 ± 35.0 μm in eyes with SFCT ≤200 μm (n = 124, 39%). In this subgroup, dilated Haller vessels (pachyvessels) were identified under the site of neovascular ingrowth in 117 eyes (94%). Choroidal thickness in the pachyvessel zone was greater (213.3 ± 52.2 μm) than SFCT (P thickness ratio (P choroidal thickening at sites of polypoidal disease. The choriocapillaris and Sattler layers were attenuated at these locations, but Haller vessels were markedly dilated. These changes were topographically associated with sites of neovascular ingrowth and support the classification of polypoidal choroidal vasculopathy as a pachychoroid disorder.

  17. 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

    was at baseline, 3 and 6 months negatively correlated to visual acuity (VA) (rbaseline = −0.65, r3 months = −0.60, and r6 months = −0.66 respectively, p ... reduced due to poor fixation as a large number of patients may use a fixation area of more than 5 deg2. Fixation monitoring during recording as well as interpretation of results should be performed with care, especially in patients with poor visual acuity.......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...

  18. Combined treatment of exudative age related macular degeneration with photodynamic therapy and intravitreal triamcinolone

    Directory of Open Access Journals (Sweden)

    José Mª Ruiz-Moreno

    2008-03-01

    Full Text Available José Mª Ruiz-Moreno1,2, Javier A Montero21Department of Ophthalmology, Miguel Hernández University School of Medicine, Alicante, Spain; 2Vitreo-Retinal Unit, Alicante Institute of Ophthalmology, Alicante, SpainAbstract: Choroidal neovascularization (CNV secondary to age related macular degeneration is among the leading causes of legal blindness in developed countries. Photodynamic therapy (PDT with verteporfin induces CNV closure causing little damage to healthy tissue, but the need to re-treat may lead to low final visual acuity at an unacceptable cost. The association of intravitreous triamcinolone or antiangiogenic drugs with PDT has been used in order to reduce these limitations of the therapy. The combination of PDT and intravitreous triamcinolone, its complications and outcome at one and two-year follow-up are discussed.Keywords: age related macular degeneration, choroidal neovascularization, photodynamic therapy, steroid, triamcinolone

  19. Molecular pathogenesis of retinal and choroidal vascular diseases.

    Science.gov (United States)

    Campochiaro, Peter A

    2015-11-01

    There are two major types of ocular neovascularization that affect the retina, retinal neovascularization (NV) and subretinal or choroidal NV. Retinal NV occurs in a group of diseases referred to as ischemic retinopathies in which damage to retinal vessels results in retinal ischemia. Most prevalent of these are diabetic retinopathy and retinal vein occlusions. Subretinal and choroidal NV occur in diseases of the outer retina and Bruch's membrane, the most prevalent of which is age-related macular degeneration. Numerous studies in mouse models have helped to elucidate the molecular pathogenesis underlying retinal, subretinal, and choroidal NV. There is considerable overlap because the precipitating event in each is stabilization of hypoxia inducible factor-1 (HIF-1) which leads to upregulation of several hypoxia-regulated gene products, including vascular endothelial growth factor (VEGF), angiopoietin 2, vascular endothelial-protein tyrosine phosphatase (VE-PTP), and several others. Stimulation of VEGF signaling and suppression of Tie2 by angiopoietin 2 and VE-PTP are critical for sprouting of retinal, subretinal, and choroidal NV, with perturbation of Bruch's membrane also needed for the latter. Additional HIF-1-regulated gene products cause further stimulation of the NV. It is difficult to model macular edema in animals and therefore proof-of-concept clinical trials were done and demonstrated that VEGF plays a central role and that suppression of Tie2 is also important. Neutralization of VEGF is currently the first line therapy for all of the above disease processes, but new treatments directed at some of the other molecular targets, particularly stabilization of Tie2, are likely to provide additional benefit for subretinal/choroidal NV and macular edema. In addition, the chronicity of these diseases as well as the implication of VEGF as a cause of retinal nonperfusion and progression of background diabetic retinopathy make sustained delivery approaches for VEGF

  20. Molecular Pathogenesis of Retinal and Choroidal Vascular Diseases

    Science.gov (United States)

    Campochiaro, Peter A.

    2015-01-01

    There are two major types of ocular neovascularization that affect the retina, retinal neovascularization (NV) and subretinal or choroidal NV. Retinal NV occurs in a group of diseases referred to as ischemic retinopathies in which damage to retinal vessels results in retinal ischemia. Most prevalent of these are diabetic retinopathy and retinal vein occlusions. Subretinal and choroidal NV occur in diseases of the outer retina and Bruch’s membrane, the most prevalent of which is age-related macular degeneration. Numerous studies in mouse models have helped to elucidate the molecular pathogenesis underlying retinal, subretinal, and choroidal NV. There is considerable overlap because the precipitating event in each is stabilization of hypoxia inducible factor-1 (HIF-1) which leads to upregulation of several hypoxia-regulated gene products, including vascular endothelial growth factor (VEGF), angiopoietin 2, vascular endothelial-protein tyrosine phosphatase (VE-PTP), and several others. Stimulation of VEGF signaling and suppression of Tie2 by angiopoietin 2 and VE-PTP are critical for sprouting of retinal, subretinal, and choroidal NV, with perturbation of Bruch’s membrane also needed for the latter. Additional HIF-1-regulated gene products cause further stimulation of the NV. It is difficult to model macular edema in animals and therefore proof-of-concept clinical trials were done and demonstrated that VEGF plays a central role and that suppression of Tie2 is also important. Neutralization of VEGF is currently the first line therapy for all of the above disease processes, but new treatments directed at some of the other molecular targets, particularly stabilization of Tie2, are likely to provide additional benefit for subretinal/choroidal NV and macular edema. In addition, the chronicity of these diseases as well as the implication of VEGF as a cause of retinal nonperfusion and progression of background diabetic retinopathy make sustained delivery approaches for

  1. Peripapillary subretinal neovascularization and serous macular detachment. Association with congenital optic nerve pits.

    Science.gov (United States)

    Borodic, G E; Gragoudas, E S; Edward, W O; Brockhurst, R J

    1984-02-01

    Congenital anomalous disc changes were associated with acquired macular detachment and peripapillary choroidal neovascularization in two cases. The anomalous disc changes resembled optic nerve pits. In one case, the peripapillary choroidal neovascularization was treated with argon laser photocoagulation, with subsequent reattachment of the macula and considerable improvement in the visual acuity. Although the pathogenesis of macular detachment occurring with optic nerve pits is usually not disclosed by fluorescein angiography, leakage from choroidal neovascularization can occur with this congenital defect and may contribute to the formation of a neurosensory macular detachment. If found, choroidal neovascularization may represent a remedial cause for visual loss in a condition with an otherwise poor prognosis.

  2. Device for fluorescent control and photodynamic therapy of age-related macula degeneration

    Science.gov (United States)

    Loschenov, Victor B.; Meerovich, Gennadii A.; Budzinskaya, M. V.; Ermakova, N. A.; Shevchik, S. A.; Kharnas, Sergey S.

    2004-07-01

    Age-related macula degeneration (AMD) is a wide spread disease the appearance of which leads to poor eyesight and blindness. A method of treatment is not determined until today. Traditional methods, such as laser coagulation and surgical operations are rather traumatic for eye and often bring to complications. That's why recently a photodynamic method of AMD treatment is studied. Based on photodynamic occlusion of choroidal neovascularization (CNV) with minimal injury to overlying neurosensory retina what increases the efficiency.

  3. Aging Is Not a Disease: Distinguishing Age-Related Macular Degeneration from Aging

    OpenAIRE

    Ardeljan, Daniel; Chan, Chi-Chao

    2013-01-01

    Age-related macular degeneration (AMD) is a disease of the outer retina, characterized most significantly by atrophy of photoreceptors and retinal pigment epithelium accompanied with or without choroidal neovascularization. Development of AMD has been recognized as contingent on environmental and genetic risk factors, the strongest being advanced age. In this review, we highlight pathogenic changes that destabilize ocular homeostasis and promote AMD development. With normal aging, photorecept...

  4. Combined treatment of exudative age related macular degeneration with photodynamic therapy and intravitreal triamcinolone

    OpenAIRE

    Ruiz-Moreno , Jose

    2008-01-01

    José Mª Ruiz-Moreno1,2, Javier A Montero21Department of Ophthalmology, Miguel Hernández University School of Medicine, Alicante, Spain; 2Vitreo-Retinal Unit, Alicante Institute of Ophthalmology, Alicante, SpainAbstract: Choroidal neovascularization (CNV) secondary to age related macular degeneration is among the leading causes of legal blindness in developed countries. Photodynamic therapy (PDT) with verteporfin induces CNV closure causing little damage to healt...

  5. The effect of intravitreal administration of bevacizumab on macular edema and visual acuity in age-related macular degeneration with subfoveolar choroidal neovascularisation

    Directory of Open Access Journals (Sweden)

    Ristić Dragana

    2013-01-01

    Full Text Available Background/Aim. Age-related macular degeneration (AMD is a leading cause of the loss of central visual acuity in population older than 70 years. We can distinguish wet and dry form of AMD. The aim of the study was to present our early results in treatment of the wet (neovascular form of AMD with intravitreal administration of bevacizumab. Methods. The study included 39 patients. Each patient underwent a complete ophthalmological examination, fluorescein angiography (FA and optical coherence tomography (OCT. All the patients received 1.25 mg of intravitreal bevacizumab (0.05 mL of commercial phial of Avastin®. The total of three doses was given with a one-month interval between doses. Results. Among 39 patients, 24 were women and 15 men. The average best corrected visual acuity (BCVA was improved from 0.09 before the therapy to 0.24 after the administration of all the three doses of bevacizumab (p < 0.001. The average central macular thickness (CMT measured by OCT was improved from 474 μm in the beginning to 341 μm after the administration of all the three doses of the drug (p < 0.001. There were no side effects. Conclusions. Our short-term experience indicates that intravitreal administration of three doses of bevacizumab in one-month intervals between the doses leads to a significant reduction of macular edema and improvement of BCVA in patients with neovascular AMD.

  6. Evaluation of contrast sensitivity and other visual function outcomes in neovascular age-related macular degeneration patients after treatment switch to aflibercept from ranibizumab.

    Science.gov (United States)

    Nixon, Donald R; Flinn, Nicholas Ap

    2017-01-01

    This study evaluated visual function and anatomic and vision-related quality-of-life outcomes in recalcitrant neovascular age-related macular degeneration (AMD) subjects switched to aflibercept (Eylea(®)) from ranibizumab (Lucentis(®)). In a single-center study conducted in Barrie, ON, 40 patients with persistent fluid despite previous ranibizumab treatment were switched to aflibercept with 3 consecutive monthly doses. Main outcome measure was mean change from baseline to week 12 in Pelli-Robson contrast sensitivity (CS). Secondary outcomes were mean change in best corrected visual acuity (BCVA), central retinal thickness (CRT), and National Eye Institute 25-Item Visual Function Questionnaire (NEI VFQ-25) score. A two-sided paired t-test was used in the statistical data analysis to compare the means of continuous variables. Forty-nine eyes (baseline visual acuity [VA] >6/120) were evaluated. Ranibizumab injections (mean ± standard deviation [SD] 28.2±22.1 [range 3-86]) were administered prior to treatment switch. Mean CS improved from 1.32 at baseline to 1.40 log units at week 12. VA was stable throughout. Mean CRT decreased from 354 µm at baseline to 332 µm at week 12 (-22 µm, P=0.004). Twenty-six (65%) patients experienced an overall improvement in NEI VFQ-25 score. Interestingly, a correlation was observed between improvement in log CS and CRT change (P=0.000046). Contrast sensitivity improved statistically and significantly, and CRT decreased from baseline to week 12 after a switch to aflibercept from ranibizumab. Analysis of CS as an independent outcome end point in neovascular AMD treatment switch studies may provide a more complete understanding of visual response.

  7. Long-term Results of Carbon Ion Radiation Therapy for Locally Advanced or Unfavorably Located Choroidal Melanoma: Usefulness of CT-based 2-Port Orthogonal Therapy for Reducing the Incidence of Neovascular Glaucoma

    Energy Technology Data Exchange (ETDEWEB)

    Toyama, Shingo [Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Department of Heavy Particle Therapy and Radiation Oncology, Faculty of Medicine, Saga University, Saga (Japan); Tsuji, Hiroshi, E-mail: h_tsuji@nirs.go.jp [Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Mizoguchi, Nobutaka; Nomiya, Takuma; Kamada, Tadashi [Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Tokumaru, Sunao [Department of Heavy Particle Therapy and Radiation Oncology, Faculty of Medicine, Saga University, Saga (Japan); Mizota, Atsushi [Department of Ophthalmology, Teikyo University School of Medicine, Tokyo (Japan); Ohnishi, Yoshitaka [Department of Ophthalmology, Wakayama Medical University, Wakayama (Japan); Tsujii, Hirohiko [Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan)

    2013-06-01

    Purpose: To determine the long-term results of carbon ion radiation therapy (C-ion RT) in patients with choroidal melanoma, and to assess the usefulness of CT-based 2-port irradiation in reducing the risk of neovascular glaucoma (NVG). Methods and Materials: Between January 2001 and February 2012, a total of 116 patients with locally advanced or unfavorably located choroidal melanoma received CT-based C-ion RT. Of these patients, 114 were followed up for more than 6 months and their data analyzed. The numbers of T3 and T2 patients (International Union Against Cancer [UICC], 5th edition) were 106 and 8, respectively. The total dose of C-ion RT varied from 60 to 85 GyE, with each dose given in 5 fractions. Since October 2005, 2-port therapy (51 patients) has been used in an attempt to reduce the risk of NVG. A dose-volume histogram analysis was also performed in 106 patients. Results: The median follow-up was 4.6 years (range, 0.5-10.6 years). The 5-year overall survival, cause-specific survival, local control, distant metastasis-free survival, and eye retention rates were 80.4% (95% confidence interval 89.0%-71.8%), 82.2% (90.6%-73.8%), 92.8% (98.5%-87.1%), 72.1% (81.9%-62.3%), and 92.8% (98.1%-87.5%), respectively. The overall 5-year NVG incidence rate was 35.9% (25.9%-45.9%) and that of 1-port group and 2-port group were 41.6% (29.3%-54.0%) and 13.9% (3.2%-24.6%) with statistically significant difference (P<.001). The dose-volume histogram analysis showed that the average irradiated volume of the iris-ciliary body was significantly lower in the non-NVG group than in the NVG group at all dose levels, and significantly lower in the 2-port group than in the 1-port group at high dose levels. Conclusions: The long-term results of C-ion RT for choroidal melanoma are satisfactory. CT-based 2-port C-ion RT can be used to reduce the high-dose irradiated volume of the iris-ciliary body and the resulting risk of NVG.

  8. The NEI/NCBI dbGAP database: Genotypes and haplotypes that may specifically predispose to risk of neovascular age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Miller Joan W

    2008-06-01

    Full Text Available Abstract Background To examine if the significantly associated SNPs derived from the genome wide allelic association study on the AREDS cohort at the NEI (dbGAP specifically confer risk for neovascular age-related macular degeneration (AMD. We ascertained 134 unrelated patients with AMD who had one sibling with an AREDS classification 1 or less and was past the age at which the affected sibling was diagnosed (268 subjects. Genotyping was performed by both direct sequencing and Sequenom iPLEX system technology. Single SNP analyses were conducted with McNemar's Test (both 2 × 2 and 3 × 3 tests and likelihood ratio tests (LRT. Conditional logistic regression was used to determine significant gene-gene interactions. LRT was used to determine the best fit for each genotypic model tested (additive, dominant or recessive. Results Before release of individual data, p-value information was obtained directly from the AREDS dbGAP website. Of the 35 variants with P -6 examined, 23 significantly modified risk of neovascular AMD. Many variants located in tandem on 1q32-q22 including those in CFH, CFHR4, CFHR2, CFHR5, F13B, ASPM and ZBTB were significantly associated with AMD risk. Of these variants, single SNP analysis revealed that CFH rs572515 was the most significantly associated with AMD risk (P -6. Haplotype analysis supported our findings of single SNP association, demonstrating that the most significant haplotype, GATAGTTCTC, spanning CFH, CFHR4, and CFHR2 was associated with the greatest risk of developing neovascular AMD (P -6. Other than variants on 1q32-q22, only two SNPs, rs9288410 (MAP2 on 2q34-q35 and rs2014307 (PLEKHA1/HTRA1 on 10q26 were significantly associated with AMD status (P = .03 and P -6 respectively. After controlling for smoking history, gender and age, the most significant gene-gene interaction appears to be between rs10801575 (CFH and rs2014307 (PLEKHA1/HTRA1 (P -11. The best genotypic fit for rs10801575 and rs2014307 was an

  9. Neuropilin 1 Involvement in Choroidal and Retinal Neovascularisation

    Science.gov (United States)

    Fernández-Robredo, Patricia; Sim, Dawn A.; Fruttiger, Marcus

    2017-01-01

    Purpose Inhibiting VEGF is the gold standard treatment for neovascular age-related macular degeneration (AMD). It is also effective in preventing retinal oedema and neovascularisation (NV) in diabetic retinopathy (DR) and retinal vein occlusions (RVO). Neuropilin 1 (Nrp1) is a co-receptor for VEGF and many other growth factors, and therefore a possible alternative drug target in intra ocular neovascular disease. Here we assessed choroidal and retinal NV in an inducible, endothelial specific knock out model for Nrp1. Methods Crossing Nrp1 floxed mice with Pdgfb-CreERT2 mice produced tamoxifen-inducible, endothelial specific Nrp1 knock out mice (Nrp1ΔEC) and Cre-negative, control littermates. Cre-recombinase activity was confirmed in the Ai3(RCL-EYFP) reporter strain. Animals were subjected to laser-induced CNV (532 nm) and spectral domain-optical coherence tomography (SD-OCT) was performed immediately after laser and at day 7. Fluorescein angiography (FA) evaluated leakage and postmortem lectin staining in flat mounted RPE/choroid complexes was also used to measure CNV. Furthermore, retinal neovascularisation in the oxygen induced retinopathy (OIR) model was assessed by immunohistochemistry in retinal flatmounts. Results In vivo FA, OCT and post-mortem lectin staining showed a statistically significant reduction in leakage (p<0.05), CNV volume (p<0.05) and CNV area (p<0.05) in the Nrp1ΔEC mice compared to their Cre-negative littermates. Also the OIR model showed reduced retinal NV in the mutant animals compared to wild types (p<0.001). Conclusion We have demonstrated reduced choroidal and retinal NV in animals that lack endothelial Nrp1, confirming a role of Nrp1 in those processes. Therefore, Nrp1 may be a promising drug target for neovascular diseases in the eye. PMID:28107458

  10. Spectral-domain Optical Coherence Tomography Retinal and Choroidal Thickness Metric Repeatability in Age-related Macular Degeneration

    DEFF Research Database (Denmark)

    Hanumunthadu, Daren; Ilginis, Tomas; Restori, Marie

    2016-01-01

    ) macular subfields. Center point thickness and total macular volume were also included in the analysis. Manual subfoveal choroidal thickness measurements were made by a masked observer. RESULTS: A total of 40 eyes of 40 patients were included in this analysis (mean [± standard deviation] age: 74.1 [± 7...... for the center point was 47.5 μm (95% CI 46.2-48.7 μm). Images were also reviewed for the presence of segmentation error in the central macular subfield, and after exclusion of these eyes the revised CR for this subfield was 13.7 μm (95% CI 13.3-14.1 μm). The intrasession CR of subfoveal choroidal thickness...... was 34.7 μm (95% CI 33.7-35.7 μm). CONCLUSIONS: This study suggests that a change of greater than 31 μm in Spectralis SDOCT-derived retinal thickness measurement of the central macular subfield and 35 μm in subfoveal choroidal thickness is necessary to detect true clinical change associated with disease...

  11. 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...

  12. Bilateral visual outcomes and service utilization of patients treated for 3 years with ranibizumab for neovascular age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    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

  13. Modelling Cost Effectiveness in Neovascular Age-Related Macular Degeneration: The Impact of Using Contrast Sensitivity vs. Visual Acuity.

    OpenAIRE

    Butt, T.; Patel,P J; Tufail, A; Rubin, G. S.

    2014-01-01

    The cost utility of treatments of age-related macular degeneration (AMD) is commonly assessed using health state transition models defined by levels of visual acuity. However, there is evidence that another measure of visual function, contrast sensitivity, may be better associated with utility than visual acuity. This paper investigates the difference in cost effectiveness resulting from models based on visual acuity and contrast sensitivity using the example of bevacizumab (Avastin) for neov...

  14. Broad spectrum antiangiogenic treatment for ocular neovascular diseases.

    Directory of Open Access Journals (Sweden)

    Ofra Benny

    Full Text Available UNLABELLED: 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. METHODS AND FINDINGS: 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. CONCLUSIONS: 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

  15. Comparative study between a spectral domain and a high-speed single-beam swept source OCTA system for identifying choroidal neovascularization in AMD

    Science.gov (United States)

    Told, R.; Ginner, L.; Hecht, A.; Sacu, S.; Leitgeb, R.; Pollreisz, A.; Schmidt-Erfurth, U.

    2016-12-01

    This comparative study between a SD- and SS-OCTA system for visualizing neovascular patterns in AMD, also assessed the influence of cataract on OCTA imaging. 25 eyes with active CNV (AMD) were documented by FA, ICGA and SD-OCT. Two OCTA devices were used: A custom built SS-OCTA (1050 nm, 400,000 A-scans/s, 5 × 5 mm, no image segmentation); AngioVue (OptoVue, CA, USA) SD-OCTA (840 nm, 70.000 A-scans/s, 3 × 3 mm, SSADA technology). Two retina experts graded CNV types and vascular patterns. Cataract influence on OCTA image quality was reported for the superficial retinal plexus (6 eyes). The SS-OCTA prototype showed more CNV lesions compared to the SD-OCTA system (p = 0.01). Overall sensitivity of SD- and SS-OCTA systems to detect CNV lesions was.32 and.68, respectively. The SS-OCTA system was able to detect discrete lesion characteristics better than the SD-OCTA. No significant difference was found in the ability to identify CNV in treatment-naïve eyes. There was no significant influence of cataract. The SS-OCTA prototype detected CNV-associated vascular patterns more reliably than the SD-OCTA system. This is attributed to the SS-OCTA system’s longer center wavelength and higher A-scan rate yielding higher definition and contrast of small neovascular structures. The SS-OCTA system used showed no advantage regarding cataract influence.

  16. THE MULTIFUNCTIONAL CHOROID

    Science.gov (United States)

    Nickla, Debora L.; Wallman, Josh

    2010-01-01

    The choroid of the eye is primarily a vascular structure supplying the outer retina. It has several unusual features: It contains large membrane-lined lacunae, which, at least in birds, function as part of the lymphatic drainage of the eye and which can change their volume dramatically, thereby changing the thickness of the choroid as much as four-fold over a few days (much less in primates). It contains non-vascular smooth muscle cells, especially behind the fovea, the contraction of which may thin the choroid, thereby opposing the thickening caused by expansion of the lacunae. It has intrinsic choroidal neurons, also mostly behind the central retina, which may control these muscles and may modulate choroidal blood-flow as well. These neurons receive sympathetic, parasympathetic and nitrergic innervation. The choroid has several functions: Its vasculature is the major supply for the outer retina; impairment of the flow of oxygen from choroid to retina may cause Age-Related Macular Degeneration. The choroidal blood flow, which is as great as in any other organ, may also cool and warm the retina. In addition to its vascular functions, the choroid contains secretory cells, probably involved in modulation of vascularization and in growth of the sclera. Finally, the dramatic changes in choroidal thickness move the retina forward and back, bringing the photoreceptors into the plane of focus, a function demonstrated by the thinning of the choroid that occurs when the focal plane is moved back by the wearing of negative lenses, and, conversely, by the thickening that occurs when positive lenses are worn. In addition to focusing the eye, more slowly than accommodation and more quickly than emmetropization, we argue that the choroidal thickness changes also are correlated with changes in the growth of the sclera, and hence of the eye. Because transient increases in choroidal thickness are followed by a prolonged decrease in synthesis of extracellular matrix molecules and a

  17. Comparison of Progression Rate of Retinal Pigment Epithelium Loss in Patients with Neovascular Age-Related Macular Degeneration Treated with Ranibizumab and Aflibercept

    Directory of Open Access Journals (Sweden)

    Juliana Wons

    2017-01-01

    Full Text Available Purpose. Retinal pigment epithelium (RPE loss in neovascular age-related macular degeneration (nAMD seem to have a linear progression but might be influenced by the treatment. The purpose of the study is the comparison of RPE loss over three years in patients treated with intravitreal ranibizumab to patients who were switched to aflibercept. Methods. A retrospective analysis with 96 eyes switched to aflibercept was conducted. The progression rate of RPE loss was evaluated in patients who showed atrophy one year prior to switch (n=17 or on switch date (n=19. The RPE loss was evaluated by spectral domain optical coherence tomography (SD-OCT. Further, 22 eyes from patients treated with ranibizumab were compared. Results. The median yearly progression of RPE loss after square root transformation showed no significant difference in the year prior to switch compared to the year after switch (p=0.854. In patients who received only ranibizumab, the median yearly progression of RPE loss was 0.15 mm/y, for aflibercept patients, 0.13 mm/y. This difference was not statistically significant (p=0.172. Conclusions. There seems to be a linear progression rate of RPE loss in patients treated with ranibizumab as well as in patients with aflibercept. No significant increase of progression rate was found after switch to aflibercept.

  18. Progression of study of macrophage and choroidal neovascularization%巨噬细胞与脉络膜新生血管形成研究进展

    Institute of Scientific and Technical Information of China (English)

    高小燕(综述); 何守志(审校)

    2005-01-01

    新生血管形成在各种病理状态中起重要作用,脉络膜新生血管(choroidal neovascularization,CNV)形成是老年黄斑变性(age-related macular degeneration,ARMD)的一个主要并发症,发生率至少0.6%~0.7%,是发达国家中老年人视力丧失的主要原因。CNV的生长是一个动态过程,其进展变化和巨噬细胞的浸润相关,巨噬细胞被发现存在于变薄和即将穿透的Bruch’s膜区。作者仅就近期有关巨噬细胞在CNV中的作用研究做一综述。

  19. [Age related macular degeneration].

    Science.gov (United States)

    Sayen, Alexandra; Hubert, Isabelle; Berrod, Jean-Paul

    2011-02-01

    Age-related macular degeneration (ARMD) is a multifactorial disease caused by a combination of genetic and environmental factors. It is the first cause of blindness in patients over 50 in the western world. The disease has been traditionally classified into early and late stages with dry (atrophic) and wet (neovascular) forms: neovascular form is characterized by new blood vessels development under the macula (choroidal neovascularisation) which lead to a rapid decline of vision associated with metamorphopsia and requiring an urgent ophtalmological examination. Optical coherence tomography is now one of the most important part of the examination for diagnosis and treatment. Patient with age related maculopathy should consider taking a dietary supplement such that used in AREDS. The treatment of the wet ARMD has largely beneficied since year 2006 of anti-VEGF (vascular endothelial growth factor) molecules such as ranibizumab or bevacizumab given as repeated intravitreal injections. A systematic follow up each 4 to 8 week in required for several years. There is no effective treatment at the moment for dry AMD. For patients with binocular visual acuity under 60/200 rehabilitation includes low vision specialist, vision aids and psychological support.

  20. The role of proteases and inflammatory molecules in triggering neovascular age-related macular degeneration: basic science to clinical relevance.

    Science.gov (United States)

    Balasubramanian, Sivaraman A; Krishna Kumar, Kaavya; Baird, Paul N

    2014-09-01

    Age-related macular degeneration (AMD) causes severe vision impairment in aged individuals. The health impact and cost of the disease will dramatically increase over the years, with the increase in the aging population. Currently, antivascular endothelial growth factor agents are routinely used for managing late-stage AMD, and recent data have shown that up to 15%-33% of patients do not respond to this treatment. Henceforth, there is a need to develop better treatment options. One avenue is to investigate the role proteases and inflammatory molecules might have in regulating and being regulated by vascular endothelial growth factor. Moreover, emerging data indicate that proteases and inflammatory molecules might be critical in the development and progression of AMD. This article reviews recent literature that investigates proteases and inflammatory molecules involved in the development of AMD. Gaining insights into the proteolytic and inflammatory pathways associated with the pathophysiology of AMD could enable the development of additional or alternative drug strategies for the treatment of AMD.

  1. Effects of a human VEGF antibody (Bevacizumab) on deprivation myopia and choroidal thickness in the chicken.

    Science.gov (United States)

    Mathis, Ute; Ziemssen, Focke; Schaeffel, Frank

    2014-10-01

    Vascular endothelial growth factor (VEGF) is a dimeric glycoprotein which is responsible for neovascularization and fenestrations of the choriocapillaris. In neovascular maculopathies secondary to age-related degeneration (nAMD) or pathologic myopia (PM-CNV), its inhibition by humanized antibodies is currently the most successful therapy. The choroid has an important role in maintaining retinal health and its thickness declines with age and with myopia. Since choroidal thickness depends on its perfusion rate, one would expect that anti-VEGF agents can also change choroidal thickness. We have tested the hypothesis in the chicken model, using a humanized antibody, Bevacizumab, and also studied the distribution of VEGF-A in the chicken fundal layers by immunohistochemical techniques. Even though it was raised against human VEGF, Bevacizumab had several long lasting effects in the chicken eye (1) after a single unilateral intravitreal injection of 0.5 mg, it partially suppressed the development of deprivation myopia, similarly in both eyes, (2) it completely suppressed choroidal thickening that normally occurs when eyes recover from induced myopia over a time period of about 10 days, (3) it had little effect on the choroidal thickness in eyes that had normal visual experience, (4) VEGF-A was absent in sclera, but highly expressed in the walls of choroidal blood vessels and presumed nerve fiber bundles, as well as in retinal photoreceptors and cells of the inner and outer nuclear layer. One day after the injection of Bevacizumab, the immunoreactivity against VEGF-A had largely disappeared. In conclusion, Bevacizumab is similary effective in human and chicken tissue, has similar time constants (few days), has almost symmetrical effects on myopia in both eyes even after monocular application, and fully suppresses choroidal thickening that normally occurs during recovery from deprivation myopia. The mechanisms by which Bevacizumab acts on the choroidal thickness are

  2. Segmentation error and macular thickness measurements obtained with spectral-domain optical coherence tomography devices in neovascular age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Moosang Kim

    2013-01-01

    Full Text Available Purpose: To evaluate frequency and severity of segmentation errors of two spectral-domain optical coherence tomography (SD-OCT devices and error effect on central macular thickness (CMT measurements. Materials and Methods: Twenty-seven eyes of 25 patients with neovascular age-related macular degeneration, examined using the Cirrus HD-OCT and Spectralis HRA + OCT, were retrospectively reviewed. Macular cube 512 × 128 and 5-line raster scans were performed with the Cirrus and 512 × 25 volume scans with the Spectralis. Frequency and severity of segmentation errors were compared between scans. Results: Segmentation error frequency was 47.4% (baseline, 40.7% (1 month, 40.7% (2 months, and 48.1% (6 months for the Cirrus, and 59.3%, 62.2%, 57.8%, and 63.7%, respectively, for the Spectralis, differing significantly between devices at all examinations (P < 0.05, except at baseline. Average error score was 1.21 ± 1.65 (baseline, 0.79 ± 1.18 (1 month, 0.74 ± 1.12 (2 months, and 0.96 ± 1.11 (6 months for the Cirrus, and 1.73 ± 1.50, 1.54 ± 1.35, 1.38 ± 1.40, and 1.49 ± 1.30, respectively, for the Spectralis, differing significantly at 1 month and 2 months (P < 0.02. Automated and manual CMT measurements by the Spectralis were larger than those by the Cirrus. Conclusions: The Cirrus HD-OCT had a lower frequency and severity of segmentation error than the Spectralis HRA + OCT. SD-OCT error should be considered when evaluating retinal thickness.

  3. Switching to aflibercept among patients with treatment-resistant neovascular age-related macular degeneration: a systematic review with meta-analysis

    Science.gov (United States)

    Spooner, Kimberly; Hong, Thomas; Wijeyakumar, Wijeyanthy; Chang, Andrew A

    2017-01-01

    Purpose To systematically review anatomical and functional outcomes subsequent to switching from bevacizumab/ranibizumab to aflibercept monotherapy in patients with treatment-resistant neovascular age-related macular degeneration (nAMD). Design Systematic review and meta-analysis. Methods Medline, PubMed, Embase, and Cochrane databases were searched up to July 2016 for available scientific literature which met inclusion criteria. Eligible studies reported visual and anatomical outcomes with at least 6 months of follow-up among patients with nAMD and persistent or resistant exudative fluid despite previous anti-vascular endothelial growth factor (VEGF) therapy (bevacizumab and/or ranibizumab) and were switched to aflibercept monotherapy. Mean changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were pooled using random-effects models with 95% confidence intervals (CIs). Results Of 82 papers reviewed, 28 studies met inclusion criteria of this review. Pooled results showed a small mean improvement in BCVA at 6 and 12 months following switching (1.11 letters, 95% CI −0.25 to 2.46, P=0.17 and 0.63 letters, 95% CI −0.26 to 1.52, P=0.17, respectively). There was a significant improvement in mean CRT following switching (−61.90 µm, 95% CI −77.10 to −46.80, P<0.001 and −50.00 µm, 95% CI −63.20 to −36.80, P<0.001 at 6 and 12 months, respectively). Conclusion Pooled analysis demonstrated significantly improved anatomical outcomes; however, visual function remained stable, having a comparable effect to other anti-VEGF agents in preservation of vision. These patients had poorly responsive chronic disease with limited potential for visual recovery. Switching to aflibercept with frequent monitoring may be a suitable option for patients who have developed treatment resistance.

  4. Regulation of signaling events involved in the pathophysiology of neovascular AMD.

    Science.gov (United States)

    Wang, Haibo; Hartnett, M Elizabeth

    2016-01-01

    Neovascular age-related macular degeneration (AMD) is a complex disease in which an individual's genetic predisposition is affected by aging and environmental stresses, which trigger signaling pathways involving inflammation, oxidation, and/or angiogenesis in the RPE cells and choroidal endothelial cells (CECs), to lead to vision loss from choroidal neovascularization. Antiangiogenic therapies have greatly improved clinical outcomes in the last decade; however, vision improves in less than half of patients treated for neovascular AMD, and treatments remain inadequate for atrophic AMD. Many studies focus on genetic predisposition or the association of outcomes in trials of human neovascular AMD but are unable to evaluate the effects between different cell types involved in AMD and the signaling events that take place to cause pathologic biologic events. This manuscript complements other reviews in that it describes what is known generally in human AMD studies and clinical trials testing methods to inhibit vascular endothelial growth factor (VEGF inhibitors) and presents pathologic signaling events that develop in two important cell types, the RPE cells and the CECs, when stimulated by stresses or placed into conditions similar to what is currently understood to occur in neovascular AMD. This manuscript complements other reviews by discussing signaling events that are activated by cell-cell or cell-matrix interactions. These considerations are particularly important when considering growth factors, such as VEGF, which are important in physiologic and pathologic processes, or GTPases that are present but active only if GTP bound. In either case, it is essential to understand the role of signaling activation to distinguish what is pathologic from what is physiologic. Particularly important is the essential role of activated Rac1 in CEC transmigration of the RPE monolayer, an important step in blindness associated with neovascular AMD. Other concepts discussed include

  5. Switching to aflibercept among patients with treatment-resistant neovascular age-related macular degeneration: a systematic review with meta-analysis

    Directory of Open Access Journals (Sweden)

    Spooner K

    2017-01-01

    Full Text Available Kimberly Spooner,1–3 Thomas Hong,1,2 Wijeyanthy Wijeyakumar,1–3 Andrew A Chang1–3 1Sydney Retina Clinic & Day Surgery, 2Sydney Institute of Vision Science, Sydney, 3Save Sight Institute, Department of Ophthalmology, University of Sydney, Camperdown, NSW, Australia Purpose: To systematically review anatomical and functional outcomes subsequent to switching from bevacizumab/ranibizumab to aflibercept monotherapy in patients with treatment-resistant neovascular age-related macular degeneration (nAMD. Design: Systematic review and meta-analysis. Methods: Medline, PubMed, Embase, and Cochrane databases were searched up to July 2016 for available scientific literature which met inclusion criteria. Eligible studies reported visual and anatomical outcomes with at least 6 months of follow-up among patients with nAMD and persistent or resistant exudative fluid despite previous anti-vascular endothelial growth factor (VEGF therapy (bevacizumab and/or ranibizumab and were switched to aflibercept monotherapy. Mean changes in best-corrected visual acuity (BCVA and central retinal thickness (CRT were pooled using random-effects models with 95% confidence intervals (CIs. Results: Of 82 papers reviewed, 28 studies met inclusion criteria of this review. Pooled results showed a small mean improvement in BCVA at 6 and 12 months following switching (1.11 letters, 95% CI -0.25 to 2.46, P=0.17 and 0.63 letters, 95% CI -0.26 to 1.52, P=0.17, respectively. There was a significant improvement in mean CRT following switching (-61.90 µm, 95% CI -77.10 to -46.80, P<0.001 and -50.00 µm, 95% CI -63.20 to -36.80, P<0.001 at 6 and 12 months, respectively. Conclusion: Pooled analysis demonstrated significantly improved anatomical outcomes; however, visual function remained stable, having a comparable effect to other anti-VEGF agents in preservation of vision. These patients had poorly responsive chronic disease with limited potential for visual recovery. Switching to

  6. Choroidal osteoma - case reports.

    Science.gov (United States)

    Khan, N; Rahman, N A; Uddin, M S

    2014-07-01

    Choroidal osteoma is a rare disease. In this article four case histories were described. All were female and young patient. One patient had bilateral and other three had unilateral involvement. They had no family history. One patient reported at eye department in Bangabandhu Sheikh Mujib Medical University (BSMMU) and the other three patients reported in Bangladesh Eye Hospital. Choroidal osteoma is a benign tumor. It is diagnosed by fundoscopy, ocular B-scan ultrasonography, x-ray orbit, FFA, OCT and CT-scan of orbit. Most patients do not require treatment. Hemorrhage on the lesion suggests the presence of sub-retinal neovascularization which are typically treated with laser or intra-vitreal anti-VEGF.

  7. 巨噬细胞极化与脉络膜新生血管形成的相关性研究现状与进展%The status and progress of relationship between macrophages polarization and choroidal neovascularization

    Institute of Scientific and Technical Information of China (English)

    张鹏飞; 孙晓东

    2016-01-01

    巨噬细胞是非特异性免疫反应的主要效应细胞,极化的巨噬细胞在炎症反应、损伤修复、血管生成等病理过程中扮演了重要角色.根据其极化方式,巨噬细胞分为经典活化型(M1型)和选择性活化型(M2型).M1型抑制新生血管形成,M2型促进新生血管形成.因此,调控脉络膜新生血管(CNV)的生长主要取决于M1型/M2型的比例.在视网膜老化和损伤的微环境下,巨噬细胞极化成促血管纤维生成的M2型,产生包括血管内皮生长因子(VEGF)在内的多种促血管生成因子,启动并推进新生血管和纤维瘢痕的形成.调控巨噬细胞极化有望从源头上控制促血管生成因子的生成及由此触发的CNV;针对巨噬细胞极化的靶向治疗,可以协同抗VEGF药物治疗,为CNV患者的治疗提供新的选择.%Macrophages are major effecter cells of nonspecific immune response,the polarization of which plays a great role in inflammation,repairing and angiogenesis.According to functional phenotypes,macrophages can be polarized to classically activated type (M1),which could promote angiogenesis,and alternatively activated type (M2),which could inhibit angiogenesis.The proportion of M1/M2 could modulate the growth of choroidal neovascularization (CNV).Under the conditions of aging and injury within the retina,macrophages may polarize to M2,which could generate several proangiogenic factors,initiating and promoting the formation of angiogenesis and fibrous scar.Therefore,regulation of macrophage polarization is expected to inhibit angiogenesis and provide new insight for treatment of CNV.

  8. A Retrospective Study of Ranibizumab Treatment Regimens for Neovascular Age-Related Macular Degeneration (nAMD) in Australia and the United Kingdom.

    Science.gov (United States)

    Johnston, Robert L; Carius, Hans-Joachim; Skelly, Adrian; Ferreira, Alberto; Milnes, Fran; Mitchell, Paul

    2017-03-01

    Neovascular age-related macular degeneration (nAMD) is the leading cause of vision loss among persons aged 65 years and older. Anti-vascular endothelial growth factor (anti-VEGF) treatment is the recommended standard of care. The current study compares the effectiveness of ranibizumab in routine clinical practice in two countries that generally apply two different treatment regimens, treat-and-extend (T&E) in Australia or pro re nata (PRN) in the UK. This retrospective, comparative, non-randomised cohort study is based on patients' data from electronic medical record (EMR) databases in Australia and the UK. Treatment regimens were defined based on location, with Australia as a proxy for analysing T&E and UK as a proxy for analysing PRN. The study included patients with a diagnosis of nAMD who started treatment with ranibizumab between January 2009 and July 2014. A total of 647 eyes of 570 patients in Australia and 3187 eyes of 2755 patients in the UK with complete 12-months follow-up were analysed. Baseline patient characteristics were comparable between the two cohorts. After 1 year of treatment, T&E-treated eyes achieved higher mean (±SE) visual acuity (VA) gains (5.00 ± 0.54 letters [95% confidence interval (CI) 3.93-6.06]) than PRN-treated eyes [3.04 ± 0.24 letters (95% CI 2.57-3.51); difference in means 2.07 ± 0.69 (95% CI 0.73-3.41), p < 0.001]. Non-inferiority of T&E compared to PRN was concluded based on the change in mean visual acuity gains at 12 months. Over the 12-month follow-up, T&E-treated eyes received a higher mean [±standard deviation (SD)] number of injections (9.29 ± 2.43) than PRN-treated eyes (6.04 ± 2.19) (p < 0.0001). Australian patients had a lower mean (±SD) number of total clinic visits (10.29 ± 2.90) than UK patients (11.47 ± 2.93) (p < 0.0001). The higher injection frequency in the T&E cohort may account for the trend toward improved vision. Novartis Pharma AG, Basel, Switzerland.

  9. Fluorescent antibody labeling for experimental choroidal neovascularization in mice%荧光抗体标记法在小鼠脉络膜新生血管中的应用

    Institute of Scientific and Technical Information of China (English)

    顾丽萍; 陈莉; 陈辉; 庹旌生; 高小伟

    2011-01-01

    背景 脉络膜新生血管(CNV)是导致多种眼底疾病视力损害的主要原因,准确建立CNV模型对于其实验和临床研究具有重要的意义,但目前尚无一种可重复且可靠的评估CNV模型及其有效治疗的方法.目的 探讨荧光抗体标记法在定性和定量评价氪激光诱导的小鼠CNV中的应用价值.方法 选取15只雄性SPF级 C57BL/6J小鼠,用氪激光(波长为647.1nm)视网膜光凝的方式建立CNV模型.分别于光凝后5min,4、7、14 及28d随机选取3只模型小鼠行眼底照相和荧光素眼底血管造影(FFA)检查.摘除眼球行脉络膜铺片,用荧光抗体(DAPI、isolectin-B4及phalloidin)分别标记光凝区域的细胞核、内皮细胞和肌动蛋白.用Image pro plus 6.0软件测量CNV面积.结果 FFA和脉络膜铺片检查结果显示激光光凝后5min及4d无CNV形成,光凝后7d开始出现CNV.光凝后7、14、28d有荧光素渗漏的光凝斑的百分率分别为76.47%(26/34)、81.81%(18/22)和50.00%(5/10).脉络膜铺片后荧光显微镜检测结果显示,在正常的未光凝区域,视网膜色素上皮(RPE)细胞呈均匀一致的六边形排列;光凝后5min,在光凝部位可检测到一个环形荧光素缺损区,表明脉络膜-Bruch膜-RPE复合体已被破坏;光凝后4d出现一些细胞碎片以及核碎片,Bruch膜破损处可见自发荧光环.光凝后7d时,激光损伤区出现界限清楚的CNV网,并持续到28d.7、14及28d时根据脉络膜铺片所测得的CNV面积分别为(7.99±0.42)×103、(16.89±8.77)×103、(14.37±4.02)×103μm2,差异有统计学意义(F=17.340,P=0.000).光凝后14d和28d脉络膜铺片上CNV面积相差不大,但与7d时相比面积均明显增加(q=16.46、q=15.54,P<0.01).结论 荧光抗体标记法不仅能很好地显示氪激光诱导的小鼠实验性CNV及其形态,而且能测定CNV的面积,为抗新生血管药物应用的疗效研究提供依据.%Background Choroidal neovascularization (CNV) is a main cause of visual

  10. Bietti crystalline dystrophy and choroidal neovascularisation.

    Science.gov (United States)

    Gupta, B; Parvizi, S; Mohamed, M D

    2011-02-01

    Bietti crystalline dystrophy is a rare autosomal recessive condition characterised by the presence of crystals in the retina and is followed by retinal and choroidal degeneration. We present a novel finding of juxtafoveal choroidal neovascularisation in Bietti crystalline dystrophy and demonstrate a spectral domain optical coherence tomography image of this disorder.

  11. A randomised, double-masked phase III/IV study of the efficacy and safety of Avastin® (Bevacizumab intravitreal injections compared to standard therapy in subjects with choroidal neovascularisation secondary to age-related macular degeneration: clinical trial design

    Directory of Open Access Journals (Sweden)

    Bunce Catey

    2008-10-01

    Full Text Available Abstract Background The management of neovascular age-related macular degeneration (nAMD has been transformed by the introduction of agents delivered by intravitreal injection which block the action of vascular endothelial growth factor-A (anti-VEGF agents. One such agent in widespread use is bevacizumab which was initially developed for use in oncology. Most of the evidence supporting the use of bevacizumab for nAMD has come from interventional case series and this clinical trial was initiated because of the increasing and widespread use of this agent in the treatment of nAMD (an off-label indication despite a lack of definitive unbiased safety and efficacy data. Methods and design The Avastin® (bevacizumab for choroidal neovascularisation (ABC trial is a double-masked randomised controlled trial comparing intravitreal bevacizumab injections to standard therapy in the treatment of nAMD. Patients are randomised to intravitreal bevacizumab or standard therapy available at the time of trial initiation (verteporfin photodynamic therapy, intravitreal pegaptanib or sham treatment. Ranibizumab treatment was not included in the control arm as it had not been licensed for use at the start of recruitment for this trial. The primary outcome is the proportion of patients gaining ≥ 15 letters of visual acuity at 1 year and secondary outcomes include the proportion of patients with stable vision and mean visual acuity change. Discussion The ABC Trial is the first double-masked randomised control trial to investigate the efficacy and safety of intravitreal bevacizumab in the treatment of nAMD. This trial fully recruited in November 2007 and results should be available in early 2009. Important design issues for this clinical trial include (a defining the control group (b use of gain in vision as primary efficacy end-point and (c use of pro re nata treatment using intravitreal bevacizumab rather than continuous therapy. Trial registration Current controlled

  12. Swept Source OCT Angiography of Neovascular Macular Telangiectasia Type 2

    Science.gov (United States)

    Zhang, Qinqin; Wang, Ruikang K.; Chen, Chieh-Li; Legarreta, Andrew D.; Durbin, Mary K.; An, Lin; Sharma, Utkarsh; Stetson, Paul F.; Legarreta, John E.; Roisman, Luiz; Gregori, Giovanni; Rosenfeld, Philip J.

    2015-01-01

    Objective To image subretinal neovascularization in proliferative macular telangiectasia type 2 (MacTel2) using swept source optical coherence tomography based microangiography (OMAG). Study Design Patients with MacTel2 were enrolled in a prospective, observational study known as the MacTel Project and evaluated using a high-speed 1050nm swept-source OCT (SS-OCT) prototype system. The OMAG algorithm generated en face flow images from three retinal layers, as well as the region bounded by the outer retina and Bruch’s membrane, the choriocapillaris, and the remaining choroidal vasculature. The en face OMAG images were compared to images from fluorescein angiography (FA) and indocyanine green angiography (ICGA). Results Three eyes with neovascular MacTel2 were imaged. The neovascularization was best identified from the en face OMAG images that included a layer between the outer retinal boundary and Bruch’s membrane. OMAG images identified these abnormal vessels better than FA and were comparable to the images obtained using ICGA. In all three cases, OMAG identified choroidal vessels communicating with the neovascularization, and these choroidal vessels were evident in the two cases with ICGA imaging. In one case, monthly injections of bevacizumab reduced the microvascular complexity of the neovascularization, as well as the telangiectatic changes within the retinal microvasculature. In another case, less frequent bevacizumab therapy was associated with growth of the subretinal neovascular complex. Conclusions OMAG imaging provided detailed, depth-resolved information about subretinal neovascularization in MacTel2 eyes demonstrating superiority to FA imaging and similarities to ICGA imaging for documenting the retinal microvascular changes, the size and extent of the neovascular complex, the communications between the neovascular complex and the choroidal circulation, and the response to monthly bevacizumab therapy. PMID:26457402

  13. Choroidal neovascularization and angioid streaks in pseudoxanthoma elasticum%弹性假黄瘤的脉络膜新生血管和血管样条纹症

    Institute of Scientific and Technical Information of China (English)

    Melisa Nika; Cagri G Besirli

    2011-01-01

    creases. Pathologic examination of skin biopsy confirmed the diagnosis of PXE, showing calcium deposition and fragmented, clumped elastic fibers in the deep reticular dermis. She responded well to intravitreal bevacizumab injections and visual acuity improved to 20/25 OD. Preventative care was emphasized and the patient was referred to cardiology, gastroenterology and human genetics for counseling. CONCLUSION: PXE is a multisystem disorder affecting the dermatologic, ocular, and cardiovascular systems. Ophthalmic findings of angioid streaks and choroidal neovascularization in the presence of stereotypical skin changes and prominent mental creases should prompt evaluation for PXE.

  14. Clinical applications of choroidal imaging technologies

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    Jay Chhablani

    2015-01-01

    Full Text Available Choroid supplies the major blood supply to the eye, especially the outer retinal structures. Its understanding has significantly improved with the advent of advanced imaging modalities such as enhanced depth imaging technique and the newer swept source optical coherence tomography. Recent literature reports the findings of choroidal changes, quantitative as well as qualitative, in various chorioretinal disorders. This review article describes applications of choroidal imaging in the management of common diseases such as age-related macular degeneration, high myopia, central serous chorioretinopathy, chorioretinal inflammatory diseases, and tumors. This article briefly discusses future directions in choroidal imaging including angiography.

  15. Age-related macular degeneration: beyond anti-angiogenesis.

    Science.gov (United States)

    Kent, David L

    2014-01-06

    Recently, anti-vascular endothelial growth factor therapies for neovascular age-related macular degeneration have been developed. These agents, originally developed for their anti-angiogenic mechanism of action, probably also work through an anti-permeability effect in preventing or reducing the amount of leakage from submacular neovascular tissue. Other treatment modalities include laser photocoagulation, photodynamic therapy with verteporfin, and submacular surgery. In reality, these latter treatments can be similarly categorized as anti-angiogenic because their sole aim is destroying or removing choroidal neovascularization (CNV). At the cellular level, CNV resembles stereotypical tissue repair that consists of several matricellular components in addition to neovascularization. In the retina, the clinical term CNV is a misnomer since the term may more appropriately be referred to as aberrant submacular repair. Furthermore, CNV raises a therapeutic conundrum: To complete or correct any reparative process in the body, angiogenesis becomes an essential component. Anti-angiogenic therapy, in all its guises, arrests repair and causes the hypoxic environment to persist, thus fueling pro-angiogenesis and further development of CNV as a component of aberrant repair. However, we realize that anti-vascular endothelial growth factor therapy preserves vision in patients with age-related macular degeneration, albeit temporarily and therefore, repeated treatment is needed. More importantly, however, anti-angiogenic therapy demonstrates that we can at the very least tolerate neovascular tissue beneath the macula and preserve vision in contrast to our historical approach of total vascular destruction. In this clinical scenario, it may be possible to look beyond anti-angiogenesis if our goal is facilitating submacular repair without destroying the neurosensory retina. Thus, in this situation of neovascular tolerance, it may be timely to consider treatments that facilitate

  16. The Choroid and Optical Coherence Tomography

    Directory of Open Access Journals (Sweden)

    Taha Sezer

    2016-01-01

    Full Text Available The choroid is the most vascular tissue in the eye and it plays an important role in the pathophysiology of various common chorioretinal diseases such as central serous retinopathy, age-related macular degeneration and degenerative myopia. Quantitative assessment of the choroid has been quite challenging with traditional imaging modalities such as indocyanine green angiography and ultrasonography due to limited resolution and repeatability. With the advent of optical coherence tomography (OCT technology, detailed visualization of the choroid in vivo is now possible. Measurements of choroidal thickness have also enabled new directions in research to study normal and pathological processes within the choroid. The aim of the present study is to review the current literature on choroidal imaging using OCT

  17. The Choroid and Optical Coherence Tomography

    Science.gov (United States)

    Sezer, Taha; Altınışık, Muhammet; Koytak, İbrahim Arif; Özdemir, Mehmet Hakan

    2016-01-01

    The choroid is the most vascular tissue in the eye and it plays an important role in the pathophysiology of various common chorioretinal diseases such as central serous retinopathy, age-related macular degeneration and degenerative myopia. Quantitative assessment of the choroid has been quite challenging with traditional imaging modalities such as indocyanine green angiography and ultrasonography due to limited resolution and repeatability. With the advent of optical coherence tomography (OCT) technology, detailed visualization of the choroid in vivo is now possible. Measurements of choroidal thickness have also enabled new directions in research to study normal and pathological processes within the choroid. The aim of the present study is to review the current literature on choroidal imaging using OCT. PMID:27800255

  18. Genetics of immunological and inflammatory components in age-related macular degeneration.

    Science.gov (United States)

    Tuo, Jingsheng; Grob, Seanna; Zhang, Kang; Chan, Chi-Chao

    2012-02-01

    Age-related macular degeneration (AMD), affecting 30 to 50 million elder individuals worldwide, is a disease affecting the macular retina and choroid that can lead to irreversible central vision loss and blindness. Recent findings support a role for immunologic processes in AMD pathogenesis, including generation of inflammatory related molecules in the Bruch's membrane, recruitment of macrophages, complement activation, microglial activation and accumulation in the macular lesions. Pro-inflammatory effects of chronic inflammation and oxidative stress can result in abnormal retinal pigment epithelium, photoreceptor atrophy and choroidal neovascularization. The associations of immunological and inflammatory genes, in particular the genes related to innate immunity with AMD support the involvement of various immunological pathways in the AMD pathogenesis. We review the literature on the involvements of inflammatory genes in AMD, highlight recent genetic discoveries, and discuss the potential application of such knowledge in the management of patients with AMD.

  19. The past, present, and future of exudative age-related macular degeneration treatment

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    Yoreh Barak

    2012-01-01

    Full Text Available Treatment of exudative age-related macular degeneration has been revolutionized within the last 6 years with the introduction of vascular endothelial growth factor neutralizing agents. Previously popular "destructive treatments," such as laser photocoagulation and photodynamic treatment have either been abandoned or used as an adjunct to pharmacotherapy. Despite the increase in vision after antivascular endothelial growth factor (VEGF agents, they require repetitive and costly intravitreal injections that also carry the inherit risks of infection, retinal tears, and detachment. Several new and more potent VEGF inhibitors are at different stages of development. The goal of evolving pharmacotherapy is to preserve the therapeutic effect while reducing or eliminating the discomfort of intravitreal drug delivery, as well as identify new therapeutic targets. Complement inhibitors, immunomodulators, integrin inhibitors are a few of the new class of drugs that are expected to be in our armamentarium soon. Current medications act to decrease leakage through abnormal subretinal choroidal vasculature and promote involution. However, these medications are only effective in treating the active stage of the choroidal neovascular membrane. Restoration of vision of a large number of patients with involuted choroidal neovascular membranes is warranted. For this purpose, tissue engineering techniques have been employed to reconstruct the subretinal anatomy. Discovery of biomarkers, pharmacogenetics, and very specific targeting holds the promise of increased potency and safety in the future.

  20. Use of intravitreal injection of triamcinolone acetonide in the treatment of age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Gopal Lekha

    2007-01-01

    Full Text Available Age-related macular degeneration (AMD is now considered an important and leading cause of blindness among elderly patients in developed and developing countries. AMD has two forms, dry and wet; both can lead to visual loss. However, occurrence of subfoveal choroidal neovascular (CNV membrane in the wet form results in severe visual impairment. Treatment options for choroidal neovascularization are available in order to maintain and in some cases improve vision. Photodynamic therapy (PDT has been used to treat both classic and occult membranes. It has known to cause choroidal hypoperfusion and production of vascular endothelial growth factor. Intravitreal steroid can possibly reduce the damage caused due to these undesirable effects. In the recent past, intravitreal injection of triamcinolone acetonide (IVTA has been used extensively as an adjunct to PDT in AMD in order to reduce the number of PDT sessions and evaluate possible beneficial effects on vision. This article reviews the pharmacological attributes of triamcinolone, available evidence of its use as monotherapy or combination therapy to treat AMD, ocular side-effects thereof and ongoing clinical trials on IVTA.

  1. [Macular serpiginous choroiditis complicated by macular hole].

    Science.gov (United States)

    Brănişteanu, D; Moraru, Andreea

    2014-01-01

    Macular serpiginouschoroiditis is a rare variant of serpiginous choroiditis characterized by a severe recurrent inflammation of both central choroid and retinal pigment epithelium. Visual prognosis is severe due to subsequent distruction of retinal structures. Permanent central visual loss is the consequence of retinal pigment epithelium hyper or hypoplasia and/or subretinal neovascularization leading to fibrous scarring. This article reports the unusual case of rapid development of a macular hole soon after the onset of characteristic clinical features. Despite anti-inflammatory treatment and successful macular hole surgery the visual function remained significantly impaired by secondary central retinal pigment epithelium changes.

  2. [Bilateral choroidal osteoma--a case report].

    Science.gov (United States)

    Jędrychowska-Jamborska, Justyna; Kulig-Stochmal, Agnieszka; Markiewicz, Anna; Jakubowska, Barbara; Romanowska-Dixon, Bożena

    2014-01-01

    Choroidal osteoma is a an extremely rare (especially located bilaterally), benign, intraocular tumor, the type of choristoma. It occurs between 2-3 decades of life, women are particularly vulnerable. The main complication in 1/3 cases is a subretinal neovascularization which may cause bleeding. The gradually progressive decalcification develops within the tumour over time, which causes atrophy of the retinal pigment epithelium and Bruch's membrane deformity. The article presents a case of a 26-year-old woman with bilateral choroidal osteoma complicated by subretinal hemorrhage; the diagnosis was based on clinical examination (biomicroscopy and indirect ophthalmoscopy) as well as specialised tests including: ultrasonography, optical coherence tomography, and fluorescein angiography.

  3. IL-23-independent induction of IL-17 from γδT cells and innate lymphoid cells promotes experimental intraocular neovascularization.

    Science.gov (United States)

    Hasegawa, Eiichi; Sonoda, Koh-Hei; Shichita, Takashi; Morita, Rimpei; Sekiya, Takashi; Kimura, Akihiro; Oshima, Yuji; Takeda, Atsunobu; Yoshimura, Takeru; Yoshida, Shigeo; Ishibashi, Tatsuro; Yoshimura, Akihiko

    2013-02-15

    Choroidal neovascularization (CNV) is a characteristic of age-related macular degeneration. Genome-wide association studies have provided evidence that the immune system is involved in the pathogenesis of age-related macular degeneration; however, the role of inflammatory cytokines in CNV has not been established. In this study, we demonstrated that IL-17 had a strong potential for promoting neovascularization in a vascular endothelial growth factor-independent manner in laser-induced experimental CNV in mice. Infiltrated γδT cells and Thy-1(+) innate lymphoid cells, but not Th17 cells, were the main sources of IL-17 in injured eyes. IL-23 was dispensable for IL-17 induction in the eye. Instead, we found that IL-1β and high-mobility group box 1 strongly promoted IL-17 expression by γδT cells. Suppression of IL-1β and high-mobility group box 1, as well as depletion of γδT cells, reduced IL-17 levels and ameliorated experimental CNV. Our findings suggest the existence of a novel inflammatory cytokine network that promotes neovascularization in the eye.

  4. ROCK-Isoform-Specific Polarization of Macrophages Associated with Age-Related Macular Degeneration

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    Souska Zandi

    2015-02-01

    Full Text Available Age is a major risk factor in age-related macular degeneration (AMD, but the underlying cause is unknown. We find increased Rho-associated kinase (ROCK signaling and M2 characteristics in eyes of aged mice, revealing immune changes in aging. ROCK isoforms determine macrophage polarization into M1 and M2 subtypes. M2-like macrophages accumulated in AMD, but not in normal eyes, suggesting that these macrophages may be linked to macular degeneration. M2 macrophages injected into the mouse eye exacerbated choroidal neovascular lesions, while M1 macrophages ameliorated them, supporting a causal role for macrophage subtypes in AMD. Selective ROCK2 inhibition with a small molecule decreased M2-like macrophages and choroidal neovascularization. ROCK2 inhibition upregulated M1 markers without affecting macrophage recruitment, underlining the plasticity of these macrophages. These results reveal age-induced innate immune imbalance as underlying AMD pathogenesis. Targeting macrophage plasticity opens up new possibilities for more effective AMD treatment.

  5. The Choroid and Optical Coherence Tomography

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    Taha Sezer; Muhammet Altınışık; İbrahim Arif Koytak

    2016-01-01

    The choroid is the most vascular tissue in the eye and it plays an important role in the pathophysiology of various common chorioretinal diseases such as central serous retinopathy, age-related macular degeneration and degenerative myopia. Quantitative assessment of the choroid has been quite challenging with traditional imaging modalities such as indocyanine green angiography and ultrasonography due to limited resolution and repeatability. With the advent of optical coherence tomography (OCT...

  6. A 2-Year, Phase IV, Multicentre, Observational Study of Ranibizumab 0.5 mg in Patients with Neovascular Age-Related Macular Degeneration in Routine Clinical Practice: The EPICOHORT Study

    Directory of Open Access Journals (Sweden)

    Sergio Pagliarini

    2014-01-01

    Full Text Available Purpose. To assess the safety profile of ranibizumab 0.5 mg in patients with neovascular age-related macular degeneration (nAMD in routine clinical practice. Methods. This 2-year, multicentre, observational study was conducted to capture real-world early practice and outcomes across Europe, shortly after European licensing of ranibizumab for nAMD. Being observational in nature, the study did not impose diagnostic/therapeutic interventions/visit schedule. Patients were to be treated as per the EU summary of product characteristics (SmPC in effect during the study. Key outcome measures were incidence of selected adverse events (AEs, treatment exposure, bilateral treatment, compliance to the EU SmPC, and best-corrected visual acuity (BCVA over 2 years. Results. 755 of 770 patients received treatment. Ranibizumab was generally well tolerated with low incidence of selected AEs (0%–1.9%. Patients received 6.2 (mean injections and 133 patients received bilateral treatment over 2 years. Protocol deviation to treatment compliance was reported in majority of patients. The observed decline in mean BCVA (Month 12, +1.5; Month 24, –1.3 letters may be associated with undertreatment as suggested by BCVA subgroup analysis. Conclusion. The EPICOHORT study conducted in routine clinical practice reinforces the well-established safety profile of ranibizumab in nAMD. In early European practice it appeared that the nAMD patients were undertreated.

  7. The role of vascular endothelial growth factor and other endogenous interplayers in age-related macular degeneration.

    Science.gov (United States)

    Grisanti, Salvatore; Tatar, Olcay

    2008-07-01

    Age-related macular degeneration (AMD) is a multifaceted disease characterized by early subclinical changes at the choroidea-retinal pigment epithelium interface. Both the causal and formal pathogenesis of the disease is still puzzling. Similarly, the reason for progression into two distinct late forms which are "geographic atrophy" and "choroidal neovascularization" remains enigmatic. Late changes are usually responsible for the dramatic loss in central function that has a devastating effect on quality of life. In industrialized countries the disease is a major cause for visual disability among persons over 60 years of age. Due to demographic right-shift and increased life expectancy, AMD is not only a medical problem but will have a pronounced socio-economic effect. Neovascular AMD with the development of choroidal neovascularization in the macular area accounts for 80% of the severe loss of visual acuity due to AMD. In the last decades, treatment modes were merely based on the destruction or surgical removal of the neovascular complex. In the present, however, the philosophical approach to treat the disease is changing to a pathology modifying manner. Intelligent targeting of the involved relevant factors and pathways should stop disease progression, reduce complications and improve vision. The first step into this new era has been accomplished with the introduction of antiangiogenic agents. The new agents act either directly on vascular endothelial growth factor (VEGF) or indirectly on its functional cascade. VEGF makes a fundamental contribution to neovascular processes but it also acts in physiological pathways. The main purpose of this review is to summarize its physiological role especially within the eye, the role in the development of AMD and to understand and foresee both the benefits and potential side-effects of the anti-VEGF-based therapy.

  8. Prediction of Cis-Regulatory Elements Controlling Genes Differentially Expressed by Retinal and Choroidal Vascular Endothelial Cells.

    Science.gov (United States)

    Choi, Dongseok; Appukuttan, Binoy; Binek, Sierra J; Planck, Stephen R; Stout, J Timothy; Rosenbaum, James T; Smith, Justine R

    2008-01-01

    Cultured endothelial cells of the human retina and choroid demonstrate distinct patterns of gene expression. We hypothesized that differential gene expression reflected differences in the interactions of transcription factors and respective cis-regulatory motifs(s) in these two emdothelial cell subpopulations, recognizing that motifs often exist as modules. We tested this hypothesis in silico by using TRANSFAC Professional and CisModule to identify cis-regulatory motifs and modules in genes that were differentially expressed by human retinal versus choroidal endothelial cells, as identified by analysis of a microarray data set. Motifs corresponding to eight transcription factors were significantly (p < 0.05) differentially abundant in genes that were relatively highly expressed in retinal (i.e., GCCR, HMGIY, HSF1, p53, VDR) or choroidal (i.e., E2F, YY1, ZF5) endothelial cells. Predicted cis-regulatory modules were quite different for these two groups of genes. Our findings raise the possibility of exploiting specific cis-regulatory motifs to target therapy at the ocular endothelial cells subtypes responsible for neovascular age-related macular degeneration or proliferative diabetic retinopathy.

  9. Classification of wet aged related macular degeneration using optical coherence tomographic images

    Science.gov (United States)

    Haq, Anam; Mir, Fouwad Jamil; Yasin, Ubaid Ullah; Khan, Shoab A.

    2013-12-01

    Wet Age related macular degeneration (AMD) is a type of age related macular degeneration. In order to detect Wet AMD we look for Pigment Epithelium detachment (PED) and fluid filled region caused by choroidal neovascularization (CNV). This form of AMD can cause vision loss if not treated in time. In this article we have proposed an automated system for detection of Wet AMD in Optical coherence tomographic (OCT) images. The proposed system extracts PED and CNV from OCT images using segmentation and morphological operations and then detailed feature set are extracted. These features are then passed on to the classifier for classification. Finally performance measures like accuracy, sensitivity and specificity are calculated and the classifier delivering the maximum performance is selected as a comparison measure. Our system gives higher performance using SVM as compared to other methods.

  10. [Chronic central serous chorioretinopathy (cCSC): differential diagnosis to choroidal neovascularisation (CNV) secondary to age-related macular degeneration (AMD)].

    Science.gov (United States)

    Inhoffen, W; Ziemssen, F; Bartz-Schmidt, K U

    2012-09-01

    Central neurosensory detachments (NSD) with time-dependent height constitute a disease called central serous chorioretinopathy (CSC), if not arising from uveitis, choroidal neovascularisations (CNV) or leaking retinal vessels. In 10 % of these patients, CSC develops into a chronic disease with recurrent NSD, atrophy of photoreceptors and severe drop in visual acuity. This review article summarises recent progress in understanding this disease and its appearance in funduscopy, FLA, ICG, OCT, autofluorescence as well as its progress, therapy and possible development into secondary CNV. The provided examples illustrate the progression of acute CSC into chronic CSC and with CNV over years. The different appearance of polypoidal choroidal vasculopathy (PCV) in ICG and some of the signs of atypical chronic CSC are discussed. To distinguish between cCSC and wet AMD--both exhibiting leakage in FLA--typical signs are helpful, e.g., "gravitational tracks", retinal precipitates and missing drusen. However, in small lesions, it may be difficult or almost impossible to ensure the correct diagnosis of the underlying disease. The same holds for occult and classic secondary CNV in cCSC vs. CNV in AMD, where photodynamic therapy (PDT) can be successful only in cCSC-CNV and in cCSC without CNV. Corticosteroids often lead to further impairment, even in cases of atypical cCSC, when frequently misdiagnosed as uveitis. As a duration of NSD of more than 4 months is suspected to induce an impairment of photoreceptors, regular examinations are necessary not only in chronic CSC but also after acute CSC (as this form can develop into chronic CSC), while effective therapies are available to resolve the NSD (PDT, anti-VEGF).

  11. Aflibercept for age-related macular degeneration: a game-changer or quiet addition?

    Science.gov (United States)

    Browning, David J; Kaiser, Peter K; Rosenfeld, Philip J; Stewart, Michael W

    2012-08-01

    To describe the pharmacokinetics, preclinical studies, and clinical trials of the newly approved anti-vascular endothelial growth factor (VEGF) drug aflibercept (Eylea (VEGF Trap-Eye); Regeneron; and Bayer). Review with editorial commentary. A review of the medical literature and pertinent Internet postings combined with analysis of key studies with expert opinion regarding the use of aflibercept for the treatment of exudative age-related macular degeneration. Aflibercept, a fusion protein with binding domains from native VEGF receptors, binds VEGF-A, VEGF-B, and placental growth factors 1 and 2 with high affinity. Preclinical ophthalmologic studies demonstrated that aflibercept suppresses choroidal neovascularization in several animal models. The results of phase 1 and 2 trials showed excellent short-term suppression of choroidal neovascularization in patients with exudative age-related macular degeneration and suggested a longer durability of aflibercept compared with other anti-VEGF drugs. The pivotal phase 3 Vascular Endothelial Growth Factor (VEGF) Trap-Eye: Investigation of Efficacy and Safety in Wet Age-Related Macular Degeneration 1 and 2 trials showed that monthly and bimonthly aflibercept were noninferior to monthly ranibizumab at preventing vision loss (pro re nata injections with required injections every 3 months and maintained vision gains from the first year, with an average of 4.2 injections of aflibercept and 4.7 injections of ranibizumab. Aflibercept promises to deliver excellent visual outcomes for exudative age-related macular degeneration patients while undergoing fewer injections compared with ranibizumab. With a wholesale cost of $1850 per dose, the cost per patient with aflibercept treatment promises to be lower than with ranibizumab. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Semiautomated segmentation of the choroid in spectral-domain optical coherence tomography volume scans.

    Science.gov (United States)

    Hu, Zhihong; Wu, Xiaodong; Ouyang, Yanwei; Ouyang, Yanling; Sadda, Srinivas R

    2013-03-07

    Changes in the choroid, in particular its thickness, are believed to be of importance in the pathophysiology of a number of retinal diseases. The purpose of this study was to adapt the graph search algorithm to semiautomatically identify the choroidal layer in spectral-domain optical coherence tomography (SD-OCT) volume scans and compare its performance to manual delineation. A graph-based multistage segmentation approach was used to identify the choroid, defined as the layer between the outer border of the RPE band and the choroid-sclera junction. Thirty randomly chosen macular SD-OCT (1024 × 37 × 496 voxels, Heidelberg Spectralis) volumes were obtained from 20 healthy subjects and 10 subjects with non-neovascular AMD. The positions of the choroidal borders and resultant thickness were compared with consensus manual delineation performed by two graders. For consistency of the statistical analysis, the left eyes were horizontally flipped in the x-direction. The algorithm-defined position of the outer RPE border and choroid-sclera junction was consistent with the manual delineation, resulting in highly correlated choroidal thickness values with r = 0.91 to 0.93 for the healthy subjects and 0.94 for patients with non-neovascular AMD. Across all cases, the mean and absolute differences between the algorithm and manual segmentation for the outer RPE boundary was -0.74 ± 3.27 μm and 3.15 ± 3.07 μm; and for the choroid-sclera junction was -3.90 ± 15.93 μm and 21.39 ± 10.71 μm. Excellent agreement was observed between the algorithm and manual choroidal segmentation in both normal eyes and those with non-neovascular AMD. The choroid was thinner in AMD eyes. Semiautomated choroidal thickness calculation may be useful for large-scale quantitative studies of the choroid.

  13. The design and implementation of a study to investigate the effectiveness of community vs hospital eye service follow-up for patients with neovascular age-related macular degeneration with quiescent disease.

    Science.gov (United States)

    Taylor, J; Scott, L J; Rogers, C A; Muldrew, A; O'Reilly, D; Wordsworth, S; Mills, N; Hogg, R; Violato, M; Harding, S P; Peto, T; Townsend, D; Chakravarthy, U; Reeves, B C

    2016-01-01

    IntroductionStandard treatment for neovascular age-related macular degeneration (nAMD) is intravitreal injections of anti-VEGF drugs. Following multiple injections, nAMD lesions often become quiescent but there is a high risk of reactivation, and regular review by hospital ophthalmologists is the norm. The present trial examines the feasibility of community optometrists making lesion reactivation decisions.MethodsThe Effectiveness of Community vs Hospital Eye Service (ECHoES) trial is a virtual trial; lesion reactivation decisions were made about vignettes that comprised clinical data, colour fundus photographs, and optical coherence tomograms displayed on a web-based platform. Participants were either hospital ophthalmologists or community optometrists. All participants were provided with webinar training on the disease, its management, and assessment of the retinal imaging outputs. In a balanced design, 96 participants each assessed 42 vignettes; a total of 288 vignettes were assessed seven times by each professional group.The primary outcome is a participant's judgement of lesion reactivation compared with a reference standard. Secondary outcomes are the frequency of sight threatening errors; judgements about specific lesion components; participant-rated confidence in their decisions about the primary outcome; cost effectiveness of follow-up by optometrists rather than ophthalmologists.DiscussionThis trial addresses an important question for the NHS, namely whether, with appropriate training, community optometrists can make retreatment decisions for patients with nAMD to the same standard as hospital ophthalmologists. The trial employed a novel approach as participation was entirely through a web-based application; the trial required very few resources compared with those that would have been needed for a conventional randomised controlled clinical trial.

  14. Method development to quantify Bv8 expression in circulating CD11b+ cells in patients with neovascular age-related macular degeneration (nvAMD) exhibiting Anti-VEGF refractoriness.

    Science.gov (United States)

    Catchpole, Timothy; Daniels, Tad; Perkins, Jill; Csaky, Karl G

    2016-07-01

    A subset of neovascular age-related macular degeneration (nvAMD) subjects appears to be refractory to the effects of anti-VEGF treatment and require frequent intravitreal injections. Prokineticin-2 (Bv8) expression in CD11b(+) cells has been linked to anti-VEGF response. We have developed a reproducible method to quantify gene expression in circulating CD11b + cells. Utilizing this method we tested the hypothesis that high Bv8 expression in circulating CD11b(+) cells is associated with anti-VEGF refractoriness in nvAMD patients. Two groups of nvAMD subjects undergoing treatment with anti-VEGF agents were recruited and classified as refractory or non-refractory to anti-VEGF treatment (n = 33 for each group). Two blood draws were obtained from each subject 1-9 months apart. Peripheral blood mononuclear cells (PBMCs) were isolated and CD11b(+) cells were purified via magnetic bead separation. RNA was purified, and relative expression of Bv8 among the subjects was compared via quantitative PCR analysis. Utilizing this approach no significant difference was detected in the mean LogRQ values between the first and second blood draws (t-test, p = 0.826) indicating low intra-patient variability and demonstrating good reproducibility of the assay. There was no significant difference in Bv8 expression between nvAMD subjects classified as refractory versus non-refractory. We were unable to find a correlation between Bv8 expression in CD11b + cells and anti-VEGF refractoriness in human nvAMD subjects. Relatively high expression in Bv8 in these subjects did not correlate with clinical treatment history, as measured by the frequency of injections. Utilizing this well characterized technique, studies are underway to examine alternative gene expression profiles in various circulating cell populations that may contribute to anti-VEGF refractoriness.

  15. Blockade of Tumor Necrosis Factor-Alpha: A Role for Adalimumab in Neovascular Age-Related Macular Degeneration Refractory to Anti-Angiogenesis Therapy

    Directory of Open Access Journals (Sweden)

    Beatriz Fernández-Vega

    2016-03-01

    Full Text Available Aims: To report a case of wet age-related macular degeneration (wet-AMD refractory to intravitreal anti-vascular endothelial growth factor (anti-VEGF therapy in a patient who showed visual and anatomical improvement and stabilization after starting a subcutaneous treatment course with adalimumab, an anti-tumor necrosis factor-alpha (TNF-α drug, for concomitant Crohn's disease. Methods: Observational case report of a female patient. Ophthalmological evaluation was performed by slit lamp and ophthalmoscopy (posterior pole and anterior segment. Best-corrected visual acuity (BCVA was determined, and imaging was performed by fluorescein angiography, indocyanine green angiography, and optical coherence tomography (OCT. Intravitreal therapies used and treatment with anti-TNF-α were recorded. Results: A 64-year-old woman with wet-AMD was treated with fourteen intravitreal injections of ranibizumab (0.5 mg for a period of 40 months with intervals of 1-6 months. She initially showed a good visual and anatomical response to periodic anti-VEGF treatment but during check visits, anatomical and functional responses deteriorated. At the 40-month follow-up, the patient had developed Crohn's disease, and her rheumatologist started treatment with adalimumab (40 mg subcutaneously every 2 weeks. During the 25 months of treatment with adalimumab, the patient did not require any additional intravitreal anti-VEGF treatments because her BCVA, clinical, and OCT findings improved and remained stable. Conclusions: We described a case of a patient with wet-AMD refractory to anti-VEGF therapy, which clinically benefited from subcutaneous adalimumab therapy. Treatment with subcutaneous anti-TNF-α in combination with anti-VEGF therapy avoids the high cost and risks related to multiple intravitreal anti-VEGF injections with good functional and anatomic outcomes.

  16. Real-world variability in ranibizumab treatment and associated clinical, quality of life, and safety outcomes over 24 months in patients with neovascular age-related macular degeneration: the HELIOS study

    Directory of Open Access Journals (Sweden)

    Rakic JM

    2013-09-01

    < 0.0001. The mean visual acuity increase over baseline at 12 months was not significant (P = 0.08; the decline over baseline at 24 months statistically significant (P = 0.02. Overall, 94.3% of patients showed stable or improved disease at 6 months and 81.5% of patients showed stable or improved disease at 24 months. At 6 months, improvements over baseline were significant for VFQ-25 (P = 0.03 and HUI3 (P = 0.02, but not at 12 months and 24 months. Improvements in VFQ-25 and HUI3 were maintained at 24 months in 38% and 34% of patients, respectively. In total 78 serious adverse events were reported in 40 patients and 77 nonserious adverse events in 34 patients. Nine serious adverse events and nine nonserious adverse events in 14 patients were suspected to be related to ranibizumab treatment. Conclusion: The "real-world" clinical effectiveness of ranibizumab was evidenced by the initial improvements over baseline in visual acuity and quality of life, as well as the maintenance of these outcomes at baseline levels at 24 months, and this was observed under variable treatment conditions. The findings underscore the need for individualized treatment with regular monitoring to achieve optimal vision and quality of life outcomes. Keywords: ranibizumab, age-related macular degeneration, neovascular macular degeneration, visual acuity, visual function, quality of life

  17. Low-dose fractionated percutaneous teletherapy in age-related macular degeneration with subfoveolar neovascularization - 3 year results; 3 Jahre Erfahrung mit der niedrig dosierten fraktionierten perkutanen Teletherapie bei subfoveolaeren Neovaskularisationen. Klinische Ergebnisse

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    Schittkowski, M.; Schneider, H.; Guthoff, R. [Universitaetsaugenklinik Rostock (Germany); Grueschow, K.; Ziegler, P.G.; Fietkau, R. [Zentrum fuer Radiologie, Univ. Rostock (Germany)

    2001-07-01

    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.) [German] Es wurde die Wirkung der Bestrahlung auf die Sehschaerfe bei altersabhaengiger Makuladegeneration mit chorioidalen Neovaskularisationen, die nach den MPS-Kriterien einer Laserkoagulation nicht zugaenglich sind, untersucht. Patienten und Methode: 126 Augen von 118 Patienten im Alter von 55-89 Jahren (Mittel 74) wurden behandelt. Ein

  18. Pharmacogenetics of antiangiogenic and antineovascular therapies of age-related macular degeneration.

    Science.gov (United States)

    Agosta, Elisa; Lazzeri, Stefano; Orlandi, Paola; Figus, Michele; Fioravanti, Anna; Di Desidero, Teresa; Sartini, Maria Sole; Nardi, Marco; Danesi, Romano; Bocci, Guido

    2012-07-01

    Age-related macular degeneration (AMD), the most common age-related disease causing irreversible visual loss in industrialized countries, is a complex and multifactorial illness. Researchers have found components of the complement alternative pathway inside drusen and Bruch's membrane of AMD patients, underlying a possible important role of complement factor H in the pathogenesis of AMD. The neovascular (wet) AMD is the most destructive form and it is characterized by invasion of new blood vessels into subretinal spaces with subsequent exudation and bleeding, resulting in scarring of the macular region and loss of the central vision. The hallmark of the neovascular form is the choroidal neovascularization, where VEGF-A has an important role in the pathogenesis of the disease. SNPs of these genes have recently been investigated as potential pharmacogenetic markers of the antiangiogenic and antineovascular therapy of AMD, which includes verteporfin photodynamic therapy and anti-VEGF-A drugs, such as pegaptanib, bevacizumab and ranibizumab. The CFH rs1061170 CT and TT genotypes have been associated with an improvement of visual acuity in bevacizumab or ranibizumab treated patients, whereas patients harboring VEGF-A rs699946 G allele responded better to bevacizumab-based therapy if compared with patients carrying the A allele. In conclusion, the discovery of pharmacogenetic markers for the personalization of the antiangiogenic and/or antineovascular therapy could be, in the future, a key issue in ophthalmology to obtain a personalization of the therapy and to avoid unnecessary costs and adverse drug reactions.

  19. Fundus Autofluorescence in Age-related Macular Degeneration

    Science.gov (United States)

    Ly, Angelica; Nivison-Smith, Lisa; Assaad, Nagi; Kalloniatis, Michael

    2017-01-01

    ABSTRACT Fundus autofluorescence (FAF) provides detailed insight into the health of the retinal pigment epithelium (RPE). This is highly valuable in age-related macular degeneration (AMD) as RPE damage is a hallmark of the disease. The purpose of this paper is to critically appraise current clinical descriptions regarding the appearance of AMD using FAF and to integrate these findings into a chair-side reference. A wide variety of FAF patterns have been described in AMD, which is consistent with the clinical heterogeneity of the disease. In particular, FAF imaging in early to intermediate AMD has the capacity to reveal RPE alterations in areas that appear normal on funduscopy, which aids in the stratification of cases and may have visually significant prognostic implications. It can assist in differential diagnoses and also represents a reliable, sensitive method for distinguishing reticular pseudodrusen. FAF is especially valuable in the detection, evaluation, and monitoring of geographic atrophy and has been used as an endpoint in clinical trials. In neovascular AMD, FAF reveals distinct patterns of classic choroidal neovascularization noninvasively and may be especially useful for determining which eyes are likely to benefit from therapeutic intervention. FAF represents a rapid, effective, noninvasive imaging method that has been underutilized, and incorporation into the routine assessment of AMD cases should be considered. However, the practicing clinician should also be aware of the limitations of the modality, such as in the detection of foveal involvement and in the distinction of phenotypes (hypo-autofluorescent drusen from small areas of geographic atrophy). PMID:27668639

  20. 重视新生血管性年龄相关性黄斑变性的个体化治疗%Optimizing the individual treatment of neovascular age-related macular degeneration

    Institute of Scientific and Technical Information of China (English)

    孙晓东; 汪枫桦

    2012-01-01

    Neovascular age-related macular degeneration (AMD) is the major cause of visual impairment in elder people.The progress in biomedicine and the launch of new agents provide hope to the patients with AMD.Factors assoeiated with the response of AMD to treatment have been investigated,including the baseline visual acuity,age,the characteristics of the AMD lesions and the genotype of the patients,etc.Preferred Practice Pattern(R) guidelines are developed in different countries based on these evidences,which providet guidance for the pattern of practice,not for the care of a particular individual.To develop an evidence-based individual treatment strategy for the wet AMD patients,accurate and comprehensive evaluation are critical in initial visit and during the follow-up.Individual treatment strategy will not only benefit the patient with better visual outcome and higher quality of life,but also promote the best health economic efficiency for AMD treatment in our aging society.%新生血管性年龄相关性黄斑变性(AMD)严重威胁老年人的视力.随着生命科学的迅速发展,新的治疗方法为新生血管性AMD患者带来希望.目前包括患者年龄、基线视力、病损特征及其基因在内的各种因素,已被用于预测AMD患者的治疗预后.在上述循证医学证据的基础上,我国及其他多个国家都更新了 AMD诊疗指南和诊疗路径,也规范了临床医师对患者进行准确诊断、全面评价和治疗的原则.但是由于患者病变特征不同,环境和基因背景等差异,还应注意为新生血管性AMD患者提供个体化治疗方案,这不仅有望使患者获得更好的治疗效果和更高的生活质量,而且也利于在我国逐渐进入老龄化社会的背景下,获得最佳的卫生经济学效益.

  1. Prevalence of age-related macular degeneration in elderly Caucasians

    DEFF Research Database (Denmark)

    Erke, Maja G; Bertelsen, Geir; Peto, Tunde;

    2012-01-01

    To describe the sex- and age-specific prevalence of drusen, geographic atrophy, and neovascular age-related macular degeneration (AMD).......To describe the sex- and age-specific prevalence of drusen, geographic atrophy, and neovascular age-related macular degeneration (AMD)....

  2. Primary transpupillary thermotherapy of choroidal melanocytic lesions

    Directory of Open Access Journals (Sweden)

    Kaan Gündüz

    2011-01-01

    Full Text Available Purpose : To evaluate the role of primary transpupillary thermotherapy (TTT in the treatment of choroidal melanocytic lesions. Materials and Methods : Retrospective chart review of 24 patients (24 eyes with choroidal melanocytic lesions, including 20 choroidal melanoma and four choroidal nevus treated with primary TTT. Choroidal nevus cases treated with primary TTT either demonstrated risk factors for growth into an early melanoma or had overlying choroidal neovascularization. Results : The mean initial tumor basal diameter was 6.6 (3.0-10.0 mm and the mean initial tumor thickness was 3.0 (1.0-5.0 mm. The mean number of TTT sessions was 2.5 (1-6. The mean decrease in tumor thickness was 1.2 mm (from 3.0 to 1.8 mm at a mean follow-up of 22.7 (range 3-90 months. On the LogMar scale, visual acuity was stable at 1.0. Complications occurred in 50% of eyes. The most frequent complications were vitreous hemorrhage [5 patients (20.8%], focal cataract [5 patients (20.8%], iris atrophy [4 patients (16.6%] and posterior synechia [4 patients (16.6%]. There was no significant difference in the complication rate with respect to tumor thickness >3 mm versus tumor thickness ≤3 mm and juxtapapillary versus nonjuxtapapillary location (Fisher′s exact test, P>0.05. Kaplan-Meier curves showed that 9% of eyes develop recurrence by 1 year and 27% develop recurrence by 5 years after primary TTT. Two eyes (8.3% were enucleated because of neovascular glaucoma and one eye (4.1% was exenterated because of extraocular tumor recurrence. Globe salvage was achieved in 21 patients (87.5%. One patient (4.1% with extraocular tumor recurrence developed liver metastasis and expired. Conclusions : Although TTT may be useful in the treatment of small choroidal melanocytic lesions, the high complication and recurrence rates warrant close monitoring of patients after primary TTT even when a flat chorioretinal scar has been achieved.

  3. Nutritional Supplementation Inhibits the Increase in Serum Malondialdehyde in Patients with Wet Age-Related Macular Degeneration.

    Science.gov (United States)

    Matsuura, Toshiyuki; Takayama, Kei; Kaneko, Hiroki; Ye, Fuxiang; Fukukita, Hiroshi; Tsunekawa, Taichi; Kataoka, Keiko; Hwang, Shiang-Jyi; Nagasaka, Yosuke; Ito, Yasuki; Terasaki, Hiroko

    2017-01-01

    Purpose. To compare serum levels of malondialdehyde (MDA) in patients with wet age-related macular degeneration (wAMD), patients with dry AMD (dAMD), and patients without AMD and to evaluate the efficacy of nutritional supplementation for treating elevated serum MDA in patients with wAMD. Methods. MDA levels were measured in sera from 20 patients with wAMD, 20 with dAMD, and 24 without AMD. Patients with wAMD were randomized to receive or not receive nutritional supplementation (10 patients in each group), and MDA levels were measured after 3 months of treatment. Results. MDA levels in patients with wAMD were significantly greater compared with patients without AMD. In eyes with wAMD, there was a significant correlation between MDA levels and choroidal neovascularization lesion area. Serum MDA levels decreased in most patients that received supplementation and significantly increased in those who did not. Conclusion. Baseline serum MDA levels were elevated in patients with wAMD, and MDA levels were directly correlated with choroidal neovascularization lesion area. In addition, nutritional supplementation appeared to exert a protective effect against oxidative stress in patients with wAMD.

  4. Nutritional Supplementation Inhibits the Increase in Serum Malondialdehyde in Patients with Wet Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Toshiyuki Matsuura

    2017-01-01

    Full Text Available Purpose. To compare serum levels of malondialdehyde (MDA in patients with wet age-related macular degeneration (wAMD, patients with dry AMD (dAMD, and patients without AMD and to evaluate the efficacy of nutritional supplementation for treating elevated serum MDA in patients with wAMD. Methods. MDA levels were measured in sera from 20 patients with wAMD, 20 with dAMD, and 24 without AMD. Patients with wAMD were randomized to receive or not receive nutritional supplementation (10 patients in each group, and MDA levels were measured after 3 months of treatment. Results. MDA levels in patients with wAMD were significantly greater compared with patients without AMD. In eyes with wAMD, there was a significant correlation between MDA levels and choroidal neovascularization lesion area. Serum MDA levels decreased in most patients that received supplementation and significantly increased in those who did not. Conclusion. Baseline serum MDA levels were elevated in patients with wAMD, and MDA levels were directly correlated with choroidal neovascularization lesion area. In addition, nutritional supplementation appeared to exert a protective effect against oxidative stress in patients with wAMD.

  5. Mitochondrial haplogroups and control region polymorphisms in age-related macular degeneration: a case-control study.

    Directory of Open Access Journals (Sweden)

    Edith E Mueller

    Full Text Available BACKGROUND: Onset and development of the multifactorial disease age-related macular degeneration (AMD are highly interrelated with mitochondrial functions such as energy production and free radical turnover. Mitochondrial dysfunction and overproduction of reactive oxygen species may contribute to destruction of the retinal pigment epithelium, retinal atrophy and choroidal neovascularization, leading to AMD. Consequently, polymorphisms of the mitochondrial genome (mtDNA are postulated to be susceptibility factors for this disease. Previous studies from Australia and the United States detected associations of mitochondrial haplogroups with AMD. The aim of the present study was to test these associations in Middle European Caucasians. METHODOLOGY/PRINCIPAL FINDINGS: Mitochondrial haplogroups (combinations of mtDNA polymorphisms and mitochondrial CR polymorphisms were analyzed in 200 patients with wet AMD (choroidal neovascularization, CNV, in 66 patients with dry AMD, and in 385 controls from Austria by means of multiplex primer extension analysis and sequencing, respectively. In patients with CNV, haplogroup H was found to be significantly less frequent compared to controls, and haplogroup J showed a trend toward a higher frequency compared to controls. Five CR polymorphisms were found to differ significantly in the two study populations compared to controls, and all, except one (T152C, are linked to those haplogroups. CONCLUSIONS/SIGNIFICANCE: It can be concluded that haplogroup J is a risk factor for AMD, whereas haplogroup H seems to be protective for AMD.

  6. Nutritional Supplementation Inhibits the Increase in Serum Malondialdehyde in Patients with Wet Age-Related Macular Degeneration

    Science.gov (United States)

    Fukukita, Hiroshi; Tsunekawa, Taichi; Kataoka, Keiko; Hwang, Shiang-Jyi; Nagasaka, Yosuke; Ito, Yasuki; Terasaki, Hiroko

    2017-01-01

    Purpose. To compare serum levels of malondialdehyde (MDA) in patients with wet age-related macular degeneration (wAMD), patients with dry AMD (dAMD), and patients without AMD and to evaluate the efficacy of nutritional supplementation for treating elevated serum MDA in patients with wAMD. Methods. MDA levels were measured in sera from 20 patients with wAMD, 20 with dAMD, and 24 without AMD. Patients with wAMD were randomized to receive or not receive nutritional supplementation (10 patients in each group), and MDA levels were measured after 3 months of treatment. Results. MDA levels in patients with wAMD were significantly greater compared with patients without AMD. In eyes with wAMD, there was a significant correlation between MDA levels and choroidal neovascularization lesion area. Serum MDA levels decreased in most patients that received supplementation and significantly increased in those who did not. Conclusion. Baseline serum MDA levels were elevated in patients with wAMD, and MDA levels were directly correlated with choroidal neovascularization lesion area. In addition, nutritional supplementation appeared to exert a protective effect against oxidative stress in patients with wAMD. PMID:28243361

  7. lntravitreal injection of triamcinolone acetonide combined photodynamic therapy for choroidal neovascularization in high myopia efficacy%玻璃体腔注射曲安奈德联合光动力疗法治疗高度近视脉络膜新生血管疗效观察

    Institute of Scientific and Technical Information of China (English)

    葛建杰; 高夕宁; 王沫学

    2011-01-01

    Objective To observe the clinical efficacy of intravitreal injection of triamcinolone acetonide (TA) combined photodynamic therapy (PDT) of choroidal revascularization (CNV) in high myopia.Methods Based on history,age,symptoms and by visual acuity,fundus examination,fundus photography,fundus fluorescein angiography (FFA),optical coherence tomography (OCT),high myopia diagnosed with choroidal neovascularization (CNV) of 153 patients (165 eyes) were randomly divided into group A,B and C.group A consisted of 51 cases (58 eyes),group B 51 cases (54 eyes),group C of 51 cases (53 eyes).Group A treated with intravitreal injection of TA combined with photodynamic therapy,group B with photodynamic therapy alone (PDT),group C with intravitreal injection of TA alone.All cases were follow-up 3,6 months after treatment.Results At the final follow up,corrected visual acuity was 0.01-1.2.In group A,58 eyes of 51 patients accounted for 43.10% cured in 25 eyes,improved 27 for 47.37%,invalid 6 for 9.53%,the total effective rate 90.47%,5.17% recurrence in 3 eyes.In group B,51 patients were cured 9 out of 54 eyes for 16.67%,27.78% improvement in 15 eyes,55.55% invalid in 30 eyes,total effective rate of 44.45%,recurrence 13 24.07%.In group C,53 eyes of 51 patients were cured in 10 eyes 18.88%,improved 14 eyes 26.41%,invalid 29eyes 54.71%,total effective rate of 45.29%,recurrence 14 26.41%.The total efficiency of the three groups had statistically significant difference (u =2.05693,P <0.05).Conclusions Intravitreous injection of TA combined photodynamic therapy for choroidal neovascularization in high myopia is effective and safe.It solves the problems that a single treatment exist many complications and high recurrence rate.%目的 观察玻璃体腔注射曲安奈德(triamcinolone acetonide TA)联合光动力疗法治疗高度近视脉络膜新生血管的临床疗效.方法 依据病史、年龄、症状及经视力、眼底检查、眼底彩色照相

  8. Aging is not a disease: distinguishing age-related macular degeneration from aging.

    Science.gov (United States)

    Ardeljan, Daniel; Chan, Chi-Chao

    2013-11-01

    Age-related macular degeneration (AMD) is a disease of the outer retina, characterized most significantly by atrophy of photoreceptors and retinal pigment epithelium accompanied with or without choroidal neovascularization. Development of AMD has been recognized as contingent on environmental and genetic risk factors, the strongest being advanced age. In this review, we highlight pathogenic changes that destabilize ocular homeostasis and promote AMD development. With normal aging, photoreceptors are steadily lost, Bruch's membrane thickens, the choroid thins, and hard drusen may form in the periphery. In AMD, many of these changes are exacerbated in addition to the development of disease-specific factors such as soft macular drusen. Para-inflammation, which can be thought of as an intermediate between basal and robust levels of inflammation, develops within the retina in an attempt to maintain ocular homeostasis, reflected by increased expression of the anti-inflammatory cytokine IL-10 coupled with shifts in macrophage plasticity from the pro-inflammatory M1 to the anti-inflammatory M2 polarization. In AMD, imbalances in the M1 and M2 populations together with activation of retinal microglia are observed and potentially contribute to tissue degeneration. Nonetheless, the retina persists in a state of chronic inflammation and increased expression of certain cytokines and inflammasomes is observed. Since not everyone develops AMD, the vital question to ask is how the body establishes a balance between normal age-related changes and the pathological phenotypes in AMD.

  9. Relationship between the complement system, risk factors and prediction models in age-related macular degeneration.

    Science.gov (United States)

    Bora, Nalini S; Matta, Bharati; Lyzogubov, Valeriy V; Bora, Puran S

    2015-02-01

    Studies performed over the past decade in humans and experimental animals have been a major source of information and improved our understanding of how dysregulation of the complement system contributes to age-related macular degeneration (AMD) pathology. Drusen, the hall-mark of dry-type AMD are reported to be the by-product of complement mediated inflammatory processes. In wet AMD, unregulated complement activation results in increased production of angiogenic growth factors leading to choroidal neovascularization both in humans and in animal models. In this review article we have linked the complement system with modifiable and non-modifiable AMD risk factors as well as with prediction models of AMD. Understanding the association between the complement system, risk factors and prediction models will help improve our understanding of AMD pathology and management of this disease.

  10. HLA B27 as Predisposition Factor to Suffer Age Related Macular Degeneration

    Science.gov (United States)

    Becerril, Enrique Villegas; Fernández, Rafael González; Torres, Luis Pérula; Lacomba, Manuel Santos; Galera, José María Gallardo

    2009-01-01

    To research whether specific alleles HLA class I (HLA-A and HLA-B) and class II (HLA-DR) are risk factors for the development of exudative type of Age Related Macular Degeneration (ARMD), HLA antigens are expressed both in normal and affected eyes with ARMD. We designed a prospective case-controlled study. We recruited 75 patients with choroidal neovascularization predominantly classic or occult, secondary to ARMD, and treated with photodynamic therapy. Two hundred and fifty patients over 55 years old, without ophthalmologic pathology who went to hospital for an analytical routine check were used as control. The analysis of the data shows a significant difference between two groups. Allele HLA-B27 correlated positively with ARMD (p < 0.0113). However, we didn't find alleles negatively associated. Thus HLA-B27 is an allele predisposed to suffer ARMD. PMID:19728932

  11. 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

    2016-01-01

    Background/aims 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. Methods 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. Results 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). Conclusions 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. PMID:26183936

  12. Wet age related macular degeneration management and follow-up.

    Science.gov (United States)

    Alexandru, Malciolu Radu; Alexandra, Nica Maria

    2016-01-01

    Age-related macular degeneration (AMD) is referred to as the leading cause of irreversible visual loss in developed countries, with a profound effect on the quality of life. The neovascular form of AMD is characterized by the formation of subretinal choroidal neovascularization, leading to sudden and severe visual loss. Research has identified the vascular endothelial growth factor (VEGF) as an important pathophysiological component in neovascular AMD and its intraocular inhibition as one of the most efficient therapies in medicine. The introduction of anti-VEGF as a standard treatment in wet AMD has led to a great improvement in the prognosis of patients, allowing recovery and maintenance of visual function in the vast majority of cases. However, the therapeutic benefit is accompanied by a difficulty in maintaining the treatment schedule due to the increase in the amount of patients, stress of monthly assessments, as well as the associated economic burden. Therefore, treatment strategies have evolved from fixed monthly dosing, to individualized regimens, aiming for comparable results, with fewer injections. One such protocol is called "pro re nata", or "treat and observe". Patients are given a loading dose of 3 monthly injections, followed by an as-needed decision to treat, based on the worsening of visual acuity, clinical evidence of the disease activity on fundoscopy, or OCT evidence of retinal thickening in the presence of intra or subretinal fluid. A different regimen is called "treat and extend", in which the interval between injections is gradually increased, once the disease stabilization is achieved. This paper aims to review the currently available anti-VEGF agents--bevacizumab, ranibizumab, aflibercept, and the aforementioned treatment strategies.

  13. 玻璃体腔注射康柏西普联合递法明片治疗病理性近视脉络膜新生血管的疗效观察%Clinical observation of intravitreal injection of conbercept combined with difrarel in the treatment of choroidal neovas-cularization in pathologic myopia

    Institute of Scientific and Technical Information of China (English)

    史志洁

    2016-01-01

    Objective To observe the clinical effect and safety of intravitreal injection of conbercept combined with difrarel in the treatment of choroidal neovascularization in pathologic myopia. Methods The clinical records of 16 patients(16 eyes)with choroidal neovascularization in pathologic myopia were retrospectively reviewed. All patients were treated by intravitreal injection of cbonbercept 0. 5 mg(0. 05 ml)as the first initial measurement,and oral difrarel were used for 2 months after injection. BC-VA,FFA,OCT and intraocular pressure were observed 1 month,3 months,6 montha after operation. During the follow-up peri-od,intravitreal injection of conbercept was performed again if active CNV or CNV expansion or new CNV were observed. Results The best corrected visual acuity after intravitreal injection in 1 month,3 months,6 months were respectively 0. 28 ± 0. 03,0. 36 ± 0. 03,0. 38 ± 0. 04,there were statistically significant differences(F = 21. 506,P = 0. 000);There were signifi-cantly improved in 1 month,3 months,6 months compared with before treatment(P ﹤ 0. 05). The central macular retinal thick-ness after intravitreal injection in 1 month,3 months,6 months were respectively 261. 0 ± 8. 56,233. 9 ± 6. 71,229. 0 ± 5. 80, there were statistically significant differences( F = 286. 28,P = 0. 000);There were significantly decreased in 1 month,3 months,6 months compared with before treatment(P ﹤ 0. 05). After 6 months,FFA examination results showed that the CNV was completely closed in 15 eyes,and most closed in 1 eye. During the follow-up period,10 eyes were treated with 1 time,5 eyes were treated with 2 times of intravitreal injection,1 eye were treated with 3 times of intravitreal injection,the average injec-tion times was 1. 43 times;during the follow-up period,there was no high intraocular pressure after intravitreal injection. All pa-tients did not have severe ocular and systemic complications. Conclusion Intravitreal injection of conbercept combined with

  14. Choroidal vasculature characteristics based choroid segmentation for enhanced depth imaging optical coherence tomography images

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Qiang; Niu, Sijie [School of Computer Science and Engineering, Nanjing University of Science and Technology, Nanjing 210094 (China); Yuan, Songtao; Fan, Wen, E-mail: fanwen1029@163.com; Liu, Qinghuai [Department of Ophthalmology, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029 (China)

    2016-04-15

    Purpose: In clinical research, it is important to measure choroidal thickness when eyes are affected by various diseases. The main purpose is to automatically segment choroid for enhanced depth imaging optical coherence tomography (EDI-OCT) images with five B-scans averaging. Methods: The authors present an automated choroid segmentation method based on choroidal vasculature characteristics for EDI-OCT images with five B-scans averaging. By considering the large vascular of the Haller’s layer neighbor with the choroid-sclera junction (CSJ), the authors measured the intensity ascending distance and a maximum intensity image in the axial direction from a smoothed and normalized EDI-OCT image. Then, based on generated choroidal vessel image, the authors constructed the CSJ cost and constrain the CSJ search neighborhood. Finally, graph search with smooth constraints was utilized to obtain the CSJ boundary. Results: Experimental results with 49 images from 10 eyes in 8 normal persons and 270 images from 57 eyes in 44 patients with several stages of diabetic retinopathy and age-related macular degeneration demonstrate that the proposed method can accurately segment the choroid of EDI-OCT images with five B-scans averaging. The mean choroid thickness difference and overlap ratio between the authors’ proposed method and manual segmentation drawn by experts were −11.43 μm and 86.29%, respectively. Conclusions: Good performance was achieved for normal and pathologic eyes, which proves that the authors’ method is effective for the automated choroid segmentation of the EDI-OCT images with five B-scans averaging.

  15. Choroidal vasculature characteristics based choroid segmentation for enhanced depth imaging optical coherence tomography images.

    Science.gov (United States)

    Chen, Qiang; Niu, Sijie; Yuan, Songtao; Fan, Wen; Liu, Qinghuai

    2016-04-01

    In clinical research, it is important to measure choroidal thickness when eyes are affected by various diseases. The main purpose is to automatically segment choroid for enhanced depth imaging optical coherence tomography (EDI-OCT) images with five B-scans averaging. The authors present an automated choroid segmentation method based on choroidal vasculature characteristics for EDI-OCT images with five B-scans averaging. By considering the large vascular of the Haller's layer neighbor with the choroid-sclera junction (CSJ), the authors measured the intensity ascending distance and a maximum intensity image in the axial direction from a smoothed and normalized EDI-OCT image. Then, based on generated choroidal vessel image, the authors constructed the CSJ cost and constrain the CSJ search neighborhood. Finally, graph search with smooth constraints was utilized to obtain the CSJ boundary. Experimental results with 49 images from 10 eyes in 8 normal persons and 270 images from 57 eyes in 44 patients with several stages of diabetic retinopathy and age-related macular degeneration demonstrate that the proposed method can accurately segment the choroid of EDI-OCT images with five B-scans averaging. The mean choroid thickness difference and overlap ratio between the authors' proposed method and manual segmentation drawn by experts were -11.43 μm and 86.29%, respectively. Good performance was achieved for normal and pathologic eyes, which proves that the authors' method is effective for the automated choroid segmentation of the EDI-OCT images with five B-scans averaging.

  16. Avaliação da função macular por eletrorretinografia focal e por angiofluoresceinografia em pacientes com degeneração macular relacionada à idade neovascular submetidos à terapia fotodinâmica com verteporfina Evaluation of the macular function by focal electroretinography and by fluorescein angiography in patients with neovascular age-related macular degeneration submitted to verteporfin photodynamic therapy

    Directory of Open Access Journals (Sweden)

    Akiyoshi Oshima

    2009-02-01

    Full Text Available OBJETIVOS: Avaliar a função macular por eletrorretinografia focal e angiofluoresceinografia em pacientes com degeneração macular relacionada à idade neovascular submetidos à terapia fotodinâmica com verteporfina. MÉTODOS: Estudo prospectivo incluindo 22 pacientes (12 homens com degeneração macular relacionada à idade e lesão neovascular coroídea subfoveal predominantemente clássica, não consecutivos, tratados com terapia fotodinâmica com verteporfina padrão e acompanhados por um período de 12 meses. A acuidade visual melhor corrigida foi medida utilizando tabela ETDRS, as alterações das lesões foram avaliadas pela angiofluoresceinografia e a função dos cones foram obtidas pela eletrorretinografia focal na visita inicial e nas subsequentes a cada três meses. RESULTADOS: Todos os pacientes completaram as visitas programadas. Após uma média de 3,5 sessões por paciente, a variação da acuidade visual melhor corrigida não foi significante no decorrer do estudo. Em 50% dos pacientes a variação da acuidade visual melhor corrigida foi >1 linha. Ao final do estudo observou-se ausência de vazamento em 86% dos pacientes. A média da amplitude e latência do ERG focal na visita inicial foram de, respectivamente, 194,88 nV e 29,19 ms e as variações no decorrer do estudo não foram significantes. CONCLUSÕES: Não foram encontradas diferenças na amplitude e latência do eletrorretinografia focal após um período de 9 meses. A acuidade visual melhor corrigida não sofreu variações significativas ao longo dos 12 meses. A lesão foi significativamente reduzida ao longo do tempo e houve uma correlação negativa entre a amplitude e a acuidade visual melhor corrigida.PURPOSE: To evaluate macular function by focal electroretinography and fluorescein angiography (FA in patients with neovascular age-related macular degeneration submitted to verteporfin photodynamic therapy (VPT. METHODS: Prospective study involving 22 patients

  17. Profile of ranibizumab: efficacy and safety for the treatment of wet age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Chen Y

    2012-07-01

    Full Text Available Youxin Chen, Fei HanDepartment of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, ChinaAbstract: Wet age-related macular degeneration (AMD causes severe vision loss due to the development of choroidal neovascularization (CNV. The critical role of vascular endothelial growth factor in the pathogenesis of CNV is well understood. Ranibizumab plays an inhibitory role with CNV and reduces vascular permeability by binding to vascular endothelial growth factor. Intravitreal ranibizumab reduces the risk of visual acuity (VA loss and increases the chance of VA gain compared with no treatment or photodynamic therapy for CNV in AMD. Some high-quality research has shown that the optimal timing for ranibizumab treating wet AMD is the first 3 months. It is recommended that ranibizumab is intravitreally injected monthly in the initiation for at least 3 months. Subsequent managing of regimens should be made dependent on the VA change, fundus examination, and image of optical coherence topography. An individualized strategy or combined method with photodynamic therapy is beneficial to the active lesion in the consecutive treatment of ranibizumab for CNV, and may be a good choice in order to decrease injection times. Regarding the safety profile, ranibizumab has been well tolerated in clinical trials. The principal ocular adverse event detected in clinical trials is a low frequency of ocular inflammation. Key serious ocular adverse events occurred in <5% of ranibizumab-treated patients in large-scale clinical trials. It appears unlikely that treatment with ranibizumab increases the risk of vascular events significantly. Less frequent injections on an as-needed schedule, based on monthly monitoring may have the most optimal risk:benefit ratio.Keywords: age-related macular degeneration, choroidal neovascularization, ranibizumab, efficacy, safety

  18. Animal models of age related macular degeneration.

    Science.gov (United States)

    Pennesi, Mark E; Neuringer, Martha; Courtney, Robert J

    2012-08-01

    Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the histological features of AMD and provided much insight into the underlying pathological mechanisms of this disease. In spite of the large number of models developed, no one model yet recapitulates all of the features of human AMD. However, these models have helped reveal the roles of chronic oxidative damage, inflammation and immune dysregulation, and lipid metabolism in the development of AMD. Models for induced choroidal neovascularization have served as the backbone for testing new therapies. This article will review the diversity of animal models that exist for AMD as well as their strengths and limitations.

  19. The choroid in glaucoma.

    Science.gov (United States)

    Banitt, Michael

    2013-03-01

    Prior studies have not conclusively established a relationship between the choroid and glaucoma. The development of an enhanced imaging technique for spectral domain optical coherence tomography (SD-OCT) has allowed for measurements of choroidal thickness that are more accurate than previously possible. Therefore, the SD-OCT may be capable of documenting the changes in the choroid as they relate to glaucoma. When applied to the SD-OCT, the technique of enhanced depth imaging allows for reproducible measurements of choroidal thickness. Nine reports have been published about choroidal thickness within the macula, as measured by OCT, in eyes with glaucoma. In six publications, there was no significant difference between the macular choroidal thicknesses of patients with glaucoma compared with those without glaucoma. Additional five studies have reported on peripapillary choroidal thickness in glaucoma patients. Although three of the studies determined that the peripapillary choroid is thinner in glaucoma patients, two others failed to establish this relationship. The SD-OCT is capable of reproducibly measuring choroidal thickness in the peripapillary and macular areas. In those with glaucoma, choroidal thickness does not change within the macula. In a few subsets of glaucoma, the peripapillary choroid is thinner when compared with normals.

  20. A Mechanistic Model of the Intravitreal Pharmacokinetics of Large Molecules and the Pharmacodynamic Suppression of Ocular Vascular Endothelial Growth Factor Levels by Ranibizumab in Patients with Neovascular Age-Related Macular Degeneration.

    Science.gov (United States)

    Hutton-Smith, Laurence A; Gaffney, Eamonn A; Byrne, Helen M; Maini, Philip K; Schwab, Dietmar; Mazer, Norman A

    2016-09-06

    Intravitreal injection of anti-VEGF (vascular endothelial growth factor) antibodies or antibody fragments has been shown to be a highly effective treatment for neovascular age-related macular degeneration (wet AMD). The ocular half-life (t1/2) of these large molecules, determined in ocular fluids or derived from serum levels, varies with molecular size and is larger in humans than in preclinical animal species. The high affinity binding of VEGF to these molecules lowers the free concentration of VEGF and reduces its occupancy on VEGF receptors in ocular tissues. To understand the biophysical determinants of t1/2 for anti-VEGF antibodies and the time-course of VEGF in ocular fluids, we developed a mechanistic model of intravitreal pharmacokinetics (IVT PK) for anti-VEGF antibodies and combined it with a mechanistic model of the pharmacodynamics (RVR PD) of VEGF suppression by ranibizumab, an anti-VEGF recombinant, humanized monoclonal antibody fragment (Fab). Our IVT PK model predicts that the ocular t1/2 of a large molecule will be approximately four-times the calculated value of its vitreous diffusion time (Tdiff), defined as rvit(2)/6D, where rvit is the radius of the vitreous chamber in that species (modeled as a sphere), and D is the diffusion coefficient of the molecule in physiological saline at 37 °C obtained from the Stokes-Einstein relation. This prediction is verified from a compilation of data and calculations on various large molecules in the human, monkey, rabbit, and rat and is consistent with the reported t1/2 values of ranibizumab in humans (mean value 7.9 days) and the calculated Tdiff of 1.59 days. Our RVR PD model is based on the publication of Saunders et al. (Br. J. Ophthalmol. 2015, 99, 1554-1559) who reported data on the time-course of VEGF levels in aqueous humor samples obtained from 31 patients receiving ranibizumab treatment for wet AMD and developed a compartmental mathematical model to describe the VEGF suppression profiles. We

  1. Flare up of choroiditis and choroidal neovasculazation associated with punctate inner choroidopathy during early pregnancy

    Directory of Open Access Journals (Sweden)

    Rao Vinita

    2011-01-01

    Full Text Available A 28-year-old, healthy female, who had a recent repeated history of miscarriage, presented with bilateral choroidal neovascular membranes (CNVM, for which she received photodynamic therapy with three doses of lucentis, at intervals of one month each, to which she responded. After five months, the patient again presented with complaints of diminution of vision since 15 days. She had a history of miscarriage two days before presenting to our clinic. CNVM was scarred at this time and the fundus picture showed multiple small punctate spots around the fovea at the level of the choroid, which showed early hyperfluroscence on fundus fluorescein angiography, suggestive of punctate inner choroidopathy. She was advised systemic steroids, to which she responded dramatically.

  2. Analysis and follow-up of type 1 choroidal neovascularisation with optical coherence tomography-angiography after antiangiogenic treatment.

    Science.gov (United States)

    Torrecillas-Picazo, R; Cerdà-Ibáñez, M; Almor Palacios, I; Hervás Hernandis, J M; Ramón-Cosín, R; Ruiz Del Rio, N; Duch-Samper, A

    2017-06-01

    To describe the characteristics of type 1 choroidal neovascularisation (CNV) in age-related macular degeneration (ARMD) using two different optical coherence tomography angiography (OCT-A) devices sequentially during a standard protocol of three intravitreal injections of an anti-vascular endothelial growth factor (anti-VEGF). The study included 6 eyes with naïve neovascular ARMD. Macular OCT-A images were acquired using AngioPlex Cirrus HD-OCT 5000 (Carl Zeiss Meditec, Inc., Dublin, USA) and DRI OCT Triton SS-OCT Angio (Topcon, Medical Systems, Inc. Oakland, NJ, USA). The macular OCT-A scan covered an area of 3×3mm. Distinct morphological patterns and quantifiable features of the neovascular membranes were studied on en face projection images, which were taken at different stages of the follow-up. Treatment response could be estimated using the OCT-A criteria of CNV activity. Higher activity scores before treatment resulted in a greater decrease in the membrane area. The estimated net decline in area ranged from 83.5% to 1.4%. The OCT-A performed one-week after treatment revealed the greatest area reductions. OCT-A provides new possibilities for the non-invasive assessment of features of neovascular networks and CNV structural morphology. Newly described activity criteria can also guide therapeutic decisions, and help in evaluating responses. Quantitative and qualitative information can be provided with this technique. However, further software development and future investigation are essential to define the role of this tool on a daily basis. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  3. Autofluorescence Imaging of Choroidal Neovascularization Due to Age-Related Macular Degeneration%年龄相关性黄斑变性产生的脉络膜新生血管自发荧光成像

    Institute of Scientific and Technical Information of China (English)

    Samantha S. Dandekar; Sharon A. Jenkins; Tunde Peto; Hendrik P. N. Scholl; Kulwant S. Sehmi; Fred W. Fitzke; Alan C. Bird; Andrew R. Webster; 李越

    2006-01-01

    @@ 目的:描述年龄相关性黄斑变性(AMD)患者中脉络膜新生血管(CNV)的自发荧光(AF)特征. 方法:对连续的患者不同发展阶段的65只CNV眼的自发荧光图像作了分析.其中25幅图像为新近发生的CNV(第1组),8幅为诊断CNV后1到6个月(第2组),37幅为晚期CNV(第3组).对第1组和第2组的自发荧光图像与荧光素眼底血管造影(FFA)图像进行了比较.

  4. Analysis of the Effect Factors of Choroidal Neovascularization in Age Related Macular Degeneration%AMD并发CNV的影像学研究及相关因素分析

    Institute of Scientific and Technical Information of China (English)

    张海侠; 冯长生; 都亚娟

    2010-01-01

    目的:研究FFA和OCT对AMD并发CNV观察的相关性,及AMD并发CNV的相关危险因素分析.方法:回顾性分析自2006年5月~2008年3月期间在我院就诊的81例(127眼)的AMD患者均经裂隙灯、显微立体检眼镜、FFA、眼底照相及OCT检查.根据FFA及OCT各自检查出CNV的病例数,将结果用卡方检验进行统计学分析;根据这组已确诊为AMD并发CNV患者的年龄、性别、教育程度、高血压、远视及吸烟史进行统计,并运用多因素Logistic回归分析法进行统计学分析.结果:以OCT为依据诊断出AMD并发CNV的患者55例(87眼),以FFA为依据诊断出AMD并发CNV的患者26例(32眼),2者对CNV的检出率有显著的统计学意义(χ2=41.95,p0.05).结论:在AMD并发CNV的诊断中OCT与FFA相比具有优异的敏感性和准确率,是AMD并发CNV诊断的首选检测方法.高龄、低学历、高血压、吸烟是发生AMD并发CNV的危险因素.

  5. 基质金属蛋白酶抑制剂GM6001抑制大鼠脉络膜新生血管形成的初步研究%Effects of matrix metalloproteinases inhibitor GM6001 on choroidal neovascularization

    Institute of Scientific and Technical Information of China (English)

    陈学国; 何守志

    2012-01-01

    Objective To explore the efficiency of GM6001 for the inhibition of choroidal neovascularization. Methods Experimental study. Twenty-four Brown Norvy ( BN ) rats after photocoagulation were randomly divided into 3 groups as GM6001 group,DMSO group and CONT group.GM6001 (0.2 ml of 0.1% suspension) was injected retrobulbarly for GM6001 group and0.2 ml DMSO was injected for DMSO group on days 1,3,6,9,and 12 after photocoagulation.No injection was performed in the CONT group.Fundus fluorescence angiography,histopathology,immunohistochemistry and quantitative analysis of choroidal neovascularization ( CNV ) were performed 3 weeks after photocoagulation. One-way ANOVA was used in conjunction with SNK-t test to assess statistical significance within groups. Resufts The fluorescein leakage appeared in all three groups; but fluorescein leakage of GM6001 group( 74.56 ± 2.33 ) was less than that of DMSO group ( 119.57 ± 1.15 ) and CONT group ( 122.36 ± 2.38 ) ( F =403.23,P =0.001 ;LSD-t test,all P value <0.01 ),whereas fluoresecin leakage of DMSO group was similar to that in the CONT group.The retinal and choroidal capillaries in the CONT group were damaged and disordered;a great deal of CNV and migration and proliferation of retinal pigment epithelium cells,fibrocytes and collagen fibers were discovered.Pathological changes in DMSO group were similar to those in the CONT group.There were a small quantity of retinal pigment epithelium cells,fibrocytes and CNV in GM6001 group.Although the immunohistochemical staining for CD105 displayed positive results in all three groups,positive staining of GM6001 group ( 19.85 ± 1.59 ) was significantly less than that of the CONT group (38.02 ± 2.57 ) and DMSO group (39.02 ± 3.12 ) (F =55.57,P =0.001 ; LSD-t test,all P value < 0.01 ).Positive staining of CD105 in the CONT group was similar to that of DMSO group (P > 0.05 ).The size of CNV in GM6001 group ( 15.35 ±0.77) was significantly less than that of CONT group( 28.38

  6. THE MACULAR HOLE AFTER INTRAVITREAL INJECTIONS OF RANIBIZUMAB IN A PATIENT WITH EXUDATIVE AGE-RELATED MACULAR DEGENERATION – A CASE STUDY

    Directory of Open Access Journals (Sweden)

    Magdalena Kal

    2013-11-01

    Full Text Available There are two forms of age-related macular degeneration (AMD, the dry one and the exudative one. The exudative form of AMD can be treated using repeated intravitreal injections of antibodies against vascular endothelial growth factor (VEGF. Optical coherence tomography (OCT of the retina is a standard examination in monitoring patients treated with ranibizumab due to an exudative form of AMD. VEGF plays a key role in the development of choroidal neovascularization in the exudative form of AMD. The subject-matter of our observation was to present the development of the macular hole after treatment of the exudative form of AMD through repeated intravitreal injections of ranibizumab. Ranibizumab is an antibody against VEGF. This substance is registered for the treatment of the exudative form of AMD. Ranibizumab may produce focal sites with traction forces on the surface of the retina during the contraction of the choroidal neovascular membrane. Both of these effects may cause contraction and delamination of the retina causing the macular hole to form.

  7. Our Treatment Results of Circumscribed and Diffuse Choroidal Hemangiomas

    Directory of Open Access Journals (Sweden)

    Esra Savku

    2013-08-01

    Full Text Available Purpose: To discuss our treatment results of choroidal hemangiomas. Material and Method: The records of 39 cases of choroidal hemangioma followed up at our clinic between July 1999–October 2012 were reviewed retrospectively. Asymptomatic cases were followed up. Symptomatic cases with subretinal fluid and impaired vision received treatment. Results: Mean age of the 39 patients was 44 (12-80 years. Thirty-five of 39 cases had circumscribed choroidal hemangioma, and 4 cases had diffuse choroidal hemangioma. Sturge-Weber syndrome was present in 3 cases with diffuse choroidal hemangioma. Cases with circumscribed choroidal hemangioma and minimal subretinal fluid were treated with TTT in 11 cases, PDT in 12 cases, and PDT+TTT in 1 case. Cases with circumscribed choroidal hemangioma and excessive subretinal fluid were treated with Ru-106 plaque radiotherapy in 1 case, Ru-106 plaque radiotherapy+TTT in 1 case, EBRT in 3 cases, and TTT+EBRT in 1 case. One painful blind eye with neovascular glaucoma and complicated cataract was enucleated. Cases with diffuse choroidal hemangioma and excessive subretinal fluid were treated with Ru-106 plaque radiotherapy+TTT in 1 case and EBRT in 1 case. Ahmed glaucoma valve implantation and FAKO emulsification were applied to a case with neovascular glaucoma and complicated cataract. Complete resorption of subretinal fluid was achieved in 23 (72% of treated 32 cases. When mean initial tumor thickness was 2.6 mm (0.5-6, mean final tumor thickness was 1.4 mm (0-6. When mean initial visual acuity (LogMAR was 1.5 (0-3, mean final visual acuity was 1.1 (0-3. No recurrence was observed. Discussion: The amount of the subretinal fluid determines the method of treatment in circumscribed choroidal hemangioma. While TTT and PDT are effective treatment modalities for minimal subretinal fluid, plaque radiotherapy and EBRT are applied in cases with excessive subretinal fluid. Combination therapies may be necessary according to the

  8. Surgical induction of choroidal neovascularization in a porcine model

    DEFF Research Database (Denmark)

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

    2007-01-01

    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...... microscopy and by immunohistochemical staining. In addition to these 30 eyes, two eyes underwent surgery with the purpose of subsequent scanning electron microscopic (SEM) examination. RESULTS: In eyes enucleated immediately after surgery neuroretinas overlying the induced lesions were intact without...... apparent atrophy of cells regardless of the surgical technique applied. The process of RPE removal was found to induce breaks in Bruch's membrane and both the size and the number of breaks varied between eyes. CNV membranes were identified in 15 of 15 eyes enucleated after 14 days. CNV membranes induced...

  9. 口服酪氨酸激酶抑制剂CM082对实验大鼠脉络膜新生血管的影响%Effects of oral tyrosine kinase inhibitor CM082 on experimental choroidal neovascularization in rat

    Institute of Scientific and Technical Information of China (English)

    危清泉; 任成达; 时慧; 刘晴雨; 杜亚茹; 何梦梅; 刘俊伶; 王倩怡; 蔡雯婷

    2016-01-01

    目的 建立脉络膜新生血管(choroidal neovascularization,CNV)大鼠模型,观察药物酪氨酸激酶抑制剂CM082对CNV的影响.方法 采用532 nm倍频激光视网膜光凝法制备棕色挪威(brown norway,BN)大鼠CNV模型.将50只光凝造模后大鼠随机分为对照组(n=25)、实验组(n=25).造模7d后给予实验组口服给药CM082 30 mg·kg-1·d-1,对照组造模后给予药物溶媒5mL· kg-1·d-1.分别于造模后7d及给药后7d、14 d行眼底荧光血管造影(fundus fluorescein angiography,FFA)、组织病理学和视网膜色素上皮(reti-nal pigment epithelium,RPE)-脉络膜-巩膜铺片进行评估.结果 FFA结果显示,实验组给药后7d、14 d光凝斑部位荧光渗漏强度(0.43 ±0.17、0.55±0.15)显著低于对照组(0.74±0.19、0.80±0.13),差异有统计学意义(P<0.05).苏木精-伊红染色的CNV病理组织学显示,实验组中病变范围较小.免疫组织化学检查表明,CM082的治疗可以明显抑制p-VEGFR-2的表达.RPE-脉络膜-巩膜铺片显示,给药后7d、14d,实验组中CNV损伤区域为(4.26±0.93)×104 μm2、(3.58±0.72)×104 μm2,明显小于对照组(12.90±6.40)×104 μm2、(17.81±5.34)×104 μm2,差异有统计学意义(P<0.05).结论 CM082口服给药30mg·kg-1·d-1能有效抑制激光诱导的BN大鼠CNV病变.

  10. Complement Factor H Expressed by Retinal Pigment Epithelium Cells Can Suppress Neovascularization of Human Umbilical Vein Endothelial Cells: An in vitro Study.

    Directory of Open Access Journals (Sweden)

    Yi Zhang

    Full Text Available Complement factor H (CFH is one of the most important soluble complement regulatory proteins and is closely associated with age-related macular degeneration (AMD, the leading cause of irreversible central vision loss in the elderly population in developed countries. Our study searches to investigate whether CFH expression is changed in oxidative damaged retinal pigment epithelium (RPE cells and the role of CFH in the in vitro neovascularization. First, it was confirmed by immunofluorescence staining that CFH was expressed by ARPE-19 cells. CFH mRNA and protein in oxidative (H2O2 damaged ARPE-19 cells were both reduced, as determined by Real-time PCR and Western blotting analysis. Enzyme-linked immunosorbent assay (ELISA also showed that ARPE-19 cells treated with H2O2 caused an increase in C3a content, which indicates complement activation. Then, wound assays were performed to show that CFH expression suppression promoted human umbilical vein endothelial cell (HUVECs migration. Thereafter, ARPE-19 cells were transfected with CFH-specific siRNA and CFH knockdown was confirmed with the aid of Real-time PCR, immunofluorescence staining and Western blotting. The ELISA results showed that specific CFH knockdown in ARPE-19 cells activated the complement system. Finally, in vitro matrigel tube formation assay was performed to determine whether change of CFH expression in RPE would affect tube formation by HUVECs. More tubes were formed by HUVECs co-cultured with ARPE-19 cells transfected with CFH specific-siRNA when compared with controls. Our results suggested that RPE cells might be the local CFH source, and RPE cell injuries (such as oxidative stress may cause CFH expression suppression, which in turn may lead to complement activation and promotion of tube formation by HUVECs. This finding is of importance in elucidating the role of complement in the pathogenesis of ocular neovascularization including choroidal neovascularization.

  11. CCR3 is a target for age-related macular degeneration diagnosis and therapy.

    Science.gov (United States)

    Takeda, Atsunobu; Baffi, Judit Z; Kleinman, Mark E; Cho, Won Gil; Nozaki, Miho; Yamada, Kiyoshi; Kaneko, Hiroki; Albuquerque, Romulo J C; Dridi, Sami; Saito, Kuniharu; Raisler, Brian J; Budd, Steven J; Geisen, Pete; Munitz, Ariel; Ambati, Balamurali K; Green, Martha G; Ishibashi, Tatsuro; Wright, John D; Humbles, Alison A; Gerard, Craig J; Ogura, Yuichiro; Pan, Yuzhen; Smith, Justine R; Grisanti, Salvatore; Hartnett, M Elizabeth; Rothenberg, Marc E; Ambati, Jayakrishna

    2009-07-09

    Age-related macular degeneration (AMD), a leading cause of blindness worldwide, is as prevalent as cancer in industrialized nations. Most blindness in AMD results from invasion of the retina by choroidal neovascularisation (CNV). Here we show that the eosinophil/mast cell chemokine receptor CCR3 is specifically expressed in choroidal neovascular endothelial cells in humans with AMD, and that despite the expression of its ligands eotaxin-1, -2 and -3, neither eosinophils nor mast cells are present in human CNV. Genetic or pharmacological targeting of CCR3 or eotaxins inhibited injury-induced CNV in mice. CNV suppression by CCR3 blockade was due to direct inhibition of endothelial cell proliferation, and was uncoupled from inflammation because it occurred in mice lacking eosinophils or mast cells, and was independent of macrophage and neutrophil recruitment. CCR3 blockade was more effective at reducing CNV than vascular endothelial growth factor A (VEGF-A) neutralization, which is in clinical use at present, and, unlike VEGF-A blockade, is not toxic to the mouse retina. In vivo imaging with CCR3-targeting quantum dots located spontaneous CNV invisible to standard fluorescein angiography in mice before retinal invasion. CCR3 targeting might reduce vision loss due to AMD through early detection and therapeutic angioinhibition.

  12. Segmentation of the macular choroid in OCT images acquired at 830nm and 1060nm

    Science.gov (United States)

    Lee, Sieun; Beg, Mirza F.; Sarunic, Marinko V.

    2013-06-01

    Retinal imaging with optical coherence tomography (OCT) has rapidly advanced in ophthalmic applications with the broad availability of Fourier domain (FD) technology in commercial systems. The high sensitivity afforded by FD-OCT has enabled imaging of the choroid, a layer of blood vessels serving the outer retina. Improved visualization of the choroid and the choroid-sclera boundary has been investigated using techniques such as enhanced depth imaging (EDI), and also with OCT systems operating in the 1060-nm wavelength range. We report on a comparison of imaging the macular choroid with commercial and prototype OCT systems, and present automated 3D segmentation of the choroid-scleral layer using a graph cut algorithm. The thickness of the choroid is an important measurement to investigate for possible correlation with severity, or possibly early diagnosis, of diseases such as age-related macular degeneration.

  13. Examining the Choroid in Ocular Inflammation: A Focus on Enhanced Depth Imaging

    Directory of Open Access Journals (Sweden)

    Abeir Baltmr

    2014-01-01

    Full Text Available The choroid is the vascular layer that supplies the outer retina and is involved in the pathogenesis of several ocular conditions including choroidal tumors, age related macular degeneration, central serous chorioretinopathy, diabetic retinopathy, and uveitis. Nevertheless, difficulties in the visualization of the choroid have limited our understanding of its exact role in ocular pathology. Enhanced depth imaging optical coherent topography (EDI-OCT is a novel, noninvasive technique that is used to evaluate choroidal thickness and morphology in these diseases. The technique provides detailed objective in vivo visualization of the choroid and can be used to characterize posterior segment inflammatory disorders, monitor disease activity, and evaluate efficacy of treatment. In this review we summarize the current application of this technique in ocular inflammatory disorders and highlight its utility as an additional tool in monitoring choroidal involvement in ocular inflammation.

  14. 柚皮素β-环糊精包合物对大鼠实验性脉络膜新生血管的抑制作用%Inhibition of naringenin complex with β-cyclodextrin on experimental choroidal neovascularization in rats

    Institute of Scientific and Technical Information of China (English)

    徐新荣; 于海涛; 杭丽; 邵雁; 丁淑华; 杨学文

    2015-01-01

    Background Choroidal neovascularization (CNV) leads to blindness in many fundus diseases.Study showed that naringenin suppresses CNV,but it presents with poor bioavailability because of its poor solubility in water.β-cyclodextrin (β-CD) can increase the water-solubility of drugs, however, whether the inhibitory effect of naringenin on CNV can be improved after clathrated with β-CD remains unclear.Objective This study was to compare the inhibitory effects of naringenin with naringenin/β-CD compounds on CNV in rats.Methods Naringenin/β-CD clathrate compounds were prepared with saturated solution,the solubility of naringenin in water was calculated based on standard curve.Thirty-two male Brown Norway rats were randomized into normal control group, model control group, naringenin group and naringenin/β-CD group.Laser-induced CNV models were created in the right eyes of rats from the model control group, naringenin group and naringenin/β-CD group.Naringenin and naringenin/β-CD clathrate compounds were intraperitoneally injected at a dose of 20 mg/kg in the rats of naringenin group and naringenin/β-CD group since the day after modeling, respectively, once per day for 4 weeks, and equal volume of DMSO was injected in the same way in the model control group.Fluorescein isothiocyanate dextran (FITC-D) was injected via rat hypoglossal vein for the preparation of flatmounts of choroid in the fourth week,and the areas of CNV were measured and compared among the groups.The retinal pigment epithelium (RPE)-choroid-sclera tissues were isolated from the rats, and the relative expression levels of vascular endothelial growth factor (VEGF) , cyclooxygenase-2 (COX-2),phosphatidylinositol-3-kinase (PI3K),p38mitogen-activated protein kinase (p38MAPK), matrix metalloproteinase (MMP)-2, MMP-9 mRNA and their proteins in RPE-choroid-sclera tissue were detected using real-time PCR and Western blot.Results The solubility of naringenin in water increased by 11.8 folds after

  15. Choroidal neovascularisation on optical coherence tomography angiography in punctate inner choroidopathy and multifocal choroiditis.

    Science.gov (United States)

    Levison, Ashleigh L; Baynes, Kimberly M; Lowder, Careen Y; Kaiser, Peter K; Srivastava, Sunil K

    2017-05-01

    To describe the findings seen on optical coherence tomography angiography (OCTA) in patients with punctate inner choroidopathy (PIC) and multifocal choroiditis and panuveitis (MCP) complicated by choroidal neovascular membranes. This was an Institutional Review Board-approved prospective, descriptive case series. 12 patients with PIC and MCP complicated by choroidal neovascularisation (CNV) were included. Each patient underwent slit-lamp examination by a uveitis specialist followed by conventional spectral domain OCT imaging of the macula. OCTA images of the macula were then obtained. 12 patients were enrolled in the study, out of which 9 patients were followed longitudinally. CNV was identified in 11 of the 12 patients. In all patients where fluorescein angiography (FA) was inconclusive for presence of CNV, OCTA identified CNV. Various lesions on OCT suggestive of activity correlated with changes in the vascular structure of OCTA to confirm suspicion of clinical activity. In patients with PIC and MCP complicated by CNV, OCTA successfully identified underlying CNV. Given the difficulty of differentiating inflammatory lesions from early CNV on OCT and FA, OCTA may provide a valuable method of monitoring patients with posterior uveitis highly correlated with development of CNV. 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/.

  16. De novo appearance of a choroidal osteoma in an eye with previous branch retinal vein occlusion.

    Science.gov (United States)

    Adhi, Mehreen; Bryant, Juanita Sonya; Alwassia, Ahmad A; Chen, Carolyn; Duker, Jay S

    2013-01-01

    This report describes the de novo appearance of a choroidal osteoma occurring 8 years after laser photocoagulation for previous branch retinal vein occlusion (BRVO). A 62-year-old man presented with an asymptomatic yellowish orange lesion in the macula on fundus examination of his left eye during a regular follow-up visit for bilateral BRVO associated with macular edema that had previously been treated with laser photocoagulation. The lesion was observed for 1.5 years until a decrease in vision occurred. Fundus photography revealed a yellow-to-orange, well-defined lesion in the macular region. Fluorescein angiography was consistent with choroidal neovascularization (CNV). Optical coherence tomography and B-scan ultrasonography showed features consistent with choroidal osteoma. This is the first report of the de novo appearance of a choroidal osteoma occurring years after laser photocoagulation for BRVO. CNV developed secondary to the lesion, which was treated with intravitreal bevacizumab, leading to subjective and anatomic improvement.

  17. Choroidal osteoma: a very unusual form of intraocular clarification; Osteoma coroideo. Una inusual forma de calcificacion del globo ocular

    Energy Technology Data Exchange (ETDEWEB)

    Garcia, Y.; Lasierra, R.; Pina, J. I.; Madariaga, B. [Hospital Clinico Universitario Lozano Blesa. Zaragoza (Spain)

    2000-07-01

    Choroidal osteoma is a very uncommon benign choroidal tumor that is capable of producing real bone tissue. It is normally found in healthy young women. It tends to be located in the juxtapapillary region, and is generally unilateral. The etiology is unknown. Both ultrasonography and computed tomography demonstrate the presence of calcified plaquet the identifies the lesions. The major complications is choroidal neovascularization, which can occur in up to one third of cases. Choroidal osteoma must be differentiated mainly from other intraocular tumors and dystrophic or metastatic calcifications We present a case of choroidal osteoma in a 16-year-old girl who had loss of visual acuity in both eyes and possible optic nerve glioma in her right eye. (Author) 11 refs.

  18. Laser Therapy for Age-Related Macular Degeneration%激光在治疗黄斑变性中的应用

    Institute of Scientific and Technical Information of China (English)

    王顺昱; 李迎新

    2004-01-01

    目的年龄相关性黄斑变性(age-related macular degeneration,ARMD)是老年人重要的致盲疾病之一,由它引起的脉络膜新生血管(choroidal neovascularization,CNV)是导致视力严重下降的主要原因,利用激光处理CNV是ARMD临床治疗的主要方法.激光光凝法、经瞳孔温热疗法(transpupillary thermotherapy,TTT)及光动力疗法(photodynamic therapy,PDT)对ARMD的治疗均有一定效果,从目前的研究看,光动力疗法是一种很有前途的治疗方法.

  19. Rap1 GTPase Inhibits Tumor Necrosis Factor-α-Induced Choroidal Endothelial Migration via NADPH Oxidase- and NF-κB-Dependent Activation of Rac1.

    Science.gov (United States)

    Wang, Haibo; Fotheringham, Lori; Wittchen, Erika S; Hartnett, M Elizabeth

    2015-12-01

    Macrophage-derived tumor necrosis factor (TNF)-α has been found in choroidal neovascularization (CNV) surgically removed from patients with age-related macular degeneration. However, the role of TNF-α in CNV development remains unclear. In a murine laser-induced CNV model, compared with un-lasered controls, TNF-α mRNA was increased in retinal pigment epithelial and choroidal tissue, and TNF-α colocalized with lectin-stained migrating choroidal endothelial cells (CECs). Inhibition of TNF-α with a neutralizing antibody reduced CNV volume and reactive oxygen species (ROS) level around CNV. In CECs, pretreatment with the antioxidant apocynin or knockdown of p22phox, a subunit of NADPH oxidase, inhibited TNF-α-induced ROS generation. Apocynin reduced TNF-α-induced NF-κB and Rac1 activation, and inhibited TNF-α-induced CEC migration. TNF-α-induced Rac1 activation and CEC migration were inhibited by NF-κB inhibitor Bay11-7082. Overexpression of Rap1a prevented TNF-α-induced ROS generation and reduced NF-κB and Rac1 activation. Activation of Rap1 by 8-(4-chlorophenylthio)adenosine-2'-O-Me-cAMP prevented TNF-α-induced CEC migration and reduced laser-induced CNV volume, ROS generation, and activation of NF-κB and Rac1. These findings provide evidence that active Rap1a inhibits TNF-α-induced CEC migration by inhibiting NADPH oxidase-dependent NF-κB and Rac1 activation and suggests that Rap1a de-escalates CNV development by interfering with ROS-dependent signaling in several steps of the pathogenic process. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  20. Rap1 GTPase Inhibits Tumor Necrosis Factor-α–Induced Choroidal Endothelial Migration via NADPH Oxidase– and NF-κB–Dependent Activation of Rac1

    Science.gov (United States)

    Wang, Haibo; Fotheringham, Lori; Wittchen, Erika S.; Hartnett, M. Elizabeth

    2016-01-01

    Macrophage-derived tumor necrosis factor (TNF)-α has been found in choroidal neovascularization (CNV) surgically removed from patients with age-related macular degeneration. However, the role of TNF-α in CNV development remains unclear. In a murine laser-induced CNV model, compared with un-lasered controls, TNF-α mRNA was increased in retinal pigment epithelial and choroidal tissue, and TNF-α colocalized with lectin-stained migrating choroidal endothelial cells (CECs). Inhibition of TNF-α with a neutralizing antibody reduced CNV volume and reactive oxygen species (ROS) level around CNV. In CECs, pretreatment with the antioxidant apocynin or knockdown of p22phox, a subunit of NADPH oxidase, inhibited TNF-α–induced ROS generation. Apocynin reduced TNF-α–induced NF-κB and Rac1 activation, and inhibited TNF-α–induced CEC migration. TNF-α–induced Rac1 activation and CEC migration were inhibited by NF-κB inhibitor Bay11-7082. Overexpression of Rap1a prevented TNF-α–induced ROS generation and reduced NF-κB and Rac1 activation. Activation of Rap1 by 8-(4-chlorophenylthio)adenosine-2′-O-Me-cAMP prevented TNF-α–induced CEC migration and reduced laser-induced CNV volume, ROS generation, and activation of NF-κB and Rac1. These findings provide evidence that active Rap1a inhibits TNF-α–induced CEC migration by inhibiting NADPH oxidase-dependent NF-κB and Rac1 activation and suggests that Rap1a de-escalates CNV development by interfering with ROS-dependent signaling in several steps of the pathogenic process. PMID:26476350

  1. Analysis of morphological features and vascular layers of choroid in diabetic retinopathy using spectral-domain optical coherence tomography.

    Science.gov (United States)

    Adhi, Mehreen; Brewer, Erika; Waheed, Nadia K; Duker, Jay S

    2013-10-01

    Diabetic retinopathy (DR) is characterized by microaneurysms, capillary nonperfusion, and ischemia within the retina, ultimately leading to neovascularization and/or macular edema. Evidence suggests that choroidal angiopathy may coexist with retinal vascular damage. Recent advances in spectral-domain optical coherence tomography (SD-OCT) permit an efficient visualization of the choroid. To analyze the morphological features and vascular layers of the choroid in patients with DR using SD-OCT. A cross-sectional retrospective review identified patients with DR and healthy (control) subjects who underwent 1-line raster scanning from February 1, 2010, through June 30, 2012. Patients were classified into the following 3 groups: nonproliferative DR without macular edema (9 eyes), proliferative DR without macular edema (PDR) (10 eyes), and diabetic macular edema (DME) (14 eyes). Two independent raters experienced in analyzing OCT images evaluated the morphological features and vasculature of the choroid. New England Eye Center. Thirty-three eyes of 33 patients with DR and 24 eyes of 24 controls. Diabetic retinopathy. Choroidal morphological features and vasculature analysis. The choroidoscleral interface had an irregular contour in 8 of 9 eyes with nonproliferative DR (89%), 9 of 10 eyes with PDR (90%), and 13 of 14 eyes with DME (93%) compared with 0 of 24 controls. The thickest point of the choroid was displaced from under the fovea, and focal choroidal thinning was observed in eyes with DR. Mean subfoveal choroidal thickness and mean subfoveal medium choroidal vessel layer and choriocapillaris layer thickness were significantly reduced in eyes with PDR (P Choroidal morphological features are altered in patients with moderate to severe DR. The subfoveal choroidal thickness and the subfoveal medium choroidal vessel layer and choriocapillaris layer thicknesses are significantly reduced in patients with PDR and DME. To our knowledge, this is the first study to analyze the

  2. Degeneração macular relacionada à idade: novas perspectivas Age-related macular degeneration: new perspectives

    Directory of Open Access Journals (Sweden)

    Marcio Bittar Nehemy

    2006-12-01

    Full Text Available A degeneração macular relacionada à idade (DMRI é a principal causa de cegueira legal em indivíduos acima de 50 anos de idade. Embora estudos recentes tenham mostrado que o fator genético é significativo, a patogênese da degeneração macular relacionada à idade permanece obscura, e os fatores de risco não estão ainda completamente estabelecidos. Estudos multicêntricos randomizados, publicados nos últimos anos, demonstraram que uma combinação de vitaminas e minerais é eficaz na redução do risco de desenvolvimento de neovascularização e de progressão para os estágios mais avançados da degeneração macular relacionada à idade. De maneira análoga, a terapia fotodinâmica (PDT e a terapia antiangiogênica também tiveram sua eficácia comprovada no tratamento de membrana neovascular coroideana subfoveal associada à degeneração macular relacionada à idade. Ambas reduzem o risco de perda de visão e, eventualmente, permitem melhora temporária da acuidade visual. Outras modalidades de tratamento, tais como fotocoagulação a laser, remoção cirúrgica da membrana e termoterapia transpupilar (TTT, podem beneficiar apenas um pequeno subgrupo de pacientes. Uma melhor compreensão dos mecanismos fisiopatológicos e dos eventos moleculares nas diversas fases da doença deverão propiciar, em futuro próximo, melhores estratégias para o controle e tratamento da degeneração macular relacionada à idade.Age-related macular degeneration (ARMD is a major source of legal blindness in individuals older than 50 years. Even though recent reports suggest that genetics plays an important role, its pathogenesis remains puzzling and the risk factors for its occurrence are not completely established. Vitamin and mineral supplementation reduced the risk of development of choroidal neovascularization (CNV or progression to the most advanced stages of age-related macular degeneration. Photodynamic therapy (PDT and antiangiogenic therapy

  3. Current and emerging therapies for the treatment of age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    M Vaughn Emerson

    2008-06-01

    Full Text Available M Vaughn Emerson, Andreas K LauerCasey Eye Institute, Oregon Health and Science University, Portland, OR, USAAbstract: Age-related macular degeneration (AMD is the leading cause of vision loss in the industrialized world. In the last few decades, the mainstay of treatment for choroidal neovascularization (CNV due to AMD has been thermal laser photocoagulation. In the last decade, photodynamic therapy with verteporfin extended treatment for more patients. While both of these treatments have prevented further vision loss in a subset of patients, improvement in visual acuity is rare. Anti-vascular endothelial growth factor A (VEGF therapy has revolutionized the treatment of AMD-related CNV. Pegaptanib, an anti-VEGF aptamer prevents vision loss in CNV, although the performance is similar to that of photodynamic therapy. Ranibizumab, an antibody fragment and bevacizumab, a full-length humanized monoclonal antibody against VEGF have both shown promising results with improvements in visual acuity with either agent. VEGF trap, a modified soluble VEGF receptor analogue, binds VEGF more tightly than all other anti-VEGF agents and has also shown promising results in early trials. Other treatment strategies to decrease the effect of VEGF have used small interfering ribonucleic acid (RNA to inhibit VEGF production and VEGF receptor production. Steroids, including anecortave acetate in the treatment and prevention of CNV, have shown promise in controlled trials. Receptor tyrosine kinase inhibitors, such as vatalanib, inhibit downstream effects of VEGF, and have been effective in the treatment of CNV in early studies. Squalamine lactate inhibits plasma membrane ion channels with downstream effects on VEGF, and has shown promising results with systemic administration. Other growth factors, including pigment epithelium-derived growth factor that has been administered via an adenoviral vector has shown promising initial results. In some patients ciliary

  4. Characterization of a spontaneous retinal neovascular mouse model.

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    Eiichi Hasegawa

    Full Text Available BACKGROUND: Vision loss due to vascular disease of the retina is a leading cause of blindness in the world. Retinal angiomatous proliferation (RAP is a subgroup of neovascular age-related macular degeneration (AMD, whereby abnormal blood vessels develop in the retina leading to debilitating vision loss and eventual blindness. The novel mouse strain, neoretinal vascularization 2 (NRV2, shows spontaneous fundus changes associated with abnormal neovascularization. The purpose of this study is to characterize the induction of pathologic angiogenesis in this mouse model. METHODS: The NRV2 mice were examined from postnatal day 12 (p12 to 3 months. The phenotypic changes within the retina were evaluated by fundus photography, fluorescein angiography, optical coherence tomography, and immunohistochemical and electron microscopic analysis. The pathological neovascularization was imaged by confocal microscopy and reconstructed using three-dimensional image analysis software. RESULTS: We found that NRV2 mice develop multifocal retinal depigmentation in the posterior fundus. Depigmented lesions developed vascular leakage observed by fluorescein angiography. The spontaneous angiogenesis arose from the retinal vascular plexus at postnatal day (p15 and extended toward retinal pigment epithelium (RPE. By three months of age, histological analysis revealed encapsulation of the neovascular lesion by the RPE in the photoreceptor cell layer and subretinal space. CONCLUSIONS: The NRV2 mouse strain develops early neovascular lesions within the retina, which grow downward towards the RPE beginning at p15. This retinal neovascularization model mimics early stages of human retinal angiomatous proliferation (RAP and will likely be a useful in elucidating targeted therapeutics for patients with ocular neovascular disease.

  5. Progress on retinal image analysis for age related macular degeneration.

    Science.gov (United States)

    Kanagasingam, Yogesan; Bhuiyan, Alauddin; Abràmoff, Michael D; Smith, R Theodore; Goldschmidt, Leonard; Wong, Tien Y

    2014-01-01

    Age-related macular degeneration (AMD) is the leading cause of vision loss in those over the age of 50 years in the developed countries. The number is expected to increase by ∼1.5 fold over the next ten years due to an increase in aging population. One of the main measures of AMD severity is the analysis of drusen, pigmentary abnormalities, geographic atrophy (GA) and choroidal neovascularization (CNV) from imaging based on color fundus photograph, optical coherence tomography (OCT) and other imaging modalities. Each of these imaging modalities has strengths and weaknesses for extracting individual AMD pathology and different imaging techniques are used in combination for capturing and/or quantification of different pathologies. Current dry AMD treatments cannot cure or reverse vision loss. However, the Age-Related Eye Disease Study (AREDS) showed that specific anti-oxidant vitamin supplementation reduces the risk of progression from intermediate stages (defined as the presence of either many medium-sized drusen or one or more large drusen) to late AMD which allows for preventative strategies in properly identified patients. Thus identification of people with early stage AMD is important to design and implement preventative strategies for late AMD, and determine their cost-effectiveness. A mass screening facility with teleophthalmology or telemedicine in combination with computer-aided analysis for large rural-based communities may identify more individuals suitable for early stage AMD prevention. In this review, we discuss different imaging modalities that are currently being considered or used for screening AMD. In addition, we look into various automated and semi-automated computer-aided grading systems and related retinal image analysis techniques for drusen, geographic atrophy and choroidal neovascularization detection and/or quantification for measurement of AMD severity using these imaging modalities. We also review the existing telemedicine studies which

  6. Application of anti-vascular endothelial growth factor on the treatment of neovascular glaucoma

    Directory of Open Access Journals (Sweden)

    Ping Wu

    2015-11-01

    Full Text Available Neovascular glaucoma(NVGis a common secondary glaucoma, often occurs secondary to diabetic retinopathy, central retinal vein occlusion and retinal ischemia syndrome. Its pathogenesis is complicated. Though conventional treatmentscan brieflyreduce elevated intraocular pressure, degenerate iris neovascularization, the long-term effect for controlling NVG is not obvious. The treatment of NVG ushers in a new dawn with the in-depth study on the pathogenesis of NVG and the use of vascular endothelial growth factor(VEGFinhibitors in ophthalmic diseases. In this paper, the applications of VEGF inhibitors on the treatment of neovascular glaucoma are reviewed to provide new thoughts for the treatment of NVG.

  7. Economic evaluation of bevacizumab versus ranibizumab in neovascular age-related macular degeneration%贝伐单克隆抗体与雷珠单克隆抗体治疗新生血管性年龄相关性黄斑变性的经济学评价

    Institute of Scientific and Technical Information of China (English)

    李洪超; 黎晓新; 谢锋

    2014-01-01

    Objective To evaluate the cost-effectiveness of bevacizumab versus ranibizumab for patients with neovascular age-related macular degeneration ( AMD) in China.Methods A Markov model was constructed to compare cost per quality-adjusted life year of bevacizumab with ranibizumab in patients with neovascular AMD.In the Markov model, with cycle length of 3 months and time horizon of 10 years, three health states were defined by visual acuity.One way deterministic and probabilistic sensitivity analyses were conducted to explore the uncertainties from a number of variables.Results In the base case analysis , patients in ranibizumab group obtained 0.007 QALY more than patients in bevacizumab group , while the average total cost was ¥794 400 higher.The ICUR reached ¥109.23 million per QALY.In all sensitivity analyses, the ICURs were over ¥ 2.48 million per QALY between ranibizumab and bevacizumab groups. Conclusions Ranibizumab for neovascular AMD patients gained similar QALY at significantly higher costs in comparison with bevacizumab.The ICURs generated in this study were much higher than the possible QALY threshold in the society of China.Compared with ranibizumab , bevacizumab was cost-effective for neovascular AMD patients.%目的:评价在我国采用贝伐单克隆抗体( bevacizumab )与雷珠单克隆抗体( ranibizumab )治疗新生血管性AMD的经济性。方法成本效用分析。构建了一个Markov模型进行成本效用分析。根据视力定义了3个状态和1个死亡状态,模型周期为3个月,研究时限为10年。对多种因素进行了单因素敏感性分析和概率敏感性分析。结果在基础分析中,雷珠单克隆抗体组相对于贝伐单克隆抗体组患者平均多获得0.007质量调整生命年( QALY ),但是平均成本增加了79.44万元,增量成本效用比( ICUR)为10923万元/QALY。在所有敏感性分析中,雷珠单克隆抗体组与贝伐单克

  8. Hyperhomocysteinemia disrupts retinal pigment epithelial structure and function with features of age-related macular degeneration.

    Science.gov (United States)

    Ibrahim, Ahmed S; Mander, Suchreet; Hussein, Khaled A; Elsherbiny, Nehal M; Smith, Sylvia B; Al-Shabrawey, Mohamed; Tawfik, Amany

    2016-02-23

    The disruption of retinal pigment epithelial (RPE) function and the degeneration of photoreceptors are cardinal features of age related macular degeneration (AMD); however there are still gaps in our understanding of underlying biological processes. Excess homocysteine (Hcy) has been reported to be elevated in plasma of patients with AMD. This study aimed to evaluate the direct effect of hyperhomocysteinemia (HHcy) on structure and function of RPE. Initial studies in a mouse model of HHcy, in which cystathionine-β-synthase (cbs) was deficient, revealed abnormal RPE cell morphology with features similar to that of AMD upon optical coherence tomography (OCT), fluorescein angiography (FA), histological, and electron microscopic examinations. These features include atrophy, vacuolization, hypopigmentation, thickened basal laminar membrane, hyporeflective lucency, choroidal neovascularization (CNV), and disturbed RPE-photoreceptor relationship. Furthermore, intravitreal injection of Hcy per se in normal wild type (WT) mice resulted in diffuse hyper-fluorescence, albumin leakage, and CNV in the area of RPE. In vitro experiments on ARPE-19 showed that Hcy dose-dependently reduced tight junction protein expression, increased FITC dextran leakage, decreased transcellular electrical resistance, and impaired phagocytic activity. Collectively, our results demonstrated unreported effects of excess Hcy levels on RPE structure and function that lead to the development of AMD-like features.

  9. Physics of Lipofuscin Formation and Growth in Age Related Macular Degeneration

    Science.gov (United States)

    Family, Fereydoon; Mazzitello, K. I.; Arizmendi, C. M.; Grossniklaus, Hans E.

    2010-02-01

    Age-related macular degeneration (AMD) is the leading cause of blindness beyond the age of 50 years. The most common pathogenic mechanism that leads to AMD is choroidal neovascularization (CNV). CNV is produced by accumulation of residual material caused by aging of retinal pigment epithelium cells (RPE). With time, incompletely degraded membrane material builds up in the RPE in the form of lipofuscin. Lipofuscin is made of free-radical-damaged protein and fat, which forms not only in AMD, but also Alzheimer disease, and Parkinson disease. We will present the results of a study of the kinetics of lipofuscin growth in RPE cells using Kinetic Monte Carlo simulations and scaling theory on a cluster aggregation model. The model captures the essential physics of lipofuscin growth in the cells. A remarkable feature is that small particles may be removed from the cells while the larger ones become fixed and grow by aggregation. We compare our results to the number of lipofuscin granules in eyes with early age-related degeneration. )

  10. NLRP3 Inflammasome: Activation and Regulation in Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Jiangyuan Gao

    2015-01-01

    Full Text Available Age-related macular degeneration (AMD is the leading cause of legal blindness in the elderly in industrialized countries. AMD is a multifactorial disease influenced by both genetic and environmental risk factors. Progression of AMD is characterized by an increase in the number and size of drusen, extracellular deposits, which accumulate between the retinal pigment epithelium (RPE and Bruch’s membrane (BM in outer retina. The major pathways associated with its pathogenesis include oxidative stress and inflammation in the early stages of AMD. Little is known about the interactions among these mechanisms that drive the transition from early to late stages of AMD, such as geographic atrophy (GA or choroidal neovascularization (CNV. As part of the innate immune system, inflammasome activation has been identified in RPE cells and proposed to be a causal factor for RPE dysfunction and degeneration. Here, we will first review the classic model of inflammasome activation, then discuss the potentials of AMD-related factors to activate the inflammasome in both nonocular immune cells and RPE cells, and finally introduce several novel mechanisms for regulating the inflammasome activity.

  11. Role of pigment epithelium-derived factor on proliferation and migration of choroidal capillary endothelium induced by vascular endothelial growth factor in vitro

    Institute of Scientific and Technical Information of China (English)

    WANG Feng-hua; SUN Xiao-dong; ZHANG Xi; XU Xun; ZHU Qi; HUANG Jian-nan; FAN Ying; GU Qing; LIU Hai-yang

    2007-01-01

    Background Pigment epithelium-derived factor (PEDF) is expressed in several normal organs and identified as an inhibitor of neovascularization. In the present study, we investigated the effect of PEDF in an in vitro model of ocular choroidal neovascularization.Methods Microdissection was used to isolate the human choroidal endothelial cells (CECs), followed by the use of superparamagnetic beads (Dynabeads) coated with the CD31 antibody, which selectively binds to the endothelial cell surface. The mitogenic and motogenic effects of vascular endothelial growth factor (VEGF) on cultured choroidal capillary endothelial cells were examined in the presence or absence of PEDF (1, 10, 100, and 1000 ng/ml) using cell counts and migration assays.Results Cells bound to the beads were isolated using a magnetic particle concentrator and they were successfully cultured and characterized to be endothelial cells that possessed greater than 95% immunoreactivity to von Willebrand factor. PEDF suppressed the proliferation and migration of VEGF-induced choroidal capillary endothelial cells. However,the concentration of PEDF which we used has little effect on normal CECs.Conclusions PEDF played an important role on the growth and migration of VEGF-stimulated choroidal endothelial cell.These findings suggest that PEDF may be an effective approach to the treatment of choroidal neovascular disorders.

  12. Circumscribed choroidal hemangioma

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    Saeed Karimi

    2015-01-01

    Full Text Available Circumscribed choroidal hemangiomas are benign vascular hamartomas without systemic associations. Generally, they are orange-red elevated masses, which are found posterior to the equator. Lesions are usually solitary and unilateral. Overlying subretinal fluid, serous retinal detachment and cystoid macular edema are common findings. Intravenous fluorescein angiography, indocyanine green angiography, ultrasonography, optical coherence tomography and enhanced depth imaging are helpful ancillary tests for diagnosis of circumscribed choroidal hemangiomas. Asymptomatic circumscribed choroidal hemangiomas do not require treatment. For symptomatic lesions with exudative retinal detachment or cystoid macular edema, photodynamic therapy has emerged as the treatment of choice with high rates of tumor regression, subretinal fluid resorption and minimal complications. Lens-sparing external beam radiotherapy, plaque brachytherapy, proton beam therapy, stereotactic radiosurgery, transpupillary thermotherapy, laser photocoagulation and anti-VEGF injections are other treatment modalities.

  13. Polymeric materials for neovascularization

    Science.gov (United States)

    DeVolder, Ross John

    Revascularization therapies have emerged as a promising strategy to treat various acute and chronic wounds, cardiovascular diseases, and tissue defects. It is common to either administer proangiogenic growth factors, such as vascular endothelial growth factor (VEGF), or transplant cells that endogenously express multiple proangiogenic factors. Additionally, these strategies utilize a wide variety of polymeric systems, including hydrogels and biodegradable plastics, to deliver proangiogenic factors in a sophisticated manner to maintain a sustained proangiogenic environment. Despite some impressive results in rebuilding vascular networks, it is still a challenging task to engineer mature and functional neovessels in target tissues, because of the increasing complexities involved with neovascularization applications. To resolve these challenges, this work aims to design a wide variety of proangiogenic biomaterial systems with tunable properties used for neovascularization therapies. This thesis describes the design of several biomaterial systems used for the delivery of proangiogenic factors in neovascularization therapies, including: an electrospun/electrosprayed biodegradable plastic patch used for directional blood vessel growth (Chapter 2), an alginate-g-pyrrole hydrogel system that biochemically stimulates cellular endogenous proangiogenic factor expression (Chapter 3), an enzyme-catalyzed alginate-g-pyrrole hydrogel system for VEGF delivery (Chapter 4), an enzyme-activated alginate-g-pyrrole hydrogel system with systematically controllable electrical and mechanical properties (Chapter 5), and an alginate-g-pyrrole hydrogel that enables the decoupled control of electrical conductivity and mechanical rigidity and is use to electrically stimulate cellular endogenous proangiogenic factor expression (Chapter 6). Overall, the biomaterial systems developed in this thesis will be broadly useful for improving the quality of a wide array of molecular and cellular based

  14. Morphological patterns of indirect choroidal rupture on spectral domain optical coherence tomography

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    Nair U

    2013-07-01

    Full Text Available Unnikrishnan Nair,1 Manoj Soman,1 Sunil Ganekal,2 Vaishnavi Batmanabane,1 KGR Nair11Chaithanya Eye Hospital and Research Institute, Trivandrum, Kerala, 2Nayana Super Specialty Eye Hospital and Research Center, Davangere, Karnataka, IndiaPurpose: To evaluate the morphological types of indirect choroidal rupture (ICR using spectral domain optical coherence tomography (SD-OCT.Methods: This was a prospective interventional study of 18 eyes of 18 patients who presented with a history of blunt ocular trauma resulting in choroidal rupture. All patients underwent detailed ophthalmic evaluation and SD-OCT examination.Results: Mean age of the patients was 32±9.6 years. Morphologically, two types of choroidal rupture were seen on SD-OCT. The first type seen (Type 1 ICR was a forward protrusion of the retinal pigment epithelium-choriocapillaris (RPE-CC layer with an acutely angled pyramid or dome shape. This was associated with either a small loss of continuity of the retinal pigment epithelium layer or elevated RPE-CC projection accompanied by a significant quantity of subretinal hemorrhage. The second type observed (Type 2 ICR was a larger area of disruption of the RPE-CC layer, photoreceptor inner segment/outer segment junction, and external limiting membrane, with a posteriorly directed concave contour depression at that area and downward sliding of tissues into the defect. At presentation, ten eyes were observed to have Type 1 ICR and eight to have Type 2 ICR. Of the 18 eyes, one with Type 1 ICR and two with Type 2 ICR developed choroidal neovascularization (16.6%.Conclusion: Two distinct tomographic patterns of choroidal ruptures were identified on SD-OCT, which may allow ruptures to be classified into two morphological types. There are morphometric and clinical differences between the two types, which may help to prognosticate visual outcome and anticipate complications following choroidal ruptures.Keywords: SD-OCT, ICR, blunt ocular trauma

  15. Inhibition of ocular neovascularization by co-inhibition of VEGF-A and PLGF.

    Science.gov (United States)

    Huo, Xiaochuan; Li, Youxiang; Jiang, Yuhua; Sun, Xiaoyun; Gu, Lixue; Guo, Wenshi; Sun, Dapeng

    2015-01-01

    Age-related macular degeneration (AMD) appears to be a disease with increasing incidence in Western countries and may develop into acquired blindness. Choroidal neovascularization (CNV) is the most frequent cause for AMD, and is commonly induced by regional inflammation. Past studies have highlighted vascular endothelial growth factor A (VEGF-A) as a major trigger for CNV. However, studies on the associated angiogenic factors other than VEGF-A are lacking. Here, we used a well-established laser burn (LB)-induced experimental CNV mouse model to study the molecular mechanisms underlying the development of CNV after ocular injury. We analyzed vessel density by lectin labeling. We isolated macrophages, endothelial cells and other cell types by flow cytometry, and analyzed levels of different angiogenic factors in these populations. We used antisera against VEGF-A (aVEGF) and/or antisera against placental growth factor (PLGF; aPLGF) to antagonize CNV. We used an antibody-driven toxin to selectively eliminate macrophages to evaluate the role of macrophages in CNV. We also examined expression of PLGF in macrophage subtypes. The choroidal vessel density increased significantly 7 days after LB. LB increased significantly the levels of VEGF-A and PLGF in mouse eyes. Treatment with aVEGF significantly blunted increases in vessel density by LB. Treatment with aPLGF alone did not significantly reduce increases in vessel density. However, aPLGF significantly increased the inhibitory effects of aVEGF on vessel density increases. While VEGF-A was produced by endothelial cells, macrophages and other types at similar levels, PLGF seemed to be predominantly produced by macrophages. Selective macrophage depletion significantly reduced CNV. M2, but M1 macrophages produced high levels of PLGF. Together, our data suggest a previously unappreciated role of PLGF in coordination with VEGF-A to regulate CNV during ocular injury. Our study highlights macrophages and their production of PLGF

  16. Inhibition of Ocular Neovascularization by Co-Inhibition of VEGF-A and PLGF

    Directory of Open Access Journals (Sweden)

    Xiaochuan Huo

    2015-03-01

    Full Text Available Background/Aims: Age-related macular degeneration (AMD appears to be a disease with increasing incidence in Western countries and may develop into acquired blindness. Choroidal neovascularization (CNV is the most frequent cause for AMD, and is commonly induced by regional inflammation. Past studies have highlighted vascular endothelial growth factor A (VEGF-A as a major trigger for CNV. However, studies on the associated angiogenic factors other than VEGF-A are lacking. Methods: Here, we used a well-established laser burn (LB-induced experimental CNV mouse model to study the molecular mechanisms underlying the development of CNV after ocular injury. We analyzed vessel density by lectin labeling. We isolated macrophages, endothelial cells and other cell types by flow cytometry, and analyzed levels of different angiogenic factors in these populations. We used antisera against VEGF-A (aVEGF and/or antisera against placental growth factor (PLGF; aPLGF to antagonize CNV. We used an antibody-driven toxin to selectively eliminate macrophages to evaluate the role of macrophages in CNV. We also examined expression of PLGF in macrophage subtypes. Results: The choroidal vessel density increased significantly 7 days after LB. LB increased significantly the levels of VEGF-A and PLGF in mouse eyes. Treatment with aVEGF significantly blunted increases in vessel density by LB. Treatment with aPLGF alone did not significantly reduce increases in vessel density. However, aPLGF significantly increased the inhibitory effects of aVEGF on vessel density increases. While VEGF-A was produced by endothelial cells, macrophages and other types at similar levels, PLGF seemed to be predominantly produced by macrophages. Selective macrophage depletion significantly reduced CNV. M2, but M1 macrophages produced high levels of PLGF. Conclusions: Together, our data suggest a previously unappreciated role of PLGF in coordination with VEGF-A to regulate CNV during ocular injury

  17. Transvitreal retino-choroidal biopsy of suspected malignant lesions of the choroid

    DEFF Research Database (Denmark)

    Jensen, O.A.; Prause, J.U.; Scherfig, E.

    1997-01-01

    ophthalmology, intraocular biopsy, transvitreal retino-choroidal biopsy, malignant melanoma of choroid, histopathology, brachytherapy......ophthalmology, intraocular biopsy, transvitreal retino-choroidal biopsy, malignant melanoma of choroid, histopathology, brachytherapy...

  18. A comparison of two methods to measure choroidal thickness by enhanced depth imaging optical coherence tomography

    DEFF Research Database (Denmark)

    Lundberg, Lars Kristian; Vestergaard, Anders Højslet; Vergmann, Anna Stage

    coherence tomography (EDI-SD OCT) has made it possible to visualize the choroid, and it is generally accepted that Heidelberg Spectralis OCT provides valid measurements of choroidal thickness (CT), although no fully automated software is commercially available. Two methods for CT-measurement are available...... the CT: 1: Segmentation method; by the use of the thickness profile window we manually edited and moved the inner limiting membrane (ILM) line to the choroid-scleral border (CSB), while we kept the automated defined Bruchs membrane (BM). Hereafter, the software calculated the vertical distance between......Introduction The choroid is believed to be involved in the pathophysiology of several vision threatening diseases such as age-related macular degeneration, central serous chorioretinopathy, inflammatory disorders and myopic macular degeneration. Enhanced depth imaging spectral-domain optical...

  19. Inflammation and its role in age-related macular degeneration.

    Science.gov (United States)

    Kauppinen, Anu; Paterno, Jussi J; Blasiak, Janusz; Salminen, Antero; Kaarniranta, Kai

    2016-05-01

    Inflammation is a cellular response to factors that challenge the homeostasis of cells and tissues. Cell-associated and soluble pattern-recognition receptors, e.g. Toll-like receptors, inflammasome receptors, and complement components initiate complex cellular cascades by recognizing or sensing different pathogen and damage-associated molecular patterns, respectively. Cytokines and chemokines represent alarm messages for leukocytes and once activated, these cells travel long distances to targeted inflamed tissues. Although it is a crucial survival mechanism, prolonged inflammation is detrimental and participates in numerous chronic age-related diseases. This article will review the onset of inflammation and link its functions to the pathogenesis of age-related macular degeneration (AMD), which is the leading cause of severe vision loss in aged individuals in the developed countries. In this progressive disease, degeneration of the retinal pigment epithelium (RPE) results in the death of photoreceptors, leading to a loss of central vision. The RPE is prone to oxidative stress, a factor that together with deteriorating functionality, e.g. decreased intracellular recycling and degradation due to attenuated heterophagy/autophagy, induces inflammation. In the early phases, accumulation of intracellular lipofuscin in the RPE and extracellular drusen between RPE cells and Bruch's membrane can be clinically detected. Subsequently, in dry (atrophic) AMD there is geographic atrophy with discrete areas of RPE loss whereas in the wet (exudative) form there is neovascularization penetrating from the choroid to retinal layers. Elevations in levels of local and systemic biomarkers indicate that chronic inflammation is involved in the pathogenesis of both disease forms.

  20. Management of neovascular glaucoma.

    Science.gov (United States)

    Ajvazi, Halil; Goranci, Ilhami; Lutaj, Pajtim

    2013-01-01

    Neovascular glaucoma is an atrophic optic neuropathy resulting from the neovascularization of the iridocorneal angle increasing the intraocular pressure. To show the incidence of NVG in comparison to the other types of glaucoma and to compare with the relevant literature data and other referent clinics. In this study were included 116 patients with NVG, of whom 75 or 64.7% male and 41 or 35.3% female, treated from January 2003 until February 2013. Visual acuity damages from NVG, were classified as big damages with 84.7% of cases and minor damages with 15.3% of cases. Cases with heavy damages were the cases with blindness, L+P+/- up to V = 0.3 and cases with slightly damages with V = 0.4-1.0. NVG caused by PDR with 52 cases or 44.8% and CRVO with 12 cases or 10.3%. We should be focused on prevention of diabetic retinopathy which requires interdisciplinary cooperation. In cases when diabetic retinopathy is present, we have to advise patients to undergo PRP as soon as possible, since it is the only way to prevent NVG and heavy consequences.

  1. Deletion of autophagy inducer RB1CC1 results in degeneration of the retinal pigment epithelium.

    Science.gov (United States)

    Yao, Jingyu; Jia, Lin; Khan, Naheed; Lin, Chengmao; Mitter, Sayak K; Boulton, Michael E; Dunaief, Joshua L; Klionsky, Daniel J; Guan, Jun-Lin; Thompson, Debra A; Zacks, David N

    2015-01-01

    Autophagy regulates cellular homeostasis and response to environmental stress. Within the retinal pigment epithelium (RPE) of the eye, the level of autophagy can change with both age and disease. The purpose of this study is to determine the relationship between reduced autophagy and age-related degeneration of the RPE. The gene encoding RB1CC1/FIP200 (RB1-inducible coiled-coil 1), a protein essential for induction of autophagy, was selectively knocked out in the RPE by crossing Best1-Cre mice with mice in which the Rb1cc1 gene was flanked with Lox-P sites (Rb1cc1(flox/flox)). Ex vivo and in vivo analyses, including western blot, immunohistochemistry, transmission electron microscopy, fundus photography, optical coherence tomography, fluorescein angiography, and electroretinography were performed to assess the structure and function of the retina as a function of age. Deletion of Rb1cc1 resulted in multiple autophagy defects within the RPE including decreased conversion of LC3-I to LC3-II, accumulation of autophagy-targeted precursors, and increased numbers of mitochondria. Age-dependent degeneration of the RPE occurred, with formation of atrophic patches, subretinal migration of activated microglial cells, subRPE deposition of inflammatory and oxidatively damaged proteins, subretinal drusenoid deposits, and occasional foci of choroidal neovascularization. There was secondary loss of photoreceptors overlying the degenerated RPE and reduction in the electroretinogram. These observations are consistent with a critical role of autophagy in the maintenance of normal homeostasis in the aging RPE, and indicate that disruption of autophagy leads to retinal phenotypes associated with age-related degeneration.

  2. Central areolar choroidal dystrophy.

    NARCIS (Netherlands)

    Boon, C.J.F.; Klevering, B.J.; Cremers, F.P.M.; Zonneveld-Vrieling, M.N.; Theelen, T.; Hollander, A.I. den; Hoyng, C.B.

    2009-01-01

    OBJECTIVE: To describe the clinical characteristics, follow-up data and molecular genetic background in a large group of patients with central areolar choroidal dystrophy (CACD). DESIGN: Retrospective case series study. PARTICIPANTS: One hundred three patients with CACD from the Netherlands. METHODS

  3. Inflammatory Cytokines Induce Expression of Chemokines by Human Retinal Cells: Role in Chemokine Receptor Mediated Age-related Macular Degeneration.

    Science.gov (United States)

    Nagineni, Chandrasekharam N; Kommineni, Vijay K; Ganjbaksh, Nader; Nagineni, Krishnasai K; Hooks, John J; Detrick, Barbara

    2015-11-01

    Chemokine reeptor-3 (CCR-3) was shown to be associated with choroidal neovascularization (CNV) in age-related macular degeneration (AMD). AMD is a vision threatening retinal disease that affects the aging population world-wide. Retinal pigment epithelium and choroid in the posterior part of the retina are the key tissues targeted in the pathogenesis of CNV in AMD. We used human retinal pigment epithelial (HRPE) and choroidal fibroblast (HCHF) cells, prepared from aged adult human donor eyes, to evaluate the expression of major CCR-3 ligands, CCL-5, CCL -7, CCL-11,CCL-24 and CCL-26. Microarray analysis of gene expression in HRPE cells treated with inflammatory cytokine mix (ICM= IFN-γ+TNF-α+IL-1β) revealed 75 and 23-fold increase in CCL-5 and CCL-7 respectively, but not CCL-11, CCL-24 and CCL-26. Chemokine secretion studies of the production of CCL5 and CCL7 by HRPE corroborated with the gene expression analysis data. When the HRPE cells were treated with either individual cytokines or the ICM, both CCL-5 and CCL-7 were produced in a dose dependent manner. Similar to the gene expression data, the ICM did not enhance HRPE production of CCL-11, CCL-24 and CCL-26. CCL-11 and CCL-26 were increased with IL-4 treatment and this HRPE production was augmented in the presence of TNF-α and IL1β. When HCHF cells were treated with either individual cytokines or the ICM, both CCL-5 and CCL-7 were produced in a dose dependent fashion. IL-4 induced low levels of CCL-11 and CCL-26 in HCHF and this production was significantly enhanced by TNF-α. Under these conditions, neither HRPE nor HCHF were demonstrated to produce CCL-24. These data demonstrate that chronic inflammation triggers CCL-5 and CCL-7 release by HRPE and HCHF and the subsequent interactions with CCR3 may participate in pathologic processes in AMD.

  4. A retrospective analysis of triple combination therapy with intravitreal bevacizumab, posterior sub-tenon's triamcinolone acetonide, and low-fluence verteporfin photodynamic therapy in patients with neovascular age-related macular degeneration.

    Science.gov (United States)

    Kovacs, Kyle D; Quirk, Matthew T; Kinoshita, Taiga; Gautam, Shiva; Ceron, Olga M; Murtha, Timothy J; Arroyo, Jorge G

    2011-03-01

    To assess the efficacy of triple combination therapy (TCT) including bevacizumab (BEV), low-fluence photodynamic therapy, and posterior sub-Tenon's triamcinolone acetonide in patients with wet age-related macular degeneration. This institutional review board-approved retrospective consecutive case series included 31 eyes treated for wet age-related macular degeneration with TCT at the Beth Israel Deaconess Medical Center between June 2004 and November 2008. Outcome measures included visual acuity, retinal thickness as measured by optical coherence tomography, time to retreatment, and complications. Triple combination therapy eyes showed significant 3-month and 6-month improvement in visual acuity of 0.140 ± 0.273 logarithm of the minimum angle of resolution and 0.182 ± 0.383 logarithm of the minimum angle of resolution after treatment, respectively (P = 0.0219 and 0.0470, respectively). Central retinal thickness significantly improved at 3 months (-123.8 ± 102.7 μm), 6 months (-87.7 ± 99.8 μm), and 12 months (-101.6 ± 103.3 μm) on optical coherence tomography. Half of eyes that underwent TCT required retreatment by the conclusion of their follow-up, and eyes that underwent TCT had a 1-year Kaplan-Meier survival rate of 62.1 ± 10.8%. Triple combination therapy (TCT) appears to effectively improve visual acuity and decrease retinal thickness often without need for subsequent retreatment within the first year of follow-up. Further investigation of TCT in prospective trials is warranted.

  5. [Photodynamic therapy in treatment of chorioid neovascularization].

    Science.gov (United States)

    Avetisov, S E; Budzinskaia, M V; Kiseleva, T N; Kazarian, E E; Gurova, I V; Loshchenov, V B; Shevchik, S A; Kuz'min, S G; Vorozhtsov, G N

    2007-01-01

    The authors studied the effectiveness of photodynamic therapy (PDT) with Photosence, a Russian photosensitizer, in treatment of chorioid neovascularization (CNV) in cases of age-related macular degeneration (ARMD) and pathological myopia (PM). The subjects were 73 patients with CNV suffering from ARMD and PM. The efficiency of PDT and complex conservative therapy was compared using vision acuity measurement, retinal morphometry, and fluorescent eye ground angiography (FEGA), performed before treatment, immediately after treatment, and 1, 3, 6, and 12 months later. The study showed that PDT in patients with CNV, ARMD and PM was more efficient than pharmacotherapy. Vision acuity improved or stabilized, and the parameters of retinal morphometry and FEGA improved as well. The results of the study evidence high efficiency of PDT with Photosence in treatment of CNV with ARMD and PM.

  6. 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

  7. [Comparison of Preferential Hyperacuity Perimeter (PHP) test and Amsler grid test in the diagnosis of different stages of age-related macular degeneration].

    Science.gov (United States)

    Kampmeier, J; Zorn, M M; Lang, G K; Botros, Y T; Lang, G E

    2006-09-01

    Age-related macular degeneration (ARMD) is the leading cause of blindness in people over 65 years of age. A rapid loss of vision occurs especially in cases with choroidal neovascularisation. Early detection of ARMD and timely treatment are mandatory. We have prospectively studied the results of two diagnostic self tests for the early detection of metamorphopsia and scotoma, the PHP test and the Amsler grid test, in different stages of ARMD. Patients with ARMD and best corrected visual acuity of 6/30 or better (Snellen charts) were examined with a standardised protocol, including supervised Amsler grid examination and PHP, a new device for metamorphopsia or scotoma measurement, based on the hyperacuity phenomenon in the central 14 degrees of the visual field. The stages of ARMD were independently graded in a masked fashion by stereoscopic ophthalmoscopy, stereoscopic fundus colour photographs, fluorescein angiography, and OCT. The patients were subdivided into 3 non-neovascular groups [early, late (RPE atrophy > 175 microm) and geographic atrophy], a neovascular group (classic and occult CNV) and an age-matched control group (healthy volunteers). 140 patients, with ages ranging from 50 to 90 years (median 68 years), were included in the study. Best corrected visual acuity ranged from 6/30 to 6/6 with a median of 6/12. 95 patients were diagnosed as non-neovascular ARMD. Thirty eyes had early ARMD (9 were tested positive by the PHP test and 9 by the Amsler grid test), and 50 late ARMD (positive: PHP test 23, Amsler grid test 26). The group with geographic atrophy consisted of 15 eyes (positive: PHP test 13, Amsler grid test 10). Forty-five patients presented with neovascular ARMD (positive: PHP test 38, Amsler grid test 36), 34 volunteers served as control group (positive: PHP test 1, Amsler grid test 5). The PHP and Amsler grid tests revealed comparable results detecting metamorphopsia and scotoma in early ARMD (30 vs. 30 %) and late ARMD (46 vs. 52 %). However, the

  8. Long-term effectiveness of ranibizumab for age-related macular degeneration and diabetic macular edema

    OpenAIRE

    Fong, Angie HC; Lai, Timothy YY

    2013-01-01

    Neovascular age-related macular degeneration (AMD) and diabetic macular edema (DME) are major causes of visual impairment in the elderly population worldwide. With the aging population, the prevalence of neovascular AMD and DME has increased substantially over the recent years. Vascular endothelial growth factor (VEGF) has been implicated as playing an important role in the pathogenesis of both neovascular AMD and DME. Since its introduction in 2006, ranibizumab, a recombinant, humanized, mon...

  9. Oxalomalate reduces expression and secretion of vascular endothelial growth factor in the retinal pigment epithelium and inhibits angiogenesis: Implications for age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Sung Hwan Kim

    2016-12-01

    Full Text Available Clinical and experimental observations indicate a critical role for vascular endothelial growth factor (VEGF, secreted by the retinal pigment epithelium (RPE, in pathological angiogenesis and the development of choroidal neovascularization (CNV in age-related macular degeneration (AMD. RPE-mediated VEGF expression, leading to angiogenesis, is a major signaling mechanism underlying ocular neovascular disease. Inhibiting this signaling pathway with a therapeutic molecule is a promising anti-angiogenic strategy to treat this disease with potentially fewer side effects. Oxalomalate (OMA is a competitive inhibitor of NADP+-dependent isocitrate dehydrogenase (IDH, which plays an important role in cellular signaling pathways regulated by reactive oxygen species (ROS. Here, we have investigated the inhibitory effect of OMA on the expression of VEGF, and the associated underlying mechanism of action, using in vitro and in vivo RPE cell models of AMD. We found that OMA reduced the expression and secretion of VEGF in RPE cells, and consequently inhibited CNV formation. This function of OMA was linked to its capacity to activate the pVHL-mediated HIF-1α degradation in these cells, partly via a ROS-dependent ATM signaling axis, through inhibition of IDH enzymes. These findings reveal a novel role for OMA in inhibiting RPE-derived VEGF expression and angiogenesis, and suggest unique therapeutic strategies for treating pathological angiogenesis and AMD development.

  10. Clinical and differential utility of VEGF inhibitors in wet age-related macular degeneration: focus on aflibercept

    Directory of Open Access Journals (Sweden)

    Stewart MW

    2012-07-01

    Full Text Available Michael W StewartCollege of Medicine, Mayo Clinic, Jacksonville, FL, USAAbstract: Age-related macular degeneration (AMD has become a major public health problem and a leading cause of blindness in industrialized nations. AMD results from the ageing eye's inability to metabolize and dispose completely of photoreceptor outer segments and other waste products. As a result, lipids, particularly apolipoproteins, accumulate within Bruch's membrane, leading to chronic ischemia and inflammation. The subsequent upregulation of inflammatory cytokines and growth factors, including vascular endothelial growth factor (VEGF, induces the growth of neovascular membranes from the choriocapillaris into the subretinal or subretinal pigment epithelium spaces. To counter this, intravitreally administered drugs (pegaptanib, bevacizumab, ranibizumab that specifically target VEGF have become the standard treatment for exudative AMD. Aflibercept, a recently approved fusion protein, binds to all isoforms of both VEGF-A and placental growth factor with high affinity. Phase III trials showed that monthly or every other month injections of aflibercept prevent vision loss (fewer than 15 letters in 95% of patients. Additionally, aflibercept injections every 4 or 8 weeks produce average vision gains of 6.9 letters to 10.9 letters, comparable with those achieved with monthly ranibizumab. After one year of regularly administered aflibercept injections, patients required an average of only 4.2 injections during the second year. Aflibercept promises to decrease the injection frequency required for many patients and appears to serve as an effective “salvage” therapy for patients who respond poorly to other anti-VEGF drugs.Keywords: age-related macular degeneration, choroidal neovascularization, vascular endothelial growth factor, aflibercept, ranibizumab, bevacizumab, VEGF trap

  11. A Case of Choroidal Tubercles

    Institute of Scientific and Technical Information of China (English)

    Chaoran Zhang

    2004-01-01

    Purpose: To report a case of choroidal tubercles in a miliary tuberculosis boy.Method: Clinical features description.Results: A 14-year-old boy was found to have multifocal choroidal tubercles. Angiography was performed. He was followed up for 12 months. The choroidal lesions regressed after using anti-tuberculosis drugs for 8 months. Pigment changes remained. Conclusion: Tuberculosis may present as a posterior segment inflammation. In miliary tuberculosis, choroid is also a target tissue. Eye Science 2004;20:23-24.

  12. Malignant melanoma of choroid

    Directory of Open Access Journals (Sweden)

    Manohar S

    1991-01-01

    Full Text Available Four cases of malignant melanoma of the choroid are reported due to rarity of the condition in India. One of the cases presented with Naevus of Ota. All the cases had typical clinical and investigative features. All cases were enucleated. Histopathologically three of them were of mixed type and one was of the epithelioid type. Two of the cases were seen in patients below 40 years of age.

  13. Visual outcomes of age-related macular degeneration patients undergoing intravitreal ranibizumab monotherapy in an urban population

    Directory of Open Access Journals (Sweden)

    Basheer K

    2015-05-01

    Full Text Available Khadijah Basheer, Evelyn Mensah, Tina Khanam, Neda Minakaran Ophthalmology Department, Central Middlesex Hospital, London, UK Aim: To compare the visual outcomes of an urban population with age-related macular degeneration (AMD undergoing ranibizumab monotherapy to the results from major clinical trials.Procedures: Prospective data was collected from 164 wet AMD patients receiving intravitreal ranibizumab. Visual acuities were obtained with the Early Treatment Diabetic Retinopathy Study chart. All patients underwent a loading phase of three monthly treatments of ranibizumab. Patients were monitored monthly using a retreatment criterion. Treatment was further individualized by sequentially lengthening follow-up intervals when stable.Results: At 12 and 24 months, respectively, the percentage of eyes that maintained vision was 91% and 88.6%. We found that 20.3% of eyes had improved vision at 12 months and 20% at 24 months. At 12 months, 8.3% of eyes’ vision worsened and 12% worsened at 24 months.Conclusion: Individualized ranibizumab monotherapy is effective in preserving vision in wet AMD and follows the same trends as the pivotal trials. Keywords: visual acuity, comparison of age-related macular degeneration treatment trials, choroidal neovascular membrane

  14. Fuchs' adenoma of the choroid simulating a choroidal hemangioma.

    NARCIS (Netherlands)

    Razzaq, L.; Marinkovic, M.; Swart, W.; Duinen, S.G. van; Keunen, J.E.E.; Luyten, G.P.M.

    2012-01-01

    We report the case of a 54-year-old female who was referred to us with an amelanotic mass on the posterior pole of the left eye involving the macula. Fundus fluorescein angiography revealed a hyperfluorescent choroidal mass. Indocyanine green chorioangiography revealed a hypofluorescent choroidal

  15. Long-term results after external radiotherapy in age-related macular degeneration. A prospective study

    Energy Technology Data Exchange (ETDEWEB)

    Prettenhofer, U.; Mayer, R.; Stranzl, H.; Oechs, A.; Hackl, A. [Dept. of Radiotherapy, Univ. Medical School, Graz (Austria); Haas, A. [Dept. of Opthalmology, Univ. Medical School, Graz (Austria)

    2004-02-01

    Purpose: to prospectively evaluate the short- and long-term efficacy of external radiotherapy (RT) in patients with age-related macular degeneration (AMD) by comparing two different dose schedules. Patients and methods: in this prospective, nonrandomized, comparative study including 80 patients, the efficacy of external RT with a total dose of 14.4 Gy (group A, n = 40) and 25.2 Gy (group B, n = 40) was compared. Patients of group a were irradiated between September 1995 and July 1996, patients of group b between August 1996 and November 1997. 67 patients presented with occult choroidal neovascularization (CNV), 13 with classic subfoveal lesions. Complete ophthalmologic investigation was performed before RT, at intervals of 3 months during the 1st year after RT, and of 6 months thereafter. Results: 12 months after RT, vision deteriorated in 85% (14.4 Gy) and 65% (25.2 Gy) of patients. Central visual field decreased with both dose schedules. There was no morphological benefit in neovascular changes. After 48 months, complete follow-up was possible in 46 patients who showed a significant loss of vision similar to the natural course of AMD. Conclusion: external RT of AMD with 14.4 Gy as well as with the escalated dose of 25.2 Gy showed a poor beneficial outcome after 6 and 12 months, respectively. After a follow-up of 4 years, visual outcome in irradiated patients was similar to the natural course of the disease. A conspicuous efficacy of RT in prevention of blindness could not be demonstrated. (orig.)

  16. The effects of chemokines in ocular neovascular diseases%趋化因子与眼部新生血管性疾病研究进展

    Institute of Scientific and Technical Information of China (English)

    苏梦茹

    2013-01-01

    Chemokine is a family of small chemotactic cytokines.Chemokine mainly locates in neutrophile granulocyte,monocyte,macrophage,T lymphocyte and B lymphocyte,and some cells and immunoactive cells also secret cytokines.Researches showed that chemokine plays important roles in many patho-physiological activities,such as inflammatory response,infection procedure,wound healing,regulation of immunity,angiogenesis,invasion and metastases of cancer,etc..Some chemokine factors,such as hyperglycemia,hypoxia,oxidative stress,stimulate the ocular histiocytes to up-regulate the expressions of CXC chemokines and CC chemokines,which participate in the development of choroidal neovascularization and ocular neovascular diseases.This article reviews current progress in chemokine and the relationship between chemokines and ocular neovascular diseases,especially in diabetic retinopathy (DR) and age-related macular degeneration (AMD) etc..%趋化因子是机体内一组具有趋化作用的细胞因子,主要表达于中性粒细胞、单核细胞、巨噬细胞、T淋巴细胞和B淋巴细胞,眼部的组织细胞及免疫活性细胞亦可分泌产生多种趋化因子.研究表明,趋化因子在炎症反应、感染、创伤愈合、免疫调节、血管发生、肿瘤的侵袭和转移等生理病理过程中发挥重要作用.高糖、缺氧、氧化应激等因素刺激眼部组织细胞上调CXC趋化因子、CC趋化因子的表达,参与脉络膜新生血管(CNV)及眼部新生血管性疾病的发展.就趋化因子的基本概念和功能以及其与常见眼部新生血管性疾病,如糖尿病视网膜病变(DR)、年龄相关性黄斑变性(AMD)的关系进行综述.

  17. Clinical and histological findings after intravitreal injection of bevacizumsb (Avastin®) in a porcine model of choroidal neovascularisation

    DEFF Research Database (Denmark)

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

    2010-01-01

    was identified immunohistochemically in the inner limiting membrane (ILM) and to a lesser degree in the remaining retina. Strong staining was also detected in both retinal blood vessels and entire CNV membranes with no cellular predisposition. Vascular endothelial growth factor expression was found in the CNV...... membranes, in the ILM, in the ganglion cell layer, in Müller cells throughout the neuroretina and in retinal blood vessels. CONCLUSIONS: Bevacizumab significantly reduced the proliferation of vascular endothelial cells in CNV membranes and showed a strong trend towards a reduction of leakage from......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...

  18. Treatment of choroid metastases.

    Science.gov (United States)

    Dobrowsky, W

    1988-02-01

    Sixteen patients with choroid secondary tumours were treated with irradiation consisting of 40-50 Gy in 3-5 weeks. There were 14 female patients with breast cancer, one male patient with prostatic cancer and one male patient with cancer of unknown origin. In four cases bilateral ocular metastases were seen. Ten out of 20 treated eyes showed complete response to treatment, seven out of 20 showed partial response and three out of 20 were not influenced by irradiation. Survival of patients, all having widespread metastatic disease, was 3-48 months (median 20 months). All patients responding to treatment showed increased quality of life.

  19. Bevasiranib for the treatment of wet, age-related macular degeneration.

    Science.gov (United States)

    Garba, Adinoyi O; Mousa, Shaker A

    2010-01-01

    Age- related Macular Degeneration (AMD) is the leading cause of severe visual impairment in people 65 years and older in industrialized nations. Exudative, or "wet", AMD is a late form of AMD (as distinguished from atrophic, so-called dry, AMD) and is responsible for over 60% of all cases of blindness due to AMD. It is widely accepted that vascular endothelial growth factor (VEGF) is a key component in the pathogenesis of choroidal neo-vascularization (CNV), which is a precursor to wet AMD. The current gold-standard for treating wet AMD is the monoclonal antibody fragment ranibizumab (trade name Lucentis), which targets VEGF. Other agents used to treat wet AMD include pegaptanib (Macugen), bevacizumab (Avastin; off-label use), and several other experimental agents. The advent of small interfering RNA (siRNA) has presented a whole new approach to inhibiting VEGF. This article reviews the status of a novel siRNA-based therapeutic, bevasiranib, for the treatment of wet AMD. Bevasiranib is believed to work by down regulating VEGF production in the retina. Studies in human cell-lines and animal models have shown that VEGF siRNAs are effective in inhibiting VEGF production. Although there is a lack of sufficient published data on human studies supporting the use of bevasiranib for wet AMD, available data indicates that due to its unique mechanism of action, bevasiranib might hold some promise as a primary or adjunct treatment for wet AMD.

  20. The vitreomacular interface in different types of age-related macular degeneration

    Science.gov (United States)

    El-Hifnawy, Mohamed Abd ElMonaem; Ibrahim, Hisham Ali; Gomaa, Amir Ramadan; Elmasry, Mohamed A

    2017-01-01

    AIM To evaluate the vitreomacular interface in cases with wet age-related macular degeneration (AMD) and to compare them to eyes with dry AMD and normal eyes. METHODS This was a cross-sectional comparative study that included 87 eyes with wet AMD, 42 eyes with dry AMD and 40 eyes without AMD as a control group. Optical coherence tomography (OCT) examination was performed for all patients to assess the vitreomacular interface. RESULTS In the wet AMD group, 34.5% of cases had vitreomacular adhesion (VMA). Only 14.3% of dry AMD cases and 10% of control cases had VMA. There was a significant difference between the control group and the wet AMD group (P=0.004) as well as the dry and wet AMD group (P=0.017). There was also a significant difference between the incidence of VMA in patients with subretinal choroidal neovascularization (CNV, type 1) and intraretinal CNV (type 2 or type 3) (P=0.020). CONCLUSION There is an association between posterior vitreous attachment and AMD. There is also an increased incidence of VMA with intra-retinal CNV. PMID:28251084

  1. Is age-related macular degeneration a problem in Ibadan, Sub-Saharan Africa?

    Directory of Open Access Journals (Sweden)

    Oluleye TS

    2012-04-01

    Full Text Available Tunji Sunday OluleyeRetina and Vitreous Unit, Department of Ophthalmology, University College Hospital, Ibadan, Nigeria, West AfricaBackground: Age-related macular degeneration (AMD is considered uncommon in black populations including those of Sub-Saharan Africa. The aim of this review was to determine the pattern of presentation of AMD in our hospital located in Ibadan, the largest city in Sub-Saharan Africa.Methods: A retrospective review of all cases with AMD presenting to the Eye and Retinal Clinic of the University College Hospital, Ibadan, West Africa was undertaken between October 2007 and September 2010.Results: In the 3 years reviewed, 768 retinal cases were seen in the hospital, 101 (14% of which were diagnosed with AMD. The peak age was 60–79 years. The male to female ratio was approximately 2:3. More males presented with the advanced form of dry AMD than females (odds ratio = 2.33. However, more females had advanced wet AMD than males (odds ratio = 1.85. Wet AMD was seen in 40 cases (40%.Conclusion: The review determined that, as AMD is not uncommon and wet AMD is relatively more common in our hospital than has been reported previously, this is probably true of Ibadan in general.Keywords: age-related maculopathy, choroidal neovascular membrane, retinal, vitreoretinal, drusen

  2. PPAR-α Ligands as Potential Therapeutic Agents for Wet Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Marisol del V Cano

    2008-01-01

    Full Text Available The peroxisome proliferator-activated receptors (PPAR's are members of the steroid/thyroid nuclear receptor, superfamily of transcription factors. There are currently three known PPAR subtypes, α, β, and γ. The PPARs are now recognized participants in a number of biological pathways some of which are implicated in the pathogenesis of age-related macular degeneration (AMD. These include immune modulation, lipid regulation, and oxidant/antioxidant pathways important to the onset and progression of “dry” AMD, and vascular endothelial growth factor (VEGF mediated pathways that stimulate choroidal neovascularization (CNV, characteristic of “wet” AMD. PPAR-α is found in retina and also on vascular cells important to formation of CNV. At this time, however, relatively little is known about potential contributions of PPAR-α to the pathogenesis of dry and wet AMD. This review examines current literature for potential roles of PPAR-α in the pathogenesis and potential treatment of AMD with emphasis on prevention and treatment of wet AMD.

  3. Peripapillary choroidal thickness in childhood.

    Science.gov (United States)

    Read, Scott A; Alonso-Caneiro, David; Vincent, Stephen J; Collins, Michael J

    2015-06-01

    Changes in the thickness of the invivo peripapillary choroid have been documented in a range of ocular conditions in adults; however, choroidal thickness in the peripapillary region of children has not been examined in detail. This study therefore aimed to investigate the thickness of the peripapillary choroid and the overlying retinal nerve fibre layer (RNFL) in a population of normal children with a range of refractive errors. Ninety-three children (37 myopes and 56 non-myopes) aged between 11 and 16 years, had measurements of peripapillary choroidal and RNFL thickness derived from enhanced depth imaging optical coherence tomography images (EDI-OCT, Heidelberg Spectralis). The average thickness was determined in a series of five 0.25 mm width concentric annuli (each divided into 8 equal sized 45° sectors) centred on the optic nerve head boundary, accounting for individual ocular magnification factors and the disc-fovea angle. Significant variations in peripapillary choroidal thickness were found to occur with both annulus location (p choroid (mean 77 ± 16 μm) and the outermost annulus, the thickest choroid (191 ± 52 μm). The choroid was thinnest inferior to the optic nerve head (139 ± 38 μm) and was thickest in the superior temporal sector (157 ± 40 μm). Significant differences in the distribution of choroidal thickness were also associated with myopia, with myopic children having significantly thinner choroids in the inner and outer annuli of the nasal and temporal sectors respectively (p thickness also varied significantly with annulus location and sector (p thickness distribution associated with refractive error. This study establishes the normal variations in the thickness of the peripapillary choroid with radial distance and azimuthal angle from the optic nerve head boundary. A significant thinning of the peripapillary choroid associated with myopia in childhood was also observed in both nasal and temporal regions. The changes in peripapillary RNFL

  4. Age-related structural abnormalities in the human retina-choroid complex revealed by two-photon excited autofluorescence imaging.

    Science.gov (United States)

    Han, Meng; Giese, Guenter; Schmitz-Valckenberg, Steffen; Bindewald-Wittich, Almut; Holz, Frank G; Yu, Jiayi; Bille, Josef F; Niemz, Markolf H

    2007-01-01

    The intensive metabolism of photoreceptors is delicately maintained by the retinal pigment epithelium (RPE) and the choroid. Dysfunction of either the RPE or choroid may lead to severe damage to the retina. Two-photon excited autofluorescence (TPEF) from endogenous fluorophores in the human retina provides a novel opportunity to reveal age-related structural abnormalities in the retina-choroid complex prior to apparent pathological manifestations of age-related retinal diseases. In the photoreceptor layer, the regularity of the macular photoreceptor mosaic is preserved during aging. In the RPE, enlarged lipofuscin granules demonstrate significantly blue-shifted autofluorescence, which coincides with the depletion of melanin pigments. Prominent fibrillar structures in elderly Bruch's membrane and choriocapillaries represent choroidal structure and permeability alterations. Requiring neither slicing nor labeling, TPEF imaging is an elegant and highly efficient tool to delineate the thick, fragile, and opaque retina-choroid complex, and may provide clues to the trigger events of age-related macular degeneration.

  5. Role of ranibizumab in management of macular degeneration

    Directory of Open Access Journals (Sweden)

    Singh Rishi

    2007-01-01

    Full Text Available Age-related macular degeneration (AMD is one of the most common causes of severe vision loss in the western world. Both animal and human studies have established that vascular endothelial growth factor (VEGF plays an important role in the pathogenesis of this process. Ranibizumab (Lucentis™, Genentech, South San Francisco, CA is a monoclonal antibody fragment (Fab directed toward all isoforms of VEGF-A that was specifically designed to target wet AMD. The human antibody fragment is produced by an E. coli expression system and has a molecular weight of 48kD allowing for excellent retinal penetration. The most common ocular complaints of patients receiving ranibizumab injections in randomized clinical trials were transient conjunctival hemorrhage, vitreous floaters, intraocular inflammation, increased intraocular pressure and eye pain. The rates of serious adverse events such as retinal detachment, cataract and endophthalmitis were similar to those that have been reported with other intravitreal injections and patients should always be treated under strict aseptic conditions to reduce this risk. There were no significant non-ocular events found during any study so far and the risk of thromboembolic events was less than 4% and not different than sham. The MARINA, ANCHOR and PIER studies validated the safety and efficacy of ranibizumab amongst a large population with different choroidal neovascular membrane lesion types against sham or standard of care treatment. These studies recommended monthly intravitreal ranibizumab for patients. However, the PIER study reported that an alternative dosing of every three months is acceptable but less effective than monthly injections.

  6. SD-OCT findings in polypoidal choroidal vasculopathy.

    Science.gov (United States)

    Asensio-Sánchez, V M

    2016-01-01

    To examine patients with polypoidal choroidal vasculopathy (PCV), using spectral-domain optical coherence tomography (SD-OCT) to characterise and locate the PCV lesions. A series of 15 eyes of 10 patients diagnosed with PCV were examined. All eyes were imaged with macular SD-OCT. SD-OCT cross-sectional scan findings included atypical and typical pigment epithelial detachments (PEDs). Polyps and neovascularisation were located above Bruch membrane. All 15 eyes (100%) showed sub-retinal fluid (SRF) in association with PEDs. These SD-OCT findings located the vascular lesions of PCV in the sub-retinal pigment epithelium (RPE) space, and strongly suggest that PCV is a variant of type 1 neovascularization. Copyright © 2015. Published by Elsevier España, S.L.U.

  7. Macular epiretinal brachytherapy in treated age-related macular degeneration (MERITAGE): month 12 optical coherence tomography and fluorescein angiography.

    Science.gov (United States)

    Petrarca, Robert; Dugel, Pravin U; Nau, Jeffrey; Slakter, Jason S; Jaffe, Glenn J; Jackson, Timothy L

    2013-02-01

    To report the optical coherence tomography (OCT) and fundus fluorescein angiography (FFA) results of the Macular Epiretinal Brachytherapy in Treated Age-Related Macular Degeneration study. Prospective, multicenter, interventional, noncontrolled clinical trial. Fifty-three eyes of 53 participants with chronic, active neovascular age-related macular degeneration (AMD) requiring frequent anti-vascular endothelial growth factor retreatment. Participants underwent pars plana vitrectomy with a single 24-gray dose of epimacular brachytherapy (EMB), delivered with an intraocular, handheld, cannula containing a strontium 90/yttrium 90 source positioned over the active lesion. Participants were retreated with ranibizumab administered monthly as needed, using predefined retreatment criteria. Patients underwent FFA at baseline, month 1, and month 12. Patients underwent optical coherence tomography (OCT) at baseline and then monthly for 12 months. The FFA and OCT images were evaluated by independent, central reading facilities. Change in OCT centerpoint thickness and angiographic lesion size 12 months after EMB. Mean centerpoint thickness increased by 50 μm, from 186 to 236 μm (P = 0.292), but 70% of participants had an increase of less than the mean, with a median increase of only 1.8 μm. The FFA total lesion size increased slightly by 0.79 mm(2), from 14.69 to 15.48 mm(2) (P = 0.710). Total choroidal neovascularization (CNV) area increased by 1.17 mm(2), from 12.94 to 14.12 mm(2) (P = 0.556). The classic CNV area decreased substantially by 3.70 mm(2), from 3.90 to 0.20 mm(2) (P<0.01). Predominantly classic lesions showed the greatest response, with mean Early Treatment Diabetic Retinopathy Study visual acuity improving by 1.5 letters (versus -4.0 for all participants combined); mean centerpoint thickness decreased by 43 μm (P = 0.875). The angiographic and OCT response did not correlate with lesion size at baseline. In chronic, active, neovascular AMD, EMB is associated

  8. Expulsive choroidal haemorrhage

    Directory of Open Access Journals (Sweden)

    Srinivasan M

    1992-01-01

    Full Text Available Expulsive choroidal haemorrhage is a dramatic and serious complication of cataract surgery that occurred in five patients out of ten thousand consecutive cataract surgeries performed by the author during the year 1989 and 1990. Report about this dreaded complication after cataract surgery are scanty and as far as I can remember I have not seen any report in Indian ophthalmic literature recently. Since cataract surgery forms the major part of intra ocular surgeries performed in our country, I thought it would be appropriate to report about this rare complication which may occur to all of us. Out of five cases 3 were males and 2 were females in the age group ranging between 45-72 years. Two eyes regained vision up to 6/12 after intra operative expulsive haemorrhage. All the eyes were salvaged by doing anterior sclerotomy. Diabetes, hypertension, glaucoma and myopia are the commonest predisposing factors.

  9. [Choroidal melanoma - evolution and prognosis].

    Science.gov (United States)

    Chiruţa, Daria; Stan, Cristina

    2014-01-01

    Choroidal melanoma is the most common primary intraocular malignant tumor. We present the case of a 62 year old patient who was diagnosed with intraocular tumor in his right eye, for about three years. Regarding the fact that the patient refused any kind of treatment during this period, we just had the opportunity to monitor this case. Finally, the diagnosis was choroidal melanoma, confirmed by the histopathological exam.

  10. Behaviour of CD11b-Positive Cells in an Animal Model of Laser-Induced Choroidal Neovascularisation.

    Science.gov (United States)

    Li, Lu; Heiduschka, Peter; Alex, Anne F; Niekämper, Daniel; Eter, Nicole

    2017-01-01

    Immune cells, e.g. microglial cells of the retina, appear to be involved in pathological processes in neovascular age-related macular degeneration. Therefore, the purpose of this study was to immunohistochemically check the expression of various factors and cytokines by CD11b-positive (CD11b+) immune cells in an animal model of choroidal neovascularisation (CNV). We used the animal model of laser-induced CNV in mice. Eyes were isolated at 1, 4, 7, and 14 days after laser treatment. Cryosections were prepared and checked immunohistochemically for the presence of different growth factors and cytokines on microglial cells and other immune cells identified by CD11b immunoreactivity. We found that the number of CD11b+ cells at the laser spots increased dramatically 4 days after laser treatment, the majority of them entering the laser spot most probably by migration. CD11b+ cells in the laser spot were positive for a variety of pro-angiogenic factors, such as PDGF-β, FGF-1, FGF-2, and TGF-β1. They were also positive for some inflammatory cytokines, in particular TNF-α, IL-6, and CXCL1. In non-treated retinas, CD11b+ cells showed almost no immunoreactivity for these proteins. Microglial cells, macrophages, and other CD11b+ cells may promote the neovascularisation in the laser spot and show a moderate inflammatory behaviour. Immunoreactivity for most of these molecules was found to decrease during the time of observation. Modulation of immune cell activity may thus be a tool to reduce the extent of CNV. © 2017 S. Karger AG, Basel.

  11. Evaluation of variants in the selectin genes in age-related macular degeneration

    Di