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Sample records for intravitreal anti-vascular endothelial

  1. LOW ENDOPHTHALMITIS RATES AFTER INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR INJECTIONS IN AN OPERATION ROOM

    DEFF Research Database (Denmark)

    Freiberg, Florentina J; Brynskov, Troels; Munk, Marion R

    2017-01-01

    PURPOSE: To evaluate the rate of presumed endophthalmitis (EO) after intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections in three European hospitals performed in an operation room (OR) under sterile conditions. METHODS: A retrospective multicenter study between 2003 and 20...

  2. Subconjunctival hemorrhage after intravitreal injection of anti-vascular endothelial growth factor.

    Science.gov (United States)

    Yun, Cheolmin; Oh, Jaeryung; Hwang, Soon-Young; Kim, Seong-Woo; Huh, Kuhl

    2015-09-01

    To investigate the risk factors for subconjunctival hemorrhage (SCH) after intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) and evaluate the relationship between hemodynamic status at the time of injection and SCH. We retrospectively reviewed the medical records of 598 cases of 173 patients who underwent intravitreal injection of ranibizumab whose hemodynamic status was monitored at the time of the injection. Cases with SCH after the injection were included in the SCH group. We compared systemic factors, including the hemodynamic status between the SCH group and the control group. The SCH group included 67 cases and the control group included 531 cases without SCH. Baseline hemodynamic status was not significantly related to development of SCH. However, systolic blood pressure (BP) at injection was a significant risk factors for SCH (P = 0.034). Elevated systolic BP, mean arterial pressure (MAP), and pulse rate from baseline to time of injection were significantly related to the development of SCH (P = 0.011, P = 0.014, P = 0.036, respectively). In multivariate analysis, hypertension, a large change in MAP, and a fewer previous injections were significant risk factors for SCH after intravitreal injection (P = 0.030, P = 0.032, P = 0.028, respectively). Hemodynamic risk factors exist for SCH after intravitreal injection of anti-VEGF. To reduce the risk of SCH, strategies should seek to decrease patient anxiety, especially in those with hypertension.

  3. Efficacy of intravitreal injection of anti-vascular endothelial growth factor agents for stage 4 retinopathy of prematurity.

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    Cheng, Hui-Chen; Lee, Shui-Mei; Hsieh, Yi-Ting; Lin, Po-Kang

    2015-04-01

    To investigate the efficacy of intravitreal injection of anti-vascular endothelial growth factor agents for Stage 4 retinopathy of prematurity. Retrospective case series study. The medical records of patients receiving intravitreal injection of anti-vascular endothelial growth factor agents for Stage 4 retinopathy of prematurity from January 2007 to May 2012 in Taipei Veterans General Hospital were reviewed. A total of 13 eyes of 7 patients (3 boys and 4 girls) with Stage 4 retinopathy of prematurity were included. The mean gestational age and birth weight were 27.6 ± 2.6 weeks (range, 24.5-30.5 weeks) and 893.1 ± 293.2 g (range, 550-1422 g), respectively. The mean age at the time of injection was 38.2 ± 1.9 weeks (range, 36.0-41.5 weeks) postmenstrual age, and the mean follow-up period was 37.8 ± 19.5 months (range, 11.0-67.5 months). The active neovascularization regressed rapidly, and the anatomical outcomes were favorable in all patients. One eye developed recurrent retinal hemorrhage with localized retinal detachment 21 weeks after initial treatment, which resolved after a second injection. There were no ocular or systemic complications in these patients. Intravitreal injection of anti-vascular endothelial growth factor agents may be effective as monotherapy or as supplement to failed laser treatment for patients with Stage 4 retinopathy of prematurity without additional surgical intervention. Further randomized controlled trials are necessary to compare the clinical efficacy and safety with other conventional interventions.

  4. POOLED ESTIMATES OF INCIDENCE OF ENDOPHTHALMITIS AFTER INTRAVITREAL INJECTION OF ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR AGENTS WITH AND WITHOUT TOPICAL ANTIBIOTIC PROPHYLAXIS.

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    Reibaldi, Michele; Pulvirenti, Alfredo; Avitabile, Teresio; Bonfiglio, Vincenza; Russo, Andrea; Mariotti, Cesare; Bucolo, Claudio; Mastropasqua, Rodolfo; Parisi, Guglielmo; Longo, Antonio

    2018-01-01

    To assess the effect of topical antibiotic prophylaxis on postoperative endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor agents. A systematic literature search was performed from inception to March 2016 using PubMed, Medline, Web of Science, Embase, and the Cochrane Library, to identify articles that reported cases of endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor agents. We used a pooled analysis to estimate the incidence of cases of endophthalmitis who developed after injections performed with and without topical antibiotic prophylaxis. We used regression analysis to explore the effects of study characteristics on heterogeneity. From our search of electronic databases, we identified and screened 4,561 unique records. We judged 60 articles to have reported findings for cohorts of patients who met our inclusion criteria, (12 arms of randomized clinical trials, 11 prospective cohort studies, and 37 retrospective cohort studies), which included 244 cases of endophthalmitis and 639,391 intravitreal injections of anti-vascular endothelial growth factor agents. The final pooled estimate endophthalmitis proportions were 9/10,000 (95% confidence interval, 7/10,000-12/10,000) in the antibiotic-treated group and 3/10,000 (95% confidence interval, 2/10,000-5/10,000) in the untreated group. The estimated incidence of endophthalmitis with topical antibiotic prophylaxis was approximated three times the incidence without prophylaxis. Random effects regression showed that none of the study characteristics significantly affected the effect size in either group. Topical antibiotic after intravitreal injection of anti-vascular endothelial growth factor agents is associated with a higher risk of endophthalmitis.

  5. Experiences of patients undergoing repeated intravitreal anti-vascular endothelial growth factor injections for neovascular age-related macular degeneration.

    Science.gov (United States)

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

    2018-02-01

    Current therapy to slow disease progression in patients with neovascular age-related macular degeneration (AMD) entails regular intravitreal anti-vascular endothelial growth factor (VEGF) injections, often indefinitely. Little is known about the burden imposed on patients by this repetitive treatment schedule and how this can be best managed. The aim of this study was to explore the psychosocial impact of repeated intravitreal injections on patients with neovascular AMD. Forty patients (16 males, 24 females) with neovascular AMD undergoing anti-VEGF treatment were recruited using purposive sampling from a private ophthalmology practice and public hospital in Melbourne. Patients were surveyed using the Macular Disease Treatment Satisfaction Questionnaire (MacTSQ; Bradley, Health Psychology Research Unit, Surrey, England) and underwent semi-structured, one-on-one interviews. Interview topics were: treatment burden and satisfaction; tolerability; barriers to adherence; treatment motivation; and patient education. Interviews were audio recorded and thematic analysis performed using NVivo 10 (QSR International, Doncaster, Australia). Patients recognised the importance of treatment to preserve eyesight, yet experienced significant psychosocial and practical burden from the treatment schedule. Important issues included treatment-related anxiety, financial considerations and transport burden placed on relatives or carers. Many patients were restricted to sedentary activities post-injection owing to treatment side effects. Patients prioritised treatment, often sacrificing family, travel and social commitments owing to a fear of losing eyesight if treatment was not received. Whilst anti-VEGF injections represent the current mainstay of treatment for neovascular AMD, the ongoing treatment protocol imposes significant burden on patients. An understanding of the factors that contribute to the burden of treatment may help inform strategies to lessen its impact and assist

  6. Meta-analysis of endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor agents: causative organisms and possible prevention strategies.

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    McCannel, Colin A

    2011-04-01

    To report the rates of endophthalmitis and the spectrum of causative organisms after intravitreal injection of anti-vascular endothelial growth factor agents and possible prevention strategies. Meta-analysis of the U.S. literature from 2005 to 2009 reporting endophthalmitis bacterial isolates after intravitreal injection of anti-vascular endothelial growth factor agents and comparison with reports of endophthalmitis bacterial isolates after intraocular surgery in the United States. Endophthalmitis after intravitreal injection occurred in 52 of 105,536 injections (0.049%) (95% confidence interval [CI], 0.038-0.065%). Among 50 cases of endophthalmitis with bacterial culture isolates, 24 (48.0% [95% CI, 34.8-61.5%]) were culture negative and 26 (52% [95% CI, 38.5-65.2%]) were culture positive. Among the 26 culture-positive isolates, causative organisms were coagulase-negative Staphylococcus in 17 cases (65.4% [95% CI, 46.0-80.6%]), Streptococcus species in 8 cases (30.8% [95% CI, 16.5-50.2%]), and Bacillus cereus in 1 case (3.8% [95% CI, 0.9-19.0%]). Streptococcus species were significantly more frequent after intravitreal injection than after intraocular surgery in the Endophthalmitis Vitrectomy Study (29 of 226 isolates, 9.0% [95% CI, 6.3-12.6%], P = 0.005), a report on clear corneal cataract surgery endophthalmitis (6 of 73 isolates, 8.2% [95% CI, 3.9-16.8%], P = 0.022), and a report on postvitrectomy endophthalmitis with no cases of Streptococcus species. Streptococcal isolates are approximately three times more frequent after intravitreal anti-vascular endothelial growth factor injection than after intraocular surgery. Strategies to consider minimizing oropharyngeal droplet transmission may include avoiding talking, coughing, and sneezing or wearing surgical masks.

  7. Fundamental principles of an anti-VEGF treatment regimen: optimal application of intravitreal anti-vascular endothelial growth factor therapy of macular diseases.

    Science.gov (United States)

    Lanzetta, Paolo; Loewenstein, Anat

    2017-07-01

    Intravitreal anti-vascular endothelial growth factor (VEGF) therapy is now considered the gold standard for the treatment of various retinal disorders. As therapy has evolved, so too have the treatment regimens employed by physicians in clinical practice; however, visual outcomes observed in the real world have typically not reflected those reported in clinical trials. Possible reasons for this include a lack of consensus on treatment regimens and a lack of clarity about what the aims of treatment should be. The Vision Academy Steering Committee met to discuss the principles of an ideal treatment regimen, using evidence from the literature to substantiate each point. Literature searches were performed using the MEDLINE/PubMed database (cut-off date: March 2016) and restricted to English-language publications. Studies with fewer than ten patients were excluded from this review. The Steering Committee identified the following four key principles for the ideal treatment regimen for anti-VEGF management of retinal diseases: 1. Maximize and maintain visual acuity (VA) benefits for all patients 2. Decide when to treat next, rather than whether to treat now 3. Titrate the treatment intervals to match patients' needs 4. Treat at each monitoring visit. It is proposed that the adoption of a proactive and more personalized approach in the clinic such as a treat-and-extend regimen will lead to benefits for both the patient and the physician, through a reduction in the associated treatment burden and better utilization of clinic resources. Implementation of the four principles should also lead to better VA outcomes for each patient, with a minimized risk of vision loss.

  8. Efficacy and safety of adjuvant intravitreal injection of anti-vascular endothelial growth factors prior to vitrectomy in the treatment of proliferative diabetic retinopathy: A Meta-analysis

    Directory of Open Access Journals (Sweden)

    Jun Li

    2017-08-01

    Full Text Available AIM: To investigate the effectiveness and safety of intravitreal injection of anti-vascular endothelial growth factors(VEGFdrugs to the patients with proliferative diabetic retinopathy before vitrectomy treatment.METHODS: A Meta-analysis. A comprehensive retrieval was conducted using the database including EMbase, the Cochrane Library, Pubmed, CBM, WanFang Database, CNKI and so on. The retrieval time was limited from the building time of database to Jan. 2017. The randomized controlled trial was adopted with no requirements on languages. The Jadad scale and Cochrance cooperation were used as the tool of the risk and bias evaluation to analyze the literature quality. Quality estimation of evidence-based medicine on the parameters of each evaluation index was made via GRADEpro Software. The publishing biases of enclosed documents were inspected with funnel plot. At last, the Meta analysis was conducted with Review Manager 5.3.RESULTS: Totally 16 literatures published from 2008-2016 were finally put into randomized controlled trial. A total of 923 cases were included, among which 493 cases were grouped as intravitreal injection of anti-VEGF before the combined operation of PPV group(the experimental group, and 430 cases were involved in simple PPV group(the control group. The results of Meta-analysis show:(1The probability of intraoperative bleeding was remarkably lower than the control group \\〖OR=0.06, 95%CI(0.02, 0.15, PWMD=-29.13, 95% CI(-36.95, -21.30, POR=0.34, 95%CI(0.20, 0.58, PWMD=-0.51(LogMAR, 95%CI(-1.10, 0.08, P=0.09\\〗 with no statistical significance.(5The occurrence of iatrogenic retinal rupture was lower than that of the control group\\〖OR=0.24, 95%CI(0.14, 0.40, PCONCLUSION: It is effective and safe for the patients with proliferative diabetic retinopathy to inject anti-VEGF drugs into vitreous cavity before vitrectomy. And it can reduce the occurrence of complications during and after surgery, improving the general treatment

  9. Mechanism of retinal pigment epithelium tear formation following intravitreal anti-vascular endothelial growth factor therapy revealed by spectral-domain optical coherence tomography

    DEFF Research Database (Denmark)

    Nagiel, Aaron; Freund, K Bailey; Spaide, Richard F

    2013-01-01

    to the retracted RPE. In all eyes, the RPE ruptured along a segment of bare RPE not in contact with the CNV or Bruch membrane. CONCLUSIONS: Eyes with vascularized PEDs secondary to AMD may show specific OCT findings that increase the risk for RPE tear following intravitreal anti-VEGF injection. Rapid involution...

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

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

    2013-10-02

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

  11. Radiation Retinopathy Is Treatable With Anti-Vascular Endothelial Growth Factor Bevacizumab (Avastin)

    International Nuclear Information System (INIS)

    Finger, Paul T.

    2008-01-01

    Purpose: To report on bevacizumab treatment for radiation retinopathy affecting the macula. Patients and Methods: Twenty-one patients with radiation retinopathy (edema, hemorrhages, capillary dropout, and neovascularization) and a subjective or objective loss of vision were treated. Treatment involved intravitreal injection of bevacizumab (1.25 mg in 0.05 mL) every 6-12 weeks. Treatment was discontinued at patient request or if there was no measurable response to therapy. Main outcome measures included best corrected visual acuity, ophthalmic examination, retinal photography, and angiography. Results: Bevacizumab treatment was followed by reductions in retinal hemorrhage, exudation, and edema. Visual acuities were stable or improved in 86% (n = 18). Three patients discontinued therapy. Each was legally blind before treatment (n = 1), experienced little to no subjective improvement (n = 2), or was poorly compliant (n = 2). Three patients (14%) regained 2 or more lines of visual acuity. No ocular or systemic bevacizumab-related side effects were observed. Conclusions: Intravitreal bevacizumab can be used to treat radiation retinopathy. In most cases treatment was associated with decreased vascular leakage, stabilization, or improved vision. An anti-vascular endothelial growth factor strategy may reduce tissue damage associated with radiation vasculopathy and neuropathy

  12. Diabetic macular oedema treated with intravitreal anti-vascular endothelial growth factor - 2-4 years follow-up of visual acuity and retinal thickness in 566 patients following Danish national guidelines

    DEFF Research Database (Denmark)

    Hodzic-Hadzibegovic, Delila; Sander, Birgit Agnes; Monberg, Tine Juul

    2017-01-01

    Purpose: To investigate long-term functional and anatomical outcomes, discontinuation patterns, drug switching and rates of nonimprovement in patients treated with ranibizumab pro re nata (PRN) regimen for diabetic macular oedema (DME) according to the Danish national guidelines. Methods......: Retrospective cohort study of 566 eyes in 566 patients with centre-involved DME who started intravitreal treatment with ranibizumab between January 2011 and December 2013 in the Greater Copenhagen region. Data were retrieved from a database and patient records between January 2011 and March 2016 and analysed.......5, +2.7, +1.8, +2.3 letters and -97.4, -102.6, -106.9, -105.9, -131.6 μm, respectively. Mean number of injections was 6.1 in year 1 and 1.8 in year 4. In 93 patients, drug switching to aflibercept showed no difference between the two drugs on BCVA or CST. In 79 patients, CST decreased

  13. Role of posterior vitreous detachment on outcome of anti-vascular endothelial growth factor treatment in age-related macular degeneration.

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    Üney, Güner Ö; Ünlü, Nurten; Acar, Mehmet A; Hazirolan, Dicle; Altiparmak, Uğur E; Yalniz-Akkaya, Zuleyha; Örnek, Firdevs

    2014-01-01

    The aim of this study was to determine the effect of posterior vitreous detachment on outcome of anti-vascular endothelial growth factor injection. Sixty-one eyes with age-related macular degeneration that had received intravitreal bevacizumab or ranibizumab injections were retrospectively reviewed. The vitreomacular interface was evaluated, and eyes were grouped according to the presence of posterior vitreous detachment (Group 1, n = 25) or vitreomacular adhesion (Group 2, n = 36). All patients received three loading doses of intravitreal anti-vascular endothelial growth factor injections at monthly intervals, and subsequently, pro re nata regimen was performed. Best-corrected visual acuity and central foveal thickness measurement at follow-up were evaluated. The development of posterior vitreous detachment during the follow-up was also reported. The best-corrected visual acuity changes at each visit compared with baseline were significantly better in Group 1 (P = 0.01, 0.02, 0.02, 0.009, 0.009, respectively at third, sixth, ninth, 12th month, and last visit). When best-corrected visual acuity was classified according to the change in visual acuity of 10 letters or more, the rate of improved or stable best-corrected visual acuity was greater in Group 1 (P = 0.02). During the follow-up, 5 eyes (14.3%) developed posterior vitreous detachment. Vitreomacular adhesion seems to have an adverse effect on the visual prognosis of anti-vascular endothelial growth factor treatment for age-related macular degeneration.

  14. Bilateral concomitant intravitreal anti-vascular endothelial growth ...

    African Journals Online (AJOL)

    2015-11-18

    Nov 18, 2015 ... complications following anti-VEGF injection, further study with a larger number of patients will be necessary to definitively .... However, no drops, materials, or instrument were reused in the preparation and injection of the second eye. Postinjection, patient was counseled and .... retinal-insider/c/48731/.

  15. Reduced-fluence photodynamic therapy and anti-vascular endothelial growth factor for polypoidal choroidal vasculopathy in an Indian population

    Directory of Open Access Journals (Sweden)

    Parveen Sen

    2016-01-01

    Full Text Available Aims: The aim was to study the efficacy of combined therapy with reduced-fluence photodynamic therapy (RFPDT and intravitreal bevacizumab/ranibizumab from the Indian subcontinent. Settings and Design: This was a single-center, retrospective interventional study. Methods: Thirty-five eyes of 34 patients diagnosed with polypoidal choroidal vasculopathy were included. All the patients underwent RFPDT, followed by intravitreal bevacizumab/ranibizumab. Statistical Analysis Used: SPSS software, version 17.0 (SPSS Inc., Chicago, IL, USA was used to compare the logarithm of the minimal angle of resolution visual acuity at presentation and final follow-up. P< 0.05 was considered statistically significant. Results: Regression of polyps after a single session of RFPDT was seen in five eyes; multiple sessions of treatment were required in thirty eyes. An average number of intravitreal anti-vascular endothelial growth factor (anti-VEGF injections given were 4 ± 1.9 and average number of PDT sessions were 1.2 ± 0.5. Visual acuity improvement was seen in 21 (60% eyes (P < 0.001, decrease in visual acuity was seen in 7 (20% eyes (P = 0.016, and in 7 eyes (20%, vision remained stable. Regression of polypoidal lesions was seen in 80% of cases. No complications of massive subretinal hemorrhage or breakthrough vitreous hemorrhage were noted in our patients. The mean follow-up period was 18 months (range, 12–24 months. Conclusions: RFPDT with anti-VEGF is safe and effective treatment with polyp regression and vision improvement in 80% of cases, without any complication of subretinal hemorrhage/vitreous hemorrhage.

  16. OCT-based deep learning algorithm for the evaluation of treatment indication with anti-vascular endothelial growth factor medications.

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    Prahs, Philipp; Radeck, Viola; Mayer, Christian; Cvetkov, Yordan; Cvetkova, Nadezhda; Helbig, Horst; Märker, David

    2018-01-01

    Intravitreal injections with anti-vascular endothelial growth factor (anti-VEGF) medications have become the standard of care for their respective indications. Optical coherence tomography (OCT) scans of the central retina provide detailed anatomical data and are widely used by clinicians in the decision-making process of anti-VEGF indication. In recent years, significant progress has been made in artificial intelligence and computer vision research. We trained a deep convolutional artificial neural network to predict treatment indication based on central retinal OCT scans without human intervention. A total of 183,402 retinal OCT B-scans acquired between 2008 and 2016 were exported from the institutional image archive of a university hospital. OCT images were cross-referenced with the electronic institutional intravitreal injection records. OCT images with a following intravitreal injection during the first 21 days after image acquisition were assigned into the 'injection' group, while the same amount of random OCT images without intravitreal injections was labeled as 'no injection'. After image preprocessing, OCT images were split in a 9:1 ratio to training and test datasets. We trained a GoogLeNet inception deep convolutional neural network and assessed its performance on the validation dataset. We calculated prediction accuracy, sensitivity, specificity, and receiver operating characteristics. The deep convolutional neural network was successfully trained on the extracted clinical data. The trained neural network classifier reached a prediction accuracy of 95.5% on the images in the validation dataset. For single retinal B-scans in the validation dataset, a sensitivity of 90.1% and a specificity of 96.2% were achieved. The area under the receiver operating characteristic curve was 0.968 on a per B-scan image basis, and 0.988 by averaging over six B-scans per examination on the validation dataset. Deep artificial neural networks show impressive performance on

  17. Analysis of the Cochrane Review: Anti-vascular Endothelial Growth Factor for Prevention of Postoperative Vitreous Cavity Hemorrhage after Vitrectomy for Proliferative Diabetic Retinopathy. Cochrane Database Syst Rev. 2015;8:CD008214.

    Directory of Open Access Journals (Sweden)

    David Cordeiro Sousa

    2017-08-01

    Full Text Available Postoperative vitreous hemorrhage is a complication following vitrectomy for proliferative diabetic retinopathy, delaying visual recovery and making fundus examination and disease follow-up more difficult. Anti-vascular endothelial growth factor drugs such as bevacizumab, when injected in the vitreous cavity, reduce vascular proliferation and their use has been proposed to reduce the incidence of postoperative vitreous hemorrhage. The authors of this Cochrane systematic review evaluated all randomized controlled trials on the pre- or intraoperative use of anti-vascular endothelial growth factor to reduce postoperative vitreous hemorrhage occurrence after vitrectomy in patients with proliferative diabetic retinopathy. The results suggested that the use of intravitreal bevacizumab was effective in reducing early postoperative vitreous hemorrhage (i.e. at four weeks occurrence, with a good safety profile. This work aims to summarize and discuss the findings and clinical implications of this Cochrane systematic review.

  18. Anti-Vascular Endothelial Growth Factor Preparations in the Treatment of Retinopathy of Prematurity: Balancing Risks and Benefits.

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    Chawla, Deepak; Darlow, Brian A

    2016-11-07

    The standard of management of severe retinopathy of prematurity (ROP) is laser ablation of the peripheral retina. Intra-vitreal injection of anti- vascular endothelial growth factor antibodies has emerged as an alternative modality of treatment of ROP. The purpose of this review is to evaluate the current evidence on benefits and risks of using anti-VEGF antibodies for management of ROP. PubMed and Cochrane Register of Clinical Trials were searched for studies evaluating role of anti-VEGF agents in ROP. No study design or language restriction was used. Data were extracted using a data extraction form and presented as a summary of key findings from different study types and designs. Of 143 studies retrieved, 107 were found relevant and further screened. Seventy-three studies reporting original research were selected. These were divided into three categories: pharmacokinetics studies (n=5), observational studies without a control group (n=59) and clinical trials with a control group (n=9). The most commonly used agent was bevacizumab at a dose of 0.625 mg per eye. At this dose bevacizumab administration led to regression of ROP in the majority of cases with type 1 ROP but was associated with sustained reduction in systemic VEGF levels. The most common adverse event after anti-VEGF therapy was recurrence of ROP needing follow up for up to one-year postmenstrual age. Randomized controlled trials demonstrated better anatomical outcome with bevacizumab as compared to laser therapy. Studies lack evidence of long term effect of bevacizumab on retinal vessels, functional visual outcomes and extra-ocular effects. Anti-VEGF agents are effective in causing regression of ROP. However, until adequately powered studies with long term follow-up and recording of more holistic outcomes are available, anti-VEGF agents remain an investigational drug in ROP and should be used only as part of clinical study.

  19. Changes in Fundus Autofluorescence after Anti-vascular Endothelial Growth Factor According to the Type of Choroidal Neovascularization in Age-related Macular Degeneration.

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    Lee, Ji Young; Chung, Hyewon; Kim, Hyung Chan

    2016-02-01

    To describe the changes of fundus autofluorescence (FAF) in patients with age-related macular degeneration before and after intravitreal injection of anti-vascular endothelial growth factor according to the type of choroidal neovascularization (CNV) and to evaluate the correlation of FAF with spectral domain optical coherence tomography (SD-OCT) parameters and vision. This was a retrospective study. Twenty-one treatment-naïve patients with neovascular age-related macular degeneration were included. Study eyes were divided into two groups according to the type of CNV. Fourteen eyes were type 1 CNV and seven eyes were type 2 CNV. All eyes underwent a complete ophthalmologic examination, including an assessment of best-corrected visual acuity, SD-OCT, fluorescein angiography, and FAF imaging, before and 3 months after intravitreal anti-vascular endothelial growth factor injection. Gray scales of FAF image for CNV areas, delineated as in fluorescein angiography, were analyzed using the ImageJ program, which were adjusted by comparison with normal background areas. Correlation of changes in FAF with changes in SD-OCT parameters, including CNV thickness, photoreceptor inner and outer segment junction disruption length, external limiting membrane disruption length, central macular thickness, subretinal fluid, and intraretinal fluid were analyzed. Eyes with both type 1 and type 2 CNV showed reduced FAF before treatment. The mean gray scales (%) of type 1 and type 2 CNV were 52.20% and 42.55%, respectively. The background values were 106.72 and 96.86. After treatment, the mean gray scales (%) of type 1 CNV and type 2 CNV were changed to 57.61% (p = 0.005) and 57.93% (p = 0.008), respectively. After treatment, CNV thickness, central macular thickness, and inner and outer segment junction disruption length were decreased while FAF increased. FAF was noted to be reduced in eyes with newly diagnosed wet age-related macular degeneration, but increased after anti-vascular

  20. Anti-vascular endothelial growth factor for prevention of postoperative vitreous cavity haemorrhage after vitrectomy for proliferative diabetic retinopathy.

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    Smith, Jonathan M; Steel, David H W

    2015-08-07

    Postoperative vitreous cavity haemorrhage (POVCH) is a significant complication following vitrectomy for proliferative diabetic retinopathy (PDR). It delays visual recovery and can make further treatment difficult if the view of the fundus is significantly obscured. A number of interventions to reduce the incidence of POVCH have been proposed, including the perioperative use of anti-vascular endothelial growth factor (anti-VEGF). Anti-VEGFs reduce vascular proliferation and the vascularity of neovascular tissue, which is often the source of bleeding following vitrectomy. This updated review aimed to summarise the effects of anti-VEGF use to reduce the occurrence of POVCH after vitrectomy surgery for PDR. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2015, Issue 4), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to May 2015), PubMed (January 1966 to May 2015), EMBASE (January 1980 to May 2015), Latin American and Caribbean Health Sciences (LILACS) (January 1982 to May 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 26 May 2015. We included all randomised controlled trials (RCTs) and quasi-RCTs that looked at the use of anti-VEGFs and the incidence of POVCH in people undergoing vitrectomy for PDR. Both review authors independently assessed and extracted the data. We used standard methodological procedures expected by Cochrane.The primary outcomes of the review were the incidence of early and late POVCH following perioperative anti-VEGF administration. Secondary outcomes included best-corrected visual acuity at six months following

  1. RETINAL PIGMENT EPITHELIAL ATROPHY AFTER ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR INJECTIONS FOR RETINAL ANGIOMATOUS PROLIFERATION.

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

    2017-11-01

    To investigate the incidence rate and risk factors for development of retinal pigment epithelial (RPE) atrophy during anti-vascular endothelial growth factor (anti-VEGF) treatment for retinal angiomatous proliferation. This study included 46 eyes with treatment-naive retinal angiomatous proliferation. All patients were treated with ranibizumab or aflibercept injections. Color fundus photography, spectral-domain optical coherence tomography, and fundus autofluorescence were evaluated for RPE atrophy diagnosis. Baseline characteristics and gene polymorphisms of ARMS2 A69S, and CFH I62V were analyzed for association with development and progression of RPE atrophy. Among 21 eyes treated with ranibizumab without preexisting RPE atrophy at baseline, 5 eyes (23.8%) developed RPE atrophy at 12 months. Among 20 eyes treated with aflibercept without preexisting RPE atrophy at baseline, 10 eyes (50.0%) developed RPE atrophy at 12 months. Refractile drusen at baseline was associated with RPE atrophy development at 12 months (P = 0.014), and the progression rate of RPE atrophy area was negatively correlated with subfoveal choroidal thickness at baseline (R = -0.595, P = 0.019). Gene polymorphisms were not associated with RPE atrophy. Retinal pigment epithelial atrophy developed in 36.6% during 12 months after anti-VEGF treatment for retinal angiomatous proliferation. The presence of refractile drusen at baseline was identified as a novel significant risk factor for RPE atrophy development.

  2. Cost and Selection of Ophthalmic Anti-Vascular Endothelial Growth Factor Agents.

    Science.gov (United States)

    Li, Emily; Greenberg, Paul B; Voruganti, Indu; Krzystolik, Magdalena G

    2016-05-02

    Anti-vascular endothelial growth factor (anti-VEGF) drugs - ranibizumab, aflibercept, and off-label bevacizumab - are vital to the treatment of common retinal diseases, including exudative age-related macular degeneration (AMD), diabetic macular edema (DME), and macular edema (ME) associated with retinal vein occlusion (RVO). Given the high prevalence of AMD and retinal vascular diseases, anti-VEGF agents represent a large cost burden to the United States (US) healthcare system. Although ranibizumab and aflibercept are 30-fold more expensive per injection than bevacizumab, the two more costly medications are commonly used in the US, even though all three have been shown to be effective and safe for treatment of these retinal diseases. We investigated the availability and content of professional ophthalmic guidelines on cost consideration in the selection of anti-VEGF agents. We found that current professional guidelines were limited in availability and lacked specific guidance on cost-based anti-VEGF drug selection. This represents a missed opportunity to encourage the practice of value-based medicine. [Full article available at http://rimed.org/rimedicaljournal-2016-05.asp, free with no login].

  3. Anti vascular endothelial growth factor (bevacizumab) in central retinal vein occlusion: an interventional case series

    International Nuclear Information System (INIS)

    Jan, S.; Khan, M.N.; Karim, S.; Khan, M.T.; Hussain, Z.; Khan, S.; Nazim, M.

    2010-01-01

    Vascular endothelial growth factor plays major role in ocular angio genesis and retinal edema production and is a step forward in the management of ocular neovascularization and retinal edematous pathologies. To determine the efficacy and safety of intra-vitreal Avastin (Bevacizumab) in cases having central retinal vein occlusion. All patients with central retinal occlusion occurring in the past 3 months and seen between the study period were included in the study. Diagnosis of central retinal vein occlusion was made clinically by slit lamp biomicroscopy with 78D examination Patients who had received any treatment for and eyes which already had developed Anterior Segment Neovascularization, Neovascularization elsewhere or Neovascularization on disc at presentation were excluded. Dose of 0.05 ml (1.25mg) of Avastin (Bevacizumab) was used as intra vitreal injection every month for 3 months in cases that presented within a month of occlusion and less injections were given in dose presenting later. Follow-up was done at 30th, 60th, 90th and 120th day after the onset of disease. Visual outcome was defined as Snellen's or LogMar Best Corrected Visual Acuity at final follow up, of 120th day, compared to the visual acuity at presentation. Data were analyzed by SPSS version 17. Total of 17 eyes of 17 patients were included in this study. Eleven (64.7%) patients were males while 6(35.3%) were females. Total of 40 intra-vitreal injections of Avastin were given to patients with a mean of 2.35 injections per eye. Good visual outcome was achieved in 10(58.8%) eyes, while 7(41.2%) had stable visual outcome. Mean initial Best Corrected Visual Acuity (LogMar) in all 17 eyes was 1.79(SD+0.87) which significantly improved to a mean of 1.18 (SD+0.77) at final follow up. Mean improvement in Best Corrected Visual Acuity (LogMar) after paired sample test in all patients at final follow up on day 120 was 0.61(SD+0.84). Retinal hemorrhages and macular edema decreased clinically on

  4. 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.

  5. Integration of anti-vascular endothelial growth factor therapies with cytotoxic chemotherapy in the treatment of colorectal cancer.

    Science.gov (United States)

    Oliveira, Suilane Coelho Ribeiro; Machado, Karime Kalil; Sabbaga, Jorge; Hoff, Paulo M

    2010-01-01

    Colorectal cancer is one of the most prevalent malignancies worldwide, and its incidence continues to rise. The treatment for advanced colorectal cancer has significantly evolved in the last decade, with the addition of a number of new therapeutic agents; however, 5-fluorouracil remains at the core of most therapeutic approaches for this disease. Novel therapies targeting specific pathways have been developed for this disease, and the vascular endothelial growth factor ligand and receptor have been of particular interest. The blockade of what is considered the main angiogenic pathway is considered one of the main advances in cancer treatment. The aim of this article is to review the current status of the integration between anti-vascular endothelial growth factor therapies and cytotoxic chemotherapy, investigate what is known about development of resistance, and to explore new options of antiangiogenic treatments currently in late phases of development against colorectal cancer.

  6. Anti-vascular endothelial growth factor for diabetic macular oedema: a network meta-analysis.

    Science.gov (United States)

    Virgili, Gianni; Parravano, Mariacristina; Evans, Jennifer R; Gordon, Iris; Lucenteforte, Ersilia

    2017-06-22

    Diabetic macular oedema (DMO) is a common complication of diabetic retinopathy. Antiangiogenic therapy with anti-vascular endothelial growth factor (anti-VEGF) modalities can reduce oedema and thereby improve vision and prevent further visual loss. These drugs have replaced laser photocoagulation as the standard of care for people with DMO. The 2014 update of this review found high-quality evidence of benefit with antiangiogenic therapy with anti-VEGF modalities, compared to laser photocoagulation, for the treatment of DMO.The objective of this updated review is to compare the effectiveness and safety of the different anti-VEGF drugs in preserving and improving vision and quality of life using network meta-analysis methods. We searched various electronic databases on 26 April 2017. We included randomised controlled trials (RCTs) that compared any anti-angiogenic drug with an anti-VEGF mechanism of action versus another anti-VEGF drug, another treatment, sham or no treatment in people with DMO. We used standard Cochrane methods for pair-wise meta-analysis and we augmented this evidence using network meta-analysis methods. We focused on the relative efficacy and safety of the three most commonly used drugs as interventions of direct interest for practice: aflibercept and ranibizumab, used on-label; and off-label bevacizumab.We collected data on three efficacy outcomes (gain of 15 or more Early Treatment Diabetic Retinopathy Study (ETDRS) letters; mean change in best-corrected visual acuity (BCVA); mean change in central retinal thickness (CRT)), three safety outcomes (all severe systemic adverse events (SSAEs); all-cause death; arterial thromboembolic events) and quality of life.We used Stata 'network' meta-analysis package for all analyses. We investigated the risk of bias of mixed comparisons based on the variance contribution of each study, having assigned an overall risk of bias to each study. Twenty-four studies included 6007 participants with DMO and moderate

  7. Design of a humanized anti vascular endothelial growth factor nanobody and evaluation of its in vitro function.

    Science.gov (United States)

    Kazemi-Lomedasht, Fatemeh; Muyldermans, Serge; Habibi-Anbouhi, Mahdi; Behdani, Mahdi

    2018-03-01

    Nanobodies, the single domain antigen binding fragments of heavy chain-only antibodies occurring naturally in camelid sera, are the smallest intact antigen binding entities. Their minimal size assists in reaching otherwise largely inaccessible regions of antigens. However, their camelid origin raises a possible concern of immunogenicity when used for human therapy. Humanization is a promising approach to overcome the problem. Here, we designed a humanized version of previously developed nanobody (anti vascular endothelial growth factor nanobody), evaluated and compared its predicted 3D structure, affinity and biological activity with its original wild type nanobody. Our in silico results revealed an identical 3D structure of the humanized nanobody as compare to original nanobody. In vitro studies also demonstrated that the humanization had no significant visible effect on the nanobody affinity or on its biological activity. The humanized nanobody could be developed and proposed as a promising lead to target pathologic angiogenesis.

  8. Anti-Vascular Endothelial Growth Factors Protect Retinal Pigment Epithelium Cells Against Oxidation by Modulating Nitric Oxide Release and Autophagy

    Directory of Open Access Journals (Sweden)

    Stefano De Cillà

    2017-07-01

    Full Text Available Background/Aims: the anti-vascular endothelial growth factors (VEGF, Aflibercept and Ranibizumab, are used for the treatment of macular degeneration. Here we examined the involvement of nitric oxide (NO, mitochondria function and of apoptosis/autophagy in their antioxidant effects in human retinal pigment epithelium cells (RPE. Methods: RPE were exposed to Ranibizumab/Aflibercept in the absence or presence of NO synthase (NOS inhibitor and of autophagy activator/blocker, rapamicyn/3-methyladenine. Specific kits were used for cell viability, NO and reactive oxygen species detection and mitochondrial membrane potential measurement, whereas Western Blot was performed for apoptosis/ autophagy markers and other kinases detection. Results: In RPE cultured in physiological conditions, Aflibercept/Ranibizumab increased NO release in a dose and time-dependent way. Opposite results were obtained in RPE pretreated with hydrogen peroxide. Moreover, both the anti-VEGF agents were able to prevent the fall of cell viability and of mitochondrial membrane potential. Those effects were reduced by the NOS inhibitor and 3-methyladenine and were potentiated by rapamycin. Finally, Aflibercept and Ranibizumab counteracted the changes of apoptosis/autophagy markers, NOS, Phosphatidylinositol-3-Kinase/Protein Kinase B and Extracellular signal–regulated kinases 1/2 caused by peroxidation. Conclusion: Aflibercept and Ranibizumab protect RPE against peroxidation through the modulation of NO release, apoptosis and autophagy.

  9. Design of a humanized anti vascular endothelial growth factor nanobody and evaluation of its in vitro function

    Directory of Open Access Journals (Sweden)

    Fatemeh Kazemi-Lomedasht

    2018-03-01

    Full Text Available Objective(s: Nanobodies, the single domain antigen binding fragments of heavy chain-only antibodies occurring naturally in camelid sera, are the smallest intact antigen binding entities. Their minimal size assists in reaching otherwise largely inaccessible regions of antigens. However, their camelid origin raises a possible concern of immunogenicity when used for human therapy. Humanization is a promising approach to overcome the problem.   Materials and Methods: Here, we designed a humanized version of previously developed nanobody (anti vascular endothelial growth factor nanobody, evaluated and compared its predicted 3D structure, affinity and biological activity with its original wild type nanobody. Results: Our in silico results revealed an identical 3D structure of the humanized nanobody as compare to original nanobody. In vitro studies also demonstrated that the humanization had no significant visible effect on the nanobody affinity or on its biological activity.  Conclusion: The humanized nanobody could be developed and proposed as a promising lead to target pathologic angiogenesis.

  10. Refractive errors in premature infants with retinopathy of prematurity after anti-vascular endothelial growth factor (anti-VEGF therapy

    Directory of Open Access Journals (Sweden)

    Vujanović Milena S.

    2017-01-01

    Full Text Available Background/Aim. Retinopathy of prematurity (ROP is a vasoproliferative retinopathy which affects the blood vessels of the retina during its development. The aim of this study was to evaluate the incidence and the degree of refractive errors in premature infants with severe ROP treated with antivascular endothelial growth factor (anti-VEGF (bevacizumab. Methods. This prospective study included 21 patients (42 eyes nine months old who received intravitreal injection of anti-VEGF therapy. The control group consisted of 45 patients (90 eyes who were subjected to laser treatment. In cycloplegia each patient underwent retinoscopy, keratorefractometry, and A-scan ultrasonography. Results. Myopia was present in 47.62% of the eyes in the study group and in 33.33% of the eyes in the control group, but there were no statistically significant differences between these groups. Seven (16.67% eyes in the study group and 17 (18.89% eyes in the control group were discovered to have high myopia (SE– spherical equivalents < -3.0 D – dioptre. Clinically significant hypermetropia was higher in the study group (47.62% than in the control group (34.44%, but with no statistically significant difference. In addition, high hypermetropia was significantly greater in the control group (15.56% than in the study group (11.90% (p < 0.001. Astigmatism was more common in the control group than in the study group (81.11% vs 71.43%, respectively, especially high astigmatism (56% vs 43%, respectively. Also the more common form of astigmatism was with the rule (WTR both in the study and the control group (42.86% vs 55.56%, respectively. Anisometropia was significantly greater in the control group (24.44% than in the study group (9.52% (p < 0.05. The children from the study group had significantly greater lens thickness, and a shorter anterior chamber depth than children from the control group (p < 0.01. There was no significant difference in the axial length of the eye between

  11. RETINAL PIGMENT EPITHELIAL TEAR AND ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY IN EXUDATIVE AGE-RELATED MACULAR DEGENERATION: Clinical Course and Long-Term Prognosis.

    Science.gov (United States)

    Heimes, Britta; Farecki, Marie-Louise; Bartels, Sina; Barrelmann, Anna; Gutfleisch, Matthias; Spital, Georg; Lommatzsch, Albrecht; Pauleikhoff, Daniel

    2016-05-01

    To document the long-term outcome in cases of retinal pigment epithelial (RPE) tears after treatment of vascularized pigment epithelial detachments with anti-vascular endothelial growth factor therapy. A retrospective analysis of the long-term outcome of a consecutive series of eyes with RPE tear developed during anti-vascular endothelial growth factor therapy for pigment epithelial detachment associated with choroidal neovascularization or retinal angiomatous proliferation (vascularized pigment epithelial detachment) was performed. Best-corrected visual acuity (BCVA), spectral domain optical coherence tomography, and autofluorescence images and also fluorescein angiograms were analyzed to determine the functional and morphologic development over time. The long-term outcome of 22 eyes (21 patients, 13 women and 8 men; 65-85 years; mean: 76 years) with RPE tear was performed with minimal follow-up of 3 years (range: 3-5 years, mean: 44 months) and re-treatment with different therapeutic strategies. The eyes were differentiated in 2 groups according to the course of BCVA after the first 2 years of follow-up: Group 1 (11 eyes) demonstrated a stabilized or improved BCVA after 2 years and Group 2 (11 eyes) demonstrated a decrease in BCVA after 2 years. The initial BCVA between both groups was comparable. Also the mean initial size of the RPE tear was the same between the 2 groups, the area of the RPE tear decreased continuously during follow-up in Group 1, whereas this was the case in Group 2 only at the beginning of treatment with a further increase of the size of the RPE tear with longer follow-up. This corresponded with a different morphologic development between the two groups. In Group 1, increasing recovery of autofluorescence at the RPE-free area was visible beginning from the outer border, whereas in Group 2, further growth of the neovascular complex in the area of the RPE tear was observed resulting in larger fibrovascular scars. In addition, in both groups

  12. Anti vascular endothelial growth factor sequential therapy for neovascular age-related macular degeneration: is this the new deal?

    Science.gov (United States)

    Neri, Piergiorgio; Mariotti, Cesare; Arapi, Ilir; Bambini, Elisa; Giovannini, Alfonso

    2012-03-01

    To review clinical data on the sequential use of the non-selective vascular endothelial growth factor (VEGF) inhibitors (ranibizumab and bevacizumab) and the selective VEGF inhibitor (pegaptanib) in the treatment of neovascular age related macular degeneration (n-AMD). This is a selective review of the literature based on a PubMed search using the terms 'age-related macular degeneration', 'selective anti-VEGF', 'non-selective anti-VEGF' and 'combination therapy' from 2000 to date in the English language. Studies on the management of n-AMD reporting adherence, patient-reported outcomes, costs, side effects, resource use and cost effectiveness were also included. The trial data suggest that pan-VEGF inhibition provides improved treatment outcomes in patients with n-AMD with selective anti-VEGF agents offering better tolerability on long-term treatment. A pilot trial and a large-scale, multicentre study confirmed the long-term efficacy of a selective VEGF inhibitor when used as maintenance therapy. Importantly, there is evidence that selective VEGF inhibition also reduces the risks associated with pan-VEGF blockade in patients with n-AMD. Anti-VEGF agents play a principal role in the management of n-AMD. The most potent are the pan-VEGF agents although there is some discussion regarding their long-term tolerability. The sequential use of non-selective VEGF inhibitors as booster therapy with a selective VEGF inhibitor as maintenance therapy seems to offer a promising safety/efficacy profile, as well as improved cost/effectiveness.

  13. The effect of intravitreal bevacizumab injection on the corneal endothelial cells

    Directory of Open Access Journals (Sweden)

    Akbar Derakhshan

    2016-04-01

    Full Text Available Introduction:Bevacizumab (Avastin, as an effectiveness treatment modality, is currently used in patients with various ocular disease. However the results have been promising, the use of bevacizumab in the treatment of ocular disease is an off-label application. Hence, the aim of this study was to systematically review the effectiveness of intravitreal injection of bevacizumab on various ocular tissues, especially corneal endothelial cells. Methods: The articles related to the effect of application of Avastin in the treatment of ophthalmic diseases and especially its effect on corneal endothelial cells were collected and reviewed. We searched PubMed, Google scholar, and Scopus databases and used Avastin, ocular diseases and corneal endothelial cells as search keywords.Result: Of all 55 articles found in all databases, only 10 were relevant to the purpose of this study, and 45 articles were excluded in several step by step process of article selection according to the inclusion/exclusion criteria. The results revealed that intracameral bevacizumab injection caused no changes in specular microscopy and corneal pachymetry. Moreover, it had no significant toxicity on corneal endothelial cells.Discussion: Effectiveness of bevacizumab as a new modality in the treatment of different ophthalmic diseases have been suggested. Recent data on both human and animal models showed that intravitreal injection of bevacizumab resulted in no significant toxicity on various ocular cells, and it could be considered as a suitable therapeutic approach in clinical use.Conclusion: According to the results of included documents, bevacizumab was not toxic to corneal endothelial cells at various clinically relevant doses.

  14. INTRAVITREAL AFLIBERCEPT IN THE TREATMENT OF POLYPOIDAL CHOROIDAL VASCULOPATHY ASSOCIATED WITH MORNING GLORY SYNDROME.

    Science.gov (United States)

    Iovino, Claudio; Fossarello, Maurizio; Peiretti, Enrico

    2018-01-10

    To describe an unusual case of polypoidal choroidal vasculopathy secondary to morning glory syndrome successfully treated with three aflibercept intravitreal injections. Case report. A 68-year-old white man presented with a 2-month history of diminished vision of his left eye. Fundus examination showed a morning glory syndrome disk anomaly with some perimacular subretinal hemorrhages and lipid depositions. Fundus autofluorescence, fluorescein and green indocyanine angiography, spectral domain optical coherence tomography, and optical coherence tomography angiography were performed and confirmed the presence of a juxtapapillary polypoidal choroidal vasculopathy with intraretinal and subretinal fluid. Patient underwent 3 monthly intravitreal injections of aflibercept and at 4-month follow-up visit, multimodal imaging findings did not show any kind of neovascular lesion activity. Polypoidal choroidal vasculopathy can occur in morning glory syndrome and it can be successfully treated with anti-vascular endothelial growth factor intravitreal injections of aflibercept.

  15. 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

    Abstract. Purpose: To report the effects of intravitreal bevacizumab (Avastin((R))) in treatment-naive patients with exudative age-related macular degeneration (ARMD) assessed by visual acuity (VA), optical coherence tomography (OCT) and contrast sensitivity. Methods: A prospective, uncontrolled......, 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...... points. The results indicate that 1.25 mg intravitreal bevacizumab is associated with functional as well as morphological improvement among treatment-naive ARMD patients....

  16. In vivo tumor targeting and imaging with anti-vascular endothelial growth factor antibody-conjugated dextran-coated iron oxide nanoparticles

    Directory of Open Access Journals (Sweden)

    Hsieh WJ

    2012-06-01

    Full Text Available Wan-Ju Hsieh,1 Chan-Jung Liang,1 Jen-Jie Chieh,4 Shu-Huei Wang,1 I-Rue Lai,1 Jyh-Horng Chen,2 Fu-Hsiung Chang,3 Wei-Kung Tseng,4–6 Shieh-Yueh Yang,4 Chau-Chung Wu,7 Yuh-Lien Chen11Institute of Anatomy and Cell Biology, College of Medicine, 2Department of Electrical Engineering, 3Institute of Biochemistry and Molecular Biology, National Taiwan University, Taipei, Taiwan; 4Institute of Electro-Optical Science and Technology, National Taiwan Normal University, Taipei, Taiwan; 5Division of Cardiology, Department of Internal Medicine, E-Da Hospital, Taipei, Taiwan; 6Department of Medical Imaging and Radiological Sciences, I-Shou University, Taipei, Taiwan; 7Department of Internal Medicine and Primary Care Medicine, National Taiwan University Hospital, Taipei, TaiwanBackground: Active targeting by specific antibodies combined with nanoparticles is a promising technology for cancer imaging and detection by magnetic resonance imaging (MRI. The aim of the present study is to investigate whether the systemic delivery of antivascular endothelial growth factor antibodies conjugating to the surface of functionalized supermagnetic iron oxide nanoparticles (anti-VEGF-NPs led to target-specific accumulation in the tumor.Methods: The VEGF expression in human colon cancer and in Balb/c mice bearing colon cancers was examined by immunohistochemistry. The distribution of these anti-VEGF-NPs particles or NPs particles were evaluated by MRI at days 1, 2, or 9 after the injection into the jugular vein of Balb/c mice bearing colon cancers. Tumor and normal tissues (liver, spleen, lung, and kidney were collected and were examined by Prussian blue staining to determine the presence and distribution of NPs in the tissue sections.Results: VEGF is highly expressed in human and mouse colon cancer tissues. MRI showed significant changes in the T*2 signal and T2 relaxation in the anti-VEGF-NP- injected-mice, but not in mice injected with NP alone. Examination of paraffin

  17. Anti-vascular endothelial growth factor treatment induces blood flow recovery through vascular remodeling in high-fat diet induced diabetic mice.

    Science.gov (United States)

    Xiao, Lamei; Yan, Kai; Yang, Yan; Chen, Ni; Li, Yongjie; Deng, Xin; Wang, Liqun; Liu, Yan; Mu, Lin; Li, Rong; Luo, Mao; Ren, Meiping; Wu, Jianbo

    2016-05-01

    Diabetes mellitus (DM) leads to the development of microvascular diseases and is associated with impaired angiogenesis. The presence of vascular endothelial growth factor (VEGF) can block PDGF-BB dependent regulation of neovascularization and vessel normalization. We tested the hypothesis that the inhibition of VEGF improves blood flow in a mouse hindlimb ischemia model produced by femoral artery ligation. In this study, we examined the effect of bevacizumab, a humanized monoclonal antibody against VEGF-A, on blood perfusion and angiogenesis after hindlimb ischemia. We showed that bevacizumab induces functional blood flow in high fat chow (HFC)-fed diabetic mice. Treatment with bevacizumab increased the expression of platelet derived growth factor-BB (PDGF-BB) in ischemic muscle, and led to vascular normalization. It also blocked vascular leakage by improving the recruitment of pericytes associated with nascent blood vessels, but it did not affect capillary formation. Furthermore, treatment with an anti-PDGF drug significantly inhibited blood flow perfusion in diabetic mice treated with bevacizumab. These results indicate that bevacizumab improves blood flow recovery through the induction of PDGF-BB in a diabetic mouse hindlimb ischemia model, and that vessel normalization may represent a useful strategy for the prevention and treatment of diabetic peripheral arterial disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Anti-Vascular Endothelial Growth Factor Antibody Suppresses ERK and NF-κB Activation in Ischemia-Reperfusion Lung Injury.

    Directory of Open Access Journals (Sweden)

    Chou-Chin Lan

    Full Text Available Ischemia-reperfusion (IR-induced acute lung injury (ALI is implicated in several clinical conditions like lung transplantation, acute pulmonary embolism after thrombolytic therapy, re-expansion of collapsed lung from pneumothorax or pleural effusion, cardiopulmonary bypass and etc. Because mortality remains high despite advanced medical care, prevention and treatment are important clinical issues for IR-induced ALI. Vascular endothelial growth factor (VEGF has a controversial role in ALI. We therefore conducted this study to determine the effects of anti-VEGF antibody in IR-induced ALI. In the current study, the IR-induced ALI was conducted in a rat model of isolated-perfused lung in situ in the chest. The animals were divided into the control, control + preconditioning anti-VEGF antibody (bevacizumab, 5mg/kg, IR, IR + preconditioning anti-VEGF antibody (1mg/kg, IR+ preconditioning anti-VEGF antibody (5mg/kg and IR+ post-IR anti-VEGF antibody (5mg/kg group. There were eight adult male Sprague-Dawley rats in each group. The IR caused significant pulmonary micro-vascular hyper-permeability, pulmonary edema, neutrophilic infiltration in lung tissues, increased tumor necrosis factor-α, and total protein concentrations in bronchoalveolar lavage fluid. VEGF and extracellular signal-regulated kinase (ERK were increased in IR-induced ALI. Administration of preconditioning anti-VEGF antibody significantly suppressed the VEGF and ERK expressions and attenuated the IR-induced lung injury. This study demonstrates the important role of VEGF in early IR-induced ALI. The beneficial effects of preconditioning anti-VEGF antibody in IR-induced ALI include the attenuation of lung injury, pro-inflammatory cytokines, and neutrophilic infiltration into the lung tissues.

  19. Dexamethasone intravitreal implant in the treatment of diabetic macular edema

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    Dugel PU

    2015-07-01

    dexamethasone intravitreal implant in Phase III trials included cataract-related events (66.0% in phakic patients, intraocular pressure elevation ≥25 mmHg (29.7%, conjunctival hemorrhage (23.5%, vitreous hemorrhage (10.0%, macular fibrosis (8.3%, conjunctival hyperemia (7.2%, eye pain (6.1%, vitreous detachment (5.8%, and dry eye (5.8%; injection-related complications (eg, retinal tear/detachment, vitreous loss, endophthalmitis were infrequent (<2%. Dexamethasone intravitreal implant offers a viable treatment option for DME, especially in cases that are persistent or treatment (anti-vascular endothelial growth factor/laser refractory. Keywords: corticosteroids, dexamethasone, intravitreal, implant, macular edema, diabetic retinopathy

  20. Anti-vascular endothelial growth factor treatment decreases bladder pain in cyclophosphamide cystitis: a Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network animal model study.

    Science.gov (United States)

    Lai, H Henry; Shen, Baixin; Vijairania, Pooja; Zhang, Xiaowei; Vogt, Sherri K; Gereau, Robert W

    2017-10-01

    To investigate whether treatment with anti-vascular endothelial growth factor (VEGF)-neutralizing antibodies can reduce pain and voiding dysfunction in the cyclophosphamide (CYP) cystitis model of bladder pain in mice. Adult female mice received anti-VEGF-neutralizing antibodies (10 mg/kg i.p. B20-4.1.1 VEGF mAb) or saline (control) pre-treatment, followed by CYP (150 mg/kg i.p.) to induce acute cystitis. Pelvic nociceptive responses were assessed by applying von Frey filaments to the pelvic area. Spontaneous micturition was assessed using the void spot assay. Systemic anti-VEGF-neutralizing antibody treatment significantly reduced the pelvic nociceptive response to CYP cystitis compared with control (saline). In the anti-VEGF pre-treatment group, there was a significant increase in pelvic hypersensitivity, measured by the area under the curve (AUC) using von Frey filaments at 5 h post-CYP administration (P = 0.004); however, by 48 h and 96 h post-CYP administration, pelvic hypersensitivity had reduced by 54% and 47%, respectively, compared with the 5 h post-CYP administration time point, and were no longer significantly different from baseline (P = 0.22 and 0.17, respectively). There was no difference in urinary frequency and mean voided volume between the two pre-treatment groups. Systemic blockade of VEGF signalling with anti-VEGF-neutralizing antibodies was effective in reducing pelvic/bladder pain in the CYP cystitis model of bladder pain. Our data support the further investigation of the use of anti-VEGF antibodies to manage bladder pain or visceral pain. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

  1. Aqueous vascular endothelial growth factor and aflibercept concentrations after bimonthly intravitreal injections of aflibercept for age-related macular degeneration.

    Science.gov (United States)

    Sawada, Tomoko; Wang, Xiying; Sawada, Osamu; Saishin, Yoshitsugu; Ohji, Masahito

    2018-01-01

    Clinical evidence supports the efficacy of bimonthly aflibercept injection for age-related macular degeneration. The study aimed to evaluate aqueous vascular endothelial growth factor and aflibercept concentrations and the efficacy of bimonthly aflibercept in patients with age-related macular degeneration. This study is a prospective, interventional case series. Enrolled were 35 eyes with exudative age-related macular degeneration from 35 patients. Patients received three bimonthly intravitreal aflibercept without loading doses. We collected the aqueous humor just before each injection, measured vascular endothelial growth factor and aflibercept concentrations by enzyme-linked immunosorbent assay and measured best-corrected visual acuity and central retinal subfield thickness before and after the injections. Aqueous vascular endothelial growth factor and aflibercept concentrations were measured. The vascular endothelial growth factor concentration was 135.4 ± 60.5 pg/mL (mean ± standard deviation, range 60.6-323.4) at baseline and below the lowest detectable limit in all eyes at month 2 and in 32 eyes at month 4 (P macular degeneration. © 2017 Royal Australian and New Zealand College of Ophthalmologists.

  2. Role of implants in the treatment of diabetic macular edema: focus on the dexamethasone intravitreal implant

    Directory of Open Access Journals (Sweden)

    Cebeci Z

    2015-11-01

    Full Text Available Zafer Cebeci, Nur KirDepartment of Ophthalmology, Istanbul Faculty of Medicine, Istanbul University, Capa, Istanbul, TurkeyAbstract: Diabetic macular edema (DME is the leading cause of sight-threatening complication in diabetic patients, and several treatment modalities have been developed and evaluated to treat this pathology. Intravitreal agents, such as anti-vascular endothelial growth factors (anti-VEGF or corticosteroids, have become more popular in recent years and are widely used for treating DME. Sustained release drugs appear to be mentioned more often nowadays for extending the period of intravitreal activity, and corticosteroids play a key role in inhibiting the inflammatory process in DME. A potent corticosteroid, dexamethasone (Ozurdex®, in the form of an intravitreal implant, has been approved for various ocular etiologies among which DME is also one. This review evaluates the role of implants in the treatment of DME, mainly focusing on the dexamethasone intravitreal implant.Keywords: diabetes mellitus, diabetic macular edema, vascular endothelial growth factor, dexamethasone, Iluvien, corticosteroid

  3. The efficacy of intravitreal antivascular endothelial growth factor as primary treatment of retinopathy of prematurity: Experience from a tertiary hospital

    Directory of Open Access Journals (Sweden)

    H Kana

    2017-03-01

    Full Text Available Background. Retinopathy of prematurity (ROP is a vasoproliferative disease affecting premature babies and a major cause of blindness in childhood. Appropriate screening and treatment can prevent blindness. Objective. To report on the efficacy of using antivascular endothelial growth factor (bevacizumab as first-line therapy in ROP. Methods. This was a retrospective analysis of patients with ROP treated at St John Eye Hospital, Johannesburg, South Africa, over a 3-year period. Outcome measures were the clinical response to intravitreal bevacizumab (IVB as well as the economic impact of IVB therapy. Results. Twenty-three patients were treated for active ROP or type 1 disease, in 44 eyes. Two patients required treatment in one eye only. The mean birth weight of these patients was 1 074 g (range 810 - 1 480. Response to treatment outcome was available for 22 patients (43 eyes. The mean follow-up period was 9 months (range 1 - 18. Forty-one eyes (95.3% showed complete regression or non-progression of the disease. Two eyes (one eye each in two patients progressed to advanced disease. There were no short-term adverse events. A cost-effective model showed that IVB treatment was much more economical than laser therapy. Conclusion. IVB is a safe and effective first-line treatment for ROP and should be considered in resource-limited centres.

  4. Anti-vascular internal high LET targeted radiotherapy for cancer

    International Nuclear Information System (INIS)

    Allen, Barry J.

    2006-01-01

    Targeted alpha therapy (TAT) is an emerging therapeutic modality, thought to be best suited to cancers such as leukaemia and cancer micrometastases, but not solid tumours. However, several subjects in our phase 1 clinical trial of systemic TAT for melanoma experienced marked regression of subcutaneous and internal tumours. The MCSP receptor is expressed on both tumour capillary pericytes and melanoma cells, and is targeted by the 9.2.27 monoclonal antibody. When this is labelled with the alpha-emitting radioisotope Bi-213, the resulting alpha-immunoconjugate can extravasate through capillary fenestrations and selectively kill these cells, as well as the contiguous endothelial cells in the capillaries, causing capillary closure and subsequent tumour regression. These results suggest that tumours can be regressed by a process called tumour anti-vascular alpha therapy (TAVAT). By analogy, tumour regression in boron neutron capture therapy could be achieved by similar means, where in the alpha and Li-7 ions emitted by boron-10 neutron capture events in cancer cells contiguous to the endothelial cells could shut down tumour capillaries by a process of tumour anti-vascular neutron capture therapy (TAVNCT). (author)

  5. 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.

  6. Assessment of patient pain experience during intravitreal 27-gauge bevacizumab and 30-gauge ranibizumab injection.

    Science.gov (United States)

    Güler, Mete; Bilgin, Burak; Çapkın, Musa; Şimşek, Ali; Bilak, Şemsettin

    2015-06-01

    To compare pain scores of patients during intravitreal 27-gauge bevacizumab and 30-gauge ranibizumab injection procedures. Seventy eyes of 70 patients who had not previously undergone intravitreal anti-vascular endothelial growth factor therapy were included in this study. Thirty-five patients received ranibizumab and 35 patients received bevacizumab. The diagnoses of the patients were: 27 age related macular degeneration, 15 diabetic macular edema, 9 diabetic vitreous hemorrhage, 6 central retinal vein occlusion, 11 branch retinal vein occlusion and 2 central serous chorioretinopathy. Bevacizumab (1.25 mg/0.05 mL) was injected into the vitreous cavity using a 27-gauge needle, and ranibizumab (0.5 mg/0.05 mL) was injected with 30-gauge needle. Patients were asked just after the injection to rate their perceived pain during the injection using the visual analogue scale (VAS) of 0 (no pain) to 10 (unbearable/worst pain). The average of these scores was used as the primary outcome. The VAS pain scores in the ranibizumab and bevacizumab groups were 1.06 ± 0.91 (range, 0 to 3) and 1.94 ± 1.55 (range, 0 to 7), respectively, a significant difference (p = 0.005). Patients gauge intravitreal injection is more comfortable than 27-gauge injection. Injection of bevacizumab with 30-gauge needle syringes may be more tolerable for patients.

  7. Intravitreal anti-VEGF injections for treating wet age-related macular degeneration: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Ba J

    2015-09-01

    Full Text Available Jun Ba,1,2,* Run-Sheng Peng,2,* Ding Xu,1 Yan-Hong Li,1 Hui Shi,1,3 Qianyi Wang,1 Jing Yu11Department of Ophthalmology, Shanghai Tenth People’s Hospital Affiliated with Tongji University, 2Department of Cardiac Surgery, Institute of Cardiovascular Diseases of Fudan University, Affiliated Zhongshan Hospital of Fudan University, Shanghai, People’s Republic of China; 3Department of First Clinical Medical College, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China*Co-first authors of this workAims: Age-related macular degeneration (AMD is the main cause of blindness. Anti-vascular endothelial growth factor is used to prevent further neovascularization due to wet AMD. The purpose of this systematic review was to investigate the effect and protocol of anti-vascular endothelial growth factor treatment on wet AMD.Methods: A comprehensive literature search was performed in PubMed, Embase, the Cochrane Library, CNKI, and reference lists. Meta-analysis was performed using Stata12.0 software, best corrected visual acuity (BCVA, retinal thickness, and lesion size were evaluated.Results: Twelve randomized controlled trials spanning from 2010 to 2014 and involving 5,225 patients were included. A significant difference was observed between the intravitreal ranibizumab (IVR group and the intravitreal bevacizumab group (standard mean difference =-0.14, 95% confidence interval [CI] =-0.23 to -0.05. No significant differences were observed in best corrected VA, retinal thickness, or lesion size between IVR and the intravitreal aflibercept group. Compared to monthly injection, IVR as-needed injections (PRN can raise VA by 1.97 letters (weighted mean difference =1.97, 95% CI =0.14–3.794. Combination therapy of IVR and photodynamic therapy can significantly raise VA by 2.74 letters when combined with IVR monotherapy (weighted mean difference =2.74, 95% CI =0.26–5.21.Conclusion: The superiority remains unclear between IVR and

  8. The effect of prophylactic topical antibiotics on bacterial resistance patterns in endophthalmitis following intravitreal injection.

    Science.gov (United States)

    Storey, Philip; Dollin, Michael; Rayess, Nadim; Pitcher, John; Reddy, Sahitya; Vander, James; Hsu, Jason; Garg, Sunir

    2016-02-01

    The purpose of this study was to evaluate the effect of prophylactic topical antibiotics on bacterial resistance patterns in endophthalmitis following intravitreal injection of anti-vascular endothelial growth factor (VEGF) medications. In this retrospective case-control study, billing records and an infection log were used to identify all cases of endophthalmitis following intravitreal injection of ranibizumab, bevacizumab, or aflibercept between January 1, 2009 and September 30, 2013 at a single retina practice. A 28-month period when topical antibiotic drops were prescribed for use four times a day for 4 days following intravitreal injection was compared to a 21-month period when topical antibiotics were not prescribed. Patients treated during an 8-month transition period were excluded as prescription practices were changed. During the study period, a total of 172,096 anti-VEGF injections were performed. During the period when antibiotics were prescribed, 28 cases of suspected infectious endophthalmitis occurred from a total of 57,654 injections, ten of which were culture-positive. During the period when antibiotics were not used, 24 cases of suspected endophthalmitis occurred from a total of 89,825 injections, six of which were culture-positive. During the antibiotic period, four of the ten (40 %) culture-positive cases grew bacteria resistant to the prescribed prophylactic antibiotics. In contrast, none of the six culture-positive cases grew bacteria resistant to those antibiotics during the period when antibiotics were not used (odds ratio = 9.0; 95 % confidence interval = 0.40-203.3; p = 0.17). The use of prophylactic topical antibiotics following intravitreal injection may lead to higher rates of antibiotic-resistant bacteria in culture-positive endophthalmitis cases.

  9. Transformational change: nurses substituting for ophthalmologists for intravitreal injections – a quality-improvement report

    Directory of Open Access Journals (Sweden)

    Michelotti MM

    2014-04-01

    Full Text Available Monica M Michelotti,1 Salwa Abugreen,2 Simon P Kelly,1 Jiten Morarji,1 Debra Myerscough,2 Tina Boddie,2 Ann Haughton,1 Natalie Nixon,2 Brenda Mason,1 Evangelos Sioras11Ophthalmology Department, Royal Bolton Hospital NHS Foundation Trust, Bolton, UK; 2Ophthalmology Department, East Lancashire NHS Trust, Blackburn, UKBackground: The dramatic increase in need for anti-vascular endothelial growth factor (anti-VEGF intravitreal therapy in the treatment of retinal disease and the absence of an equivalent increase in ophthalmologists to undertake such intravitreal injections created a patient-safety risk. Timing of intravitreal therapy (IVT is critical to prevent vision loss and local clinics lacked capacity to treat patients appropriately. We aimed to improve capacity for IVT by nurse injections.Materials and methods: A multidisciplinary prospective service-improvement process was undertaken at two adjacent general hospitals in the northwest of England. IVT injections by nurses were a principal component of solution development. After we had obtained appropriate institutional approval, experienced ophthalmic nurses were trained, supervised, and assessed to undertake IVT. Ophthalmologists directly supervised the first 200 injections, and a retina specialist was always on site.Results: Nurses undertook 3,355 intravitreal injections between June 2012 and November 2013, with minor adverse events (0.3% subconjunctival hemorrhage and corneal abrasion. There were no patient complaints at either hospital.Conclusion: Experienced ophthalmic nurses quickly learned how to perform such injections safely. IVT by nurses was well accepted by patients and staff. Hospital A trained three nurses sequentially for improved flexibility in scheduling. Novel use of appropriately trained nonmedical staff can improve efficiency and access in an overburdened service with time-sensitive disease. Retinal assessment was undertaken by ophthalmologists only. Improved access to IVT

  10. Comparison of intravitreal ranibizumab and bevacizumab treatment for retinopathy of prematurity

    Directory of Open Access Journals (Sweden)

    Muhammet Kazim Erol

    2015-12-01

    Full Text Available ABSTRACT Purpose: To compare the efficacy of intravitreal ranibizumab and bevacizumab treatment for type 1 retinopathy of prematurity (ROP. Methods: 36 eyes of 20 patients with type 1 ROP who received anti-vascular endothelial growth factor (anti-VEGF intravitreal injections between August 2011 and February 2013 were retrospectively evaluated. Fifteen eyes of 8 patients received 0.25 mg ranibizumab (group 1, and 21 eyes of 12 patients received 0.625 mg bevacizumab (group 2. Eyes were examined by indirect ophthalmoscopy on the first day, third day, first week, and first month and as required after injections. Laser photocoagulation was performed in cases with progression of ROP. Results: The mean gestation time was 26.2 ± 2.7 weeks in group 1 patients and 27.1 ± 2.5 weeks in group 2 patients. No statistical difference in the time of gestation was observed between the two groups. The mean follow-up period was 20 ± 4.5 months. Laser photocoagulation was performed in 6 of 15 eyes from group 1 and 2 of 21 eyes from group 2. No eyes developed retinal detachment during the follow-up period. Conclusion: Ranibizumab and bevacizumab showed an efficacy in the treatment of type 1 ROP. The incidence of disease relapse was higher in eyes which received ranibizumab. Further randomized, controlled clinical trials are required to compare the efficacy of ranibizumab and bevacizumab.

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

    Directory of Open Access Journals (Sweden)

    Meng Cai

    2017-10-01

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

  12. Effect of intravitreal ranibizumab injections on aqueous humour concentrations of vascular endothelial growth factor and pigment epithelium-derived factor in patients with myopic choroidal neovascularisation.

    Science.gov (United States)

    Costagliola, Ciro; Semeraro, Francesco; dell'Omo, Roberto; Romano, Mario R; Russo, Andrea; Aceto, Fabiana; Mastropasqua, Rodolfo; Porcellini, Antonio

    2015-07-01

    To investigate aqueous humour changes in vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) levels in patients with choroidal neovascularisation (CNV) secondary to pathological myopia (mCNV) before and after intravitreal ranibizumab injection (IVR). This was a prospective, case-control study investigating aqueous levels of VEGF and PEDF in eyes with mCNV treated with IVR. Mean VEGF and PEDF levels in the aqueous humour of control patients were 25.7±4.9 pg/mL and 12.6±3.5 ng/mL, respectively. Lower levels of both VEGF (19.5±5.4 pg/mL) and PEDF (4.7±2.2 ng/mL) were found in patients with mCNV before IVR. After IVR, aqueous VEGF levels significantly reduced to 6.5±2.7 pg/mL, while PEDF levels significantly increased to 35.8±11.4 ng/mL. VEGF and PEDF levels significantly correlated with each other, and with best-corrected visual acuity and central retinal thickness. The VEGF and PEDF levels in aqueous humour were significantly lower in the myopic group than in controls. Moreover, IVR resulted in reduced VEGF and increased PEDF levels in patients with mCNV. In mCNV, neovascularisation is associated with inappropriate VEGF and PEDF expression. A balance between VEGF and PEDF is crucial to prevent CNV development. NCT02175940. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  13. Aqueous humor levels of vascular endothelial growth factor before and after intravitreal bevacizumab in type 3 versus type 1 and 2 neovascularization. A prospective, case-control study.

    Science.gov (United States)

    dell'Omo, Roberto; Cassetta, Marilluccia; dell'Omo, Ermanno; di Salvatore, Angela; Hughes, John M; Aceto, Fabiana; Porcellini, Antonio; Costagliola, Ciro

    2012-01-01

    To determine the aqueous levels of vascular endothelial growth factor (VEGF) in patients with type 3 neovascularization (NV) secondary to age-related macular degeneration (AMD) and to compare the levels of those with type 1 and 2 NV secondary to AMD before and after administration of intravitreal bevacizumab (IVB). Prospective, case-control study. Aqueous samples were collected from 29 eyes of 29 patients with untreated wet AMD at baseline (day of the first IVB), month 1 (day of the second IVB), and month 2 (day of the third IVB). Among them, 10 eyes presented with type 1, 9 with type 2, and 10 with type 3 NV. A group of 14 aqueous samples from 14 patients who underwent cataract surgery without other ocular or systemic disease comprised the controls. Main outcome measures were concentration of VEGF at baseline and after IVB in the 3 NV groups; secondary outcome measures included best-corrected visual acuity (BCVA) and central macular thickness (CMT) changes after IVB. Levels of VEGF were determined by commercially available enzyme-linked immunosorbent assay kits. VEGF concentrations in aqueous humor at baseline were higher in patients with type 3 NV when compared to controls (P = .0001) and type 1 and 2 NV patients (P = .002 and P = .0001 respectively). At month 1, levels of VEGF were significantly reduced compared to baseline (P < .05) and significantly lower compared to the controls (P < .005) in each NV group. These low levels were maintained at the 2-month interval. BCVA significantly improved in type 1 and 2 NV groups (P < .05). CMT significantly reduced in each NV group compared to baseline (P < .05). In eyes with untreated wet AMD, aqueous levels of VEGF are significantly higher in type 3 NV than in type 1 or 2 NV. Regardless of the type of NV, aqueous VEGF levels significantly reduce 1 month after IVB as compared to both the baseline measurements and the values recorded in age-matched controls. These decreases are maintained at 2 months after administering

  14. Indications and treatment outcomes of intravitreal bevacizumab and ...

    African Journals Online (AJOL)

    Background: The emergence of intravitreal antivascular endothelial growth factors (antiVEGF) has revolutionalised the treatment and prognosis of many retinal diseases. Aim: To determine the indications and treatment outcomes for use of intravitreal antiVEGF agents in retinal diseases among patients in a tertiary hospital ...

  15. Incidence of endophthalmitis and use of antibiotic prophylaxis after intravitreal injections.

    Science.gov (United States)

    Cheung, Crystal S Y; Wong, Amanda W T; Lui, Alex; Kertes, Peter J; Devenyi, Robert G; Lam, Wai-Ching

    2012-08-01

    To report the incidence of endophthalmitis in association with different antibiotic prophylaxis strategies after intravitreal injections of anti-vascular endothelial growth factors and triamcinolone acetonide. Retrospective, comparative case series. Fifteen thousand eight hundred ninety-five intravitreal injections (9453 ranibizumab, 5386 bevacizumab, 935 triamcinolone acetonide, 121 pegaptanib sodium) were reviewed for 2465 patients between January 5, 2005, and August 31, 2010. The number of injections was determined from billing code and patient records. The indications for injection included age-related macular degeneration, diabetic macular edema, central and branch retinal vein occlusion, and miscellaneous causes. Three strategies of topical antibiotic prophylaxis were used by the respective surgeons: (1) antibiotics given for 5 days after each injection, (2) antibiotics given immediately after each injection, and (3) no antibiotics given. The primary outcome measures were the incidence of culture-positive endophthalmitis and culture-negative cases of suspected endophthalmitis. Nine eyes of 9 patients with suspected endophthalmitis after injection were identified. Three of the 9 cases had culture-positive results. The overall incidence of endophthalmitis was 9 in 15 895. The incidence of culture-negative cases of suspected endophthalmitis and culture-proven endophthalmitis after injection was 6 in 15 895 and 3 in 15 895, respectively. Taking into account both culture-positive endophthalmitis and culture-negative cases of suspected endophthalmitis, the incidence per injection was 5 in 8259 for patients who were given antibiotics for 5 days after injection, 2 in 2370 for those who received antibiotics immediately after each injection, and 2 in 5266 who received no antibiotics. However, if considering culture-proven endophthalmitis alone, the use of topical antibiotics, given immediately or for 5 days after injection, showed lower rates of endophthalmitis

  16. The effect of intravitreal injections on dry eye, and proposed management strategies.

    Science.gov (United States)

    Laude, Augustinus; Lim, Jimmy Wk; Srinagesh, Vishwanath; Tong, Louis

    2017-01-01

    Intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents has become a commonly used treatment method for a number of ophthalmic conditions, including age-related macular degeneration. Although anti-VEGF therapy has shown promising results for many patients, there are several aspects of its application that have not been thoroughly investigated. One of these is the development and/or escalation of concurrent dry eye syndrome. Many patients undergoing treatment are already predisposed to dry eye disease due to their age and overall ocular health. As dry eye can have a substantial impact on quality of life, it has become increasingly apparent that the clinical signs and symptoms should be closely monitored and aggressively managed. This will allow for the optimization of patient comfort and visual potential. Here, we discuss the reasons why dry eye may develop during the course of repeated ocular anti-VEGF therapy, highlighting the key concerns about current practices and proposing possible solutions to improve the outcome for the patients.

  17. Anti-vascular agent Combretastatin A-4-P modulates Hypoxia Inducible Factor-1 and gene expression

    Directory of Open Access Journals (Sweden)

    Currie Margaret J

    2006-12-01

    Full Text Available Abstract Background A functional vascular network is essential for the survival, growth and spread of solid tumours, making blood vessels a key target for therapeutic strategies. Combretastatin A-4 phosphate (CA-4-P is a tubulin-depolymerising agent in Phase II clinical trials as a vascular disrupting agent. Not much is known of the molecular effect of CA-4-P under tumour conditions. The tumour microenvironment differs markedly from that in normal tissue, specifically with respect to oxygenation (hypoxia. Gene regulation under tumour conditions is governed by hypoxia inducible factor 1 (HIF-1, controlling angiogenic and metastatic pathways. Methods We investigated the effect of CA-4-P on factors of the upstream and downstream signalling pathway of HIF-1 in vitro. Results CA-4-P treatment under hypoxia tended to reduce HIF-1 accumulation in a concentration-dependent manner, an effect which was more prominent in endothelial cells than in cancer cell lines. Conversely, CA-4-P increased HIF-1 accumulation under aerobic conditions in vitro. At these concentrations of CA-4-P under aerobic conditions, nuclear factor κB was activated via the small GTPase RhoA, and expression of the HIF-1 downstream angiogenic effector gene, vascular endothelial growth factor (VEGF-A, was increased. Conclusion Our findings advance the understanding of signal transduction pathways involved in the actions of the anti-vascular agent CA-4-P.

  18. Aqueous Humor Levels of Vascular Endothelial Growth Factor Before and After Intravitreal Bevacizumab in Type 3 Versus Type 1 and 2 Neovascularization. A Prospective, Case-Control Study

    NARCIS (Netherlands)

    Dell'Omo, Roberto; Cassetta, Marilluccia; Dell'Omo, Ermanno; di Salvatore, Angela; Hughes, John M.; Aceto, Fabiana; Porcellini, Antonio; Costagliola, Ciro

    2012-01-01

    PURPOSE: To determine the aqueous levels of vascular endothelial growth factor (VEGF) in patients with type 3 neovascularization (NV) secondary to age-related macular degeneration (AMD) and to compare the levels of those with type 1 and 2 NV secondary to AMD before and after administration of

  19. The effect of intravitreal injections on dry eye, and proposed management strategies

    Directory of Open Access Journals (Sweden)

    Laude A

    2017-08-01

    Full Text Available Augustinus Laude,1–3 Jimmy WK Lim,1,2 Vishwanath Srinagesh,4 Louis Tong2,5–7 1National Healthcare Group Eye Institute, Tan Tock Seng Hospital, 2Singapore Eye Research Institute, 3Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore; 4Krieger Eye Institute, Baltimore, MD, USA; 5Singapore National Eye Centre, 6Duke NUS Medical School, 7Yong Loo Lin School of Medicine, National University of Singapore, Singapore Abstract: Intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF agents has become a commonly used treatment method for a number of ophthalmic conditions, including age-related macular degeneration. Although anti-VEGF therapy has shown promising results for many patients, there are several aspects of its application that have not been thoroughly investigated. One of these is the development and/or escalation of concurrent dry eye syndrome. Many patients undergoing treatment are already predisposed to dry eye disease due to their age and overall ocular health. As dry eye can have a substantial impact on quality of life, it has become increasingly apparent that the clinical signs and symptoms should be closely monitored and aggressively managed. This will allow for the optimization of patient comfort and visual potential. Here, we discuss the reasons why dry eye may develop during the course of repeated ocular anti-VEGF therapy, highlighting the key concerns about current practices and proposing possible solutions to improve the outcome for the patients. Keywords: age-related macular degeneration, povidone–iodine, toxicity, ocular health, chronic ophthalmic treatment

  20. Quality of bevacizumab (Avastin®) repacked in single-use glass vials for intravitreal administration.

    Science.gov (United States)

    Sugimoto, Michelle A A; Toledo, Vicente de Paulo Coelho Peixoto de; Cunha, Mariem Rodrigues Ribeiro; Carregal, Virginia M; Jorge, Rodrigo; Leão, Pedro; Fialho, Sílvia Ligorio; Silva-Cunha, Armando

    2017-01-01

    Avastin® (bevacizumab) is an anti-vascular endothelial growth factor (VEGF) monoclonal antibody given as an off-label drug by intravitreal administration for treatment of ocular diseases. The drug's clinical application and its cost-benefit profile has generated demand for its division into single-use vials to meet the low volume and low-cost doses necessary for intraocular administration. However, the safety of compounding the drug in single-use vials is still under discussion. In this study, the stability and efficacy of Avastin® repacked in individual single-use glass vials and glass ampoules by external compounding pharmacies were evaluated. Polyacrylamide gel electrophoresis (PAGE), size-exclusion chromatography (SEC), dynamic light scattering (DLS), and turbidimetry were selected to detect the formation of aggregates of various sizes. Changes in bevacizumab biological efficacy were investigated by using an enzyme-linked immunosorbent assay (ELISA). Repacked and reference bevacizumab showed similar results when analyzed by PAGE. By SEC, a slight increase in high molecular weight aggregates and a reduction in bevacizumab monomers were observed in the products of the three compounding pharmacies relative to those in the reference bevacizumab. A comparison of repacked and reference SEC chromatograms showed that the mean monomer loss was ≤1% for all compounding pharmacies. Protein aggregates in the nanometer- and micrometer-size ranges were not detected by DLS and turbidimetry. In the efficacy assay, the biological function of repacked bevacizumab was preserved, with <3% loss of VEGF binding capacity relative to that of the reference. The results showed that bevacizumab remained stable after compounding in ampoules and single-use glass vials; no significant aggregation, fragmentation, or loss of biological activity was observed.

  1. Pre-clinical longitudinal monitoring of hemodynamic response to anti-vascular chemotherapy by hybrid diffuse optics.

    Science.gov (United States)

    Farzam, Parisa; Johansson, Johannes; Mireles, Miguel; Jiménez-Valerio, Gabriela; Martínez-Lozano, Mar; Choe, Regine; Casanovas, Oriol; Durduran, Turgut

    2017-05-01

    The longitudinal effect of an anti-vascular endothelial growth factor receptor 2 (VEGFR-2) antibody (DC 101) therapy on a xenografted renal cell carcinoma (RCC) mouse model was monitored using hybrid diffuse optics. Two groups of immunosuppressed male nude mice (seven treated, seven controls) were measured. Tumor microvascular blood flow, total hemoglobin concentration and blood oxygenation were investigated as potential biomarkers for the monitoring of the therapy effect twice a week and were related to the final treatment outcome. These hemodynamic biomarkers have shown a clear differentiation between two groups by day four. Moreover, we have observed that pre-treatment values and early changes in hemodynamics are highly correlated with the therapeutic outcome demonstrating the potential of diffuse optics to predict the therapy response at an early time point.

  2. Intravitreal anti-VEGF agents, oral glucocorticoids, and laser photocoagulation combination therapy for macular edema secondary to retinal vein occlusion: preliminary report

    Directory of Open Access Journals (Sweden)

    Xiao-Xiao Feng

    2018-03-01

    Full Text Available AIM: To evaluate the efficacy and safety of combined anti-vascular endothelial growth factor (VEGF agents, oral glucocorticoid, and laser photocoagulation therapy for macular edema (ME secondary to retinal vein occlusion (RVO. METHODS: This study included 16 eyes of 16 patients with RVO-associated ME. Patients were initially treated with oral prednisone and an intravitreal anti-VEGF agent. Two weeks later, patients underwent standard laser photocoagulation. Best-corrected visual acuity (BCVA, central retinal thickness (CRT, and retinal vessel oxygenation were examined over 12mo. RESULTS: Patients received 1.43±0.81 anti-VEGF injections. Mean baseline and 12-month logMAR BCVA were 0.96±0.51 (20/178 and 0.31±0.88 (20/40, respectively, in eyes with central retinal vein occlusion (CRVO (P<0.00, and 1.02±0.45 (20/209 and 0.60±0.49 (20/80, respectively, in eyes with branch retinal vein occlusion (BRVO (P<0.00. At 12mo, CRT had significantly decreased in eyes with CRVO (P<0.00 and BRVO (P<0.00. Venous oxygen saturation had significantly increased in eyes with CRVO (P<0.00 and BRVO (P<0.00. No examined parameters were significantly different between the 2 RVO groups. No serious adverse effects occurred. CONCLUSION: Anti-VEGF, glucocorticoid, and photocoagulation combination therapy improves visual outcome, prolongs therapeutic effect, and reduces the number of intravitreal injections in eyes with RVO-associated ME.

  3. Intravitreal bevacizumab (avastin for circumscribed choroidal hemangioma

    Directory of Open Access Journals (Sweden)

    Subrata Mandal

    2011-01-01

    Full Text Available Circumscribed choroidal hemangiomas are rare ophthalmic entities that cause diminution in vision due to accumulation of subretinal and/or intraretinal fluid in the macular area. Various treatment options ranging from conventional laser to photodynamic therapy have been employed to destroy the tumor and reduce the exudation; however, either the inability to penetrate through the exudative fluid or the collateral retinal damage induced by these treatment modalities make them unsuitable for lesions within the macula. We evaluated the role of intravitreal bevacizumab, a pan-vascular endothelial growth factor (VEGF inhibitor, in reducing the sub- and intraretinal fluid in three patients with circumscribed choroidal hemangiomas. All the patients had complete resolution of the serous retinal detachment that was maintained till at least 12 months after the first injection. Intravitreal bevacizumab may be used in combination with thermal laser or photodynamic therapy in treating circumscribed choroidal hemangiomas with subretinal fluid.

  4. Aqueous humor levels of vascular endothelial growth factor and adiponectin in patients with type 2 diabetes before and after intravitreal bevacizumab injection.

    Science.gov (United States)

    Costagliola, Ciro; Daniele, Aurora; dell'Omo, Roberto; Romano, Mario R; Aceto, Fabiana; Agnifili, Luca; Semeraro, Francesco; Porcellini, Antonio

    2013-05-01

    To determine the levels of vascular endothelial growth factor (VEGF) and adiponectin (APN) in the aqueous humor of patients with type 2 diabetes before and after injection of bevacizumab (IVB). Twenty eyes of twenty consecutive patients with type 2 diabetes with PDR and clinically significant macular edema were enrolled in this study. Aqueous samples were collected at baseline and one month after IVB to evaluate VEGF and APN levels. Twenty age-matched patients undergoing cataract surgery were used as control. Best-corrected visual acuity (BCVA) and foveal thickness (FT) changes after IVB were also measured. Safety was assessed by recording the incidence of ocular and non-ocular adverse events. At baseline APN and VEGF levels were significantly lower in controls than in PDR patients (APN: 3.6 ± 1.1 vs 18.7 ± 4.5 ng/ml; VEGF: 22.6 ± 16.1 vs 146.2 ± 38.71 pg/ml). After IVB, both compounds significantly decreased. FT and BCVA at baseline were significantly different between controls and patients (FT: 215.6 ± 34.8 vs 532.7 ± 112.4 μm; BCVA: 23.6 ± 4.2 vs 18.4 ± 7.3 letters). After IVB a significant decrease of FT with a concomitant improvement of BCVA occurred. Neither ocular nor systemic adverse events were reported. Our findings demonstrate that patients with type 2 diabetes, PDR and macular edema show VEGF and APN levels in aqueous humor higher than those found in control subjects. IVB significantly reduced the levels of both compounds, which remained anyway at concentrations higher than those recorded in control subjects. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Prefilled syringes for intravitreal injection reduce preparation time

    DEFF Research Database (Denmark)

    Subhi, Yousif; Kjer, Birgit; Munch, Inger Christine

    2016-01-01

    INTRODUCTION: The demand for intravitreal therapy has increased dramatically with the introduction of vascular endo-thelial growth factor inhibitors. Improved utilisation of existing resources is crucial to meeting the increased future demand. We investigated time spent preparing intravitreal...... injection treatment using either prefilled syringes or vials in routine clinical practice. METHODS: We video-recorded preparations of intravitreal injections (n = 172) for each preparation type (ranibizumab prefilled syringe (n = 56), ranibizumab vial (n = 56) and aflibercept vial (n = 60)) in a multi......-centre time and motion study. The preparation times for each step were extracted from videos and the three preparation types were compared. RESULTS: Prefilled syringes eliminated several steps in the preparation process. Total preparation time was 40.3-45.1 sec. using vials, and the use of prefilled syringes...

  6. Management of noninfectious posterior uveitis with intravitreal drug therapy

    Directory of Open Access Journals (Sweden)

    Tan HY

    2016-10-01

    Full Text Available Hui Yi Tan,1 Aniruddha Agarwal,2 Cecilia S Lee,3 Jay Chhablani,4 Vishali Gupta,5 Manoj Khatri,6 Jayabalan Nirmal,7 Carlos Pavesio,8 Rupesh Agrawal1,7–9 1Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 2Department of Vitreoretina, Stanley M Truhlsen Eye Institute, University of Nebraska Medical Center, Omaha, NE, 3Department of Ophthalmology, University of Washington, Seattle, WA, USA; 4Department of Vitreoretina, L V Prasad Eye Institute, Hyderabad, Telangana, 5Department of Retina and Uvea, Post Graduate Institute of Medical Education and Research, Chandigarh, 6Department of Retina, Rajan Eye Care Hospital, Chennai, Tamil Nadu, India; 7School of Material Science and Engineering, Nanyang Technological University, Singapore; 8Department of Medical Retina, Moorfields Eye Hospital, NHS Foundation Trust, London, UK; 9Department of Ophthalmology, National Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore Abstract: Uveitis is an important cause of vision loss worldwide due to its sight-threatening complications, especially cystoid macular edema, as well as choroidal neovascularization, macular ischemia, cataract, and glaucoma. Systemic corticosteroids are the mainstay of therapy for noninfectious posterior uveitis; however, various systemic side effects can occur. Intravitreal medication achieves a therapeutic level in the vitreous while minimizing systemic complications and is thus used as an exciting alternative. Corticosteroids, antivascular endothelial growth factors, immunomodulators such as methotrexate and sirolimus, and nonsteroidal anti-inflammatory drugs are currently available for intravitreal therapy. This article reviews the existing literature for efficacy and safety of these various options for intravitreal drug therapy for the management of noninfectious uveitis (mainly intermediate, posterior, and panuveitis. Keywords: intravitreal therapy, noninfectious uveitis, posterior uveitis

  7. Sterile Endophthalmitis after Intravitreal Injections

    Directory of Open Access Journals (Sweden)

    Joaquín Marticorena

    2012-01-01

    Full Text Available Sterile endophthalmitis appears as an infrequent complication of intravitreal injections and seems to develop mainly in the context of the off-label use of drugs that have not been conceived for intravitreous administration. The aetiology of sterile endophthalmitis, independently of the administered drug, remains uncertain and a multifactorial origin cannot be discarded. Sterile inflammation secondary both to intravitreal triamcinolone acetonide and to intravitreal bevacizumab share many characteristics such as the acute and painless vision loss present in the big majority of the cases. Dense vitreous opacity is a common factor, while anterior segment inflammation appears to be mild to moderate. In eyes with sterile endophthalmitis, visual acuity improves progressively as the intraocular inflammation reduces without any specific treatment. If by any chance the ophthalmologist is not convinced by the sterile origin of the inflammation, this complication must be treated as an acute endophthalmitis because of the devastating visual prognosis of this intraocular infection in the absence of therapy.

  8. Analysis of the association between CFH Y402H polymorphism and response to intravitreal ranibizumab in patients with neovascular age-related macular degeneration (nAMD

    Directory of Open Access Journals (Sweden)

    Nur Afiqah Mohamad

    2018-03-01

    Full Text Available Pharmacogenetic studies indicate that a variable response to anti-vascular endothelial growth factor (VEGF therapy in patients with neovascular form of AMD (nAMD may be due to polymorphisms in the complement factor H gene (CFH. This study is the first to investigate the association between CFH Y402H polymorphism and the response to ranibizumab therapy in Malaysian patients with nAMD. We included 134 patients with nAMD, examined between September 2014 and February 2016. The diagnosis of nAMD was confirmed by ophthalmologic examination, before ranibizumab therapy was started. Each patient received an intravitreal injection of 0.5 mg/0.05 ml ranibizumab following a treat-and-extend (TE regimen. Best-corrected visual acuity (BCVA and central retinal thickness (CRT were recorded after 3 and 6 months following the first injection and compared with the baseline values. Genotyping of Y402H (rs1061170 polymorphism was performed using PCR-RFLP and the amplified product was digested with MluCI restriction enzyme. Association between the Y402H genotypes and response to treatment was determined by a logistic regression analysis of responder (n = 49 and non-responder (n = 84 group. Significantly worse mean BCVA was observed for the CC genotype compared to the TT + CT genotype in the total sample after 6-month follow-up (p = 0.018. Comparing the baseline and 6-month point measurements, improved mean BCVA was observed in responder group, while worse mean BCVA was recorded for non-responder group. However, our regression analysis, adjusted for confounding factors, showed no significant association between the Y402H genotypes and response to treatment in nAMD patients under the recessive model (p > 0.05. Overall, our results suggest that factors other than Y402H polymorphism may be involved in the progression of nAMD after treatment with anti-VEGF agents, in Malaysian population.

  9. Survey of intravitreal injection techniques among retina specialists in Israel

    Directory of Open Access Journals (Sweden)

    Segal O

    2016-06-01

    Full Text Available Ori Segal,1,2 Yael Segal-Trivitz,1,3 Arie Y Nemet,1,2 Noa Geffen,1,2 Ronit Nesher,1,2 Michael Mimouni4 1Department of Ophthalmology, Meir Medical Center, Kfar Saba, 2The Sackler School of Medicine, Tel Aviv University, Tel Aviv, 3Department of Psychiatry, Geha Psychiatric Hospital, Petah Tikva, 4Department of Ophthalmology, Rambam Health Care Campus, Haifa, Israel Purpose: The purpose of this study was to describe antivascular endothelial growth factor intravitreal injection techniques of retinal specialists in order to establish a cornerstone for future practice guidelines. Methods: All members of the Israeli Retina Society were contacted by email to complete an anonymous, 19-question, Internet-based survey regarding their intravitreal injection techniques. Results: Overall, 66% (52/79 completed the survey. Most (98% do not instruct patients to discontinue anticoagulant therapy and 92% prescribe treatment for patients in the waiting room. Three quarters wear sterile gloves and prepare the patient in the supine position. A majority (71% use sterile surgical draping. All respondents apply topical analgesics and a majority (69% measure the distance from the limbus to the injection site. A minority (21% displace the conjunctiva prior to injection. A majority of the survey participants use a 30-gauge needle and the most common quadrant for injection is superotemporal (33%. Less than half routinely assess postinjection optic nerve perfusion (44%. A majority (92% apply prophylactic antibiotics immediately after the injection. Conclusion: The majority of retina specialists perform intravitreal injections similarly. However, a relatively large minority performs this procedure differently. Due to the extremely low percentage of complications, it seems as though such differences do not increase the risk. However, more evidence-based medicine, a cornerstone for practice guidelines, is required in order to identify the intravitreal injection techniques

  10. The Chinese medicine formula HB01 reduces choroidal neovascularization by regulating the expression of vascular endothelial growth factor

    Directory of Open Access Journals (Sweden)

    Jin Ming

    2012-06-01

    Full Text Available Abstract Background Choroidal neovascularization (CNV remains the leading cause of newly acquired blindness in the developed world. Currently anti-vascular endothelial growth factor (VEGF therapies are broadly used to treat neovascular ocular disorders. Here we demonstrate the effect of a traditional Chinese medicine formula, HB01, on CNV. Methods A rat model of laser-induced CNV was used to investigate the effect of HB01 in vivo. The CNV lesions in the eye were evaluated using fundus fluorescein angiography and visualized/quantified using confocal microscopy. Expression of VEGF in the choroidal and retinal tissues was measured using quantitative real-time PCR and immunohistochemistry. Results We demonstrated that a traditional Chinese Medicine formula, named HB01, significantly reduced neovascularization in a rat CNV model. The effect of HB01 on CNV was comparable to the intravitreal injection of bevacizumab (Avastin. Our results also suggested that HB01 may reduce CNV partially through inhibiting the expression of VEGF. Conclusions These data support HB01 as an alternative therapy for ocular neovascular disorders.

  11. Non-physician delivered intravitreal injection service is feasible and safe

    DEFF Research Database (Denmark)

    Rasul, Asrin; Subhi, Yousif; Sørensen, Torben Lykke

    2016-01-01

    INTRODUCTION: Non-physicians such as nurses are trained to give injections into the vitreous body of the eye to meet the increasing demand for intravitreal therapy with vascular endothelial growth factor inhibitors against common eye diseases, e.g. age-related macular degeneration and diabetic...... by 16 nurses. The studies found that having nurses perform the intravitreal injections produced to a short-term capacity improvement and liberated physicians for other clinical work. Training was provided through courses and direct supervision. The rates of endophthalmitis were 0-0.40‰, which...

  12. 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...

  13. Efficacy of Intravitreal Bevacizumab for Stage 3+ Retinopathy of Prematurity

    Science.gov (United States)

    Mintz-Hittner, Helen A.; Kennedy, Kathleen A.; Chuang, Alice Z.

    2011-01-01

    BACKGROUND Retinopathy of prematurity is a leading cause of childhood blindness worldwide. Peripheral retinal ablation with conventional (confluent) laser therapy is destructive, causes complications, and does not prevent all vision loss, especially in cases of retinopathy of prematurity affecting zone I of the eye. Case series in which patients were treated with vascular endothelial growth factor inhibitors suggest that these agents may be useful in treating retinopathy of prematurity. METHODS We conducted a prospective, controlled, randomized, stratified, multicenter trial to assess intravitreal bevacizumab monotherapy for zone I or zone II posterior stage 3+ (i.e., stage 3 with plus disease) retinopathy of prematurity. Infants were randomly assigned to receive intravitreal bevacizumab (0.625 mg in 0.025 ml of solution) or conventional laser therapy, bilaterally. The primary ocular outcome was recurrence of retinopathy of prematurity in one or both eyes requiring retreatment before 54 weeks’ postmenstrual age. RESULTS We enrolled 150 infants (total sample of 300 eyes); 143 infants survived to 54 weeks’ postmenstrual age, and the 7 infants who died were not included in the primary-outcome analyses. Retinopathy of prematurity recurred in 4 infants in the bevacizumab group (6 of 140 eyes [4%]) and 19 infants in the laser-therapy group (32 of 146 eyes [22%], P = 0.002). A significant treatment effect was found for zone I retinopathy of prematurity (P = 0.003) but not for zone II disease (P = 0.27). CONCLUSIONS Intravitreal bevacizumab monotherapy, as compared with conventional laser therapy, in infants with stage 3+ retinopathy of prematurity showed a significant benefit for zone I but not zone II disease. Development of peripheral retinal vessels continued after treatment with intravitreal bevacizumab, but conventional laser therapy led to permanent destruction of the peripheral retina. This trial was too small to assess safety. PMID:21323540

  14. Prognostic value and kinetics of circulating endothelial cells in patients with recurrent glioblastoma randomised to bevacizumab plus lomustine, bevacizumab single agent or lomustine single agent. A report from the Dutch Neuro-Oncology Group BELOB trial

    NARCIS (Netherlands)

    Beije, N.; Kraan, J.; Taal, W.; van der Holt, B.; Oosterkamp, H. M.; Walenkamp, A. M.; Beerepoot, L.; Hanse, M.; van Linde, M. E.; Otten, A.; Vernhout, R. M.; de Vos, F. Y. F.; Gratama, J. W.; Sleijfer, S.; van den Bent, M. J.

    2015-01-01

    Background: Angiogenesis is crucial for glioblastoma growth, and anti-vascular endothelial growth factor agents are widely used in recurrent glioblastoma patients. The number of circulating endothelial cells (CECs) is a surrogate marker for endothelial damage. We assessed their kinetics and explored

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

    Directory of Open Access Journals (Sweden)

    Jeong Hun Bae

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

  16. Design of a humanized anti vascular endothelial growth factor nanobody and evaluation of its in vitro function

    OpenAIRE

    Fatemeh Kazemi-Lomedasht; serge muyldermans; Mahdi Habibi-Anbouhi; Mahdi Behdani

    2018-01-01

    Objective(s): Nanobodies, the single domain antigen binding fragments of heavy chain-only antibodies occurring naturally in camelid sera, are the smallest intact antigen binding entities. Their minimal size assists in reaching otherwise largely inaccessible regions of antigens. However, their camelid origin raises a possible concern of immunogenicity when used for human therapy. Humanization is a promising approach to overcome the problem.   Materials and Methods: Here, we designed a humanize...

  17. The Use of Intravitreal Aflibercept in the Treatment of Wet Type of Age Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Rejith Rag

    2015-04-01

    Full Text Available Aflibercept, an anti vascular endothelial growth factor (anti-VEGF which was originally developed in the treatment of large bowel cancers, has been found to be effective in the treatment of wet type of age related macular degeneration (ARMD, a potentially sight threatening condition affecting the retina. Chemically this biological drug is C4318 H6788 N1164 O1304 S12 with a molecular weight of 96.9 KDa. This is manufactured as a lipid soluble recombinant fusion glycoprotein that binds with both forms of vascular endothelial growth factors, i.e. A and B as well as placental growth factors, thus blocking the angiogenic action and consequent neovascular membrane growth, the pathognomonic feature of wet ARMD.

  18. The efficacy of intravitreal antivascular endothelial growth factor as ...

    African Journals Online (AJOL)

    The findings of a multicentre trial of cryotherapy for ROP (CRYO-. ROP)[3] have shown the benefit of treatment with cryotherapy in reducing unfavourable visual outcome by 50% in infants at risk of proliferative retinopathy. Subsequently, the Early Treatment of. ROP (ETROP) study[4] showed laser ablation to be superior to.

  19. The efficacy of intravitreal antivascular endothelial growth factor as ...

    African Journals Online (AJOL)

    such as retinal vein occlusion[6] and diabetic retinopathy[7] have led to a paradigm shift in the management of these conditions. As an extension of this, anti-VEGF (bevacizumab) therapy has been used in treating ROP, initially as an adjunct to laser therapy and subsequently as primary treatment. Several case studies have ...

  20. The efficacy of intravitreal antivascular endothelial growth factor as ...

    African Journals Online (AJOL)

    Retinopathy of prematurity (ROP) is a vasoproliferative disease affecting premature babies and a major cause of blindness in childhood. Appropriate screening and treatment can prevent ... Forty-one eyes (95.3%) showed complete regression or non-progression of the disease. Two eyes (one eye each in two patients) ...

  1. Indications and Treatment Outcomes of Intravitreal Bevacizumab ...

    African Journals Online (AJOL)

    angiogenesis, reduces vascular permeability and licensed for use in neovascular macular degeneration. However, its use is on the decline.[11]. The study was conducted to determine the indications and treatment outcomes in the use of intravitreal antiVEGF in a group of patients presenting to a tertiary hospital in Southern.

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

    Directory of Open Access Journals (Sweden)

    Zheng-Jun Hu

    2015-05-01

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

  3. Intravitreal ranibizumab for diabetic macular oedema in previously vitrectomized eyes

    DEFF Research Database (Denmark)

    Laugesen, Caroline Schmidt; Ostri, Christoffer; Brynskov, Troels

    2017-01-01

    PURPOSE: There is little information about the efficacy of intravitreal vascular endothelial growth factor (VEGF) inhibition in vitrectomized eyes. This study aimed to evaluate the efficacy of anti-VEGF (ranibizumab) on diabetic macular oedema in previously vitrectomized eyes. METHODS: A nationwide...... retrospective review of medical records from 2010 to 2013. RESULTS: We identified 33 previously vitrectomized eyes in 28 patients treated with ranibizumab injections for diabetic macular oedema. Median follow-up was 323 days (interquartile range 72-1404 days). Baseline mean visual acuity was 0.57 logMAR (95% CI...... 0.13-1.01) before injections. After an average of 4.7 injections (range 1-15), mean visual acuity remained stable at 0.54 logMAR (95% CI 0.13-0.95) with a mean improvement of 0.03 (p = 0. 45, 95% CI -0.12 to 0.06). In 12 eyes (36%), visual acuity improved 0.1 logMAR or more, in 12 eyes (36%), vision...

  4. A Mathematical Analysis of Intravitreal Drug Transport | Avtar ...

    African Journals Online (AJOL)

    Purpose: The aim of our present work is the development of a quasi steady-state model for the distribution of intravitreally injected drugs and investigation of the effects of various model parameters on the drug distribution in normal and diseased eyes. Method: A simple mathematical model for the intravitreal transport of ...

  5. The role of intravitreal chemotherapy for retinoblastoma

    Directory of Open Access Journals (Sweden)

    Fairooz P Manjandavida

    2015-01-01

    Full Text Available Targeted therapy in retinoblastoma (RB is widely accepted as the current management tool with an aim of increasing drug availability at the tumor location. Inevitably the effect is several times higher compared to systemic delivery of chemotherapeutic drugs and carries less systemic toxicity. Despite tremendous advancement in saving life, eye salvage in advanced RB especially with active vitreous seeds remains a challenge. The hypoxic environment of the vitreous and reduced vitreous concentration of the drugs delivered makes these tumor seeds resistant to chemotherapy. Direct delivery of chemotherapeutic drugs into the vitreous cavity aids to overcome these challenges and is progressively being accepted worldwide. However, intraocular procedure in RB was abandoned due to high risk of extraocular tumor dissemination. Recently, the forbidden therapeutic technique was re-explored and modified for safe use. Although eye salvage rate has tremendously improved after intravitreal chemotherapy (IVitC, retinal toxicity, and vision salvage are yet to be validated. In our preliminary report of intravitreal melphalan in 11 eyes, we reported 100% eye salvage and 0% recurrence with an extended 15 months mean follow-up. In this review, we analyzed published reports on IVitC in RB via PubMed, Medline, and conference proceedings citation index, electronic database search, without language restriction that included case series and reports of humans and experimental animal eyes with RB receiving IVitC.

  6. Intravitreal triamcinolone for diffuse diabetic macular oedema.

    LENUS (Irish Health Repository)

    Gibran, S K

    2012-02-03

    AIM: To evaluate the efficacy of intravitreal triamcinolone (IVTA) for the treatment of diffuse diabetic macular oedema (DME) refractory to conventional argon macular laser therapy. METHODS: A prospective, consecutive, and noncomparative case series was undertaken involving 38 eyes of 38 patients with refractory DME. Triamcinolone acetonide (4 mg) in 0.1 ml was injected intravitreally. LogMar visual acuity (VA) and macular thickness measured by ocular coherence tomography (OCT) were assessed preoperatively and postoperatively at 1, 3, and 6 months. RESULTS: All patients completed 6 months of follow up. VA (mean+\\/-SD) improved from 0.905+\\/-0.23 to 0.605+\\/-0.28, 0.555+\\/-0.29, and 0.730+\\/-0.30 at 1, 3, and 6 months, respectively. Macular thickness baseline (mean+\\/-SD) on OCT was 418.7+\\/-104.2 microm and this decreased to 276.9+\\/-72.6 microm, 250.6+\\/-53.1 microm, and 308.8+\\/-87.3 microm at 1, 3, and 6 months, respectively. CONCLUSIONS: IVTA may be a potential temporary treatment for refractory DME. It is effective in decreasing macular thickness and improving VA but the effect lasts approximately for 6 months in the majority of patients. Further investigations are required to establish the safety of IVTA for the treatment of DME.

  7. Isolated sixth nerve palsy after intravitreal bevacizumab injection.

    Science.gov (United States)

    Cakmak, Hasan Basri; Toklu, Yasin; Yorgun, Mücella Arikan; Simşek, Saban

    2010-03-01

    To report a case of sixth nerve palsy after intravitreal bevacuzimab injection. After intravitreal bevacizumab injection in a 64-year-old man, the patient admitted to our clinic with the complaint of diplopia. A complete ophthalmologic examination was done to clear the symptomatology of patient. Examination of ductions revealed marked limitation of abduction of the right eye and full ductions of the left eye, consistent with right lateral rectus paralysis. Although intravitreal bevacizumab injections are generally well tolerated, it is possible that some serious systemic adverse events may occur. For this reason, patients must be closely monitored following these injections.

  8. Efficacy of Intravitreal injection of 2-Methoxyestradiol in regression of neovascularization of a retinopathy of prematurity rat model.

    Science.gov (United States)

    Said, Azza Mohamed Ahmed; Zaki, Rania Gamal Eldin; Salah Eldin, Rania A; Nasr, Maha; Azab, Samar Saad; Elzankalony, Yaser Abdelmageuid

    2017-04-04

    Retinopathy of prematurity (ROP) is one of the targets for early detection and treatment to prevent childhood blindness in world health organization programs. The purpose of study was to evaluate the efficacy of intravitreal injection of 2-Methoxyestradiol (2-ME) nanoemulsion in regressing neovascularization of a ROP rat model. A prospective comparative case - control animal study conducted on 56 eyes of 28 healthy new born Sprague Dawley male albino rat. ROP was induced in 21 rats then two concentrations of 2-ME nanoparticles were injected in right eyes of 14 rats (low dose; study group I, high dose; study group II). A blank nanoemulsion was injected in the right eyes of seven rats (control positive group I). No injections performed in contralateral left eyes (control positive group II). Seven rats (14 eyes) were kept in room air (control negative group). On postnatal day 17, eyeballs were enucleated. Histological structure of the retina was examined using Hematoxylin and eosin staining. Vascular endothelial growth factor (VEGF) and glial fibrillary acidic protein (GFAP) expressions were detected by immunohistochemical studies. Intravitreal injection of 2-ME (in the two concentrations) caused marked regression of the new vascular tufts on the vitreal side with normal organization and thickness of the retina especially in study group II, which also show negative VEGF immunoreaction. Positive GFAP expression was detected in the control positive groups and study group (I). Intravitreal injection of 2-Methoxyestradiol nanoemulsion is a promising effective method in reduction of neovascularization of a ROP rat model.

  9. NONINFECTIOUS VITRITIS AFTER INTRAVITREAL INJECTION OF ANTI-VEGF AGENTS: Variations in Rates and Presentation by Medication.

    Science.gov (United States)

    Williams, Patrick D; Chong, Deborah; Fuller, Timothy; Callanan, David

    2016-05-01

    The purpose of this study was to describe and compare the rates and characteristics of noninfectious vitritis after intravitreal injection of bevacizumab (Avastin, Genentech, South San Francisco, CA), ranibizumab (Lucentis, Genentech), and aflibercept (Eylea, Regeneron, Tarrytown, NY). A retrospective case series evaluated intravitreal injections from 2006 to 2013. Cases of inflammatory response were separated into culture-positive endophthalmitis, noninfectious vitritis (not treated with intravitreal antibiotics), and indeterminate. Noninfectious cases were analyzed for rate, presentation, and clinical course. A total of 66,356 bevacizumab, 26,161 ranibizumab, and 8071 aflibercept injections were screened. The rates of noninfectious vitritis were 0.10% (67 cases) for bevacizumab, 0.02% (6 cases) for ranibizumab, and 0.16% (13 cases) for aflibercept. The differences were statistically significant based on Chi-square analysis (P medication according to Fisher exact test (P medication based on Fisher exact testing (P = 0.2, P = 0.18, P = 0.16, respectively). Bevacizumab and aflibercept cases tended to present in separate chronological clusters. The results suggest a difference in rates of noninfectious vitritis for antivascular endothelial growth factor medications. Many cases tended to cluster instead of occurring at a consistent rate each year.

  10. The role of the gene SERPINH1 as a pharmacogenetic biomarker for choroidal neovascularization (CNV) responses to anti vascular endothelial growth factor (VEGF) treatment in clinical practice

    OpenAIRE

    Pierce, Charles

    2015-01-01

    Age related macular degeneration is the commonest cause of blindness in the western world and current treatment regimens represent a significant output for national health services. The disease process is multifactorial in origin and has a variable progression and response to current methods of treatment. A targeted approach with individualized therapy based on recognized biomarkers to predict disease outcome would be the ideal treatment modality.We plan to investigate the role of genes known...

  11. QUANTITATIVE ANALYSIS OF PIGMENT EPITHELIAL DETACHMENT RESPONSE TO DIFFERENT ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR AGENTS IN WET AGE-RELATED MACULAR DEGENERATION.

    Science.gov (United States)

    Balaskas, Konstantinos; Karampelas, Michael; Horani, Mania; Hotu, Oana; Keane, Pearse; Aslam, Tariq

    2017-07-01

    To assess whether best-corrected visual acuity and pigment epithelial detachment (PED) height, volume, and reflectivity in patients with wet age-related macular degeneration are influenced by baseline anatomical and functional parameters, including quantifiable metrics of PED morphology and choice of treatment. One hundred two consecutive, treatment-naive wet age-related macular degeneration patients with PED (>50 μm) treated with aflibercept (52) or ranibizumab (50) were retrospectively included. Pigment epithelial detachment height, horizontal and vertical dimensions, and volume were recorded at baseline, 3 months, and 1 year, respectively. Bespoke image analysis software provided a quantifiable measure of reflectivity. Best-corrected visual acuity at 3 months was influenced by baseline best-corrected visual acuity (P = 0.006). Pigment epithelial detachment height was influenced by baseline height (P = 0.009), subretinal fluid (P = 0.008), central macular thickness (P = 0.006), and use of aflibercept (P = 0.003) at 3 months and by baseline height (P = 0.018), volume (P = 0.017), vertical dimension (P = 0.0004), and aflibercept (P = 0.015) at 1 year. Pigment epithelial detachment reflectivity increased from 43.59 to 55.86 (3 months) and 57.35 (1 year) (P detachments respond better in the context of more active disease. More hyporeflective PED content may predispose to better treatment response, especially with aflibercept.

  12. Changes in aqueous concentrations of various cytokines after intravitreal bevacizumab and subtenon triamcinolone injection for diabetic macular edema.

    Science.gov (United States)

    Yu, Seung-Young; Nam, Dong Heun; Lee, Dae Yeong

    2018-01-01

    The purpose of this study was to compare the changes in the aqueous cytokine levels after intravitreal bevacizumab with those after combined intravitreal bevacizumab and subtenon triamcinolone injection in diabetic macular edema (DME). This study examined 24 eyes of 23 patients with DME. Each patient with DME received randomly either an intravitreal injection of bevacizumab (IVBe) or IVBe with a subtenon triamcinolone injection (IVBe + STTA). Best corrected visual acuity and foveal thickness were evaluated and aqueous samples were obtained before and 4 weeks after the injection. The aqueous concentrations of interleukin (IL)-6, IL-8, interferon-induced protein (IP)-10, monocyte chemotactic protein (MCP)-1, platelet-derived growth factor (PDGF)-AA, and vascular endothelial growth factor (VEGF) were measured using a multiplex bead assay. After the injection, the foveal thickness decreased more in the IVBe + STTA group than in the IVBe group (P = 0.042). The MCP-1, PDGF-AA, and VEGF levels decreased significantly in the IVBe + STTA group (p = 0.013, p = 0.004 and p = 0.018 respectively), but only the VEGF level decreased in the IVBe group (p = 0.001). IL-8 was significantly increased in the IVBe + STTA group (p = 0.003) but the changes in the VEGF levels were smaller than in the IVBe group (p = 0.025). Intravitreal bevacizumab and subtenon triamcinolone injection reduces the VEGF, MCP-1 and PDGF-AA levels and increases the IL-8 level in the plural cytokine profiles of patients with DME, which might explain the limited therapeutic effect of combination therapy.

  13. Fulminant toxoplasmic retinochoroiditis following intravitreal triamcinolone administration

    Directory of Open Access Journals (Sweden)

    Ryan Rush

    2012-01-01

    Full Text Available We report two cases of fulminant toxoplasmic retinochoroiditis following intravitreal triamcinolone acetonide (IVTA administration. Case 1: A 42-year-old female received IVTA for presumed non-infectious panuveitis. Within 2 months, she developed diffuse macular retinochoroiditis with optic disc edema. Upon starting anti-toxoplasmic therapy (ATT, her intraocular inflammation resolved with catastrophic damage to the disc and macula. Case 2: A 30-year-old male received IVTA for presumed reactivation of previously scarred toxoplasmic retinochoroiditis. Despite simultaneous ATT, within 6 weeks, he developed extensive, multifocal macular retinochoroiditis. He continued to require ATT for 18 months and later underwent vitrectomy with silicone oil placement for severe epiretinal proliferation. Aqueous tap polymerase chain reactions were found positive for Toxoplasma gondii in both cases. In conclusion, IVTA administration can lead to fulminant toxoplasmic retinochoroiditis even when used with appropriate ATT. Extreme caution should be exercised while administering depot corticosteroids in eyes with panuveitis of unknown origin.

  14. Scleral melt following Retisert intravitreal fluocinolone implant

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    Georgalas I

    2014-11-01

    Full Text Available Ilias Georgalas,1 Chrysanthi Koutsandrea,1 Dimitrios Papaconstantinou,1 Dimitrios Mpouritis,1 Petros Petrou1,2 1Ophthalmology Department, University of Athens, Athens, Greece; 2Moorfields Eye Hospital, London, UKAbstract: Intravitreal fluocinolone acetonide implant (Retisert has a high potency, a low solubility, and a very short duration of action in the systemic circulation, enabling the steroid pellet to be small and reducing the risk of systemic side effects. Scleral melt has not been reported as a possible complication of Retisert implant. The authors describe the occurrence of scleral melt 18 months after the implantation of fluocinolone acetonide implant in a 42-year-old Caucasian woman. To the authors’ knowledge, this is the first report of this possible complication.Keywords: Retisert, scleral melt, complication, surgical management

  15. The effect of intravitreal bevacizumab and ranibizumab on cutaneous tensile strength during wound healing

    Directory of Open Access Journals (Sweden)

    Christoforidis JB

    2013-01-01

    Full Text Available John B Christoforidis,1 Jillian Wang,2 Angela Jiang,2 James Willard,5 Cedric Pratt,2 Mahmoud Abdel-Rasoul,3 Sashwati Roy,4 Heather Powell51Department of Ophthalmology and Vision Science, College of Medicine, The University of Arizona, Tucson, AZ, USA; 2Department of Ophthalmology, College of Medicine, The Ohio State University, Columbus, OH, USA; 3Center for Biostatistics, The Ohio State University, Columbus, OH, USA; 4Center Surgery, The Ohio State University, Columbus, OH, USA; 5Department of Materials Science, College of Engineering, The Ohio State University, Columbus, OH, USAPurpose: To investigate the effect of intravitreal bevacizumab and ranibizumab on wound tension and by histopathology during cutaneous wound healing in a rabbit model and to compare this effect to placebo intravitreal saline controls 1 and 2 weeks following intravitreal injection.Methods: A total of 120 New Zealand white rabbits were randomly assigned to one of three treatment groups each consisting of 40 rabbits. Each group received intravitreal injections of bevacizumab, ranibizumab, or normal saline. Immediately afterwards, each rabbit underwent four 6 mm full-thickness dermatologic punch biopsies. Twenty rabbits from each agent group underwent wound harvesting on day 7 or day 14. The skin samples were stained for CD34 for vascular endothelial cells on day 7, and maximal wound tensile load was measured on days 7 and 14. Quantitative assessment of mean neovascularization (MNV scores was obtained from 10 contiguous biopsy margin 400× fields of CD34-stained sections by two independent observers.Results: Wound tension reading means (N with standard error and adjusted P-values on day 7 were: saline placebos, 7.46 ± 0.87; bevacizumab, 4.50 ± 0.88 (P = 0.041; and ranibizumab, 4.67 ± 0.84 (P = 0.025. On day 14 these were: saline placebos, 7.34 ± 0.55; bevacizumab, 6.05 ± 0.54 (P = 0.18; and ranibizumab 7.99 ± 0.54 (P = 0.40. MNV scores in CD34 stained sections were

  16. Evaluation of the effectiveness and safety of glucocorticoids intravitreal implant therapy in macular edema due to retinal vein occlusion

    Science.gov (United States)

    Michalska-Małecka, Katarzyna; Gaborek, Aneta; Nowak, Mariusz; Halat, Tomasz; Pawłowska, Mariola; Śpiewak, Dorota

    2016-01-01

    The purpose of this study was to evaluate the impact of intravitreal dexamethasone implant (Ozurdex) on macular morphology and functions in eyes with macular edema (ME) secondary to retinal vein occlusion. Efficacy outcomes of the treatment were best-corrected visual acuity (BCVA) and central retinal thickness (CRT). Safety outcomes were intraocular pressure and cornea endothelial cell density. The study was conducted by the prospective analysis on 36 patients (17 women and 19 men) aged 28–77 years (the average age was 58±15 years) treated with the injection of dexamethasone implant because of the persistent ME at the Department of Ophthalmology and Ophthalmology Outpatient Clinic of the University Centre of Ophthalmology and Oncology in Katowice. The studied group included 16 patients with central retinal vein occlusion (16 eyes), and 20 patients with branch retinal vein occlusion (20 eyes). We found a significant increase of BCVA after first, second, and third month of treatment. Six months after the treatment, BCVA decreased, although not significantly compared with the value obtained in the third month. Two months after the intravitreal implantation of dexamethasone delivery system, CRT was 338±163 μm and was significantly lower compared with pretreatment value. Between third and sixth month after the treatment, we found insignificant increase of CRT compared with thickness observed in second month. Two months after the treatment, we found an increase in intraocular pressure in 36% of cases and a further decrease during the final visit 6 months after the treatment. During the treatment, there were no significant differences in endothelial cell density in branch retinal vein occlusion and central retinal vein occlusion. We found the intravitreal dexamethasone implant to be safe, well tolerated, and likely to lead to fast morphological and functional improvement of the macula and visual rehabilitation in patients with ME due to retinal vein occlusion. PMID

  17. [The results of intravitreal bevacizumab in high myopic subretinal neovascularisation].

    Science.gov (United States)

    Branisteanu, D; Moraru, Andreea

    2013-01-01

    To asses the anatomical and functional results after intravitreal bevacizumab administration in choroidal neovascularization secondary to pathologic myopia; To asses the safety and results stability; Prospective, interventional case study of 18 eyes with choroidal neovascularization secondary to pathologic myopia treated with 1.25 mg. intravitreal bevacizumab (AVASTIN). Intravitreal injection was repeated, if needed, at 4-6 weeks until leakage stopped. In all cases fluorescein angiograms and Spectral 3D OCTs were performed. Visual acuity was measured with ETDRS optotype. Cases were followed-up at least 6 months. Statistical analysis was performed using ANOVA and Wilcoxon tests. Mean age of patients in the study was 43.86%--6.32 years (ranging 24-62 years). The mean number of intravitreal injections was 2.62%--0.53 (ranging between 1 - 4 injections). Mean visual acuity improved in all cases. An increase of more than 15 letters was noted in 44.44.% of the cases. OCT confirmed a reduced depth of lesion and also a reduced lesion volume after treatment. No major local or systemic side-effects were noted. At 6 months follow-up the choroidal neovascularization reappeared in 5 cases (27.77%) requiring additional treatment. These results confirm the efficacy and safety of intravitreal bevacizumab in controlling the choroidal neovascularization secondary to pathologic myopia. More than 40% of the cases regained at least 3 lines in ETDRS chart but a recurrence was noted in 27.77% of the cases at 6 months.

  18. Evaluation of the effectiveness and safety of glucocorticoids intravitreal implant therapy in macular edema due to retinal vein occlusion

    Directory of Open Access Journals (Sweden)

    Michalska-Małecka K

    2016-05-01

    Full Text Available Katarzyna Michalska-Małecka,1,2 Aneta Gaborek,2 Mariusz Nowak,3 Tomasz Halat,4 Mariola Pawłowska,2 Dorota Śpiewak2 1Department of Ophthalmology, School of Medicine in Katowice, Medical University of Silesia, Katowice, 2University Center of Ophthalmology and Oncology, Independent Public Clinical Hospital, Medical University of Silesia, Katowice, 3Pathophysiology Division, Department of Pathophysiology and Endocrinology, Medical University of Silesia, School of Medicine with Division of Density, Zabrze, 4Education and Medical Simulation Center, Medical University of Silesia, Katowice, Poland Abstract: The purpose of this study was to evaluate the impact of intravitreal dexamethasone implant (Ozurdex on macular morphology and functions in eyes with macular edema (ME secondary to retinal vein occlusion. Efficacy outcomes of the treatment were best-corrected visual acuity (BCVA and central retinal thickness (CRT. Safety outcomes were intraocular pressure and cornea endothelial cell density. The study was conducted by the prospective analysis on 36 patients (17 women and 19 men aged 28–77 years (the average age was 58±15 years treated with the injection of dexamethasone implant because of the persistent ME at the Department of Ophthalmology and Ophthalmology Outpatient Clinic of the University Centre of Ophthalmology and Oncology in Katowice. The studied group included 16 patients with central retinal vein occlusion (16 eyes, and 20 patients with branch retinal vein occlusion (20 eyes. We found a significant increase of BCVA after first, second, and third month of treatment. Six months after the treatment, BCVA decreased, although not significantly compared with the value obtained in the third month. Two months after the intravitreal implantation of dexamethasone delivery system, CRT was 338±163 µm and was significantly lower compared with pretreatment value. Between third and sixth month after the treatment, we found insignificant increase of

  19. Intravitreal injection of perfluoropropane for the treatment of vitreomacular traction

    Directory of Open Access Journals (Sweden)

    Xiao-Ping Wan

    2013-07-01

    Full Text Available AIM: To study the efficacy of a single intravitreal injection of perfluoropropane(C3F8in releasing vitreomacular traction. METHODS: Twelve eyes of 12 consecutive patients with vitreomacular traction received a single intravitreal injection of 0.3mL 100%(C3F8were retrospectively analyzed. The best corrected vision acuity and the neural epithelium thickness of central macular were observed. RESULTS: One month following treatment, vitreomacular traction was released in 5 eyes(42%, mean final visual acuity(VAimproved 0.04 and mean central foveal thickness decreased by 69μm. The vision acuity before and after treatment were 0.20±0.07, 0.25±0.04 respectively.CONCLUSION: Intravitreal C3F8 injection could offer a minimally invasive alternative to pars plana vitrectomy in patients with vitreomacular traction.

  20. Acute anterior uveitis following intravitreal bevacizumab but not subsequent ranibizumab

    Directory of Open Access Journals (Sweden)

    Antonopoulos C

    2011-11-01

    Full Text Available Christina Antonopoulos1, Maxwell Stem2, Grant M Comer21Department of Ophthalmology, Boston University, Boston, MA, USA; 2WK Kellogg Eye Center, Department of Ophthalmology, University of Michigan, Ann Arbor, MI, USAPurpose: Previous reports have identified noninfectious uveitis as a potential sequela following both intravitreal bevacizumab and ranibizumab injections. We present two unique cases of acute anterior uveitis following intravitreal bevacizumab that did not occur with subsequent ranibizumab injections.Methods: Case report.Conclusion: These cases may reflect differences in the etiology of anterior uveitis following intravitreal bevacizumab and ranibizumab. Given these differences, it may be reasonable to offer ranibizumab to patients who have experienced presumed bevacizumab-induced anterior uveitis.Keywords: adverse effect, age-related macular degeneration, anterior uveitis, bevacizumab, ranibizumab, uveitis

  1. Acute sterile endophthalmitis following intravitreal bevacizumab: case series

    Science.gov (United States)

    Orozco-Hernández, Axel; Ortega-Larrocea, Ximena; Sánchez-Bermúdez, Gustavo; García-Aguirre, Gerardo; Cantón, Virgilio Morales; Velez-Montoya, Raul

    2014-01-01

    Background Since the ophthalmological community adopted the use of intravitreal bevacizumab as an accepted off-label treatment for neovascular diseases, the amount of knowledge regarding its effects and properties has been increasing continually. In the last few years, there have been an increasing number of reports about sterile intraocular inflammation and intraocular pressure elevations after intravitreal bevacizumab. In the following case series, we describe the clinical presentation and outcomes of ten consecutive cases of patients developing mild-to-severe sterile intraocular inflammation after intravitreal bevacizumab and their management. Methods This report presents a retrospective case series. We reviewed the medical records of ten consecutive patients from a group of 46, in whom repackaged bevacizumab in individual aliquots from two vials from the same batch were used. All surgical procedures were performed using standard sterile techniques in the operating room. At each follow-up visit, patients underwent a complete ophthalmological examination including visual acuity assessment, intraocular pressure, biomicroscopy, and posterior fundus examination. Results Ten patients presented sterile endophthalmitis with an onset time of 3.5±1.95 days. The clinical characteristics were mild pain, slight visual loss, conjunctival hyperemia, and various degrees of intraocular inflammation with microhypopyon. All cultures were negative. All patients were managed with topical steroids and antibiotics, except two, in whom, due to severe vitreous cells, intravitreal antibiotics were used. Three patients showed a transient elevation of intraocular pressure. Only 50% of the patients regained a visual acuity equal or better to the baseline visual acuity on file. Conclusion The increasing number of intravitreal injections of bevacizumab applied every day, due to its widespread acceptance, might be one reason why the number of cases of sterile endophthalmitis is rising. Fast

  2. Endothelial dysfunction

    OpenAIRE

    Yaylalı, Yalın Tolga; Küçükaslan, Mete

    2011-01-01

    Endothelium is a multi-functional cluster of cells within the vascular system consisting of a single layer ofsquamous epithelium. Physiologically, endothelium performs various arrangement and protection functions.However, when these functions are disturbed toward derangement, endothelium also mediates pathologicalfunctions with negative effects on the body. Endothelial dysfunction is mediated by several mediators (nitricoxide, endothelins, prostaglandins, angiotensin 2, etc). Endothelial dysf...

  3. Rothia dentocariosa endophthalmitis following intravitreal injection-a case report.

    Science.gov (United States)

    Hayes, R A; Bennett, H Y; O'Hagan, S

    2017-12-16

    This report describes the first recognised case of Rothia dentocariosa endophthalmitis following intravitreal injection. A 57-year-old indigenous Australian diabetic female developed pain, redness and decreased vision 3 days after intravitreal aflibercept injection to the right eye-administered for diabetic vitreous haemorrhage with suspected macular oedema and proliferative diabetic retinopathy. Examination revealed best corrected visual acuity (BCVA) of hand movements, ocular hypertension and marked anterior chamber inflammation. The left eye was unaffected but had a BCVA of 6/24 due to pre-existing diabetic retinopathy. Vitreous culture isolated Rothia dentocariosa as the organism responsible for the endophthalmitis. The following treatment with intraocular cephazolin, vancomycin and ceftazidime, topical ciprofloxacin and gentamicin and systemic ciprofloxacin, the patient underwent vitrectomy. Nine weeks after onset, the patient's BCVA had improved to 6/36, and fundal examination revealed extensive retinal necrosis. Rothia dentocariosa is presented as a rare cause of endophthalmitis following intravitreal injection and reports the appearance of 'pink hypopyon' previously observed with other organisms. Its identification also demonstrates the risk of oral bacterial contamination during intraocular injections. Vigilance with strategies to minimise bacterial contamination in the peri-injection period are important. Further research to identify additional techniques to prevent contamination with oral bacteria would be beneficial, including whether a role exists for patients wearing surgical masks during intravitreal injections.

  4. Intravitreal Triamcinolone in Posterior Segment Diseases – Method ...

    African Journals Online (AJOL)

    DR OLULEYE

    Intravitreal Triamcinolone in Posterior Segment Diseases – Method of administration. TS Oluleye, O Ajayi. 1. 2. Retina Unit, Department of Ophthalmology, University College Hospital, Ibadan. 1. Department of Ophthalmology, Obafemi Awolowo University Teaching Hospital, Ile-Ife. 2. Triamcinolone is an intermediate-acting ...

  5. Acute sterile endophthalmitis following intravitreal bevacizumab: case series

    Directory of Open Access Journals (Sweden)

    Orozco-Hernández A

    2014-09-01

    Full Text Available Axel Orozco-Hernández,1 Ximena Ortega-Larrocea,1 Gustavo Sánchez-Bermúdez,1 Gerardo García-Aguirre,1 Virgilio Morales Cantón,1 Raul Velez-Montoya2 1Retina Department, Asociación para Evitar la Ceguera en México IAP, Mexico City, Mexico; 2Department of Ophthalmology, University of Colorado School of Medicine, Rocky Mountain Lions Eye Institute, Aurora, CO, USA Background: Since the ophthalmological community adopted the use of intravitreal bevacizumab as an accepted off-label treatment for neovascular diseases, the amount of knowledge regarding its effects and properties has been increasing continually. In the last few years, there have been an increasing number of reports about sterile intraocular inflammation and intraocular pressure elevations after intravitreal bevacizumab. In the following case series, we describe the clinical presentation and outcomes of ten consecutive cases of patients developing mild-to-severe sterile intraocular inflammation after intravitreal bevacizumab and their management. Methods: This report presents a retrospective case series. We reviewed the medical records of ten consecutive patients from a group of 46, in whom repackaged bevacizumab in individual aliquots from two vials from the same batch were used. All surgical procedures were performed using standard sterile techniques in the operating room. At each follow-up visit, patients underwent a complete ophthalmological examination including visual acuity assessment, intraocular pressure, biomicroscopy, and posterior fundus examination. Results: Ten patients presented sterile endophthalmitis with an onset time of 3.5±1.95 days. The clinical characteristics were mild pain, slight visual loss, conjunctival hyperemia, and various degrees of intraocular inflammation with microhypopyon. All cultures were negative. All patients were managed with topical steroids and antibiotics, except two, in whom, due to severe vitreous cells, intravitreal antibiotics were

  6. Ranibizumab-induced retinal reperfusion and regression of neovascularization in diabetic retinopathy: An angiographic illustration.

    Science.gov (United States)

    Chandra, Shruti; Sheth, Jay; Anantharaman, Giridhar; Gopalakrishnan, Mahesh

    2018-03-01

    To report regression of neovascularization and reperfusion of ischemic areas of the retina on Wide-field Digital Fluorescein Angiography following anti-vascular endothelial growth factor injections in a patient with active Proliferative Diabetic Retinopathy. Case report of sixty-one-year-old male patient with proliferative diabetic retinopathy and diabetic macular edema documented on wide field digital fluorescein angiography. The patient was treated with three intravitreal injections of ranibizumab given at monthly intervals. Repeat angiography after third intravitreal injection revealed complete regression of new vessels. Moreover, there was evident improvement in perfusion in the previously noted ischemic areas of the retina. Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections are a valuable treatment option for reversing neovascularization in eyes with proliferative diabetic retinopathy with fewer side effects when compared to standard pan-retinal photocoagulation. Additionally, we also illustrate restoration of retinal perfusion post anti-VEGF therapy indicative of pre-existingsalvageableischemic retina tissue.

  7. Effects of intravitreal injection of netrin-1 in retinal neovascularization of streptozotocin-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Yu Y

    2015-12-01

    Full Text Available Yao Yu,1,2,* Jing Zou,3,* Yun Han,4 Luowa Quyang,4 Hui He,4 Peihong Hu,2 Yi Shao,2 Ping Tu11Nanchang Key Laboratory of Diabetes, Department of Endocrinology and Metabolism, The Third Hospital of Nanchang, Jiangxi, People’s Republic of China; 2Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Province Clinical Ophthalmology Institute, Jiangxi, People’s Republic of China; 3Department of Ophthalmology, Xiangya Hospital, Central South University, Hunan, People’s Republic of China; 4Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Eye Institute of Xiamen University, Fujian, People’s Republic of China*These authors have contributed equally to this workBackground: In a previous study, we confirmed that netrin-1 acts as an antiangiogenic factor by inhibiting alkali burn-induced corneal neovascularization in rats. Here, we continue working on the role of netrin-1 in retinal neovascularization.Methods: Using an in vitro angiogenesis assay, we detected the effects of netrin-1 on human umbilical vein endothelial cell tube formation, viability and proliferation, migration, and invasion at concentrations of 0.1 µg/mL or 5 µg/mL. We intravitreally injected 0.1 µg/mL or 5 µg/mL netrin-1 into streptozotocin-induced rats to assess retinal neovascularization using retinal electrophysiology and electroretinography, enzyme-linked immunosorbent assay, fundus fluoresce in angiography, measurement of inner blood retinal barrier, retinal hematoxylin-eosin staining, and retinal flat-mount fluorescence assays.Results: Human umbilical vein endothelial cell tube formation, viability and proliferation, migration, and invasion were upregulated by netrin-1 at a concentration of 0.1 µg/mL (P<0.05, while 5 µg/mL netrin-1 had an opposite effect (P<0.05 in our in vitro angiogenesis assay. Retinal electrophysiology testing revealed that intravitreal injection of netrin-1 affected the amplitude of a- and b

  8. Dexamethasone Intravitreal Implant for Diabetic Macular Edema During Pregnancy

    DEFF Research Database (Denmark)

    Concillado, Michael; Lund-Andersen, Henrik; Mathiesen, Elisabeth R

    2016-01-01

    PURPOSE: To describe the management of diabetic macular edema during pregnancy with the use of a dexamethasone slow-release intravitreal implant. DESIGN: Retrospective, observational, consecutive case series. METHODS: The study included 5 pregnant women who presented with diabetic macular edema...... during pregnancy in the period from 2011 to 2014. Review of charts and photographs comprised best-corrected visual acuity (BCVA), foveal center field thickness assessed by optical coherence tomography, blood pressure, glycated hemoglobin, medications, and changes in such parameters after implant...... injection. RESULTS: Diabetic macular edema involving the foveal center was observed between gestational weeks 9 and 23 in 10 eyes of 5 patients. Dexamethasone intravitreal implant injection was given 10 times in 9 eyes with a mean preinjection center field retinal thickness of 535 μm (range, 239-727 μm...

  9. Repeat Intravitreal Dexamethasone Implant for Refractory Cystoid Macular Edema in Syphilitic Uveitis

    Directory of Open Access Journals (Sweden)

    Cassandra C. Lautredou

    2018-01-01

    Full Text Available Purpose. To report the successful utilization of adjunctive repeat intravitreal corticosteroid therapy for the treatment of cystoid macular edema in syphilis-related uveitis. Methods/Patients. An HIV-positive patient with treated ocular syphilis who developed refractory cystoid macular edema (CME was treated with repeat intravitreal corticosteroid therapy including dexamethasone intravitreal implants. Results. Treatment led to the resolution of CME and improvement in visual acuity. Conclusions. Intravitreal corticosteroid therapy may be a viable adjunctive treatment for refractory CME in patients with treated syphilitic uveitis. Corticosteroid-induced exacerbation of infection is unlikely in patients with an adequate serologic treatment response.

  10. Safety of intravitreal quinupristin/dalfopristin in an animal model

    Directory of Open Access Journals (Sweden)

    Veronica E. Giordano

    2016-03-01

    Full Text Available AIM: To determine whether different intravitreal doses of quinupristin/dalfopristin lead to electroretinographic or histological changes in the rabbit retina over one month period after injection. METHODS: Eighteen New Zealand white rabbits were divided into three treatment groups (groups 1 to 3 and different intravitreal doses of quinupristin/dalfopristin were tested in each group. The right eye was injected with the drug and the left eye received intravitreal injection of 5% dextrose water and served as control eye. The doses delivered to each group were 0.1 mg/0.1 mL, 1 mg/0.1 mL and 10 mg/0.1 mL. Simultaneous, bilateral, dark-adapted electroretinography and clinical images of both eyes were obtained in all groups before injection (baseline and after 7, 14, 21 and 28d, followed by enucleation for histological examination. RESULTS: Subjects in the group 1 showed no signs of toxicity in the electroretinogram when compared with groups 2 and 3 (Kruskall-Wallis test, P=0.000. By day 7, no electrical response to light stimuli was recorded in the treated eyes in groups 2 and 3, consistent with severe damage due to retinal toxicity. Light microscopy revealed no significant histopathological changes in the group 1, while rabbits in groups 2 and 3 had signs of granulomatous inflammation in most cases. CONCLUSION: Intravitreal 0.1 mg/0.1 mL doses of quinupristin/dalfopristin do not lead to electroretinographic or histological signs of retinal toxicity compared with 1 mg/0.1 mL and 10 mg/0.1 mL in this rabbit model.

  11. Isolated sixth nerve palsy after intravitreal ranibizumab injection.

    Science.gov (United States)

    Caglar, Cagatay; Kocamis, Sücattin Ilker; Durmus, Mustafa

    2016-09-01

    After intravitreal ranibizumab injection for diabetic macular edema (DME) in a 55-year-old man, the patient was admitted to our ophthalmology clinic with the complaint of diplopia. Given the results of the patient's history, physical exam, and negative magnetic resonance imaging (MRI), we believed that the patient had a sixth nerve palsy related to ranibizumab injection. To the best of our knowledge, this is the first case with isolated abducens palsy after ranibizumab injection.

  12. Intravitreal bevacizumab (Avastin in choroidal neovascular membrane in angioid streaks

    Directory of Open Access Journals (Sweden)

    Sachdev Nishant

    2007-01-01

    Full Text Available Angioid streaks are crack-like dehiscences in the Bruch′s membrane, which predispose to the development of a choroidal neovascular membrane (CNVM that carries a poor visual outcome. We report successful treatment in a 25-year-old woman with bilateral angioid streaks and subfoveal CNVM in the left eye who received two doses of intravitreal bevacizumab (1.25 mg injections six weeks apart, resulting in rapid regression of the CNVM.

  13. Intravitreal ranibizumab injections in patients with retinopathy of prematurity (ROP

    Directory of Open Access Journals (Sweden)

    Zuluaga Gómez, Liliana María

    2018-01-01

    Full Text Available Purpose: To describe ocular outcomes after intravitreal ranibizumab injections in patients with retinopathy of prematurity (ROP, who had transpupillary laser thermotherapy without regression of the disease. Methods: Historical cohort in Clínica Universitaria Bolivariana (CUB during 2008-2015. Evaluation of patients with aggressive posterior ROP, threshold disease, who received intravitreal ranibizumab secondary to treatment with transpupillary thermotherapy. The primary outcome was treatment success defined as the resolution of neovascularization (NV and no recurrence. The secondary endpoints were visual acuity and ocular and systemic complications. Results: Eight eyes of four patients were included in the study. Six eyes had resolution of retinopathy, Incidence density 48 x 100 person years, 95 % CI = 17.6 - 100 with a median follow-up of 23.5 months, range 13-90 months. No ocular or systemic complications associated with the procedure was found. Conclusion: This cohort suggests that intravitreal injection of ranibizumab for ROP in refractory laser photocoagulation cases, results in apparent ocular preservation a long-term the outcome.

  14. Intravitreal Bevacizumab (Avastin) for Diabetic Retinopathy: The 2010 GLADAOF Lecture

    Science.gov (United States)

    Arevalo, J. Fernando; Sanchez, Juan G.; Lasave, Andres F.; Wu, Lihteh; Maia, Mauricio; Bonafonte, Sergio; Brito, Miguel; Alezzandrini, Arturo A.; Restrepo, Natalia; Berrocal, Maria H.; Saravia, Mario; Farah, Michel Eid; Fromow-Guerra, Jans; Morales-Canton, Virgilio

    2011-01-01

    This paper demonstrates multiple benefits of intravitreal bevacizumab (IVB) on diabetic retinopathy (DR) including diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) at 24 months of followup. This is a retrospective multicenter interventional comparative case series of intravitreal injections of 1.25 or 2.5 mg of bevacizumab for DME, PDR without tractional retinal detachment (TRD), and patients who experienced the development or progression of TRD after an intravitreal injection of 1.25 or 2.5 mg of bevacizumab before vitrectomy for the management of PDR. The results indicate that IVB injections may have a beneficial effect on macular thickness and visual acuity (VA) in diffuse DME. Therefore, in the future this new therapy could complement focal/grid laser photocoagulation in DME. In PDR, this new option could be an adjuvant agent to panretina photocoagulation so that more selective therapy may be applied. Finally, TRD in PDR may occur or progress after IVB used as an adjuvant to vitrectomy. Surgery should be performed 4 days after IVB. Most patients had poorly controlled diabetes mellitus associated with elevated HbA1c, insulin administration, PDR refractory to panretinal photocoagulation, and longer time between IVB and vitrectomy. PMID:21584260

  15. Experiment study of retinal ultrastructure after intravitreal FK506.

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    Li, Shuangnong; Tang, Shibo; Li, Wei; Li, Dongping

    2004-03-01

    To investigate the retinal toxicity of FK506 by intravitreal administration. Twenty-two eyes of 14 New Zealand rabbits were investigated. FK506 at concentrations of 5,25 and 50 micrograms/eye was injected into the vitreous cavities respectively. The control eyes were received mixed solution of balanced salt and ethanol. All eyes were examined by tonometry, slit lamp and indirect ophthalmoscopy preoperatively and postoperatively at the 1st, 3rd, 7th, and 14th day respectively. In the final examination, all eyes were enucleated and processed for light and electron microscopy. No evidence of toxic reaction was seen in the eyes received 25 micrograms FK506 or less of FK506. Several eyes received 50 micrograms FK506 and control eyes developed conjunctival congestion and slightly bloody exudates in anterior chamber which may be related to irritation of ethanol. Two of five eyes received 50 micrograms developed transient vitreous opacities. Electron microscopically, the mitochondria of the photoreceptor cells were swelled in the eyes treated with 50 micrograms FK 506. It is safety with intravitreal FK506. There are no irritation and toxicity to the rabbits eyes with the intravitreal doses of 25 micrograms FK506 or less. The doses of 50 micrograms FK506 are proved to be toxic to the retina.

  16. Selective Gene Transfer to the Retina Using Intravitreal Ultrasound Irradiation

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    Shozo Sonoda

    2012-01-01

    Full Text Available This paper aims to evaluate the efficacy of intravitreal ultrasound (US irradiation for green fluorescent protein (GFP plasmid transfer into the rabbit retina using a miniature US transducer. Intravitreal US irradiation was performed by a slight modification of the transconjunctival sutureless vitrectomy system utilizing a small probe. After vitrectomy, the US probe was inserted through a scleral incision. A mixture of GFP plasmid (50 μL and bubble liposomes (BLs; 50 μL was injected into the vitreous cavity, and US was generated to the retina using a SonoPore 4000. The control group was not exposed to US. After 72 h, the gene-transfer efficiency was quantified by counting the number of GFP-positive cells. The retinas that received plasmid, BL, and US showed a significant increase in the number (average ± SEM of GFP-positive cells (32±4.9; n=7; P<0.01 . No GFP-positive cells were observed in the control eyes (n=7. Intravitreal retinal US irradiation can transfer the GFP plasmid into the retina without causing any apparent damage. This procedure could be used to transfer genes and drugs directly to the retina and therefore has potential therapeutic value.

  17. Effect of intravitreal injection of bevacizumab-chitosan nanoparticles on retina of diabetic rats

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    Yan Lu

    2014-02-01

    Full Text Available AIM:To investigate the effects of intravitreal injection of bevacizumab-chitosan nanoparticles on pathological morphology of retina and the expression of vascular endothelial growth factor (VEGF protein and VEGF mRNA in the retina of diabetic rats.METHODS: Seventy-two 3-month aged diabetic rats were randomly divided into 3 groups, each containing 24 animals and 48 eyes. Both eyes of the rats in group A were injected into the vitreous at the pars plana with 3μL of physiological saline, while in groups B and C were injected with 3μL (75μg of bevacizumab and 3μL of bevacizumab-chitosan nanoparticles (containing 75μg of bevacizumab, respectively. Immunohistochemistry was used to assess retinal angiogenesis, real-time PCR assay was used to analyse the expression of VEGF mRNA, and light microscopy was used to evaluate the morphology of retinal capillaries.RESULTS:Real-time PCR assay revealed that the VEGF mRNA expression in the retina before injection was similar to 1 week after injection in group A (P>0.05, while theVEGF mRNA expression before injection significantly differed from those 4 and 8 weeks after injection (P<0.05. Retinal expression of VEGF protein and VEGF mRNA was inhibited 1 week and 4 weeks after injection (P<0.05 in group B, and the expression of VEGF protein and VEGF mRNA was obviously inhibited until 8 weeks after injection (P<0.05 in group C. Using multiple comparisons among group A, group B, and group C, the VEGF expression before injection was higher than at 1, 4 and 8 weeks after injection (P<0.05. The amount of VEGF expression was higher 8 weeks after injection than 1 week or 4 weeks after injection, and also higher 1 week after injection compared with 4 weeks after injection (P<0.05. No toxic effect on SD rats was observed with bevacizumab-chitosan nanoparticles injection alone.CONCLUSION: The results offer a new approach for inhibiting angiogenesis of diabetic retinopathy and indicate that the intravitreal injection of

  18. The effect of intravitreal anti-VEGF agents on peripheral wound healing in a rabbit model

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    Christoforidis J

    2012-01-01

    Full Text Available John Christoforidis1, Robert Ricketts1, Cedric Pratt1, Jordan Pierce1, Scott Bean1, Michael Wells1, Xiaoli Zhang2, Krista La Perle31College of Medicine, 2Center for Biostatistics, 3College of Veterinary Medicine, The Ohio State University, Columbus, OH, USAPurpose: To investigate the effect of intravitreal pegaptanib, bevacizumab, and ranibizumab on blood-vessel formation during cutaneous wound healing in a rabbit model and to compare this effect to placebo controls.Methods: Forty New Zealand albino rabbits underwent full thickness cutaneous wounds using 6-mm dermatologic punch biopsies. The rabbits were assigned to four groups of ten, each receiving intravitreal injections of pegaptanib, bevacizumab, ranibizumab, or no injection (untreated controls. Five rabbits from each group underwent wound harvesting on day 7 and five from each group on day 14. The skin samples were stained with hematoxylin and eosin (HE, Masson's trichrome (MT, and CD34 for vascular endothelial cells. Semiquantitative evaluation of HE- and MT-stained slides was performed by one pathologist. Quantitative assessment of mean neovascularization (MNV scores was obtained from five contiguous biopsy margin 400× fields of CD34-stained sections by four independent observers.Results: Week 1 MNV scores in CD-34 stained sections were: untreated controls: 11.51 ± 4.36; bevacizumab: 7.41 ± 2.82 (P = 0.013; ranibizumab: 8.71 ± 4.08 (P = 0.071; and pegaptanib: 10.15 ± 5.59 (P = 0.378. Week 2 MNV data were: untreated controls: 6.14 ± 2.25; bevacizumab: 7.25 ± 2.75 (P = 0.471; ranibizumab: 4.53 ± 3.12 (P = 0.297; and, pegaptanib: 6.35 ± 3.09 (P = 0.892. Interobserver variability using intraclass correlation coefficient was 0.961.Conclusions: At week 1, all three anti-VEGF agents had suppressed MNV scores compared to controls. Although not statistically significant, there was an inhibitory trend, particularly with bevacizumab and ranibizumab. These effects were diminished at 2 weeks

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

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

    2016-01-01

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

  20. Reduced occurrence of programmed cell death and gliosis in the retinas of juvenile rabbits after shortterm treatment with intravitreous bevacizumab

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    Maria Alice Fusco

    2012-01-01

    Full Text Available OBJECTIVE: Bevacizumab has been widely used as a vascular endothelial growth factor antagonist in the treatment of retinal vasoproliferative disorders in adults and, more recently, in infants with retinopathy of prematurity. Recently, it has been proposed that vascular endothelial growth factor acts as a protective factor for neurons and glial cells, particularly in developing nervous tissue. The purpose of this study was to investigate the effects of bevacizumab on the developing retinas of juvenile rabbits. METHODS: Juvenile rabbits received bevacizumab intravitreously in one eye; the other eye acted as an untreated control. Slit-lamp and fundoscopic examinations were performed both prior to and seven days after treatment. At the same time, retina samples were analyzed using immunohistochemistry to detect autophagy and apoptosis as well as proliferation and glial reactivity. Morphometric analyses were performed, and the data were analyzed using the Mann-Whitney U test. RESULTS: No clinical abnormalities were observed in either treated or untreated eyes. However, immunohistochemical analyses revealed a reduction in the occurrence of programmed cell death and increases in both proliferation and reactivity in the bevacizumab-treated group compared with the untreated group. CONCLUSIONS: Bevacizumab appears to alter programmed cell death patterns and promote gliosis in the developing retinas of rabbits; therefore, it should be used with caution in developing eyes

  1. Pharmacokinetics of intravitreal bevacizumab (Avastin® in rabbits

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    Sinapis C

    2011-05-01

    Full Text Available Christos I Sinapis1,*, John G Routsias2,*, Angelos I Sinapis1,*, Dimitrios I Sinapis1,*, George D Agrogiannis3, Alkistis Pantopoulou1, Stamatis E Theocharis4, Stefanos Baltatzis5, Efstratios Patsouris3, Despoina Perrea11Laboratory for Experimental Surgery and Surgical Research 'N.S.Christeas', 2Laboratory of Pathophysiology, 3Laboratory of Pathology, 4Laboratory of Forensic Medicine and Toxicology, 5Department of Ophthalmology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece *Contributed equally to the studyPurpose: To describe the pharmacokinetics of intravitreal bevacizumab (Avastin® in rabbits.Methods: The right eye of 20 rabbits was injected intravitreally with 1.25 mg/0.05 mL bevacizumab. Both eyes of four rabbits each time were enucleated at days 1, 3, 8, 15, and 29. Bevacizumab concentrations were measured in serum, aqueous humor, and vitreous.Results: Maximum vitreous (406.25 µg/mL and aqueous humor (5.83 µg/mL concentrations of bevacizumab in the right eye were measured at day 1. Serum bevacizumab concentration peaked at day 8 (0.413 µg/mL and declined to 0.032 µg/mL at 4 weeks. Half-life values in right vitreous, right aqueous humor, and serum were 6.61, 6.51, and 5.87 days, respectively. Concentration of bevacizumab in the vitreous of the noninjected eye peaked at day 8 (0.335 ng/mL and declined to 0.218 ng/mL at 4 weeks. In the aqueous humor of the noninjected eye, maximum concentration of bevacizumab was achieved at day 8 (1.6125 ng/mL and declined (to 0.11 ng/mL at 4 weeks.Conclusion: The vitreous half-life of 1.25 mg/0.05 mL intravitreal bevacizumab was 6.61 days in this rabbit model. Maximum concentrations of bevacizumab were reached at day 1 in both vitreous and aqueous humor of the right eye and at day 8 in the serum. Very low concentrations of bevacizumab were measured in the fellow noninjected eye.Keywords: bevacizumab, pharmacokinetics, rabbits, intravitreal

  2. 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

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    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

  3. Intravitreal gas injection for the treatment of diabetic macular edema

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    McHugh D

    2011-10-01

    Full Text Available Dominic McHugh, Bhaskar Gupta, Manzar Saeed King's College Hospital, Denmark Hill, London, England, UK Purpose: This study investigates the efficacy of an intravitreal gas injection in inducing a posterior vitreous detachment (PVD in patients with clinically significant diabetic macular edema refractory to laser therapy. Methods: A local ethics committee-approved technique of an intravitreal injection of pure perfluoropropane gas (C3F8 was performed for all participants. After a period of prone positioning, the patients underwent regular and detailed clinical review. Main outcome measures: The induction of a PVD, change in macular thickness, change in visual acuity. Results: A PVD was induced in all five eyes with subsequent signs of reduction in macular thickness and resolution of exudates. Mean visual improvement was 11 ETDRS (Early Treatment Diabetic Retinopathy Study letters (range 4–21. Apart from a transient vitreous hemorrhage in one eye, there were no significant treatment-related complications. Conclusion: The induction of a PVD by pneumatic retinopexy appears to have a significant influence on diabetic macular edema in eyes which have not successfully responded to macular laser therapy. A randomized clinical trial is justified on the basis of the initial promising data. Keywords: optical coherence tomography, OCT, posterior vitreous detachment, perfluoropropane

  4. Effects of intravitreal bevacizumab injection on the clinical manifestations of nonproliferative diabetic retinopathy in patients with macular edema: a systematic review

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    Touka Banaee

    2016-04-01

    Full Text Available Introduction: Bevacizumab (Avastin is considered as an effective strategy in the treatment of various ocular diseases. As a vascular endothelial growth factor (VEGF inhibitor, Avastin is used to control macular edema in patients with nonproliferative diabetic retinopathy (NPDR. Therefore, in this study, we systematically reviewed the effects of intravitreal bevacizumab injections on nonproliferative stage of diabetic retinopathy. Methods: Scopus and PubMed were systematically searched to find articles in which the effect of Avastin (bevacizumab had been evaluated in nonproliferative stage of diabetic retinopathy. Literature search was performed using “Avastin OR bevacizumab”, “nonproliferative stage” and “diabetic retinopathy” as keyterms in the title, keywords, and abstract.Result: All 47 articles were found in all databases, two additional records were found through reference list screening, and only 10 articles were relevant to the purpose of this study. According to the inclusion/exclusion criteria, 39 articles were excluded in several step processes of article selection. The results revealed that intravitreal injection of bevacizumab could be safely used to treat various ocular disease, particularly NPDR stage of diabetic retinopathy with macular edema.Discussion: Bevacizumab is considered as a novel and effective modality in the treatment of various ocular diseases such as retinal neovascularization, neovascular glaucoma, macular edema, and other ocular complications. Findings also suggested that bevacizumab is a suitable therapeutic approach in clinical use.Conclusion: According to the results of included documents, intravitreal injection of bevacizumab could be considered as a promising treatment modality in the clinical management of NPDR stage of diabetic retinopathy.

  5. Buckling surgery and supplemental intravitreal bevacizumab or photocoagulation on stage 4 retinopathy of prematurity eyes.

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    Futamura, Yukiko; Asami, Tetsu; Nonobe, Norie; Kachi, Shu; Ito, Yasuki; Sato, Yoshiaki; Hayakawa, Masahiro; Terasaki, Hiroko

    2015-11-01

    To report the results of scleral buckling (SB) with or without photocoagulation (PC) and intravitreal bevacizumab (IVB) for stage 4 retinopathy of prematurity (ROP) eyes. Forty-two eyes of 28 patients with SB and/or PC or IVB were studied. Twenty-nine eyes had stage 4A and 13 eyes had stage 4B ROP. Seventeen eyes underwent SB combined with additional intraoperative or postoperative treatments (combined group). Twenty-five eyes underwent SB without additional therapy (non-combined group). The concentrations of vascular endothelial growth factor (VEGF) in the aqueous humor determined by enzyme-linked immunosorbent assay were compared between the two groups. The initial and final reattachment rates were also compared. The gestational age and birth weight were 25.0 ± 2.0 weeks and 786 ± 222 g in the combined group, and 25.5 ± 2.1 weeks and 899 ± 315 g in the non-combined group. The postmenstrual age at the time of initial surgery was 38.0 ± 1.9 in the combined and 44.1 ± 4.0 weeks in the non-combined group (P < 0.001). The initial reattachment rate was 92% in stage 4A and 75% in stage 4B of ROP eyes in the combined group, and the rate was 93% in stage 4A and 33% in stage 4B of ROP eyes in the non-combined group. The mean VEGF concentration in aqueous humor was 1923 ± 779 pg/ml in the combined group and 985 ± 303 pg/ml in the non-combined group (P < 0.05). Our results show that the retinal reattachment rate after combined therapy was comparable to that in the non-combined group. We conclude that combined therapy may be effective even in ROP eyes with high activity.

  6. Efficacy of first Ranibizumab intravitreal injection on macular edema caused by retinal vein occlusion

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    Hong Cao

    2015-09-01

    Full Text Available AIM: To observe the efficacy of first Ranibizumab intravitreal injection on macular edema caused by retinal vein occlusion(RVO. METHODS: Thirty-nine eyes of 39 patients with macular edema due to RVO were treated in our hospital during June 2014 to December 2014. Patients received intravitreal injection of 0.05mL ranibizumab. Best corrected visual acuity(BCVA, central macular thickness(CMTand cube average thickness(CATwere analyzed at 2d, 2, and 4wk after injection, respectively. RESULTS: The baseline BCVA(LogMAR, CMT and CAT were 0.82±0. 45, 541±136μm and 382±107μm before treatment. After first ranibizumab intravitreal injection, mean BVCA significantly improved at 2d(0. 56±0.35,PPPPPPPPPCONCLUSION: First intravitreal injection of ranibizumab can improve macular edema caused by RVO in short-term, but long-term effects is needed further observed.

  7. Statins in rhegmatogenous retinal detachment are associated with low intravitreal angiopoietin-2, VEGF and MMP-2 levels, and improved visual acuity gain in vitrectomized patients.

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    Tuuminen, Raimo; Haukka, Jari; Loukovaara, Sirpa

    2015-10-01

    In rhegmatogenous retinal detachment (RRD), intravitreal growth factors and cytokines may compromise post-vitrectomy outcomes. Here, we analysed perioperative intravitreal protein levels of potent vasoactive, pro-inflammatory, and extracellular matrix-remodelling factors in RRD eyes of patients treated with statins and evaluated post-vitrectomy outcome in the same study eyes. Institutional, retrospective, observational study of 14 patients operated on for RRD while on statins compared to patients without statin medication (n = 82). Vitreous samples were subjected to protein measurements of angiopoietin (ANGPT)-1 and -2, transforming growth factor-β1, and vascular endothelial growth factor (VEGF) by ELISA, and of matrix metalloproteinase (MMP)-2 and -9 by gelatin zymography. A 1-month best-corrected visual acuity (BCVA) gain was modelled by Student's T-test and multivariate linear regression with concomitant perioperative medication. Cumulative 12-month revitrectomy frequency was modelled by Kaplan-Meier log-rank test. Intravitreal levels of ANGPT-2 (49.2 ± 33.1 vs. 112.8 ± 134.1 pg/ml, mean ± SD, p < 0.001), VEGF (2.3 ± 2.4 vs. 17.7 ± 57.8 pg/ml, p = 0.021), and MMP-2 (1107.1 ± 884.6 vs 1976.4 ± 970.1 AU/ml, p = 0.005) in RRD eyes of patients treated with statins were lower than in non-statin-treated controls. Patients on statins had better 1-month BCVA improvement than did those not on statins (p = 0.022), with no difference in 1-year re-vitrectomy rates. Intravitreal levels of ANGPT-2, VEGF, factors involved in vascular permeability and inflammation, and activity of MMP-2, the factor connected with breakdown of basement membrane and fibroproliferation, were lower in RRD eyes of patients with statin treatment. At 1-month, postoperative BCVA gain was improved in statin-treated RRD eyes, suggesting that statin administration may be effective in preventing inflammation-related PVR formation.

  8. Intravitreal triamcinolone for intraocular inflammation and associated macular edema

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    Steven M Couch

    2008-11-01

    Full Text Available Steven M Couch, Sophie J BakriMayo Clinic Department of Ophthalmology, Mayo Clinic, Rochester, MN, USAAbstract: Triamcinolone acetonide (TA is a corticosteroid that has many uses in the treatment of ocular diseases because of its potent anti-inflammatory and anti-permeability actions. Intraocular inflammation broadly referred to as uveitis can result from several causes, including the immune system and after ophthalmic surgery. One of the most common reasons for vision loss with uveitis is macular edema. TA has been used for many years as an intravitreal injection for the treatment of ocular diseases. Several case control studies have been reported showing the efficacy of TA in the treatment of intraocular inflammation and associated macular edema caused by Behcet’s disease, Vogt-Koyanagi-Harada syndrome, sympathetic ophthalmia and white dot syndromes. It has also been shown efficacious in cases of pars planitis and idiopathic posterior uveitis. Some authors have reported its use in postoperative cystoid macular edema. Many of the studies on the use of TA in controlling intraocular inflammation and concomitant macular edema showed its effect to be transient in many patients requiring reinjection. Complications can arise from intravitreal injection of TA including elevated intraocular pressure and cataract. Rarely, it can be associated with infectious and non-infectious endophthalmitis. TA may be useful as an adjuvant in the treatment of uveitis and its associated macular edema, especially in patients resistant or intolerant to standard treatment.Keywords: triamcinolone acetonide, Behcet’s disease, sympathetic ophthalmia, Vogt-Koyanagi-Harada syndrome, white dot syndromes, uveitis, cataract surgery, macular edema, endophthalmitis

  9. Ocular hypertension after intravitreal triamcinolone with vitrectomy and phacoemulsification

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    Parke III DW

    2012-06-01

    Full Text Available D Wilkin Parke III, Robert A Sisk, Samuel K Houston, Timothy G MurrayDepartment of Ophthalmology, Bascom Palmer Eye Institute, University of Miami, Miller School of Medicine, Miami, FL, USAObjective: To evaluate the effect of adjunctive intravitreal triamcinolone (IVTA on intraocular pressure (IOP in the setting of combined vitrectomy with phacoemulsification.Design: Retrospective case series.Participants: One hundred thirty-one consecutive eyes undergoing nonemergent vitrectomy with phacoemulsification and IVTA were reviewed and included in the analysis. All 131 eyes received 4 mg IVTA at the end of surgery.Methods: Pre- and postoperative IOP, use of pressure-lowering medications, and rate of glaucoma surgery were analyzed. Pre-operative risk factors were analyzed.Main outcome measures: IOP, glaucoma medications, or glaucoma surgery.Results: Secondary ocular hypertension (defined as IOP ≥25 mmHg was found in 28 eyes (21%, the majority during postoperative day 1 only. Twelve eyes (9% had an elevated IOP measurement noted at a visit after the first postoperative day. Five (4% had an IOP rise of ≥10 mmHg over baseline at any time after postoperative day 1. Six (5% required glaucoma medications. One eye required a glaucoma drainage implant for diabetic neovascular angle closure glaucoma, and one eye required enucleation for intractable neovascular glaucoma due to radiation retinopathy. Elevated postoperative IOP was statistically associated with higher baseline IOP and presence of preoperative glaucoma.Conclusions: Therapeutic intravitreal triamcinolone with combined vitrectomy and phacoemulsification causes infrequent and usually mild secondary ocular hypertension. Secondary ocular hypertension is associated with preoperative glaucoma and high IOP.Keywords: glaucoma, cataract, inflammation

  10. Efficacy of reduced dose of intravitreal triamcinolone acetonide in a case of active serpiginous choroiditis

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    Avirupa Ghose

    2016-01-01

    Full Text Available Active serpiginous choroiditis (SC is a vision-threatening condition which requires intensive treatment using corticosteroids and/or immunosuppressives, especially if the lesions are involving or encroaching on the macula. Use of oral and intravenous high-dose steroids are contraindicated in uncontrolled diabetics. Intravitreal steroid delivers a localized dose in such situations. This case report highlights the efficacy of reduced dose of intravitreal triamcinolone acetonide (2 mg in the treatment of active SC.

  11. Comparison of endophthalmitis rates following intravitreal injection of compounded bevacizumab, ranibizumab, and aflibercept.

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    Forooghian, Farzin; Albiani, David A; Kirker, Andrew W; Merkur, Andrew B

    2017-12-01

    Whereas the incidence of endophthalmitis after compounded intravitreal bevacizumab is known to be low, the rates of endophthalmitis after intravitreal injection of compounded ranibizumab and aflibercept are not known. The purpose of this study was to determine the incidence of endophthalmitis after treatment with compounded intravitreal ranibizumab and aflibercept and to compare this to the incidence with compounded intravitreal bevacizumab. Retrospective chart review. All patients with post-injection endophthalmitis who were seen over a 6.5-year period at a tertiary retina referral practice. We identified all cases of endophthalmitis by searching for patients who received intravitreal antibiotics and had antecedent intravitreal injection of bevacizumab, ranibizumab, or aflibercept. A total of 54,101 injections of bevacizumab, 5,614 injections of ranibizumab, and 3,468 injections of aflibercept were performed. The incidence of suspected endophthalmitis was 0.041% (95% CI: 0.026-0.062) for bevacizumab, 0.036% (95% CI: 0.0043-0.13) for ranibizumab, and 0.06% (95% CI: 0.007-0.2) for aflibercept. For culture-positive cases, the incidence was 0.017% (95% CI: 0.0076-0.032) for bevacizumab, 0.02% (95% CI: 0.0005-0.1) for ranibizumab, and 0.03% (95% CI: 0.0007-0.2) for aflibercept. There was no statistically significant difference in endophthalmitis rate between the 3 different compounded drugs with respect to both overall suspected endophthalmitis rate and culture-positive endophthalmitis rate (p = 0.87). Compounding of ranibizumab and aflibercept for intravitreal use appears to be safe because the endophthalmitis rate does not appear to be different from that of intravitreal bevacizumab. Copyright © 2017 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

  12. Change in macular thickness in a case of refractory diabetic macular edema with dexamethasone intravitreal implant in comparison to intravitreal bevacizumab: A case report

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    Ashish Sharma

    2012-01-01

    Full Text Available We report on the significant improvement of central macular thickness in a case of clinically significant macular edema after dexamethasone 0.7 mg sustained-release intravitreal implant (Ozurdex®; Allergan, Inc, Irvine, CA, USA. Patient presented to us with persistent clinically significant macular edema (CSME in both eyes. Right eye received dexamethasone implant and left eye received two intravitreal bevacizumab injections 1.25 mg/0.05 mL (Avastin®; Genentech Inc., South San Francisco, CA, USA with an interval of four weeks. After six weeks of follow-up, dexamethasone implant in the right eye showed normal macular thickness whereas persistent macular edema (ME was found even after second intravitreal bevacizumab injection in the left eye.

  13. Correlation of Vitreous Vascular Endothelial Growth Factor and Uric Acid Concentration Using Optical Coherence Tomography in Diabetic Macular Edema

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    Libuse Krizova

    2015-01-01

    Full Text Available Purpose. We investigated two factors linked to diabetic macular edema (DME, vitreous and serum levels of vascular endothelial growth factor (VEGF and uric acid (UA in patients with DME, and compared the results with changes in optical coherence tomography (OCT and visual acuity (VA. Methods. A prospective study of 29 eyes, 16 cystoid DME and nonproliferative diabetic retinopathy (DR and 13 nondiabetic controls. Biochemical analysis of vitreous and serum samples was performed and OCT scans were graded according to central retinal thickness (CRT, cube volume (CV, cube average thickness (CAT, and serous retinal detachment (SRD. Results. In DME group, intravitreal concentrations of VEGF (p<0.001, UA (p=0.038, and total protein (p<0.001 were significantly higher than in control group. In DME subjects, intravitreal UA correlated significantly with intravitreal VEGF (ƍ = 0.559, p=0.03 but not with total vitreous protein and serum UA. Increased intravitreal VEGF in DME group correlated with increase in CV (ƍ = 0.515/p=0.041. None of the OCT parameters correlated with the VA. Conclusions. The results suggest that the CV might be assessor of anti-VEGF therapy efficacy. Second, apart from VEGF, the role of UA in the pathogenesis and progression of DR should be considered.

  14. Comparison of dexamethasone intravitreal implant and intravitreal triamcinolone acetonide for the treatment of pseudophakic cystoid macular edema in diabetic patients

    Directory of Open Access Journals (Sweden)

    Dang Y

    2014-09-01

    Full Text Available Yalong Dang,1,* Yalin Mu,2,* Lin Li,3,* Yahui Mu,2 Shujing Liu,2 Chun Zhang,4 Yu Zhu,1 Yimin Xu4 1Department of Ophthalmology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, 2Department of Ophthalmology, Yellow River Hospital, Henan University of Science and Technology, Sanmenxia, Henan Province, 3Department of Ophthalmology, the First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan Province, 4Department of Ophthalmology, Peking University Third Hospital, Haidian District, Beijing, People's Republic of China *These authors contributed equally to this work. Background and objective: Our objective was to investigate the efficacy and safety of dexamethasone (DEX implant for the treatment of pseudophakic cystoid macular edema (PCME in diabetic patients. Study design: This was a prospective, non-randomized, interventional case series of 43 participants. Eighteen patients were enrolled in the DEX implant group and 25 were enrolled in an intravitreal triamcinolone acetonide (IVTA group. Main outcome measures: The primary efficacy measurement was the percentage of patients who gained improvements of more than ten letters in best corrected visual acuity (BCVA during 6 months of follow-up. Other efficacy measurements included change in BCVA, change in central macular thickness (CMT, and number of retreatments. The primary safety evaluation was the percentage of patients with intraocular hypertension and variation in intraocular pressure (IOP during 6 months of follow-up. Other adverse events, such as conjunctival hemorrhage, eye pain, secondary infection, endophthalmitis, noninfectious inflammation, retinal detachment, and implant migration, were also recorded during follow-up. Results: At month 1, we observed that the percentage of patients gaining improvement of more than ten letters was similar in both groups (P=0.625. As patients in the IVTA group were retreated several times, this

  15. Antivascular Endothelial Growth Factor Bevacizumab for Radiation Optic Neuropathy: Secondary to Plaque Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Finger, Paul T., E-mail: pfinger@eyecancer.com [New York Eye Cancer Center, New York, NY (United States); Chin, Kimberly J. [New York Eye Cancer Center, New York, NY (United States)

    2012-02-01

    Purpose: To evaluate the intravitreal antivascular endothelial growth factor, bevacizumab, for treatment of radiation optic neuropathy (RON). Methods and Materials: A prospective interventional clinical case series was performed of 14 patients with RON related to plaque radiotherapy for choroidal melanoma. The RON was characterized by optic disc edema, hemorrhages, microangiopathy, and neovascularization. The entry criteria included a subjective or objective loss of vision, coupled with findings of RON. The study subjects received a minimum of two initial injections of intravitreal bevacizumab (1.25 mg in 0.05 mL) every 6-8 weeks. The primary objectives included safety and tolerability. The secondary objectives included the efficacy as measured using the Early Treatment Diabetic Retinopathy Study chart for visual acuity, fundus photography, angiography, and optical coherence tomography/scanning laser ophthalmoscopy. Results: Reductions in optic disc hemorrhage and edema were noted in all patients. The visual acuity was stable or improved in 9 (64%) of the 14 patients. Of the 5 patients who had lost vision, 2 had relatively large posterior tumors, 1 had had the vision decrease because of intraocular hemorrhage, and 1 had developed optic atrophy. The fifth patient who lost vision was noncompliant. No treatment-related ocular or systemic side effects were observed. Conclusions: Intravitreal antivascular endothelial growth factor bevacizumab was tolerated and generally associated with improved vision, reduced papillary hemorrhage, and resolution of optic disc edema. Persistent optic disc neovascularization and fluorescein angiographic leakage were invariably noted. The results of the present study support additional evaluation of antivascular endothelial growth factor medications as treatment of RON.

  16. Nurse-led ranibizumab intravitreal injections in wet age-related macular degeneration: a literature review.

    Science.gov (United States)

    Gregg, Emma

    2017-04-12

    Aim The aim of this literature review was to explore the development of the role of specialist ophthalmic nurses in delivering ranibizumab intravitreal injections to patients with wet age-related macular degeneration (AMD), and to evaluate their contribution to reducing capacity pressures in medical retina services, while maintaining safe and effective standards of care. Method A systematic literature search was undertaken to identify relevant articles published between January 2000 and June 2015. A search of electronic databases was undertaken, and selected relevant journals were searched manually. A free text and subject heading search strategy was conducted, in which the abstracts of publications identified for review were assessed for relevance. Inclusion criteria were: nurses delivering ranibizumab intravitreal treatment; studies performed in the UK and other countries; and patients with AMD, diabetic macular oedema or central retinal vein occlusion receiving nurse-led ranibizumab (Lucentis) intravitreal treatment. Findings Five studies were identified from the literature search, which audited a total of 31,303 injections delivered by nurse practitioners between January 2007 and November 2013. The visual outcomes and the rate of complications from intravitreal injections delivered by trained ophthalmic nurse practitioners were comparable to intravitreal injections delivered by ophthalmologists. Four of the five studies reported increased patient satisfaction, patients consenting to nurse-delivered intravitreal injections, favourable pain experience, and absence of complaints. Conclusion Practice innovation is an example of a quality, innovation, productivity and prevention process. Role expansion, in which specialist ophthalmic nurses deliver intravitreal injections, has been shown to be economical, safe and effective. It enables timely delivery of the service, thereby preventing irreversible blindness for individuals with wet AMD.

  17. Panretinal photocoagulation versus intravitreal injection retreatment pain in high-risk proliferative diabetic retinopathy

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    Célia Regina Farias de Araújo Lucena

    2013-02-01

    Full Text Available PURPOSE: To compare pain related to intravitreal injection and panretinal photocoagulation in the management of patients with high-risk proliferative diabetic retinopathy. METHODS: Prospective study including patients with high-risk proliferative diabetic retinopathy and no prior laser treatment randomly assigned to receive panretinal photocoagulation (PRP group or panretinal photocoagulation plus intravitreal ranibizumab (PRPplus group. In all patients, panretinal photocoagulation was administered in two sessions (weeks 0 and 2, and intravitreal ranibizumab was administered at the end of the first laser session in the PRPplus group. Retreatment was performed at weeks 16 and 32 if active new vessels were detected at fluorescein angiography. Patients in the PRPplus group received intravitreal ranibizumab and patients in the PRP group received 500-µm additional spots per quadrant of active new vessels. After the end of retreatment, a 100-degree Visual Analog Scale was used for pain score estimation. The patient was asked about the intensity of pain during the whole procedure (retinal photocoagulation session or intravitreal ranibizumab injection. Statistics for pain score comparison were performed using a non-parametric test (Wilcoxon rank sums. RESULTS: Seventeen patients from PRPplus and 14 from PRP group were evaluated for pain scores. There were no significant differences between both groups regarding gender, glycosylated hemoglobin and disease duration. Mean intravitreal injection pain (±SEM was 4.7 ± 2.1 and was significantly lower (p<0.0001 than mean panretinal photocoagulation pain (60.8 ± 7.8. Twelve out of 17 patients from the PRPplus group referred intensity pain score of zero, while the minimal score found in PRP group was found in one patient with 10.5. CONCLUSION: In patients with high-risk proliferative diabetic retinopathy who needed retreatment for persistent new vessels, there was more comfort for the patient when retreatment

  18. [Surgery in posterior luxated lens fragments through intravitreal phacofragmentation].

    Science.gov (United States)

    Branisteanu, D; Moraru, Andreea

    2013-01-01

    To assess the intra and postoperative difficulties, the anatomical and functional results after intravitreal phacoemulsification during pars plana vitrectomy for retained intraocular lens fragments. Retrospective, non-comparative case series of 48 eyes who underwent vitrectomy for posterior dislocated lens fragments during phacoemulsification between January 2000 and January 2010. In 11 cases the vitrectomy was performed immediately, within 24 hours, and in 37 cases it was delayed 2 to 10 days after cataract surgery. During pars plana vitrectomy the lens fragments were separated of vitreous strings and then phacoemulsification was performed into the center of vitreous cavity. All cases were performed under local anesthesia by the same surgeon. During vitrectomy PFCL was used in 5 cases to protect central retina. Cases were followed-up at least 6 months. Statistical analysis was performed using Wilcoxon and chi square tests. Mean age in the study group was 65.38% 9.49 years (ranging 52-82 years). The mean visual acuity improved from 0.12% 0.07 (0.04-0.3) preoperatively to 0.3% 0.2 (0.05-0.6) postoperatively (p < 0.01). Mean intraocular pressure decreased postoperatively from 26.24% 9.3 mmHg (16-48 mmHg) to 15.95% 3.69 mmHg(12-24 mmHg) (p < 0.01). In all cases corneal edema and intraocular inflammation ceased after vitrectomy. In those 11 cases operated immediately the intravitreal phacoemulsification time was longer, as well as greater number of intraoperative complication (corneal edema, corneal leakage). In 4 out of these 11 cases (36.36%) severe postoperative retinal complications were noticed (2 cases of retinal detachment, 1 case of choroidal detachment and 1 case of choroidal hematoma). In the delayed group the only postoperative complication was cystoid macular edema in 9 out of 37 cases (24.32%). Removal of retained intraocular lens fragments suspended the intraocular inflammation and normalized intraocular pressure in all cases. Our results are in favor of

  19. Intravitreal low molecular weight heparin in PVR surgery.

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    Kumar Atul

    2003-01-01

    Full Text Available Purpose: To evaluate the efficacy of low molecular weight heparin (LMWH in prevention of postoperative fibrin formation following vitreoretinal surgery with proliferative vitreoretinopathy (PVR. Material and Methods: Thirty consecutive patients of retinal detachment with advanced PVR were enrolled in the study. They were randomised to study and control groups (n = 15 each. Study group patients received vitreoretinal surgery with 5 IU/cc of LMWH in vitrectomy infusion fluid. The control group patients received vitroretinal surgery without heparin in the infusion fluid. Patients were followed up at 1 week, 1 month and 3 months after surgery. Postoperative bleeding, media clarity, best-corrected visual acuity and success of the surgery at the end of 3 months were compared between the two groups. Results: At each follow-up visit, the study group showed a better media clarity, which was statistically significant ( P = 0.0042. The study group had a 50% better chance of retinal reattachment compared to the control group. Five patients had intraoperative bleeding in the study group (33% compared to 3 patients in the control group (20%. Conclusion: Use of intravitreal LMWH prevents postoperative fibrin formation and is beneficial in repair of retinal detachments with PVR.

  20. Aqueous Chlorhexidine for Intravitreal Injection Antisepsis: A Case Series and Review of the Literature.

    Science.gov (United States)

    Merani, Rohan; McPherson, Zachary E; Luckie, Alan P; Gilhotra, Jagjit S; Runciman, Jim; Durkin, Shane; Muecke, James; Donaldson, Mark; Aralar, Albert; Rao, Anupam; Davies, Peter E

    2016-12-01

    To determine the incidence of endophthalmitis in a large clinical series using aqueous chlorhexidine for antisepsis before intravitreal injection and to review the ophthalmic literature regarding chlorhexidine efficacy and safety. Multicenter retrospective case series. All patients receiving intravitreal injections from 7 retinal specialists. An audit of intravitreal injections performed by retinal specialists who exclusively used aqueous chlorhexidine 0.05% or 0.1% for prophylaxis of infective endophthalmitis was undertaken. The incidence of endophthalmitis was determined from August 1, 2011, to February 28, 2015. A literature review was performed to critically appraise the ocular safety and efficacy of aqueous chlorhexidine. Incidence of endophthalmitis after intravitreal injections. A total of 40 535 intravitreal injections were performed by 7 retinal specialists across 3 centers. Chlorhexidine was well tolerated, and only 1 patient with a suspected allergic reaction was noted. Three cases of endophthalmitis were identified with 1 culture-positive case. The 0.0074% (1 in 13 512) per-injection rate of endophthalmitis in this series compares favorably with previous series in which povidone-iodine has been used. Aqueous chlorhexidine was associated with a low rate of postinjection endophthalmitis and was well tolerated by patients. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  1. Fusarium Endophthalmitis following Cataract Surgery: Successful Treatment with Intravitreal and Systemic Voriconazole

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    Paulo A. Alves da Costa Pertuiset

    2016-01-01

    Full Text Available Purpose. To report a case of postoperative endophthalmitis caused by Fusarium species successfully treated with intravitreal and systemic voriconazole after treatment failure with amphotericin B. Methods. Clinical case report of a 60-year-old immunocompetent woman who presents with endophthalmitis of unknown origin 4 weeks after uneventful cataract extraction and IOL implantation surgery. IOL explantation, vitrectomy with capsular bag removal, vitreous aspiration for culture, and intravitreal injection of amphotericin B (5 μg/0.1 mL were performed. Diagnosis was established by culturing the vitreous aspirate on a Sabouraud agar medium and staining with lactophenol blue solution. Five days later, there was no clinical response. The decision was made to administer a single dose of intravitreal voriconazole (2.5 μg/0.1 mL and oral voriconazole (200 mg BID for 30 days. Results. Fusarium sp. grew on culture. Treatment with local and systemic voriconazole was started after no improvement with vitrectomy, IOL explantation, and intravitreal amphotericin B. After 1 month of treatment, the infection resolved and best-corrected visual acuity was 20/25. Conclusion. In patients with endophthalmitis caused by Fusarium sp., topical and systemic voriconazole treatment should be considered in cases resistant to intravitreal amphotericin B.

  2. Combination of Intravitreal Ranibizumab and Laser Photocoagulation for Aggressive Posterior Retinopathy of Prematurity

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    Ágata Mota

    2012-04-01

    Full Text Available Purpose: To report on 2 cases of aggressive posterior retinopathy of prematurity (ROP treated with intravitreal ranibizumab (Lucentis® and laser photocoagulation. Methods: Two premature females, born at 25 and 26 weeks’ gestation with a birth weight of 530 and 550 g, respectively, with aggressive posterior ROP received combined treatment with laser photocoagulation and intravitreal ranibizumab (0.3 mg [30 µl] to each eye. Structural outcomes were evaluated by indirect ophthalmoscopy and documented by retinography. Results: An intravitreal injection was made at 34 weeks of postmenstrual age in the first case, followed by laser photocoagulation 1 week later. There was a partial regression of ROP with treatment. Five weeks later, neovascularization regrowth with bleeding in both eyes (intraretinal and subhyaloid occurred and retreatment with combined therapy was performed. In the second case, single therapy with laser photocoagulation was made at 34 weeks of postmenstrual age. In spite of the confluent photocoagulation in the avascular area, progression to 4A ROP stage occurred 1 week later. Both eyes were retreated 1 week later with intravitreal ranibizumab and laser photocoagulation. Treatment resulted in ROP regression in both cases. There were no signs of systemic or ocular adverse side effects. Conclusion: The cases presented show that combination therapy of indirect laser photocoagulation and intravitreal ranibizumab can be effective in the management of aggressive posterior ROP. Further investigation on anti-VEGF safety in premature infants is necessary . Additional studies are needed to define the role of anti-VEGF in ROP treatment.

  3. Intravitreal injection of bone marrow mesenchymal stem cells in patients with advanced retinitis pigmentosa; a safety study

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    Leila Satarian

    2017-01-01

    Conclusion: Intravitreal injection of autologous bone marrow MSCs into patients' eyes with advanced RP does not meet safety standards. Major side effects of this therapy can include fibrosis and TRD. We propose thorough evaluation of MSCs prior to transplantation by intravitreal injection in the laboratory animals.\\

  4. Comparison of efficiency of intravitreal ceftazidime and intravitreal cefepime in the treatment of experimental Pseudomonas aeruginosa endophthalmitis

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    Nurettin Deniz

    2013-01-01

    Full Text Available In this study, we evaluated the efficiency of cefepime in the treatment of experimental Pseudomonas aeruginosa endophthalmitis. We compared the findings with the standard dose of ceftazidime (1 mg/0.1 ml. Thirty-six New-Zealand White rabbits were divided into 6 equal groups and were treated with different methods (Group 1 = sham, Group 2 = 0.5 mg/0.1 ml cefepime, Group 3 = 1 mg/0.1 ml cefepime, Group 4 = 2 mg/0.1 ml cefepime, Group 5 = 1 mg/0.1 ml ceftazidime, Group 6 = control. The eyes of rabbits in each group were examined clinically on 1 st , 3 rd , and 6 th day of the experiment. At 6 th day, 0.1 ml vitreous humor aspirates were obtained and plated for quantification on the blood agar and the results were expressed as colony-forming unit/ml. Subsequently, the eyeballs were enucleated and the histopathological evaluation was performed. Our findings denoted beneficial effects of cefepime in treatment groups (especially, in Groups 3 and 4. Intravitreal cefepime may be an alternative drug in the treatment of P. aeruginosa endophthalmitis.

  5. Optical coherence tomography and vessel diameter changes after intravitreal bevacizumab in diabetic macular oedema

    DEFF Research Database (Denmark)

    Soliman, W.; Vinten, M.; Sander, B.

    2008-01-01

    Purpose: To assess the effect of intravitreal bevacizumab on diabetic macular oedema (DMO) and retinal vessel calibres. Methods: We performed a consecutive case series study in which 10 consecutive eyes with diffuse DMO, two of which had not previously been treated, received an intravitreal...... injection of bevacizumab 1 mg, which was followed by two more injections at 6-week intervals. Fundus photography and optical coherence tomography (OCT) were carried out at baseline immediately before injection and at 1, 2.5 and 4 months after the first injection. Outcome measures were best corrected visual...... acuity (BCVA) in Early Treatment Diabetic Retinopathy Study letters, macular volume, foveal subfield thickness and vessel diameter measurement. Results: Intravitreal administration of bevacizumab was followed by a mean increase in BCVA of 7.3 +/- 17 (mean +/- standard deviation) letters between baseline...

  6. Effects of Intravitreal Ranibizumab in the Treatment of Retinopathy of Prematurity in Chinese Infants.

    Science.gov (United States)

    Yi, Zuohuizi; Su, Yu; Zhou, Yunyun; Zheng, Hongmei; Ye, Meihong; Xu, Yonghong; Chen, Changzheng

    2016-08-01

    To evaluate the efficacy associated with intravitreal ranibizumab in the treatment of retinopathy of prematurity (ROP). A retrospective case series study. Infants diagnosed with Type 1 ROP, or aggressive posterior ROP (AP-ROP) were enrolled in the study. All infants in the study received intravitreal ranibizumab (0.25 mg/0.025 ml) as the initial treatment. Follow-up examinations were performed the day after treatment, then weekly for 1 month, bi-monthly for two additional months, then monthly until vascularization of zone III occurred. Additional treatments were initiated in cases of disease recurrence. Thirty-three premature infants (a total of 66 eyes) receiving intravitreal ranibizumab were included. The mean birth weight was 1291 ± 211 g (range: 650-1650 g) and the mean gestational age was 29.8 ± 1.6 weeks (range: 27.0-33.6 weeks). The mean gestational age at the time of the first injection was 35.8 ± 1.6 weeks (range: 32.7-38.4 weeks). The mean follow-up time was 12.9 ± 4.9 months (range: 6-22 months). Single injections were administered to 58 eyes (87.9%), whereas eight eyes (12.1%) received additional treatments. Recurrence was observed in eight eyes (12.1%), with a mean time to recurrence of 6.9 ± 1.8 weeks (range: 4-8 weeks). Intravitreal ranibizumab is effective for the treatment of retinopathy of prematurity, although a small amount of patients recurred. Compared with intravitreal bevacizumab, a higher incidence and shorter time to recurrence were observed after intravitreal ranibizumab treatment, thus longer and more frequent follow-ups are needed.

  7. [The results of intravitreal bevacizumab in subretinal neovascularisation in angioid streaks].

    Science.gov (United States)

    Brănişteanu, D; Moraru, Andreea

    2014-01-01

    To assess the anatomical and functional results after intravitreal bevacizumab administration in choroidal neovascularization (CNV) due to angioid streaks; To assess the safety and results stability; Prospective, nonrandomized, interventional case study on choroidal neovascularization due to angioid streaks treated with intravitreal bevacizumab (AVASTIN). Intravitreal injection was repeated, if needed, at 4-6 weeks until leakage stopped. In all cases fluorescein angiograms and Spectral 3D OCTs were performed. Visual acuity was measured with ETDRS optotype. Cases were followed-up at least 6 months. Statistical analysis was performed using ANOVA and Wilcoxon tests. 8 cases with CNV associated to angioid streaks were evaluated between January 2007 and January 2013. Mean age of patients in the study was 52,36 +/- 4,33 years (ranging 42-64 years). The mean number of intravitreal injections was 4.64 +/- 0,42 (ranging between 3-8 injections). Mean visual acuity improved significantly in all cases after 3 intravitreal injections with a gain of more than 15 letters in 6 out of 8 cases (75%). OCT confirmed reduced depth of lesion and also a reduced lesion volume after treatment. No major local or systemic side-effects were noted. At 6 months follow-up the CNV reoccurred in 5 out of 8 cases (62.5%) requiring additional treatment. 3 out of 8 cases finally lost more than 5 letters due to subretinal fibrosis. These results confirm the efficacy and safety of intravitreal bevacizumab in controlling the CNV due to angioid streaks. High recurrence rate and quick lesion progression to subretinal fibrosis might be responsible for long-term poor functional results in this type of CNVs. More cases are needed for validation.

  8. Systemic Biodistribution and Intravitreal Pharmacokinetic Properties of Bevacizumab, Ranibizumab, and Aflibercept in a Nonhuman Primate Model.

    Science.gov (United States)

    Christoforidis, John Byron; Briley, Karen; Binzel, Katherine; Bhatia, Prayna; Wei, Lai; Kumar, Krishan; Knopp, Michael Vinzenz

    2017-11-01

    To determine the intravitreal pharmacokinetic properties and to study the systemic biodistribution characteristics of I-124-labeled bevacizumab, ranibizumab, and aflibercept with positron emission tomography-computed tomography (PET/CT) imaging in a nonhuman primate model. Three groups with four owl monkeys per group underwent intravitreal injection with 1.25 mg/0.05 mL I-124 bevacizumab, 0.5 mg/0.05 mL I-124 ranibizumab, or 2.0 mg/0.05 mL I-124 aflibercept in the right eye of each subject. All subjects were imaged using PET/CT on days 0, 1, 2, 4, 8, 14, 21, 28, and 35. Serum blood draws were performed at hours 1, 2, 4, 8, 12 and days 1, 2, 4, 8, 14, 21, 28, and 35. Radioactivity emission measurements were used to determine the intravitreal half-lives of each agent and to study the differences of radioactivity uptake in nonocular organs. The intravitreal half-lives were 3.60 days for I-124 bevacizumab, 2.73 days for I-124 ranibizumab, and 2.44 days for I-124 aflibercept. Serum levels were highest and most prolonged for bevacizumab as compared to both ranibizumab and aflibercept. All agents were primarily excreted through the renal and mononuclear phagocyte systems. However, bevacizumab was also found in significantly higher levels in the liver, heart, and distal femur bones. Among the three anti-VEGF agents used in clinical practice, bevacizumab demonstrated the longest intravitreal retention time and aflibercept the shortest. Significantly higher and prolonged levels of bevacizumab were found in the serum as well as in the heart, liver, and distal bones. These differences may be considered by clinicians when formulating treatment algorithms for intravitreal therapies with these agents.

  9. 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

  10. Intravitreal injection of ranibizumab using a pro re nata regimen for age-related macular degeneration and vision-related quality of life

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    Inoue M

    2014-09-01

    Full Text Available Maiko Inoue, Akira Arakawa, Shin Yamane, Kazuaki Kadonosono Department of Ophthalmology, Yokohama City University Medical Center, Yokohama, Japan Background: The purpose of this study was to assess visual function and vision-related ­quality of life after intravitreal injection of ranibizumab (IVR using a pro re nata regimen for the treatment of age-related macular degeneration.Methods: A prospective study of 54 eyes in 54 patients scheduled to undergo IVR for the treatment of exudative age-related macular degeneration was performed. A self-administered, 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25 was completed before and 3 and 12 months after the initial IVR treatment. We evaluated logMAR visual acuity and NEI VFQ-25 scores preoperatively and postoperatively. Further, associations between the changes in NEI VFQ-25 scores and patient characteristics were investigated at 12 months. Results: Postoperative best-corrected visual acuity improved significantly when compared with the preoperative visual acuity throughout the 12-month period (P<0.05 at 3 and 12 months, respectively. On the other hand, IVR treatment significantly improved the postoperative NEI VFQ-25 mean composite score at both 3 and 12 months (P<0.05, respectively. Better visual acuity at 12 months was associated with a greater improvement in NEI VFQ-25 score at 12 months (P<0.05. Conclusion: IVR was well tolerated and improved vision in these patients with age-related macular degeneration, as evaluated at one-year follow-up examinations. IVR also enabled good subjective perception, as indicated by higher composite NEI VFQ-25 scores. Maintaining good visual acuity may be an important factor for improving vision-related quality of life. Keywords: age-related macular degeneration, ranibizumab, intravitreal injection, vascular endothelial growth factor, vision-related quality of life

  11. Intravitreal Ampicillin Sodium for Antibiotic-Resistant Endophthalmitis: Streptococcus uberis First Human Intraocular Infection Report

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    Raul Velez-Montoya

    2010-01-01

    Full Text Available Purpose. To describe the clinical characteristics, diagnosis, and treatment with intravitreal ampicillin sodium of a postoperative endophthalmitis case due to Streptococcus uberis; an environmental pathogen commonly seen in mastitis cases of lactating cows. Methods. Case Report. A 52-year-old, Hispanic diabetic patient who suddenly developed severe pain and severe loss of vision, following vitrectomy. Results. The patient was diagnosed with postoperative endophthalmitis secondary to a highly resistant strain of Streptococcus uberis that did not respond to intravitreal antibiotics. He was treated with an air-fluid interchange, anterior chamber washout, intravitreal ampicillin sodium (5 mg/0.1 mL, and silicon oil tamponade (5000 ck. The eye was anatomically stabilized, though there was no functional recovery. Conclusion. Streptococcus uberis is an uncommon pathogen to the human eye, which has unique features that help the strain in developing resistance to antibiotics. While treatment with intravitreal ampicillin is feasible, there are still concerns about its possible toxicity.

  12. Combination systemic and intravitreal antiviral therapy in the management of acute retinal necrosis syndrome.

    Science.gov (United States)

    Yeh, Steven; Suhler, Eric B; Smith, Justine R; Bruce, Beau; Fahle, Gary; Bailey, Steven T; Hwang, Thomas S; Stout, J Timothy; Lauer, Andreas K; Wilson, David J; Rosenbaum, James T; Flaxel, Christina J

    2014-01-01

    Acute retinal necrosis (ARN) may lead to severe visual loss because of its rapid progression and high likelihood of retinal detachment (RD). This study investigates whether combination systemic and intravitreal antiviral therapy is superior to systemic antiviral therapy alone. Single-center, interventional, comparative case series of patients with ARN treated with combination systemic antiviral and intravitreal foscarnet injection therapy or systemic antiviral therapy alone. Survival analysis and incidence rates of visual acuity (VA) gain of two lines or greater, severe visual loss of 20/200 or worse, and RD were assessed. Twelve patients received combination therapy and 12 received systemic therapy alone. Patients receiving combination therapy were more likely to gain two or more lines of VA and showed decreased incidences of severe visual loss and RD. Combination oral and intravitreal antiviral therapy may improve the likelihood for VA gain and decrease the risk of RD in patients with ARN. Clinicians should consider administering combination systemic and intravitreal antiviral therapy for patients with the ARN syndrome.

  13. NO CASES OF ENDOPHTHALMITIS AFTER 20,293 INTRAVITREAL INJECTIONS IN AN OPERATING ROOM SETTING

    DEFF Research Database (Denmark)

    Brynskov, Troels; Kemp, Henrik; Sørensen, Torben Lykke

    2013-01-01

    Intravitreal injection has become a common procedure worldwide. A rare, but sight threatening, complication is bacterial endophthalmitis that has a poor visual prognosis. To identify practices that minimize the risk of endophthalmitis, the setting of a Danish University hospital is described....

  14. Use of Intravitreal Dexamethasone in a Case of Anterior Ischemic Optic Neuropathy

    Directory of Open Access Journals (Sweden)

    Raffaele Nuzzi

    2017-08-01

    Full Text Available Nowadays there is no unique and well-established treatment for nonarteritic anterior ischemic optic neuropathy, despite being the main acute pathology that affects the optic nerve in the elderly population and often resulting in a significant loss of visual acuity. The effectiveness of oral steroids is still under debate in the international literature, although many studies show that patients treated with high doses of systemic corticosteroids have a significantly higher chance of improved visual acuity and visual fields. The authors propose an intravitreal dexamethasone injection/implant as initial and acute therapy. Compared to systemic corticosteroids, intravitreal dexamethasone has the advantage of avoiding any systemic side effects of steroids. On the other hand, a rise in intraocular pressure might occur, manageable with local antiglaucoma drugs, especially in patients at risk, and there is a risk of induced cataract. The pharmacodynamics of the intravitreal dexamethasone slow-release implant is characterized by a first step with high release concentrations and a second following phase with decreasing concentrations. Therefore, the use of emergency dexamethasone (high concentration intravitreal injection is justified as a treatment after the first detection of an ischemic optic anterior neuropathy.

  15. [Clinical observation on treating diabetic macular edema with intravitreal triamcinolone acetonide and laser].

    Science.gov (United States)

    Wang, Yongbo; Shi, Anna; Shi, Xun; Liu, Weifeng

    2010-08-01

    To evaluate the effect of intravitreal injection of triamcinolone acetonide(IVTA) combining with retinal laser treating for diabetic macular edema(DME). Twenty five patients(32 eyes) with DME who has microangioma in macula lutea were randomly divided into group A, B,C and D(8 eyes each group). Eyes in group A were treated with laser photocoagulation. Eyes in group B were treated with multiplier-532 laser photocoagulation and transpupillary thermotherapy. Eyes in group C were treated with multiplier-532 laser photocoagulation and intravitreal triamcinolone acetonide. Eyes in group D were treated with multiplier-532 laser, transpupillary thermotherapy plus triamcinolone acetonide injection. Intravitreal injection of 4 mg triamcinolone acetonide was done 1 week after laser photocoagulation in group C and D. The visual acuity, intraocular pressure, macular thickness (foveal thickness) of the eyes in 4 groups were observed before and 1, 3 and 6 months after treatment. The visual acuity, intraocular pressure and foveal thickness of the 4 groups before treatment showed no significant difference(p> ). The visual acuity, intraocular pressure, macular thickness of eyes in group A, B were better than those of group C, D at 1, 3 and 6 months after treatment, and they had significant difference(p0.05). The effect of laser photocoagulation and intravitreal triamcinolone acetonide, laser photocoagulation combining with transpupillary thermotherapy plus triamcinolone acetonide injectionvisual treating for DME was better than laser photocoagulation alone, laser photocoagulation combining with transpupillary thermotherapy.

  16. Microplasmin intravitreal administration in patients with vitreomacular traction scheduled for vitrectomy: the MIVI I trial

    NARCIS (Netherlands)

    de Smet, Marc D.; Gandorfer, Arnd; Stalmans, Peter; Veckeneer, Marc; Feron, Eric; Pakola, Steve; Kampik, Anselm

    2009-01-01

    PURPOSE: To evaluate the safety and preliminary efficacy of 4 doses and several exposure times of intravitreal microplasmin given before pars plana vitrectomy for vitreomacular traction maculopathy. DESIGN: A multicenter, prospective, uncontrolled, dose-escalation, phase I/II clinical trial.

  17. Influence of dosage form on the intravitreal pharmacokinetics of diclofenac.

    Science.gov (United States)

    Durairaj, Chandrasekar; Kim, Stephen J; Edelhauser, Henry F; Shah, Jaymin C; Kompella, Uday B

    2009-10-01

    To prepare a suspension form of diclofenac and compare the influence of the injected form (suspension versus solution) on the intravitreal pharmacokinetics of diclofenac in Dutch belted pigmented rabbits. Diclofenac acid was prepared and characterized in a suspension formulation. Rabbit eyes were injected with either diclofenac sodium solution (0.3 mg) or diclofenac acid suspension (10 mg) prepared in 0.1 mL balanced salt solution. Rabbits were killed at regular time intervals, the eyes enucleated, and drug content quantified in the vitreous humor and retina-choroid tissue by high-performance liquid chromatography. Pharmacokinetic models were developed for both the dosage forms, and simulations were performed for different doses. Diclofenac acid with an approximate 5-mum particle size exhibited 3.5-fold lower solubility in vitreous humor, when compared with its sodium salt. The estimated settling velocity of the suspension in the vitreous humor was 3 cm/h. After diclofenac sodium salt solution injection, drug levels declined rapidly with no drug levels detectable after 24 hours in the vitreous humor and 4 hours in the RC. Throughout the assessed time course, drug levels were higher in the vitreous. However, sustained, high drug levels were observed in both the vitreous humor and the retina-choroid even on day 21 after diclofenac acid suspension injection, with retina-choroid drug levels being higher beginning at 0.25 hour. The elimination half-life of diclofenac suspension was 24 and 18 days in vitreous and retina-choroid, respectively, compared to 2.9 and 0.9 hours observed with diclofenac sodium. The pharmacokinetic models developed indicated a slow-release distribution or depot compartment for the diclofenac acid suspension in the posterior segment. Simulations indicated the inability of a 10-mg dose of diclofenac sodium solution to sustain drug levels in the vitreous beyond 11 days. By choosing a less soluble form of a drug such as diclofenac acid, vitreous

  18. Effect of intravitreal bevacizumab on serum, aqueous, and vitreous humor levels of erythropoietin in patients with proliferative diabetic retinopathy.

    Science.gov (United States)

    Cancarini, A; Costagliola, C; Dell'omo, R; Romano, M; Morescalchi, F; Agnifili, L; Ruggeri, G; Semeraro, F

    2014-12-01

    The aim of this study was to evaluate concentrations of erythropoietin (EPO) and vascular endothelial growth factor (VEGF) in serum, aqueous and vitreous humour of diabetic patients with proliferative retinopathy (PDR) and to verify their possible modifications induced by intravitreal injection of bevacizumab (IVB). This prospective observational study was performed on patients who underwent vitrectomy for proliferative diabetic retinopathy and macular hole or pucker. The study sample consisted of 33 patients with proliferative diabetic retinopathy and 20 non-diabetic patients with macular hole or pucker. EPO and VEGF levels in serum, aqueous and vitreous humour were measured in both groups. In diabetic patients measures were performed before and after IVB. EPO and VEGF levels in aqueous and vitreous humour were markedly increased in diabetic patients with PDR as compared with those recorded in the control group (P<0.001); contrarily, EPO serum levels were similar in both groups (p=not significant). IVB did not affect EPO levels (aqueous 39.1 ± 29.2 vs. 38.6 ± 26.1; vitreous 179.3 ± 88.3 vs. 131.6 ± 67.8; serum 9.2 ± 5.8 vs. 6.9 ± 3.7 mUI/mL); conversely, VEGF concentration significantly decreased 15 days after IVB in serum and ocular fluids (aqueous 141.6 ± 12.3 vs. 81.4 ± 5.4; vitreous 180.4 ± 45.8 vs. 95.8 ± 23.6; serum 113.9 ± 52.8 vs. 73.2 ± 65.6 mUI/mL). These findings demonstrate that the production of VEGF and EPO is regulated by different mechanisms. Intraocular levels of EPO in diabetic patients were significantly higher than those recorded in serum, suggesting a local production. In addition, bevacizumab does not influence intraocular levels of EPO.

  19. Diet and Endothelial Function

    Directory of Open Access Journals (Sweden)

    ADA M CUEVAS

    2004-01-01

    Full Text Available Endothelial dysfunction is one of the earliest events in atherogenesis. A consequence of endothelial damage is a lower availability of nitric oxide (NO, the most potent endogenous vasodilator. NO inhibits platelet aggregation, smooth muscle cell proliferation and adhesion of monocytes to endothelial cells. Endothelial dysfunction is present in patients with cardiovascular disease and/or coronary risk factors, such as hypertension, dyslipidemia, diabetes, smoking or hyperhomocysteinemia. At present, soluble markers and high resolution ultrasound of the brachial artery, have provided simple tools for the study of endothelial function and the effects of several interventions. It has been demonstrated that dietary factors may induce significant changes on vascular reactivity. Nutrients, such as fish oil, antioxidants, L-arginine, folic acid and soy protein have shown an improvement in endothelial function that can mediate, at least partially, the cardioprotective effects of these substances. Attention has been focused on dietary patterns in populations with lower prevalence of cardiovascular disease. There is some evidence suggesting that Mediterranean diet characterized by high consumption of vegetables, fish, olive oil and moderate wine consumption may have a positive effect on endothelial function. These results give us evidence on the significant role of diet on endothelial function and its impact on the pathogenesis of atherosclerosis

  20. Efficacy of systemic diclofenac sodium on intravitreal concentration.

    Science.gov (United States)

    Panahi, Yunes; Naderi, Mostafa; Jadidi, Khosrow; Hoseini, Hadise; Abrishami, Mojtaba

    2018-02-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs), as an alternative, are replacing corticosteroids in ocular inflammatory diseases. Diclofenac has been used mainly topically, and recent focus has been on intravitreal delivery. Both of these methods have been shown to have complications in long-term application. To assess the efficacy of slow release oral diclofenac sodium on intravitreal concentration in experimental model of chemically injured eyes. In an experimental double-masked clinical trial, right eyes of 24 albino rabbits were chemically injured by 1 N NaOH. One hour after chemical injury, 10 cc suspension gavage containing 100 mg slow release diclofenac sodium was administered in all cases. 2, 4, 6, 12, 24, 48 h after gavage, vitreous samples were obtained in all cases. Intravitreal concentration of diclofenac sodium was evaluated in all samples using high-performance liquid chromatography (HPLC) method. Intravitreal diclofenac levels by oral intake were enhanced by the inflammation in all the measurements. In inflamed eyes, diclofenac concentration was ten times more than control eye (2.658 ± 0.344 vs. 0.242 ± 0.0279 and 1.617 ± 0.527 vs. 0.148 ± 0.095; in 2 and 4 h, respectively). After 6 h, diclofenac concentration was statistically different, although it reduced below 1 μg/ml. Diclofenac is delivered to the inflamed eye more than healthy eye. It seems that by oral diclofenac consumption, it is possible to make a significant intravitreal concentration.

  1. Dexamethasone intravitreal implants for diabetic macular edema refractory to ranibizumab monotherapy or combination therapy.

    Science.gov (United States)

    Gutiérrez-Benítez, L; Millan, E; Arias, L; Garcia, P; Cobos, E; Caminal, M

    2015-10-01

    To determine the effectiveness and local safety of dexamethasone intravitreal implants as a treatment in diabetic macular edema (DME) refractory to intravitreal injections of ranibizumab monotherapy or combination therapy. A retrospective study conducted on patients with DME refractory to ranibizumab monotherapy or combined with other treatments treated with dexamethasone intravitreal implants. The parameters analyzed were visual acuity (VA) by ETDRS (Early Treatment Diabetic Retinopathy Study) charts and foveal thickness by spectral-domain optical coherence tomography (SD-OCT) before the treatment, 2 months after treatment, and at the end of the follow-up. A total of 14 eyes of 14 patients were included, with a mean age of 64 years (SD: 9.5; range 41-78) and a mean follow-up of 7.6 months. The mean VA improved from 53 letters to 59 letters at 2 months (P=.03), and 57 at the end of the follow-up period (P=.3). The mean foveal thickness decreased from 502 μ to 304 μ at 2 months (P=.001), and 376 μ at the end of the follow-up period (P=.009). Further treatment with intravitreal dexamethasone was required in 43% of the patients, and 21% had increased intraocular pressure, which was controlled with topical medication. Intravitreal dexamethasone implant is an effective and locally safe treatment for the management of DME refractory to ranibizumab monotherapy or combined with other treatments. Copyright © 2014 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  2. Intravitreal bevacizumab in refractory neovascular glaucoma: a prospective, observational case series.

    Science.gov (United States)

    Kotecha, Aachal; Spratt, Alexander; Ogunbowale, Lola; dell'Omo, Roberto; Kulkarni, Avinash; Bunce, Catey; Franks, Wendy A

    2011-02-01

    To examine the efficacy of intravitreal bevacizumab for pain relief in eyes with refractory neovascular glaucoma. In this prospective case series, 52 eyes with neovascular glaucoma were administered intravitreal bevacizumab, 1.25 mg, and monitored for 6 months. The primary outcome measure was change in subjective pain score. Intraocular pressure and iris neovascularization were evaluated at each visit. Surgical intervention for control of intraocular pressure was performed according to clinical need. Forty-two patients (44 eyes) completed the 6-month follow-up. Subjective pain score was reduced significantly 1 week after intravitreal bevacizumab injection and lasted throughout the follow-up period (median [interquartile range]: baseline, 3 [0-6]; week 1, 1 [0-3]; month 1, 0 [0-1]; month 3, 0 [0-1]; and month 6, 0 [0-0]; Kruskal-Wallis χ(2) 31.03; P < .001). A rapid, yet relatively transient, reduction in iris neovascularization was also noted (iris neovascularization grade at baseline, 4.0 [3-4]; week 1, 2.5 [1-4]; month 1, 2.0 [1-4]; month 3, 3.0 [2-4]; and month 6, 3.0 [2-4], χ(2) 23.33; P < .001). Four eyes (8%) required more than 1 injection to facilitate further intraocular surgery. Intravitreal bevacizumab is a useful adjunct in the management of refractory neovascular glaucoma, producing rapid relief of pain. However, we found no evidence to suggest that intravitreal bevacizumab lowers intraocular pressure in eyes with angle closure; conventional medical, laser, and surgical treatment are still needed in these eyes.

  3. Proteolytic cleavage of vascular adhesion protein-1 induced by vascular endothelial growth factor in retinal capillary endothelial cells.

    Science.gov (United States)

    Yoshida, Shiho; Murata, Miyuki; Noda, Kousuke; Matsuda, Takashi; Saito, Michiyuki; Saito, Wataru; Kanda, Atsuhiro; Ishida, Susumu

    2018-02-01

    To investigate the mechanism of soluble vascular adhesion protein-1 (sVAP-1) accumulation induced by vascular endothelial growth factor (VEGF) in the vitreous of patients with diabetic retinopathy (DR). Experimental. Protein levels of sVAP-1 and N epsilon-(hexanoyl)lysine (HEL), an oxidative stress marker, in the vitreous samples from patients with proliferative diabetic retinopathy (PDR) with or without intravitreal bevacizumab (IVB) injection were determined by ELISA. The effect of VEGF on both mRNA expression of Vap-1 and secretion of sVAP-1 in rat retinal capillary endothelial cells (TR-iBRB2) was analyzed by real-time PCR and western blotting, respectively. In addition, the impact of VEGF on production and activation ratios of matrix metalloproteinase (MMP)-2 and MMP-9 was examined by gelatin zymography. Hydrogen peroxide production and reactive oxygen species (ROS) levels were assessed in the supernatants of TR-iBRB2 cells treated with VEGF. IVB injection decreased vitreous levels of sVAP-1 and HEL in patients with PDR. VEGF stimulation released sVAP-1 protein from TR-iBRB2 cells as a consequence of membrane-anchored VAP-1 shedding by MMP-2 and MMP-9. In addition, VEGF increased hydrogen peroxide generation and ROS augmentation through spermine oxidation by sVAP-1 as semicarbazide-sensitive amine oxidase (SSAO) in the supernatant of cultured endothelial cells. The current data demonstrate that proangiogenic factor VEGF induces sVAP-1 release from retinal capillary endothelial cells and facilitates hydrogen peroxide generation via enzymatic property of sVAP-1, followed by the increase of oxidative stress, one of the crucial factors in the pathogenesis of DR.

  4. Successful Treatment of Retinal Angiomatous Proliferation with Intravitreal Triamcinolone and Ranibizumab Injections in a 67-Year-Old Male

    Directory of Open Access Journals (Sweden)

    Adnaan Haq

    2014-11-01

    Full Text Available A 67-year-old male who presented to the eye casualty department with deterioration in his vision was diagnosed with retinal angiomatous proliferation. After initial deterioration with ranibizumab intravitreal injections, we have demonstrated successful treatment and stabilised vision with ranibizumab and a single intravitreal triamcinolone injection. Stringent follow-up and top-up ranibizumab injections have stabilised his vision and have shown foveal improvement on optical coherence tomography imaging.

  5. Ocular silicon distribution and clearance following intravitreal injection of porous silicon microparticles

    Science.gov (United States)

    Nieto, Alejandra; Hou, Huiyuan; Sailor, Michael J.; Freeman, William R.; Cheng, Lingyun

    2013-01-01

    Porous silicon (pSi) microparticles have been investigated for intravitreal drug delivery and demonstrated good biocompatibility. With the appropriate surface chemistry, pSi can reside in vitreous for months or longer. However, ocular distribution and clearance pathway of its degradation product, silicic acid, are not well understood. In the current study, rabbit ocular tissue was collected at different time point following fresh pSi (day 1, 5, 9, 16, and 21) or oxidized pSi (day 3, 7, 14, 21, and 35) intravitreal injection. In addition, dual-probe simultaneous microdialysis of aqueous and vitreous humor was performed following a bolus intravitreal injection of 0.25 mL silicic acid (150 μg/mL) and six consecutive microdialysates were collected every 20 min. Silicon was quantified from the samples using inductively coupled plasma-optical emission spectroscopy. The study showed that following the intravitreal injection of oxidized pSi, free silicon was consistently higher in the aqueous than in the retina (8.1 ± 6.5 vs. 3.4 ± 3.9 μg/mL, p = 0.0031). The area under the concentration-time curve (AUC) of the retina was only about 24% that of the aqueous. The mean residence time was 16 days for aqueous, 13 days for vitreous, 6 days for retina, and 18 days for plasma. Similarly, following intravitreal fresh pSi, free silicon was also found higher in aqueous than in retina (7 ± 4.7 vs. 3.4 ± 4.1 μg/mL, p = 0.014). The AUC for the retina was about 50% of the AUC for the aqueous. The microdialysis revealed the terminal half-life of free silicon in the aqueous was 30 min and 92 min in the vitreous; the AUC for aqueous accounted for 38% of the AUC for vitreous. Our studies indicate that aqueous humor is a significant pathway for silicon egress from the eye following intravitreal injection of pSi crystals. PMID:24036388

  6. Intravenous Drug Use-Associated Scopulariopsis Endophthalmitis Treated with Systemic and Intravitreal Voriconazole

    Directory of Open Access Journals (Sweden)

    Joseph J. Raevis

    2018-01-01

    Full Text Available Purpose: To report a case of intravenous (i.v. heroin use-associated endogenous endophthalmitis caused by Scopulariopsis fungal species, and its response to intravitreal and oral voriconazole treatments. Patient: A 21-year-old-female with chronic hepatitis C and i.v. heroin use presented with subacute decreased vision to hand motion in her left eye. Results: Endogenous fungal endophthalmitis caused by Scopulariopsis was confirmed by vitreous biopsy. The patient improved clinically after vitrectomy with intravitreal voriconazole and 3 weeks of oral voriconazole. The final vision was 20/60 after 6 months. Conclusions: Scopulariopsis is a rare cause of endophthalmitis, and is often difficult to treat due to its resistance to commonly used antifungals. This case is the first report of Scopulariopsis endophthalmitis secondary to i.v. drug use.

  7. Patients' experiences of nursing actions during intravitreal treatment for wet age-related macular degeneration

    OpenAIRE

    Rönn Emsfors, Åsa; Elgán, Carina

    2015-01-01

    Purpose: The aim was to identify and describe nursing actions performed by nursing staff in which patients with wet age-related macular degeneration (AMD) experience good nursing care. Method: An explorative and descriptive qualitative design based on the Critical incident technique (CIT) was used. A strategic sample of 16 patients, aged 61-87 years (eleven women and five men) with wet AMD who received intravitreal treatment were interviewed. Results: Two main areas of good nursing care was i...

  8. Pharmacokinetics of bevacizumab after topical and intravitreal administration in human eyes

    OpenAIRE

    Moisseiev, Elad; Waisbourd, Michael; Ben-Artsi, Elad; Levinger, Eliya; Barak, Adiel; Daniels, Tad; Csaky, Karl; Loewenstein, Anat; Barequet, Irina S.

    2013-01-01

    Background Topical bevacizumab is a potential treatment modality for corneal neovascularization, and several recent studies have demonstrated its efficacy. No previous study of the pharmacokinetics of topical bevacizumab has been performed in human eyes. The purpose of this study is to investigate the pharmacokinetics of topical administration of bevacizumab in human eyes, and also to compare the pharmacokinetics of intravitreal bevacizumab injections with previously reported data. Methods Tw...

  9. Survey: technique of performing intravitreal injection among members of the Brazilian Retina and Vitreous Society (SBRV

    Directory of Open Access Journals (Sweden)

    Helio F. Shiroma

    2015-02-01

    Full Text Available Purpose: To evaluate and describe the precautions involved in the technique of intravitreal injection of antiangiogenic drugs adopted by the ophthalmologists who are members of the Brazilian Society of Retina and Vitreous (SBRV. Methods: A questionnaire containing 22 questions related to precautions taken before, during, and after intravitreal injection was sent electronically to 920 members of SBRV between November 15, 2013 and April 31, 2014. Results: 352 responses (38% were obtained. There was a predominance of men (76% from the southwest region of Brazil (51%. The professional experience varied between 6 and 15 years after medical specialization (50%. Most professionals (76% performed an average of 1 to 10 intravitreal injections a week, and 88% of the procedures were performed in the operating room using povidone iodine (99%, sterile gloves, and blepharostat (94%. For inducing topical anesthesia, usage of anesthetic eye drops was the most used technique (65%. Ranibizumab (Lucentis® was the most common drug (55%, and age-related macular degeneration (AMD was the most treated disease (57%. Regarding the complications treated, 6% of the ophthalmologists had treated at least one case of retinal detachment, 20% had treated cases of endophthalmitis, 9% had treated cases of vitreous hemorrhage, and 12% had encountered cases of crystalline lens touch. Conclusion: Intravitreal injection is a procedure routinely performed by retina specialists and has a low incidence of complications. Performing the procedure in the operating room using an aseptic technique was preferred by most of the respondents. Ranibizumab was the most used drug, and AMD was the most treated disease.

  10. The effect of intravitreal bevacizumab and transpupillary thermotherapy on choroidal metastases and literature review

    Directory of Open Access Journals (Sweden)

    Chun-Ju Lin

    2015-01-01

    Full Text Available Aims : To represent the effects of transpupillary thermotherapy (TTT and intravitreal bevacizumab on choroidal metastases and review the literature. Settings and Design : A retrospective, interventional, noncomparative case series. Materials and Methods : A retrospective, interventional, noncomparative case series of five eyes in three patients with choroidal metastases was conducted. Fundus findings of choroidal metastases were divided into two types: Solitary or diffuse type. The size of the tumor was termed small (15 mm diameter. All eyes received one session of TTT followed by 3 weekly intravitreal bevacizumab injections as an adjuvant therapy. The parameters of treatment for TTT were 1.2-3 mm spot size, 150-300 mW, 60 s with the whole lesion covered confluently. The changes in preoperative and postoperative best-corrected visual acuity (BCVA were recorded. Serial color fundus photography and optical coherent tomography were performed to measure the treatment efficacy. Results : All eight choroidal metastases were solitary type. The size of six tumors was small, the size of one tumor was medium, and the size of one tumor was large. All five eyes of the three patients had improvement of BCVA after treatment. Fundus photos revealed tumor shrinkage and the mean shrinkage percentage was 61.27 ± 21.71%. Optical coherence tomography revealed complete resolution of serous retinal detachment. There was no recurrence after 6 months follow-up. Conclusions : TTT combined with intravitreal bevacizumab injections brought about beneficial effects in reducing tumor size and improving vision in all five eyes of the three patients. Despite the retrospective nature of our study, the absence of control group and the size limitation that, of course, limit the statistical power, TTT combined with intravitreal bevacizumab seems to be efficient in providing another cost-reducing and time-saving treatment option for patients with choroidal metastases. The

  11. Efficacy of intravitreal ranibizumab injection combined with macular grid photocoagulation for diabetic macular edema

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    Hu-Lin Jiang

    2014-07-01

    Full Text Available AIM:To evaluate the clinical efficacy of intravitreal injection of ranibizumab combined with macular grid photocoagulation for diabetic macular edema(DME.METHODS:Totally 60 eyes(60 patientswith DME were randomly divided into 2 groups: 30 eyes of simple injection group underwent intravitreal injection of ranibizumab, and 30 eyes of combined treatment group underwent intravitreal injection of ranibizumab and macular grid photocoagulation 1wk later. The best corrected visual acuity(BCVA, central macular thickness(CMTmeasured by optical coherence tomography(OCTand postoperative complications were observed.RESULTS:In simple injection group, the BCVA after operation were separately 0.390±0.075(4wk, 0.367±0.088(8wkand 0.319±0.064(12wk,the CMT after operation were separately 221.63±112.34μm(4wk, 337.73±99.56μm(8wkand 432.92±100.46μm(12wk, which were much better than pre-operation. But during follow-up, the BCVA presented down trend and the CMT was on the rise slowly. In combined treatment group, the BCVA after operation were separately 0.385±0.036(4wk, 0.382±0.079(8wkand 0.377±0.097(12wk,the CMT after operation were separately 249.77±106.55μm(4wk, 270.40±92.88μm(8wkand 275.84±97.34μm(12wk, which were satisfactory and steady during follow-up, better than simple injection group(PCONCLUSION:Intravitreal injection of ranibizumab can effectively improve visual acuity and decrease central foveal thickness for patients with DME, combining with macular grid photocoagulation can ensure therapeutic effects steady and permanent.

  12. Intravitreal bevacizumab for macular edema due to branch retinal vein occlusion: 12-month results

    OpenAIRE

    Demir M; Oba E; Gulkilik G; Odabasi M; Ozdal E

    2011-01-01

    Mehmet Demir, Ersin Oba, Gökhan Gulkilik, Mahmut Odabasi, Erhan OzdalSisli Etfal Training and Research Hospital, Eye Clinic, Sisli, Istanbul, TurkeyPurpose: To present the functional and anatomic changes after intravitreal bevacizumab in eyes with macular edema (ME) due to branch retinal vein occlusion (BRVO).Design: The study was a retrospective study.Materials and methods: The study included 31 patients with ME due to BRVO. We compared the examination findings of patients with ME b...

  13. Short-term efficacy of intravitreal conbercept in treatment-naive patients with polypoidal choroidal vasculopathy

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    Peng Y

    2018-02-01

    Full Text Available Yuting Peng, Xiongze Zhang, Miaoling Li, Bing Liu, Lan Mi, Chengguo Zuo, Feng Wen State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China Introduction: To evaluate the functional and morphological outcomes of intravitreal conbercept monotherapy in patients with polypoidal choroidal vasculopathy (PCV. Materials and methods: In this retrospective, observational case series study, we reviewed medical records of 48 eyes (48 patients with naive PCV that were treated with a series of 3 monthly intravitreal injections of 0.5 mg of conbercept followed by as-needed injections (3+pro re nata. All patients completed at least 6 months of monthly follow-up. Changes in the best-corrected visual acuity, optical coherence tomography, and indocyanine green angiography were retrospectively evaluated. Results: At 6 months, the mean best-corrected visual acuity significantly improved from 0.89±0.35 (20/160 in Snellen equivalent at baseline to 0.58±0.26 (Snellen equivalent of 20/80; P<0.001, and 60.42% (29/48 of eyes had an improvement of three lines of vision; the mean central retinal thickness significantly decreased from 333.56±171.04 µm at baseline to 187.65±54.46 µm (P<0.001, and 93.75% (45/48 achieved a dry macula. At 3 months, 6 of 32 eyes (18.75% showed partial regression of branching vascular network, 14 of 32 (43.75% patients showed complete resolution of polyps. The mean number of injections was 3.4±0.9 through 6 months. No conbercept-related systemic or ocular adverse effects were observed. Conclusion: Intravitreal injection of conbercept using “3+pro re nata” regimen significantly improved visual acuity and anatomical outcomes in treatment-naive patients with PCV. Keywords: conbercept, intravitreal injection, PCV, short-term efficacy, “3+PRN”

  14. Distribution of [35S] taurine in mouse retina after intravitreal and intravascular injection

    International Nuclear Information System (INIS)

    Pourcho, R.G.

    1977-01-01

    The distribution of [ 35 S] taurine in mouse retinae was studied by autoradiographic techniques after either intravitreal or intravascular injection. The route of injection did not affect the final localization. The major sites of label accumulation were the outer nuclear layer, the inner nuclear layer, and Mueller cell processes adjacent to the vitreal surface. The distribution was consistent with the interpretation that taurine was localized within two cellular compartments of mouse retina, photoreceptor cells and Mueller cells. (author)

  15. Intravitreal bevacizumab (Avastin treatment of diffuse diabetic macular edema in an Indian population

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    Kumar Atul

    2007-01-01

    Full Text Available Background: To report the anatomic and visual acuity response after intravitreal bevacizumab (Avastin in patients with diffuse diabetic macular edema. Design: Prospective, interventional case series study. Materials and Methods: This study included 20 eyes of metabolically stable diabetes mellitus with diffuse diabetic macular edema with a mean age of 59 years who were treated with two intravitreal injections of bevacizumab 1.25 mg in 0.05 ml six weeks apart. Main outcome measures were 1 early treatment diabetic retinopathy study visual acuity, 2 central macular thickness by optical coherence tomography imaging. Each was evaluated at baseline and follow-up visits. Results: All the eyes had received some form of laser photocoagulation before (not less than six months ago, but all of these patients had persistent diffuse macular edema with no improvement in visual acuity. All the patients received two injections of bevacizumab at an interval of six weeks per eye. No adverse events were observed, including endophthalmitis, inflammation and increased intraocular pressure or thromboembolic events in any patient. The mean baseline acuity was 20/494 (log Mar=1.338±0.455 and the mean acuity at three months following the second intravitreal injection was 20/295 (log Mar=1.094±0.254, a difference that was highly significant ( P =0.008. The mean central macular thickness at baseline was 492 µm which decreased to 369 µm ( P =0.001 at the end of six months. Conclusions: Initial treatment results of patients with diffuse diabetic macular edema not responding to previous photocoagulation did not reveal any short-term safety concerns. Intravitreal bevacizumab resulted in a significant decrease in macular thickness and improvement in visual acuity at three months but the effect was somewhat blunted, though still statistically significant at the end of six months.

  16. Advanced Coats’ disease treated with intravitreal bevacizumab combined with laser vascular ablation

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    Villegas VM

    2014-05-01

    Full Text Available Victor M Villegas,1 Aaron S Gold,1 Audina M Berrocal,2 Timothy G Murray11Ocular Oncology and Retina, Miami, FL, USA; 2Department of Ophthalmology, Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, FL, USAPurpose: To evaluate the impact of intravitreal bevacizumab combined with laser vascular ablation in the management of advanced Coats’ disease presenting with exudative retinal detachment.Methods: This was a retrospective review of 24 children that presented with exudative retinal detachments associated with advanced Coats’ disease. Mean patient age was 62 months (range 9–160 months. Presenting signs included retinal detachment in 24 children (100%, vascular telangiectasia in 24 children (100%, and retinal ischemia in 24 children (100%. Twenty of 24 children presented with elevated, vascular leakage in the fovea (83%. Two children presented with sub-retinal fibrosis associated with presumed long-standing retinal detachment without evidence of rhegmatogenous retinal detachment. Ten patients exhibited vascular alterations in the periphery of the second eye without clinical evidence of exudation. All 24 children were treated with a large-spot-size diode laser directly to areas of abnormal telangiectatic vasculature. All 24 children received intravitreal bevacizumab injection. Results: All 24 children had resolution of exudative retinal detachment, ablation of vascular telangiectasia, and anatomic improvement of the retina. No child exhibited progressive retinal detachment and no eye required enucleation. No cases of neovascular glaucoma were seen. Fellow eyes with peripheral vascular alterations showed no progression to exudative vasculopathy during the observation period. Intravitreal bevacizumab injection was not associated with endophthalmitis or systemically-observed complications.Conclusion: Repetitive intravitreal bevacizumab combined with laser vascular ablation may be utilized effectively

  17. Real-time measurement of needle forces and acute pressure changes during intravitreal injections.

    Science.gov (United States)

    Christensen, Logan; Cerda, Ashlee; Olson, Jeffrey L

    2017-11-01

    The purpose of this study was to use a physiological pressure transducer to measure real-time, continuous pressure changes in an ex vivo study model of porcine eyes to record the amount of force needed for scleral penetration and to measure acute intraocular pressure rise during intravitreal injections. A pressure transducer was inserted into the anterior chamber of 30 fresh porcine eyes, and intraocular pressure was measured 2 s prior to intravitreal injection until 2 s after. A force transducer plate was used to insert various gauge needles into the vitreous cavity and the amount of force in Newtons (N) required for scleral penetration was recorded. For scleral perforation, 32- and 30-gauge needles required 0.44 N and 0.45 N, significantly less than larger gauge needles (P time continuous recordings of pressure reveal that an instantaneous intraocular pressure spike occurs during intravitreal injection and appears to be separate from the intraocular pressure spike that occurs during needle insertion. This pressure spike is transient and has not been captured by previous methods of intraocular pressure measurement, which rely on single time point measurements. The clinical significance of this brief intraocular pressure spike is unclear and warrants further investigation. © 2017 Royal Australian and New Zealand College of Ophthalmologists.

  18. Long-Term Follow-Up of Intravitreal Bevacizumab in Retinal Arterial Macroaneurysm: A Case Report

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    Shani Golan

    2011-12-01

    Full Text Available Purpose: To present the long-term effect of intravitreal bevacizumab (Avastin® therapy in a patient suffering from retinal arterial macroaneurysm. Methods: Case report of a 72-year-old female diagnosed with retinal macroaneurysm in the superior temporal artery leading to macular edema. Functional and morphological data at baseline, 4 weeks, 2 months, and 13 months following treatment with two consecutive intravitreal bevacizumab injections are presented. Results: Best-corrected visual acuity improved from 20/160 at baseline to 20/20 at the3-months follow-up and remained stable through 13 months of follow-up. Central retinal thickness measured by optical coherence tomography decreased from 364 µm at baseline to 248 µm at the 13-months follow-up. No ocular or systemic side effects were detected. Conclusions: Intravitreal bevacizumab therapy may lead to resolution of macular edema associated with retinal macroaneurysm and consequently visual improvement. This treatment may promise a long-lasting effect but warrant further investigation in larger series.

  19. Serial Intravitreal Bevacizumab Injections Slow the Progression of Radiation Maculopathy Following Iodine-125 Plaque Radiotherapy.

    Science.gov (United States)

    Stacey, Andrew W; Demirci, Hakan

    2016-01-01

    To assess the outcomes of intravitreal bevacizumab injection in the management of radiation maculopathy secondary to plaque radiotherapy, and to identify optimal treatment strategies. A retrospective review of all choroidal melanoma patients at one referral center who were treated with plaque radiotherapy, subsequently developed radiation maculopathy, and received intravitreal bevacizumab. A total of 31 patients were identified. The mean visual acuity decreased three Snellen lines in the year leading up to the first bevacizumab injection. After initiating injection therapy, the mean visual acuity remained stable for 9 months. The change in visual acuity of patients who received injections within 90 days of previous injections was significantly better than the visual acuity of those who received injections more than 90 days apart (p=0.0003). Patients who demonstrated late-phase macular leakage on fluorescein angiography at the time of the first bevacizumab injection had better long-term visual acuity outcomes than patients who had no evidence of macular leakage (average of one line improvement of vision vs. ten line loss of vision, p=0.03). Intravitreal bevacizumab injection was effective in stabilizing visual acuity in patients with radiation maculopathy. Patients benefited most from injections administered every 90 days or sooner. Fluorescein angiography can help identify patients who will respond favorably to treatment.

  20. Cytotoxicity and genotoxicity of intravitreal adalimumab administration in rabbit retinal cells

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    Álcio Coutinho de Paula

    2015-04-01

    Full Text Available Purpose: To assess the cytotoxicity and genotoxicity of intravitreal adalimumab treatment in an animal experimental model using cytological and molecular techniques. Methods: Eighteen rabbits were randomly assigned to three groups: control, adalimumab treatment, and placebo. Cytotoxicity on retinal cells was evaluated using flow cytometry assays to determine the level of apoptosis and necrosis. Genotoxicity was evaluated by comet assays to assess DNA damage, and quantitative real-time polymerase chain reaction (qPCR was used to evaluate expression of apoptosis-inducing caspases (8 and 3. Results: No cytotoxicity or genotoxicity was observed in any of the two treatment groups (adalimumab and placebo following intravitreal administration compared with the control group. Flow cytometry analysis revealed that more than 90% of the cells were viable, and only a low proportion of retinal cells presented apoptotic (~10% or necrotic (<1% activity across all groups. Molecular damage was also low with a maximum of 6.4% DNA degradation observed in the comet assays. In addition, no increase in gene expression of apoptosis-inducing caspases was observed on retinal cells by qPCR in both the adalimumab and placebo groups compared with the control group. Conclusion: The use of adalimumab resulted in no detectable cytotoxicity or genotoxicity on retinal cells for up to 60 days upon administration. These results therefore indicate that adalimumab may be a safe option for intravitreal application to treat ocular inflammatory diseases in which TNF-α is involved.

  1. Treatment of CNV secondary to presumed ocular histoplasmosis with intravitreal aflibercept 2.0 mg injection.

    Science.gov (United States)

    Walia, Harpreet S; Shah, Gaurav K; Blinder, Kevin J

    2016-04-01

    To assess the efficacy and safety of intravitreal aflibercept injection in the treatment of CNV secondary to presumed ocular histoplasmosis syndrome (POHS). To assess safety of intravitreal aflibercept for the treatment of CNV secondary to presumed ocular histoplasmosis syndrome. Masked, open-label, prospective study. Five subjects will receive 2.0 mg aflibercept injection every 8 weeks with 3 initial monthly doses over a 12 month period. No adverse systemic or ocular were reported. At month six, the mean visual acuity improved by 7.8 ETDRS letters, mean central subfoveal thickness decreased by 38.8 microns and mean OCT volume decreased by 0.076 mm3 . At month twelve, the mean visual acuity improved by 12.4 ETDRS letters, mean central subfoveal thickness decreased by 34.6 microns and mean OCT volume decreased by 0.576 mm3. The use of intravitreal 2.0 mg aflibercept injection for the treatment of CNV secondary to presumed ocular histoplasmosis syndrome yielded no systemic or ocular adverse events and produced improvement in visual acuity and reduction of OCT thickness and volume. Copyright © 2016 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

  2. Predictive factors for functional improvement following intravitreal bevacizumab injections after central retinal vein occlusion.

    Science.gov (United States)

    Januschowski, Kai; Feltgen, Nicolas; Pielen, Amelie; Spitzer, Bernhard; Rehak, Matus; Spital, Georg; Dimopoulos, Spyridon; Meyer, Carsten H; Szurman, Gesine B

    2017-03-01

    Vision loss in central retinal vein occlusion (CRVO) is mostly caused by macular edema (ME) and can be treated with intravitreal bevacizumab injections. The goal of this study was to identify predictive factors for improvement in visual acuity. Three hundred and sixteen eyes of six centres having received intravitreal bevacizumab for ME due to CRVO were enrolled in this multicentre, retrospective, interventional case series. The follow-up time was 24 to 48 weeks. Investigated patient characteristics were pretreatment, duration of CRVO prior to the first injection, initial best-corrected visual acuity (BCVA), baseline central retinal thickness as measured by optical coherence tomography, gender, eye, age, comorbidity with glaucoma, systemic hypertension, or diabetes mellitus. Multiple regression analysis confirmed the following baseline predictive factors for an increase in visual acuity: low BCVA (p  0.1). Intravitreal injections of bevacizumab in a routine clinical setting effectively improved and stabilized BCVA in CRVO. Our large multicenter study identified initial BCVA, baseline CRT, and pre-treatment as prognostic factors for visual improvement.

  3. Effect of photodynamic therapy combined with intravitreal ranibizumab injection on circumscribed choroidal hemangioma

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    Yu-Shun Xue

    2017-02-01

    Full Text Available AIM:To investigate the effect of photodynamic therapy(PDTcombined with intravitreal injection of ranibizumab on circumscribed choroidal hemangioma(CCH. METHODS:A retrospective study was performed for 6 eyes(6 casesdiagnosed as CCH. Before treatment, OCT examination showed macular cystoid edema and retinal neurepithelium layer detachment in all patients. All patients underwent photodynamic therapy, then intravitreal injection of ranibizumab 0.5mg(0.05mLwere administered at 48h after PDT. The best corrected visual acuity(BCVA, examination of the ocular fundus, fundus photography, fluorescence fundus angiography(FFA, indocyanine green angiography(ICGA, eye B ultrasonic and optical coherence tomography(OCTwere performed respectively at 1, 3 and 6mo after treatment. RESULTS:The patients were followed up for 4 to 10mo, the final vision of follow-up increased than before, it was raised 7 lines. The images of ICGA revealed hypofluorescence or no leakage in focal area. Eye B ultrasonic showed that hemangioma shrunk or faded. The images of ICGA revealed macular region retinal reattached well and edema disappeared completely. Mean flow-up was 6mo postoperative. There had no evidence of recurrence. CONCLUSION:For CCH patients, hemangioma got smaller obviously by PDT. Intravitreal ranibizumab injection promote effusion absorption under the retina. Combining use of the two therapies could improve visual acuity in a short-term.

  4. Retinoblastoma Control With Primary Intra-arterial Chemotherapy: Outcomes Before and During the Intravitreal Chemotherapy Era.

    Science.gov (United States)

    Shields, Carol L; Alset, Adel E; Say, Emil Anthony T; Caywood, Emi; Jabbour, Pascal; Shields, Jerry A

    2016-09-01

    To compare outcomes of intra-arterial chemotherapy for retinoblastoma as primary therapy before (Era I) and during (Era II) the intravitreal chemotherapy era. In this retrospective interventional case series at a tertiary referral center, 66 eyes of 66 patients with untreated unilateral retinoblastoma were used. intraarterial chemotherapy into the ophthalmic artery under fluoroscopic guidance was performed using melphalan in every case, with additional topotecan as necessary. Intravitreal chemotherapy using melphalan and/or topotecan was employed as needed for active vitreous seeding. Globe salvage was measured based on the International Classification of Retinoblastoma (ICRB) during two eras. The two eras encompassed 2008 to 2012 (intraarterial chemotherapy alone, Era I) and 2012 to 2015 (intraarterial chemotherapy plus intravitreal chemotherapy, Era II). Over this period, there were 66 patients with unilateral untreated retinoblastoma treated with primary intra-arterial chemotherapy. A comparison of features (Era I vs Era II) revealed no significant difference in mean patient age (24 vs 24 months), ICRB groups, mean largest tumor diameter (19 vs 17 mm), mean largest tumor thickness (10 vs 10 mm), vitreous seed presence (56% vs 59%), subretinal seed presence (67% vs 62%), retinal detachment (70% vs 66%), or vitreous hemorrhage (0% vs 5%). There was no significant difference in mean number of intra-arterial chemotherapy cycles (3 vs 3.1) or intraarterial chemotherapy dosages. Following therapy, there was a significant difference (Era I vs Era II) in the need for enucleation overall (44% vs 15%, P = .012), especially for group E eyes (75% vs 27%, P = .039). Four of the eyes that initiated therapy in Era I later required intravitreal chemotherapy during Era II. The enucleation rate was 0% for groups B and C in both eras and non-significant for group D (23% vs 13%). There were no patients with stroke, seizure, limb ischemia, extraocular tumor extension, secondary

  5. Treatment of experimental autoimmune uveoretinitis with intravitreal injection of infliximab encapsulated in liposomes.

    Science.gov (United States)

    Zhang, Rui; Qian, Jiang; Li, Xiaofeng; Yuan, Yifei

    2017-12-01

    To evaluate the safety and efficacy of intravitreal injection of liposomes encapsulating infliximab in experimental autoimmune uveoretinitis (EAU) rats. Liposomes containing infliximab were prepared and characterised for mean particle size, entrapment efficiency, polydispersity index (PDI) and zeta potential. In vitro release profile and the stability of infliximab-lip were evaluated. EAU rats were intravitreally injected with saline, infliximab, infliximab-lip or unloaded liposomes. Clinical signs and ocular histological sections were graded. Infliximab concentrations were determined with competitive ELISA. Safety of the intravitreal injections was evaluated by electroretinography (ERG) and histopathological examination. Retinal biodistribution and clearance of rhodamine-conjugated liposomes containing infliximab were evaluated with a laser scanning confocal microscope. The mean particle size of infliximab liposomes was 351.3±58 nm and entrapment efficiency was 90.65%±2.68%. PDI and zeta potential of infliximab liposomes were 0.386 and -20.8±9.78 mV, respectively. Stability test data showed that the infliximab-lip was stable for 60 days at room temperature. In EAU rats, intravitreal injection of infliximab and infliximab-lip greatly reduced intraocular inflammation determined by clinical scores and histopathological analyses (n=4). The mean concentrations of infliximab decreased quickly in infliximab injection group and were lower than those in infliximab-lip injection group (n=4 eyes, pinfliximab-lip in ERG (n=4 rats, p>0.05) and histopathological sections compared with normal rats. Confocal microscopy showed that fluorescent liposomes were observed in almost every layer of the retina and remained detectable for >30 days after injection. Intravitreal injection of liposomal infliximab can prolong the persistence of the drug in vitreous body and demonstrated a satisfactory safety and significant therapeutic potentials in EAU. The use of biodegradable

  6. Evolution of endothelial keratoplasty.

    Science.gov (United States)

    Price, Francis W; Price, Marianne O

    2013-11-01

    Endothelial keratoplasty has evolved into a popular alternative to penetrating keratoplasty (PK) for the treatment of endothelial dysfunction. Although the earliest iterations were challenging and were not widely adopted, the iteration known as Descemet stripping endothelial keratoplasty (DSEK) has gained widespread acceptance. DSEK combines a simplified technique for stripping dysfunctional endothelium from the host cornea and microkeratome dissection of the donor tissue, a step now commonly completed in advance by eye bank technicians. Studies show that a newer endothelial keratoplasty iteration, known as Descemet membrane endothelial keratoplasty (DMEK), provides an even faster and better visual recovery than DSEK does. In addition, DMEK significantly reduces the risk of immunologic graft rejection episodes compared with that in DSEK or in PK. Although the DMEK donor tissue, consisting of the bare endothelium and Descemet membrane without any stroma, is more challenging to prepare and position in the recipient eye, recent improvements in instrumentation and surgical techniques are increasing the ease and the reliability of the procedure. DSEK successfully mitigates 2 of the main liabilities of PK: ocular surface complications and structural problems (including induced astigmatism and perpetually weak wounds), whereas DMEK further mitigates the 2 principal remaining liabilities of PK: immunologic graft reactions and secondary glaucoma from prolonged topical corticosteroid use.

  7. Massive choroidal hemorrhage after intravitreal administration of bevacizumab (Avastin® for AMD followed by controlateral sympathetic ophthalmia

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    Dimitrios Brouzas

    2009-08-01

    Full Text Available Dimitrios Brouzas, Chryssanthi Koutsandrea, Marilita Moschos, Spiros Papadimitriou, Ioannis Ladas, Michael Apostolopoulos1st Eye Department , University of Athens, Athens, GreecePurpose: To report a severe ocular complication initiated ten days after intravitreal administration of bevacizumab (Avastin®, in a patient with exudative age-related macular degeneration (AMD.Patients and method: Case report.Results: Ten days after intravitreal injection of 1.25 mg Avastin®, the patient manifested acute loss of vision with excruciating pain. An extensive choroidal detachment was evident in close contact with the lens, which necessitated an emergency sclerotomy with reconstruction of the anterior chamber. Four months later, the eye proceeded to phthisis bulbi. Five months after the injection, the patient complained of mild pain, photophobia, and visual acuity deterioration from the fellow eye. The diagnosis of sympathetic ophthalmia was suggested and treated with intravitreal injections of triamcinolone acetonide every three months with good response, complicated by elevation of intraocular pressure which we managed with Ahmet valve implantation.Conclusion: Serious ocular complications after intravitreal of Avastin® can not be excluded, including massive choroidal hemorrhage and sympathetic ophthalmia of the fellow eye.Keywords: Avastin® complication, intravitreal injection, choroidal detachment, Phthisis bulbi, sympathetic ophthalmia

  8. Effect of laser photocoagulation and bevacizumab intravitreal in proliferative diabetic retinopathy: review on biomarkers of oxidative stress

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    Andi A. Victor

    2014-06-01

    Full Text Available Background: This study was aimed to compare the effect of laser photocoagulation (LF, intravitreal bevacizumab (IVB and combined treatments on biomarkers of oxidative stress such as aldehhyde dehidrogenase (ALDH, malondialdehyde (MDA level, superoxide dismutase (SOD activities, and vitreal vascular endothelial growth factor (VEGF on proliferative diabetic retinopathy (DR patients.Methods: In this single blind randomized clinical trial, 72 eyes from 69 cases of proliferative DR in Cipto Mangunkusumo Hospital between February 2011 - June 2013 were randomized into 4 groups : 1 control (n = 18; 2 LF pre-vitrectomy (n = 18; 3 IVB pre-vitrectomy (n = 18; and 4 combined IVB and LF pre-vitrectomy (n = 18. One-way ANOVA was used to compare oxidative stress parameters in the four groups.Results: There were no statistically significant differences in the average plasma ALDH activity (0.034 ± 0.02; 0.027 ± 0.02; 0.025 ± 0.02; 0.031 ± 0.11 IU/mg protein; p = 0.66, vitreal MDA level (1.661 ± 1.21; 1.557 ± 1.32; 1.717 ± 1.54; 1.501 ± 1.09 nmol/mL; p = 0.96 and SOD activity (0.403 ± 0.50; 0.210 ± 0.18; 0.399 ± 0.49; 0.273 ± 0.32 U/mL; p = 0.38 among these four groups, respectively. However, the VEGF vitreal level (pg/mL showed a statistically significant difference (0.356 ± 0.60; 0.393 ± 0.45; 0.150 ± 0.24; 0.069 ± 0.13; p = 0.05. The VEGF level in combination group was five times lower than the control group (p = 0.05.Conclusion: Combined treatments of DR by IVB and LF were correlated with lower vitreal MDA and plasma VEGF level, but did not have any effect on plasma ALDH and vitreal SOD in proliferative DR. Combined treatments with IVB and LF are recommended for the management of proliferative DR patients.  

  9. Infections and endothelial cells

    NARCIS (Netherlands)

    Keller, Tymen T.; Mairuhu, Albert T. A.; de Kruif, Martijn D.; Klein, Saskia K.; Gerdes, Victor E. A.; ten Cate, Hugo; Brandjes, Dees P. M.; Levi, Marcel; van Gorp, Eric C. M.

    2003-01-01

    Systemic infection by various pathogens interacts with the endothelium and may result in altered coagulation, vasculitis and atherosclerosis. Endothelium plays a role in the initiation and regulation of both coagulation and fibrinolysis. Exposure of endothelial cells may lead to rapid activation of

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

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    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.

  11. Toxoplasma gondii: an atypical presentation of toxoplasma as optic disc swelling and hemispherical retinal vein occlusion treated with intravitreal clindamycin.

    Science.gov (United States)

    Wong, Roger; dell'Omo, Roberto; Marino, Michele; Hussein, Badrul; Okhravi, Narciss; Pavesio, Carlos E

    2009-06-01

    To present a case of toxoplasmosis with an atypical presentation and treated successfully with intravitreal clindamycin. A young Brazilian woman presented with panuveitis and disc swelling with associated hemispheric vascular occlusion in one eye. The presumed diagnosis was of a papillitis with vasculitis due to an unknown inflammatory condition. Following treatment with intravenous corticosteroids, macular star appeared 1 week after treatment. On the 2nd week, a focus of retinitis appeared, and the patient was started on antitoxoplasma treatment. This was poorly tolerated, and the patient was injected with intravitreal clindamycin. Inflammation eventually settled and an organized lesion typical of toxoplasma chorioretinitis was observed. We describe an unusual presentation and the detrimental effects of toxoplasmosis in an otherwise immunocompetent subject. As the patient was not tolerating systemic antitoxoplasma treatment, intravitreal injection was administered and proved to be effective and well tolerated.

  12. Contralateral eye-to-eye comparison of intravitreal ranibizumab and a sustained-release dexamethasone intravitreal implant in recalcitrant diabetic macular edema

    Directory of Open Access Journals (Sweden)

    Thomas BJ

    2016-08-01

    Full Text Available Benjamin J Thomas, Yoshihiro Yonekawa, Jeremy D Wolfe, Tarek S Hassan Department of Vitreoretinal Surgery, William Beaumont Hospital, Royal Oak, MI, USA Objective: To compare the effects of intravitreal ranibizumab (RZB or dexamethasone (DEX intravitreal implant in cases of recalcitrant diabetic macular edema (DME.Methods: Retrospective, interventional study examining patients with symmetric bilateral, center-involved DME recalcitrant to treatment with RZB, who received DEX in one eye while the contralateral eye continued to receive RZB every 4–5 weeks for a study period of 3 months.Results: Eleven patients (22 eyes were included: mean logarithm of the minimal angle of resolution (logMAR visual acuity (VA for the DEX arm improved from 0.415 (standard deviation [SD] ±0.16 to 0.261 (SD ±0.18 at final evaluation, and mean central macular thickness (CMT improved from 461 µm (SD ±156 to 356 µm (SD ±110; net decrease: 105 µm, P=0.01. Mean logMAR VA for the RZB arm improved from 0.394 (SD ±0.31 to 0.269 (SD ±0.19 at final evaluation. Mean CMT improved from 421 µm (SD ±147 to 373 µm (SD ±129; net decrease: 48 µm, P=0.26.Conclusion: A subset of recalcitrant DME patients demonstrated significant CMT reduction and VA improvement after a single DEX injection. Keywords: aflibercept, bevacizumab, central macular thickness, macular edema, dexamethasone implant, diabetic macular edema, diabetic retinopathy, ranibizumab

  13. Comparison of intravitreal bevacizumab with intravitreal triamcinolone acetonide for treatment of cystoid macular edema secondary to retinal vein occlusion: a Meta-analysis.

    Science.gov (United States)

    Sun, Yan; Qu, Yi

    2015-01-01

    To compare the effects of intravitreal injection of bevacizumab (IVB) with intravitreal triamcinolone acetonide (IVTA) on the treatment of cystoid macular edema (CME) secondary to retinal vein occlusion (RVO). A literature search was conducted using PubMed, the Cochrane Central Register of Controlled Trials, Web of Science and the Chinese Biomedical Database. The comparison was divided into two groups, group 1 conducted comparison in branch RVO (BRVO) or central RVO (CRVO), group 2 conducted comparison in ischemic-RVO or nonischemic-RVO. Pooled mean differences (MDs) for changes in visual acuity (VA), central macular thickness (CMT) and intraocular pressure (IOP) were calculated in groups at 4, 12 and 24wk after treatment respectively. Eight studies comparing the efficacy of IVB with IVTA were included in the Meta-analysis. In group 1, in BRVO, significant difference was shown on the comparison of CMT at 24wk (MD, -45.66; 95% CI, -76.03 to -15.28; P=0.003), IVB was effective on BRVO for at least 24wk; no significant differences were found in the comparison of VA at each time points (P>0.05 respectively). In CRVO, no significant differences were found in the comparison of VA or CMT between IVB and IVTA at each time points (P>0.05, respectively). In group 2, in ischemic-RVO, significant differences were shown in the comparison of VA (MD, -0.28; 95% CI, -0.42 to -0.14; Pcomparison of VA or CMT between IVB and IVTA at each time points (P>0.05, respectively). The occurrence of high IOP was much lower in IVB group. This Meta-analysis suggested that IVB was effective in decreasing CMT in BRVO for at least 24wk, IVB is more effective on improving VA and reducing CMT in ischemic-RVO. IVB is more promising on RVO than IVTA.

  14. Intravitreous injection of AAV2-sFLT01 in patients with advanced neovascular age-related macular degeneration: a phase 1, open-label trial.

    Science.gov (United States)

    Heier, Jeffrey S; Kherani, Saleema; Desai, Shilpa; Dugel, Pravin; Kaushal, Shalesh; Cheng, Seng H; Delacono, Cheryl; Purvis, Annie; Richards, Susan; Le-Halpere, Annaig; Connelly, John; Wadsworth, Samuel C; Varona, Rafael; Buggage, Ronald; Scaria, Abraham; Campochiaro, Peter A

    2017-07-01

    Long-term intraocular injections of vascular endothelial growth factor (VEGF)-neutralising proteins can preserve central vision in many patients with neovascular age-related macular degeneration. We tested the safety and tolerability of a single intravitreous injection of an AAV2 vector expressing the VEGF-neutralising protein sFLT01 in patients with advanced neovascular age-related macular degeneration. This was a phase 1, open-label, dose-escalating study done at four outpatient retina clinics in the USA. Patients were assigned to each cohort in order of enrolment, with the first three patients being assigned to and completing the first cohort before filling positions in the following treatment groups. Patients aged 50 years or older with neovascular age-related macular degeneration and a baseline best-corrected visual acuity score of 20/100 or less in the study eye were enrolled in four dose-ranging cohorts (cohort 1, 2 × 10 8 vector genomes (vg); cohort 2, 2 × 10 9 vg; cohort 3, 6 × 10 9 vg; and cohort 4, 2 × 10 10 vg, n=3 per cohort) and one maximum tolerated dose cohort (cohort 5, 2 × 10 10 vg, n=7) and followed up for 52 weeks. The primary objective of the study was to assess the safety and tolerability of a single intravitreous injection of AAV2-sFLT01, through the measurement of eye-related adverse events. This trial is registered with ClinicalTrials.gov, number NCT01024998. 19 patients with advanced neovascular age-related macular degeneration were enrolled in the study between May 18, 2010, and July 14, 2014. All patients completed the 52-week trial period. Two patients in cohort 4 (2 × 10 10 vg) experienced adverse events that were possibly study-drug related: pyrexia and intraocular inflammation that resolved with a topical steroid. Five of ten patients who received 2 × 10 10 vg had aqueous humour concentrations of sFLT01 that peaked at 32·7-112·0 ng/mL (mean 73·7 ng/mL, SD 30·5) by week 26 with a slight decrease to

  15. Combination systemic and intravitreal antiviral therapy in the management of acute retinal necrosis syndrome (an American Ophthalmological Society thesis).

    Science.gov (United States)

    Flaxel, Christina J; Yeh, Steven; Lauer, Andreas K

    2013-09-01

    To compare the outcomes of combination systemic and intravitreal antiviral therapy vs systemic antiviral therapy alone for treating acute retinal necrosis syndrome (ARN). We hypothesize that combination therapy might result in superior visual acuity (VA) and retinal detachment (RD) outcomes vs traditional systemic antiviral therapy alone. A retrospective, interventional, comparative single-center study of patients with ARN. We reviewed demographic data, herpesvirus diagnoses, polymerase chain reaction (PCR) results, VA, RD, and the use of systemic and intravitreal antiviral therapy. Outcome measures included VA improvement by 2 or more lines, severe visual loss, VA ≤20/200, and RD. We studied 29 eyes of 24 patients, treated from 1987 through 2009. Mean age was 42.6 years and mean follow-up was 44.0 months. Twelve patients (14 eyes) were treated with combined systemic and intravitreal antiviral therapy and 12 patients (15 eyes) with systemic therapy alone. Kaplan-Meier survival analysis revealed that patients receiving combination intravitreal and systemic antiviral therapy were more likely to have VA improved by 2 lines or greater (P=.006). Patients receiving combination therapy also showed a decreased incidence of progression to severe visual loss (0.13/patient-years [PY]) compared to patients receiving systemic therapy alone (0.54/PY, P=.02) and had decreased incidence of RD (0.29/PY vs 0.74/PY, P=.03). Combination oral and intravitreal antiviral therapy may improve visual and functional outcomes in patients with ARN. Clinicians should consider prompt administration of combination systemic and intravitreal antiviral therapy as first-line treatment for patients with clinical features of ARN.

  16. Effect of intravitreal triamcinolone acetonide injection on central macular thickness in diabetic patients having phacoemulsification.

    Science.gov (United States)

    Ahmadabadi, Hooshang Faghihi; Mohammadi, Massood; Beheshtnejad, Hooshang; Mirshahi, Ahmad

    2010-06-01

    To assess the effect of intraoperative intravitreal injection of triamcinolone acetonide on the central macular thickness, visual outcomes, and development of cystoid macular edema (CME) after phacoemulsification in diabetic patients. Farabi Eye Hospital, Tehran, Iran. In this prospective randomized controlled study, patients with diabetes were randomly assigned to a treatment group, which received an intravitreal injection of triamcinolone acetonide at the end of phacoemulsification, and a control group, which had routine phacoemulsification. Visual acuity, center-point thickness, central 1.0 mm subfield mean thickness, CME development, and diabetic retinopathy progression were compared between the 2 groups 1, 3, and 6 months postoperatively. The treatment group comprised 20 eyes and the control group, 21 eyes. There was no statistically significant difference between the 2 groups in the mean corrected distance visual acuity at any follow-up examination (P>.05). The mean change in center-point thickness and central 1.0 mm subfield mean thickness was statistically significantly lower in the treatment group than in the control group at all follow-up visits (P<.05). Four eyes in the control group and no eye in the treatment group developed CME (P = .059). Three eyes (15%) in the treatment group developed an intraocular pressure rise that was managed by topical medication. Intravitreal injection of triamcinolone reduced the amount of increase in center-point thickness and central 1.0 mm subfield mean thickness after phacoemulsification in eyes of diabetic patients. Although it also reduced the incidence of CME, it had no effect on visual acuity gain. (c) 2010 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

  17. Pharmacokinetics and tolerance study of intravitreal injection of dexamethasone-loaded nanoparticles in rabbits

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    Linhua Zhang

    2009-09-01

    Full Text Available Linhua Zhang1, Yue Li2, Chao Zhang1, Yusheng Wang2, Cunxian Song11Institute of Biomedical Engineering, Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, China; 2Department of Ophthalmology, Institute of Ophthalmology of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi’an, ChinaAbstract: The aim of the study was to investigate the tolerance and pharmacokinetics of dexamethasone (DEX-loaded poly(lactic acid–co-glycolic acid nanoparticles (DEX-NPs in rabbits after intravitreal injection. The DEX-NPs were prepared and characterized in terms of morphology, particle size and size distribution, encapsulation efficiency, and in vitro release. Ophthalmic investigations were performed, including fundus observation and photography, intraocular pressure measurement, and B-scan ocular ultrasonography. There were no abnormalities up to 50 days after administration of DEX-NPs in rabbits. The DEX concentrations in plasma and the ocular tissues such as the cornea, aqueous humor, lens, iris, vitreous humor, and chorioretina were determined by high-pressure liquid chromatography. The DEX-NPs maintained a sustained release of DEX for about 50 days in vitreous and provided relatively constant DEX levels for more than 30 days with a mean concentration of 3.85 mg/L-1. Based on the areas under the curve, the bioavailability of DEX in the experimental group was significantly higher than that in the control group injected with regular DEX. These results suggest that intravitreal injection of DEX-NPs lead to a sustained release of DEX with a high bioavailability, providing a basis for a novel approach to the treatment of posterior segment diseases.Keywords: dexamethasone, nanoparticles, intravitreal injection, pharmacokinetics

  18. Effect of intravitreal bevacizumab on diabetic macular edema with hard exudates

    Science.gov (United States)

    Jeon, Sohee; Lee, Won Ki

    2014-01-01

    Background We evaluated the efficacy of intravitreal bevacizumab on diabetic macular edema with subfoveal and perifoveal hard exudates. Materials and methods Eleven eyes (11 patients) exhibiting diabetic macular edema with subfoveal and perifoveal hard exudates were included in this prospective, nonrandomized interventional pilot study. All patients were treated with monthly scheduled intravitreal bevacizumab injections for 6 months. Changes in the Early Treatment Diabetic Retinopathy Study best corrected visual acuity, amount of hard exudates on fundus photography, and macular edema detected by central subfield thickness on spectral domain optical coherence tomography after six serial injections, were assessed. The amount of hard exudates at each visit was evaluated as pixels in fundus photography, using an Adobe Photoshop program. Results Ten of 11 patients completed follow-up. The mean Early Treatment Diabetic Retinopathy Study best corrected visual acuity was 59.9±5.7 letters (Snellen equivalent, 20/63) at baseline evaluation. The best corrected visual acuity exhibited no significant difference at month 6 compared with at baseline (57.9±6.0 letters or 20/70 at month 6; P=0.085). At month 6, mean central subfield thickness decreased from 370.4±56.5 to 334.6±65.0 μm (P=0.009). The mean amount of hard exudates increased from 4467.1±2736.1 to 6592.4±2498.3 pixels at month 6 (P=0.022). No serious adverse events occurred. Conclusion Continuous intravitreal bevacizumab was found to have no benefit in visual acuity and amount of hard exudates, despite the improvement of macular edema at 6 months. PMID:25143708

  19. Results of Intravitreal Ranibizumab Treatment for Exudative Age-Related Macular Degeneration

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    Umut Karaca

    2012-01-01

    Full Text Available Pur po se: To evaluate the efficacy and safety of intravitreal ranibizumab injection for exudative age-related macular degeneration. Ma te ri al and Met hod: In this study, we included forty-eight eyes of 43 age-related macular degeneration patients followed for at least twelve months. Mean age was 73.65±8.93 years and mean follow-up time was 14.2 months. All patients received three consecutive monthly intravitreal ranibizumab injections and then were followed up with clinical examination and optic coherence tomography monthly. Re-injection was executed as needed. Re sults: Twenty patients were male (46.5% and twenty-three patients were female (53.5%. The average number of ranibizumab injection was 3.7 (3-7 per eye. Twenty-six lesions (54.2% were classic (predominantly and minimally and twenty-two (45.8% were occult. Mean best-corrected visual acuity was 46.8 letters with ETDRS chart at the initial examination and 55.5 letters at twelfth month. Mean central foveal thickness decreased from 320 microns to 269 microns. There was a statistically significant improvement in visual acuity and central foveal thickness. On the other hand, this improvement was not significant between lesion types. During follow-up, there were no systemic or serious ocular complications determined. Dis cus si on: Intravitreal ranibizumab injection is safe and effective, both anatomically and functionally, for age-related macular degeneration. (Turk J Ophthalmol 2012; 42: 25-9

  20. Real-world evidence of safety profile of intravitreal bevacizumab (Avastin) in an Indian scenario.

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    Jain, Prashant; Sheth, Jay; Anantharaman, Giridhar; Gopalakrishnan, Mahesh

    2017-07-01

    The purpose of this study was to evaluate the safety profile of intravitreal bevacizumab (Avastin) as an off-label pharmacotherapeutic agent for various ocular conditions. Retrospective analysis was carried out on 3806 injections of 1761 patients that were administered with intravitreal bevacizumab injection at a tertiary eye care center in India. The injections were administered on a pro re nata basis for various indications such as age-related macular degeneration (AMD), diabetic macular edema (DME), and retinal vein occlusion (RVO). The mean age of the patients was 61.8 ± 11.59 years. A total of 59.2% of the patients were men and 40.8% women. The most common indications for which the injection was administered were DME (27.5%), AMD (26%), and branch RVO (12.3%). Among the ocular side effects, endophthalmitis was seen in three eyes (0.08%), retinal breaks in none of the eyes whereas 35 eyes had a rise in intraocular pressure (IOP) >21 mmHg (0.9%). Preexisting glaucoma was present in four eyes while remaining 31 eyes did not have any history of glaucoma. IOP rise was significantly more in eyes with preexisting glaucoma as compared to nonglaucomatous eyes (P = 0.04). No systemic adverse events were noted in our study population. Our study provides real-world evidence regarding the safety profile of intravitreal bevacizumab (Avastin). These data suggest that bevacizumab is a safe and economical pharmacotherapeutic agent that can be administered for a variety of ocular disorders. Analyzing the safety of bevacizumab is necessary for a developing country like India as the majority of the population cannot afford the costly ranibizumab as compared to bevacizumab for ocular healthcare.

  1. Phacoemulsification with intravitreal bevacizumab injection in diabetic patients with macular edema and cataract.

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    Akinci, Arsen; Batman, Cosar; Ozkilic, Ersel; Altinsoy, Ali

    2009-01-01

    The purpose of this study was to evaluate the results of phacoemulsification with intravitreal bevacizumab injection in patients with diabetic clinically significant macular edema and cataract. The records of 31 patients with diabetic clinically significant macular edema and cataract, which would interfere with macular laser photocoagulation, who have undergone phacoemulsification with intravitreal injection of 1.25 mg bevacizumab were retrospectively evaluated. All patients had undergone focal or modified grid laser photocoagulation 1 month after the surgery. All patients were evaluated by spectral optical coherence tomography/optical coherence tomography SLO before and 1 and 3 months after the surgery beyond complete ophthalmologic examination. The best-corrected visual acuity (BCVA) levels and central macular thickness (CMT) recorded at the first and third months after the surgery were compared with the initial values. Paired samples t test was used for statistical analysis. The mean initial BCVA was 0.10 +/- 0.04 (range, 0.05-0.2). The mean BCVA at the first and third months after the surgery were 0.47 +/- 0.16 (standard deviation) (range, 0.2-0.5) and 0.51 +/- 0.12 (standard deviation) (range, 0.3-0.6), respectively. The BCVA level recorded at the first and third months after the surgery were significantly higher than the initial BCVA (P = 0.004). The mean initial CMT was 387.5 +/- 109.5 microm. The mean CMT at the first and third months after the surgery were 292.7 +/- 57.2 and 275.5 +/- 40.3. The CMT recorded at the first and third months after the surgery were significantly lower than the initial CMT (P < 0.001, P < 0.001). Phacoemulsification with intravitreal injection of bevacizumab provides improvement in clinically significant macular edema with a gain in BCVA in patients with diabetes with clinically significant macular edema and cataract.

  2. Intravitreal NGF administration counteracts retina degeneration after permanent carotid artery occlusion in rat

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    De Sordi Nadia

    2009-05-01

    Full Text Available Abstract Background The neurotrophin nerve growth factor (NGF is produced by different cell types in the anterior and posterior eye, exerting a neuroprotective role in the adult life. The visual system is highly sensitive to NGF and the retina and optic nerve provides suitable subjects for the study of central nervous system degeneration. The model of bilateral carotid occlusion (two-vessel occlusion, 2VO is a well-established model for chronic brain hypoperfusion leading to brain capillary pathology, to retina and optic nerve degeneration. In order to study if a single intravitreal injection of NGF protects the retina and the optic nerve from degeneration during systemic circulatory diseases, we investigated morphological and molecular changes occurring in the retina and optic nerve of adult rats at different time-points (8, 30 and 75 days after bilateral carotid occlusion. Results We demonstrated that a single intravitreal injection of NGF (5 μg/3 μl performed 24 hours after 2VO ligation has a long-lasting protective effect on retina and optic nerve degeneration. NGF counteracts retinal ganglion cells degeneration by early affecting Bax/Bcl-2 balance- and c-jun- expression (at 8 days after 2VO. A single intravitreal NGF injection regulates the demyelination/remyelination balance after ischemic injury in the optic nerve toward remyelination (at 75 days after 2VO, as indicated by the MBP expression regulation, thus preventing optic nerve atrophy and ganglion cells degeneration. At 8 days, NGF does not modify 2VO-induced alteration in VEFG and related receptors mRNA expression. Conclusion The protective effect of exogenous NGF during this systemic circulatory disease seems to occur also by strengthening the effect of endogenous NGF, the synthesis of which is increased by vascular defect and also by the mechanical lesion associated with NGF or even vehicle intraocular delivery.

  3. Results of the treatment with intravitreal bevacizumab injection in branch retinal vein occlusion

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    Osman Sayýn

    2017-06-01

    Material and Method: The files of patients who had macular edema caused by branch retinal vein occlusion and who were applied intravitreal bevacizumab injection were studied retrospectively. Visual acuity (logMAR in follow-ups of the patients before and after the injection and the macular thickness values of the quadrant of the occlusion were recorded and the effect of intravitreal bevacizumab on these parameters were analyzed. Results: 24 eyes of 24 patients, 17 of which are male and 7 of which are female, were included in the study. The mean age of the patients were 59.1±7.7. The mean visual acuity prior to the injection was determined to be 0.7±0.5 logMAR, and the mean macular thickness value 489.7±129.6 μm. The mean injection number applied was 1.5±0.7. The mean follow-up time after the injection was 3.5±2.7 months. The mean macular thickness was determined to be 393.1±5.7 μm and mean visual acuity was 0.5±0.1 logMAR in the 1st month. In the last follow-ups of the patients, the mean visual acuity was 0.26±0.28 logMAR and the mean macular thickness value was 317.4±71.5 μm. The increase in visual acuity and decrease in macular thickness between first and last control after the injection was found statistically significant. (p<0.001. Conclusion: The intravitreal bevacizumab injection used in macular edema secondary to BRVO increases visual acuity and decreases macular thickness. [J Contemp Med 2017; 7(2.000: 143-148

  4. Predictors of 1-year visual outcome in neovascular age-related macular degeneration following intravitreal ranibizumab treatment

    DEFF Research Database (Denmark)

    Bloch, Sara Brandi; la Cour, Morten; Sander, Birgit

    2013-01-01

    Purpose: To describe predictors of visual outcome in patients treated with intravitreal ranibizumab for choroidal neovascularisation (CNV) in age-related macular degeneration (AMD). Methods: Retrospective review of 279 patients with CNV in AMD who fulfilled MARINA/ANCHOR study eligibility criteria...... and were treated with repeated intravitreal injections of ranibizumab 0.5 mg in routine clinical practice, beginning with three initial injections at 4-week intervals followed by individualized retreatment for the subsequent 9 months. Study parameters included best-corrected visual acuity (BCVA...

  5. Peristence of triamcinolone crystals after intra-vitreal injection: Benign crystalline hyaloidopathy

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    Rafik Zarifa

    2013-01-01

    Full Text Available We report a case of unusually long persistence of triamcinolone crystals after intra-vitreal injection. Crystals were noted on fundus examination predominantly confined to the posterior pole. Optical coherence tomography localized the crystals to the posterior hyaloidal surface. Over 6 years of follow-up the patient has retained good visual acuity and no observable changes in the retina. As the condition clinically resembles both crystalline maculopathy and asteroid hyalosis, we suggest the term ′drug-induced benign crystalline hyaloidopathy′.

  6. Pharmacokinetics of intravitreal glial cell line-derived neurotrophic factor: experimental studies in pigs

    DEFF Research Database (Denmark)

    Ejstrup, Rasmus; Kiilgaard, J F; Tucker, B A

    2010-01-01

    a retinal ganglion cell line (RGC5) bioassay. Indirect ophthalmoscopy, intraocular pressure assessment, and fundus photography were performed before enucleation. There was initial variability in the cGDNF, but after 24h GDNF was cleared in a monoexponential fashion with a half-life of 37 h (CL 33-43 h......The purpose of this study was to establish the intravitreal (ITV) pharmacokinetics of glial cell line-derived neurotrophic factor (GDNF) and observe possible complications after ITV injection. Twenty Danish landrace pigs and 34 eyes were included in the study; 30 were injected with 100 ng of GDNF...

  7. Pharmacokinetics of intravitreal glial cell line-derived neurotrophic factor: experimental studies in pigs

    DEFF Research Database (Denmark)

    Ejstrup, Rasmus; Kiilgaard, J F; Tucker, B A

    2010-01-01

    The purpose of this study was to establish the intravitreal (ITV) pharmacokinetics of glial cell line-derived neurotrophic factor (GDNF) and observe possible complications after ITV injection. Twenty Danish landrace pigs and 34 eyes were included in the study; 30 were injected with 100 ng of GDNF...... a retinal ganglion cell line (RGC5) bioassay. Indirect ophthalmoscopy, intraocular pressure assessment, and fundus photography were performed before enucleation. There was initial variability in the cGDNF, but after 24h GDNF was cleared in a monoexponential fashion with a half-life of 37 h (CL 33-43 h...

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

    Science.gov (United States)

    Sánchez-Castro, Grimelda Yuriana; Hitos-Fájer, Alejandra; Mendoza-Schuster, Erick; Velez-Montoya, Raul; Velasco-Barona, Cecilio Francisco

    2008-01-01

    We reported a 75-year-old diabetic man, who developed opacification and neovascularization of the posterior capsule after extracapsular cataract extraction and posterior chamber intraocular lens implantation. The patient was treated with two injections of 2.5 mg of intravitreal bevacizumab. The treatment produced an important regression of the posterior capsular new vessels, allowing us to perform a successful Nd:YAG capsulotomy, clearing the visual axis and improving the visualization of the posterior pole. Even though, best corrected visual acuity was 20/200 due to diabetic macular edema. PMID:19668770

  9. Intravitreal bevacizumab therapy for idiophatic juxtafoveolar retinal telangiectasis associated with serous macular detachment

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    Paulo Escarião

    2014-01-01

    Full Text Available The authors describe a 50-year-old woman with group 2 juxtafoveolar retinal telangiectasis and macular detachment treated with a single-dose of intravitreous bevacizumab injection. There was an improvement in her visual acuity, with a decrease in retinal thickness showed by the optical coherence tomography and fluorescein leakage in the angiography on follow-up visits. No adverse events were observed as a result of the treatment used. After one year of follow-up, the vision remained stable and macular detachment did not recur.

  10. Fellow Eye Macular Edema Improvement after Intravitreal Bevacizumab for Radiation Retinopathy

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    Isis A. S. Brito

    2015-01-01

    Full Text Available Radiation retinopathy (RR is a progressive, chronic condition directly related to the amount of radiation administered to the retina. We report a 37-year-old patient with medulloblastoma that was treated with external beam radiation and presented to us with bilateral cystoid macular edema. He was treated with monthly bevacizumab injections only in his worst seeing eye. There was a significant improvement in his fellow eye, with marked retinal thickness reduction. Therefore, we present clinical evidence of systemic absorption and fellow eye activity of the drug (bevacizumab. One must be aware of distant side effects after intravitreal injections.

  11. Pharmacokinetics of intravitreal 5-flurouracil prodrugs in silicone oil. Experimental studies in pigs

    DEFF Research Database (Denmark)

    Laugesen, Caroline S; Steffansen, Bente; Scherfig, Erik

    2005-01-01

    PURPOSE: To examine the in vivo pharmacokinetics of intravitreal 5-Fluorouracil (5-FU) following tamponade with 5-FU prodrug silicone oil formulations. METHOD: Two different alkoxycarbonyl 5-FU prodrugs denoted C12 and C18 were synthesized and formulated as silicone oil suspensions. A total of 26...... vitreal 5-FU never reached 1 microg/ml during the 7 days these experiments lasted. A mathematical model is presented that can explain the measured data if the clearance of 5-FU from the vitreous water phase follows first order kinetics with a half-life of 20 min. CONCLUSION: These experiments...

  12. Vascular endothelial growth factor trap-eye and trap technology: Aflibercept from bench to bedside.

    Science.gov (United States)

    Al-Halafi, Ali M

    2014-09-01

    Anti-vascular endothelial growth factor (VEGF) currently used to treat eye diseases have included monoclonal antibodies, antibody fragments, and an aptamer. A different method of achieving VEGF blockade in retinal diseases includes the concept of a cytokine trap. Cytokine traps technology are being evaluated for the treatment of various diseases that are driven by excessive cytokine levels. Traps consist of two extracellular cytokine receptor domains fused together to form a human immunoglobulin G (IgG). Aflibercept/VEGF trap-eye (VTE) is a soluble fusion protein, which combines ligand-binding elements taken from the extracellular components of VEGF receptors 1 and 2 fused to the Fc portion of IgG. This protein contains all human amino acid sequences, which minimizes the potential for immunogenicity in human patients. This review presents the latest data on VTE in regard to the pharmacokinetics, dosage and safety, preclinical and clinical experiences. Method of the literature search: A systematic search of the literature was conducted on PubMed, Scopus, and Google Scholar with no limitation on language or year of publication databases. It was oriented to articles published for VTE in preclinical and clinical studies and was focused on the pharmacokinetics, dosage and safety of VTE.

  13. [Strategies of Intravitreal Injections with Anti-VEGF: "Pro re Nata versus Treat and Extend"].

    Science.gov (United States)

    Hufendiek, K; Pielen, A; Framme, C

    2017-01-23

    The goal of this report is to provide a review on different strategies for the use of pro re nata (PRN) and treat and extend (T&E) regimens with intravitreal anti-VEGF agents (bevacizumab, ranibizumab or aflibercept) in patients with retinal diseases such as neovascular AMD, diabetic macular oedema and macular oedema due to retinal vein occlusion. The main focus is to present the effectiveness and visual outcomes of both PRN and T&E regimens in the main pivotal trials and studies based on currently available evidence. We also discuss the advantages and disadvantages of both regimens, as well as monitoring and treatment of the disease, including treatment intervals and injection frequency. Currently there is increasing interest in establishing a regimen which offers the best visual outcome with lower injection frequency, and with reduced treatment burden by individualising treatment intervals and minimising the number of clinic visits and costs. Studies have shown that the PRN regimens in a clinical setting are insufficient in assuring the best visual outcome. The PRN regime requires frequent clinic visits to monitor disease status and intravitreal treatment if needed in a reactive approach. Individualised T&E regimens can improve visual outcome and require fewer injections than those administered in a monthly regimen and fewer monitoring visits than those in a PRN regimen. Georg Thieme Verlag KG Stuttgart · New York.

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

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    Grimelda Yuriana Sánchez-Castro

    2008-10-01

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

  15. Intravitreal injection of the chimeric phage endolysin Ply187 protects mice from Staphylococcus aureus endophthalmitis.

    Science.gov (United States)

    Singh, Pawan Kumar; Donovan, David M; Kumar, Ashok

    2014-08-01

    The treatment of endophthalmitis is becoming very challenging due to the emergence of multidrug-resistant bacteria. Hence, the development of novel therapeutic alternatives for ocular use is essential. Here, we evaluated the therapeutic potential of Ply187AN-KSH3b, a chimeric phage endolysin derived from the Ply187 prophage, in a mouse model of Staphylococcus aureus endophthalmitis. Our data showed that the chimeric Ply187 endolysin exhibited strong antimicrobial activity against both methicillin-sensitive S. aureus and methicillin-resistant S. aureus (MRSA) strains, as evidenced by MIC determinations, reductions in turbidity, and disruption of biofilms. Moreover, exposure of S. aureus to Ply187 for up to 10 generations did not lead to resistance development. The intravitreal injection of chimeric Ply187 (at 6 or 12 h postinfection) significantly improved the outcome of endophthalmitis, preserved retinal structural integrity, and maintained visual function as assessed by electroretinogram analysis. Furthermore, phage lysin treatment significantly reduced the bacterial burden and the levels of inflammatory cytokines and neutrophil infiltration in the eyes. These results indicate that the intravitreal administration of a phage lytic enzyme attenuates the development of bacterial endophthalmitis in mice. To the best of our knowledge, this is the first study demonstrating the therapeutic use of phage-based antimicrobials in ocular infections. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  16. Retinal toxicity of intravitreally injected plain and liposome formulation of fluconazole in rabbit eye

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    Velpandian Thirumurthy

    2006-01-01

    Full Text Available Purpose: Candidal endophthalmitis is a sight-threatening ocular infection that most frequently occurs as a complication of candidemia. Fluconazole has been effective against Candida albicans in various animal models. Our objective was to evaluate retinal toxicity of plain and liposome formulation of fluconazole at various dose levels after intravitreal injection. Materials and Methods: Twelve New Zealand albino rabbits weighing 2-2.5 kg were used. Two rabbits were used for every dose level. Liposome formulation containing 100 and 200 µg of fluconazole in sterile phosphate buffer solution and plain fluconazole at concentrations of 100, 200, 400 and 800 µg in 0.1 ml of sterile normal saline were injected intravitreally into the right eyes. The left eyes received 0.1 ml normal saline or 0.1 ml of liposome formulation without fluconazole. One week later, the animals were sacrificed, their eyes enucleated and processed for light microscopy and scanning electron microscopy. Results: It showed that plain fluconazole at a concentration of 100 µg and above caused retinal changes, with disorganization of the photoreceptor outer segments. However, liposome formulation of fluconazole (200 µg/0.1 ml did not show any significant microscopic changes of the retina. Conclusion: The liposome formulation decreased the retinal toxicity of fluconazole up to the studied concentration of 200 µg/0.1 ml.

  17. Intravitreal Triamcinolone Acetonide for Macular Edema in HLA-B27 Negative Ankylosing Spondylitis

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    M.M. Moschos

    2010-12-01

    Full Text Available We report a case of a human leukocyte antigen B27 (HLA-B27-negative patient with cystoid macular edema (CME and ankylosing spondylitis (AS after treatment with triamcinolone acetonide. The patient complained of deterioration of visual acuity of the right eye during the last 10 days. At presentation visual acuity of the right eye was 0.2, and the ophthalmic examination did not reveal any sign of active uveitis. Fluorescein angiography (FA and ocular coherent tomography (OCT showed CME. The left eye was normal with a visual acuity of 0.9. Eight weeks after intravitreal injection of triamcinolone acetonide, visual acuity improved to 0.8 and OCT revealed regression of macular edema. Six months later no recurrence was observed. Our case report indicates for the first time that CME may occur in AS independently of the presence of HLA-B27 and intraocular inflammation. Intravitreal use of triamcinolone acetonide can reduce macular edema and restore visual acuity.

  18. Clinical study of Conbercept intravitreal injection for the treatment of wet age-related macular degeneration

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    Xu-Ting He

    2015-09-01

    Full Text Available AIM: To observe the clinical curative effect of conbercept intravitreal injection for the treatment of wet age-related macular degeneration.METHODS: Sixty patients with wet age related macular degeneration were randomly divided into treatment group 30 cases and control group 30 cases according to the random number table. The treatment group was injected with Conbercept 0.05mL, the control group was injected with triamcinolone acetonide 0.1mL. The best corrected visual acuity(BCVAwas performed before and after 1d, 1 and 3mo after treatment, and the thickness of macular was detected by optical coherence tomography(OCT. The complications of patients were observed after 1d, 1 and 3mo,including inflammatory reaction, corneal edema, anterior chamber, high intraocular pressure, etc.RESULTS:In treatment group 1d, 1 and 3mo after treatment, eyesight was improved significantly better than the control group(PPCONCLUSION: Intravitreal injection of Conbercept in the treatment of wet age-related macular degeneration can improve the curative effect.

  19. MACULAR CHOROIDAL VOLUME CHANGES AFTER INTRAVITREAL BEVACIZUMAB FOR EXUDATIVE AGE-RELATED MACULAR DEGENERATION.

    Science.gov (United States)

    Palkovits, Stefan; Seidel, Gerald; Pertl, Laura; Malle, Eva M; Hausberger, Silke; Makk, Johanna; Singer, Christoph; Osterholt, Julia; Herzog, Sereina A; Haas, Anton; Weger, Martin

    2017-12-01

    To evaluate the effect of intravitreal bevacizumab on the macular choroidal volume and the subfoveal choroidal thickness in treatment naïve eyes with exudative age-related macular degeneration. The macular choroidal volume and the subfoveal choroidal thickness were measured using enhanced depth imaging optical coherence tomography. After a screening examination, each patient received 3 monthly intravitreal injections of 1.25 mg bevacizumab. One month after the third injection was a final assessment. Forty-seven patients with a mean age of 80 ± 6.4 years were included. The macular choroidal volume decreased significantly from median 4.1 mm (interquartile range 3.4-5.9) to median 3.9 mm (interquartile range 3.1-5.6) between the baseline and final examination (difference -0.46 mm, 95% confidence interval: -0.57 to 0.35, P macular choroidal volume at baseline and subfoveal choroidal thickness at baseline were not associated with the response to treatment. The macular choroidal volume and the subfoveal choroidal thickness decreased significantly after 3 monthly bevacizumab injections for exudative age-related macular degeneration.

  20. CLINICAL AND ELECTROPHYSIOLOGICAL EVALUATION AFTER INTRAVITREAL ZIV-AFLIBERCEPT FOR EXUDATIVE AGE-RELATED MACULAR DEGENERATION.

    Science.gov (United States)

    de Oliveira Dias, João Rafael; de Andrade, Gabriel Costa; Kniggendorf, Vinicius Ferreira; Novais, Eduardo Amorim; Maia, André; Meyer, Carsten; Watanabe, Sung Eun Song; Farah, Michel Eid; Rodrigues, Eduardo Büchele

    2017-08-01

    To evaluate the 6-month safety and efficacy of ziv-aflibercept intravitreal injections for treating exudative age-related macular degeneration. Fifteen patients with unilateral exudative age-related macular degeneration were enrolled. The best-corrected visual acuity was measured and spectral domain optical coherence tomography was performed at baseline and monthly. Full-field electroretinography and multifocal electroretinography were obtained at baseline and 4, 13, and 26 weeks after the first injection. All patients received three monthly intravitreal injections of ziv-aflibercept (1.25 mg) followed by as-needed treatment. Between baseline and 26 weeks, the mean logMAR best-corrected visual acuity improved (P = 0.00408) from 0.93 ± 0.4 (20/200) to 0.82 ± 0.5 (20/160) logarithm of the minimum angle of resolution, respectively; the central retinal thickness decreased significantly (P = 0.0007) from 490.3 ± 155.1 microns to 327.9 ± 101.5 microns; the mean total macular volume decreased significantly (P macular responses within the first central 15° showed significantly (P macular volume from baseline to 26 weeks. No retinal toxicity on full-field electroretinography or adverse events occurred during the follow-up period.

  1. Retinoblastoma frontiers with intravenous, intra-arterial, periocular, and intravitreal chemotherapy

    Science.gov (United States)

    Shields, C L; Fulco, E M; Arias, J D; Alarcon, C; Pellegrini, M; Rishi, P; Kaliki, S; Bianciotto, C G; Shields, J A

    2013-01-01

    In this report, we explore retinoblastoma diagnostic accuracy and review chemotherapy alternatives for retinoblastoma using intravenous, intra-arterial, periocular, and intravitreal routes. A review of 2775 patients referred for management of retinoblastoma, disclosed 78% with confirmed retinoblastoma and 22% with simulating lesions, termed pseudoretinoblastomas. Children ≤2 years old showed leading pseudoretinoblastomas of persistent fetal vasculature, Coats disease, and vitreous haemorrhage, whereas those >5 years showed simulators of Coats, toxocariasis, and familial exudative vitreoretinopathy. The diagnosis of retinoblastoma should be established before planning therapeutic strategy. Chemotherapy strategy depends on tumour laterality and stage of disease. If bilateral retinoblastoma, intravenous chemotherapy (IVC) is important as first-line therapy for control of intraocular disease, prevention of metastasis, and reduction in prevalence of pinealoblastoma and long-term second malignant neoplasms. Bilateral groups D and E retinoblastoma receive additional subtenon's carboplatin boost for improved local control. If unilateral disease is present, then intra-arterial chemotherapy (IAC) is often considered. IAC can be salvage therapy following chemoreduction failure. Unilateral retinoblastoma of groups D and E are managed with enucleation or globe-conserving IVC and/or IAC. Intravitreal chemotherapy is cautiously reserved for recurrent vitreous seeds following other therapies. In conclusion, the strategy for retinoblastoma management with chemotherapy depends on tumour laterality and stage of disease. Bilateral retinoblastoma is most often managed with IVC and unilateral retinoblastoma with IAC, but if advanced stage, combination IVC plus IAC or enucleation. PMID:22995941

  2. Evaluation of toxicity after periocular and intravitreal administration of carboplatin in rabbit eyes

    Directory of Open Access Journals (Sweden)

    Denisa Darsová

    2011-01-01

    Full Text Available The aim of this study was to characterize the extent of toxicity of focal carboplatin administration and to identify the dose limiting toxicity in rabbit eyes depending on administered concentrations. New Zealand white male rabbits (n = 18 were treated with 1 of 3 regimens: a single periocular injection of 15 mg of carboplatin (group I, a single periocular injection of 30 mg of carboplatin (group II and a single transcorneal intravitreal injection of 0.05 mg of carboplatin (group III. Ophthalmologic examinations and vitreous samplings were performed under dissociative anaesthesia at regular intervals during next 2 (groups I and III or 3 (group II weeks. Carboplatin concentrations in vitreous samples were assessed by atomic absorption spectroscopy. At the end of experiments, all rabbit eyes were obtained for histopathologic examination. Clinical and histological evidence of toxicity was graded into four grades according to anatomical structures of the rabbit eye. The dose limiting toxicity was reached in group II after periocular injection of 30 mg of carboplatin and in group III after intravitreal injection of 0.05 mg of carboplatin. No systemic toxicity was observed in any group. Focal carboplatin administration may decrease systemic exposure to this cytotoxic drug in the retinoblastoma treatment. This moreover suggests that focal carboplatin administration is a promising approach and challenge for advanced retinoblastoma chemotherapy.

  3. DEPLOYMENT OF SIX SIGMA METHODOLOGY TO REDUCE COMPLICATIONS IN INTRAVITREAL INJECTIONS

    Directory of Open Access Journals (Sweden)

    İbrahim SAHBAZ

    2014-04-01

    Full Text Available The purpose of this study is to show how a private eye care center in Turkey initiated Six Sigma principles to reduce the number of complications encountered during and after intravitreal injections. Data were collected for 30-months. To analyse the complications among 229 injections administered on 106 patients, main tools of Six Sigma’s Define-Measure-Analyze-Improve-Control (DMAIC improvement cycle such as SIPOC table, Fishbone Diagram and, Failure, Mode and Effect Analysis were implemented. Sources and root causes of seven types of complications were identified and reported. For a successful intravitreal injection, experience of the retina specialist, attention of the retina specialist and patient’s ocular pathology were determined to be the “critical few” factors whereas, sterilization and hygiene, dosage of drug/agent and chemical properties of drug/agent were found to be the “trivial many”factors. The most frequently occuring and the complication with the highest hazard score was found to be subconjunctival haemorrhage. The process sigma level of the process was measured to be 3.2657. The surgical team concluded that six of the complications (out of seven should be significantly reduced by taking the necessary preventative measures.

  4. Biomechanical Properties of the Internal Limiting Membrane after Intravitreal Ocriplasmin Treatment.

    Science.gov (United States)

    Vielmuth, Franziska; Schumann, Ricarda G; Spindler, Volker; Wolf, Armin; Scheler, Renate; Mayer, Wolfgang J; Henrich, Paul B; Haritoglou, Christos

    2016-01-01

    To assess the stiffness of the human internal limiting membrane (ILM) and evaluate potential changes of mechanical properties following intravitreal ocriplasmin injection for vitreomacular traction. This is an interventional comparative case series of 12 surgically excised ILM specimens consecutively obtained from 9 eyes of 9 patients after unsuccessful pharmacologic vitreolysis with ocriplasmin. During the same time period, 16 specimens from 13 other eyes without ocriplasmin treatment were harvested during vitrectomy and served as controls. All patients presented with macular holes or vitreomacular traction and underwent vitrectomy with ILM peeling either with or without brilliant blue (BB) staining. All specimens were analyzed using atomic force microscopy with scan regions of 25 × 25 μm. In all specimens, both the retinal side and vitreal side of the ILM were analyzed. Atomic force microscopy revealed no significant differences in elasticity of ILM specimens removed from eyes with or without ocriplasmin treatment. Undulated areas of the retinal side presented stiffer than the vitreal side of the ILM. Topographical mapping of both the vitreal and retinal side of the ILM showed no apparent alteration of the morphology in ocriplasmin-treated eyes compared to untreated eyes. Staining with BB resulted in an increase of tissue stiffness. Intravitreal injection of ocriplasmin does not change biomechanical properties of the human ILM. There is no evidence of a potential enzymatic effect of ocriplasmin interfering with the stiffness of this basement membrane. © 2016 S. Karger AG, Basel.

  5. Intravitreal dexamethasone implant for cystoid macular edema and inflammation after scleral buckling.

    Science.gov (United States)

    Bonfiglio, Vincenza; Fallico, Matteo R; Russo, Andrea; De Grande, Vittorio; Longo, Antonio; Uva, Maurizio G; Reibaldi, Michele; Avitabile, Teresio

    2015-07-30

    Cystoid macular edema may occur following scleral buckling and therefore deteriorate the visual outcome. Inflammation may be the major causative factor in the development of postoperative cystoid macular edema. This case demonstrates the effectiveness of a dexamethasone implant as a treatment after the onset of choroidal inflammation and cystoid macular edema 6 months following scleral buckling and having visual acuity restored. A 59-year-old phakic woman treated with scleral buckling for macula-off retinal detachment presented 2 months after surgery with cystoid macular edema with choroidal inflammation. Optical coherence tomography and fluorescein angiography were performed. From the time of the diagnosis, the patient's condition had been nonresponsive to medical therapy and only partially responsive to sub-Tenon triamcinolone acetonide. An intravitreal implant with a sustained release of 0.7 mg dexamethasone was implanted. Following an intravitreal injection with a dexamethasone implant, the macular edema subsided completely and optical coherence tomography showed decreased foveal thickness from 510 μm to 220 μm. Choroidal fluorescein leakage disappeared. Best-corrected visual acuity improved from 0.70 to 0.20 logMAR, a condition maintained throughout the 6 months of follow-up. Cystoid macular edema and choroidal inflammation are difficult to treat, but the improvement observed in this case of post scleral buckling macular edema and choroidal inflammation showed how a dexamethasone implant proved to be useful during the 6-month follow-up.

  6. Myopic Choroidal Neovascularization

    DEFF Research Database (Denmark)

    Cheung, Chui Ming Gemmy; Arnold, Jennifer J; Holz, Frank G

    2017-01-01

    : In the United States, myopia affects approximately 34 million people (2010), and similar figures have been reported in Europe. Pathologic myopia (PM), a possible consequence of myopia, is estimated to affect up to 3% of the global population. One of the most serious complications of PM is myopic CNV, which...... often leads to a sudden onset but progressive decline in central vision and is associated with a poor prognosis unless treated. Furthermore, 35% of patients with myopic CNV develop bilateral disease in the fellow eye within 8 years. Although intravitreal anti-vascular endothelial growth factor (VEGF...

  7. Assessment of the effect of intravitreal triamcinolone acetonide on the chorioretinal and vitreous inflammatory reaction to cryotherapy in rabbits

    Directory of Open Access Journals (Sweden)

    Eugênio Santana de Figueirêdo

    2012-10-01

    Full Text Available PURPOSE: To evaluate the inflammatory response in the choroid, retina and vitreous in rabbit eyes underwent cryotherapy followed by intravitreal triamcinolone acetonide and to compare with those underwent cryotherapy followed by intravitreal injection of saline solution. METHODS: This is a prospective case-control study. Surgical procedures were performed in eleven rabbits. Two animals were excluded because they did not complete the postoperative period or had intraoperative or postoperative complications. All rabbits underwent superior temporal peritomy and transscleralcryotherapy in both eyes. After cryotherapy, animals received intravitreal injection of triamcinolone acetonide in one eye and saline solution in the fellow eye. Animals were sacrificed seven days after the procedure and their eyes were enucleated. Histological sections of eyeballs were prepared and the vitreous humor was aspirated. The count of inflammatory cells was performed by light microscopy. RESULTS: Histological sections of both eyes of nine rabbits were analyzed. Inflammatory cells were found only in the choroid. There was no statistically significant difference in the number of inflammatory cells between the two groups, regardless of cell type analyzed. CONCLUSION: This study showed no statistically significant difference between the use or absence of intravitreal triamcinolone acetonide in the inflammatory response to cryotherapy in rabbit eyes. Studies with larger samples are needed to confirm the trend of this paper.

  8. Comparison of Intravitreal Bevacizumab, Intravitreal Ranibizumab and Laser Photocoagulation for Treatment of Type 1 Retinopathy of Prematurity in Turkish Preterm Children.

    Science.gov (United States)

    Kabataş, Emrah Utku; Kurtul, Bengi Ece; Altıaylık Özer, Pınar; Kabataş, Naciye

    2017-07-01

    To evaluate effectiveness of treatment modalities, major complications and refractive errors in children who were treated with intravitreal bevacizumab (IVB), intravitreal ranibizumab (IVR) or laser photocoagulation (LP) for type 1 retinopathy of prematurity (ROP). Premature infants who underwent IVB monotherapy (Group 1), IVR monotherapy (Group 2) or LP (Group 3) for type 1 ROP and infants with spontaneously regressed ROP (Group 4) were included for the study. Major complications, recurrence rate, recurrence time, total retinal vascularization time and refractive errors at 18 months of corrected age (CA) were determined. Groups 1, 2, 3 and 4 included 24 eyes of 12 patients, 12 eyes of six patients, 72 eyes of 36 patients and 148 eyes of 74 patients, respectively. Recurrence of the disease occurred in two eyes of one patient in Group 1 at 52 weeks of postmenstrual age (PMA) and two eyes of one patient at 48 weeks of PMA in Group 2. In Group 3, disease did not regress after the first treatment in 10 eyes of five patients. The mean vascularization time in Group 1 was 73 ± 10.1 weeks of PMA and 61.8 ± 6.6 weeks of PMA in Group 2 (p = 0.027). Macular ectopia was seen in two eyes of one patient and exudative retinal detachment (ERD) occurred in two eyes of one patient in Group 3. Mean spherical equivalent was 1.49 ± 3.04 diopters (D) in Group 1, -1.79 ± 2.87D in Group 2, -1.27 ± 2.8 D in Group 3 and 1.52 ± 1.07 D in Group 4 at 18 months of CA. There was no significant difference in astigmatism values in all groups. IVB, IVR and LP are options that can successfully treat ROP. Myopia was observed to be the main refractive error in all treatment groups. Vascularization of the retina was completed later in the IVB group than in the IVR group.

  9. Endothelial RIG-I activation impairs endothelial function

    International Nuclear Information System (INIS)

    Asdonk, Tobias; Motz, Inga; Werner, Nikos; Coch, Christoph; Barchet, Winfried; Hartmann, Gunther; Nickenig, Georg; Zimmer, Sebastian

    2012-01-01

    Highlights: ► RIG-I activation impairs endothelial function in vivo. ► RIG-I activation alters HCAEC biology in vitro. ► EPC function is affected by RIG-I stimulation in vitro. -- Abstract: Background: Endothelial dysfunction is a crucial part of the chronic inflammatory atherosclerotic process and is mediated by innate and acquired immune mechanisms. Recent studies suggest that pattern recognition receptors (PRR) specialized in immunorecognition of nucleic acids may play an important role in endothelial biology in a proatherogenic manner. Here, we analyzed the impact of endothelial retinoic acid inducible gene I (RIG-I) activation upon vascular endothelial biology. Methods and results: Wild type mice were injected intravenously with 32.5 μg of the RIG-ligand 3pRNA (RNA with triphosphate at the 5′end) or polyA control every other day for 7 days. In 3pRNA-treated mice, endothelium-depended vasodilation was significantly impaired, vascular oxidative stress significantly increased and circulating endothelial microparticle (EMP) numbers significantly elevated compared to controls. To gain further insight in RIG-I dependent endothelial biology, cultured human coronary endothelial cells (HCAEC) and endothelial progenitor cells (EPC) were stimulated in vitro with 3pRNA. Both cells types express RIG-I and react with receptor upregulation upon stimulation. Reactive oxygen species (ROS) formation is enhanced in both cell types, whereas apoptosis and proliferation is not significantly affected in HCAEC. Importantly, HCAEC release significant amounts of proinflammatory cytokines in response to RIG-I stimulation. Conclusion: This study shows that activation of the cytoplasmatic nucleic acid receptor RIG-I leads to endothelial dysfunction. RIG-I induced endothelial damage could therefore be an important pathway in atherogenesis.

  10. Endothelial RIG-I activation impairs endothelial function

    Energy Technology Data Exchange (ETDEWEB)

    Asdonk, Tobias, E-mail: tobias.asdonk@ukb.uni-bonn.de [Department of Medicine/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Motz, Inga; Werner, Nikos [Department of Medicine/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Coch, Christoph; Barchet, Winfried; Hartmann, Gunther [Institute for Clinical Chemistry and Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Nickenig, Georg; Zimmer, Sebastian [Department of Medicine/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany)

    2012-03-30

    Highlights: Black-Right-Pointing-Pointer RIG-I activation impairs endothelial function in vivo. Black-Right-Pointing-Pointer RIG-I activation alters HCAEC biology in vitro. Black-Right-Pointing-Pointer EPC function is affected by RIG-I stimulation in vitro. -- Abstract: Background: Endothelial dysfunction is a crucial part of the chronic inflammatory atherosclerotic process and is mediated by innate and acquired immune mechanisms. Recent studies suggest that pattern recognition receptors (PRR) specialized in immunorecognition of nucleic acids may play an important role in endothelial biology in a proatherogenic manner. Here, we analyzed the impact of endothelial retinoic acid inducible gene I (RIG-I) activation upon vascular endothelial biology. Methods and results: Wild type mice were injected intravenously with 32.5 {mu}g of the RIG-ligand 3pRNA (RNA with triphosphate at the 5 Prime end) or polyA control every other day for 7 days. In 3pRNA-treated mice, endothelium-depended vasodilation was significantly impaired, vascular oxidative stress significantly increased and circulating endothelial microparticle (EMP) numbers significantly elevated compared to controls. To gain further insight in RIG-I dependent endothelial biology, cultured human coronary endothelial cells (HCAEC) and endothelial progenitor cells (EPC) were stimulated in vitro with 3pRNA. Both cells types express RIG-I and react with receptor upregulation upon stimulation. Reactive oxygen species (ROS) formation is enhanced in both cell types, whereas apoptosis and proliferation is not significantly affected in HCAEC. Importantly, HCAEC release significant amounts of proinflammatory cytokines in response to RIG-I stimulation. Conclusion: This study shows that activation of the cytoplasmatic nucleic acid receptor RIG-I leads to endothelial dysfunction. RIG-I induced endothelial damage could therefore be an important pathway in atherogenesis.

  11. In Vitro Endothelialization Test of Biomaterials Using Immortalized Endothelial Cells.

    Directory of Open Access Journals (Sweden)

    Ken Kono

    Full Text Available Functionalizing biomaterials with peptides or polymers that enhance recruitment of endothelial cells (ECs can reduce blood coagulation and thrombosis. To assess endothelialization of materials in vitro, primary ECs are generally used, although the characteristics of these cells vary among the donors and change with time in culture. Recently, primary cell lines immortalized by transduction of simian vacuolating virus 40 large T antigen or human telomerase reverse transcriptase have been developed. To determine whether immortalized ECs can substitute for primary ECs in material testing, we investigated endothelialization on biocompatible polymers using three lots of primary human umbilical vein endothelial cells (HUVEC and immortalized microvascular ECs, TIME-GFP. Attachment to and growth on polymer surfaces were comparable between cell types, but results were more consistent with TIME-GFP. Our findings indicate that TIME-GFP is more suitable for in vitro endothelialization testing of biomaterials.

  12. Strategies for Improving Patient Comfort During Intravitreal Injections: Results from a Survey-Based Study.

    Science.gov (United States)

    Gomez, Jessica; Koozekanani, Dara D; Feng, Alex Z; Holt, Mitchell; Drayna, Paul; Mackley, Melissa R; van Kuijk, Frederik J G M; Beardsley, Robert M; Johnston, Richard H; Terry, Joseph M; Montezuma, Sandra R

    2016-12-01

    Many ocular diseases require intravitreal injections of pharmacological agents. Optimizing patients' experiences during injections is important to ensure compliance and maintenance of quality of life. The objective of this study was to identify strategies to help alleviate discomfort during intravitreal injections. A cross-sectional study surveying 128 patients during clinic visits between 2014 and 2015 in two outpatient Retina Clinics (one academic and one private). Patients receiving an intravitreal injection(s) for any retinal disorder were given a questionnaire with 10-yes/no responses for various potential strategies. Responses were stratified by sex, age (60 years) and total number of prior injections (0-9 injections, 10-20 injections and >20 injections). A total of 128 patients were surveyed: 59 males, 41 females and 28 with no sex specified. Our results identified four favorable strategies as those receiving more than 50% "yes" votes. These included the presence of technician/staff during the procedure, the use of a neck pillow, a verbal warning before the injection and performing injections in both eyes on the same day. Other specific strategies were identified for females, younger patients and those with greatest experience. These included: females preferred having their hand held during injections (P = 0.001) and using a stress ball (P = 0.000) when compared to males. Stratifying by age, patients 30-60 years old preferred having their hand held (P = 0.008) and background music (P = 0.007). Stratifying by prior injections, patients with >20 prior injections preferred having their hand held (P = 0.001), using a stress ball (P = 0.021) and, if necessary, having bilateral injections performed the same day to improve comfort (P = 0.037). Having an extra staff member present during the injection, having a neck pillow, having a verbal warning prior to injection and having both eyes injected on the same day were indicated as favorable strategies

  13. Posterior vitreous detachment with microplasmin alters the retinal penetration of intravitreal bevacizumab (Avastin) in rabbit eyes.

    Science.gov (United States)

    Goldenberg, David T; Giblin, Frank J; Cheng, Mei; Chintala, Shravan K; Trese, Michael T; Drenser, Kimberly A; Ruby, Alan J

    2011-02-01

    Intravitreal bevacizumab (BV) (Avastin, Genentech Inc., South San Francisco, CA) is frequently used for the treatment of age-related macular degeneration. Previous studies have demonstrated full-thickness retinal penetration. Intravitreal recombinant microplasmin (MP) has been shown to successfully induce a posterior vitreous detachment (PVD) and vitreous liquefaction in animals. It has been suggested that a PVD may alter the retinal penetration of molecules in the vitreous cavity. The aim of this study was to compare BV retinal penetration in rabbit eyes with and without an MP-induced PVD. Twelve adult rabbits were injected with 0.1 mL (0.4 mg) of MP into the vitreous cavity of 1 eye. One week later, the rabbits were injected with 0.05 mL (1.25 mg) of BV into both eyes. Both eyes of 3 rabbits were harvested at 6 hours, 12 hours, 24 hours, and 72 hours after the BV injection. Frozen retinal cross sections were prepared, and BV retinal penetration was evaluated with immunohistochemistry using a fluorescence-labeled antibody against BV. Two eyes from one rabbit were not injected with either agent and used as controls to compare the background autofluorescence. Peripapillary retinal sections were recorded with a digital camera, and intraretinal BV fluorescence-labeled antibody was measured by qualitative photographic interpretation. Two additional rabbits received an intravitreal injection of 0.1 mL of MP in 1 eye. One week later, both eyes from each rabbit were enucleated, and frozen retinal sections were prepared and analyzed with light microscopy to evaluate histologic damage. Full-thickness BV retinal penetration was observed throughout the retina in both eyes of each rabbit. All the MP-injected eyes exhibited increased antibody labeling in retinas evaluated at 6 hours, 12 hours, and 24 hours after BV injection when compared with the contralateral non-MP-injected eyes. By 3 days after BV injection, all eyes demonstrated decreased antibody labeling compared with

  14. Intravitreal bevacizumab combined with plaque brachytherapy reduces melanoma tumor volume and enhances resolution of exudative detachment

    Directory of Open Access Journals (Sweden)

    Houston SK

    2013-01-01

    Full Text Available Samuel K Houston,1 Nisha V Shah,1 Christina Decatur,1 Marcela Lonngi,1 William Feuer,1 Arnold M Markoe,2 Timothy G Murray1–31Department of Ophthalmology, 2Department of Radiation Oncology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, 3Murray Ocular Oncology and Retina, Miami, FL, USABackground: The purpose of this study was to evaluate intravitreal bevacizumab as an adjuvant treatment to plaque brachytherapy in the treatment of choroidal melanoma.Methods: This was a retrospective, consecutive study of 124 patients treated from 2007 to 2009 for choroidal melanoma with plaque brachytherapy. Patients were treated with I-125 plaque brachytherapy with 2 mm margins and 85 Gy to the tumor apex. Consecutive patients were injected intravitreally with 2.5 mg/0.1 mL bevacizumab at a site away from the primary tumor and immediately following plaque removal. Choroidal melanomas were observed using indirect ophthalmoscopy, wide-angle photography, and ultrasound. The main outcome measures were tumor volume, resolution of exudative retinal detachment, and visual acuity.Results: One hundred and twenty-four patients met our inclusion criteria and were included in the analysis. The mean patient age was 65.7 years, and the mean apical tumor height was 4.0 ± 2.7 mm and basal diameter was 12.7 ± 3.0 mm. Mean follow-up was 24 months. Prior to treatment, 100% of tumors had exudative retinal detachment, and pretreatment visual acuity was 20/55 (median 20/40. Tumor control was 100%, metastasis was 0% at last follow-up, and 89.8% had complete resolution of exudative retinal detachment, with a mean time to resolution of 3.36 months. At one month, 43% had complete resolution of exudative retinal detachment, which increased to 73% at 4 months. Visual acuity was 20/62 (median 20/40 at 4 months, with stabilization to 20/57 (median 20/40 at 8 months, 20/56 (median 20/30 at 12 months, and 20/68 (median 20/50 at 24 months. Tumor

  15. The endothelial border to health

    DEFF Research Database (Denmark)

    Hansen, Nina Wærling; Hansen, Anker Jon; Sams, Anette

    2017-01-01

    by hyperglycemic events because the endothelium transduces “high glucose” signaling into significant pathophysiological phenomena leading to reduced endothelial barrier function, compromised vascular tone regulation and inflammation (e.g., cytokine secretion and RAGE activation). In addition, endothelial...... extracellular proteins form epitopes for potential specific antibody formation upon interactions with reducing sugars. This paper reviews the endothelial metabolism, biology, inflammatory processes, physical barrier functions, and summarizes evidence that although stochastic in nature, endothelial responses...... for several endothelial dysfunctions. There is also mounting epidemiological evidence that dietary intake of refined sugars is important for the development of a number of diseases beyond obesity and type 2 diabetes. Various diseases involving inflammatory and immunological components are accelerated...

  16. Influence of intravitreal triamcinolone acetonide injection in scleral buckling surgery for macula-off retinal detachment.

    Science.gov (United States)

    Mirshahi, Ahmad; Karkhaneh, Reza; Zamani Amir, Javad; Movassat, Morteza; Azadi, Pejvak

    2014-01-01

    To investigate the effect of intravitreal triamcinolone acetonide injection on the resolution of subretinal fluid (SRF), and its correlation with visual outcome after scleral buckle (SB) surgery. A prospective consecutive case series was conducted in patients who underwent SB surgery for macula-off rhegmatogenous retinal detachment (RRD) at Farabi Eye Hospital from February 1, 2012 to August 30, 2013. Exclusion criteria included previous ocular surgery (e.g. primary surgical failure) except cataract surgery, recurrent retinal detachment, macular hole, epiretinal membrane, proliferative vitreoretinopathy grade C, history of trauma, other retinal diseases, and diabetes mellitus. Patients were assigned to two groups. In group 1, patients received 2 mg of intravitreal triamcinolone acetonide injection at the end of surgery while patients in group 2 received intravitreal balanced saline solution for balancing the intraocular pressure (IOP). Patients were followed up at 1 day, 1 week, 1 month, 2 months and 3 months after the surgery by best-corrected visual acuity (BCVA), slitlamp examination, indirect ophthalmoscopy and optical coherence tomography (OCT). OCT (Heidelberg Engineering, Heidelberg, Germany) was used at all visits except day 1 after the surgery. Student's t test and χ(2) tests were used for comparisons; p value ≤ 0.05 was considered significant. Sixty-two eyes of 62 patients were enrolled in the study. There were 33 male patients (53%) and 29 female patients (47%). The average age was 43.8 years (18-72 years). The mean duration of symptoms was 34.7 ± 46.8 days. There were 29 eyes in group 1 and 33 eyes in group 2. Twelve weeks after the operation, 25 patients (40%) had SRF beneath the macula, but there was no significant difference (p = 0.24, χ(2) test) between the two groups. Improvement in BCVA in both groups was statistically significant (p ≤ 0.001) but did not differ between the two groups (p = 0.09) apart from week 12, in which the improvement

  17. Progression of choroidal metastasis of ovarian serous cystoadenocarcinoma after intravitreal bevacizumab treatment

    Directory of Open Access Journals (Sweden)

    Victor E. Reviglio

    2013-02-01

    Full Text Available A 57-year-old woman presented to her ophthalmologist because of rapid deterioration in vision. Dilated funduscopic examination of the right eye showed an elevated, yellow-orange choroidal mass temporal to the fovea; a complete retinal detachment was present in the left eye. The patient was referred to an oncologist. Computerized tomography of the brain, thorax, abdomen, and pelvis were obtained. They revealed an 11-mm mass in the right parietal lobe, a 30-mm mass in the left temporal lobe, 23-mm mass in the right kidney, and multiple nodules in both lungs. Supported by published experience with intravitreal bevacizumab for choroidal metastasis, the patient was injected into the vitreous through the pars plana of the left eye. The tumor mass did not show signs of regression and the visual acuity was unchanged. The patient suffered from end-state complications tumor metastasis and expired one month after the invitreal injection.

  18. Juxtapapillary neovascular membrane secondary to idiopathic intracranial hypertension treated with intravitreal bevacizumab: A case report.

    Science.gov (United States)

    Hernández-Ortega, V; Soler-Sanchís, M I; Jiménez-Escribano, R M; Sanz-López, A M

    2016-05-01

    A 48 year-old woman with visual acuity loss in left eye (0.3). Funduscopic examination showed papillary oedema and neovascular membrane in the left eye. All neurological tests were normal, except the lumbar puncture with opening pressure of 35cmH2O, being diagnosed with idiopathic intracranial hypertension (IIH). After four doses of bevacizumab, the visual acuity of the left eye has not improved and is counting fingers. Pathogenesis of the juxtapapillary neovascular membrane associated with IIH is not well known. An effect was observed after the anti-VEGF treatment. In our case, there was no improvement after four doses of intravitreal bevacizumab. Copyright © 2016 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Pukhraj Rishi

    2012-01-01

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

  20. Subconjunctival and Orbital Silicone Oil Granuloma (Siliconoma Complicating Intravitreal Silicone Oil Tamponade

    Directory of Open Access Journals (Sweden)

    Jung Hye Lee

    2014-01-01

    Full Text Available A 30-year-old male, who underwent previous pars plana vitrectomy and silicone oil tamponade due to endogenous endophthalmitis originated from Klebsiella liver abscess, was referred for evisceration. At 2 months after vitrectomy with silicon oil tamponade, conjunctival chemosis and ocular pain were aggravated. Diffuse eyelid swelling and large subconjunctival mass with lipid droplets were noted. On MRI examination, subconjunctival mass and intra- and extraconal orbital mass around superior rectus muscle were observed. Excision of subconjunctival and orbital mass was performed. Histopathologic examination showed multiple silicone oil vacuoles surrounded by foreign body giant cells and fibrosis, which confirmed silicone oil granuloma. In a patient with suspicious melting sclera in diseases such as endophthalmitis, large silicone oil granuloma may be complicated in a rapid fashion after intravitreal silicone oil tamponade due to silicone oil leakage.

  1. Mortality in patients treated with intravitreal bevacizumab for age-related macular degeneration.

    Science.gov (United States)

    Hanhart, Joel; Comaneshter, Doron S; Freier Dror, Yossi; Vinker, Shlomo

    2017-10-10

    The aim of this study is to analyze mortality in patients treated with bevacizumab for wet AMD. We conducted a retrospective case-control study between patients who received intravitreal injections of bevacizumab as the sole treatment for exudative AMD between September 2008 and October 2014 (n = 5385) and age and gender matched controls (n = 10,756). All individuals included in the study were reviewed for sociodemographic data and comorbidities. Survival analysis was performed using adjusted Cox regression, using relevant adjusted variables. During follow-up (maximum: 73 months), 1063 (19.7%) individuals after bevacizumab died compared with 1298 (12.1%) in the control group (P bevacizumab compared to a same age and gender group without wet AMD.

  2. Intravitreal bevacizumab as a treatment for choroidal neovascularisation secondary to myopia: 4-year study results.

    Science.gov (United States)

    Peiretti, Enrico; Vinci, Michela; Fossarello, Maurizio

    2012-02-01

    To report long-term follow-up results from intravitreal bevacizumab (IVB) treatment of choroidal neovascularisation (CNV) secondary to pathologic myopia (PM). The study was designed as a retrospective analysis of consecutive patients presenting with PM. Twenty-one eyes were examined from 20 different patients. The study was designed as a retrospective, consecutive, nonrandomised, interventional case series. Twenty-one eyes from 20 patients with CNV secondary to PM who were treated with bevacizumab were followed for a maximum of 52 months. Best-corrected visual acuity (BCVA), optical coherence tomography, and fluorescein and indocyanine green angiography were performed on each patient at baseline presentation and every 3 months thereafter for the entire follow-up period. The continuation therapy was based on dosing as needed regimen (PRN) for treatment assessment. Overall, 15 (71.4%) of the 21 eyes studied demonstrated an improvement of ≥ 1 line on the Snellen chart. A total of 3 (14.3%) eyes showed no change with this analysis, and 3 (14.3%) eyes lost 1 line of discrimination. After the 4-year study period, fluorescein angiography suggested absence of angiographic leakage or fibrotic lesions in 15 eyes, and 3 eyes showed partial regression of myopic CNV. The remaining 3 eyes demonstrated total regression of CNV. Intravitreal bevacizumab appears to be an effective therapy for myopic CNV and its benefit may persist in a long-term follow-up, on the basis of PRN treatment compared to the natural history of the disease. Copyright © 2012 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

  3. Evaulation of Incidence and Risk Factors for Intraocular Pressure Elevation After Intravitreal Triamcinolone Acetonide Injection

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    Didar Uçar

    2015-05-01

    Full Text Available Objectives: To investigate the effect of intravitreal triamcinolone acetonide (IVTA used for the macular edema on intraocular pressure (IOP and to determine the risk factors for IOP elevation. Materials and Methods: This retrospective study included 93 eyes of 85 patients who had 4 mg intravitreal triamcinolone injection. Of the 85 patients, 56 (65.8% had diabetic macular edema, 22 (25.8% had branch retinal, and 7 (8.2% had central retinal vein occlusion. IOP changes after injection as well as the relation between IOP elevation and age, sex, lens status, etiology of macular edema, baseline IOP were evaluated. Results: Fourty-six male and 39 female patients with mean age 61.58±9.5 years were evaluated. IOP was recorded to be >24 mmHg in 30 eyes (32.2% at follow-up visit after an average of 7.5 weeks. Normalization of IOP with medication was achieved in all IOP elevated eyes. Fifteen of 29 eyes (51.7% with vein occlusion and 15 of 64 eyes (23.3% with diabetic macula edema had IOP elevation (p=0.01. Twenty-six of 73 phakic (35.6% and 4 of 20 pseudophakic eyes (20% had IOP >24 mmHg (p=0.16. There was no association between IOP elevation and sex (p=0.33. Baseline IOP was 16.47±2.8 mmHg in eyes which had elevated IOP and 14.78±2.4 mmHg in the remaining. There was significant relation between IOP elevation and baseline IOP level (p=0.01. Conclusion: Elevated IOP is common side effect after IVTA, but normalization is usually achieved by topical medication. Patients with baseline IOP ≥15 mmHg and vein occlusion have higher risk for IOP elevation. (Turk J Ophthalmol 2015; 45: 86-91

  4. The effects of intravitreal bevacizumab in infectious and noninfectious uveitic macular edema.

    Science.gov (United States)

    Al-Dhibi, Hassan; Hamade, Issam H; Al-Halafi, Ali; Barry, Maan; Chacra, Charbel Bou; Gupta, Vishali; Tabbara, Khalid F

    2014-01-01

    Background/Aims. To assess the effect of intravitreal bevacizumab injection (IVBI) for the treatment of macular edema due to infectious and noninfectious uveitides. Design. Retrospective interventional case series. Methods. A chart review was performed on all the patients who were diagnosed with uveitic macular edema (UME) and received 1.25 mg of IVBI at two referral centers in Riyadh, Saudi Arabia. All included patients had their visual acuity and macular thickness analyzed at baseline and at 1 and 3 months following IVBI and any sign of reactivation was noted. Results. The mean age of patients was 41 ± 16 years with a mean followup of 4 ± 1 months. Ten patients had idiopathic intermediate uveitis, 9 patients had Behcet's disease, 10 had idiopathic panuveitis, and twelve patients had presumed ocular tuberculosis uveitis. Following IVBI, the mean LogMAR visual acuity improved from 0.8 ± 0.8 at baseline to 0.4 ± 0.5 at 1 month and 0.3 ± 0.5 at 3 months (P < 0.002, at 3 months). The mean macular thickness was 430 ± 132 μm at baseline. Following IVBI macular thickness improved to 286 ± 93 μm at 1 month and to 265 ± 88 μm at 3 months of followup (P < 0.001, at 3 months). Conclusion. Bevacizumab was effective in the management of UME associated with both infectious and noninfectious uveitides. Intravitreal bevacizumab induced remission of UME with infectious uveitis and had no immunosuppressive effect against infectious agents.

  5. The Effects of Intravitreal Bevacizumab in Infectious and Noninfectious Uveitic Macular Edema

    Directory of Open Access Journals (Sweden)

    Hassan Al-Dhibi

    2014-01-01

    Full Text Available Background/Aims. To assess the effect of intravitreal bevacizumab injection (IVBI for the treatment of macular edema due to infectious and noninfectious uveitides. Design. Retrospective interventional case series. Methods. A chart review was performed on all the patients who were diagnosed with uveitic macular edema (UME and received 1.25 mg of IVBI at two referral centers in Riyadh, Saudi Arabia. All included patients had their visual acuity and macular thickness analyzed at baseline and at 1 and 3 months following IVBI and any sign of reactivation was noted. Results. The mean age of patients was 41±16 years with a mean followup of 4±1 months. Ten patients had idiopathic intermediate uveitis, 9 patients had Behcet’s disease, 10 had idiopathic panuveitis, and twelve patients had presumed ocular tuberculosis uveitis. Following IVBI, the mean LogMAR visual acuity improved from 0.8±0.8 at baseline to 0.4±0.5 at 1 month and 0.3±0.5 at 3 months (P<0.002, at 3 months. The mean macular thickness was 430±132 μm at baseline. Following IVBI macular thickness improved to 286±93 μm at 1 month and to 265±88 μm at 3 months of followup (P<0.001, at 3 months. Conclusion. Bevacizumab was effective in the management of UME associated with both infectious and noninfectious uveitides. Intravitreal bevacizumab induced remission of UME with infectious uveitis and had no immunosuppressive effect against infectious agents.

  6. Extent of Detached Retina and Lens Status Influence Intravitreal Protein Expression in Rhegmatogenous Retinal Detachment.

    Science.gov (United States)

    Pollreisz, Andreas; Sacu, Stefan; Eibenberger, Katharina; Funk, Marion; Kivaranovic, Danijel; Zlabinger, Gerhard J; Georgopoulos, Michael; Schmidt-Erfurth, Ursula

    2015-08-01

    The aim of the study was to compare intravitreal cytokines and chemokines to clinical parameters in patients with rhegmatogenous retinal detachment (RRD). In this prospective study vitreous samples were taken undiluted from 60 patients with RRD and 20 age-matched controls with idiopathic epiretinal membranes at the beginning of primary vitrectomy. The following clinical parameters were assessed from RRD patients prior to surgery: number of quadrants detached, RD height, lens status, symptom duration, and refractive power. Concentrations of 40 different proteins in the vitreous of RRD eyes were measured by multiplex protein array, compared with controls and correlated to clinical parameters. Ten cytokines and chemokines were significantly upregulated in the vitreous of RRD eyes compared with controls (tissue inhibitors of metalloproteinases [TIMP]-1 and -2, macrophage inflammatory protein [MIP]-1α, monocyte chemoattractant protein [MCP]-1, IL-6, and -8, inducible protein (IP)-10, brain-derived neurotrophic factor [BDNF], TGFβ-3, and platelet-derived growth factor [PDGF]-AB/BB). Linear regression analysis revealed that IL-8 and TGFβ-3 increased with the number of retinal quadrants detached, while TIMP-1 rose in eyes with greater RD heights. Concentrations of IP-10 and myeloperoxidase (MPO) peaked in eyes with two or more quadrants detached, while TIMP-2 was highest expressed in the vitreous of eyes with great RD height. In pseudophakic eyes with higher detachment height levels of vascular cell adhesion molecule (VCAM)-1 were significantly increased, while neural cell adhesion molecule (NCAM) was decreased in pseudophakic patients with shallow RD height. Extent of RRD and lens status significantly influence intravitreal proinflammatory, profibrotic, and proapoptotic protein expression. These data contribute to the fundamental understanding of pathophysiological mechanisms in RRD and may serve as a basis for development of adjunct therapeutics to facilitate

  7. RETINAL PIGMENT EPITHELIAL TEAR AFTER INTRAVITREAL RANIBIZUMAB TREATMENT FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

    Science.gov (United States)

    Cho, Han Joo; Kim, Hyoung Seok; Yoo, Seul Gi; Han, Jung Il; Lew, Young Ju; Cho, Sung Won; Lee, Tae Gon; Kim, Jong Woo

    2016-10-01

    To evaluate the risk factors for retinal pigment epithelium (RPE) tears after intravitreal ranibizumab injections in neovascular age-related macular degeneration (nAMD) and to determine the efficacy of continued ranibizumab treatment after RPE tears. A total of 407 treatment-naïve eyes (377 patients) with nAMD were retrospectively included. All patients were treated with an initial series of 3 monthly loading injections, followed by further injections as required. Baseline characteristics and pigment epithelial detachment (PED) lesion features were evaluated as potential risk factors for RPE tear. The visual and anatomical outcomes after treatment during 12 months were also evaluated. By 12 months, RPE tears developed in 32 eyes (7.9%). Pigment epithelial detachment height was associated with a higher risk of RPE tear (odds ratio [OR], 1.318; 95% confidence interval [CI], 1.217-2.031, P = 0.018). Fibrovascular PED compared with serous PED had a higher risk of developing tears (OR, 9.129; 95% CI, 6.228-32.124, P = 0.039), and typical nAMD (OR, 4.166; 95% CI, 2.030-14.913, P = 0.031) and retinal angiomatous proliferation (OR, 3.778; 95% CI, 2.185-9.277, P = 0.040) had a higher risk of developing tears compared with polypoidal choroidal vasculopathy. Mean best-corrected visual acuity (BCVA) of RPE tear patients showed no significant improvement after treatment at 12 months; however, patients with RPE tears without foveal involvement (19 eyes) showed significant BCVA improvement at 12 months (P = 0.034). PED type and nAMD subtype are associated with the development of RPE tears after intravitreal ranibizumab injections. Continued ranibizumab therapy after RPE tear development can maintain visual acuity when the fovea is not involved.

  8. Comparative toxicity of 4 commonly used intravitreal corticosteroids on rat retina.

    Science.gov (United States)

    Citirik, Mehmet; Dilsiz, Nihat; Batman, Cosar; Zilelioglu, Orhan

    2009-06-01

    To investigate the effects of 4 commonly used steroids (dexamethasone, triamcinolone, betamethasone, and methylprednisolone) on 50 retinas of 25 adult pigmented rats. Experimental animal study. Twenty-five pigmented Long-Evans male rats. Each steroid drug with 2 different doses (0.025 mL and 0.050 mL) was injected into the vitreous of each eye of 5 rats. The low drug dose was injected into the right eye and the high dose was injected into the left eye. Ten eyes of 5 randomly selected rats were used as a control group and intravitreal saline was injected into these eyes. Oxidative damage and intrinsic antioxidative capacity were determined by measuring retinal malondialdehyde (MDA) and glutathione (GSH) levels, respectively. No statistically meaningful difference was observed in retinal GSH and MDA measurements in the low- and high-dose triamcinolone (1 and 2 mg), low-dose betamethasone (0.075 mg), and low-dose dexamethasone (0.1 mg) groups, compared with the control group. Both doses of methylprednisolone (1.6 mg and 3.2 mg), high-dose betamethasone (0.15 mg), and high-dose dexamethasone (0.2 mg) markedly altered retinal GSH and MDA levels. The results of our study show that the toxicity of triamcinolone is not evident even in high doses. It may be used safely. We also suggest that intravitreal use of low doses of betamethasone and dexamethasone is safer than higher doses of these drugs and both doses of methylprednisolone.

  9. Successful use of intravitreal and systemic colistin in treating multidrug resistant Pseudomonas aeruginosa post-operative endophthalmitis

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    Preetam Samant

    2014-01-01

    Full Text Available We report a case series of post-operative endophthalmitis due to Pseudomonas aeruginosa. A total of 8 patients operated for cataract, were referred to our facility with acute onset of decreased vision 1-2 days following surgery. All patients had clinical evidence of acute exogenous endophthalmitis with severe anterior chamber exudative reaction. Ocular samples (aqueous aspirate and vitreous tap for microbiology were taken from all eyes. Microbiology from all revealed P. aeruginosa which was resistant to all antibiotics except colistin. With prompt and accurate microbiological support it was possible to control the infection in all the eyes with the use of colistin intravitreally and intravenously which to the best of our knowledge, has been never reported. Intravitreal injection of colistin could be an option effective in the management of multi-drug-resistant endophthalmitis caused by Gram-negative bacteria.

  10. Intravitreal bevacizumab associated with photodynamic therapy in a case of polypoidal choroidal vasculopathy associated with choroidal nevus: A case report.

    Science.gov (United States)

    Rangel, Carlos M; Villota, Eva; Fernández-Vega González, Álvaro; Sanchez-Avila, Ronald M

    2017-12-01

    Report the clinical findings and management of a case of polypoidal choroidal vasculopathy associated with choroidal nevus which received combination therapy. Decreased visual acuity in a woman with polypoidal choroidal vasculopathy and choroidal nevus. Polypoidal choroidal vasculopathy and choroidal nevus. The initial visual acuity was 0.5. After the first treatment with photodynamic therapy, exudation and bleeding appeared around the lesion. After this, the patient received 3 doses of intravitreal bevacizumab. After treatment with combination therapy, visual acuity, clinical and imaging findings improved, with no recurrence of exudation and bleeding. Intravitreal bevacizumab as an adjunctive treatment after photodynamic therapy is a good option for patients with polypoidal choroidal vasculopathy associated with choroidal nevus. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  11. Safety study of 38 503 intravitreal ranibizumab injections performed mainly by physicians in training and nurses in a hospital setting

    DEFF Research Database (Denmark)

    Hasler, Pascal W; Bloch, Sara Brandi; Villumsen, Jørgen

    2015-01-01

    PURPOSE: To evaluate and to compare the safety of intravitreal ranibizumab injections performed by physicians and nurses at a single large hospital clinic in Denmark during 5 years. DESIGN: Retrospective, interventional, non-comparative study. METHODS: SETTING: All eyes that underwent...... a protocolized ranibizumab injection procedure performed in an operating room mainly by nurses and physicians in their first year of ophthalmology training. STUDY POPULATION: A total of 4623 eyes in 3679 patients with subretinal neovascularization secondary to a variety of retinal diseases, mainly neovascular...... detachment from 2007 to 2012. RESULTS: Overall, 38,503 intravitreal ranibizumab injections were performed in 4623 eyes. Injections were performed by nurses (32.5%), ophthalmology residents (61.3%) and vitreoretinal surgeons (6.2%). Severe complications to treatment were observed in 17 eyes: Endophthalmitis...

  12. Retinal hypoxia induces vascular endothelial growth factor through induction of estrogen-related receptor γ

    Energy Technology Data Exchange (ETDEWEB)

    Do, Ji Yeon; Choi, Young Keun [Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University School of Medicine, Kyungpook National University, Daegu (Korea, Republic of); Kook, Hyun [Department of Pharmacology, Chonnam National University Medical School, Gwangju (Korea, Republic of); Suk, Kyoungho [Department of Pharmacology, Brain Science & Engineering Institute, Kyungpook National University School of Medicine, Daegu (Korea, Republic of); Lee, In-Kyu [Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University School of Medicine, Kyungpook National University, Daegu (Korea, Republic of); Division of Endocrinology and Metabolism, Department of Internal Medicine, Research Institute of Aging and Metabolism, Kyungpook National University School of Medicine, Daegu (Korea, Republic of); Park, Dong Ho, E-mail: sarasate2222@gmail.com [Department of Ophthalmology, Kyungpook National University School of Medicine, Daegu (Korea, Republic of)

    2015-05-01

    Ischemic retinopathies causing overexpression of pro-angiogenic factors, including vascular endothelial growth factor (VEGF), are the most common cause of blindness. Thus, understanding the pathophysiology of targetable pathways that regulate retinal VEGF is of great interest. A conserved binding site for estrogen-related receptor γ (ERRγ) has been identified in the promoter of the Vegfa gene. ERRγ is a constitutively active orphan nuclear receptor and its expression is increased by hypoxic stimuli in metabolically active tissues. This study evaluated the role of ERRγ in the ischemic retina and the anti-VEGF potential of GSK5182, a selective inverse agonist of ERRγ. In an oxygen-induced retinopathy (OIR) mouse model, immunohistochemistry showed significantly increased ERRγ expression in the ganglion cell layer at postnatal day (P) 17. In a ganglion cell line (RGC-5), mRNA and protein levels of ERRγ were increased by desferrioxamine treatment and hypoxic conditions (1% O{sub 2}). Transient transfection of RGC-5 cells revealed that ERRγ regulated Vegfa expression and this was inhibited by GSK5182. Intravitreal injection of GSK5182 into the OIR model at P14 inhibited retinal Vegfa mRNA expression at P17. GSK5182 suppresses hypoxia-induced VEGF expression via ERRγ; therefore, ERRγ could be a treatment target for ischemic retinopathies. - Highlights: • OIR mice exhibited increased ERRγ expression in the ganglion cell layer. • Hypoxia-induced ERRγ expression was observed in retinal ganglion cells. • ERRγ overexpression increased VEGFA expression in retinal ganglion cells. • An ERRγ inverse agonist suppressed VEGFA expression in retinal ganglion cells. • Intravitreal injection of an ERRγ inverse agonist suppressed VEGFA in OIR mice.

  13. Treatment of vitreous hemorrhage in Rh-positive patients by intravitreal injection of anti-Rho-immunoglobulin.

    Science.gov (United States)

    Morawiecki, J; Geursen, R G

    1985-01-01

    22 Rh-positive patients suffering from vitreous hemorrhage caused by injuries to the eye, hypertension, or associated with subarachnoid hemorrhage, were treated with anti-Rh-immunoglobulin by intravitreal injection. 8 patients (36.4%) needed only one immunoglobulin injection and rapidly regained their former visual acuity. In 2 cases with repeated hemorrhage the result of the treatment was not satisfactory. The incidence of adverse effects was low.

  14. Vitrectomy combined with periocular/intravitreal injection of steroids for rhegmatogenous retinal detachment associated with choroidal detachment.

    Science.gov (United States)

    Wei, Yong; Wang, Ningli; Chen, Fenghua; Wang, Huaizhou; Bi, Chuncao; Zu, Zhongqiao; Yang, Xingguang

    2014-01-01

    To study the anatomical outcome of rhegmatogenous retinal detachment combined with choroidal detachment after pars plana vitrectomy with periocular/intravitreal injection of steroids. Seventy-seven eyes that have rhegmatogenous retinal detachment combined with choroidal detachment were treated by pars plana vitrectomy with oral prednisolone (Group A) or periocular/intravitreal injection of steroids (Group B) and then divided into 5 subgroups according to different intraocular tamponade agents; Group A1: oral steroids and silicone oil, Group A2: oral steroids and C(3)F(8), Group B1: periocular/intravitreal steroid injections and silicone oil, Group B2: periocular steroid injection and silicone oil, and Group B3: periocular steroid injection and C(3)F(8). Anatomical reattachment of the retina was measured at 12 months after surgery. There was no significant difference in retinal reattachment rate between eyes in Group A and eyes in Group B (77.4% vs. 73.9%, P = 0.726). The retinal reattachment rates were 83.3% in Group A1, 69.2% in Group A2, 82.4% in Group B1, 73.3% in Group B2, and 64.3% in Group B3. There was no statistical difference in the retinal reattachment rates between any of the groups. For the treatment of rhegmatogenous retinal detachment combined with choroidal detachment, pars plana vitrectomy with periocular/intravitreal corticosteroids was comparable in reattachment rate to pars plana vitrectomy with systemic steroids, suggesting an acceptable alternative for patients with this condition who cannot tolerate systemic steroids.

  15. 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

    2012-01-01

    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. PMID:22948997

  16. Endothelial signaling in leukocyte transmigration

    NARCIS (Netherlands)

    Hordijk, Peter

    2003-01-01

    Leukocyte transendothelial migration is a multistep process coordinated by chemokine receptors, integrins and cell adhesion molecules. The interaction between leukocytes and endothelial cells is accompanied by bidirectional signaling in both cell types, which is initiated following formation of

  17. Quantitative evaluation of hard exudates in diabetic macular edema after short-term intravitreal triamcinolone, dexamethasone implant or bevacizumab injections.

    Science.gov (United States)

    Shin, Yong Un; Hong, Eun Hee; Lim, Han Woong; Kang, Min Ho; Seong, Mincheol; Cho, Heeyoon

    2017-10-03

    To quantitatively compare short-term hard exudates (HEs) alteration in patients with diabetic macular edema (DME) after intravitreal triamcinolone, dexamethasone implant or bevacizumab injections. This retrospective study enrolled DME eyes with HEs that underwent a single-dose intravitreal injection of triamcinolone (25 eyes), dexamethasone implant (20 eyes), or three monthly injections of bevacizumab (25 eyes) and completed at least three months of follow-up. All patients were examined before and after 1, 2 and 3 months of injections. Using color fundus photographs, the amount of HEs was quantified by two masked graders. The difference in HEs area between baseline and each follow-up visit was compared among the three groups. After three months, HEs area was reduced to 52.9 ± 4.21% (P bevacizumab group. A significant reduction in HEs appeared at one month in the triamcinolone group (53.5 ± 4.91%, P bevacizumab does not. Therefore, intravitreal steroids may be useful in DME with HEs in the fovea.

  18. Short-term effects of intravitreal dexamethasone implant (OZURDEX® on choroidal thickness in patients with naive branch retinal vein occlusion

    Directory of Open Access Journals (Sweden)

    Hasan Basri Arifoglu

    Full Text Available ABSTRACT Purpose: The objective of this study was to evaluate subfoveal choroidal thickness (SFCT using enhanced depth imaging optical coherence tomography (EDI-OCT in patients with naïve branch retinal vein occlusion (BRVO before and after intravitreal dexamethasone implant (Ozurdex® injection. Methods: Thirty-nine patients with unilateral BRVO and 35 healthy subjects were included in this prospective study. Choroidal thickness was evaluated by EDI-OCT at baseline and 1 month after dexamethasone implant. Results: The mean SFCT measured in 39 patients with BRVO was 299.41 ± 55.86 µm, significantly greater than that in contralateral eyes (283.76 ± 57.44 µm; p=0.009 and control eyes (276.14 ± 39.06 µm; p=0.044. The mean SFCT after the treatment was 279.64 ± 50.96 µm, significantly thinner than that before intravitreal dexamethasone therapy (p=0.004. Conclusions: SFCT in treatment-naive BRVO eyes was significantly greater than that in contralateral eyes and healthy eyes and decreased significantly after intravitreal dexamethasone implantation.

  19. Inhibition of retinopathy of prematurity in rat by intravitreal injection of sorafenib

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    Li-Li Tian

    2014-04-01

    Full Text Available AIM:To investigate the effect of intravitreal injection administered sorafenib, a multikinase inhibitor, in a rat model of oxygen-induced retinopathy (OIR.METHODS:Seven-day-old Sprague-Dawley rats (n=144 were randomly assigned to six groups. Group A received normal partial oxygen pressure and groups B, C, D, E and F were exposed to hyperoxia (75±2% from postnatal 7d (P7 to P12 to induce retinopathy of prematurity. The rats in groups C, D, E and F were received intravitreal injections of either vehicle (DMSO or sorafenib at P12 (5, 20 and 80 μg, respectively. Then they returned to normoxia after P12. The retinas were whole-mounted and imaged with a confocal microscopy. The vascular branching points were counted to quantify neovascularization at P17. Cross-sections of the retina were stained with hematoxylin and eosin (HE. The nuclei of new vessels breaking the internal limiting membrane were counted to quantify the proliferative neovascular response.RESULTS:The retinal vessel in groups B and C turned into tortuosity and a great deal of neovascularization were observed. Sorafenib-treated rats had significantly less neovascularization as compared with vehicle-treated and control rats in a dose dependent manner (P<0.05. The number of vascular branching points in A, B, C, D, E and F were 16.50±3.90, 37.44±6.47, 37.08±5.10, 30.80±6.85, 26.08±5.08 and 19.83±3.51, respectively. The number of the nuclei of retinal new vessel in A, B, C, D, E and F were 0.22±0.42, 35.66±4.70, 35.30±4.54, 27.30±4.28, 21.41±3.53, and 7.41±2.87, respectively. There were significant difference between each group (P<0.05 except groups B and C.CONCLUSION: In the rat OIR model, sorafenib could inhibit retinal neovascularization in a dose dependent manner.

  20. Surface Engineering of Porous Silicon Microparticles for Intravitreal Sustained Delivery of Rapamycin

    Science.gov (United States)

    Nieto, Alejandra; Hou, Huiyuan; Moon, Sang Woong; Sailor, Michael J.; Freeman, William R.; Cheng, Lingyun

    2015-01-01

    Purpose. To understand the relationship between rapamycin loading/release and surface chemistries of porous silicon (pSi) to optimize pSi-based intravitreal delivery system. Methods. Three types of surface chemical modifications were studied: (1) pSi-COOH, containing 10-carbon aliphatic chains with terminal carboxyl groups grafted via hydrosilylation of undecylenic acid; (2) pSi-C12, containing 12-carbon aliphatic chains grafted via hydrosilylation of 1-dodecene; and (3) pSiO2-C8, prepared by mild oxidation of the pSi particles followed by grafting of 8-hydrocarbon chains to the resulting porous silica surface via a silanization. Results. The efficiency of rapamycin loading follows the order (micrograms of drug/milligrams of carrier): pSiO2-C8 (105 ± 18) > pSi-COOH (68 ± 8) > pSi-C12 (36 ± 6). Powder X-ray diffraction data showed that loaded rapamycin was amorphous and dynamic drug-release study showed that the availability of the free drug was increased by 6-fold (compared with crystalline rapamycin) by using pSiO2-C8 formulation (P = 0.0039). Of the three formulations in this study, pSiO2-C8-RAP showed optimal performance in terms of simultaneous release of the active drug and carrier degradation, and drug-loading capacity. Released rapamycin was confirmed with the fingerprints of the mass spectrometry and biologically functional as the control of commercial crystalline rapamycin. Single intravitreal injections of 2.9 ± 0.37 mg pSiO2-C8-RAP into rabbit eyes resulted in more than 8 weeks of residence in the vitreous while maintaining clear optical media and normal histology of the retina in comparison to the controls. Conclusions. Porous silicon–based rapamycin delivery system using the pSiO2-C8 formulation demonstrated good ocular compatibility and may provide sustained drug release for retina. PMID:25613937

  1. Intravitreal bevacizumab for neovascular glaucoma in uveal melanoma treated by proton beam therapy.

    Science.gov (United States)

    Mahdjoubi, Amir; Najean, Marie; Lemaitre, Stéphanie; Dureau, Sylvain; Dendale, Rémi; Levy, Christine; Rouic, Livia Lumbroso-Le; Desjardins, Laurence; Cassoux, Nathalie

    2018-02-01

    To evaluate the efficacy of bevacizumab on reduction of the enucleation rate and control of intraocular pressure (IOP) in neovascular glaucoma (NVG)-complicating proton beam therapy for UM and to identify the determinants of the efficacy of bevacizumab. Retrospective comparative study of patients with rubeosis following proton therapy for uveal melanoma. Patients were divided into two groups: a bevacizumab group and a control group which comprised two subgroups: panretinal photocoagulation (PRP)/cryotherapy and observation subgroups. Bevacizumab was administered by three intravitreal injections at 1-month intervals. A second series of injections was administered when necessary. Data concerning IOP and the secondary enucleation rate were collected and compared between the two groups. Univariate and multivariate analyses were performed to determine predictive factors of response to bevacizumab. A total of 169 patients who developed rubeosis following proton therapy between 2006 and 2016 were included: 44 patients in the bevacizumab group and 125 in the control group (38 in the PRP/cryotherapy subgroup and 87 in the observation subgroup). The two groups presented the same baseline characteristics apart from hypertension, retro-equatorial site, and proximity of the optic disk, which were more frequent in the control group, while initial retinal detachment and larger tumor volume were more frequent in the bevacizumab group. After a mean follow-up of 31 months, IOP was less than 21 mmHg in 54.54% of patients after IVB versus 72.7% before treatment (p = 0.06). Statistical analysis did not reveal any statistically significant reduction of the enucleation rate in the bevacizumab group compared to the observational group, whereas the PRP/cryotherapy group showed better eye retention rate (p = 0.15). No enucleation was performed when IOP was bevacizumab. Despite the improvement of IOP level, intravitreal bevacizumab (IVB) did not reduce the overall enucleation rate in

  2. Effects of moxifloxacin exposure on the conjunctival flora and antibiotic resistance profile following repeated intravitreal injections

    Directory of Open Access Journals (Sweden)

    Mustafa Ataş

    2014-10-01

    Full Text Available AIM:To evaluate the effects of moxifloxacin exposure on the conjunctival flora and antibiotic resistance profile following repeated intravitreal injections.METHODS:Seventy-two eyes of 36 patients [36 eyes in control group, 36 eyes in intravitreal injection (IVI group] were enrolled in the study. All the eyes had at least one IVI and had diabetic macular edema (DME or age-related macular degeneration (ARMD. Moxifloxacin was prescribed to all the patients four times a day for five days following injection. Conjunctival cultures were obtained from the lower fornix via standardized technique with every possible effort made to minimize contamination from the lids, lashes, or skin. Before the application of any ophthalmic medication, conjunctival cultures were obtained from both eyes using sterile cotton culture. An automated microbiology system was used to identify the growing bacteria and determine antibiotic sensitivity. RESULTS:The bacterial cultures were isolated from 72 eyes of 36 patients, sixteen of whom patients (44.4% were male and twenty (55.6% were female. Average age was 68.4±9.0 (range 50-86. The average number of injections before taking cultures was 3.1+1.0. Forty-eight (66.7% of 72 eyes had at least one significant organism. There was no bacterial growth in 8 (20.5% of IVI eyes and in 16 (44.4% of control eyes (P=0.03. Of the bacteria isolated from culture, 53.8% of coagulase negative staphylococci (CoNS in IVI eyes and 47.2% CoNS in control eyes. This difference between IVI eyes and control eyes about bacteria isolated from culture was not statistically significant (P=0.2. Eleven of 25 bacteria (44.0% isolated from IVI eyes and 11 (57.9% of 19 bacteria isolated from control eyes were resistant to oxacillin. The difference in frequency of moxifloxacine resistance between two groups was not statistically significant (12.0% in IVI eyes and 21.1% in control eyes (P=0.44. There were no cases of resistance to vancomycin, teicoplanin and

  3. Clinical research on intravitreal injection of bevacizumab in the treatment of macula lutea and retinal edema of ocular fundus disease.

    Science.gov (United States)

    Yan, Ying; Wang, Tao; Cao, Jing; Wang, Meng; Li, Fenghua

    2015-07-01

    This paper aimed to explore clinically curative effect of intravitreal injection of bevacizumab in the treatment of macula lutea and retinal edema of ocular fundus disease. The number of 300 patients (390 eyes) with ocular fundus diseases including retinal vein occlusion (RVO), diabetic retinopathy (DR), age-related macular degeneration (ARMD), central serous chorioretinopathy (CSC), choridal new vessel (CNV) received and cured in the hospital from February 2010 to February 2014 were given intravitreal injection of bevacizumab (1.5mg) with once per month and a total of 2-3 times. Results of patients' vision and fluorescence fundus angiography (FFA), optical coherence tomography (OCT) before and after treatment were compared and curative effects were evaluated. Vision of 349 eyes (89.49%) improved obviously with the average of more than 2 lines, patient's intraocular pressure (IOP) was normal and all indexes were clearly better; vision of 26 eyes (6.67%) was stable before the treatment and without any changes after the treatment, the situation of fundus got better without increased IOP; vision of 15 eyes (3.85%) decreased to some extent, and the symptoms eased slightly after symptomatic treatment. In the 1st day after intravitreal injection, best-corrected visual acuity increased to 0.239±0.175, best-corrected visual acuity in 1 m was 0.315±0.182, in 3m continuously climbed to 0.350±0.270, and in 6 m was 0.362±0.282. Compared with vision before injection, t value was t=3.184, t=7.213, t=9.274 and t=9.970 (P=0.002, P=0.000, P=0.000 and P=0.000) respectively, and all P were less than 0.01. Furthermore, the difference was significant if a=0.01, which could confirm that 1m best corrected visual acuity of patients after intravitreal injection improved clearly in combination with before injection and 3m and 6 m visions enhanced constantly after injection. To sum up, intravitreal injection of bevacizumab in treating ocular fundus disease improves patient's vision

  4. Effects of intravitreal ranibizumab on the untreated eye and systemic gene expression profile in age-related macular degeneration

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    Michalska-Małecka K

    2016-03-01

    Full Text Available Katarzyna Michalska-Małecka,1,2 Adam Kabiesz,2 Malgorzata W Kimsa,3 Barbara Strzałka-Mrozik,3 Maria Formińska-Kapuścik,2,4 Malgorzata Nita,5 Urszula Mazurek31Clinical Department of Ophthalmology, Medical University of Silesia, Katowice, Poland; 2University Center for Ophthalmology and Oncology, Independent Public Clinical Hospital, Medical University of Silesia, Katowice, Poland; 3Department of Molecular Biology, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Katowice, Poland; 4Clinical Department of Children Ophthalmology, Medical University of Silesia, Katowice, Poland; 5Domestic and Specialized Medicine Centre “Dilmed”, Katowice, PolandAbstract: The purpose of this study was to evaluate the systemic effects of intravitreal ranibizumab (Lucentis treatment in patients with neovascular age-related macular degeneration (AMD. The impact of intravitreal ranibizumab injections on central retinal thickness (CRT of treated and contralateral untreated eyes, and differences in gene expression patterns in the peripheral blood mononuclear cells were analyzed. The study included 29 patients aged 50 years old and over with diagnosed neovascular AMD. The treatment was defined as 0.5 mg of ranibizumab injected intravitreally in the form of one injection every month during the period of 3 months. CRT was measured by optical coherence tomography. The gene expression profile was assigned using oligonucleotide microarrays of Affymetrix HG-U133A. Studies have shown that there was a change of CRT between treated and untreated eyes, and there were differences in CRT at baseline and after 1, 2, and 3 months of ranibizumab treatment. Three months after intravitreal injection, mean CRT was reduced in the treated eyes from 331.97±123.62 to 254.31±58.75 µm, while mean CRT in the untreated fellow eyes reduced from 251.07±40.29 to 235.45±36.21 µm at the same time. Furthermore, the research has shown

  5. What do Cochrane systematic reviews say about diabetic retinopathy?

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    Vania Mozetic

    Full Text Available ABSTRACT CONTEXT AND OBJECTIVE: Diabetic retinopathy is a disease caused by increased permeability of retinal vessels. Its incidence and prevalence have been increasing due to urbanization, greater life expectancy and the habits of modern life. Its onset is insidious and it may lead to blindness in 75% of individuals who have been diabetic for more than 20 years. The aim here was to evaluate the evidence from Cochrane systematic reviews on interventions relating to diabetic retinopathy. DESIGN AND SETTING: Review of systematic reviews, conducted at Cochrane Brazil. METHODS: We included Cochrane systematic reviews on interventions relating to diabetic retinopathy. Two researchers evaluated the inclusion criteria, summarized the reviews and presented the results narratively. RESULTS: Ten reviews met the inclusion criteria. They showed some evidence of benefits from: (a photocoagulation for diabetic retinopathy; (b strict glucose and pressure control for postponing the onset of retinopathy; (c antiangiogenic drugs for macular edema (high-quality evidence; (d anti-vascular endothelial growth factor agents for proliferative diabetic retinopathy (very low to low-quality evidence; and (e intravitreal injection or surgical implantation for treating persistent or refractory macular edema. However, blood pressure control seems to have no benefit after the onset of retinopathy. CONCLUSION: Only a few options are likely to be effective for treating diabetic retinopathy. These include photocoagulation and anti-vascular endothelial growth factor agents. Strict glucose and pressure control seem to postpone the onset of retinopathy. For macular edema, antiangiogenic drugs, intravitreal injection and surgical implantation seem to have some benefit.

  6. Intravitreal Triamcinolone for Acute Branch Retinal Vein Occlusion: a Randomized Clinical Trial

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    Alireza Ramezani

    2011-01-01

    Full Text Available Purpose: To evaluate the therapeutic effect of intravitreal triamcinolone (IVT injection for recent branch retinal vein occlusion (BRVO. Methods: In a randomized controlled clinical trial, 30 phakic eyes with recent (less than 10 weeks′ duration BRVO were assigned to two groups. The treatment group (16 eyes received 4 mg IVT and the control group (14 eyes received subconjunctival sham injections. Changes in visual acuity (VA were the main outcome measure. Results: VA and central macular thickness (CMT changes were not significantly different between the study groups at any time point. Within group analysis showed significant VA improvement from baseline in the IVT group up to three months (P 0.05. Significant reduction in CMT was noticed only in the treatment group (‑172 ± 202 μm, P = 0.029 and at 4 months. Ocular hypertension occurred in 4 (25% and 2 (14.3% eyes in the IVT and control groups, respectively. Conclusion: A single IVT injection had a non-significant beneficial effect on VA and CMT in acute BRVO as compared to the natural history of the condition. The 3-month deferred treatment protocol advocated by the Branch Vein Occlusion Study Group may be a safer option than IVT injection considering its potential side effects.

  7. A prospective randomized evaluation of topical gatifloxacin on conjunctival flora in patients undergoing intravitreal injections.

    Science.gov (United States)

    Moss, Jason M; Sanislo, Steven R; Ta, Christopher N

    2009-08-01

    We sought to assess the efficacy of 3-day topical gatifloxacin use in combination with povidone-iodine (PVI) versus PVI alone in eliminating conjunctival bacterial flora in patients scheduled to undergo intravitreal (IVT) injection. Prospective, randomized single-blind clinical trial. We included 129 patients scheduled to undergo 273 IVT injections at California Vitreoretinal Center at Stanford University. Study patients were randomized to self-administration of gatifloxacin drops for 3 days before injection, or no pretreatment antibiotics. Cultures were collected from the bulbar conjunctiva at the injection site and at the corresponding location in the fellow eye before PVI preparation. After topical PVI treatment and immediately before injection, a third culture was obtained at the injection site. Additionally, the injection needle was also cultured after the procedure. Incidence of positive bacterial samples collected from injection site conjunctiva and injection needles. Three-day gatifloxacin use resulted in a significantly lower rate of SeptiChek (Becton Dickinson, Franklin Lakes, NJ) positive cultures compared with untreated controls (21% vs 48% respectively, P = 0.005). After topical PVI, the rate of positive bacterial cultures in gatifloxacin-treated and control eyes were similar (8% and 4%, respectively; P = 0.324). Although 3-day topical gatifloxacin use is effective in reducing the frequency of conjunctival bacterial growth relative to untreated eyes, antibiotic use confers no additional benefit in combination with PVI than eyes receiving PVI alone. This supports that topical PVI is an effective preinjection monotherapy for infection prophylaxis in the setting of IVT injections.

  8. Antibiotic susceptibility patterns of ocular bacterial flora in patients undergoing intravitreal injections.

    Science.gov (United States)

    Moss, Jason M; Sanislo, Steven R; Ta, Christopher N

    2010-11-01

    To determine the antibiotic susceptibility patterns of conjunctival flora in patients undergoing intravitreal (IVT) injection. Prospective, observational study. Patients (n = 85) scheduled to undergo 136 IVT injections at California Vitreoretinal Center at Stanford University. Conjunctival cultures were obtained on the day of the IVT injection from the injection site bulbar conjunctiva before the application of povidone-iodine or antibiotics. Bacterial isolates were identified and tested for antibiotic susceptibility using either the Kirby-Bauer disc-diffusion technique or MicroScan-WalkAway system. Our analysis included 136 samples collected from 90 eyes of 85 patients. Of those with positive cultures (n = 65), the most common bacterial isolates were coagulase-negative staphylococci (CNS), comprising 59 (83%) of the 71 bacterial strains. Among the CNS, all were susceptible to vancomycin and >80% were susceptible to gentamicin, chloramphenicol, tetracycline, and imipenem. Between 60% and 80% of the CNS were susceptible to the cephalosporins and newer generation fluoroquinolones. Fewer than 60% were susceptible to the penicillin analogs, erythromycin, and the earlier generation fluoroquinolones. Nearly half of the CNS (47%) were resistant to oxacillin/methicillin. Bacteria isolated from the injection site of patients undergoing IVT injections were mostly CNS. Most are sensitive to vancomycin, gentamicin, and chloramphenicol. Proprietary or commercial disclosure may be found after the references. Copyright © 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  9. Letter to the editor: dexamethasone intravitreal implant in the treatment of diabetic macular edema

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    Hall J

    2015-11-01

    Full Text Available John Hall Alimera Sciences Ltd., Aldershot, Hampshire, UK I read “Dexamethasone intravitreal implant in the treatment of diabetic macular edema” published July 2015 by Dugel et al.1This article is very interesting in terms of providing an outline of the role of inflammation in the pathogenesis of diabetic macular edema and explaining the value of corticosteroids in the treatment of diabetic macular edema. However, I would like to draw your attention to the data presented for ILUVIEN® (fluocinolone acetonide; FAc in Table 2, which has been presented incorrectly and does not reflect the approved product and dose in Europe. ILUVIEN is indicated in Europe for the treatment of vision impairment associated with chronic diabetic macular edema, considered insufficiently responsive to available therapies2 and is approved in Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Ireland, Italy, Luxembourg, the Netherlands, Norway, Poland, Portugal, Spain, Sweden, and the United Kingdom. ILUVIEN was launched in the United Kingdom in April 2013, Germany in May 2013, and Portugal in January 2015.3View original paper by Dugel et al.

  10. Intravitreal Implantation of Genetically Modified Autologous Bone Marrow-Derived Stem Cells for Treating Retinal Disorders.

    Science.gov (United States)

    Tracy, Christopher J; Sanders, Douglas N; Bryan, Jeffrey N; Jensen, Cheryl A; Castaner, Leilani J; Kirk, Mark D; Katz, Martin L

    2016-01-01

    A number of retinal degenerative diseases may be amenable to treatment with continuous intraocular delivery of therapeutic agents that cannot be delivered effectively to the retina via systemic or topical administration. Among these disorders are lysosomal storage diseases resulting from deficiencies in soluble lysosomal enzymes. Most cells, including those of the retina, are able to take up these enzymes and incorporate them in active form into their lysosomes. In theory, therefore, continuous intraocular administration of a normal form of a soluble lysosomal enzyme should be able to cure the molecular defect in the retinas of subjects lacking this enzyme. Experiments were conducted to determine whether genetically modified bone marrow-derived stem cells implanted into the vitreous could be used as -vehicles for continuous delivery of such enzymes to the retina. Bone marrow-derived mesenchymal stem cells (MSCs) from normal mice were implanted into the vitreous of mice undergoing retinal degeneration as a result of a mutation in the PPT1 gene. The implanted cells appeared to survive indefinitely in the vitreous without proliferating or invading the retina. This indicates that intravitreal implantation of MSCs is likely a safe means of long-term delivery of proteins synthesized by the implanted cells. Experiments have been initiated to test the efficacy of using genetically modified autologous MSCs to inhibit retinal degeneration in a canine model of neuronal ceroid lipofuscinosis.

  11. Macular Edema Formation and Deterioration of Retinal Function after Intravitreal Bevacizumab Injection for Proliferative Diabetic Retinopathy

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    Hisanori Imai

    2011-09-01

    Full Text Available Purpose: To report a case of proliferative diabetic retinopathy (PDR showing transient macular edema (ME and deteriorated retinal function after intravitreal bevacizumab injection (IVB. Methods and Results: A 53-year-old man received IVB (1.25 mg/0.05 ml in both eyes for the treatment of PDR. There was no treatment-related complication. However, he complained of photopsia in both eyes 6 h after the injection. Slit-lamp examination revealed mild cellular infiltrations (1+ in the anterior chamber in both eyes. Optical coherence tomography showed ME formation in the left eye. Both full-field and multifocal electroretinography (ERG revealed the deterioration of all parameters in both eyes compared with pretreatment. The inflammation in the anterior segment and ME disappeared 1 day after the injection. ERG parameters were improved 9 days after the injection, except for the N1 and P1 amplitude of multifocal ERG in the left eye. Conclusion: We propose that patients who undergo IVB should be carefully informed and followed up for possible complications including temporal ME formation and retinal function deterioration.

  12. Flicker electroretinograms before and after intravitreal ranibizumab injection in eyes with central retinal vein occlusion.

    Science.gov (United States)

    Yasuda, Shunsuke; Kachi, Shu; Ueno, Shinji; Piao, Chang-Hua; Terasaki, Hiroko

    2015-09-01

    To compare the amplitudes and implicit times of the flicker electroretinograms before and after an intravitreal injection of ranibizumab (IVR) in eyes with a central retinal vein occlusion (CRVO). We reviewed the medical records of 15 consecutive patients who had macular oedema secondary to CRVO and had received an IVR at the Nagoya University Hospital from November 2013 to July 2014. Flicker ERGs were recorded with both the RETeval(™) system and a conventional ERG system before the IVR. One month after the IVR, recordings were repeated with only the RETeval(™) system. The mean implicit times of the flicker ERGs of the affected eyes recorded with the RETeval(™) system were significantly longer than that of the fellow eyes (32.2 ± 2.6 msec versus 28.1 ± 1.2 msec, p flicker ERGs of affected eyes were significantly shortened from 32.2 ± 2.6 to 30.6 ± 2.2 msec (p flicker ERGs after the IVR indicates an improvement of retinal function after anti-VEGF therapy for CRVO eyes. © 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  13. Retreatment of Exudative Age-Related Macular Degeneration after Loading 3-Monthly Intravitreal Ranibizumab.

    Science.gov (United States)

    Sugiyama, Atsushi; Sakurada, Yoichi; Honda, Shigeru; Miki, Akiko; Matsumiya, Wataru; Yoneyama, Seigo; Kikushima, Wataru; Iijima, Hiroyuki

    2018-01-01

    The aim of this study was to investigate the clinical implications of required retreatment after 3-monthly intravitreal ranibizumab (IVR) injections followed by as-needed reinjections up to 5 years in eyes with exudative age-related macular degeneration (AMD). A retrospective cohort study was conducted for 165 treatment-naïve eyes from 165 patients with exudative AMD. Visual changes were investigated in terms of the required retreatments. Retreatment-free proportions were 37.0, 23.7, 16.6, 12.1, and 10.5% at 12, 24, 36, 48, and 60 months, respectively. Visual changes were significantly better in eyes which did not require retreatment at every yearly checkpoint within the 5 years. A multivariate logistic regression analysis revealed that requirement of additional IVR treatments in the first 12-24 months was associated with the T allele (risk allele) of ARMS2 A69S (p = 0.010 and 0.015, respectively). Cox regression analysis revealed that older age (p = 0.046) and the T allele of ARMS2 A69S (p = 0.036) were associated with required retreatment within the 5-year follow-up period. Age and the T allele of ARMS2 A69S are the risk factors requiring retreatments, leading to poor visual change in eyes with exudative AMD following the initial 3-monthly IVR. © 2017 S. Karger AG, Basel.

  14. Tempol protects against intravitreous indocyanine green-induced retinal damage in rats.

    Science.gov (United States)

    Thaler, Sebastian; Voykov, Bogomil; Willmann, Gabriel; Fiedorowicz, Michal; Rejdak, Robert; Gekeler, Florian; May, C Albrecht; Schatz, Andreas; Schuettauf, Frank

    2012-11-01

    Indocyanine green (ICG) has been widely used as a vital dye for macular surgery. However, ICG can be toxic to retinal cells. Here we evaluate whether tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl), a free radical scavenger, can protect against ICG-induced retinal damage in rats. Brown Norway rats received intravitreal injections of ICG 0.5 % or BSS as controls. Tempol (20 mg/kg BW) or PBS as a control was administered intraperitoneally 24 h and 30 min before ICG and once daily for 7 consecutive days. Tempol was detected in the retina using electron paramagnetic resonance (EPR) spectroscopy. One week after ICG injections, the effects of tempol on retinal toxicity were assessed by retinal ganglion cell (RGC) back-labeling and by light microscopy. Electroretinography (ERG) was performed after 1 and 2 weeks. ICG administration reduced RGC numbers by 17 % (1,943 ± 45 vs. 2,342 ± 31 RGCs/mm(2)). Tempol treatment rescued RGCs in a significant manner (2,258 ± 36, p tempol-treated group. Tempol significantly attenuates ICG-induced toxicity in rat retinas and may therefore be considered for further evaluation as accompanying treatment in ICG-assisted chromovitrectomy.

  15. Sustaining Intravitreal Residence With L-Arginine Peptide-Conjugated Nanocarriers.

    Science.gov (United States)

    Li, Hao; Liu, Wenzhong; Sorenson, Christine M; Sheibani, Nader; Albert, Daniel M; Senanayake, Thulani; Vinogradov, Serguei; Henkin, Jack; Zhang, Hao F

    2017-10-01

    Intravitreal injection of antiangiogenic agents is becoming a standard treatment for neovascular retinal diseases. Sustained release of therapeutics by injecting colloidal carriers is a promising approach to reduce the injection frequency, which reduces treatment burdens and the risk of complications on patients. Such sustained release often requires carriers to have micrometer-scale dimension that, however, can potentially promote glaucoma and inflammation. Small, polycationic particles can be immobilized in vitreous through multiple cooperative ionic interactions with hyaluronic acid of the vitreous interior, but such particles are generally toxic. Here, we synthesized and examined a biocompatible dextran-based nanocarrier (L-arginine with minimal toxicity, aiming to provide sustained release of therapeutic drugs in vitreous. We synthesized the nanocarriers with condensed cholesteryl dextran (CDEX) as core material. Cationic peptides containing 1 to 4 arginine groups, along with fluorescence tags, were conjugated to the CDEX surface. We monitored the carrier diffusion rate ex vivo and half-lives in vivo in rodent vitreous using fluorescence imaging. We evaluated the toxicity by histological examinations at the second, third, eighth, and thirty-sixth week. The diffusion rate of nanocarriers was inversely related to zeta potential values in freshly isolated vitreous humor. We observed increased half-lives in vivo with increasing zeta potential (up to 240 days). Histological examinations confirmed no adverse effects on ocular morphology and organization. We demonstrated the potential of L-arginine peptide-conjugated nanocarriers toward safe and sustained therapeutic release system for posterior eye diseases.

  16. Low fluence rate photodynamic therapy combined with intravitreal bevacizumab for neovascular age-related macular degeneration.

    Science.gov (United States)

    Costagliola, Ciro; Romano, Mario R; Rinaldi, Michele; dell'Omo, Roberto; Chiosi, Flavia; Menzione, Massimo; Semeraro, Francesco

    2010-02-01

    To report the efficacy and safety of intravitreal bevacizumab (IVB) alone versus IVB plus low-fluence photodynamic therapy (PDT) in age-related macular degeneration (AMD) patients and to verify the occurrence of a synergistic effect of the combined approach on visual acuity, size and morphology of lesion, as well as on the treatment rate. Prospective comparative interventional study on 85 patients with treatment-naive classic, or predominantly classic, subfoveal choroidal neovascularisation secondary to AMD. Patients were randomly assigned to group 1 (IVB injections) and group 2 (IVB plus low fluence PDT). In group 2, the PDT with verteporfin was delivered with a low fluence rate (300 mW/cm2 for 83 s, 25 J/cm2). The follow-up was scheduled at 1, 3, 6, 9 and 12 months. The eye without recurrence received a mean of 2.8 (group 1) versus 1.4 (group 2) IVB injections, whereas the eyes with recurrence received a mean of 3.2 (group 1) versus 2.2 (group 2) IVB injections. The difference in reinjection rate between the two groups was statistically significant (p=0.03, ANOVA test). Visual acuity improvement was not statistically significant between the two groups (p=0.31). The combination of IVB with low fluence PDT for the treatment of classic or predominantly classic neovascular AMD works in a synergistic fashion with a significant reduction in IVB reinjections rate.

  17. Posterior Pole Sparing Laser Photocoagulation Combined with Intravitreal Bevacizumab Injection in Posterior Retinopathy of Prematurity

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    Rebecca Kim

    2014-01-01

    Full Text Available Purpose. To report the results of the posterior pole sparing laser photocoagulation combined with intravitreal bevacizumab injection (IVB in retinopathy of prematurity (ROP. Methods. A retrospective chart review of premature babies with ROP, all of whom received laser photocoagulation with IVB. Eleven eyes of 6 infants with advanced zone I ROP underwent laser ablation sparing posterior pole with concurrent IVB. The results were compared with those of full-laser treatment combined with IVB to 8 eyes of 5 infants with advanced ROP without involvement of the posterior pole. Results. The posterior pole sparing laser with IVB was performed with zone I, stage 3+ ROP at the mean postmenstrual age of 36 weeks and 5 days. The plus sign decreased significantly at postoperative day 1, the neovascular proliferation regressed by postoperative week 1, and the normal vascularization started at postoperative day 32 on the average. Two months after treatment, vascularization of the spared avascular area was completed. There was no macular dragging, tractional retinal detachment, foveal destruction by laser scars, or any other adverse event. No significant anatomical differences were identified from those of full-laser ablation combined with IVB. Conclusions. Posterior pole sparing laser with IVB can give favorable results without destruction of posterior pole retina.

  18. Obesity, inflammation and endothelial dysfunction.

    Science.gov (United States)

    Iantorno, M; Campia, U; Di Daniele, N; Nistico, S; Forleo, G B; Cardillo, C; Tesauro, M

    2014-01-01

    Cardiovascular disease is the leading cause of morbidity and mortality in obese individuals. Obesity dramatically increases the risk of development of metabolic and cardiovascular disease. This risk appears to originate from disruption in adipose tissue function leading to a chronic inflammatory state and to dysregulation of the endocrine and paracrine actions of adipocyte-derived factors. These, in turn, impair vascular homeostasis and lead to endothelial dysfunction. An altered endothelial cell phenotype and endothelial dysfunction are common among all obesity-related complications. A crucial aspect of endothelial dysfunction is reduced nitric oxide (NO) bioavailability. A systemic pro-inflammatory state in combination with hyperglycemia, insulin resistance, oxidative stress and activation of the renin angiotensin system are systemic disturbances in obese individuals that contribute independently and synergistically to decreasing NO bioavailability. On the other hand, pro-inflammatory cytokines are locally produced by perivascular fat and act through a paracrine mechanism to independently contribute to endothelial dysfunction and smooth muscle cell dysfunction and to the pathogenesis of vascular disease in obese individuals. The promising discovery that obesity-induced vascular dysfunction is, at least in part, reversible, with weight loss strategies and drugs that promote vascular health, has not been sufficiently proved to prevent the cardiovascular complication of obesity on a large scale. In this review we discuss the pathophysiological mechanisms underlying inflammation and vascular damage in obese patients.

  19. Endothelial keratoplasty: evolution and horizons

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    Gustavo Teixeira Grottone

    2012-12-01

    Full Text Available Endothelial keratoplasty has been adopted by corneal surgeons worldwide as an alternative to penetrating keratoplasty (PK in the treatment of corneal endothelial disorders. Since the first surgeries in 1998, different surgical techniques have been used to replace the diseased endothelium. Compared with penetrating keratoplasty, all these techniques may provide faster and better visual rehabilitation with minimal change in refractive power of the transplanted cornea, minimal induced astigmatism, elimination of suture-induced complications and late wound dehiscence, and a reduced demand for postoperative care. Translational research involving cell-based therapy is the next step in work on endothelial keratoplasty. The present review updates information on comparisons among different techniques and predicts the direction of future treatment.

  20. Recovery of plasma vascular endothelial growth factor concentrations during aflibercept loading phase and after the transition to bimonthly treatment for neovascular age-related macular degeneration.

    Science.gov (United States)

    Roald, Anca B; Aass, Hans C D; Moe, Morten C

    2015-12-01

    To provide data on plasma vascular endothelial growth factor (VEGF) concentration during three consecutive monthly intravitreal aflibercept injections and after transition to bimonthly treatment in patients with neovascular age-related macular degeneration (nAMD). Sixteen consecutive treatment-naïve Caucasian patients with nAMD were included in the study. The treatment consisted of one intravitreal aflibercept (2 mg) injection every 28 days for three consecutive months followed by a fourth injection 8 weeks later. VEGF plasma concentrations were measured with Luminex on day 0 (baseline, prior to first injection); days 1, 6 and 27 (prior to second injection); day 55 (prior to third injection) and days 97 and 111 (after third injection). Baseline plasma VEGF concentration was 59.6±13.3 pg/mL. Aflibercept decreased plasma VEGF concentration to 32.5±3 pg/mL on day 1 (precovery 6 weeks after the third injection. Identifier no. NCT02125864. 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/

  1. Ex vivo investigation of ocular tissue distribution following intravitreal administration of connexin43 mimetic peptide using the microdialysis technique and LC-MS/MS.

    Science.gov (United States)

    Bisht, Rohit; Mandal, Abhirup; Rupenthal, Ilva D; Mitra, Ashim K

    2016-12-01

    This study aimed to develop and evaluate an ex vivo eye model for intravitreal drug sampling and tissue distribution of connexin43 mimetic peptide (Cx43MP) following intravitreal injection using the microdialysis technique and LC-MS/MS. An LC-MS/MS method was developed, validated, and applied for quantification of Cx43MP in ocular tissues. Microdialysis probes were calibrated for in vitro recovery studies. Bovine eyes were fixed in a customized eye holder and after intravitreal injection of Cx43MP, microdialysis probes were implanted in the vitreous body. Vitreous samples were collected at particular time intervals over 24 h. Moreover, 24 and 48 h after intravitreal injection ocular tissues were collected, processed, and analyzed for Cx43MP concentrations using LC-MS/MS. The LC-MS/MS method showed good linearity (r 2  = 0.9991). The mean percent recovery for lower (LQC), medium (MQC), and higher quality control (HQC) (0.244, 3.906, and 125 μg/mL) was found to be 83.83, 84.92, and 94.52, respectively, with accuracy ranges between 96 and 99 % and limits of detection (LOD) and quantification (LOQ) of 0.122 and 0.412 μg/mL. The in vitro recovery of the probes was found to be over 80 %. As per microdialysis sample analysis, the Cx43MP concentration was found to increase slowly in the vitreous body up to 16 h and thereafter declined. After 48 h, the Cx43MP concentration was higher in vitreous, cornea, and retina compared to lens, iris, and aqueous humor. This ex vivo model may therefore be a useful tool to investigate intravitreal kinetics and ocular disposition of therapeutic molecules after intravitreal injection.

  2. Intravitreal injection of (99)Tc-MDP inhibits the development of laser-induced choroidal neovascularization in rhesus monkeys.

    Science.gov (United States)

    Lai, Kunbei; Jin, Chenjin; Tu, Shu; Xiong, Yunfan; Huang, Rui; Ge, Jian

    2014-07-01

    The aim of this study was to investigate the safety and efficacy of intravitreal injection of (99)Tc-MDP, a decay product of (99m)Tc-MDP, on the development of laser-induced choroidal neovascularization (CNV) in rhesus monkeys. Experimental CNV was induced by argon laser with a small high-energy laser spot. Monkeys were given 50 μL of (99)Tc-MDP at a concentration of 0.005 μg/mL (n = 6) or 0.01 μg/mL (n = 6) by intravitreal injection once a week immediately after laser injury for a period of 56 days. Control animals were treated with the same volume of PBS (n = 6) in the same way. Eyes were monitored by ophthalmic examination, color fundus photography, fluorescence fundus angiography (FFA), optical coherence tomography (OCT) and histology. Incidences of grade 4 CNV lesions as well as the leakage areas of grade 4 CNVs on the late-phase of fluorescein angiograms were measured in a standardized, randomized and masked fashion fortnightly. The maximum widths and heights of grade 4 CNVs were also calculated by histology at the end of the experiment. Toxicity of (99)Tc-MDP on the retina was evaluated by electroretinogram (ERG) and histologic analysis. (99)Tc-MDP reduced the incidences of grade 4 CNVs by 33.33 % and 39.40 % in the 0.005 μg/mL and 0.01 μg/mL groups, respectively, compared with the PBS group on day 28 (P MDP treated groups than those in the PBS group. Although intravitreal injection of (99)Tc-MDP led to mild inflammatory reaction in the anterior chamber, histology and ERG findings demonstrated that (99)Tc-MDP did not cause any change in histological structure or function of the retina (p>0.05). Intravitreal injection of (99)Tc-MDP can inhibit the development of laser-induced CNV without toxic effect on retina, suggesting that (99)Tc-MDP has therapeutic potential for CNV related diseases.

  3. Preclinical safety evaluation of a recombinant AAV8 vector for X-linked retinoschisis after intravitreal administration in rabbits.

    Science.gov (United States)

    Marangoni, Dario; Wu, Zhijian; Wiley, Henry E; Zeiss, Caroline J; Vijayasarathy, Camasamudram; Zeng, Yong; Hiriyanna, Suja; Bush, Ronald A; Wei, Lisa L; Colosi, Peter; Sieving, Paul A

    2014-12-01

    X-linked retinoschisis (XLRS) is a retinal disease caused by mutations in the gene encoding the protein retinoschisin (RS1) and one of the most common causes of macular degeneration in young men. Currently, no FDA-approved treatments are available for XLRS and a replacement gene therapy could provide a promising strategy. We have developed a novel gene therapy approach for XLRS, based on the administration of AAV8-scRS/IRBPhRS, an adeno-associated viral vector coding the human RS1 protein, via the intravitreal route. On the basis of our prior study in an Rs1-KO mouse, this construct transduces efficiently all the retinal layers, resulting in an RS1 expression similar to that observed in the wild-type and improving retinal structure and function. In support of a clinical trial, we carried out a study to evaluate the ocular safety of intravitreal administration of AAV8-scRS/IRBPhRS into 39 New Zealand White rabbits. Two dose levels of vector, 2e(10) and 2e(11) vector genomes per eye (vg/eye), were tested and ocular inflammation was monitored over a 12-week period by serial ophthalmological and histopathological analysis. A mild ocular inflammatory reaction, consisting mainly of vitreous infiltrates, was observed within 4 weeks from injection, in both 2e(10) and 2e(11) vg/eye groups and was likely driven by the AAV8 capsid. At 12-week follow-up, ophthalmological examination revealed no clinical signs of vitreitis in either of the dose groups. However, while vitreous inflammatory infiltrate was significantly reduced in the 2e(10) vg/eye group at 12 weeks, some rabbits in the higher dose group still showed persistence of inflammatory cells, histologically. In conclusion, intravitreal administration of AAV8-scRS/IRBPhRS into the rabbit eye produces a mild and transient intraocular inflammation that resolves, at a 2e(10) vg/eye dose, within 3 months, and does not cause irreversible tissue damages. These data support the initiation of a clinical trial of intravitreal

  4. Combination therapy of intravitreal triamcinolone and photodynamic therapy with verteporfin for subfoveal choroidal neovascularization

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    Hussain Nazimul

    2006-01-01

    Full Text Available Aim: To evaluate the six months follow-up outcome of combined intravitreal triamcinolone acetonide (IVTA and photodynamic therapy (PDT for subfoveal choroidal neovascularization compared to PDT alone. Study design: Prospective interventional pilot study. Materials and Methods: Patients with six months follow-up of IVTA following PDT (Group I, eight eyes and PDT alone (Group II, eight eyes were included. Four mg/ 0.1 ml of IVTA was injected 7-10 days following PDT. The patients were reevaluated every month for the first two months and every three months thereafter in both the groups. Results: Group I: The mean age was 65.8±11.8 years (range: 47-79 years. Five patients were male. The total treatment sessions in six months were 11 (mean: 1.36. At six months, one eye had ³ 10 letters gain and three eyes had > 10 letters loss. Four eyes had stable vision. Two eyes (25% developed increased intraocular pressure (>40 mmHg during follow-up. Group II: The mean age was 58.7±11.7 years (range: 46-76 years. Five patients were male. The total treatment sessions in six months were 17 (mean: 2.13. At six months, six eyes had ³ 10 letters gain and none had > 10 letters loss. Two eyes had stable vision. Conclusion: The mean number of treatment sessions following combination therapy of IVTA (4 mg and PDT appears relatively less (1.36 at six months compared to PDT alone (mean: 2.13. ( P =0.02

  5. Long-term retinal toxicity of intravitreal commercially available preserved triamcinolone acetonide (Kenalog) in rabbit eyes.

    Science.gov (United States)

    Albini, Thomas A; Abd-El-Barr, Muhammad M; Carvounis, Petros E; Iyer, Mohan N; Lakhanpal, Rohit R; Pennesi, Mark E; Chevez-Barrios, Patricia; Wu, Samuel M; Holz, Eric R

    2007-01-01

    To investigate whether intravitreal Kenalog (IVTK; Bristol Meyers Squibb Company, Princeton, NJ) produces histologic or electroretinographic changes in the rabbit retina up to 3 months after injection. Ten Dutch-belted rabbits were injected with 4 mg/0.1 mL Kenalog in one eye and 0.1 mL physiologic salt solution (PSS) in the fellow eye. Simultaneous bilateral dark-adapted electroretinography was performed 2 weeks and 12 weeks after injection in 10 and 6 rabbits, respectively. Saturated a-wave amplitude, maximal scotopic b-wave amplitude, and individual a-wave and b-wave amplitudes of IVTK-injected and control eyes were compared at 2 and 12 weeks after injection. Light microscopy was performed on both eyes of three animals 3 months after injection. Immunohistochemistry was performed with antibodies recognizing vimentin and human alveolar macrophage (HAM)-56, markers of glial cells and macrophages, respectively. No significant difference was observed in the saturated a-wave or maximal scotopic b-wave amplitudes between the PSS-injected eyes and the IVTK-injected eyes at 2 weeks (P = 0.95 and P = 0.56, respectively) and 12 weeks (P = 0.82 and P = 0.17) after injection. Light microscopy and immunohistochemistry disclosed only rare macrophages in the vitreous of IVTK-injected eyes. Retinal layers, retinal pigment epithelium, and choriocapillaris in treatment and control eyes were unremarkable. No demonstrable electroretinographic or histologic changes occurred to suggest immediate or delayed widespread retinal toxicity of IVTK.

  6. Hydrosilylated Porous Silicon Particles Function as an Intravitreal Drug Delivery System for Daunorubicin

    Science.gov (United States)

    Hartmann, Kathrin I.; Nieto, Alejandra; Wu, Elizabeth C.; Freeman, William R.; Kim, Jae Suk; Chhablani, Jay; Sailor, Michael J.

    2013-01-01

    Abstract Purpose To evaluate in vivo ocular safety of an intravitreal hydrosilylated porous silicon (pSi) drug delivery system along with the payload of daunorubicin (DNR). Methods pSi microparticles were prepared from the electrochemical etching of highly doped, p-type Si wafers and an organic linker was attached to the Si-H terminated inner surface of the particles by thermal hydrosilylation of undecylenic acid. DNR was bound to the carboxy terminus of the linker as a drug-loading strategy. DNR release from hydrosilylated pSi particles was confirmed in the excised rabbit vitreous using liquid chromatography–electrospray ionization–multistage mass spectrometry. Both empty and DNR-loaded hydrosilylated pSi particles were injected into the rabbit vitreous and the degradation and safety were studied for 6 months. Results The mean pSi particle size was 30×46×15 μm with an average pore size of 15 nm. Drug loading was determined as 22 μg per 1 mg of pSi particles. An ex vivo drug release study showed that intact DNR was detected in the rabbit vitreous. An in vivo ocular toxicity study did not reveal clinical or pathological evidence of any toxicity during a 6-month observation. Hydrosilylated pSi particles, either empty or loaded with DNR, demonstrated a slow elimination kinetics from the rabbit vitreous without ocular toxicity. Conclusions Hydrosilylated pSi particles can host a large quantity of DNR by a covalent loading strategy and DNR can be slowly released into the vitreous without ocular toxicity, which would appear if an equivalent quantity of free drug was injected. PMID:23448595

  7. Efficacy of Intravitreal Bevacizumab in Treatment of Proliferative Type 2 Idiopathic Juxtafoveal Telangiectasia

    Directory of Open Access Journals (Sweden)

    Ökkeş Baz

    2017-06-01

    Full Text Available Objectives: To evaluate the effectiveness of intravitreal bevacizumab (IVB in patients with subretinal neovascularization secondary to type 2 juxtafoveal telangiectasia. Materials and Methods: Ten eyes of 10 patients were included in this retrospective study. All cases were treated with IVB (1.25 mg bevacizumab. Visual acuity and slit-lamp anterior and posterior segment examinations were performed at each visit. Central macular thickness (CMT and intraretinal/subretinal fluid were evaluated via spectral domain optical coherence tomography (OCT. Loss of a line in visual acuity chart and presence of fluid on OCT were defined as criteria for repeated treatment. Results: The mean age of patients was 66.0±7.0 years (56-75. The mean follow-up time was 54.7±16.0 month (24-72. The mean BCVA was 0.62±0.35 (0.00-1.00 logMAR at baseline and 0.54±0.35 (0.00-1.00 logMAR at final exam (p=0.03. The mean CMT was 251±25.4 µm at baseline and 239±39.3 µm at final exam (p=0.01. Patients received an average of 1.7±1.0 IVB injections during follow-up. At baseline, all cases had intraretinal/subretinal fluid. There was no fluid at final examination of all cases. Conclusion: IVB treatment may be effective in the treatment of subretinal neovascularization secondary to type 2 juxtafoveal telangiectasia.

  8. Symmetry in early response to intravitreal ranibizumab in bilateral diabetic macular oedema.

    Science.gov (United States)

    Guillard, Margaux; Dupas, Bénédicte; El Sanharawi, Mohamed; Erginay, Ali; Tadayoni, Ramin; Massin, Pascale

    2016-08-01

    To study the symmetry in response to bilateral diabetic macular oedema (DME) treated with bilateral intravitreal injections of ranibizumab (IVR). The charts of 36 eyes of 18 patients treated with a loading dose of three monthly IVR in both eyes were retrospectively reviewed. Favourable anatomical response was defined as a decrease by more than 10% in baseline central macular thickness (CMT), and favourable functional response was defined as an increase in visual acuity (VA) ≥5 letters. A symmetric response was defined as a similar anatomical and/or functional response in the first (FE) and second (SE) treated eyes. The VA improved significantly after ranibizumab treatment in both eyes (p < 0.01). A statistically significant positive correlation was found for the functional response to ranibizumab between the FE and the SE (R(2)  = 0.26, p = 0.03). The mean CMT decreased significantly in both eyes (p < 0.01). A strong positive correlation was observed between the anatomical response to ranibizumab in the FE and the SE (R(2)  = 0.37, p = 0.01). Symmetric favourable anatomical and functional responses were observed in 13 patients (72%). In two additional patients, an asymmetric functional response was observed despite a decrease in retinal thickness in both eyes. Symmetric anatomical and functional responses were observed in 72% of patients with DME after three initial IVR in each eye. This finding could be of clinical interest in the decision to treat the fellow eye, in a disease where a bilateral involvement is frequent. © 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  9. Antibacterial properties of 2% lidocaine and reduced rate of endophthalmitis after intravitreal injection.

    Science.gov (United States)

    Tustin, Aaron; Kim, Stephen J; Chomsky, Amy; Hubbard, G Baker; Sheng, Jinsong

    2014-05-01

    To determine whether the application of subconjunctival 2% lidocaine/0.1% methylparaben for anesthesia may reduce rates of endophthalmitis after intravitreal (IVT) injection. We performed in vitro experiments to determine the antibacterial properties of 2% lidocaine/0.1% methylparaben (lidocaine) against causative organisms of endophthalmitis. Isolates of Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus viridans from patients with endophthalmitis were incubated with or without lidocaine. Aliquots (100 µL) were plated on Mueller-Hinton (S. aureus and S. epidermidis) or blood agar plates (S. viridans) at 0, 10, 30, 120, and 240 minutes, and colonies were counted after 24 hours. A retrospective review of 15,042 IVT injections was performed from January 2004 to February 2011 to determine the rate of endophthalmitis with or without application of subconjunctival lidocaine for anesthesia. Lidocaine demonstrated rapid bactericidal effects against all 3 organisms. After 10 minutes of exposure, there was approximately a 90% (P < 0.01), 95% (P < 0.001), and 92% (P < 0.001) reduction in colony forming units when compared with time 0 for S. aureus, S. epidermidis, and S. viridans, respectively. Complete elimination of colony forming units occurred at subsequent time points for each organism in contrast to logarithmic increase for control plates. There were a total of 0 cases of endophthalmitis of 6,853 IVT injections performed with subconjunctival lidocaine and 8 cases of endophthalmitis of 8,189 (0.1%) IVT injections performed with other methods of anesthesia (P = 0.03). Application of subconjunctival 2% lidocaine/0.1% methylparaben for anesthesia may reduce the incidence of endophthalmitis after IVT injection.

  10. Protective effect of intravitreal administration of tresperimus, an immunosuppressive drug, on experimental autoimmune uveoretinitis.

    Science.gov (United States)

    Bousquet, Elodie; Camelo, Serge; Leroux les Jardins, Guillaume; Goldenberg, Brigitte; Naud, Marie-Christine; Besson-Lescure, Bernadette; Lebreton, Luc; Annat, Jocelyne; Behar-Cohen, Francine; de Kozak, Yvonne

    2011-07-20

    To test the efficiency of locally administrated tresperimus in experimental autoimmune uveoretinitis (EAU). EAU was induced in Lewis rats by S-antigen (S-Ag) immunization. Three intravitreal injections of tresperimus (prevention or prevention/treatment protocols) were performed at different time points after immunization. The pharmacokinetics of tresperimus was evaluated in the ocular tissues and plasma. The in vitro effect of tresperimus was evaluated on macrophages. EAU was graded clinically and histologically. Blood ocular barrier permeability was evaluated by protein concentration in ocular fluids. Immune response to S-Ag was examined by delayed type hypersensitivity, the expression of inflammatory cytokines in lymph nodes, ocular fluids and serum by multiplex ELISA, and in ocular cells by RT-PCR. In vitro, tresperimus significantly reduced the production of inflammatory cytokines by lipopolysaccharide-stimulated macrophages. In vivo, in the treatment protocol, efficient tresperimus levels were measured in the eye but not in the plasma up to 8 days after the last injection. Tresperimus efficiently reduced inflammation, retinal damage, and blood ocular barrier permeability breakdown. It inhibited nitric oxide synthase-2 and nuclear factor κBp65 expression in ocular macrophages. IL-2 and IL-17 were decreased in ocular media, while IL-18 was increased. By contrast, IL-2 and IL-17 levels were not modified in inguinal lymph nodes draining the immunization site. Moreover, cytokine levels in serum and delayed type hypersensitivity to S-Ag were not different in control and treated rats. In the prevention/treatment protocol, ocular immunosuppressive effects were also observed. Locally administered tresperimus appears to be a potential immunosuppressive agent in the management of intraocular inflammation.

  11. Endothelial dysfunction in diabetes mellitus

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    Hadi AR Hadi

    2008-01-01

    Full Text Available Hadi AR Hadi, Jassim Al SuwaidiDepartment of Cardiology and Cardiovascular Surgery, Hamad General Hospital – Hamad Medical Corporation, Doha, State of Qatar; Department of Cardioscience, Sheikh Khalifa Medical City, Abu Dhabi, UAEAbstract: Diabetes mellitus is associated with an increased risk of cardiovascular disease, even in the presence of intensive glycemic control. Substantial clinical and experimental evidence suggest that both diabetes and insulin resistance cause a combination of endothelial dysfunctions, which may diminish the anti-atherogenic role of the vascular endothelium. Both insulin resistance and endothelial dysfunction appear to precede the development of overt hyperglycemia in patients with type 2 diabetes. Therefore, in patients with diabetes or insulin resistance, endothelial dysfunction may be a critical early target for preventing atherosclerosis and cardiovascular disease. Microalbuminuria is now considered to be an atherosclerotic risk factor and predicts future cardiovascular disease risk in diabetic patients, in elderly patients, as well as in the general population. It has been implicated as an independent risk factor for cardiovascular disease and premature cardiovascular mortality for patients with type 1 and type 2 diabetes mellitus, as well as for patients with essential hypertension. A complete biochemical understanding of the mechanisms by which hyperglycemia causes vascular functional and structural changes associated with the diabetic milieu still eludes us. In recent years, the numerous biochemical and metabolic pathways postulated to have a causal role in the pathogenesis of diabetic vascular disease have been distilled into several unifying hypotheses. The role of chronic hyperglycemia in the development of diabetic microvascular complications and in neuropathy has been clearly established. However, the biochemical or cellular links between elevated blood glucose levels, and the vascular lesions remain

  12. Endothelial cells in dengue hemorrhagic fever.

    Science.gov (United States)

    Srikiatkhachorn, Anon; Kelley, James F

    2014-09-01

    Therapies to prevent or reverse endothelial dysfunction and vascular leak found in dengue hemorrhagic fever (DHF) have not been identified. In this review we summarize dengue viruses and the spectrum of human disease and highlight evidence of endothelial cell dysfunction in DHF based on studies in patients and mouse and tissue culture models. Evidence suggests that both virus antigen and host immune response, can cause endothelial cell dysfunction and weaken endothelial barrier integrity. We suggest possible therapeutic interventions and highlight how therapies targeting altered endothelial function might be evaluated in animal models and in patients with DHF. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Intravitreal anti-VEGF therapy for neovascular age-related macular degeneration and the risk of stroke.

    LENUS (Irish Health Repository)

    Cleary, C A

    2011-05-01

    The purpose of this study was to compare the vascular event rate in AMD patients treated with an intravitreal VEGF inhibitor with a historical control group treated with photodynamic therapy. We reviewed medical records of 83 patients treated with intravitreal anti-VEGF for AMD between 2005-2007, and 60 patients treated with PDT between 2001-2004. Mean follow-up in the anti-VEGF group was 40 months versus 95 months in the PDT group. Mean age (76 +\\/- 9 years, versus 74 +\\/- 10 years, p=n.s.) and cardiovascular risk factor profile were similar. Vascular event rates in each group were 2.6 per 100 patient years versus 2.3 per 100 patient years, (p = n.s). Age over 80 years was associated with an increased risk of a vascular event (odds ratio = 1.113, p<0.05). Despite the high prevalence of risk factors in AMD patients, the incidence of vascular events was low and associated with older age rather than therapy received.

  14. Endothelial dysfunction: a comprehensive appraisal

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    Vilariño Jorge O

    2006-02-01

    Full Text Available Abstract The endothelium is a thin monocelular layer that covers all the inner surface of the blood vessels, separating the circulating blood from the tissues. It is not an inactive organ, quite the opposite. It works as a receptor-efector organ and responds to each physical or chemical stimulus with the release of the correct substance with which it may maintain vasomotor balance and vascular-tissue homeostasis. It has the property of producing, independently, both agonistic and antagonistic substances that help to keep homeostasis and its function is not only autocrine, but also paracrine and endocrine. In this way it modulates the vascular smooth muscle cells producing relaxation or contraction, and therefore vasodilatation or vasoconstriction. The endothelium regulating homeostasis by controlling the production of prothrombotic and antithrombotic components, and fibrynolitics and antifibrynolitics. Also intervenes in cell proliferation and migration, in leukocyte adhesion and activation and in immunological and inflammatory processes. Cardiovascular risk factors cause oxidative stress that alters the endothelial cells capacity and leads to the so called endothelial "dysfunction" reducing its capacity to maintain homeostasis and leads to the development of pathological inflammatory processes and vascular disease. There are different techniques to evaluate the endothelium functional capacity, that depend on the amount of NO produced and the vasodilatation effect. The percentage of vasodilatation with respect to the basal value represents the endothelial functional capacity. Taking into account that shear stress is one of the most important stimulants for the synthesis and release of NO, the non-invasive technique most often used is the transient flow-modulate "endothelium-dependent" post-ischemic vasodilatation, performed on conductance arteries such as the brachial, radial or femoral arteries. This vasodilatation is compared with the

  15. Improvement of visual acuity based on optical coherence tomography patterns following intravitreal bevacizumab treatment in patients with diabetic macular edema

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    Haider R. Cheema

    2014-04-01

    Full Text Available AIM:To report the visual outcome based on various patterns of optical coherence tomography (OCT morphology in diabetic macular edema (DME, following treatment with anti-VEGF intravitreal bevacizumab (IVB injection.METHODS:Sixty-seven consecutive subjects with centre involving DME underwent intravitreal injection of Bevacizumab (1.25 mg/0.05 mL in this retrospective, comparative, non randomized study. The DME was classified into one of four categories:focal, diffuse, focal cystoid and neurosensory detachment based on OCT. Best corrected visual acuity (BCVA, macular appearance, and OCT findings were used to decide whether the subject should have a repeat injection of intravitreal bevacizumab. Outcome measures were a change in mean BCVA (Snellen converted to logMAR and central macular thickness (CMT in each group during the six month follow-up period.RESULTS:The mean BCVA improved to logMAR 0.23 at final follow-up from a baseline of 0.32 logMAR (P=0.040 in the focal group, logMAR 0.80 at final follow-up from a baseline of 0.82 logMAR (P=0.838 in the diffuse group, worsened to logMAR 0.53 at final follow-up from a baseline of 0.43 logMAR (P=0.276 in the focal cystoid group, and improved to logMAR 0.79 at final follow-up from a baseline of 0.93 logMAR (P=0.490 in the neurosensory detachment group. The mean CMT before treatment were 298.8±25.03 μm in the focal group, 310.8±40.6 μm in the diffuse group, 397.15±31.05 μm in the focal cystoid group and 401.03±75.1 μm in the neurosensory detachment group. A mean of 2.05 (range:1-5 injections in the focal group, 1.32 (range:1-2 in the diffuse group, 2.6 (range:1-6 in the focal cystoid group and 2.6 (range:1-6 in the neurosensory detachment group were performed during the six month follow-up period. Following intravitreal bevacizumab treatment, vision improved, remained unchanged or worsened in 11, 7 and 2 subjects in focal group; 11, 9 and 8 in diffuse group; 0, 2 and 4 in focal cystoid group and 5

  16. Cytotoxicity of VEGF121/rGel on vascular endothelial cells resulting in inhibition of angiogenesis is mediated via VEGFR-2

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    Hittelman Walter N

    2011-08-01

    Full Text Available Abstract Background The fusion protein VEGF121/rGel composed of the growth factor VEGF121 and the plant toxin gelonin targets the tumor neovasculature and exerts impressive anti-vascular effects. We have previously shown that VEGF121/rGel is cytotoxic to endothelial cells overexpressing VEGFR-2 but not to endothelial cells overexpressing VEGFR-1. In this study, we examined the basis for the specific toxicity of this construct and assessed its intracellular effects in vitro and in vivo. Methods We investigated the binding, cytotoxicity and internalization profile of VEGF121/rGel on endothelial cells expressing VEGFR-1 or VEGFR-2, identified its effects on angiogenesis models in vitro and ex vivo, and explored its intracellular effects on a number of molecular pathways using microarray analysis. Results Incubation of PAE/VEGFR-2 and PAE/VEGFR-1 cells with 125I-VEGF121/rGel demonstrated binding specificity that was competed with unlabeled VEGF121/rGel but not with unlabeled gelonin. Assessment of the effect of VEGF121/rGel on blocking tube formation in vitro revealed a 100-fold difference in IC50 levels between PAE/VEGFR-2 (1 nM and PAE/VEGFR-1 (100 nM cells. VEGF121/rGel entered PAE/VEGFR-2 cells within one hour of treatment but was not detected in PAE/VEGFR-1 cells up to 24 hours after treatment. In vascularization studies using chicken chorioallantoic membranes, 1 nM VEGF121/rGel completely inhibited bFGF-stimulated neovascular growth. The cytotoxic effects of VEGF121/rGel were not apoptotic since treated cells were TUNEL-negative with no evidence of PARP cleavage or alteration in the protein levels of select apoptotic markers. Microarray analysis of VEGF121/rGel-treated HUVECs revealed the upregulation of a unique "fingerprint" profile of 22 genes that control cell adhesion, apoptosis, transcription regulation, chemotaxis, and inflammatory response. Conclusions Taken together, these data confirm the selectivity of VEGF121/rGel for VEGFR-2

  17. Intravitreal injection analysis at the Bascom Palmer Eye Institute: evaluation of clinical indications for the treatment and incidence rates of endophthalmitis

    Directory of Open Access Journals (Sweden)

    Ludimila L Cavalcante

    2010-05-01

    Full Text Available Ludimila L Cavalcante, Milena L Cavalcante, Timothy G Murray, Michael M Vigoda, Yolanda Piña, Christina L Decatur, R Prince Davis, Lisa C Olmos, Amy C Schefler, Michael B Parrott, Kyle J Alliman, Harry W Flynn, Andrew A MoshfeghiBascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, FL, USAObjective: To report the incidence of endophthalmitis, in addition to its clinical and microbiological aspects, after intravitreal injection of vascular-targeting agents.Methods: A retrospective review of a consecutive series of 10,142 intravitreal injections of vascular targeting agents (bevacizumab, ranibizumab, triamcinolone acetonide, and preservative-free triamcinolone acetonide between June 1, 2007 and January 31, 2010, performed by a single service (TGM at the Bascom Palmer Eye Institute.Results: One case of clinically-suspected endophthalmitis was identified out of a total of 10,142 injections (0.009%, presenting within three days of injection of bevacizumab. The case was culture-positive for Staphylococcus epidermidis. Final visual acuity was 20/40 after pars plana vitrectomy surgery.Conclusions: In this series, the incidence of culture-positive endophthalmitis after intravitreal injection of vascular agents in an outpatient setting was very low. We believe that following a standardized injection protocol, adherence to sterile techniques and proper patient follow-up are determining factors for low incidence rates.Keywords: endophthalmitis, intravitreal injections, vascular targeting agents 

  18. Durable recovery of the macular architecture and functionality of a diagnosed age-related macular degeneration 1 year after a single intravitreal injection of dobesilate

    Science.gov (United States)

    Cuevas, P; Outeiriño, L A; Azanza, C; Giménez-Gallego, G

    2013-01-01

    Among the age-related diseases that affect vision, age-related macular degeneration is the most frequent cause of blindness in patients older than 60 years. In this communication, we report the full anatomical and functional recovery of a patient diagnosed with wet age-related macular degeneration 1 year after a single intravitreal injection of dobesilate. PMID:24225910

  19. Challenges in pediatric endothelial keratoplasty

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    Vikas Mittal

    2014-01-01

    Full Text Available We performed endothelial keratoplasty (EK in three eyes of two siblings (2.5 years, male and 3.5 years, female with congenital hereditary endothelial dystrophy (CHED and report the intraoperative and postoperative difficulties. Repeated iris prolapse, apprehension of crystalline lens touch due to positive vitreous pressure, and need for frequent air injections to attach the graft were intraoperative challenges in all three eyes. These were addressed by use of Sheet′s glide instead of Busin′s glide during graft insertion and suturing of main and side ports before air injection. One eye had graft dislocation on second postoperative day due to eye rubbing by the child. Graft was repositioned with air and a venting incision was created. Postoperative examination required repeated general anesthesia. Corneal edema resolved completely in all three eyes. Present case series highlights the possible intraoperative and postoperative challenges and their solutions in pediatric EK for CHED.

  20. Endothelial Glycocalyx and Cardiopulmonary Bypass.

    Science.gov (United States)

    Myers, Gerard J; Wegner, Julie

    2017-09-01

    On the outer surface of a human cell there is a dense layer of complex carbohydrates called glycocalyx, also referred to as glycans or the sugar coating on the cell surface, which is composed of a complex array of oligosaccharide and polysaccharide glucose chains that are covalently bonded to proteoglycans and lipids bound to the cell membrane surface. Studies of an intact endothelial glycocalyx layer (EGL) have revealed a number of critical functions that relate the importance of this protective layer to vascular integrity and permeability. These functions include the following: stabilization and maintenance of the vascular endothelium, an active reservoir of essential plasma proteins (i.e., albumin, antithrombin, heparan sulfate, and antioxidants), a buffer zone between the blood (formed elements) and the surface of the endothelium, and a mechanotransducer to detect changes in shear stress that facilitate vascular tone. There have been numerous review articles about the structure and function of endothelial glycocalyx over the past two decades, yet there still remains a significant knowledge gap in the perfusion literature around the importance of EGL. Perioperative fluid management and gaseous microemboli can both contribute to the damage/degradation of endothelial glycocalyx. A damaged EGL can result in systemic and myocardial edema, platelet and leukocyte adhesion, fluid extravasation, and contributes to microvascular perfusion heterogeneity. Knowledge of the importance of endothelial glycocalyx will enable clinicians to have a better understanding of the impact of gaseous microbubbles, hyperoxia, and ischemic reperfusion injury during cardiac surgery. The purpose of this article is to provide an in depth review of the EGL and how this protective barrier impacts the microcirculation, fluid homeostasis, inflammation, and edema during cardiac surgery.

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2014-04-01

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

  3. Retinoblastoma Vitreous Seed Clouds (Class 3): A Comparison of Treatment with Ophthalmic Artery Chemosurgery with or without Intravitreous and Periocular Chemotherapy.

    Science.gov (United States)

    Francis, Jasmine H; Iyer, Saipriya; Gobin, Y Pierre; Brodie, Scott E; Abramson, David H

    2017-10-01

    To compare the efficacy and toxicity of treating class 3 retinoblastoma vitreous seeds with ophthalmic artery chemosurgery (OAC) alone versus OAC with intravitreous chemotherapy. Retrospective cohort study. Forty eyes containing clouds (class 3 vitreous seeds) of 40 retinoblastoma patients (19 treated with OAC alone and 21 treated with OAC plus intravitreous and periocular chemotherapy). Ocular survival, disease-free survival and time to regression of seeds were estimated with Kaplan-Meier estimates. Ocular toxicity was evaluated by clinical findings and electroretinography: 30-Hz flicker responses were compared at baseline and last follow-up visit. Continuous variables were compared with Student t test, and categorical variables were compared with the Fisher exact test. Ocular survival, disease-free survival, and time to regression of seeds. There were no disease- or treatment-related deaths and no patient demonstrated externalization of tumor or metastatic disease. There was no significant difference in the age, laterality, disease, or disease status (treatment naïve vs. previously treated) between the 2 groups. The time to regression of seeds was significantly shorter for eyes treated with OAC plus intravitreous chemotherapy (5.7 months) compared with eyes treated with OAC alone (14.6 months; P clouds with OAC and intravitreous and periocular chemotherapy, compared with OAC alone, resulted in a shorter time to regression and was associated with fewer recurrences requiring additional treatment and fewer enucleations. The toxicity to the retina does not seem to be significantly worse in the OAC plus intravitreous chemotherapy group. Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. [Endothelial dysfunction in hypertension--clinical implications].

    Science.gov (United States)

    Kosmala, Wojciech

    2002-04-01

    Endothelial cells produce both vasodilatating compounds as nitric oxide, prostacycline, endothelial derived hyperpolarising factor and counteracting substances known as endothelial derived contracting factors: endothelin, tromboxan A2, prostaglandin H2, free oxygen radicals. Natural balance between both groups affects blood perfusion of various tissues and constitutes important element in blood pressure control. More and more attention is paid to endothelial dysfunction in patogenesis of hypertension. In a number of studies endothelial dysfunction in hypertensive patients was found out as decreased release of nitric oxide or increased production of endothelin. Principle mechanism of impaired function of endothelium in hypertension seems to be decreased production and increased degradation of nitric oxide mainly due to free oxygen radicals. Favorable effects in improvement of endothelial function were achieved by using ACE inhibitors, AT1 receptor blockers and calcium channel antagonists.

  6. Isolation and culture of pulmonary endothelial cells.

    OpenAIRE

    Ryan, U S

    1984-01-01

    Methods for isolation, identification and culture of pulmonary endothelial cells are now routine. In the past, methods of isolation have used proteolytic enzymes to detach cells; thereafter, traditional methods for cell passaging have used trypsin/EDTA mixtures. Cells isolated and passaged using proteolytic enzymes have been useful in establishing the field and in verifying certain endothelial properties. However, there is a growing awareness of the role of endothelial cells in processing vas...

  7. Health-related quality of life, visual function and treatment satisfaction following intravitreal dexamethasone implant for diabetic macular edema

    Directory of Open Access Journals (Sweden)

    Ramu J

    2017-03-01

    Full Text Available Jayashree Ramu,1 Irini Chatziralli,1 Yit Yang,2 Geeta Menon,3 Clare Bailey,4 Michael Eckstein,5 Phil Hykin,1 Sobha Sivaprasad1 On behalf of the OZDRY Study Group 1NIHR Moorfields Biomedical Research Centre, London, 2The Royal Wolverhampton Hospitals NHS Trust, Wolverhampton, 3Frimley Health NHS Foundation Trust, Surrey, 4Bristol Eye Hospital, Bristol, 5Brighton and Sussex University Hospital, Brighton, UK Purpose: The aim of this study was to explore and describe quantitatively patient-reported outcome measures (PROMs, ie, health-related quality of life (QoL, visual function and treatment satisfaction, in patients with diabetic macular edema (DME receiving two different regimens of Ozurdex (intravitreal dexamethasone implant. Methods: In this multicenter, prospective study, 100 patients with center-involving refractory DME were randomized 1:1 to either five monthly fixed dosing or optical coherence tomography (OCT-guided pro re nata (PRN regimen of dexamethasone intravitreal implant therapy. The primary outcome was the difference between arms in change in PROMs and health-related QoL from baseline to 12 months, as measured by the Retinopathy-Dependent Quality of Life (RetDQoL questionnaire, Visual Function Questionnaire-25 (VFQ-25 and Retinopathy Treatment Satisfaction Questionnaire (RetTSQ. Results: There was no statistically significant difference in the RetDQoL score and VFQ-25 score at month 12 compared to those at baseline, whereas the total mean RetTSQ score increased significantly at the exit visit. The two treatment arms did not differ significantly regarding the change in PROMs and health-related QoL questionnaires. Logistic regression analysis showed that visual acuity (VA of ≥55 letters, central foveal thickness <300 µm and macular volume <9.2 mm3 at the exit visit (month 12 predicted a higher change in RetTSQ. Conclusion: This study showed that there is a statistically significant improvement in treatment satisfaction, as

  8. Kaempferol induces ATM/p53-mediated death receptor and mitochondrial apoptosis in human umbilical vein endothelial cells.

    Science.gov (United States)

    Lee, Chiu-Fang; Yang, Jai-Sing; Tsai, Fuu-Jen; Chiang, Ni-Na; Lu, Chi-Cheng; Huang, Yu-Syuan; Chen, Chun; Chen, Fu-An

    2016-05-01

    Kaempferol is a member of the flavonoid compounds found in vegetables and fruits. It is shown to exhibit biological impact and anticancer activity, but no report exists on the angiogenic effect of kaempferol and induction of cell apoptosis in vitro. In this study, we investigated the role of kaempferol on anti-angiogenic property and the apoptotic mechanism of human umbilical vein endothelial cells (HUVECs). Our results demonstrated that kaempferol decreased HUVEC viability in a time- and concentration-dependent manner. Kaempferol also induced morphological changes and sub-G1 phase cell population (apoptotic cells). Kaempferol triggered apoptosis of HUVECs as detecting by DNA fragmentation, comet assay and immunofluorescent staining for activated caspase-3. The caspase signals, including caspase-8, -9 and -3, were time-dependently activated in HUVECs after kaempferol exposure. Furthermore, pre-treatment with a specific inhibitor of caspase-8 (Z-IETD-FMK) significantly reduced the activity of caspase-8, -9 and -3, indicating that extrinsic pathway is a major signaling pathway in kaempferol-treated HUVECs. Importantly, kaempferol promoted reactive oxygen species (ROS) evaluated using flow cytometric assay in HUVECs. We further investigated the upstream extrinsic pathway and showed that kaempferol stimulated death receptor signals [Fas/CD95, death receptor 4 (DR4) and DR5] through increasing the levels of phosphorylated p53 and phosphorylated ATM pathways in HUVECs, which can be individually confirmed by N-acetylcysteine (NAC), ATM specific inhibitor (caffeine) and p53 siRNA. Based on these results, kaempferol-induced HUVEC apoptosis was involved in an ROS-mediated p53/ATM/death receptor signaling. Kaempferol might possess therapeutic effects on cancer treatment in anti-vascular targeting.

  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

    PURPOSE: To examine the effect of intravitreally injected bevacizumab (Avastin) on the histological and angiographic morphology of choroidal neovascularization (CNV) in a masked and placebo-controlled animal study. METHODS: Choroidal neovascularization was induced surgically in 11 porcine eyes...... by perforating Bruch's membrane with a retinal perforator. After closure of the ports used for the vitrectomy, which was performed to facilitate the Bruch's membrane rupture, 0.05 ml of either bevacizumab or Ringer-Lactat (placebo) was injected into the vitreous cavity. Eyes were enucleated after 14 days. Fundus...... photographs and fluorescein angiograms (FAs) were obtained immediately prior to enucleation. Sections of formalin- and paraffin-embedded eyes were examined by light microscopy and by immunohistochemical staining. RESULTS: Placebo-injected eyes exhibited the highest propensity to leak, with five of six eyes...

  10. 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

    PURPOSE: To examine the effect of intravitreally injected bevacizumab (Avastin) on the histological and angiographic morphology of choroidal neovascularization (CNV) in a masked and placebo-controlled animal study. METHODS: Choroidal neovascularization was induced surgically in 11 porcine eyes...... by perforating Bruch's membrane with a retinal perforator. After closure of the ports used for the vitrectomy, which was performed to facilitate the Bruch's membrane rupture, 0.05 ml of either bevacizumab or Ringer-Lactat (placebo) was injected into the vitreous cavity. Eyes were enucleated after 14 days. Fundus...... photographs and fluorescein angiograms (FAs) were obtained immediately prior to enucleation. Sections of formalin- and paraffin-embedded eyes were examined by light microscopy and by immunohistochemical staining. RESULTS: Placebo-injected eyes exhibited the highest propensity to leak, with five of six eyes...

  11. Minimizando erros na administração de drogas intravítreas Minimizing errors in intravitreal drug injection

    Directory of Open Access Journals (Sweden)

    Shu I Yeh

    2003-01-01

    Full Text Available OBJETIVO: Avaliar possíveis erros na administração de drogas intravítreas para o tratamento da endoftalmite e propor técnica que seja reprodutível e acessível. MÉTODOS: Avaliação de técnicas utilizadas e aferição dos volumes retidos nas agulhas utilizando balança analítica. RESULTADOS: A média e o desvio padrão dos volumes retidos nas agulhas de 26, 22 (25 x 0,7 mm e 30 x 0,7 mm e 18 G (gauge foram 0,051±0,006, 0,056±0,005, 0,055±0,004 e 0,075±0,004, respectivamente, para a marca Ryncos® e 0,050±0,003, 0,056±0,002, 0,063±0,002 e 0,084±0,004, respectivamente, para a marca Becton-Dickinson®. Houve diferença estatisticamente significante entre os volumes retidos das duas marcas para as agulhas de 26, 22 (30 x 0,7 mm e 18 G com p = 0,01, p PURPOSE: To assess evaluate the accuracy of intravitreal drug administration in the treatment of endophthalmitis and to suggest a reproducible and accessible technique for this procedure. METHODS: To assess the retained volumes in needles used for the intravitreal injection of antibiotics using an analytical scale. RESULTS: Means and standard deviations of retained volumes in the 26, 22 ( 25 x 0.7 mm and 30 x 0.7 mm and 18 G were respectively 0.051±0.006, 0.056±0.005, 0.055±0.004 and 0.075±0.004 for needles Ryncos® and 0.050±0.003, 0.056±0.002, 0.063±0.002 and 0.084±0.004 for Becton-Dickinson®. There were statistically significant differences in the retained volumes between the two needle brands for 26, 22 (30 x 0.7 mm and 18 G needles with p = 0.01, p < 0.01 and p < 0.01 respectively. No difference was found only for 25 x 0.7 mm 22 G needle with p = 0.83. CONCLUSION: Most needles used for intravitreal injection hold a retained volume in the reserve needle compartment that should be considered during the injection technique, therefore minimizing errors during intravitreal injection of antibiotics.

  12. Use of intravitreal bevacizumab or triamcinolone acetonide as a preoperative adjunct to vitrectomy for vitreous haemorrhage in diabetics

    Directory of Open Access Journals (Sweden)

    Daniel Araújo Ferraz

    2013-02-01

    Full Text Available PURPOSE: To evaluate the effect of preoperative intravitreal bevacizumab (IVB or triamcinolone (IVT on the rate of early postvitrectomy hemorrhage in proliferative diabetic retinopathy (PDR. METHODS: Eligible eyes were assigned randomly to 1 of 3 groups: the IVB group received 1.25 mg bevacizumab, the IVT group received 4,0mg triamcinolone and the control group underwent a sham procedure. The primary outcome measure was the incidence of early postvitrectomy hemorrhage. Secondary outcome measures included changes in visual acuity (BCVA and adverse events. RESULTS: Twenty and seven eyes, 9 in each group were randomized. The incidence of vitreous hemorrhage was lower in the IVB group (p=0.18. Postoperative vitreous hemorrhage at 1 month also was less in the IVB group compared with the control group (p > 0.05. The rate of bleeding immediately after surgery was higher in IVT group with 4 (44.4% cases. The overall mean visual acuity was 1.72 ± 0.37 logMAR preoperatively and 1.32 ± 0.73 logMAR in 6 months after surgery. Accessing visual acuity by group evidenced that the IVB group had initial mean logMAR VA of 1.87 and 1.57 logMAR VA at the six months (p = 0.84. In IVT group, initial mean VA was 1.75 logMAR and 0.96 logMAR VA at six months (p < 0.001. And in control group, the initial mean VA was 1.85 logMAR and 1.57 logMAR VA at six months (p= 0.34. CONCLUSION: Intravitreal injection of bevacizumab 1 week before vitrectomy seems to reduce the incidence of early postvitrectomy hemorrhage in diabetic patients. There was a better visual acuity outcome in the triamcinolone group.

  13. Combined photodynamic therapy and intravitreal bevacizumab for idiopathic polypoidal choroidal vasculopathy: one-year follow-up

    Directory of Open Access Journals (Sweden)

    Mario R Romano

    2010-10-01

    Full Text Available Mario R Romano1, Ugo Cipollone2, Francesco Semeraro3, Michele Rinaldi4, Ciro Costagliola11Dipartimento di Scienze per la Salute, Università degli Studi del Molise, Campobasso; 2Dipartimento di Oftalmologia, Ospedale G Vietri, Larino, Campobasso; 3Clinica Oculistica, Università degli Studi di Brescia, Brescia; 4Clinica Oculistica, II Università degli Studi di Napoli, Napoli, ItalyObjective: To report the efficacy and safety of combined photodynamic therapy (PDT and intravitreal bevacizumab (IVB injection in the treatment of idiopathic polypoidal choroidal vasculopathy (IPCV.Material and methods: A prospective case series of 10 eyes of 10 consecutive patients affected by IPCV with subfoveal involvement. PDT plus IVB (1.25 mg/0.05 mL injection two weeks later was performed in all patients. Two adjunctive injections of bevacizumab were scheduled at four and eight weeks after the initial treatment. Best-corrected visual acuity (BCVA, fluorescein and indocyanine green angiographies, and optical coherence tomography were obtained at baseline, and at one, three, six, nine, and 12 months.Results: The combined treatment led to an improvement of both neurosensory detachment and pigmented epithelial detachment in all eyes, with a decrease of exudation and regression of macular thickness, which remained stable to the end of follow-up. However, BCVA remained stable over the 12 months of follow-up.Conclusion: These findings demonstrate that PDT/IVB combined therapy is able to achieve morphologic stabilization of the IPCV lesion, through a rapid decrease of macular thickness and regression of the size of polypoidal vascular lesion.Keywords: combined treatment, idiopathic polypoidal choroidal vasculopathy, age-related macular degeneration, intravitreal bevacizumab, photodynamic therapy

  14. SAFETY AND EFFICACY OF INTRAVITREAL DEXAMETHASONE IMPLANTS IN THE MANAGEMENT OF MACULAR EDEMA SECONDARY TO INFECTIOUS UVEITIS.

    Science.gov (United States)

    Fonollosa, Alex; Llorenç, Victor; Artaraz, Joseba; Jimenez, Beatriz; Ruiz-Arruza, Ioana; Agirrebengoa, Koldo; Cordero-Coma, Miguel; Costales-Mier, Felipe; Adan, Alfredo

    2016-09-01

    To assess the safety and efficacy of intravitreal dexamethasone implants in the treatment of macular edema secondary to infectious uveitis. We retrospectively reviewed clinical records from three uveitis referral units in Spain. The main outcome measures were rate of reactivation of infection, improvements in visual acuity and resolution of macular edema, as measured by optical coherence tomography. We included eight eyes from seven patients with a median age of 64 years (30-75). Etiologies of the infections were Herpes simplex virus-type 1, Varicela-Zoster virus, Treponema pallidum, Brucella mellitensis, Borrelia burgdorferi, Toxoplasma gondii, and cytomegalovirus. Median visual acuity was 20/160 (20/30-20/400) at baseline and 20/70 (20/25-20/200) at the last follow-up visit. Mean macular thickness was 516 μm (115) at baseline and 266.3 μm (40) at the last follow-up visit. Visual acuity improved in 100% of the eyes and none of the eyes showed macular edema at the last follow-up visit. Five patients required reinjections of the implant. Only one patient required antiglaucoma drops for a temporary increase in ocular pressure. There were no cases of reactivation of the infectious ocular disease. Median follow-up time was 18 months. In this small case series of eyes with macular edema secondary to infectious uveitis, treatment with dexamethasone intravitreal implants was not associated with reactivation of the infectious ocular disease. Furthermore, significant improvements in visual acuity and macular thickness were observed in our patients.

  15. Intravitreal Ciliary Neurotrophic Factor Transiently Improves Cone-Mediated Function in a CNGB3-/- Mouse Model of Achromatopsia.

    Science.gov (United States)

    Marangoni, Dario; Vijayasarathy, Camasamudram; Bush, Ronald A; Wei, Lisa L; Wen, Rong; Sieving, Paul A

    2015-10-01

    Ciliary neurotrophic factor (CNTF) was recently shown to augment cone function in CNGB3 mutant achromat dogs. However, testing CNTF-releasing implant in human CNGB3 achromats failed to show benefit. We evaluated the effects of CNTF protein on the retinal function in an additional achromatopsia model, the CNGB3-/- mouse. Fifty-nine CNGB3-/- mice (postnatal day [PD] ± SD = 30 ± 7) received a unilateral intravitreal injection of 1 or 2 μg CNTF protein, and 15 wild-type (WT) mice (PD = 34 ± 3) received 1 μg CNTF. Retinal function was evaluated by flash ERG and photopic flicker ERG (fERG) at 7 and 14 days after treatment. Seven days post CNTF, the photopic b-wave Vmax was significantly increased in CNGB3-/- mice (P < 0.01), whereas it was reduced in WT mice (P < 0.05). Ciliary neurotrophic factor significantly increased the amplitude of photopic fERG and the photopic oscillatory potentials (OPs) in CNGB3-/- mice. Ciliary neurotrophic factor did not alter the scotopic a-wave in either CNGB3-/- or WT mice, but it increased the scotopic b-wave k (P < 0.01) in CNGB3-/- mice, indicating diminished scotopic sensitivity, and reduced the scotopic b-wave Vmax in WT mice (P < 0.05). No difference was found in ERG parameters between 1 or 2 μg CNTF. Fourteen days after CNTF injection the ERG changes in CNGB3-/- mice were lost. Intravitreal bolus CNTF protein caused a small and transient improvement of cone-mediated function in CNGB3-/- mice, whereas it reduced rod-mediated function. The increase in photopic OPs and the lack of changes in scotopic a-wave suggest a CNTF effect on the inner retina.

  16. Intravitreal pegaptanib sodium (Macugen®) for treatment of diabetic macular oedema: a morphologic and functional study.

    Science.gov (United States)

    Rinaldi, Michele; Chiosi, Flavia; dell'Omo, Roberto; Romano, Mario R; Parmeggiani, Francesco; Semeraro, Francesco; Mastropasqua, Rodolfo; Costagliola, Ciro

    2012-12-01

    To study whether morphologic (foveal thickness, FT) variations of clinically significant macular oedema (CMO) in patients suffering from diabetes following intravitreal pegaptanib sodium (IVP) injection were associated with functional [macular sensitivity (MS) and colour discrimination (CD)] changes. A longitudinal, interventional, non-randomized study was performed. FT was assessed by optical coherence tomography (OCT), MS by microperimetry, best-corrected visual acuity (BCVA) by early treatment diabetic retinopathy study charts (ETDRS) and CD by Farnswoth-Munsell test. The treatment protocol consisted of three consecutive injections (0.3 mg/0.05 ml; baseline, week 6 and week 12). Follow-up checks were scheduled at 18, 24, 36 and 48 weeks, after injections. Thirty eyes of 30 patients with clinically significant CMO were included for analysis. After IVP a significant decrease of FT occurred with a mean reduction from baseline of 56.9% (P= 0.0001). An improvement of functional parameters was recorded in all patients (BCVA from 18.2 ± 8.5 letters to 25.5 ± 8.4 letters, P < 0.005, MS from 8.6 ± 2.16 dB to 10.6 ± 2.61 dB, P < 0.001, colour analysis from 376.1 ± 125.6 TES to 116 ± 34.6 TES, P= 0.0001). A statistically significant correlation between FT and BCVA as well as MS and CD was also found. Neither ocular nor systemic adverse events were reported. Intravitreal pegaptanib significantly reduced FT, with a concomitant improvement of MS and CD. This association emphasizes the efficacy of IVP in the treatment of CMO. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

  17. Endothelial dysfunction after non-cardiac surgery

    DEFF Research Database (Denmark)

    Søndergaard, E S; Fonnes, S; Gögenur, I

    2015-01-01

    BACKGROUND: More than 50% of patients with increased troponin levels after non-cardiac surgery have an impaired endothelial function pre-operatively. Non-invasive markers of endothelial function have been developed for the assessment of endothelial dysfunction. The aim of this paper was to system......BACKGROUND: More than 50% of patients with increased troponin levels after non-cardiac surgery have an impaired endothelial function pre-operatively. Non-invasive markers of endothelial function have been developed for the assessment of endothelial dysfunction. The aim of this paper...... was to systematically review the literature to evaluate the association between non-cardiac surgery and non-invasive markers of endothelial function. METHODS: A systematic search was conducted in MEDLINE, EMBASE and Cochrane Library Database according to the PRISMA guidelines. Endothelial dysfunction was described only...... with non-invasive measurements done both pre- and post-operatively and published in English. All types of non-cardiac surgery and both men and women of all ages were included. RESULTS: We found 1722 eligible studies in our search, and of these, five studies fulfilled our inclusion and exclusion criteria...

  18. INTRAVITREAL DEXAMETHASONE IMPLANT AS ADJUVANT TREATMENT FOR BEVACIZUMAB- AND RANIBIZUMAB-RESISTANT NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: A Prospective Pilot Study.

    Science.gov (United States)

    Barikian, Anita; Salti, Haytham; Safar, Ammar; Mahfoud, Ziyad R; Bashshur, Ziad F

    2017-07-01

    To study the benefit of intravitreal dexamethasone implant in the management of neovascular age-related macular degeneration resistant to bevacizumab and ranibizumab. Patients with persistent macular fluid on optical coherence tomography despite monthly treatment with at least three consecutive bevacizumab injections followed by at least three ranibizumab injections were prospectively enrolled. A single dexamethasone implant was administered followed by intravitreal ranibizumab 1 week later. Ranibizumab was continued afterward on an as-needed basis. Main outcomes were improvement in central retinal thickness and best-corrected visual acuity. Nineteen patients (19 eyes) were enrolled. There was no significant change in best-corrected visual acuity over 6 months. Greatest reduction in mean central retinal thickness, from 295.2 μm to 236.2 μm, occurred 1 month after dexamethasone implant (P macular intraretinal fluid in eyes with neovascular age-related macular degeneration resistant to bevacizumab and ranibizumab. However, this treatment had a limited duration.

  19. Resveratrol and Endothelial Nitric Oxide

    Directory of Open Access Journals (Sweden)

    Ning Xia

    2014-10-01

    Full Text Available Nitric oxide (NO derived from the endothelial NO synthase (eNOS has antihypertensive, antithrombotic, anti-atherosclerotic and antiobesogenic properties. Resveratrol is a polyphenol phytoalexin with multiple cardiovascular and metabolic effects. Part of the beneficial effects of resveratrol are mediated by eNOS. Resveratrol stimulates NO production from eNOS by a number of mechanisms, including upregulation of eNOS expression, stimulation of eNOS enzymatic activity and reversal of eNOS uncoupling. In addition, by reducing oxidative stress, resveratrol prevents oxidative NO inactivation by superoxide thereby enhancing NO bioavailability. Molecular pathways underlying these effects of resveratrol involve SIRT1, AMPK, Nrf2 and estrogen receptors.

  20. Dysfunctional Endothelial Progenitor Cells in Metabolic Syndrome

    Science.gov (United States)

    Devaraj, Sridevi; Jialal, Ishwarlal

    2012-01-01

    The metabolic syndrome (MetS) is highly prevalent and confers an increased risk of diabetes and cardiovascular disease. A key early event in atherosclerosis is endothelial dysfunction. Numerous groups have reported endothelial dysfunction in MetS. However, the measurement of endothelial function is far from optimum. There has been much interest recently in a subtype of progenitor cells, termed endothelial progenitor cells (EPCs), that can circulate, proliferate, and dfferentiate into mature endothelial cells. EPCs can be characterized by the assessment of surface markers, CD34 and vascular endothelial growth factor receptor-2, VEGFR-2 (KDR). The CD34+KDR+ phenotype has been demonstrated to be an independent predictor of cardiovascular outcomes. MetS patients without diabetes or cardiovascular diseases have decreased EPC number and functionality as evidenced by decreased numbers of colony forming units, decreased adhesion and migration, and decreased tubule formation. Strategies that have been shown to upregulate and enhance EPC number and functionality include statins, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and peroxisome-proliferator-activating-receptor gamma agonists. Mechanisms by which they affect EPC number and functionality need to be studied. Thus, EPC number and/or functionality could emerge as novel cellular biomarkers of endothelial dysfunction and cardiovascular disease risk in MetS. PMID:21941528

  1. Progressive outer retinal necrosis in the era of highly active antiretroviral therapy: successful management with intravitreal injections and monitoring with quantitative PCR.

    Science.gov (United States)

    Yin, Philip D; Kurup, Shree K; Fischer, Steven H; Rhee, Henry H; Byrnes, Gordon A; Levy-Clarke, Grace A; Buggage, Ronald R; Nussenblatt, Robert B; Mican, JoAnn M; Wright, Mary E

    2007-03-01

    Progressive outer retinal necrosis (PORN) is an ocular disease in individuals with AIDS and is associated with substantial morbidity. The optimal management of PORN and its clinical course in the HAART era is unclear. We report a case of successfully managed PORN that provides insight into the monitoring and treatment of this disease. Intravitreal injections and intravenous therapy targeted towards varicella zoster virus (VZV) were used to treat PORN. HAART was initiated for HIV-1 therapy. Serial PCR for VZV was performed on aqueous humor to monitor the clinical course. The presence of VZV DNA from aqueous humor correlated with clinical exacerbations of disease. Initiation of twice weekly intravitreal injections with dual antiviral drugs appeared to be an important therapeutic intervention that resulted in remission of PORN. Secondary prophylaxis against VZV was successfully withdrawn after HAART induced partial immune recovery. In addition to aggressive therapy with intravitreal injections, HAART and quantitative measurements of VZV DNA from aqueous humor have important roles in the management of PORN. A multidisciplinary approach involving specialists in infectious diseases, ophthalmology, and clinical microbiology will improve the chances for successful long-term outcomes.

  2. Management of recurrent inflammatory choroidal neovascular membrane secondary to Vogt-Koyanagi-Harada syndrome, using combined intravitreal injection of bevacizumab and triamcinolone acetate

    Directory of Open Access Journals (Sweden)

    Sivakami A Pai

    2012-01-01

    Full Text Available The purpose of this report is to evaluate the efficacy and safety of combined intravitreal injection of bevacizumab and intravitreal triamcinolone acetonide (IVTA for recurrent inflammatory choroidal neovascular membrane (CNVM. It was a prospective interventional study of a young female, who was a known case of Vogt-Koyanagi-Harada syndrome. She presented with an inflammatory choroidal neovascualar membrane and signs of panuveitis in the right eye. She underwent a complete ophthalmic examination. She was given intravitreal injection of bevacizumab and IVTA at different sites. There was complete regression of CNVM and ocular inflammation within a week. After six months, she had recurrence of CNVM in the same eye, which was treated similarly. There was a complete resolution of CNVM and ocular inflammation after the combination therapy and systemic steroids, until one year of follow-up. No serious systemic or ocular adverse events were noted. Combination therapy appears to be an effective and safe method in the management of recurrent inflammatory CNVM.

  3. Efficacy of 12-month treatment of neovascular age-related macular degeneration with intravitreal bevacizumab based on individually determined injection strategies after three consecutive monthly injections.

    Science.gov (United States)

    Mekjavic, Polona Jaki; Kraut, Aleksandra; Urbancic, Mojca; Lenassi, Eva; Hawlina, Marko

    2011-11-01

    To report the results of intravitreal treatment with bevacizumab in neovascular age-related macular degeneration (AMD) after a loading dose (LD) of three monthly injections followed by an optical coherence tomography (OCT)-guided strategy, based on best-corrected visual acuity (VA) and number of injections required over 1 year. A series of consecutive cases of 149 eyes of 147 patients received three or more intravitreal injections of bevacizumab (1.25 mg) for neovascular AMD over a 1-year period. The patients underwent ophthalmological examinations: measurement of the VA, fluorescein angiography, dilated fundus examination at baseline; VA, OCT and dilated fundus examination at monthly follow-up visits. Repeated injections were given each month for the first 3 months (LD); thereafter, injections were only administered if leakage or macular oedema were present. Mean baseline VA was 51 ± 14 letters, which improved to 58 ± 15 letters (p injections per patient treated for 1 year was 5.1 (range 3-9). No systemic side-effects were noted. Treatment of neovascular AMD with intravitreal bevacizumab administered in LD of three monthly injections and followed by an OCT-guided strategy provides functional and anatomical improvements for up to 1 year. © 2009 The Authors. Journal compilation © 2009 Acta Ophthalmol.

  4. 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.

  5. Uso de la triamcinolona subtenoniana en pacientes con rubeosis del iris Use of intravitreal triamcinolone in patients with iris rubeosis

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    Irene Rojas Rondón

    2008-12-01

    Full Text Available OBJETIVO: Describir el comportamiento de la rubeosis del iris luego de la aplicación de triamcinolona subtenoniana. MÉTODOS: Se realizó un estudio descriptivo de corte longitudinal con 25 pacientes para un total de 32 ojos con diferentes afecciones oculares. Se efectuaron pruebas estadísticas con las variables del estudio y en algunas se utilizó la prueba de los signos de comparación para datos pareados y en otras se aplicó chi cuadrado. Se caracterizaron las variables: edad, sexo, causa de rubeosis del iris y sus estadios, síntomas y tratamiento con láser de panfotocoagulación retiniana. RESULTADOS: La retinopatía diabética proliferativa fue la afección más frecuente en el 76 % de los pacientes, seguida de la oclusión de la vena central retiniana. Del total de pacientes tratados, el 37,5 % evolucionó satisfactoriamente el estado de la rubeosis del iris. Fue mayor el número de pacientes que mejoraron el grado de la rubeosis con tratamiento combinado de láser y triamcinolona subtenoniana, aunque estadísticamente no fue significativo. El estado de la rubeosis mejoró en más de la mitad de los pacientes con tiempo de evolución menor de 6 meses. En aquellos con un tiempo mayor de 6 meses y neovascularización del iris grado III, se pudo estabilizar el glaucoma neovascular. CONCLUSIÓN: Se plantea que la triamcinolona subtenoniana constituye una alternativa para el manejo de este tipo de pacientes.OBJECTIVE: To describe the behaviour of iris rubeosis after using intravitreal triamcinolone. METHODS: A longitudinal descriptive study was performed on 25 patients for a total number of 32 eyes with several ocular diseases. Statistical tests were made with the study variables; sign comparison for paired data and Chi square tests were applied. The variables were age, sex, cause of iris rubeosis and its staging, symptoms and treatment with retinal photocoagulation laser. RESULTS: Proliferative diabetic retinopathy was the most common

  6. Systematic review and mixed treatment comparison of intravitreal aflibercept with other therapies for diabetic macular edema (DME).

    Science.gov (United States)

    Korobelnik, Jean-Francois; Kleijnen, Jos; Lang, Shona H; Birnie, Richard; Leadley, Regina M; Misso, Kate; Worthy, Gill; Muston, Dominic; Do, Diana V

    2015-05-15

    This was an indirect comparison of the effectiveness of intravitreal aflibercept (IVT-AFL) 2 mg every 8 weeks after 5 initial monthly doses (or if different periods, after an initial monthly dosing period) (2q8) and other diabetic macular edema (DME) therapies at doses licensed outside the USA. A comprehensive search was undertaken to source relevant studies. Feasibility networks were prepared to identify viable comparisons of 12-month outcomes between IVT-AFL 2q8 and therapies licensed outside the USA, which were assessed for clinical and statistical homogeneity. Pooled effect sizes (mean difference [MD] and relative risk/risk ratio [RR]) were calculated using fixed- and random-effects models. Indirect comparisons were performed using Bucher analysis. If at least one 'head-to-head' study was found then a mixed treatment comparison (MTC) was performed using Bayesian methods. Two 12-month comparisons could be undertaken based on indirect analyses: IVT-AFL 2q8 versus intravitreal ranibizumab (IVR) 0.5 mg as needed (PRN) (10 studies) and IVT-AFL 2q8 versus dexamethasone 0.7 mg implants (three studies). There was an increase in mean best-corrected visual acuity (BCVA) with IVT-AFL 2q8 over IVR 0.5 mg PRN by 4.67 letters [95% credible interval (CrI): 2.45-6.87] in the fixed-effect MTC model (10 studies) and by 4.82 letters [95% confidence interval (CI): 2.52-7.11] in the Bucher indirect analysis (four studies). IVT-AFL 2q8 doubled the proportion of patients gaining ≥ 10 Early Treatment Diabetic Retinopathy Study letters at 12 months compared with dexamethasone 0.7 mg implants (RR = 2.10 [95% CI: 1.29-3.40]) in the fixed-effect model. There were no significant differences in safety outcomes between IVT-AFL 2q8 and IVR 0.5 mg PRN or dexamethasone 0.7 mg implants. Studies of IVT-AFL 2q8 showed improved 12-month visual acuity measures compared with studies of IVR 0.5 mg PRN and dexamethasone 0.7 mg implants based on indirect comparisons. These analyses are subject to a

  7. Heparan Sulfate Binding Promotes Accumulation of Intravitreally Delivered Adeno-associated Viral Vectors at the Retina for Enhanced Transduction but Weakly Influences Tropism.

    Science.gov (United States)

    Woodard, Kenton T; Liang, Katharine J; Bennett, William C; Samulski, R Jude

    2016-11-01

    Many adeno-associated virus (AAV) serotypes efficiently transduce the retina when delivered to the subretinal space but show limited success when delivered to the vitreous due to the inner limiting membrane (ILM). Subretinal delivery of AAV serotype 2 (AAV2) and its heparan sulfate (HS)-binding-deficient capsid led to similar expression, indicating transduction of the outer retina occurred by HS-independent mechanisms. However, intravitreal delivery of HS-ablated recombinant AAV2 (rAAV2) led to a 300-fold decrease in transduction compared to AAV2. Fluorescence in situ hybridization of AAV transgenes was used to identify differences in retinal trafficking and revealed that HS binding was responsible for AAV2 accumulation at the ILM. This mechanism was tested on human ex vivo retinas and showed similar accumulation with HS-binding AAV2 capsid only. To evaluate if HS binding could be applied to other AAV serotypes to enhance their transduction, AAV1 and AAV8 were modified to bind HS with a single-amino-acid mutation and tested in mice. Both HS-binding mutants of AAV1 and AAV8 had higher intravitreal transduction than their non-HS-binding parent capsid due to increased retinal accumulation. To understand the influence that HS binding has on tropism, chimeric AAV2 capsids with dual-glycan usage were tested intravitreally in mice. Compared to HS binding alone, these chimeric capsids displayed enhanced transduction that was correlated with a change in tropism. Taken together, these data indicate that HS binding serves to sequester AAV capsids from the vitreous to the ILM but does not influence retinal tropism. The enhanced retinal transduction of HS-binding capsids provides a rational design strategy for engineering capsids for intravitreal delivery. Adeno-associated virus (AAV) has become the vector of choice for viral gene transfer and has shown great promise in clinical trials. The need for development of an easy, less invasive injection route for ocular gene therapy

  8. Leukocytes Breach Endothelial Barriers by Insertion of Nuclear Lobes and Disassembly of Endothelial Actin Filaments

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    Sagi Barzilai

    2017-01-01

    Full Text Available The endothelial cytoskeleton is a barrier for leukocyte transendothelial migration (TEM. Mononuclear and polymorphonuclear leukocytes generate gaps of similar micron-scale size when squeezing through inflamed endothelial barriers in vitro and in vivo. To elucidate how leukocytes squeeze through these barriers, we co-tracked the endothelial actin filaments and leukocyte nuclei in real time. Nuclear squeezing involved either preexistent or de novo-generated lobes inserted into the leukocyte lamellipodia. Leukocyte nuclei reversibly bent the endothelial actin stress fibers. Surprisingly, formation of both paracellular gaps and transcellular pores by squeezing leukocytes did not require Rho kinase or myosin II-mediated endothelial contractility. Electron-microscopic analysis suggested that nuclear squeezing displaced without condensing the endothelial actin filaments. Blocking endothelial actin turnover abolished leukocyte nuclear squeezing, whereas increasing actin filament density did not. We propose that leukocyte nuclei must disassemble the thin endothelial actin filaments interlaced between endothelial stress fibers in order to complete TEM.

  9. Mitochondria, endothelial cell function, and vascular diseases.

    Science.gov (United States)

    Tang, Xiaoqiang; Luo, Yu-Xuan; Chen, Hou-Zao; Liu, De-Pei

    2014-01-01

    Mitochondria are perhaps the most sophisticated and dynamic responsive sensing systems in eukaryotic cells. The role of mitochondria goes beyond their capacity to create molecular fuel and includes the generation of reactive oxygen species, the regulation of calcium, and the activation of cell death. In endothelial cells, mitochondria have a profound impact on cellular function under both healthy and diseased conditions. In this review, we summarize the basic functions of mitochondria in endothelial cells and discuss the roles of mitochondria in endothelial dysfunction and vascular diseases, including atherosclerosis, diabetic vascular dysfunction, pulmonary artery hypertension, and hypertension. Finally, the potential therapeutic strategies to improve mitochondrial function in endothelial cells and vascular diseases are also discussed, with a focus on mitochondrial-targeted antioxidants and calorie restriction.

  10. Mitochondria, Endothelial Cell Function and Vascular Diseases

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    Xiaoqiang eTang

    2014-05-01

    Full Text Available Mitochondria are perhaps the most sophisticated and dynamic responsive sensing systems in eukaryotic cells. The role of mitochondria goes beyond their capacity to create molecular fuel and includes the generation of reactive oxygen species, the regulation of calcium, and the activation of cell death. In endothelial cells, mitochondria have a profound impact on cellular function under both healthy and diseased conditions. In this review, we summarize the basic functions of mitochondria in endothelial cells and discuss the roles of mitochondria in endothelial dysfunction and vascular diseases, including atherosclerosis, diabetic vascular dysfunction, pulmonary artery hypertension and hypertension. Finally, the potential therapeutic strategies to improve mitochondrial function in endothelial cells and vascular diseases are also discussed, with a focus on mitochondrial-targeted antioxidants and calorie restriction.

  11. Type 2 Diabetes: Endothelial dysfunction and Exercise

    OpenAIRE

    Hwang, Moon-Hyon; Kim, Sangho

    2014-01-01

    [Purpose] Vascular endothelial dysfunction is an early marker of atherosclerosis characterized by decreased nitric oxide bioavailability in the vascular endothelium and smooth muscle cells. Recently, some animal models and in vitro trials demonstrated that excessive superoxide production from mitochondria within vascular endothelial cells played a role in the pathogenesis of atherosclerosis in type 2 diabetes. This review provides a systematic assessment of the effectiveness of exercise to id...

  12. An ?All-laser? Endothelial Transplant

    OpenAIRE

    Rossi, Francesca; Canovetti, Annalisa; Malandrini, Alex; Lenzetti, Ivo; Pini, Roberto; Menabuoni, Luca

    2015-01-01

    The ?all laser? assisted endothelial keratoplasty is a procedure that is performed with a femtosecond laser used to cut the donor tissue at an intended depth, and a near infrared diode laser to weld the corneal tissue. The proposed technique enables to reach the three main goals in endothelial keratoplasty: a precise control in the thickness of the donor tissue; its easy insertion in the recipient bed and a reduced risk of donor lenticule dislocation. The donor cornea thickness is measured in...

  13. Comparative cyto-histological study of needle tip aspirates and entry sites after intravitreal injection using different needle types.

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    Lyubomyr Lytvynchuk

    Full Text Available A comparison of the cellular content of needle tip aspirates and entry sites after transconjunctival intravitreal injection (IVI using different needle types was performed. White outbred rats and human cadaver eyes were used for IVI by hypodermic 27 gauge (G and 30G needles, and spinal anesthesia Pencan 27G needles. Aspiration of vitreous for quantitative morphological and cell cultivation analysis, as well as cyto-histological analysis of aspirates and entry sites were carried out. The most common cells in the aspirates from all needle types were conjunctival epithelial-, ciliary body non-pigmented epithelial- and sclerocyte-like cells and granular proteins. Crystallized vitreous specimens were present in each aspirate. The entry sites of hypodermic needles showed marked trauma in all wall layers of rat and human eyes accompanied by cellular destruction and hemorrhages. Pencan 27G needle caused less tissue trauma with partial reposition of sclerocytes. Transconjunctival IVIs with hypodermic 27G and 30G, and Pencan 27G needles result in trauma of all layers of the eyeball. The possible consequences of cellular content being cut and injected into the eye, as well as the entry site wound shape deserve future consideration and improvements.

  14. Effects of Vitrectomy on Recurrent Macular Edema due to Branch Retinal Vein Occlusion after Intravitreal Injection of Bevacizumab

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    Tatsuya Yunoki

    2013-01-01

    Full Text Available Purpose. To evaluate the effects of pars plana vitrectomy (PPV on recurrent macular edema due to branch retinal vein occlusion (BRVO after intravitreal injections of bevacizumab (IVB. Methods. This retrospective study included 22 eyes of 22 patients who underwent single or multiple IVB injections for macular edema due to BRVO and showed a recurrence of macular edema. All patients then underwent PPV and were followed up for more than 6 months after the surgery with examinations of best corrected visual acuity (BCVA and optical coherence tomography (OCT. OCT parameters were central macular thickness (CMT and average retinal thickness in a 1-mm-diameter circular region at the fovea (MRT. Results. Mean BCVA, CRT, and MRT were significantly improved from the baseline after PPV. Greater improvement of BCVA, CRT, and MRT was obtained after 1 month of IVB than after 6 months of PPV. No eyes showed worsening of macular edema after the surgery. Conclusion. PPV improved BCVA and recurrent macular edema due to BRVO, but PPV that was less effective than IVB had been in the same patients. PPV may be one of the treatment options for recurrent macular edema due to BRVO after IVB.

  15. Intravitreal administration of HA-1077, a ROCK inhibitor, improves retinal function in a mouse model of huntington disease.

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    Mei Li

    Full Text Available Huntington disease (HD is an inherited neurodegenerative disease that affects multiple brain regions. It is caused by an expanded polyglutamine tract in huntingtin (Htt. The development of therapies for HD and other neurodegenerative diseases has been hampered by multiple factors, including the lack of clear therapeutic targets, and the cost and complexity of testing lead compounds in vivo. The R6/2 HD mouse model is widely used for pre-clinical trials because of its progressive and robust neural dysfunction, which includes retinal degeneration. Profilin-1 is a Htt binding protein that inhibits Htt aggregation. Its binding to Htt is regulated by the rho-associated kinase (ROCK, which phosphorylates profilin at Ser-137. ROCK is thus a therapeutic target in HD. The ROCK inhibitor Y-27632 reduces Htt toxicity in fly and mouse models. Here we characterized the progressive retinopathy of R6/2 mice between 6-19 weeks of age to determine an optimal treatment window. We then tested a clinically approved ROCK inhibitor, HA-1077, administered intravitreally via liposome-mediated drug delivery. HA-1077 increased photopic and flicker ERG response amplitudes in R6/2 mice, but not in wild-type littermate controls. By targeting ROCK with a new inhibitor, and testing its effects in a novel in vivo model, these results validate the in vivo efficacy of a therapeutic candidate, and establish the feasibility of using the retina as a readout for CNS function in models of neurodegenerative disease.

  16. Switching to Aflibercept in Diabetic Macular Edema Not Responding to Ranibizumab and/or Intravitreal Dexamethasone Implant

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    Antoine Herbaut

    2017-01-01

    Full Text Available Purpose. To assess short-term functional and anatomical outcomes of refractory diabetic macular edema (DME following a switch from ranibizumab or dexamethasone to aflibercept. Methods. We included retrospectively eyes with persistent DME after at least 3 ranibizumab and/or one dexamethasone implant intravitreal injections (IVI. The primary endpoint was the mean change in visual acuity (VA at month 6 (M6 after switching. Results. Twenty-five eyes were included. Before switching to aflibercept, 23 eyes received a median of 9.5 ranibizumab, and among them, 6 eyes received one dexamethasone implant after ranibizumab and 2 eyes received only one dexamethasone implant. Baseline VA, before any IVI, was 52.9 ± 16.5 letters, and preswitch VA was 57.1 ± 19.6 letters. The mean VA gain was +8 letters (p=0.01 between preswitch and M6. The mean central retinal thickness was 470.8 ± 129.9 μm before the switch and 303.3 ± 59.1 μm at M6 (p=0.001. Conclusion. Switching to aflibercept in refractory DME results in significant functional and anatomical improvement. The study was approved by the France Macula Federation ethical committee (FMF 2017-138.

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

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    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.

  18. Reduced Ang2 expression in aging endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Hohensinner, P.J., E-mail: philipp.hohensinner@meduniwien.ac.at [Department of Internal Medicine II, Medical University of Vienna, Vienna (Austria); Ebenbauer, B. [Department of Internal Medicine II, Medical University of Vienna, Vienna (Austria); Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna (Austria); Kaun, C.; Maurer, G. [Department of Internal Medicine II, Medical University of Vienna, Vienna (Austria); Huber, K. [Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna (Austria); 3rd Medical Department, Wilhelminenhospital, Vienna (Austria); Sigmund Freud University, Medical Faculty, Vienna (Austria); Wojta, J. [Department of Internal Medicine II, Medical University of Vienna, Vienna (Austria); Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna (Austria); Core Facilities, Medical University of Vienna, Vienna (Austria)

    2016-06-03

    Aging endothelial cells are characterized by increased cell size, reduced telomere length and increased expression of proinflammatory cytokines. In addition, we describe here that aging reduces the migratory distance of endothelial cells. Furthermore, we observe an increase of the quiescence protein Ang1 and a decrease of the endothelial activation protein Ang2 upon aging. Supplementing Ang2 to aged endothelial cells restored their migratory capacity. We conclude that aging shifts the balance of the Ang1/Ang2 network favouring a quiescent state. Activation of endothelial cells in aging might be necessary to enhance wound healing capacities. -- Highlights: •Endothelial cells display signs of aging before reaching proliferative senescence. •Aging endothelial cells express more angiopoietin 1 and less angiopoietin 2 than young endothelial cells. •Migratory capacity is reduced in aging endothelial cells.

  19. Reduced Ang2 expression in aging endothelial cells

    International Nuclear Information System (INIS)

    Hohensinner, P.J.; Ebenbauer, B.; Kaun, C.; Maurer, G.; Huber, K.; Wojta, J.

    2016-01-01

    Aging endothelial cells are characterized by increased cell size, reduced telomere length and increased expression of proinflammatory cytokines. In addition, we describe here that aging reduces the migratory distance of endothelial cells. Furthermore, we observe an increase of the quiescence protein Ang1 and a decrease of the endothelial activation protein Ang2 upon aging. Supplementing Ang2 to aged endothelial cells restored their migratory capacity. We conclude that aging shifts the balance of the Ang1/Ang2 network favouring a quiescent state. Activation of endothelial cells in aging might be necessary to enhance wound healing capacities. -- Highlights: •Endothelial cells display signs of aging before reaching proliferative senescence. •Aging endothelial cells express more angiopoietin 1 and less angiopoietin 2 than young endothelial cells. •Migratory capacity is reduced in aging endothelial cells.

  20. Retinal vein occlusion: current treatment.

    Science.gov (United States)

    Lattanzio, Rosangela; Torres Gimeno, Ana; Battaglia Parodi, Maurizio; Bandello, Francesco

    2011-01-01

    Retinal vein occlusion (RVO) is a pathology noted for more than 150 years. Although a lot has been written on the matter, it is still a frequent condition with multifactorial etiopathogenesis with many unclear aspects. The RVO pathogenesis has varied systemic and local implications that make it difficult to elaborate treatment guidelines. The management of the patient with RVO is very complex and a multidisciplinary approach is required in order to identify and correct the associated risk factors. Laser therapy remains the gold standard in RVO, but only modest functional improvement has been shown in branch retinal occlusion forms. Multicenter studies of intravitreal drugs present them as an option to combine with laser. Anti-vascular endothelial growth factor, corticosteroids and sustained-release implants are the future weapons to stop disease progression and get a better visual outcome. Consequently, it is useful to clarify some aspects of the pathology that allow a better patient management. Copyright © 2010 S. Karger AG, Basel.

  1. Fixation stability and implication for multifocal electroretinography in patients with neovascular age-related macular degeneration after anti-VEGF treatment

    DEFF Research Database (Denmark)

    Pedersen, Karen Bjerg; Sjølie, Anne Katrin; Vestergaard, Anders Højslet

    2016-01-01

    Purpose: To quantify fixation stability in patients with neovascular age-related macular degeneration (nAMD) at baseline, 3 and 6 months after anti-vascular endothelial growth factor (anti-VEGF) treatment and furthermore asses the implications of an unsteady fixation for multifocal...... electroretinography (mfERG) measurements. Methods: Fifty eyes of 50 nAMD patients receiving intravitreal anti-VEGF treatment with either bevacizumab or ranibizumab and eight eyes of eight control subjects were included. Fixation stability measurements were performed with the Eye-Link eyetracking system...... and the retinal area in degrees2 (deg2) containing the 68 % most frequently used fixation points (RAF68) was calculated. MfERG P1 amplitude and implicit time were analyzed in six concentric rings and as a summed response. Patients were examined at baseline, 3 and 6 months. Four different mfERG recordings were...

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    Purpose To examine the outcome after cataract surgery in patients with neovascular age-related macular degeneration (AMD) treated with intravitreal anti-vascular endothelial growth factor (VEGF) injections in routine clinical practice. Methods We extracted information about patients recorded...... 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 being...... with an average of 1.5 in the 6 months before surgery versus 1.7 in the 6 months after surgery (p = 0.25). Visual improvement was greater in patients when the time from latest injection to cataract surgery was lower. Conclusions Cataract surgery improves vision in patients undergoing treatment for neovascular AMD...

  3. 6-Hydroxydopamine induces brain vascular endothelial inflammation.

    Science.gov (United States)

    Fu, Qizhi; Song, Runluo; Yang, Zhongxi; Shan, Qi; Chen, Wenna

    2017-11-01

    Disruption of the blood-brain barrier associated with endothelial dysfunction is an important hallmark of Parkinson's disease (PD). 6-Hydroxydopamine (6-OHDA) is a synthetic dopamine derivate often used to model PD as it results in retrograde degeneration of striatal dopaminergic (DA) terminals. Presently, the effects of 6-OHDA on endothelial dysfunction remain unknown. Using a 6-OHDA rodent model of PD, we found that administration of 6-OHDA could increase the expression of endothelial adhesion molecules, such as intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin. An in vitro study displayed that treatment with 6-OHDA increased the release of these molecules in human brain microvascular endothelial cells in a dose-dependent manner. Correspondingly, 6-OHDA significantly increased attachment of THP-1 monocytes to brain endothelial cells. In addition, real-time polymerase chain reaction and enzyme-linked immunosorbent assay results indicated that 6-OHDA elevated the production of proinflammatory cytokines, such as interleukin-1β, interleukin-6, and tumor necrosis factor-α. Furthermore, 6-OHDA treatment increased the expression of cyclooxygenase-2 and inducible nitric oxide synthase, as well as the production of prostaglandin E2 and nitric oxide. Importantly, 6-OHDA elevated the transcriptional activity of NF-кB by increasing the phosphorylation, degradation, and subsequent nuclear translocation of p65. Mechanistically, the angiotensin II type 1 receptor was found to mediate 6-OHDA-induced endothelial dysfunction. Our findings suggest that 6-OHDA-induced endothelial inflammation may play an important role in the pathogenesis of PD. © 2017 IUBMB Life, 69(11):887-895, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

  4. Dietary phosphorus acutely impairs endothelial function.

    Science.gov (United States)

    Shuto, Emi; Taketani, Yutaka; Tanaka, Rieko; Harada, Nagakatsu; Isshiki, Masashi; Sato, Minako; Nashiki, Kunitaka; Amo, Kikuko; Yamamoto, Hironori; Higashi, Yukihito; Nakaya, Yutaka; Takeda, Eiji

    2009-07-01

    Excessive dietary phosphorus may increase cardiovascular risk in healthy individuals as well as in patients with chronic kidney disease, but the mechanisms underlying this risk are not completely understood. To determine whether postprandial hyperphosphatemia may promote endothelial dysfunction, we investigated the acute effect of phosphorus loading on endothelial function in vitro and in vivo. Exposing bovine aortic endothelial cells to a phosphorus load increased production of reactive oxygen species, which depended on phosphorus influx via sodium-dependent phosphate transporters, and decreased nitric oxide production via inhibitory phosphorylation of endothelial nitric oxide synthase. Phosphorus loading inhibited endothelium-dependent vasodilation of rat aortic rings. In 11 healthy men, we alternately served meals containing 400 mg or 1200 mg of phosphorus in a double-blind crossover study and measured flow-mediated dilation of the brachial artery before and 2 h after the meals. The high dietary phosphorus load increased serum phosphorus at 2 h and significantly decreased flow-mediated dilation. Flow-mediated dilation correlated inversely with serum phosphorus. Taken together, these findings suggest that endothelial dysfunction mediated by acute postprandial hyperphosphatemia may contribute to the relationship between serum phosphorus level and the risk for cardiovascular morbidity and mortality.

  5. ENDOTHELIAL DYSFUNCTION IN ISCHEMIC HEART DISEASE

    Directory of Open Access Journals (Sweden)

    N. E. Zakirova

    2008-01-01

    Full Text Available Aim. To assess the role of endothelial vasodilating, vasoconstrictive and adhesive dysfunction in the development of angina pectoris (AP in patients with ischemic heart disease (IHD.Material and methods. 83 patients with IHD were included in the study. 30 patients had AP of functional class (FC-II, 27 patients - FC-III and 26 patients - FC-IV. The control group consisted of 25 healthy persons. Bicycle ergometry, daily ECG monitoring and echocardiography were used for verification of IHD. Endothelial vasodilating function was assessed by endothelium-dependent (EDVD and endothelium-independent vasodilatation (EIDVD of brachial artery. Vasoconstrictive function was assessed by the level of endothelin (ET-1. Endothelial adhesive function was evaluated by plasma concentration of intracellular adhesion molecules – JCAM-1, VCAM-1 and Е-selectin.Results. Normal EDVD and EIDVD were observed in patients with AP of FC-II. The more severe FC of AP the more prominent endothelial vasodilating dysfunction was revealed as well as the higher levels of ET-1 and intracellular adhesion molecules. Patients with AP of FC-IV had hyperexpression of JCAM-1, VCAM-1, Е-selectin and ET-1 and low levels of EDVD and EIDVD.Conclusion. Progression of IHD related with growing endothelial vasodilating, vasoconstrictive and adhesive dysfunction.

  6. [Assessment of endothelial function in autoimmune diseases].

    Science.gov (United States)

    Benhamou, Y; Bellien, J; Armengol, G; Gomez, E; Richard, V; Lévesque, H; Joannidès, R

    2014-08-01

    Numerous autoimmune-inflammatory rheumatic diseases have been associated with accelerated atherosclerosis or other types of vasculopathy leading to an increase in cardiovascular disease incidence. In addition to traditional cardiovascular risk factors, endothelial dysfunction is an important early event in the pathogenesis of atherosclerosis, contributing to plaque initiation and progression. Endothelial dysfunction is characterized by a shift of the actions of the endothelium toward reduced vasodilation, a proinflammatory and a proadhesive state, and prothrombic properties. Therefore, assessment of endothelial dysfunction targets this vascular phenotype using several biological markers as indicators of endothelial dysfunction. Measurements of soluble adhesion molecules (ICAM-1, VCAM-1, E-selectin), pro-thrombotic factors (thrombomodulin, von Willebrand factor, plasminogen activator inhibitor-1) and inflammatory cytokines are most often performed. Regarding the functional assessment of the endothelium, the flow-mediated dilatation of conduit arteries is a non-invasive method widely used in pathophysiological and interventional studies. In this review, we will briefly review the most relevant information upon endothelial dysfunction mechanisms and explorations. We will summarize the similarities and differences in the biological and functional assessments of the endothelium in different autoimmune diseases. Copyright © 2013 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  7. Endothelial Extracellular Vesicles-Promises and Challenges.

    Science.gov (United States)

    Hromada, Carina; Mühleder, Severin; Grillari, Johannes; Redl, Heinz; Holnthoner, Wolfgang

    2017-01-01

    Extracellular vesicles, including exosomes, microparticles, and apoptotic bodies, are phospholipid bilayer-enclosed vesicles that have once been considered as cell debris lacking biological functions. However, they have recently gained immense interest in the scientific community due to their role in intercellular communication, immunity, tissue regeneration as well as in the onset, and progression of various pathologic conditions. Extracellular vesicles of endothelial origin have been found to play a versatile role in the human body, since they are on the one hand known to contribute to cardiovascular diseases, but on the other hand have also been reported to promote endothelial cell survival. Hence, endothelial extracellular vesicles hold promising therapeutic potential to be used as a new tool to detect as well as treat a great number of diseases. This calls for clinically approved, standardized, and efficient isolation and characterization protocols to harvest and purify endothelial extracellular vesicles. However, such methods and techniques to fulfill stringent requirements for clinical trials have yet to be developed or are not harmonized internationally. In this review, recent advances and challenges in the field of endothelial extracellular vesicle research are discussed and current problems and limitations regarding isolation and characterization are pointed out.

  8. Endothelial Cell Response to Fusobacterium nucleatum.

    Science.gov (United States)

    Mendes, Reila Tainá; Nguyen, Daniel; Stephens, Danielle; Pamuk, Ferda; Fernandes, Daniel; Van Dyke, Thomas E; Kantarci, Alpdogan

    2016-07-01

    Vascular response is an essential aspect of an effective immune response to periodontal disease pathogens, as new blood vessel formation contributes to wound healing and inflammation. Gaining a greater understanding of the factors that affect vascular response may then contribute to future breakthroughs in dental medicine. In this study, we have characterized the endothelial cell response to the common bacterium Fusobacterium nucleatum, an important bridging species that facilitates the activity of late colonizers of the dental biofilm. Endothelial cells were infected with Fusobacterium nucleatum (strain 25586) for periods of 4, 12, 24, or 48 h. Cell proliferation and tube formation were analyzed, and expression of adhesion molecules (CD31 and CD34) and vascular endothelial growth factor (VEGF) receptors 1 and 2 was measured by fluorescence-activated cell sorter (FACS) analysis. Data indicate that F. nucleatum impaired endothelial cell proliferation and tube formation. The findings suggest that the modified endothelial cell response acts as a mechanism promoting the pathogenic progression of periodontal diseases and may potentially suggest the involvement of periodontopathogens in systemic diseases associated with periodontal inflammation. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  9. Suppression of Retinal Neovascularization in vivo by Inhibition of Vascular Endothelial Growth Factor (VEGF) Using Soluble VEGF-Receptor Chimeric Proteins

    Science.gov (United States)

    Aiello, Lloyd Paul; Pierce, Eric A.; Foley, Eliot D.; Takagi, Hitoshi; Chen, Helen; Riddle, Lavon; Ferrara, Napoleone; King, George L.; Smith, Lois E. H.

    1995-11-01

    The majority of severe visual loss in the United States results from complications associated with retinal neovascularization in patients with ischemic ocular diseases such as diabetic retinopathy, retinal vein occlusion, and retinopathy of prematurity. Intraocular expression of the angiogenic protein vascular endothelial growth factor (VEGF) is closely correlated with neovascularization in these human disorders and with ischemia-induced retinal neovascularization in mice. In this study, we evaluated whether in vivo inhibition of VEGF action could suppress retinal neovascularization in a murine model of ischemic retinopathy. VEGF-neutralizing chimeric proteins were constructed by joining the extracellular domain of either human (Flt) or mouse (Flk) high-affinity VEGF receptors with IgG. Control chimeric proteins that did not bind VEGF were also used. VEGF-receptor chimeric proteins eliminated in vitro retinal endothelial cell growth stimulation by either VEGF (P hypoxic conditioned medium (P < 0.005) without affecting growth under nonstimulated conditions. Control proteins had no effect. To assess in vivo response, animals with bilateral retinal ischemia received intravitreal injections of VEGF antagonist in one eye and control protein in the contralateral eye. Retinal neovascularization was quantitated histologically by a masked protocol. Retinal neovascularization in the eye injected with human Flt or murine Flk chimeric protein was reduced in 100% (25/25; P < 0.0001) and 95% (21/22; P < 0.0001) of animals, respectively, compared to the control treated eye. This response was evident after only a single intravitreal injection and was dose dependent with suppression of neovascularization noted after total delivery of 200 ng of protein (P < 0.002). Reduction of histologically evident neovascular nuclei per 6-um section averaged 47% ± 4% (P < 0.001) and 37% ± 2% (P < 0.001) for Flt and Flk chimeric proteins with maximal inhibitory effects of 77% and 66

  10. Pars plana vitrectomy combined with internal limiting membrane peeling for recurrent macular edema due to branch retinal vein occlusion after antivascular endothelial growth factor treatments

    Directory of Open Access Journals (Sweden)

    Shirakata Y

    2016-02-01

    Full Text Available Yukari Shirakata,1 Kouki Fukuda,1 Tomoyoshi Fujita,1 Yuki Nakano,1 Hiroyuki Nomoto,2 Hidetaka Yamaji,3 Fumio Shiraga,4 Akitaka Tsujikawa1 1Department of Ophthalmology, Faculty of Medicine, Kagawa University, Miki-cho, 2Nomoto Eye Clinic, Himeji, 3Department of Ophthalmology, Shirai Eye Hospital, Mitoyo, 4Department of Ophthalmology, Okayama University, Okayama, Japan Purpose: To evaluate the anatomic and functional outcomes of pars plana vitrectomy combined with internal limiting membrane peeling for recurrent macular edema (ME due to branch retinal vein occlusion (BRVO after intravitreal injections of antivascular endothelial growth factor (anti-VEGF agents. Methods: Twenty-four eyes of 24 patients with treatment-naive ME from BRVO were treated with intravitreal injections of anti-VEGF agents. Recurred ME was treated with pars plana vitrectomy combined with internal limiting membrane peeling. Results: After the surgery, ME was significantly reduced at 1 month (P=0.031 and the reduction increased with time (P=0.007 at the final visit. With the reduction in ME, treated eyes showed a slow improvement in visual acuity (VA. At the final visit, improvement in VA was statistically significant compared with baseline (P=0.048. The initial presence of cystoid spaces, serous retinal detachment, or subretinal hemorrhage under the fovea, as well as retinal perfusion status, showed no association with VA improvement. However, the presence of epiretinal membrane showed a significant association with the visual recovery. Although eyes without epiretinal membrane showed visual improvement (-0.10±0.32 in logarithm of the minimum angle of resolution [logMAR], eyes with epiretinal membrane showed greater visual improvement (-0.38±0.12 in logMAR, P=0.012. Conclusion: For recurrent ME due to BRVO after anti-VEGF treatment, particularly when accompanied by epiretinal membrane, pars plana vitrectomy combined with internal limiting membrane peeling might be a

  11. Effects of helium on inflammatory and oxidative stress-induced endothelial cell damage

    NARCIS (Netherlands)

    Smit, Kirsten F.; Kerindongo, Raphaela P.; Böing, Anita; Nieuwland, Rienk; Hollmann, Markus W.; Preckel, Benedikt; Weber, Nina C.

    2015-01-01

    Helium induces preconditioning in human endothelium protecting against postischemic endothelial dysfunction. Circulating endothelial microparticles are markers of endothelial dysfunction derived in response to injury. Another noble gas, xenon, protected human umbilical vein endothelial cells (HUVEC)

  12. Efficacy of intravitreal dexamethasone implant for prostaglandin-induced refractory pseudophakic cystoid macular edema: case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Sacchi M

    2014-07-01

    Full Text Available Matteo Sacchi, Edoardo Villani, Francesca Gilardoni, Paolo Nucci University Eye Clinic, San Giuseppe Hospital, University of Milan, Milan, Italy Background: Macular edema is a known complication even after uneventful cataract surgery. The chronic use of prostaglandin analogs is a risk factor for the development of pseudophakic cystoid macular edema (CME. Nonsteroidal anti-inflammatory drugs (NSAIDs are considered first-line therapy but refractory postsurgical CME represents a therapeutic challenge, as there is not an evidence-based treatment.Objective: To report the use of a single implant of intravitreal dexamethasone for tafluprost-associated pseudophakic CME refractory to NSAIDs and to sub-Tenon’s corticosteroid injections.Case report: A 64-year-old female with ocular hypertension treated with tafluprost experienced decreased vision (visual acuity 20/60 and metamorphopsia 2 months after uneventful cataract extraction. Spectral domain optical coherence tomography (SD-OCT revealed CME. After 1 month of topical and oral NSAIDs, CME was still evident on SD-OCT (visual acuity 20/50. Two sub-Tenon’s betamethasone injections were performed at a 2-week interval. As CME was still present, 2 months after the diagnosis of CME (visual acuity 20/40, the patient underwent a single dexamethasone intravitreal implant. One month later, macular appearance was normal, and visual acuity increased to 20/30. This result was maintained throughout the 6 months of follow-up.Conclusion: In this report, a single implant of intravitreal dexamethasone successfully treated pseudophakic CME associated with the use of prostaglandin analogs unresponsive to NSAIDs and sub-Tenon’s betamethasone. The results of this report need to be corroborated by powered, prospective, randomized trials. The need for repeated treatments as well as the retreatment interval in patients requiring more than a single injection are issues still needing further investigations. Keywords

  13. Intravitreal concentrations of a near-infrared fluorescence-labeled biotherapeutic determined in situ using confocal scanning laser ophthalmoscopy.

    Science.gov (United States)

    Basile, Anthony S; Glazier, Genevieve; Lee, Alice; Jiang, Li-Ying; Johnson, Theodore R; Shields, Michael J; Vezina, Mark; Doppalapudi, Venkata R

    2011-09-01

    The pharmacokinetics of ophthalmic biotherapeutics are difficult to determine in human vitreous humor. Because of the high transparency of living tissue to near-infrared (NIR) light, the temporal changes in vitreous concentrations of a biomolecule labeled with an NIR fluorescent probe can be monitored in situ with a scanning laser ophthalmoscope (SLO). A humanized IgG was labeled with the NIR probe IRDye800CW (CVX-4164). Rabbits were given CVX-4164 intravitreally, and NIR fluorescence intensity was measured in the central plane of the vitreous humor with an SLO. Fluorescence intensities were converted to concentrations by using standard curves. Little background fluorescence was detected, and the minimum detectable concentration of CVX-4164 was CVX-4164 determined in situ declined with time, with C(max) ≈ 1 μM and t½ = 145 hours (112-μg dose). The t½ of CVX-4164 was approximately three times greater than that of the IRDye800CW alone, whereas the vitreal clearance (CL) and volume of distribution (V(ss)) of the native dye were approximately 2000- and 550-fold greater than that of the conjugate. CVX-4164 concentrations determined in situ were 2.6 to 4.4 times higher than those determined by ex vivo NIR fluorescence or ELISA in homogenized vitreous humor, reflecting the greater spatial resolution of in situ imaging. Moreover, vitreal concentrations determined in situ were >3 orders of magnitude greater than plasma concentrations of CVX-4164, as determined by ELISA, and had a different kinetic profile. This study demonstrates the feasibility of determining the pharmacokinetics of intraocular biotherapeutics labeled with NIR fluorescent probes by in situ monitoring.

  14. Comparison of acute effect of systemic versus intravitreal infliximab treatment in an experimental model of endotoxin-induced uveitis.

    Science.gov (United States)

    Yuksel, Erdem; Hasanreisoglu, Berati; Yuksel, Nilay; Yilmaz, Guldal; Ercin, Ugur; Bilgihan, Ayse

    2014-02-01

    In this study, we investigated the efficacy of systemic and intravitreal (IV) infliximab treatments and compared these 2 different treatment modalities in an experimental model of endotoxin-induced uveitis (EIU). Twenty-four white New Zealand rabbits were equally divided into 4 groups. Group 1 received IV injection of lipopolysaccharide (LPS), group 2 received IV injections of LPS and saline, group 3 received IV LPS and IV 2 mg/0.1 cc infliximab, and group 4 received IV LPS and 5 mg/kg intravenous infliximab. Inflammation was determined with objective and subjective tests. The subjective test was clinical determination of uveitis, the objective tests were determination of protein concentrations and tumor necrosis factor alpha (TNF-α) levels and histopathology. Clinical examination score was lower in group 3 and group 4 (4±0.6 and 3.5±1.6, respectively) when compared with group 1 (P=0.02; P=0.04, respectively) and group 2. In group 3 and 4, the aqueous and vitreous protein and TNF-α concentration measured significantly lower than group 1 and 2. In histopathologic examination, there was no statistically significant difference between group 1, 2, and 3 (3.5±0.5, 3.6±0.5, 3.6±0.5, respectively). However, the lowest histopathologic inflammation was determined in group 4 (2.5±0.5) (compared with group 1 and group 3, respectively; P=0.03; P=0.014). In a rabbit model of experimental EIU, intravenous administration of infliximab was more effective than IV route in an acute period.

  15. Isolation and culture of pulmonary endothelial cells.

    Science.gov (United States)

    Ryan, U S

    1984-06-01

    Methods for isolation, identification and culture of pulmonary endothelial cells are now routine. In the past, methods of isolation have used proteolytic enzymes to detach cells; thereafter, traditional methods for cell passaging have used trypsin/EDTA mixtures. Cells isolated and passaged using proteolytic enzymes have been useful in establishing the field and in verifying certain endothelial properties. However, there is a growing awareness of the role of endothelial cells in processing vasoactive substances, in responding to hormones and other agonists and in cell-cell interactions with other cell types of the vascular wall, with blood cells and with cellular products. Consequently, a new requirement has arisen for cells in vitro that maintain the differentiated properties of their counterparts in vivo. The deleterious effects of trypsin and other proteolytic enzymes commonly used in cell culture on surface structures of endothelial cells such as enzymes, receptors and junctional proteins, as well as on extracellular layers such as the glycocalyx or "endothelial fuzz," have led to the development of methods that avoid use of proteolytic enzymes at both the isolation step and during subsequent subculture. This chapter describes traditional methods for isolating pulmonary endothelial cells but emphasizes newer approaches using mechanical harvest and scale-up using microcarriers. The new methods allow maintenance of long-term, large-scale cultures of cells that retain the full complement of surface properties and that maintain the cobblestone monolayer morphology and differentiated functional properties. Methods for identification of isolated cells are therefore also considered as methods for validation of cultures during their in vitro lifespan.

  16. Endothelial cells, endoplasmic reticulum stress and oxysterols

    Directory of Open Access Journals (Sweden)

    F. Luchetti

    2017-10-01

    Full Text Available Oxysterols are bioactive lipids that act as regulators of lipid metabolism, inflammation, cell viability and are involved in several diseases, including atherosclerosis. Mounting evidence linked the atherosclerosis to endothelium dysfunction; in fact, the endothelium regulates the vascular system with roles in processes such as hemostasis, cell cholesterol, hormone trafficking, signal transduction and inflammation. Several papers shed light the ability of oxysterols to induce apoptosis in different cell lines including endothelial cells. Apoptotic endothelial cell and endothelial denudation may constitute a critical step in the transition to plaque erosion and vessel thrombosis, so preventing the endothelial damaged has garnered considerable attention as a novel means of treating atherosclerosis. Endoplasmic reticulum (ER is the site where the proteins are synthetized and folded and is necessary for most cellular activity; perturbations of ER homeostasis leads to a condition known as endoplasmic reticulum stress. This condition evokes the unfolded protein response (UPR an adaptive pathway that aims to restore ER homeostasis. Mounting evidence suggests that chronic activation of UPR leads to cell dysfunction and death and recently has been implicated in pathogenesis of endothelial dysfunction. Autophagy is an essential catabolic mechanism that delivers misfolded proteins and damaged organelles to the lysosome for degradation, maintaining basal levels of autophagic activity it is critical for cell survival. Several evidence suggests that persistent ER stress often results in stimulation of autophagic activities, likely as a compensatory mechanism to relieve ER stress and consequently cell death. In this review, we summarize evidence for the effect of oxysterols on endothelial cells, especially focusing on oxysterols-mediated induction of endoplasmic reticulum stress.

  17. Identification of epigenetically silenced genes in tumor endothelial cells

    NARCIS (Netherlands)

    Hellebrekers, Debby M. E. I.; Melotte, Veerle; Vire, Emmanuelle; Langenkamp, Elise; Molema, Grietje; Fuks, Francois; Herman, James G.; Van Criekinge, Wim; Griffioen, Arjan W.; van Engeland, Manon

    2007-01-01

    Tumor angiogenesis requires intricate regulation of gene expression in endothelial cells. We recently showed that DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitors directly repress endothelial cell growth and tumor angiogenesis, suggesting that epigenetic modifications mediated

  18. Qidantongmai Protects Endothelial Cells Against Hypoxia-Induced ...

    African Journals Online (AJOL)

    induced damage. The ability of QDTM to modulate the serum VEGF-A level may play an important role in its effects on endothelial cells. Key words: Traditional Chinese Medicine, human umbilical vein endothelial cells, hypoxia, VEGF ...

  19. Corneal endothelial dysfunction in Pearson syndrome.

    Science.gov (United States)

    Kasbekar, Shivani A; Gonzalez-Martin, Jose A; Shafiq, Ayad E; Chandna, Arvind; Willoughby, Colin E

    2013-01-01

    Mitochondrial disorders are associated with well recognized ocular manifestations. Pearson syndrome is an often fatal, multisystem, mitochondrial disorder that causes variable bone marrow, hepatic, renal and pancreatic exocrine dysfunction. Phenotypic progression of ocular disease in a 12-year-old male with Pearson syndrome is described. This case illustrates phenotypic drift from Pearson syndrome to Kearns-Sayre syndrome given the patient's longevity. Persistent corneal endothelial failure was noted in addition to ptosis, chronic external ophthalmoplegia and mid-peripheral pigmentary retinopathy. We propose that corneal edema resulting from corneal endothelial metabolic pump failure occurs within a spectrum of mitochondrial disorders.

  20. Endothelial dysfunction – A predictor of atherosclerosis | Chhabra ...

    African Journals Online (AJOL)

    Endothelial dysfunction is a systemic disorder and a critical element in the pathogenesis of atherosclerotic diseases and its complications. Growing evidences suggest that the individual burden of currently known cardiovascular risk factors is not the only determinant of endothelial function; rather endothelial integrity ...

  1. Oxidative stress induced pulmonary endothelial cell proliferation is ...

    African Journals Online (AJOL)

    Cellular hyper-proliferation, endothelial dysfunction and oxidative stress are hallmarks of the pathobiology of pulmonary hypertension. Indeed, pulmonary endothelial cells proliferation is susceptible to redox state modulation. Some studies suggest that superoxide stimulates endothelial cell proliferation while others have ...

  2. Endothelial cell seeding on crosslinked collagen : Effects of crosslinking on endothelial cell proliferation and functional parameters

    NARCIS (Netherlands)

    Wissink, MJB; van Luyn, MJA; Dijk, F; Poot, AA; Engbers, GHM; Beugeling, T; van Aken, WG; Feijen, J

    Endothelial cell seeding, a promising method to improve the performance of small-diameter vascular grafts, requires a suitable substrate, such as crosslinked collagen. Commonly used crosslinking agents such as glutaraldehyde and formaldehyde cause, however, cytotoxic reactions and thereby hamper

  3. Endothelial nitric oxide synthase gene polymorphisms associated ...

    African Journals Online (AJOL)

    Endothelial nitric oxide synthase (NOS3) is involved in key steps of immune response. Genetic factors predispose individuals to periodontal disease. This study's aim was to explore the association between NOS3 gene polymorphisms and clinical parameters in patients with periodontal disease. Genomic DNA was obtained ...

  4. Lipoprotein receptors in cultured bovine endothelial cells

    International Nuclear Information System (INIS)

    Struempfer, A.E.M.

    1983-07-01

    In this study, receptors that may be involved in the uptake of low density lipoproteins (LDL) and low density lipoproteins which have been modified by acetylation (AcLDL), were characterized. Aortic epithelial cells were used and a cell culture system which closely resembled the in vivo monolayer was established. Endothelial cell and lipoprotein interactions were examined by incubating the cells with 125 l-labelled lipoproteins under various conditions. The receptor affinity of bovine aortic endothelial cells was higher for AcLDL than that for LDL. Competition studies demonstrated that there were two distinct receptors for LDL and AcLDL on the endothelial cells. AcLDL did not compete with LDL for the LDL receptor, and conversely LDL did not compete with AcLDL for the AcLDL receptor. The receptor activities for LDL and AcLDL were examined as a function of culture age. Whereas the LDL receptor could be regulated, the AcLDL receptor was not as susceptible to regulation. Upon exposing endothelial cells for 72 h to either LDL or AcLDL, it was found that the total amount of cellular cholesterol increased by about 50%. However, the increase of total cholesterol was largely in the form of free cholesterol. This is in contrast to macrophages, where the increase in total cholesterol upon exposure to AcLDL is largely in the form cholesteryl esters

  5. Mechanical control of the endothelial barrier

    NARCIS (Netherlands)

    Oldenburg, Joppe; de Rooij, Johan

    The integrity of the endothelial barrier is controlled by the combined action of chemical and mechanical signaling systems. Permeability-regulating factors signal through small GTPases to regulate the architecture of the cytoskeleton and this has a strong impact on the morphology and stability of

  6. Endothelial cell oxidative stress and signal transduction

    Directory of Open Access Journals (Sweden)

    ROCIO FONCEA

    2000-01-01

    Full Text Available Endothelial dysfunction (ED is an early event in atherosclerotic disease, preceding clinical manifestations and complications. Increased reactive oxygen species (ROS have been implicated as important mechanisms that contribute to ED, and ROS’s may function as intracellular messengers that modulate signaling pathways. Several intracellular signal events stimulated by ROS have been defined, including the identification of two members of the mitogen activated protein kinase family (ERK1/2 and big MAP kinase, BMK1, tyrosine kinases (Src and Syk and different isoenzymes of PKC as redox-sensitive kinases. ROS regulation of signal transduction components include the modification in the activity of transcriptional factors such as NFkB and others that result in changes in gene expression and modifications in cellular responses. In order to understand the intracellular mechanisms induced by ROS in endothelial cells (EC, we are studying the response of human umbilical cord vein endothelial cells to increased ROS generation by different pro-atherogenic stimuli. Our results show that Homocysteine (Hcy and oxidized LDL (oxLDL enhance the activity and expression of oxidative stress markers, such as NFkB and heme oxygenase 1. These results suggest that these pro-atherogenic stimuli increase oxidative stress in EC, and thus explain the loss of endothelial function associated with the atherogenic process

  7. Relationship between endothelial nitric oxide synthase gene ...

    African Journals Online (AJOL)

    Introduction: Endothelial nitric oxide synthase (eNOS), the enzyme in charge of nitric oxide production, plays a crucial role in vascular biology. However, the impact of single nucleotide polymorphisms (SNPs) affecting the gene encoding for eNOS (eNOS) on coronary artery diseases remains under debate and no data were ...

  8. Vascular endothelial growth factor ( VEGF ) receptor expression ...

    African Journals Online (AJOL)

    Background: Colorectal carcinoma (CRC) is the seventh-most common malignancy and is the main cause of death in Iraq. The incidence of this cancer has increased sharply after the invasion of Iraq in 2003. Aim: To estimate immunohistochemical expression of vascular endothelial growth factor (VEGF) in CRC in relation ...

  9. ORIGINAL ARTICLE Relationship between endothelial nitric oxide ...

    African Journals Online (AJOL)

    salah

    and limits the oxidation of low-density lipoproteins, all these mechanisms be- ing strongly involved in the atherogenic process5. Moreover, as a potent vasodi- latator, NO is deeply engaged in the regulation of blood pressure. In vascular endothelium, NO is con- stitutively produced from L-arginine by endothelial nitric oxide ...

  10. Characterization of intravitreally delivered capsid mutant AAV2-Cre vector to induce tissue-specific mutations in murine retinal ganglion cells.

    Science.gov (United States)

    Langouet-Astrie, Christophe J; Yang, Zhiyong; Polisetti, Sraavya M; Welsbie, Derek S; Hauswirth, William W; Zack, Donald J; Merbs, Shannath L; Enke, Raymond A

    2016-10-01

    Targeted expression of Cre recombinase in murine retinal ganglion cells (RGCs) by viral vector is an effective strategy for creating tissue-specific gene knockouts for investigation of genetic contribution to RGC degeneration associated with optic neuropathies. Here we characterize dosage, efficacy and toxicity for sufficient intravitreal delivery of a capsid mutant Adeno-associated virus 2 (AAV2) vector encoding Cre recombinase. Wild type and Rosa26 (R26) LacZ mice were intravitreally injected with capsid mutant AAV2 viral vectors. Murine eyes were harvested at intervals ranging from 2 weeks to 15 weeks post-injection and were assayed for viral transduction, transgene expression and RGC survival. 10(9) vector genomes (vg) were sufficient for effective in vivo targeting of murine ganglion cell layer (GCL) retinal neurons. Transgene expression was observed as early as 2 weeks post-injection of viral vectors and persisted to 11 weeks. Early expression of Cre had no significant effect on RGC survival, while significant RGC loss was detected beginning 5 weeks post-injection. Early expression of viral Cre recombinase was robust, well-tolerated and predominantly found in GCL neurons suggesting this strategy can be effective in short-term RGC-specific mutation studies in experimental glaucoma models such as optic nerve crush and transection experiments. RGC degeneration with Cre expression for more than 4 weeks suggests that Cre toxicity is a limiting factor for targeted mutation strategies in RGCs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Animal study on transplantation of human umbilical vein endothelial cells for corneal endothelial decompensation

    Directory of Open Access Journals (Sweden)

    Li Cui

    2014-06-01

    Full Text Available AIM: To explore the feasibility of culturing human umbilical vein endothelial cells(HUVECon acellular corneal stroma and performing the posterior lamellar endothelial keratoplasty(PLEKtreating corneal endothelial decompensation.METHODS: Thirty New-Zealand rabbits were divided into three groups randomly, 10 rabbits for experimental group, 10 for stroma group and 10 for control group. Corneal endothelial cells were removed to establish animal model of corneal endothelial failure. PLEK was performed on the rabbits of experimental group and stroma group, and nothing was transplantated onto the rabbits of control group with the deep layer excised only. Postoperative observation was taken for 3mo. The degree of corneal edema and central corneal thickness were recorded for statistical analysis.RESULTS: Corneas in experimental group were relieved in edema obviously compared with that in stroma group and the control group, and showed increased transparency 7d after the operation. The average density of endothelial cells was 2 026.4±129.3cells/mm2, and average central corneal thickness was 505.2±25.4μm in experimental group, while 1 535.6±114.5μm in stroma group and 1 493.5±70.2μm in control group 3mo after operation.CONCLUSION:We achieved preliminary success in our study that culturing HUVEC on acellular corneal stroma and performing PLEK for corneal endothelial decompensation. HUVEC transplanted could survive in vivo, and have normal biological function of keeping cornea transparent. This study provides a new idea and a new way clinically for the treatment of corneal endothelial diseases.

  12. Selective endothelial overexpression of arginase II induces endothelial dysfunction and hypertension and enhances atherosclerosis in mice.

    Directory of Open Access Journals (Sweden)

    Boris L Vaisman

    Full Text Available Cardiovascular disorders associated with endothelial dysfunction, such as atherosclerosis, have decreased nitric oxide (NO bioavailability. Arginase in the vasculature can compete with eNOS for L-arginine and has been implicated in atherosclerosis. The aim of this study was to evaluate the effect of endothelial-specific elevation of arginase II expression on endothelial function and the development of atherosclerosis.Transgenic mice on a C57BL/6 background with endothelial-specific overexpression of human arginase II (hArgII gene under the control of the Tie2 promoter were produced. The hArgII mice had elevated tissue arginase activity except in liver and in resident peritoneal macrophages, confirming endothelial specificity of the transgene. Using small-vessel myography, aorta from these mice exhibited endothelial dysfunction when compared to their non-transgenic littermate controls. The blood pressure of the hArgII mice was 17% higher than their littermate controls and, when crossed with apoE -/- mice, hArgII mice had increased aortic atherosclerotic lesions.We conclude that overexpression of arginase II in the endothelium is detrimental to the cardiovascular system.

  13. Fusobacterium nucleatum adhesin FadA binds vascular endothelial cadherin and alters endothelial integrity.

    Science.gov (United States)

    Fardini, Yann; Wang, Xiaowei; Témoin, Stéphanie; Nithianantham, Stanley; Lee, David; Shoham, Menachem; Han, Yiping W

    2011-12-01

    Fusobacterium nucleatum is a Gram-negative oral anaerobe, capable of systemic dissemination causing infections and abscesses, often in mixed-species, at different body sites. We have shown previously that F. nucleatum adheres to and invades host epithelial and endothelial cells via a novel FadA adhesin. In this study, vascular endothelial (VE)-cadherin, a member of the cadherin family and a cell-cell junction molecule, was identified as the endothelial receptor for FadA, required for F. nucleatum binding to the cells. FadA colocalized with VE-cadherin on endothelial cells, causing relocation of VE-cadherin away from the cell-cell junctions. As a result, the endothelial permeability was increased, allowing the bacteria to cross the endothelium through loosened junctions. This crossing mechanism may explain why the organism is able to disseminate systemically to colonize in different body sites and even overcome the placental and blood-brain barriers. Co-incubation of F. nucleatum and Escherichia coli enhanced penetration of the endothelial cells by the latter in the transwell assays, suggesting F. nucleatum may serve as an 'enabler' for other microorganisms to spread systemically. This may explain why F. nucleatum is often found in mixed infections. This study reveals a possible novel dissemination mechanism utilized by pathogens. © 2011 Blackwell Publishing Ltd.

  14. Endothelial progenitor cell biology in ankylosing spondylitis.

    Science.gov (United States)

    Verma, Inderjeet; Syngle, Ashit; Krishan, Pawan

    2015-03-01

    Endothelial progenitor cells (EPCs) are unique populations which have reparative potential in overcoming endothelial damage and reducing cardiovascular risk. Patients with ankylosing spondylitis (AS) have increased risk of cardiovascular morbidity and mortality. The aim of this study was to investigate the endothelial progenitor cell population in AS patients and its potential relationships with disease variables. Endothelial progenitor cells were measured in peripheral blood samples from 20 AS and 20 healthy controls by flow cytometry on the basis of CD34 and CD133 expression. Disease activity was evaluated by using Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Functional ability was monitored by using Bath Ankylosing Spondylitis Functional Index (BASFI). EPCs were depleted in AS patients as compared to healthy controls (CD34(+) /CD133(+) : 0.027 ± 0.010% vs. 0.044 ± 0.011%, P < 0.001). EPC depletions were significantly associated with disease duration (r = -0.52, P = 0.01), BASDAI (r = -0.45, P = 0.04) and C-reactive protein (r = -0.5, P = 0.01). This is the first study to demonstrate endothelial progenitor cell depletion in AS patients. EPC depletions inversely correlate with disease duration, disease activity and inflammation, suggesting the pivotal role of inflammation in depletion of EPCs. EPC would possibly also serve as a therapeutic target for preventing cardiovascular disease in AS. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  15. Mechanisms of endothelial dysfunction during aging: Predisposition to thrombosis.

    Science.gov (United States)

    Sepúlveda, Cesar; Palomo, Iván; Fuentes, Eduardo

    2017-06-01

    One of the risk factors for developing cardiovascular disease (CVD) is aging. In the elderly endothelial dysfunction occurs as altered endothelial ability to regulate hemostasis, vascular tone and cell permeability. In addition, there are changes in the expression and plasma levels of important endothelial components related to endothelial-mediated modulation in hemostasis. These include alterations in the metabolism of nitric oxide and prostanoides, endothelin-1, thrombomodulin and Von Willebrand factor. These alterations potentiate the pro-coagulant status developed with aging, highlighting the endothelial role in the development of thrombosis in aging. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Effect of intravitreal methotrexate and rituximab on interleukin-10 levels in aqueous humor of treated eyes with vitreoretinal lymphoma.

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    Harish Raja

    Full Text Available Intraocular cytokines are promising diagnostic biomarkers of vitreoretinal lymphoma. Here, we evaluate the utility of IL-10, IL-6 and IL-10/IL-6 for discriminating lymphoma from uveitis and report the effects of intraocular methotrexate and rituximab on aqueous cytokine levels in eyes with lymphoma. This is a retrospective case series including 10 patients with lymphoma and 7 patients with uveitis. Non-parametric Mann-Whitney analysis was performed to determine statistical significance of difference in interleukin levels between lymphoma and uveitis. Compared to eyes with uveitis, eyes with lymphoma had higher levels of IL-10 (U = 7.0; two-tailed p = 0.004 and IL-10/IL-6 (U = 6.0; two-tailed p = 0.003, whereas IL-6 levels were more elevated, although insignificant, in those patients with uveitis than in lymphoma (U = 15.0; two-tailed p = ns. Using a receiver operating characteristic analysis to identify threshold values diagnostic for lymphoma, optimal sensitivity and specificity improved to 80.0% and 100%, respectively, for IL-10>7.025 pg/ml and 90.0% and 100.0%, respectively, for IL-10/IL-6>0.02718. In patients in whom serial interleukin levels were available, regular intravitreal treatment with methotrexate and rituximab was associated with reduction in IL-10 levels over time. In conclusion, optimal IL-10 and IL-10/IL-6 threshold values are associated with a diagnostic sensitivity ≥80% and specificity of 100%. Therefore, these cytokines may serve as a useful adjunct in the diagnosis of lymphoma. While negative IL-10 and IL-10/IL-6 values do not exclude a diagnosis of lymphoma, elevated levels do appear to be consistent with lymphoma clinically. Moreover, elevated levels of IL-10 in the setting of a clinically quiet eye may point to impending disease recurrence. Lastly, once lymphoma is diagnosed, IL-10 levels can be monitored over time to assess disease activity and therapeutic response.

  17. Outer retina reflectivity changes on sd-oct after intravitreal ocriplasmin for vitreomacular traction and macular hole.

    Science.gov (United States)

    Quezada-Ruiz, Carlos; Pieramici, Dante J; Nasir, Maʼan; Rabena, Melvin; Steinle, Nathan; Castellarin, Alessandro A; Dhoot, Dilsher; Couvillion, Stephen; See, Robert F; Avery, Robert L

    2015-06-01

    To report initial experience with intravitreal ocriplasmin (IVO) and to describe outer retina reflectivity changes observed on spectral domain optical coherence tomography (SD-OCT) after IVO injection in patients with vitreomacular traction (VMT) with or without macular holes (MHs). A consecutive retrospective review of patients with VMT and MH who were treated with IVO was performed. Patients underwent complete ophthalmic evaluation, including nonstandardized Snellen visual acuity testing, and SD-OCT at baseline and follow-up visits. A total of 23 patients who received IVO for VMT and/or MH were included for analysis. Patient age ranged from 53 years to 93 years with a mean of 74 years. The mean follow-up was 174 days (range: 20-291 days). Vitreomacular traction release at Day 30 after IVO was achieved in 11 of 23 patients (47.82%), at an average of 14.54 days (range: 1-30 days) after treatment. The mean visual acuity improved from 0.50 to 0.38. At presentation, eight patients had MH associated with VMT. Closure of the MH with ocriplasmin was achieved in two patients, and six patients underwent pars plana vitrectomy for MH repair. Ten of 23 patients (43.47%) presented with changes in the outer retina reflectivity on SD-OCT after IVO, 4 patients of this group experienced a decrease in visual acuity. In 7 of these 10 patients (70%), VMT release was documented on OCT by Day 30 postinjection compared with 4 of 13 patients (30.76%) without outer retina changes post-IVO. Normalization of the outer retina reflectivity was achieved in all cases. In this case series of VMT/MH patients treated with ocriplasmin, changes in the SD-OCT outer retina reflectivity were relatively common. Within weeks, the outer retinal reflectivity on SD-OCT improved, as did the visual acuity. Further studies to investigate the association between outer retina reflectivity changes with the use of IVO and long-term visual acuity outcomes are warranted.

  18. A multicenter, 12-month randomized study comparing dexamethasone intravitreal implant with ranibizumab in patients with diabetic macular edema.

    Science.gov (United States)

    Callanan, David G; Loewenstein, Anat; Patel, Sunil S; Massin, Pascale; Corcóstegui, Borja; Li, Xiao-Yan; Jiao, Jenny; Hashad, Yehia; Whitcup, Scott M

    2017-03-01

    To evaluate whether treatment with dexamethasone intravitreal implant (DEX implant) 0.7 mg every 5 months provides a similar average change in best-corrected visual acuity (BCVA) from baseline as ranibizumab 0.5 mg administered as per its European Summary of Product Characteristics in patients with diabetic macular edema (DME). This was a multicenter, open-label, 12-month, randomized, parallel-group, noninferiority study in patients with DME (one eye/patient). The primary efficacy measure was BCVA using the Early Treatment Diabetic Retinopathy Study (ETDRS) method. Secondary efficacy measures included area of leakage on fluorescein angiography and central retinal thickness (CRT) on optical coherence tomography. Baseline patient characteristics were similar in the two treatment groups (DEX implant, n = 181; ranibizumab, n = 182); mean DME duration was ∼33 months. The mean average BCVA change from baseline over 12 months was 4.34 letters with DEX implant and 7.60 letters with ranibizumab. The lower limit of the 95 % confidence interval of the between-group difference was -4.74 letters, and therefore, DEX was demonstrated to be noninferior to ranibizumab based on the prespecified noninferiority margin of 5 letters. At monthly follow-up visits, the percentage of patients with ≥15-letter BCVA gain from baseline ranged from 7.2 to 17.7 % with DEX implant and 4.4 to 26.9 % with ranibizumab. Both DEX implant and ranibizumab effectively reduced CRT and reduced the area of fluorescein leakage. Between-group differences in change from baseline CRT favored DEX implant at 1, 2, 6, and 7 months (p ≤ 0.007) and ranibizumab at 4, 5, 9, and 10 months (p medication. Both DEX implant and ranibizumab were well tolerated and improved BCVA and anatomic outcomes in patients with DME. DEX implant met the a priori criterion for noninferiority to ranibizumab in average change from baseline BCVA over 12 months. Noninferiority was achieved with an average of 2

  19. The effect of intravitreal bevacizumab (Avastin® on ocular pulse amplitude in neovascular age-related macular degeneration

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    Ehud Rechtman

    2011-01-01

    Full Text Available Ehud Rechtman1, Ingeborg Stalmans2, Joseph Glovinsky1, Christophe Breusegem2, Joseph Moisseiev1, Joachim Van Calster2, Alon Harris31Goldschleger Eye Institute, Sheba Medical Center, Ramat Gan, Israel; 2Department of Ophthalmology, University Hospitals Leuven, Leuven, Belgium; 3Department of Ophthalmology, Indiana University, Indianapolis, IN, USAPurpose: To evaluate the effect of intravitreal (IVT bevacizumab in neovascular age-related macular degeneration (AMD on global choroidal hemodynamics, as measured by ocular pulse amplitude (OPA.Methods: This was a two-center prospective study (Sheba Medical Center, Israel, and University Hospitals Leuven, Belgium. AMD patients who required IVT bevacizumab (1.25 mg/0.05 mL; first or repeated were examined three times: at days 0 (prior to injection, 7 (±3, and 28 (±7 postinjection. At each visit, OPAs of both eyes were measured using the Pascal dynamic contour tonometer (DCT. A paired t-test between preoperative and postoperative OPA was conducted. Pearson correlation was used to evaluate the influence of various measured parameters on DCT–OPA.Results: A total of 38 neovascular AMD patients were recruited, and 30 patients were included in the final analysis (18 females and 12 males; age 78.8 ± 5.82 years [mean ± standard deviation]. A good correlation was found throughout the study between the DCT–intraocular pressure (IOP and Goldmann IOP and between DCT–IOP and DCT–OPA. No change in OPA of bevacizumab-treated eyes was found between the visits (2.24 ± 0.73, 2.2 ± 0.86, and 2.23 ± 0.73 mm Hg at visits 1, 2, and 3, respectively; paired t-test: P = 0.77 between visits 1 and 2, P = 0.98 between visits 1 and 3. No correlations were found between DCT–OPA and age, heart rate, systemic blood pressure, axial length, keratometry readings, and central corneal thickness.Conclusions: OPA, an indirect measure of global choroidal hemodynamics, remains unchanged following IVT off-label bevacizumab. This

  20. Real-world assessment of intravitreal dexamethasone implant (0.7 mg) in patients with macular edema: the CHROME study.

    Science.gov (United States)

    Lam, Wai-Ching; Albiani, David A; Yoganathan, Pradeepa; Chen, John Chanchiang; Kherani, Amin; Maberley, David Al; Oliver, Alejandro; Rabinovitch, Theodore; Sheidow, Thomas G; Tourville, Eric; Wittenberg, Leah A; Sigouin, Chris; Baptiste, Darryl C

    2015-01-01

    The purpose of this study was to evaluate the real-world use, efficacy, and safety of one or more dexamethasone intravitreal implant(s) 0.7 mg (DEX implant) in patients with macular edema (ME). This was a retrospective cohort study of patients with ME secondary to retinal disease treated at ten Canadian retina practices, including one uveitis center. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), intraocular pressure (IOP), glaucoma and cataract surgery, and safety data were collected from the medical charts of patients with ≥3 months of follow-up after the initial DEX implant. One hundred and one patient charts yielded data on 120 study eyes, including diagnoses of diabetic ME (DME) (n=34), retinal vein occlusion (RVO, n=30; branch in 19 and central in 11), and uveitis (n=23). Patients had a mean age of 60.9 years, and 73.3% of the study eyes had ME for a duration of ≥12 months prior to DEX implant injection(s). Baseline mean (± standard error) BCVA was 0.63±0.03 logMAR (20/86 Snellen equivalents) and mean CRT was 474.4±18.2 μm. The mean number of DEX implant injections was 1.7±0.1 in all study eyes; 44.2% of eyes had repeat DEX implant injections (reinjection interval 2.3-4.9 months). The greatest mean peak changes in BCVA lines of vision occurred in study eyes with uveitis (3.3±0.6, P0.05). Significant decreases in CRT were observed: -255.6±43.6 μm for uveitis, -190.9±23.5 μm for DME, and -160.7±39.6 μm for RVO (P<0.0001 for all cohorts). IOP increases of ≥10 mmHg occurred in 20.6%, 24.1%, and 22.7% of DME, RVO, and uveitis study eyes, respectively. IOP-lowering medication was initiated in 29.4%, 16.7%, and 8.7% of DME, RVO, and uveitis study eyes, respectively. Glaucoma surgery was performed in 1.7% of all study eyes and cataract surgery in 29.8% of all phakic study eyes receiving DEX implant(s). DEX implant(s) alone or combined with other treatments and/or procedures resulted in functional and anatomic improvements in

  1. The effect of uric acid on homocysteine-induced endothelial dysfunction in bovine aortic endothelial cells.

    Science.gov (United States)

    Papezikova, Ivana; Pekarova, Michaela; Lojek, Antonin; Kubala, Lukas

    2009-01-01

    Elevated plasma uric acid indicates an increased risk of cardiovascular diseases associated with endothelial dysfunction. However, the role of uric acid in the pathogenesis of endothelial dysfunction is still a matter of debate. It is not clear whether uric acid is a real causative risk factor, an inert marker, or even a protective molecule with respect to its antioxidant properties. We have studied the effect of uric acid on intact endothelial cells as well as cells with homocysteine-induced endothelial dysfunction. Bovine aortic endothelial cells were treated with uric acid (100 - 600 muM) and homocysteine (100 muM) or with uric acid only. After 24 hours, the cells were stimulated with 1 mug/ml of calcium ionophore A23187, and nitric oxide (NO) production was measured electrochemically with the use of a NO-sensitive microelectrode. The expression of endothelial nitric oxide synthase (eNOS) and eNOS phosphorylation at Ser1179 was estimated with the use of Western blotting. Interaction between NO and uric acid was measured with a NO electrode. Superoxide generation was measured with the use of the fluorescence dye MitoSox Red. Homocysteine strongly diminished A23187-induced NO release. 100 muM uric acid slightly restored NO production; higher concentrations were ineffective. Interestingly, a dose-dependent decrease of NO release was observed in the cells treated only with uric acid. Uric acid did not scavenge NO and did not change eNOS protein expression or phosphorylation at Ser1179, but dose-dependently increased superoxide production in A23187-stimulated cells. In conclusion, uric acid decreased NO bioavailability and enhanced superoxide generation in A23187-stimulated bovine aortic endothelial cells.

  2. Temsirolimus inhibits proliferation and migration in retinal pigment epithelial and endothelial cells via mTOR inhibition and decreases VEGF and PDGF expression.

    Directory of Open Access Journals (Sweden)

    Raffael Liegl

    Full Text Available Due to their high prevalence, retinal vascular diseases including age related macular degeneration (AMD, retinal vein occlusions (RVO, diabetic retinopathy (DR and diabetic macular edema have been major therapeutic targets over the last years. The pathogenesis of these diseases is complex and yet not fully understood. However, increased proliferation, migration and angiogenesis are characteristic cellular features in almost every retinal vascular disease. The introduction of vascular endothelial growth factor (VEGF binding intravitreal treatment strategies has led to great advances in the therapy of these diseases. While the predominant part of affected patients benefits from the specific binding of VEGF by administering an anti-VEGF antibody into the vitreous cavity, a small number of non-responders exist and alternative or additional therapeutic strategies should therefore be evaluated. The mammalian target of rapamycin (mTOR is a central signaling pathway that eventually triggers up-regulation of cellular proliferation, migration and survival and has been identified to play a key role in angiogenesis. In the present study we were able to show that both retinal pigment epithelial (RPE cells as wells as human umbilical vein endothelial cells (HUVEC are inhibited in proliferating and migrating after treatment with temsirolimus in non-toxic concentrations. Previous studies suggest that the production of VEGF, platelet derived growth factor (PDGF and other important cytokines is not only triggered by hypoxia but also by mTOR itself. Our results indicate that temsirolimus decreases VEGF and PDGF expression on RNA and protein levels significantly. We therefore believe that the mTOR inhibitor temsirolimus might be a promising drug in the future and it seems worthwhile to evaluate complementary therapeutic effects with anti-VEGF drugs for patients not profiting from mono anti-VEGF therapy alone.

  3. Arterial endothelial function measurement method and apparatus

    Science.gov (United States)

    Maltz, Jonathan S; Budinger, Thomas F

    2014-03-04

    A "relaxoscope" (100) detects the degree of arterial endothelial function. Impairment of arterial endothelial function is an early event in atherosclerosis and correlates with the major risk factors for cardiovascular disease. An artery (115), such as the brachial artery (BA) is measured for diameter before and after several minutes of either vasoconstriction or vasorelaxation. The change in arterial diameter is a measure of flow-mediated vasomodification (FMVM). The relaxoscope induces an artificial pulse (128) at a superficial radial artery (115) via a linear actuator (120). An ultrasonic Doppler stethoscope (130) detects this pulse 10-20 cm proximal to the point of pulse induction (125). The delay between pulse application and detection provides the pulse transit time (PTT). By measuring PTT before (160) and after arterial diameter change (170), FMVM may be measured based on the changes in PTT caused by changes in vessel caliber, smooth muscle tone and wall thickness.

  4. Endothelial progenitor cells in diabetes complications

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    Marina Sergeevna Michurova

    2014-12-01

    Full Text Available Patients with diabetes mellitus (DM have a 2- to 4-times higher risk of developing cardiovascular complications compared with non-diabetic controls. Hyperglycemia activates pathophysiological mechanisms that damage the endothelium. According to the current views, circulating progenitor cells derived from bone marrow repair the damage. These cells, known as endothelial progenitor cells (EPCs, maintain endothelial homeostasis and contribute to the formation of new vessels. Many clinical studies have reported that EPC population is dysfunctional and declines in numbers in patients with type 1 and type 2 DM. In addition, bone marrow doesn’t respond adequately to mobilizing stimuli in DM. Therefore, EPC alterations might have a pathogenic role in the complications of DM. In this review, EPC alterations will be examined in the context of macrovascular and microvascular complications of DM, highlighting their roles and functions in the progression of the disease.

  5. Intravitreal use of bone marrow mononuclear fraction containing CD34+ stem cells in patients with atrophic age-related macular degeneration

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    Cotrim CC

    2017-05-01

    Full Text Available Carina Costa Cotrim, Luiza Toscano, André Messias, Rodrigo Jorge, Rubens Camargo Siqueira Department of Ophthalmology, Otorhinolaryngology and Head and Neck Surgery, Ribeirao Preto School of Medicine, University of Sao Paulo, Sao Paulo, Brazil Purpose: To evaluate the therapeutic potential and safety of intravitreal injections of bone marrow mononuclear fraction (BMMF containing CD34+ cells in patients with atrophic age-related macular degeneration (AMD.Methods: Ten patients with atrophic AMD and best-corrected visual acuity (BCVA in the worse-seeing eye of ≤20/100 were enrolled in this study. The bone marrow from all patients was ­aspirated and processed for mononuclear cell separation. A 0.1 mL suspension of BMMF CD34+ cells was injected into the vitreous cavity of the worse-seeing eye. Patients were evaluated at Baseline and 1,3,6,9 and 12 months after injection. Ophthalmic evaluation included BCVA measurement, microperimetry, infrared imaging, fundus autofluorescence and SD-optical coherence tomography at all study visits. Fluorescein angiography was performed at Baseline and at 6 and 12 months after intravitreal therapy.Results: All patients completed the 6-month follow-up, and six completed the 12-month follow-up. Prior to the injection, mean BCVA was 1.18 logMAR (20/320-1, ranging from 20/125 to 20/640-2, and improved significantly at every follow-up visit, including the 12-month one, when BCVA was 1.0 logMAR (20/200 (P<0.05. Mean sensitivity threshold also improved significantly at 6, 9 and 12 months after treatment (P<0.05. Considering the area of atrophy identified by fundus autofluorescence, significant mean BCVA and mean sensitivity threshold improvement were observed in patients with the smallest areas of atrophy. Fluorescein angiography did not identify choroidal new vessels or tumor growth.Conclusion: The use of intravitreal BMMF injections in patients with AMD is safe and is associated with significant improvement in BCVA

  6. Management of cataract with macular oedema due to diabetes mellitus Type-II and hypertension with grid laser prior to surgery and intra-vitreal bevacizumab (avastin) peroperatively

    International Nuclear Information System (INIS)

    Wahab, S.; Ahmed, J.

    2010-01-01

    To study the visual outcome in patients subjected to cataract extraction with prior grid laser and intraoperative intravitreal bevacizumab injection. Methods: This prospective case series comprised of 38 patients subjected to phacoemulsification and in the bag intraocular lens implantation at Al-Noor Eye Hospital and Sindh Govt Lyari General Hospital Karachi from January 2007 to December 2008. All the patients had prior macular grid treatment and intra-operative injection of intra-vitreal Avastin. Diabetes mellitus duration, preoperative glycosylated haemoglobin (HbA1c) level and other systemic and local complications of diabetes were recorded. The patients were clinically assessed with bio microscopic examination preoperatively, and postoperatively on day 1, week 1, and in months 1, 2, 3 and 6 respectively. Visual acuity and state of macular oedema was clinically assessed and documented. Results: Out of thirty-eight patients, eighteen were males and 20 were females. Mean duration of diabetes was 9.92 +- 5.5 years (Range 4-16) while that of hypertension was 7.87 +- 3.66 years (Range = 2-15). HbA1c level was 8.36% +- 1.93% (range 6.3 - 12.3). Thirty-one (81.5%) patients had HbA1c level 8.0% or above indicating a poor control. At 6 months of follow up best corrected distant visual acuity of 6/6 to 6/9 was achieved in 23(60.5 %), 6/12 in 11(28.9%) and 6/24 in 4(10.5%) cases while best corrected near acuity of N/6 was achieved in 22(57.8%) N/8 in 12(31.4%) and N/12 in 4(10.5%) cases. At 6 months follow up visual acuity declined in two cases because of uncontrolled diabetes and hypertension. Conclusion: Cataract surgery in diabetic patients with macular oedema and hypertension has a good visual outcome if prior macular grid laser is performed and intra-vitreal anti VEGF is injected during surgery. (author)

  7. Ionizing radiation activates vascular endothelial growth factor-A transcription in human umbilical vein endothelial cells

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    Lee, Hyounji; Kim, Kwang Seok; Jeong, Jae Hoon; Lim, Young Bin [Radiation Cancer Biology Team, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2016-12-15

    Vascular endothelial growth factor (VEGF) is an essential paracrine factor for developmental and pathological angiogenesis. VEGF also exerts its effects in an autocrine manner in VEGF-producing cells. For instance, autocrine VEGF signaling occurs in tumor cells and contributes to key aspects of tumorigenesis, such as in the function of cancer stem cells and tumor initiation, which are independent of angiogenesis. In addition to tumors cells, non-transformed cells also express VEGF. For example, a VEGF dependent intracellular autocrine mechanism is crucial for the survival of hematopoietic stem cells and hematopoiesis. Stereotactic body radiation therapy (SBRT) is a novel treatment modality for early primary cancer and oligometastatic disease. SBRT delivers high-dose hypofractionated radiation, such as 20-60 Gy, to tumors in a single fraction or 2-5 fractions. As VEGF is a critical regulator of functional integrity and viability of vascular endothelial cells, we examined whether high-dose irradiation alters VEGF signaling by measuring the expression levels of VEGFA transcript. It is generally believed that endothelial cells do not produce VEGF in response to radiation. In present study, however, we provide the first demonstration of transcriptional regulation of VEGFA in human vascular endothelial cells by IR treatment. Irradiation with doses higher than 10 Gy in a single exposure triggers up-regulation of VEGFA transcription within 2 hours in HUVECs, whereas irradiation with 10 Gy does not alter VEGFA levels. Our data have shown that high-dose irradiation triggers immediate transactivation of VEGFA in human vascular endothelial cells.

  8. Elevated PTH induces endothelial-to-chondrogenic transition in aortic endothelial cells.

    Science.gov (United States)

    Wu, Min; Zhang, Jian-Dong; Tang, Ri-Ning; Crowley, Steven D; Liu, Hong; Lv, Lin-Li; Ma, Kun-Ling; Liu, Bi-Cheng

    2017-03-01

    Previous studies have shown that increased parathyroid hormone (PTH) attributable to secondary hyperparathyroidism in chronic kidney disease accelerates the arteriosclerotic fibrosis and calcification. Although the underlying mechanisms remain largely unknown, endothelial cells (ECs) have recently been demonstrated to participate in calcification in part by providing chondrogenic cells via the endothelial-to-mesenchymal transition (EndMT). Therefore, this study aimed to investigate whether elevated PTH could induce endothelial-to-chondrogenic transition in aortic ECs and to determine the possible underlying signaling pathway. We found that treatment of ECs with PTH significantly upregulated the expression of EndMT-related markers. Accordingly, ECs treated with PTH exhibited chondrogenic potential. In vivo, lineage-tracing model-subjected mice with endothelial-specific green fluorescent protein fluorescence to chronic PTH infusion showed a marked increase in the aortic expression of chondrocyte markers, and confocal microscopy revealed the endothelial origin of cells expressing chondrocyte markers in the aorta after PTH infusion. Furthermore, this in vitro study showed that PTH enhanced the nuclear localization of β-catenin in ECs, whereas β-catenin siRNA or DKK1, an inhibitor of β-catenin nuclear translocation, attenuated the upregulation of EndMT-associated and chondrogenic markers induced by PTH. In summary, our study demonstrated that elevated PTH could induce the transition of ECs to chondrogenic cells via EndMT, possibly mediated by the nuclear translocation of β-catenin. Copyright © 2017 the American Physiological Society.

  9. Activation of Endothelial Nitric Oxide (eNOS Occurs through Different Membrane Domains in Endothelial Cells.

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    Jason Tran

    Full Text Available Endothelial cells respond to a large range of stimuli including circulating lipoproteins, growth factors and changes in haemodynamic mechanical forces to regulate the activity of endothelial nitric oxide synthase (eNOS and maintain blood pressure. While many signalling pathways have been mapped, the identities of membrane domains through which these signals are transmitted are less well characterized. Here, we manipulated bovine aortic endothelial cells (BAEC with cholesterol and the oxysterol 7-ketocholesterol (7KC. Using a range of microscopy techniques including confocal, 2-photon, super-resolution and electron microscopy, we found that sterol enrichment had differential effects on eNOS and caveolin-1 (Cav1 colocalisation, membrane order of the plasma membrane, caveolae numbers and Cav1 clustering. We found a correlation between cholesterol-induced condensation of the plasma membrane and enhanced high density lipoprotein (HDL-induced eNOS activity and phosphorylation suggesting that cholesterol domains, but not individual caveolae, mediate HDL stimulation of eNOS. Vascular endothelial growth factor (VEGF-induced and shear stress-induced eNOS activity was relatively independent of membrane order and may be predominantly controlled by the number of caveolae on the cell surface. Taken together, our data suggest that signals that activate and phosphorylate eNOS are transmitted through distinct membrane domains in endothelial cells.

  10. Endothelial cell transfection of ex vivo arteries

    OpenAIRE

    sprotocols

    2015-01-01

    Authors: Alexander Lohman, Adam Straub & Brant Isakson ### Abstract The vascular endothelium plays an essential role in regulating blood vessel tone, blood flow and blood pressure. Current vascular model systems for examination of endothelial cell biology and blood vessel physiology and pathology rely on cell culture and the generation of genetically modified animals. While these systems are advantageous for studying the endothelium, many cell culture models omit the contribution of o...

  11. Endothelial progenitor cells in coronary artery disease.

    Science.gov (United States)

    Donahue, Michael; Quintavalle, Cristina; Chiariello, Giovanni Alfonso; Condorelli, Gerolama; Briguori, Carlo

    2013-10-01

    In the last two decades a great deal of evidence has been collected on the key role of endothelial progenitor cells (EPC) in the mechanisms of vascular healing. The role of EPC as a marker of vascular health and prognosis of cardiovascular disease is already consolidated. This review aims to examine and evaluate recent data regarding EPC, as biomarkers, prognostic factor and potential therapy in cardiovascular disease.

  12. Arecoline is cytotoxic for human endothelial cells.

    Science.gov (United States)

    Ullah, Mafaz; Cox, Stephen; Kelly, Elizabeth; Boadle, Ross; Zoellner, Hans

    2014-11-01

    Oral submucous fibrosis is a pre-malignant fibrotic condition caused by areca nut use and involves reduced mucosal vascularity. Arecoline is the principal areca nut alkaloid and is cytotoxic for epithelium and fibroblasts. Endothelial cell cycle arrest is reported on exposure to arecoline, as is cytotoxicity for endothelial-lung carcinoma hybrid cells. We here describe cytotoxicity for primary human endothelial cultures from seven separate donors. Human umbilical vein endothelial cells were exposed to increasing concentrations of arecoline and examined by: phase-contrast microscopy, haemocytometer counts, transmission electron microscopy, lactate dehydrogenase release and the methyl-thiazol-tetrazolium assay. Vacuolation and detachment of endothelium were observed at and above arecoline concentrations of 333 μg/ml or more. Ultrastructural features of cellular stress were seen after 24-h treatment with 111 μg/ml arecoline and included reduced ribosomal studding of endoplasmic reticulum, increased autophagolysosomal structures, increased vacuolation and reduced mitochondrial cristae with slight swelling. Similar changes were seen at 4 h with arecoline at 333 μg/ml or above, but with more severe mitochondrial changes including increased electron density of mitochondrial matrix and greater cristal swelling, while by 24 h, these cells were frankly necrotic. Haemocytometer counts were paralleled by both lactate dehydrogenase release and the methyl-thiazol-tetrazolium assays. Arecoline is cytotoxic via necrosis for endothelium, while biochemical assays indicate no appreciable cellular leakage before death and detachment, as well as no clear effect on mitochondrial function in viable cells. Arecoline toxicity may thus contribute to reduced vascularity in oral submucous fibrosis. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. [Endothelial microparticles (EMP) in physiology and pathology].

    Science.gov (United States)

    Sierko, Ewa; Sokół, Monika; Wojtukiewicz, Marek Z

    2015-08-18

    Endothelial microparticles (EMP) are released from endothelial cells (ECs) in the process of activation and/or apoptosis. They harbor adhesive molecules, enzymes, receptors and cytoplasmic structures and express a wide range of various constitutive antigens, typical for ECs, at their surface. Under physiological conditions the concentration of EMP in the blood is clinically insignificant. However, it was reported that under pathological conditions EMP concentration in the blood might slightly increase and contribute to blood coagulation, angiogenesis and inflammation. It has been shown that EMP directly and indirectly contribute to the activation of blood coagulation. Endothelial microparticles directly participate in blood coagulation through their surface tissue factor (TF) - a major initiator of blood coagulation. Furthermore, EMP exhibit procoagulant potential via expression of negatively charged phospholipids at their surface, which may promote assembly of coagulation enzymes (TF/VII, tenases and prothrombinase complexes), leading to thrombus formation. In addition, they provide a binding surface for coagulation factors: IXa, VIII, Va and IIa. Moreover, it is possible that EMP transfer TF from TF-bearing EMP to activated platelets and monocytes by binding them through adhesion molecules. Also, EMP express von Willebrand factor, which may facilitate platelet aggregation. Apart from their procoagulant properties, it was demonstrated that EMP may express adhesive molecules and metalloproteinases (MMP-2, MMP-9) at their surface and release growth factors, which may contribute to angiogenesis. Additionally, surface presence of C3 and C4 - components of the classical pathway - suggests pro-inflammatory properties of these structures. This article contains a summary of available data on the biology and pathophysiology of endothelial microparticles and their potential role in blood coagulation, angiogenesis and inflammation.

  14. Brain endothelial dysfunction in cerebral adrenoleukodystrophy.

    Science.gov (United States)

    Musolino, Patricia L; Gong, Yi; Snyder, Juliet M T; Jimenez, Sandra; Lok, Josephine; Lo, Eng H; Moser, Ann B; Grabowski, Eric F; Frosch, Matthew P; Eichler, Florian S

    2015-11-01

    See Aubourg (doi:10.1093/awv271) for a scientific commentary on this article.X-linked adrenoleukodystrophy is caused by mutations in the ABCD1 gene leading to accumulation of very long chain fatty acids. Its most severe neurological manifestation is cerebral adrenoleukodystrophy. Here we demonstrate that progressive inflammatory demyelination in cerebral adrenoleukodystrophy coincides with blood-brain barrier dysfunction, increased MMP9 expression, and changes in endothelial tight junction proteins as well as adhesion molecules. ABCD1, but not its closest homologue ABCD2, is highly expressed in human brain microvascular endothelial cells, far exceeding its expression in the systemic vasculature. Silencing of ABCD1 in human brain microvascular endothelial cells causes accumulation of very long chain fatty acids, but much later than the immediate upregulation of adhesion molecules and decrease in tight junction proteins. This results in greater adhesion and transmigration of monocytes across the endothelium. PCR-array screening of human brain microvascular endothelial cells after ABCD1 silencing revealed downregulation of both mRNA and protein levels of the transcription factor c-MYC (encoded by MYC). Interestingly, MYC silencing mimicked the effects of ABCD1 silencing on CLDN5 and ICAM1 without decreasing the levels of ABCD1 protein itself. Together, these data demonstrate that ABCD1 deficiency induces significant alterations in brain endothelium via c-MYC and may thereby contribute to the increased trafficking of leucocytes across the blood-brain barrier as seen in cerebral adrenouleukodystrophy. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. Targeted endothelial nanomedicine for common acute pathological conditions.

    Science.gov (United States)

    Shuvaev, Vladimir V; Brenner, Jacob S; Muzykantov, Vladimir R

    2015-12-10

    Endothelium, a thin monolayer of specialized cells lining the lumen of blood vessels is the key regulatory interface between blood and tissues. Endothelial abnormalities are implicated in many diseases, including common acute conditions with high morbidity and mortality lacking therapy, in part because drugs and drug carriers have no natural endothelial affinity. Precise endothelial drug delivery may improve management of these conditions. Using ligands of molecules exposed to the bloodstream on the endothelial surface enables design of diverse targeted endothelial nanomedicine agents. Target molecules and binding epitopes must be accessible to drug carriers, carriers must be free of harmful effects, and targeting should provide desirable sub-cellular addressing of the drug cargo. The roster of current candidate target molecules for endothelial nanomedicine includes peptidases and other enzymes, cell adhesion molecules and integrins, localized in different domains of the endothelial plasmalemma and differentially distributed throughout the vasculature. Endowing carriers with an affinity to specific endothelial epitopes enables an unprecedented level of precision of control of drug delivery: binding to selected endothelial cell phenotypes, cellular addressing and duration of therapeutic effects. Features of nanocarrier design such as choice of epitope and ligand control delivery and effect of targeted endothelial nanomedicine agents. Pathological factors modulate endothelial targeting and uptake of nanocarriers. Selection of optimal binding sites and design features of nanocarriers are key controllable factors that can be iteratively engineered based on their performance from in vitro to pre-clinical in vivo experimental models. Targeted endothelial nanomedicine agents provide antioxidant, anti-inflammatory and other therapeutic effects unattainable by non-targeted counterparts in animal models of common acute severe human disease conditions. The results of animal

  16. Photodynamic therapy combined with antivascular endothelial growth factor treatment for recalcitrant chronic central serous chorioretinopathy

    Directory of Open Access Journals (Sweden)

    Asahi MG

    2017-11-01

    Full Text Available Masumi G Asahi,1 Andrew T Chon,1 Esmeralda Gallemore,1 Ron P Gallemore1,2 1Clinical Research Department, Retina Macula Institute, Torrance, CA, USA; 2Jules Stein Eye Institute, University of California, Los Angeles, CA, USA Purpose: To determine whether combination photodynamic therapy (PDT and antivascular endothelial growth factor (VEGF therapy is effective in the management of chronic central serous chorioretinopathy (CSC recalcitrant to conventional therapy. Methods: This was a retrospective analysis of eight patients with chronic CSC unresponsive to topical nonsteroidal anti-inflammatory drugs, focal photocoagulation, anti-VEGF alone, or PDT alone. All patients were evaluated with a full ophthalmic examination, spectral-domain optical coherence tomography (OCT, fluorescein angiography (FA, and most with indocyanine green angiography (ICGA followed by treatment with half-fluence PDT and intravitreal anti-VEGF injection (seven bevacizumab, one aflibercept. Patients were seen in follow-up 1 month after treatment. Results: All eight patients achieved complete resolution in subretinal fluid following combination treatment. Average duration of CSC prior to initiation of combination therapy was 7.5 months. Mean central macular thickness on OCT decreased significantly from 401.2±52.7 µm to 297.9±18.2 µm (p=0.0010 by 4 months after treatment (1.63±1.18 months. Seven of eight patients were followed up for an average of 13 months with no recurrence during that time. One case recurred at 8 months and was treated with repeat combination at that time. Frank choroidal neovascularization (CNV was not identified in these cases on FA or ICGA studies. Eight of eight patients showed significant improvement in vision from a logMAR of 0.1125±0.099 to 0.0125±0.064 (p=0.019. Conclusion: Combination PDT and anti-VEGF is effective for chronic CSC which has failed conventional therapy. Associated CNV and/or inflammation may be reasons for greater success in

  17. Protective effects of Donepezil against endothelial permeability.

    Science.gov (United States)

    Tang, Xuelu; Di, Xiuhua; Liu, Yilin

    2017-09-15

    The endothelium lines the interior surface of blood vessels, and under pathophysiologic conditions, its integrity can be compromised due to a disturbance in the expression of tight junctions. Donepezil is a licensed drug used in the palliative treatment of Alzheimer's disease (AD). Increasing evidence has reported that donepezil has an anti-inflammatory activity. However, little information is available regarding the role of donepezil in vascular diseases. In this study, we found that pretreatment with donepezil significantly ameliorated endothelial permeability induced by tumor necrosis factor (TNF-α) by restoring the expression of the tight junction proteins vascular endothelial cadherin (VE-cadherin) and zonula occludens-1 (ZO-1) in human umbilical vein endothelial cells (HUVECs). Mechanistically, our results indicate that donepezil regulates the expression and activity of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinases 1 (TIMP-1), but not matrix metalloproteinase-2 (MMP-2) or tissue inhibitor of metalloproteinases 2 (TIMP-2). Importantly, the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/ serine-threonine kinase (AKT)/ nuclear factor kappa B (NF-κB) pathway was found to be involved in this process. These results suggest that donepezil may potentially play an important therapeutic role in vascular diseases. Copyright © 2017. Published by Elsevier B.V.

  18. Doinseunggitang Ameliorates Endothelial Dysfunction in Diabetic Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Jung Joo Yoon

    2013-01-01

    Full Text Available Atherosclerosis, a chronic and progressive disease characterized by vascular inflammation, is a leading cause of death in diabetes patients. Doinseunggitang (DYSGT, traditional prescription, has been used for promoting blood circulation to remove blood stasis. The aim of this study was to investigate the beneficial effects of DYSGT on endothelial dysfunction in diabetic atherosclerosis animal model. Apolipoprotein E knockout (ApoE KO mice fed on a Western diet were treated with DYSGT (200 mg/kg/day. DYSGT significantly lowered blood glucose level and glucose tolerance as well as systolic blood pressure. Metabolic parameter showed that DYSGT markedly decreased triglyceride and LDL-cholesterol levels. In the thoracic aorta, the impairment of vasorelaxation response to acetylcholine and atherosclerotic lesion was attenuated by DYSGT. Furthermore, DYSGT restored the reduction of endothelial nitric oxide synthase (eNOS expression, leading to the inhibition of intracellular adhesion molecule-1 (ICAM-1 and endothelin-1 (ET-1 expression. In conclusion, DYSGT improved the development of diabetic atherosclerosis via attenuation of the endothelial dysfunction, possibly by inhibiting ET-1, cell adhesion molecules, and lesion formation. Therefore, these results suggest that Korean traditional prescription Doinseunggitang may be useful in the treatment and prevention of diabetic vascular complications.

  19. Visual outcomes of age-related macular degeneration patients undergoing intravitreal ranibizumab monotherapy in an urban population: letter to the editor

    Directory of Open Access Journals (Sweden)

    Stewart MW

    2015-09-01

    Full Text Available Michael W Stewart Department of Ophthalmology, Mayo Clinic Florida, Jacksonville, FL, USA In their recently published manuscript entitled “Visual outcomes of age-related macular degeneration patients undergoing intravitreal ranibizumab monotherapy in an urban population” Basheer et al1 reported on the prospectively acquired results of 123 eyes (106 patients treated for 2 years with ranibizumab as needed. Visual acuity (VA outcomes from this series were summarized by the following statement: “Although our results, and those from other clinical settings, do not quite match the degree of vision preservation and gain as the large clinical trials, they are not dramatically dissimilar”.1 Unfortunately, the authors provide no statistical analysis to support this statement.View original paper by Basheer and colleagues.

  20. Intravitreal Bevacizumab Alone or Combined with Macular Laser Photocoagulation for Recurrent or Persistent Macular Edema Secondary to Branch Retinal Vein Occlusion

    Directory of Open Access Journals (Sweden)

    Takafumi Hirashima

    2014-01-01

    Full Text Available Background. To evaluate the efficacy of intravitreal bevacizumab (IVB injection with or without macular laser photocoagulation (MLP for recurrent or persistent macular edema (ME secondary to branch retinal vein occlusion (BRVO. Methods. Thirty-four eyes underwent IVB injection for ME secondary to BRVO as a primary treatment. Twenty of the 34 eyes experienced recurrent or persistent ME after the first IVB. Nine of the 20 eyes (Group 1 were retreated with IVB combined with MLP. The remaining 11 eyes (Group 2 were retreated with IVB alone. Results. In Group 1, the postoperative best corrected visual acuity (BCVA improved compared with the preoperative value at all follow-up visits, although no statistically significant improvement was observed at 6 months. In contrast, BCVA significantly improved from 0.53 to 0.40 at 6 months (P<0.05 in Group 2. Conclusion. Combined therapy tended to have a smaller effect on visual acuity compared with IVB monotherapy.

  1. Radiation Effects on the Cytoskeleton of Endothelial Cells and Endothelial Monolayer Permeability

    International Nuclear Information System (INIS)

    Gabrys, Dorota; Greco, Olga; Patel, Gaurang; Prise, Kevin M.; Tozer, Gillian M.; Kanthou, Chryso

    2007-01-01

    Purpose: To investigate the effects of radiation on the endothelial cytoskeleton and endothelial monolayer permeability and to evaluate associated signaling pathways, which could reveal potential mechanisms of known vascular effects of radiation. Methods and Materials: Cultured endothelial cells were X-ray irradiated, and actin filaments, microtubules, intermediate filaments, and vascular endothelial (VE)-cadherin junctions were examined by immunofluorescence. Permeability was determined by the passage of fluorescent dextran through cell monolayers. Signal transduction pathways were analyzed using RhoA, Rho kinase, and stress-activated protein kinase-p38 (SAPK2/p38) inhibitors by guanosine triphosphate-RhoA activation assay and transfection with RhoAT19N. The levels of junction protein expression and phosphorylation of myosin light chain and SAPK2/p38 were assessed by Western blotting. The radiation effects on cell death were verified by clonogenic assays. Results: Radiation induced rapid and persistent actin stress fiber formation and redistribution of VE-cadherin junctions in microvascular, but not umbilical vein endothelial cells, and microtubules and intermediate filaments remained unaffected. Radiation also caused a rapid and persistent increase in microvascular permeability. RhoA-guanosine triphosphatase and Rho kinase were activated by radiation and caused phosphorylation of downstream myosin light chain and the observed cytoskeletal and permeability changes. SAPK2/p38 was activated by radiation but did not influence either the cytoskeleton or permeability. Conclusion: This study is the first to show rapid activation of the RhoA/Rho kinase by radiation in endothelial cells and has demonstrated a link between this pathway and cytoskeletal remodeling and permeability. The results also suggest that the RhoA pathway might be a useful target for modulating the permeability and other effects of radiation for therapeutic gain

  2. Endothelial glycocalyx on brain endothelial cells is lost in experimental cerebral malaria

    DEFF Research Database (Denmark)

    Hempel, Casper; Hyttel, Poul; Kurtzhals, Jørgen Al

    2014-01-01

    We hypothesized that the glycocalyx, which is important for endothelial integrity, is lost in severe malaria. C57BL/6 mice were infected with Plasmodium berghei ANKA, resulting in cerebral malaria, or P. chabaudi AS, resulting in uncomplicated malaria. We visualized the glycocalyx with transmission...... electron microscopy and measured circulating glycosaminoglycans by dot blot and ELISA. The glycocalyx was degraded in brain vasculature in cerebral and to a lesser degree uncomplicated malaria. It was affected on both intact and apoptotic endothelial cells. Circulating glycosaminoglycan levels suggested...

  3. Intravitreal Ciliary Neurotrophic Factor Transiently Improves Cone-Mediated Function in a CNGB3−/− Mouse Model of Achromatopsia

    Science.gov (United States)

    Marangoni, Dario; Vijayasarathy, Camasamudram; Bush, Ronald A.; Wei, Lisa L.; Wen, Rong; Sieving, Paul A.

    2015-01-01

    Purpose Ciliary neurotrophic factor (CNTF) was recently shown to augment cone function in CNGB3 mutant achromat dogs. However, testing CNTF-releasing implant in human CNGB3 achromats failed to show benefit. We evaluated the effects of CNTF protein on the retinal function in an additional achromatopsia model, the CNGB3−/− mouse. Methods Fifty-nine CNGB3−/− mice (postnatal day [PD] ± SD = 30 ± 7) received a unilateral intravitreal injection of 1 or 2 μg CNTF protein, and 15 wild-type (WT) mice (PD = 34 ± 3) received 1 μg CNTF. Retinal function was evaluated by flash ERG and photopic flicker ERG (fERG) at 7 and 14 days after treatment. Results Seven days post CNTF, the photopic b-wave Vmax was significantly increased in CNGB3−/− mice (P < 0.01), whereas it was reduced in WT mice (P < 0.05). Ciliary neurotrophic factor significantly increased the amplitude of photopic fERG and the photopic oscillatory potentials (OPs) in CNGB3−/− mice. Ciliary neurotrophic factor did not alter the scotopic a-wave in either CNGB3−/− or WT mice, but it increased the scotopic b-wave k (P < 0.01) in CNGB3−/− mice, indicating diminished scotopic sensitivity, and reduced the scotopic b-wave Vmax in WT mice (P < 0.05). No difference was found in ERG parameters between 1 or 2 μg CNTF. Fourteen days after CNTF injection the ERG changes in CNGB3−/− mice were lost. Conclusions Intravitreal bolus CNTF protein caused a small and transient improvement of cone-mediated function in CNGB3−/− mice, whereas it reduced rod-mediated function. The increase in photopic OPs and the lack of changes in scotopic a-wave suggest a CNTF effect on the inner retina. PMID:26567794

  4. Intravitreal Diclofenac plus Bevacizumab versus Bevacizumab alone in treatment-naive diabetic macular edema: a randomized double-blind clinical trial.

    Science.gov (United States)

    Ghanbari, Heshmatollah; Kianersi, Farzan; Sonbolestan, Seyed Ali; Abtahi, Mohammad-Ali; Akbari, Mojataba; Abtahi, Zahra-Alsadat; Abtahi, Seyed-Hossein

    2017-08-01

    The aim of this study is to evaluate the short-term effects of a single intravitreal injection of 1.25 mg Bevacizumab combined with 300 lg/0.1 mL Diclofenac (IVB/D) versus 1.25 mg intravitreal Bevacizumab (IVB) alone in the treatment of naive diabetic macular edema (DME). In this prospective, randomized clinical trial, 80 eyes were included in the final analysis; 42 and 38 of which in the IVB and IVB/D groups, respectively. The primary outcome measure was a change in best-corrected visual acuity (BCVA) in logMAR at week 4. The secondary outcomes included changes in central macular thickness (CMT), macular volume, and potential injection-related complications. Significant improvement of BCVA was demonstrated in both study arms (mean reductions in LogMAR: -0.088 ± 0.278, -0.228 ± 0.330 for IVB and IVB/D, respectively). The difference in BCVA changes was in favor of IVB/D; however, not to a statistically significant level (P = 0.160). Significant reduction of CMT was documented in both study arms (mean reductions: 82.43 ± 160.09 and 153.26 ± 163.85 for IVB and IVB + IVD, respectively). Comparison of CMT changes between groups showed that IVB/D reduced CMT more than that of IVB (P = 0.04). Effects on macular volume corresponded to those of CMT. No injection-related complications or significant alterations in intraocular pressure were observed in any of the study arms. In treatment-naive DME, superiority of IVB/D combination therapy over IVB monotherapy may exist; especially as regards anatomical features. In our therapeutic arsenal for DME, IVD can be added as an adjunct to Bevacizumab.

  5. EFFECT OF INTRAVITREAL RANIBIZUMAB ON GANGLION CELL COMPLEX AND PERIPAPILLARY RETINAL NERVE FIBER LAYER IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION USING SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY.

    Science.gov (United States)

    Zucchiatti, Ilaria; Cicinelli, Maria V; Parodi, Maurizio Battaglia; Pierro, Luisa; Gagliardi, Marco; Accardo, Agostino; Bandello, Francesco

    2017-07-01

    To analyze the changes in ganglion cell complex and peripapillary retinal nerve fiber layer thickness, in central macular thickness and choroidal thickness on spectral domain optical coherence tomography in patients with neovascular age-related macular degeneration treated with intravitreal ranibizumab injections. All consecutive patients with untreated neovascular age-related macular degeneration received loading phase of three monthly intravitreal ranibizumab, followed by retreatments on a pro re nata protocol for 12 months. changes in ganglion cell complex and retinal nerve fiber layer at the end of follow-up. Secondary outcome: changes in best-corrected visual acuity, central macular thickness, and choroidal thickness at the end of follow-up. Choroidal thickness was measured at 500 μm, 1000 μm, and 1,500 μm intervals nasally, temporally, superiorly, and inferiorly to the fovea, respectively, on horizontal and vertical line scans centered on the fovea. Twenty-four eyes were included. Ganglion cell complex and peripapillary retinal nerve fiber layer thickness did not show statistically significant changes through 12 months (55.6 ± 18.5 and 81.9 ± 9.9 μm at baseline, 52.7 ± 19.3 and 84.6 ± 15.5 μm at month 12, P > 0.05). Central macular thickness showed progressive decrease from baseline to month 12, with maximum reduction at month 3 (P retinal nerve fiber layer and ganglion cell complex thickness in 1-year follow-up. Choroidal thickness in papillomacular area and central macular thickness was significantly reduced at the end of treatment. Further studies, with larger sample, longer follow-up, and greater number of injections, are warranted.

  6. Sickle erythrocytes inhibit human endothelial cell DNA synthesis

    International Nuclear Information System (INIS)

    Weinstein, R.; Zhou, M.A.; Bartlett-Pandite, A.; Wenc, K.

    1990-01-01

    Patients with sickle cell anemia experience severe vascular occlusive phenomena including acute pain crisis and cerebral infarction. Obstruction occurs at both the microvascular and the arterial level, and the clinical presentation of vascular events is heterogeneous, suggesting a complex etiology. Interaction between sickle erythrocytes and the endothelium may contribute to vascular occlusion due to alteration of endothelial function. To investigate this hypothesis, human vascular endothelial cells were overlaid with sickle or normal erythrocytes and stimulated to synthesize DNA. The erythrocytes were sedimented onto replicate monolayers by centrifugation for 10 minutes at 17 g to insure contact with the endothelial cells. Incorporation of 3H-thymidine into endothelial cell DNA was markedly inhibited during contact with sickle erythrocytes. This inhibitory effect was enhanced more than twofold when autologous sickle plasma was present during endothelial cell labeling. Normal erythrocytes, with or without autologous plasma, had a modest effect on endothelial cell DNA synthesis. When sickle erythrocytes in autologous sickle plasma were applied to endothelial monolayers for 1 minute, 10 minutes, or 1 hour and then removed, subsequent DNA synthesis by the endothelial cells was inhibited by 30% to 40%. Although adherence of sickle erythrocytes to the endothelial monolayers was observed under these experimental conditions, the effect of sickle erythrocytes on endothelial DNA synthesis occurred in the absence of significant adherence. Hence, human endothelial cell DNA synthesis is partially inhibited by contact with sickle erythrocytes. The inhibitory effect of sickle erythrocytes occurs during a brief (1 minute) contact with the endothelial monolayers, and persists for at least 6 hours of 3H-thymidine labeling

  7. MicroRNA-34a regulation of endothelial senescence

    Energy Technology Data Exchange (ETDEWEB)

    Ito, Takashi; Yagi, Shusuke [Department of Medicine, Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, West Henrietta, NY 14586 (United States); Yamakuchi, Munekazu, E-mail: munekazu_yamakuchi@urmc.rochester.edu [Department of Medicine, Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, West Henrietta, NY 14586 (United States)

    2010-08-06

    Research highlights: {yields} MicroRNA-34a (miR-34a) regulates senescence and cell cycle progression in endothelial cells. {yields} MiR-34a expression increases during endothelial cell senescence and in older mice. {yields} SIRT1 is a miR-34a target gene in endothelial cells. {yields} SIRT1 mediates the effects of miR-34a upon cell senescence in endothelial cells. -- Abstract: Endothelial senescence is thought to play a role in cardiovascular diseases such as atherosclerosis. We hypothesized that endothelial microRNAs (miRNAs) regulate endothelial survival and senescence. We found that miR-34a is highly expressed in primary endothelial cells. We observed that miR-34a expression increases in senescent human umbilical cord vein endothelial cells (HUVEC) and in heart and spleen of older mice. MiR-34a over-expression induces endothelial cell senescence and also suppresses cell proliferation by inhibiting cell cycle progression. Searching for how miR-34a affects senescence, we discovered that SIRT1 is a target of miR-34a. Over-expressing miR-34a inhibits SIRT1 protein expression, and knocking down miR-34a enhances SIRT1 expression. MiR-34a triggers endothelial senescence in part through SIRT1, since forced expression of SIRT1 blocks the ability of miR-34a to induce senescence. Our data suggest that miR-34a contributes to endothelial senescence through suppression of SIRT1.

  8. Effects of high glucose on human cavernous endothelial cells.

    Science.gov (United States)

    Ning, Hongxiu; Qiu, Xuefeng; Baine, Lia; Lin, Guiting; Lue, Tom F; Lin, Ching-Shwun

    2012-11-01

    To obtain experimental evidence for a causal effect of high glucose (HG) on cavernous endothelial dysfunction. Cavernous tissues were obtained from patients undergoing surgery for penile prosthesis implantation. Endothelial cells were isolated by binding to anti-CD31 antibody, followed by magnetic capture. Their endothelial identity was verified by flow cytometry and immunofluorescence staining for endothelial markers CD31, von Willebrand factor, and endothelial nitric oxide synthase, and by their ability to form tube-like structures in matrigel (tube formation) and to endocytose acetylated low-density lipoprotein (low-density lipoprotein uptake). The cells were then cultured under normal glucose (NG) (5 mM) or HG (25 mM) conditions, followed by analysis for endothelial gene expression, function, proliferation, apoptosis, and mitochondrial fragmentation. Human cavernous endothelial cell (HCEC) strains were established and determined to be nearly 100% pure endothelial cells. In the HG culture condition, HCECs expressed approximately 50% less CD31, von Willebrand factor, and endothelial nitric oxide synthase, but nearly twice as much collagen IV compared with HCECs grown in NG medium. HG also suppressed low-density lipoprotein uptake and tube formation by approximately 50%. HCECs grew significantly slower in the high-glucose medium than in the NG medium. Approximately 3 times as many cells exhibited apoptosis in the HG medium as in the NG medium. Approximately 4 times as many cells contained fragmented mitochondria in the HG medium as in the NG medium. HG caused a decrease in endothelial proliferation, function, and marker expression. It also caused an increase in endothelial collagen IV expression, apoptosis, and mitochondrial fragmentation. Together, these HG-induced changes in cavernous endothelial cells provide an explanation for hyperglycemia's detrimental effects on erectile function. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Eldecalcitol prevents endothelial dysfunction in postmenopausal osteoporosis model rats.

    Science.gov (United States)

    Serizawa, Kenichi; Yogo, Kenji; Tashiro, Yoshihito; Takeda, Satoshi; Kawasaki, Ryohei; Aizawa, Ken; Endo, Koichi

    2016-02-01

    Postmenopausal women have high incidence of cardiovascular events as estrogen deficiency can cause endothelial dysfunction. Vitamin D is reported to be beneficial on endothelial function, but it remains controversial whether vitamin D is effective for endothelial dysfunction under the treatment for osteoporosis in postmenopausal women. The aim of this study was to evaluate the endothelial protective effect of eldecalcitol (ELD) in ovariectomized (OVX) rats. ELD (20  ng/kg) was orally administrated five times a week for 4 weeks from 1 day after surgery. After that, flow-mediated dilation (FMD) as an indicator of endothelial function was measured by high-resolution ultrasound in the femoral artery of living rats. ELD ameliorated the reduction of FMD in OVX rats. ELD inhibited the increase in NOX4, nitrotyrosine, and p65 and the decrease in dimer/monomer ratio of nitric oxide synthase in OVX rat femoral arteries. ELD also prevented the decrease in peroxisome proliferator-activated receptor gamma (PPARγ) in femoral arteries and cultured endothelial cells. Although PPARγ is known to inhibit osteoblastogenesis, ELD understandably increased bone mineral density of OVX rats without increase in PPARγ in bone marrow. These results suggest that ELD prevented the deterioration of endothelial function under condition of preventing bone loss in OVX rats. This endothelial protective effect of ELD might be exerted through improvement of endothelial nitric oxide synthase uncoupling, which is mediated by an antioxidative effect through normalization of vascular PPARγ/NF-κB signaling. © 2016 Society for Endocrinology.

  10. Endothelial Function in Migraine With Aura – A Systematic Review

    DEFF Research Database (Denmark)

    Butt, Jawad H; Franzmann, Ulriche; Kruuse, Christina

    2015-01-01

    BACKGROUND: An increased risk of ischemic stroke is repeatedly reported in young subjects with migraine with aura (MA). Such may be caused by changes in endothelial function. The present review evaluates current evidence on endothelial function in MA patients. METHODS: A systematic search...... in patients indicating a possible subtle change in the endothelium. Further investigations on larger groups of patients combining testing of endothelial dysfunction as well as biomarkers are warranted to identify whether or not endothelial changes may play a role in the increased risk of stroke in young MA...

  11. Endothelial Cell-Targeted Adenoviral Vector for Suppressing Breast Tumors

    National Research Council Canada - National Science Library

    Huang, Shuang

    2003-01-01

    .... We incorporated five previously published endothelial cell-specific peptide sequences into adenovirus capsid fiber sequence and the modified fibers were added to Beta-galactosidase- containing...

  12. Endothelialization of Artificial Surfaces: Does Surface Tension Determine in vitro Growth of Human Saphenous Vein Endothelial Cells?

    OpenAIRE

    Fasol, Roland; Zilla, Peter; Deutsch, Manfred; Fischlein, Teddy; Kadletz, Margit; Griesmacher, Andrea; Müller, Mathias M.

    1987-01-01

    To evaluate the possibility of providing, in vitro, an endothelial lining for artificial hearts, we cultivated adult autologous endothelial cells on two polyurethane and two silicone rubber surfaces. Over the ensuing 11-day period, we investigated the resulting cell proliferation and morphology by means of scanning electron and light microscopy. On the silicone rubber surfaces, seeding of 200,000 human saphenous vein endothelial cells per cm2 produced an ideal cobblestone monolayer within a s...

  13. The effect of uric acid on homocysteine-induced endothelial dysfunction in bovine aortic endothelial cells

    Czech Academy of Sciences Publication Activity Database

    Papežíková, Ivana; Pekarová, Michaela; Lojek, Antonín; Kubala, Lukáš

    2009-01-01

    Roč. 30, č. 1 (2009), s. 112-115 ISSN 0172-780X R&D Projects: GA ČR(CZ) GP204/07/P539 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : uric acid * homocysteine * endothelial dysfunction Subject RIV: BO - Biophysics Impact factor: 1.047, year: 2009

  14. Human liver endothelial cells, but not macrovascular or microvascular endothelial cells, engraft in the mouse liver

    NARCIS (Netherlands)

    Filali, Ebtisam El; Hiralall, Johan K.; van Veen, Henk A.; Stolz, Donna B.; Seppen, Jurgen

    2013-01-01

    Liver cell transplantation has had limited clinical success so far, partly due to poor engraftment of hepatocytes. Instead of hepatocytes. other cell types, such as endothelial cells, could be used in ex vivo liver gene therapy. The goal of the present study was to compare the grafting and

  15. Nitro-oleic acid inhibits vascular endothelial inflammatory responses and the endothelial-mesenchymal transition

    Czech Academy of Sciences Publication Activity Database

    Ambrožová, Gabriela; Fidlerová, Táňa; Vereščáková, Hana; Koudelka, Adolf; Rudolph, T.K.; Woodcock, S.R.; Freeman, B.A.; Kubala, Lukáš; Pekarová, Michaela

    2016-01-01

    Roč. 1860, č. 11 (2016), s. 2428-2437 ISSN 0304-4165 R&D Projects: GA ČR(CZ) GP13-40824P Institutional support: RVO:68081707 Keywords : Nitro-oleic acid * Endothelial cells * Macrophages Subject RIV: BO - Biophysics Impact factor: 4.702, year: 2016

  16. Obstructive sleep apnea and endothelial progenitor cells

    Directory of Open Access Journals (Sweden)

    Wang Q

    2013-10-01

    Full Text Available Qing Wang,1,* Qi Wu,2,* Jing Feng,3,4 Xin Sun5 1The Second Respiratory Department of the First People's Hospital of Kunming, Yunnan, People's Republic of China; 2Tianjin Haihe Hospital, Tianjin, People's Republic of China; 3Respiratory Department of Tianjin Medical University General Hospital, Tianjin, People's Republic of China; 4Division of Pulmonary and Critical Care Medicine, Duke University Medical Center, Durham, NC, USA; 5Respiratory Department of Tianjin Haihe Hospital, Tianjin, People's Republic of China *These authors contributed equally to this work Background: Obstructive sleep apnea (OSA occurs in 4% of middle-aged men and 2% of middle-aged women in the general population, and the prevalence is even higher in specific patient groups. OSA is an independent risk factor for a variety of cardiovascular diseases. Endothelial injury could be the pivotal determinant in the development of cardiovascular pathology in OSA. Endothelial damage ultimately represents a dynamic balance between the magnitude of injury and the capacity for repair. Bone marrow–derived endothelial progenitor cells (EPCs within adult peripheral blood present a possible means of vascular maintenance that could home to sites of injury and restore endothelial integrity and normal function. Methods: We summarized pathogenetic mechanisms of OSA and searched for available studies on numbers and functions of EPCs in patients with OSA to explore the potential links between the numbers and functions of EPCs and OSA. In particular, we tried to elucidate the molecular mechanisms of the effects of OSA on EPCs. Conclusion: Intermittent hypoxia cycles and sleep fragmentation are major pathophysiologic characters of OSA. Intermittent hypoxia acts as a trigger of oxidative stress, systemic inflammation, and sympathetic activation. Sleep fragmentation is associated with a burst of sympathetic activation and systemic inflammation. In most studies, a reduction in circulating EPCs has

  17. Do endothelial cells dream of eclectic shape?

    Science.gov (United States)

    Bentley, Katie; Philippides, Andrew; Ravasz Regan, Erzsébet

    2014-04-28

    Endothelial cells (ECs) exhibit dramatic plasticity of form at the single- and collective-cell level during new vessel growth, adult vascular homeostasis, and pathology. Understanding how, when, and why individual ECs coordinate decisions to change shape, in relation to the myriad of dynamic environmental signals, is key to understanding normal and pathological blood vessel behavior. However, this is a complex spatial and temporal problem. In this review we show that the multidisciplinary field of Adaptive Systems offers a refreshing perspective, common biological language, and straightforward toolkit that cell biologists can use to untangle the complexity of dynamic, morphogenetic systems. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Production of soluble Neprilysin by endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Kuruppu, Sanjaya, E-mail: Sanjaya.Kuruppu@monash.edu [Department of Biochemistry and Molecular Biology, Building 77, Monash University, Wellington Rd, Clayton, Vic 3800 (Australia); Rajapakse, Niwanthi W. [Department of Physiology, Building 13F, Monash University, Wellington Rd, Clayton, Vic 3800 (Australia); Minond, Dmitriy [Torrey Pines Institute for Molecular Studies, 11350 SW Village Parkway, Port Saint Lucie, FL 34987 (United States); Smith, A. Ian [Department of Biochemistry and Molecular Biology, Building 77, Monash University, Wellington Rd, Clayton, Vic 3800 (Australia)

    2014-04-04

    Highlights: • A soluble full-length form of Neprilysin exists in media of endothelial cells. • Exosomal release is the key mechanism for the production of soluble Neprilysin. • Inhibition of ADAM-17 by specific inhibitors reduce Neprilysin release. • Exosome mediated release of Neprilysin is dependent on ADAM-17 activity. - Abstract: A non-membrane bound form of Neprilysin (NEP) with catalytic activity has the potential to cleave substrates throughout the circulation, thus leading to systemic effects of NEP. We used the endothelial cell line Ea.hy926 to identify the possible role of exosomes and A Disintegrin and Metalloprotease 17 (ADAM-17) in the production of non-membrane bound NEP. Using a bradykinin based quenched fluorescent substrate (40 μM) assay, we determined the activity of recombinant human NEP (rhNEP; 12 ng), and NEP in the media of endothelial cells (10% v/v; after 24 h incubation with cells) to be 9.35 ± 0.70 and 6.54 ± 0.41 μmols of substrate cleaved over 3 h, respectively. The presence of NEP in the media was also confirmed by Western blotting. At present there are no commercially available inhibitors specific for ADAM-17. We therefore synthesised two inhibitors TPI2155-14 and TPI2155-17, specific for ADAM-17 with IC{sub 50} values of 5.36 and 4.32 μM, respectively. Treatment of cells with TPI2155-14 (15 μM) and TPI2155-17 (4.3 μM) resulted in a significant decrease in NEP activity in media (62.37 ± 1.43 and 38.30 ± 4.70, respectively as a % of control; P < 0.0001), implicating a possible role for ADAM-17 in NEP release. However, centrifuging media (100,000g for 1 h at 4 °C) removed all NEP activity from the supernatant indicating the likely role of exosomes in the release of NEP. Our data therefore indicated for the first time that NEP is released from endothelial cells via exosomes, and that this process is dependent on ADAM-17.

  19. Endothelial juxtaposition of distinct adult stem cells activates angiogenesis signaling molecules in endothelial cells.

    Science.gov (United States)

    Mohammadi, Elham; Nassiri, Seyed Mahdi; Rahbarghazi, Reza; Siavashi, Vahid; Araghi, Atefeh

    2015-12-01

    Efficacy of therapeutic angiogenesis needs a comprehensive understanding of endothelial cell (EC) function and biological factors and cells that interplay with ECs. Stem cells are considered the key components of pro- and anti-angiogenic milieu in a wide variety of physiopathological states, and interactions of EC-stem cells have been the subject of controversy in recent years. In this study, the potential effects of three tissue-specific adult stem cells, namely rat marrow-derived mesenchymal stem cells (rBMSCs), rat adipose-derived stem cells (rADSCs) and rat muscle-derived satellite cells (rSCs), on the endothelial activation of key angiogenic signaling molecules, including VEGF, Ang-2, VEGFR-2, Tie-2, and Tie2-pho, were investigated. Human umbilical vein endothelial cells (HUVECs) and rat lung microvascular endothelial cells (RLMECs) were cocultured with the stem cells or incubated with the stem cell-derived conditioned media on Matrigel. Following HUVEC-stem cell coculture, CD31-positive ECs were flow sorted and subjected to western blotting to analyze potential changes in the expression of the pro-angiogenic signaling molecules. Elongation and co-alignment of the stem cells were seen along the EC tubes in the EC-stem cell cocultures on Matrigel, with cell-to-cell dye communication in the EC-rBMSC cocultures. Moreover, rBMSCs and rADSCs significantly improved endothelial tubulogenesis in both juxtacrine and paracrine manners. These two latter stem cells dynamically up-regulated VEGF, Ang-2, VREGR-2, and Tie-2 but down-regulated Tie2-pho and the Tie2-pho/Tie-2 ratio in HUVECs. Induction of pro-angiogenic signaling in ECs by marrow- and adipose-derived MSCs further indicates the significance of stem cell milieu in angiogenesis dynamics.

  20. Choroidal haemangioma and photodynamic therapy. Anatomical and functional response of patients with choroidal hemangioma treated with photodynamic therapy.

    Science.gov (United States)

    Subirà, O; Brosa, H; Lorenzo-Parra, D; Arias-Barquet, L; Català-Mora, J; Cobos, E; Garcia-Bru, P; Rubio-Caso, M J; Caminal-Mitjana, J M

    2017-06-01

    To study the effectiveness and limitations of photodynamic therapy (PDT) as treatment of choice in patients with symptomatic circumscribed choroidal haemangioma. A retrospective study was conducted on 16 patients (13 men and 3 women, with mean age of 54.88 years) with circumscribed choroidal haemangioma, who attended our centre and were treated with PDT in the last 7 years. All patients had circumscribed choroidal haemangioma, which caused a decrease in visual acuity (VA) secondary to the presence of intraretinal microcystic oedema or neurosensory detachment. The mean initial VA was 0.23, and the final mean VA after performing PDT was 0.38 (all the VA were measured in decimal scale). It should be noted that patients needed a mean of 1.69 PDT sessions. Three of the patients needed rescue treatment with trans-pupillary thermotherapy, intravitreal injection of anti-vascular endothelial growth factor (ranibizumab, aflibercept) or a dexamethasone intravitreal implant (Ozurdex ® ). The indication for a change of treatment was the persistence of intraretinal microcystic oedema and/or neurosensory detachment (or incomplete resolution) after 3 PDT sessions. As overall results, 62.5% of patients evolved into anatomical and functional (increase in AV or stability) resolution. PDT is a straight forward and fast procedure, with a good anatomical and functional response, causing minimal damage to adjacent vessels. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  1. Change of ranibizumab-induced human vitreous protein profile in patients with proliferative diabetic retinopathy based on proteomics analysis.

    Science.gov (United States)

    Zou, Chen; Han, Changjing; Zhao, Minjie; Yu, Jingjing; Bai, Lin; Yao, Yuan; Gao, Shuaixin; Cao, Hui; Zheng, Zhi

    2018-01-01

    Preoperative treatment of anti-vascular endothelial growth factor (VEGF) agents is extensively used in proliferative diabetic retinopathy (PDR), but the molecular mechanism is not fully understood. The objective of this research is to observe change of protein profile induced by ranibizumab (an anti-VEGF agent) in vitreous humor from PDR patients and reveal the effects of anti-VEGF treatment on PDR. A proteomic method was used to identify differentially expressed proteins in vitreous humor. Untreated PDR patients were defined as PDR group, while those who treated with intravitreal injection of ranibizumab (IVR) were defined as IVR. Gene Ontology (GO) annotation and REACTOME pathways were obtained from DAVID Bioinformatics Resources. Intravitreal level of apolipoprotein C-I (APOC1), serpin peptidase inhibitor clade A member 5 (SERPINA5), tissue inhibitor of metalloproteinases (TIMP2), and keratin 1 (KRT1) were determined by enzyme-linked immuno sorbent assay (ELISA). 339 differentially expressed proteins were identified in response to IVR. The most notable GO annotation describes the altered proteins was "innate immune response". The most notable REACTOME pathway was "platelet degranulation". ELISA result showed increased level of APOC1, SERPINA5, KRT1 and a decreased level of TIMP2 in PDR group compared with IVR. In addition to decreasing VEGF level, ranibizumab is associated with change of human vitreous protein profile in patients with PDR, in which the differential proteins are involved in immune response, platelet degranulation, complement activation etc., suggesting that the effects of VEGF are involved in these signaling pathways.

  2. The Effect of Different Dosing Schedules of Intravitreal Sirolimus, a Mammalian Target of Rapamycin (mTOR) Inhibitor, in the Treatment of Non-Infectious Uveitis (An American Ophthalmological Society Thesis).

    Science.gov (United States)

    Nguyen, Quan Dong; Sadiq, Mohammad Ali; Soliman, Mohamed Kamel; Agarwal, Aniruddha; Do, Diana V; Sepah, Yasir J

    2016-08-01

    To determine if two different doses of intravitreal sirolimus, an mTOR inhibitor, can decrease inflammation and is safe in eyes with non-infectious posterior, intermediate, or panuveitis in the Sirolimus as a Therapeutic Approach UVEitis: Protocol-2 (SAVE-2) Study. SAVE-2 is a prospective randomized, phase II, open-label interventional clinical trial conducted at 4 clinical centers in the United States. Eligible subjects were randomized into one of two treatments. Group 1 received 440µg of intravitreal sirolimus in study eyes on days 0, 30, 60, 90, 120, and 150; group 2 received 880µg of intravitreal sirolimus on days 0, 60, and 120. Fellow eyes were also eligible to receive sirolimus (of opposite dose to that of study eye). Primary endpoint of the study was at month 6 (M6). 24 subjects have been randomized in SAVE-2 and are included in the analysis. Vitreous haze decreased by ≥2 steps in 63.6% and 50% of patients in groups 1 and 2, respectively at M6 (p=0.695). Mean change in best-corrected visual acuity for subjects was +3.66 and -2.91 ETDRS letters in group 1 and 2, respectively. Among subjects with macular edema at baseline (n=13), the mean change in foveal thickness was -89.42µm in group 1 and +81.5µm in group 2 at M6. Both low and high doses of intravitreal sirolimus were found to decrease vitreous haze in eyes with non-infectious uveitis. Low dose (440µg) sirolimus administered monthly may be more efficacious in reducing uveitic macular edema than high dose (880µg) administered every 2 months.

  3. Recent insights into endothelial control of leukocyte extravasation

    NARCIS (Netherlands)

    Hordijk, Peter L.

    2016-01-01

    In the process of leukocyte migration from the circulation across the vascular wall, the crosstalk with endothelial cells that line the blood vessels is essential. It is now firmly established that in endothelial cells important signaling events are initiated upon leukocyte adhesion that impinge on

  4. Towards clinical application of microvascular endothelial cell seeding

    NARCIS (Netherlands)

    Arts, C.H.P. (Catharina Henrica Paulina)

    2002-01-01

    The central question in this thesis is whether microvascular endothelial cells (MVEC) from subcutaneous fat tissue are suitable for the seeding of prosthetic vascular grafts and deendothelialized surfaces. The aim of the application of endothelial cells (EC) is the inhibition of thrombogenicity and

  5. Comparison of Endothelial Cell Loss by Specular Microscopy ...

    African Journals Online (AJOL)

    Group A had undergone phacoemulsification and Group B had under gone manual SICS. In Group A 50 cases were performed by temporal CCI and remaining 50 cases were performed by superior SI technique. Endothelial cell count was evaluated by using a noncontact specular microscope. Results: Mean endothelial cell ...

  6. Endothelial cell cultures as a tool in biomaterial research

    NARCIS (Netherlands)

    Kirkpatrick, CJ; Otto, M; van Kooten, T; Krump, [No Value; Kriegsmann, J; Bittinger, F

    1999-01-01

    Progress in biocompatibility and tissue engineering would today be inconceivable without the aid of in vitro techniques. Endothelial cell cultures represent a valuable tool not just in haemocompatibility testing, but also in the concept of designing hybrid organs. In the past endothelial cells (EC)

  7. Magnesium deficiency and endothelial dysfunction: is oxidative stress involved?

    NARCIS (Netherlands)

    Wolf, F.I.; Trapani, V.; Simonacci, M.; Ferre, S.; Maier, J.A.

    2008-01-01

    Low magnesium (Mg) has been associated with oxidative stress, an important player in aging, atherosclerosis and other vascular diseases. In vivo, low Mg and immune system activation seem to cooperate to promote endothelial dysfunction. We therefore evaluated whether exposure of human endothelial

  8. Valvular interstitial cells suppress calcification of valvular endothelial cells

    NARCIS (Netherlands)

    Hjortnaes, Jesper; Shapero, Kayle; Goettsch, Claudia; Hutcheson, Joshua D; Keegan, Joshua; Kluin, J; Mayer, John E; Bischoff, Joyce; Aikawa, Elena

    BACKGROUND: Calcific aortic valve disease (CAVD) is the most common heart valve disease in the Western world. We previously proposed that valvular endothelial cells (VECs) replenish injured adult valve leaflets via endothelial-to-mesenchymal transformation (EndMT); however, whether EndMT contributes

  9. Emerging Role of Endothelial and Inflammatory Markers in Preeclampsia

    Directory of Open Access Journals (Sweden)

    Menha Swellam

    2009-01-01

    Full Text Available Objectives: Endothelial disturbance and excess inflammatory response are pathogenic mechanisms in pre-eclampsia (PE. Authors determine the clinical diagnostic role for thrombomodulin (TM, plasminogen activator inhibitor-1 (PAI-1 as endothelial markers and C-reactive protein (CRP, and interlukin-6 (IL-6 as inflammatory markers when tested independently or in combinations.

  10. Weight loss improves biomarkers endothelial function and systemic ...

    African Journals Online (AJOL)

    Background: Although postmenopausal associated disorders are important public health problems worldwide, to date limited studies evaluated the endothelial function and systemic inflammation response to weight loss in obese postmenopausal women. Objective: This study was done to evaluate the endothelial function ...

  11. Complement activation, endothelial dysfunction, insulin resistance and chronic heart failure

    DEFF Research Database (Denmark)

    Bjerre, M.; Kistorp, C.; Hansen, T.K.

    2010-01-01

    CRP), endothelial activation (soluble E-selectin, sEsel)), endothelial damage/dysfunction (von Willebrand factor, vWf) and insulin resistance (IR) and prognosis in CHF remains unknown. Design. We investigated the association(s) between plasma sMAC, hsCRP, sEsel, vWf and IR (assessed by homeostatic model assessment...

  12. Endothelial Progenitor Cells Enter the Aging Arena.

    Directory of Open Access Journals (Sweden)

    Kate eWilliamson

    2012-02-01

    Full Text Available Age is a significant risk factor for the development of vascular diseases, such as atherosclerosis. Although pharmacological treatments, including statins and anti-hypertensive drugs, have improved the prognosis for patients with cardiovascular disease, it remains a leading cause of mortality in those aged 65 years and over. Furthermore, given the increased life expectancy of the population in developed countries, there is a clear need for alternative treatment strategies. Consequently, the relationship between aging and progenitor cell-mediated repair is of great interest. Endothelial progenitor cells (EPCs play an integral role in the cellular repair mechanisms for endothelial regeneration and maintenance. However, EPCs are subject to age-associated changes that diminish their number in circulation and function, thereby enhancing vascular disease risk. A great deal of research is aimed at developing strategies to harness the regenerative capacity of these cells.In this review, we discuss the current understanding of the cells termed ‘EPCs’, examine the impact of age on EPC-mediated repair and identify therapeutic targets with potential for attenuating the age-related decline in vascular health via beneficial actions on EPCs.

  13. An "All-laser" Endothelial Transplant.

    Science.gov (United States)

    Rossi, Francesca; Canovetti, Annalisa; Malandrini, Alex; Lenzetti, Ivo; Pini, Roberto; Menabuoni, Luca

    2015-07-06

    The "all laser" assisted endothelial keratoplasty is a procedure that is performed with a femtosecond laser used to cut the donor tissue at an intended depth, and a near infrared diode laser to weld the corneal tissue. The proposed technique enables to reach the three main goals in endothelial keratoplasty: a precise control in the thickness of the donor tissue; its easy insertion in the recipient bed and a reduced risk of donor lenticule dislocation. The donor cornea thickness is measured in the surgery room with optical coherence tomography (OCT), in order to correctly design the donor tissue dimensions. A femtosecond laser is used to cut the donor cornea. The recipient eye is prepared by manual stripping of the descemetic membrane. The donor endothelium is inserted into a Busin-injector, the peripheral inner side is stained with a proper chromophore (a water solution of Indocyanine Green) and then it is pulled in the anterior chamber. The transplanted tissue is placed in the final and correct location and then diode laser welding is induced from outside the eyeball. The procedure has been performed on more than 15 patients evidencing an improvement in surgery performances, with a good recovery of visual acuity and a reduced donor lenticule dislocation event.

  14. An “All-laser” Endothelial Transplant

    Science.gov (United States)

    Rossi, Francesca; Canovetti, Annalisa; Malandrini, Alex; Lenzetti, Ivo; Pini, Roberto; Menabuoni, Luca

    2015-01-01

    The “all laser” assisted endothelial keratoplasty is a procedure that is performed with a femtosecond laser used to cut the donor tissue at an intended depth, and a near infrared diode laser to weld the corneal tissue. The proposed technique enables to reach the three main goals in endothelial keratoplasty: a precise control in the thickness of the donor tissue; its easy insertion in the recipient bed and a reduced risk of donor lenticule dislocation. The donor cornea thickness is measured in the surgery room with optical coherence tomography (OCT), in order to correctly design the donor tissue dimensions. A femtosecond laser is used to cut the donor cornea. The recipient eye is prepared by manual stripping of the descemetic membrane. The donor endothelium is inserted into a Busin-injector, the peripheral inner side is stained with a proper chromophore (a water solution of Indocyanine Green) and then it is pulled in the anterior chamber. The transplanted tissue is placed in the final and correct location and then diode laser welding is induced from outside the eyeball. The procedure has been performed on more than 15 patients evidencing an improvement in surgery performances, with a good recovery of visual acuity and a reduced donor lenticule dislocation event. PMID:26167711

  15. Diagnosis and Management of Iridocorneal Endothelial Syndrome

    Directory of Open Access Journals (Sweden)

    Marta Sacchetti

    2015-01-01

    Full Text Available The iridocorneal endothelial (ICE syndrome is a rare ocular disorder that includes a group of conditions characterized by structural and proliferative abnormalities of the corneal endothelium, the anterior chamber angle, and the iris. Common clinical features include corneal edema, secondary glaucoma, iris atrophy, and pupillary anomalies, ranging from distortion to polycoria. The main subtypes of this syndrome are the progressive iris atrophy, the Cogan-Reese syndrome, and the Chandler syndrome. ICE syndrome is usually diagnosed in women in the adult age. Clinical history and complete eye examination including tonometry and gonioscopy are necessary to reach a diagnosis. Imaging techniques, such as in vivo confocal microscopy and ultrasound biomicroscopy, are used to confirm the diagnosis by revealing the presence of “ICE-cells” on the corneal endothelium and the structural changes of the anterior chamber angle. An early diagnosis is helpful to better manage the most challenging complications such as secondary glaucoma and corneal edema. Treatment of ICE-related glaucoma often requires glaucoma filtering surgery with antifibrotic agents and the use of glaucoma drainage implants should be considered early in the management of these patients. Visual impairment and pain associated with corneal edema can be successfully managed with endothelial keratoplasty.

  16. Erythrocytes induce proinflammatory endothelial activation in hypoxia.

    Science.gov (United States)

    Huertas, Alice; Das, Shonit R; Emin, Memet; Sun, Li; Rifkind, Joseph M; Bhattacharya, Jahar; Bhattacharya, Sunita

    2013-01-01

    Although exposure to ambient hypoxia is known to cause proinflammatory vascular responses, the mechanisms initiating these responses are not understood. We tested the hypothesis that in systemic hypoxia, erythrocyte-derived H(2)O(2) induces proinflammatory gene transcription in vascular endothelium. We exposed mice or isolated, perfused murine lungs to 4 hours of hypoxia (8% O(2)). Leukocyte counts increased in the bronchoalveolar lavage. The expression of leukocyte adhesion receptors, reactive oxygen species, and protein tyrosine phosphorylation increased in freshly recovered lung endothelial cells (FLECs). These effects were inhibited by extracellular catalase and by the removal of erythrocytes, indicating that the responses were attributable to erythrocyte-derived H(2)O(2). Concomitant nuclear translocation of the p65 subunit of NF-κB and hypoxia-inducible factor-1α stabilization in FLECs occurred only in the presence of erythrocytes. Hemoglobin binding to the erythrocyte membrane protein, band 3, induced the release of H(2)O(2) from erythrocytes and the p65 translocation in FLECs. These data indicate for the first time, to our knowledge, that erythrocytes are responsible for endothelial transcriptional responses in hypoxia.

  17. The barrier within: endothelial transport of hormones.

    Science.gov (United States)

    Kolka, Cathryn M; Bergman, Richard N

    2012-08-01

    Hormones are involved in a plethora of processes including development and growth, metabolism, mood, and immune responses. These essential functions are dependent on the ability of the hormone to access its target tissue. In the case of endocrine hormones that are transported through the blood, this often means that the endothelium must be crossed. Many studies have shown that the concentrations of hormones and nutrients in blood can be very different from those surrounding the cells on the tissue side of the blood vessel endothelium, suggesting that transport across this barrier can be rate limiting for hormone action. This transport can be regulated by altering the surface area of the blood vessel available for diffusion through to the underlying tissue or by the permeability of the endothelium. Many hormones are known to directly or indirectly affect the endothelial barrier, thus affecting their own distribution to their target tissues. Dysfunction of the endothelial barrier is found in many diseases, particularly those associated with the metabolic syndrome. The interrelatedness of hormones may help to explain why the cluster of diseases in the metabolic syndrome occur together so frequently and suggests that treating the endothelium may ameliorate defects in more than one disease. Here, we review the structure and function of the endothelium, its contribution to the function of hormones, and its involvement in disease.

  18. Diagnosis and Management of Iridocorneal Endothelial Syndrome

    Science.gov (United States)

    Sacchetti, Marta; Mantelli, Flavio; Macchi, Ilaria; Ambrosio, Oriella; Rama, Paolo

    2015-01-01

    The iridocorneal endothelial (ICE) syndrome is a rare ocular disorder that includes a group of conditions characterized by structural and proliferative abnormalities of the corneal endothelium, the anterior chamber angle, and the iris. Common clinical features include corneal edema, secondary glaucoma, iris atrophy, and pupillary anomalies, ranging from distortion to polycoria. The main subtypes of this syndrome are the progressive iris atrophy, the Cogan-Reese syndrome, and the Chandler syndrome. ICE syndrome is usually diagnosed in women in the adult age. Clinical history and complete eye examination including tonometry and gonioscopy are necessary to reach a diagnosis. Imaging techniques, such as in vivo confocal microscopy and ultrasound biomicroscopy, are used to confirm the diagnosis by revealing the presence of “ICE-cells” on the corneal endothelium and the structural changes of the anterior chamber angle. An early diagnosis is helpful to better manage the most challenging complications such as secondary glaucoma and corneal edema. Treatment of ICE-related glaucoma often requires glaucoma filtering surgery with antifibrotic agents and the use of glaucoma drainage implants should be considered early in the management of these patients. Visual impairment and pain associated with corneal edema can be successfully managed with endothelial keratoplasty. PMID:26451377

  19. The Barrier Within: Endothelial Transport of Hormones

    Science.gov (United States)

    Kolka, Cathryn M.; Bergman, Richard N.

    2015-01-01

    Hormones are involved in a plethora of processes including development and growth, metabolism, mood, and immune responses. These essential functions are dependent on the ability of the hormone to access its target tissue. In the case of endocrine hormones that are transported through the blood, this often means that the endothelium must be crossed. Many studies have shown that the concentrations of hormones and nutrients in blood can be very different from those surrounding the cells on the tissue side of the blood vessel endothelium, suggesting that transport across this barrier can be rate limiting for hormone action. This transport can be regulated by altering the surface area of the blood vessel available for diffusion through to the underlying tissue or by the permeability of the endothelium. Many hormones are known to directly or indirectly affect the endothelial barrier, thus affecting their own distribution to their target tissues. Dysfunction of the endothelial barrier is found in many diseases, particularly those associated with the metabolic syndrome. The interrelatedness of hormones may help to explain why the cluster of diseases in the metabolic syndrome occur together so frequently and suggests that treating the endothelium may ameliorate defects in more than one disease. Here, we review the structure and function of the endothelium, its contribution to the function of hormones, and its involvement in disease. PMID:22875454

  20. Hemostasis and endothelial damage during sepsis.

    Science.gov (United States)

    Johansen, Maria Egede

    2015-08-01

    The sepsis syndrome represents a disease continuum, including severe sepsis and septic shock associated with high mortality. One of the main problems in severe sepsis and septic shock, resulting in organ failure and death, are disturbances in the hemostasis due to sepsis-related coagulopathy. Sepsis-related coagulopathy affects not only traditional coagulation factors, but also the platelets and endothelium. Functional testing of the hemostatic system has found application in critical illness. Thrombelastography (TEG) provides an overview of the hemostatic system allowing for an evaluation of interactions between coagulation factors and platelets. Additionally, the role of the endothelium during sepsis can be explored through testing of biomarkers of endothelial damage. The three studies comprising this PhD thesis all investigate important aspects of the disturbed hemostasis during sepsis, including endothelial damage. Together, the specific findings from the three studies improve the existing understanding of sepsis-related coagulopathy, and the possible influences of some of the treatments offered these patients. The first study investigates the occurrence of antimicrobial-induced thrombocytopenia among critically ill patients. In sepsis, thrombocytopenia is a predictor of poor outcome, and reports, of mainly casuistic nature, have previously hypothesized that specific antimicrobial agents could induce in sepsis-related thrombocytopenia. This hypothesis was tested using a randomized designed set-up, encompassing 1147 critically ill patients, and no significant difference in risk of thrombocytopenia was observed among patients receiving large amounts of antimicrobials vs. patients receiving standard-of-care. As a consequence, the risk of antimicrobial-induced thrombocytopenia in the general population of critically ill patients seemingly does not represent a substantial problem and thrombocytopenia during critical illness is most likely due to other factors such

  1. Impact of Hemorheological and Endothelial Factors on Microcirculation

    Science.gov (United States)

    Turchetti, Vera; Boschi, Letizia; Donati, Giovanni; Trabalzini, Luca; Forconi, Sandro

    Previous studies showed that endothelial alterations caused by physical stress worsened the hemorheological parameters mainly in patients affected by ischemic vascular diseases: major vascular alterations have been found in patients with very high endothelial dysfunction indexes: these indexes are given by the various substances produced by the endothelium, but it is very difficult to have a value which clearly identifies the real state of the endothelial alteration. The function of the NO, an endogenous vasodilator whose synthesis is catalyzed by NOs, can be determined by the Citrulline/Arginine ratio, which represents the level of activity of the enzyme. A very good index of the endothelial dysfunction is asymmetric dimethylarginine (ADMA), a powerful endogenous inhibitor of NOs; in fact several studies have demonstrated a strong relationship between ischemic vascular disease and high levels of plasmatic ADMA. Our recent studies on heart failure and on ischemic cerebrovascular diseases evaluate endothelial dysfunctions and hemorheological parameters.

  2. The role of endothelial-mesenchymal transition in heterotopic ossification

    Science.gov (United States)

    Medici, Damian; Olsen, Bjorn R.

    2012-01-01

    Heterotopic ossification (HO) is a process by which bone forms in soft tissues, in response to injury, inflammation or genetic disease. This usually occurs by initial cartilage formation, followed by endochondral ossification. A rare disease called Fibrodysplasia Ossificans Progressiva (FOP) allows this mechanism to be induced by a combination of genetic mutation and acute inflammatory responses. FOP patients experience progressive HO throughout their lifetime and form an ectopic skeleton. Recent studies on FOP have suggested that heterotopic cartilage and bone is of endothelial origin. Vascular endothelial cells differentiate into skeletal cells through a mesenchymal stem cell intermediate that is generated by endothelial-mesenchymal transition (EndMT). Local inflammatory signals and/or other changes in the tissue microenvironment mediate the differentiation of endothelial-derived mesenchymal stem cells into chondrocytes and osteoblasts to induce HO. Here we discuss the current evidence for the endothelial contribution to heterotopic bone formation. PMID:22806925

  3. Syncytin is involved in breast cancer-endothelial cell fusions

    DEFF Research Database (Denmark)

    Bjerregaard, Bolette; Holck, S.; Christensen, I.J.

    2006-01-01

    Cancer cells can fuse spontaneously with normal host cells, including endothelial cells, and such fusions may strongly modulate the biological behaviour of tumors. However, the underlying mechanisms are unknown. We now show that human breast cancer cell lines and 63 out of 165 (38%) breast cancer...... specimens express syncytin, an endogenous retroviral envelope protein, previously implicated in fusions between placental trophoblast cells. Additionally, endothelial and cancer cells are shown to express ASCT-2, a receptor for syncytin. Syncytin antisense treatment decreases syncytin expression...... and inhibits fusions between breast cancer cells and endothelial cells. Moreover, a syncytin inhibitory peptide also inhibits fusions between cancer and endothelial cells. These results are the first to show that syncytin is expressed by human cancer cells and is involved in cancer-endothelial cell fusions....

  4. Propranolol treatment of infantile hemangioma endothelial cells: A molecular analysis

    Science.gov (United States)

    STILES, JESSICA; AMAYA, CLARISSA; PHAM, ROBERT; ROWNTREE, REBECCA K.; LACAZE, MARY; MULNE, ARLYNN; BISCHOFF, JOYCE; KOKTA, VICTOR; BOUCHERON, LAURA E.; MITCHELL, DIANNE C.; BRYAN, BRAD A.

    2012-01-01

    Infantile hemangiomas (IHs) are non-malignant, largely cutaneous vascular tumors affecting approximately 5–10% of children to varying degrees. During the first year of life, these tumors are strongly proliferative, reaching an average size ranging from 2 to 20 cm. These lesions subsequently stabilize, undergo a spontaneous slow involution and are fully regressed by 5 to 10 years of age. Systemic treatment of infants with the non-selective β-adrenergic receptor blocker, propranolol, has demonstrated remarkable efficacy in reducing the size and appearance of IHs. However, the mechanism by which this occurs is largely unknown. In this study, we sought to understand the molecular mechanisms underlying the effectiveness of β blocker treatment in IHs. Our data reveal that propranolol treatment of IH endothelial cells, as well as a panel of normal primary endothelial cells, blocks endothelial cell proliferation, migration, and formation of the actin cytoskeleton coincident with alterations in vascular endothelial growth factor receptor-2 (VEGFR-2), p38 and cofilin signaling. Moreover, propranolol induces major alterations in the protein levels of key cyclins and cyclin-dependent kinase inhibitors, and modulates global gene expression patterns with a particular affect on genes involved in lipid/sterol metabolism, cell cycle regulation, angiogenesis and ubiquitination. Interestingly, the effects of propranolol were endothelial cell-type independent, affecting the properties of IH endothelial cells at similar levels to that observed in neonatal dermal microvascular and coronary artery endothelial cells. This data suggests that while propranolol markedly inhibits hemangioma and normal endothelial cell function, its lack of endothelial cell specificity hints that the efficacy of this drug in the treatment of IHs may be more complex than simply blockage of endothelial function as previously believed. PMID:23170111

  5. Curcumin and Endothelial Function: Evidence and Mechanisms of Protective Effects.

    Science.gov (United States)

    Karimian, Maryam S; Pirro, Matteo; Johnston, Thomas P; Majeed, Muhammed; Sahebkar, Amirhossein

    2017-01-01

    The endothelium is a large paracrine organ regulating cell growth, vascular tone and thrombogenicity as well as platelet and leukocyte interactions. Endothelial function can be assessed by noninvasive techniques [e.g. flow-mediated vasodilation, nitroglycerin-mediated dilation and pulse wave velocity] and measuring specific circulating biomarkers [cell adhesion molecules, endothelial microparticles and endothelial progenitor cells]. Impaired endothelial function plays a key role in the development of atherosclerosis, arterial hypertension, heart failure, ischemia-reperfusion injury, Alzheimer's disease and other conditions. Endothelial function is also involved in growth and proliferation of tumor cells. We performed a literature review and assessed the role of the natural polyphenol, curcumin, as a potential inexpensive, well-tolerated, and safe agent for improving endothelial function. Curcumin exerts several positive pharmacological effects; these include anti-inflammatory, antioxidant, anti-hypertensive, anti-cancer, antiviral, anti-infective and wound-healing properties. Specifically, curcumin's anti-inflammatory effects are thought to be caused by reducing trans-endothelial monocyte migration by reduction of mRNA and protein expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and P-selectin and by modulating NFκB, JNK, p38 and STAT-3 in endothelial cells. Dietary curcumin supplementation can also increase antioxidant activity through the induction of heme oxygenase-1, a scavenger of free radicals, and by reduction of reactive oxygen species and Nox-2. Curcumin appears to improve endothelial function but additional research is needed to determine the precise mechanism(s) and biomarkers involved in curcumin's therapeutic effects on endothelial dysfunction. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Efficacy and tolerability of bilateral sustained-release dexamethasone intravitreal implants for the treatment of noninfectious posterior uveitis and macular edema secondary to retinal vein occlusion

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    Ryder SJ

    2015-06-01

    Full Text Available Steven J Ryder,1 Danilo Iannetta,1 Swetangi D Bhaleeya,2 Szilárd Kiss1 1Department of Ophthalmology, Weill Cornell Medical College, New York, NY, USA; 2Department of Ophthalmology, University of South Florida, Tampa, FL, USA Purpose: To report our experience with bilateral placement of dexamethasone 0.7 mg (DEX sustained-release intravitreal implant in the management of noninfectious posterior uveitis or macular edema secondary to retinal vein occlusion.Methods: A retrospective chart review of patients with bilateral noninfectious posterior uveitis and macular edema secondary to retinal vein occlusion who were treated with DEX intravitreal implant was performed. Ocular side effects such as intraocular pressure (IOP, cataract, and tolerability of bilateral injections was reviewed.Results: Twenty-two eyes of eleven patients treated with a total of 32 DEX implants were included. Ten of eleven patients received bilateral implants due to active noninfectious uveitis while the other demonstrated macular edema in both eyes following separate central retinal vein occlusions. Among the patients with bilateral uveitis, the mean interval between DEX implant in the initial eye and the subsequent DEX in the fellow eye was 15.6 days (range 2–71 days. Seven of the ten patients received the second implant in the fellow eye within 8 days of the initial implantation. None of the patients had bilateral implantations on the same day. Seven eyes required reimplantation for recurrence of inflammation (mean interval between first and repeat implantation was 6.00±2.39 months. Following single or, in the case of the aforementioned seven eyes, repeat DEX implantation, all 20 uveitic eyes demonstrated clinical and/or angiographic evidence of decreased inflammation in the form of reduction in vitreous cells on slit lamp ophthalmoscopy, macular edema on ophthalmoscopy, or optical coherence tomography and/or disc and vascular leakage on fluorescein angiography. The mean

  7. Proteomic analysis of endothelial cold-adaptation

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    Zieger Michael AJ

    2011-12-01

    Full Text Available Abstract Background Understanding how human cells in tissue culture adapt to hypothermia may aid in developing new clinical procedures for improved ischemic and hypothermic protection. Human coronary artery endothelial cells grown to confluence at 37°C and then transferred to 25°C become resistant over time to oxidative stress and injury induced by 0°C storage and rewarming. This protection correlates with an increase in intracellular glutathione at 25°C. To help understand the molecular basis of endothelial cold-adaptation, isolated proteins from cold-adapted (25°C/72 h and pre-adapted cells were analyzed by quantitative proteomic methods and differentially expressed proteins were categorized using the DAVID Bioinformatics Resource. Results Cells adapted to 25°C expressed changes in the abundance of 219 unique proteins representing a broad range of categories such as translation, glycolysis, biosynthetic (anabolic processes, NAD, cytoskeletal organization, RNA processing, oxidoreductase activity, response-to-stress and cell redox homeostasis. The number of proteins that decreased significantly with cold-adaptation exceeded the number that increased by 2:1. Almost half of the decreases were associated with protein metabolic processes and a third were related to anabolic processes including protein, DNA and fatty acid synthesis. Changes consistent with the suppression of cytoskeletal dynamics provided further evidence that cold-adapted cells are in an energy conserving state. Among the specific changes were increases in the abundance and activity of redox proteins glutathione S-transferase, thioredoxin and thioredoxin reductase, which correlated with a decrease in oxidative stress, an increase in protein glutathionylation, and a recovery of reduced protein thiols during rewarming from 0°C. Increases in S-adenosylhomocysteine hydrolase and nicotinamide phosphoribosyltransferase implicate a central role for the methionine

  8. Endothelial cell senescence with aging in healthy humans: prevention by habitual exercise and relation to vascular endothelial function.

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    Rossman, Matthew J; Kaplon, Rachelle E; Hill, Sierra D; McNamara, Molly N; Santos-Parker, Jessica R; Pierce, Gary L; Seals, Douglas R; Donato, Anthony J

    2017-11-01

    Cellular senescence is emerging as a key mechanism of age-related vascular endothelial dysfunction, but evidence in healthy humans is lacking. Moreover, the influence of lifestyle factors such as habitual exercise on endothelial cell (EC) senescence is unknown. We tested the hypothesis that EC senescence increases with sedentary, but not physically active, aging and is associated with vascular endothelial dysfunction. Protein expression (quantitative immunofluorescence) of p53, a transcription factor related to increased cellular senescence, and the cyclin-dependent kinase inhibitors p21 and p16 were 116%, 119%, and 128% greater (all P 0.05) in venous ECs from older exercising adults (57 ± 1 yr, n = 13). Furthermore, venous EC protein levels of p53 ( r  = -0.49, P = 0.003), p21 ( r  = -0.38, P = 0.03), and p16 ( r  = -0.58, P = 0.002) were inversely associated with vascular endothelial function (brachial artery flow-mediated dilation). Similarly, protein expression of p53 and p21 was 26% and 23% higher (both P 0.05) in older habitually exercising adults (59 ± 1 yr, n = 14). These data indicate that EC senescence is associated with sedentary aging and is linked to endothelial dysfunction. Moreover, these data suggest that prevention of EC senescence may be one mechanism by which aerobic exercise protects against endothelial dysfunction with age. NEW & NOTEWORTHY Our study provides novel evidence in humans of increased endothelial cell senescence with sedentary aging, which is associated with impaired vascular endothelial function. Furthermore, our data suggest an absence of age-related increases in endothelial cell senescence in older exercising adults, which is linked with preserved vascular endothelial function. Copyright © 2017 the American Physiological Society.

  9. Detection and Quantification of Vascular Endothelial Growth Factor Receptor Tyrosine Kinases in Primary Human Endothelial Cells.

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    Fearnley, Gareth W; Wheatcroft, Stephen B; Ponnambalam, Sreenivasan

    2015-01-01

    Proteins differ widely in their pattern of expression depending on organism, tissue, and regulation in response to changing conditions. In the mammalian vasculature, the endothelium responds to vascular endothelial growth factors (VEGFs) via membrane-bound receptor tyrosine kinases (VEGFRs) to modulate many aspects of vascular physiology including vasculogenesis, angiogenesis, and blood pressure. Studies on VEGFR biology are thus dependent on detecting expression levels in different cell types and evaluating how changes in protein levels correlate with changing conditions including circulating VEGF levels. Here, we present a robust immunoblot-based protocol for detecting and quantifying VEGFRs in human endothelial cells. Using internal and external standards, we can rapidly evaluate receptor copy number and assess how this is altered in response to the cellular environment.

  10. Intravitreal injection of ciliary neurotrophic factor (CNTF) causes peripheral remodeling and does not prevent photoreceptor loss in canine RPGR mutant retina.

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    Beltran, William A; Wen, Rong; Acland, Gregory M; Aguirre, Gustavo D

    2007-04-01

    Ciliary neurotrophic factor (CNTF) rescues photoreceptors in several animal models of retinal degeneration and is currently being evaluated as a potential treatment for retinitis pigmentosa in humans. This study was conducted to test whether CNTF prevents photoreceptor cell loss in XLPRA2, an early onset canine model of X-linked retinitis pigmentosa caused by a frameshift mutation in RPGR exon ORF15. Four different treatment regimens of CNTF were tested in XLPRA2 dogs. Under anesthesia, the animals received at different ages an intravitreal injection of 12 microg of CNTF in the left eye. The right eye served as a control and was injected with a similar volume of phosphate buffered saline (PBS). Ocular examinations were performed regularly during the treatment periods. At termination, the dogs were euthanatized, eyes collected and the retinas were processed for embedding in optimal cutting temperature (OCT) medium. The outer nuclear layer (ONL) thickness was evaluated on H&E sections and values in both CNTF- and PBS-treated eyes were compared. Morphologic alterations in the peripheral retina were characterized by immunohistochemistry using cell-specific markers. Cell proliferation in the retinas was examined on semi-thin plastic sections, and by BrdU pulse-labeling and Ki67 immunohistochemistry on cryosections. All CNTF-treated eyes showed early clinical signs of corneal epitheliopathy, subcapsular cataracts and uveitis. No statistically significant difference in ONL thickness was seen between the CNTF- and PBS-injected eyes. Prominent retinal remodeling that consisted in an abnormal increase in the number of rods, and in misplacement of some rods, cones, bipolar and Müller cells, was observed in the peripheral retina of CNTF-treated eyes. This was only seen when CNTF was in injected before the age at which the canine retina reaches full maturation. In XLPRA2 dogs, intravitreal injections of CNTF failed to prevent photoreceptors from undergoing cell death in the

  11. Intravitreal injection of ciliary neurotrophic factor (CNTF) causes peripheral remodeling and does not prevent photoreceptor loss in canine RPGR mutant retina

    Science.gov (United States)

    Beltran, William A.; Wen, Rong; Acland, Gregory M.; Aguirre, Gustavo D.

    2009-01-01

    Ciliary neurotrophic factor (CNTF) rescues photoreceptors in several animal models of retinal degeneration and is currently being evaluated as a potential treatment for retinitis pigmentosa in humans. This study was conducted to test whether CNTF prevents photoreceptor cell loss in XLPRA2, an early onset canine model of X-linked retinitis pigmentosa caused by a frameshift mutation in RPGR exon ORF15. Four different treatment regimens of CNTF were tested in XLPRA2 dogs. Under anesthesia, the animals received at different ages an intravitreal injection of 12 μg of CNTF in the left eye. The right eye served as a control and was injected with a similar volume of phosphate buffered saline (PBS). Ocular examinations were performed regularly during the treatment periods. At termination, the dogs were euthanatized, eyes collected and the retinas were processed for embedding in optimal cutting temperature (OCT) medium. The outer nuclear layer (ONL) thickness was evaluated on H&E sections and values in both CNTF- and PBS-treated eyes were compared. Morphologic alterations in the peripheral retina were characterized by immunohistochemistry using cell-specific markers. Cell proliferation in the retinas was examined on semi-thin plastic sections, and by BrdU pulse-labeling and Ki67 immunohistochemistry on cryosections. All CNTF-treated eyes showed early clinical signs of corneal epitheliopathy, subcapsular cataracts and uveitis. No statistically significant difference in ONL thickness was seen between the CNTF- and PBS-injected eyes. Prominent retinal remodeling that consisted in an abnormal increase in the number of rods, and in misplacement of some rods, cones, bipolar and Müller cells, was observed in the peripheral retina of CNTF-treated eyes. This was only seen when CNTF was in injected before the age at which the canine retina reaches full maturation. In XLPRA2 dogs, intravitreal injections of CNTF failed to prevent photoreceptors from undergoing cell death in the

  12. Nitro-oleic acid inhibits vascular endothelial inflammatory responses and the endothelial-mesenchymal transition.

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    Ambrozova, Gabriela; Fidlerova, Tana; Verescakova, Hana; Koudelka, Adolf; Rudolph, Tanja K; Woodcock, Steven R; Freeman, Bruce A; Kubala, Lukas; Pekarova, Michaela

    2016-11-01

    Inflammatory-mediated pathological processes in the endothelium arise as a consequence of the dysregulation of vascular homeostasis. Of particular importance are mediators produced by stimulated monocytes/macrophages inducing activation of endothelial cells (ECs). This is manifested by excessive soluble pro-inflammatory mediator production and cell surface adhesion molecule expression. Nitro-fatty acids are endogenous products of metabolic and inflammatory reactions that display immuno-regulatory potential and may represent a novel therapeutic strategy to treat inflammatory diseases. The purpose of our study was to characterize the effects of nitro-oleic acid (OA-NO2) on inflammatory responses and the endothelial-mesenchymal transition (EndMT) in ECs that is a consequence of the altered healing phase of the immune response. The effect of OA-NO2 on inflammatory responses and EndMT was determined in murine macrophages and murine and human ECs using Western blotting, ELISA, immunostaining, and functional assays. OA-NO2 limited the activation of macrophages and ECs by reducing pro-inflammatory cytokine production and adhesion molecule expression through its modulation of STAT, MAPK and NF-κB-regulated signaling. OA-NO2 also decreased transforming growth factor-β-stimulated EndMT and pro-fibrotic phenotype of ECs. These effects are related to the downregulation of Smad2/3. The study shows the pleiotropic effect of OA-NO2 on regulating EC-macrophage interactions during the immune response and suggests a role for OA-NO2 in the regulation of vascular endothelial immune and fibrotic responses arising during chronic inflammation. These findings propose the OA-NO2 may be useful as a novel therapeutic agent for treatment of cardiovascular disorders associated with dysregulation of the endothelial immune response. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. High glucose induced endothelial to mesenchymal transition in human umbilical vein endothelial cell.

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    Yu, Chun-Hong; Suriguga; Gong, Meng; Liu, Wen-Juan; Cui, Ning-Xuan; Wang, Ying; Du, Xin; Yi, Zong-Chun

    2017-06-01

    Studies have shown that endothelial-to-mesenchymal transition (EndMT) could contribute to the progression of diabetic nephropathy, diabetic renal fibrosis, and cardiac fibrosis. The aim of this study was to investigate the influence of high glucose and related mechanism of MAPK inhibitor or specific antioxidant on the EndMT. In vitro human umbilical vein endothelial cells (HUVEC) were cultured with 11mM, 30mM, 60mM and 120mM glucose for 0, 24, 48, 72 and 168h. Endothelial cell morphology was observed with microscope, and RT-PCR was used to detect mRNA expression of endothelial markers VE-cadherin and CD31, mesenchymal markers α-SMA and collagen I, and transforming growth factor TGF-β1. Immunofluorescence staining was performed to detect the expression of CD31 and α-SMA. The concentration of TGF-β1 in the supernatant was detected by ELISA. ERK1/2 phosphorylation level was detected by Western blot analysis. High glucose induced EndMT and increased the TGF-β1 level in HUVEC cells. Cells in high glucose for 7 days showed a significant decrease in mRNA expression of CD31 and VE-cadherin, and a significant increase in that of α-SMA and collagen I, while lost CD31 staining and acquired α-SMA staining. ERK signaling pathway blocker PD98059 significantly attenuated the high glucose-induced increase in the ERK1/2 phosphorylation level. PD98059 and NAC both inhibited high glucose-induced TGF-β1 expression and attenuated EndMT marker protein synthesis. High glucose could induce HUVEC cells to undergo EndMT. NAC and ERK signaling pathway may play important role in the regulation of the TGF-β1 biosynthesis during high glucose-induced EndMT. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Targeting Pulmonary Endothelial Hemoglobin α Improves Nitric Oxide Signaling and Reverses Pulmonary Artery Endothelial Dysfunction.

    Science.gov (United States)

    Alvarez, Roger A; Miller, Megan P; Hahn, Scott A; Galley, Joseph C; Bauer, Eileen; Bachman, Timothy; Hu, Jian; Sembrat, John; Goncharov, Dmitry; Mora, Ana L; Rojas, Mauricio; Goncharova, Elena; Straub, Adam C

    2017-12-01

    Pulmonary hypertension is characterized by pulmonary endothelial dysfunction. Previous work showed that systemic artery endothelial cells (ECs) express hemoglobin (Hb) α to control nitric oxide (NO) diffusion, but the role of this system in pulmonary circulation has not been evaluated. We hypothesized that up-regulation of Hb α in pulmonary ECs contributes to NO depletion and pulmonary vascular dysfunction in pulmonary hypertension. Primary distal pulmonary arterial vascular smooth muscle cells, lung tissue sections from unused donor (control) and idiopathic pulmonary artery (PA) hypertension lungs, and rat and mouse models of SU5416/hypoxia-induced pulmonary hypertension (PH) were used. Immunohistochemical, immunocytochemical, and immunoblot analyses and transfection, infection, DNA synthesis, apoptosis, migration, cell count, and protein activity assays were performed in this study. Cocultures of human pulmonary microvascular ECs and distal pulmonary arterial vascular smooth muscle cells, lung tissue from control and pulmonary hypertensive lungs, and a mouse model of chronic hypoxia-induced PH were used. Immunohistochemical, immunoblot analyses, spectrophotometry, and blood vessel myography experiments were performed in this study. We find increased expression of Hb α in pulmonary endothelium from humans and mice with PH compared with controls. In addition, we show up-regulation of Hb α in human pulmonary ECs cocultured with PA smooth muscle cells in hypoxia. We treated pulmonary ECs with a Hb α mimetic peptide that disrupts the association of Hb α with endothelial NO synthase, and found that cells treated with the peptide exhibited increased NO signaling compared with a scrambled peptide. Myography experiments using pulmonary arteries from hypoxic mice show that the Hb α mimetic peptide enhanced vasodilation in response to acetylcholine. Our findings reveal that endothelial Hb α functions as an endogenous scavenger of NO in the pulmonary endothelium

  15. Topographic characteristics after Descemet's membrane endothelial keratoplasty and Descemet's stripping automated endothelial keratoplasty.

    Directory of Open Access Journals (Sweden)

    Takahiko Hayashi

    Full Text Available To investigate the topographic characteristics of the posterior corneal surface after Descemet's endothelial membrane keratoplasty (DMEK and Descemet's stripping automated endothelial keratoplasty (DSAEK and their effects on postoperative visual acuity.Nineteen eyes of 19 patients after DMEK, 23 eyes of 23 patients after DSAEK, and 18 eyes of 18 control subjects were retrospectively analyzed. Best spectacle-corrected visual acuity (BSCVA, aberration factors (higher-order aberrations [HOAs], spherical aberrations [SAs], and coma aberrations [Comas] at 6.0 mm were evaluated preoperatively and at 1, 3, and 6 months postoperatively. The posterior refractive pattern of the topography map was classified into 5 grades (0-5 (posterior color grade using anterior segment optical coherence tomography. Correlations between BSCVA and some factors (abbreviation factors, posterior color grade were analyzed.BSCVA was significantly better after DMEK than after DSAEK (P < 0.001. Posterior HOAs, SAs, and Comas after each type of endothelial keratoplasty were significantly greater compared to control (P < 0.01. Posterior HOAs, total/anterior/posterior SAs, and posterior color grade were significantly lower in the DMEK group than in the DSAEK group at 3 months (P < 0.024 [posterior HOAs], P = 0.047 [total SA], P < 0.001 [anterior SAs], P = 0.021 [posterior SAs], and P < 0.001 [posterior color grade] and 6 months postoperatively (P = 0.034 [posterior HOAs], P < 0.001 [total SAs], P < 0.001 [anterior SAs], P = 0.013 [posterior SAs], and P = 0.004 [posterior color grade]. BSCVA was significantly correlated with HOAs, SAs, and posterior color grade (P < 0.001 for all except anterior HOAs [P = 0.004].High posterior color grades were associated with larger aberration factors and had a negative effect on visual function after endothelial keratoplasty. Rapid improvement of visual function after DMEK may be attributed to less change at the posterior surface.

  16. Endoderm Generates Endothelial Cells during Liver Development

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    Orit Goldman

    2014-10-01

    Full Text Available Organogenesis requires expansion of the embryonic vascular plexus that migrates into developing organs through a process called angiogenesis. Mesodermal progenitors are thought to derive endothelial cells (ECs that contribute to both embryonic vasculogenesis and the subsequent organ angiogenesis. Here, we demonstrate that during development of the liver, which is an endoderm derivative, a subset of ECs is generated from FOXA2+ endoderm-derived fetal hepatoblast progenitor cells expressing KDR (VEGFR2/FLK-1. Using human and mouse embryonic stem cell models, we demonstrate that KDR+FOXA2+ endoderm cells developing in hepatic differentiation cultures generate functional ECs. This introduces the concept that ECs originate not exclusively from mesoderm but also from endoderm, supported in Foxa2 lineage-tracing mouse embryos by the identification of FOXA2+ cell-derived CD31+ ECs that integrate the vascular network of developing fetal livers.

  17. Torcetrapib impairs endothelial function in hypertension.

    Science.gov (United States)

    Simic, Branko; Hermann, Matthias; Shaw, Sidney G; Bigler, Laurent; Stalder, Urs; Dörries, Carola; Besler, Christian; Lüscher, Thomas F; Ruschitzka, Frank

    2012-07-01

    A marked increase in HDL notwithstanding, the cholesterol ester transfer protein (CETP) inhibitor torcetrapib was associated with an increase in all-cause mortality in the ILLUMINATE trial. As underlying mechanisms remain elusive, the present study was designed to delineate potential off-target effects of torcetrapib. Spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats were treated with torcetrapib (100 mg/kg/day; SHR-T and WKY-T) or placebo (SHR-P and WKY-P) for 3 weeks. Blood pressure transiently increased during the first 3 days of torcetrapib administration in SHRs and returned to baseline thereafter despite continued drug administration. Acetylcholine-induced endothelium-dependent relaxations of aortic rings were markedly impaired, and endothelial nitric oxide synthase (eNOS) mRNA and protein were down-regulated after 3 weeks of torcetrapib treatment in SHR (P risk is exposed to these compounds.

  18. Endothelial-Mesenchymal Transition in Regenerative Medicine.

    Science.gov (United States)

    Medici, Damian

    2016-01-01

    Endothelial-mesenchymal transition (EndMT) is a fundamental cellular mechanism that regulates embryonic development and diseases such as cancer and fibrosis. Recent developments in biomedical research have shown remarkable potential to harness the EndMT process for tissue engineering and regeneration. As an alternative to traditional or artificial stem cell therapies, EndMT may represent a safe method for engineering new tissues to treat degenerative diseases by mimicking a process that occurs in nature. This review discusses the signaling mechanisms and therapeutic inhibitors of EndMT, as well as the role of EndMT in development, disease, acquiring stem cell properties and generating connective tissues, and its potential as a novel mechanism for tissue regeneration.

  19. Human Endothelial Cell Models in Biomaterial Research.

    Science.gov (United States)

    Hauser, Sandra; Jung, Friedrich; Pietzsch, Jens

    2017-03-01

    Endothelial cell (EC) models have evolved as important tools in biomaterial research due to ubiquitously occurring interactions between implanted materials and the endothelium. However, screening the available literature has revealed a gap between material scientists and physiologists in terms of their understanding of these biomaterial-endothelium interactions and their relative importance. Consequently, EC models are often applied in nonphysiological experimental setups, or too extensive conclusions are drawn from their results. The question arises whether this might be one reason why, among the many potential biomaterials, only a few have found their way into the clinic. In this review, we provide an overview of established EC models and possible selection criteria to enable researchers to determine the most reliable and relevant EC model to use. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Telmisartan activates endothelial nitric oxide synthase via Ser1177 phosphorylation in vascular endothelial cells.

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    Masahiro Myojo

    Full Text Available Because endothelial nitric oxide synthase (eNOS has anti-inflammatory and anti-arteriosclerotic functions, it has been recognized as one of the key molecules essential for the homeostatic control of blood vessels other than relaxation of vascular tone. Here, we examined whether telmisartan modulates eNOS function through its pleiotropic effect. Administration of telmisartan to mice significantly increased the phosphorylation level of eNOS (Ser1177 in the aortic endothelium, but administration of valsartan had no effect. Similarly, telmisartan treatment of human umbilical vein endothelial cells significantly increased the phosphorylation levels of AMP-activated protein kinase (Thr172 and eNOS and the concentration of intracellular guanosine 3',5'-cyclic monophosphate (cGMP. Furthermore, pretreatment with a p38 mitogen-activated protein kinase (p38 MAPK inhibitor suppressed the increased phosphorylation level of eNOS and intracellular cGMP concentration. These data show that telmisartan increases eNOS activity through Ser1177 phosphorylation in vascular endothelial cells mainly via p38 MAPK signaling.

  1. [Descemet's membrane endothelial keratoplasty (DMEK): Analysis of a variation in Descemet's endothelial graft preparation].

    Science.gov (United States)

    Benoist D'azy, C; Benoist D'azy, C; Gabison, E; Sapin, V; Bosc, C; Pereira, B; Chiambaretta, F

    2017-05-01

    Descemet's membrane endothelial keratoplasty (DMEK) can replace just the corneal endothelium and respect the natural corneal anatomy. Currently, the technique of endothelial graft preparation remains manual and non-standardized. To report anatomic and functional results after DMEK, and compare two techniques of graft preparation. Single-center retrospective study, including 64 eyes of 64 patients undergoing DMEK, from September 2014 to February 2016 at Clermont-Ferrand University Medical Center. The "classic" preparation was used in 44 patients (group 1) and the "variant" preparation was used in 20 patients (group 2). An analysis of functional parameters (visual acuity), anatomy (pachymetry, corneal edema, endothelial cell count) and keratometry (sphere, cylinder, mean keratometry) was performed during the first postoperative year. The mean follow-up was 10.0±2.5 months. The average preparation time was 12.3±8.1minutes, with 14.4±8.8 in group 1 versus 7.8±3.0 in group 2 (Ppreparation saved a considerable amount of time without decreasing graft survival or postoperative results. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  2. Vascular endothelial growth factor A-stimulated signaling from endosomes in primary endothelial cells.

    Science.gov (United States)

    Fearnley, Gareth W; Smith, Gina A; Odell, Adam F; Latham, Antony M; Wheatcroft, Stephen B; Harrison, Michael A; Tomlinson, Darren C; Ponnambalam, Sreenivasan

    2014-01-01

    The vascular endothelial growth factor A (VEGF-A) is a multifunctional cytokine that stimulates blood vessel sprouting, vascular repair, and regeneration. VEGF-A binds to VEGF receptor tyrosine kinases (VEGFRs) and stimulates intracellular signaling leading to changes in vascular physiology. An important aspect of this phenomenon is the spatiotemporal coordination of VEGFR trafficking and intracellular signaling to ensure that VEGFR residence in different organelles is linked to downstream cellular outputs. Here, we describe a series of assays to evaluate the effects of VEGF-A-stimulated intracellular signaling from intracellular compartments such as the endosome-lysosome system. These assays include the initial isolation and characterization of primary human endothelial cells, performing reverse genetics for analyzing protein function; methods used to study receptor trafficking, signaling, and proteolysis; and assays used to measure changes in cell migration, proliferation, and tubulogenesis. Each of these assays has been exemplified with studies performed in our laboratories. In conclusion, we describe necessary techniques for studying the role of VEGF-A in endothelial cell function. © 2014 Elsevier Inc. All rights reserved.

  3. Secondhand smoke exposure and endothelial stress in children and adolescents.

    Science.gov (United States)

    Groner, Judith A; Huang, Hong; Nagaraja, Haikady; Kuck, Jennifer; Bauer, John Anthony

    2015-01-01

    Links between secondhand smoke exposure and cardiovascular disease in adults are well established. Little is known about the impact of this exposure on cardiovascular status during childhood. The purpose of this study was to investigate relationships between secondhand smoke exposure in children and adolescents and cardiovascular disease risk--systemic inflammation, endothelial stress, and endothelial repair. A total of 145 subjects, aged 9 to 18 years, were studied. Tobacco smoke exposure was determined by hair nicotine level. Cardiovascular risk was assessed by markers of systemic inflammation (C-reactive protein [CRP] and adiponectin); by soluble intercellular adhesion molecule 1 (s-ICAM1), which measures endothelial activation after surface vascular injury; and by endothelial repair. This was measured by prevalence of endothelial progenitor cells (EPCs), which are bone marrow-derived cells that home preferentially to sites of vascular damage. Hair nicotine was directly correlated with s-ICAM1 (r = 0.4090, P Secondhand smoke exposure during childhood and adolescence is detrimental to vascular health because s-ICAM1 is a marker for endothelial activation and stress after vascular surface injury, and EPCs contribute to vascular repair. The fact that body mass index is also a factor in the model predicting s-ICAM1 is concerning, in that 2 risk factors may both contribute to endothelial stress. Copyright © 2015 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

  4. Role of glutathione biosynthesis in endothelial dysfunction and fibrosis

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    Cristina Espinosa-Díez

    2018-04-01

    Full Text Available Glutathione (GSH biosynthesis is essential for cellular redox homeostasis and antioxidant defense. The rate-limiting step requires glutamate-cysteine ligase (GCL, which is composed of the catalytic (GCLc and the modulatory (GCLm subunits. To evaluate the contribution of GCLc to endothelial function we generated an endothelial-specific Gclc haplo-insufficient mouse model (Gclc e/+ mice. In murine lung endothelial cells (MLEC derived from these mice we observed a 50% reduction in GCLc levels compared to lung fibroblasts from the same mice. MLEC obtained from haplo-insufficient mice showed significant reduction in GSH levels as well as increased basal and stimulated ROS levels, reduced phosphorylation of eNOS (Ser 1177 and increased eNOS S-glutathionylation, compared to MLEC from wild type (WT mice. Studies in mesenteric arteries demonstrated impaired endothelium-dependent vasodilation in Gclc(e/+ male mice, which was corrected by pre-incubation with GSH-ethyl-ester and BH4. To study the contribution of endothelial GSH synthesis to renal fibrosis we employed the unilateral ureteral obstruction model in WT and Gclc(e/+ mice. We observed that obstructed kidneys from Gclc(e/+ mice exhibited increased deposition of fibrotic markers and reduced Nrf2 levels. We conclude that the preservation of endothelial GSH biosynthesis is not only critical for endothelial function but also in anti-fibrotic responses. Keywords: Glutamate-cysteine ligase, ROS, Glutathione, Endothelial dysfunction, Kidney Fibrosis

  5. Assessment of Endothelial Dysfunction in Childhood Obesity and Clinical Use

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    Luc Bruyndonckx

    2013-01-01

    Full Text Available The association of obesity with noncommunicable diseases, such as cardiovascular complications and diabetes, is considered a major threat to the management of health care worldwide. Epidemiological findings show that childhood obesity is rapidly rising in Western society, as well as in developing countries. This pandemic is not without consequences and can affect the risk of future cardiovascular disease in these children. Childhood obesity is associated with endothelial dysfunction, the first yet still reversible step towards atherosclerosis. Advanced research techniques have added further insight on how childhood obesity and associated comorbidities lead to endothelial dysfunction. Techniques used to measure endothelial function were further brought to perfection, and novel biomarkers, including endothelial progenitor cells, were discovered. The aim of this paper is to provide a critical overview on both in vivo as well as in vitro markers for endothelial integrity. Additionally, an in-depth description of the mechanisms that disrupt the delicate balance between endothelial damage and repair will be given. Finally, the effects of lifestyle interventions and pharmacotherapy on endothelial dysfunction will be reviewed.

  6. Endothelial cell energy metabolism, proliferation, and apoptosis in pulmonary hypertension.

    Science.gov (United States)

    Xu, Weiling; Erzurum, Serpil C

    2011-01-01

    Pulmonary arterial hypertension (PAH) is a fatal disease characterized by impaired regulation of pulmonary hemodynamics and excessive growth and dysfunction of the endothelial cells that line the arteries in PAH lungs. Establishment of methods for culture of pulmonary artery endothelial cells from PAH lungs has provided the groundwork for mechanistic translational studies that confirm and extend findings from model systems and spontaneous pulmonary hypertension in animals. Endothelial cell hyperproliferation, survival, and alterations of biochemical-metabolic pathways are the unifying endothelial pathobiology of the disease. The hyperproliferative and apoptosis-resistant phenotype of PAH endothelial cells is dependent upon the activation of signal transducer and activator of transcription (STAT) 3, a fundamental regulator of cell survival and angiogenesis. Animal models of PAH, patients with PAH, and human PAH endothelial cells produce low nitric oxide (NO). In association with the low level of NO, endothelial cells have reduced mitochondrial numbers and cellular respiration, which is associated with more than a threefold increase in glycolysis for energy production. The shift to glycolysis is related to low levels of NO and likely to the pathologic expression of the prosurvival and proangiogenic signal transducer, hypoxia-inducible factor (HIF)-1, and the reduced mitochondrial antioxidant manganese superoxide dismutase (MnSOD). In this article, we review the phenotypic changes of the endothelium in PAH and the biochemical mechanisms accounting for the proliferative, glycolytic, and strongly proangiogenic phenotype of these dysfunctional cells, which consequently foster the panvascular progressive pulmonary remodeling in PAH. © 2011 American Physiological Society.

  7. Circulating endothelial progenitor cells in obese children and adolescents.

    Science.gov (United States)

    Pires, António; Martins, Paula; Paiva, Artur; Pereira, Ana Margarida; Marques, Margarida; Castela, Eduardo; Sena, Cristina; Seiça, Raquel

    2015-01-01

    This study aimed to investigate the relationship between circulating endothelial progenitor cell count and endothelial activation in a pediatric population with obesity. Observational and transversal study, including 120 children and adolescents with primary obesity of both sexes, aged 6-17 years, who were recruited at this Cardiovascular Risk Clinic. The control group was made up of 41 children and adolescents with normal body mass index. The variables analyzed were: age, gender, body mass index, systolic and diastolic blood pressure, high-sensitivity C-reactive protein, lipid profile, leptin, adiponectin, homeostasis model assessment-insulin resistance, monocyte chemoattractant protein-1, E-selectin, asymmetric dimethylarginine and circulating progenitor endothelial cell count. Insulin resistance was correlated to asymmetric dimethylarginine (ρ=0.340; p=0.003), which was directly, but weakly correlated to E-selectin (ρ=0.252; p=0.046). High sensitivity C-reactive protein was not found to be correlated to markers of endothelial activation. Systolic blood pressure was directly correlated to body mass index (ρ=0.471; p<0.001) and the homeostasis model assessment-insulin resistance (ρ=0.230; p=0.012), and inversely correlated to adiponectin (ρ=-0.331; p<0.001) and high-density lipoprotein cholesterol (ρ=-0.319; p<0.001). Circulating endothelial progenitor cell count was directly, but weakly correlated, to body mass index (r=0.211; p=0.016), leptin (ρ=0.245; p=0.006), triglyceride levels (r=0.241; p=0.031), and E-selectin (ρ=0.297; p=0.004). Circulating endothelial progenitor cell c