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      Current Outcomes of Anti-VEGF Therapy in the Treatment of Macular Oedema Secondary to Branch Retinal Vein Occlusions: A Meta-Analysis

      meta-analysis

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          Abstract

          Purpose: The current body of evidence on the efficacy and safety of anti-VEGFs for macular oedema secondary to branch retinal vein occlusion (BRVO) is steadily growing as large clinical trials and observational studies are continually completed. The aim of this meta-analysis is to analyse anatomical and functional outcomes in response to anti-VEGF therapy using evidence generated from a pooled analysis of current clinical trials and observational studies. Methods: The current meta-analysis includes treatment of BRVO with aflibercept, bevacizumab and ranibizumab from randomised controlled trials and observational studies. Inclusion criteria included peer-reviewed publications with at least a 12-month follow-up period. On literature review using multiple electronic databases (PubMed, Embase and Cochrane), 22 studies met the inclusion criteria. Baseline patient characteristics, study design, sample size and 12- and 24-month change in best corrected visual acuity (BCVA) and central foveal thickness (CFT) as measured on optical coherence tomography imaging were pooled in a meta-analysis. Data were then stratified by study design and anti-VEGF therapy in subgroup analyses. Results: A total of 1,236 eyes from 22 studies were included in this meta-analysis. Mean baseline BCVA ranged from 66 ETDRS letters (20/50 Snellen equivalent) to 35 letters (20/200 Snellen). Mean baseline CFT ranged from 406.0 to 681.0 µm. Anti-VEGF treatment demonstrated an overall mean improvement in BCVA at 12 months of 14 letters (95% CI 12.0 to 16.2, p < 0.001) and CFT reduction of 228 µm (95% CI –278.9 to –176.1, p < 0.001). The BCVA gains at 12 months were maintained to month 24 with a mean gain of 12.5 letters (95% CI 6.3 to 18.8, p < 0.001), as well as reduction of CFT of 238 µm (95% CI –336.0 to –140.2, p < 0.001). No cases of endophthalmitis or glaucoma were reported in any study. Conclusion: This meta-analysis confirms the comparable safety and efficacy of anti-VEGF therapies for patients with cystoid macular oedema secondary to BRVO. There is a need for randomised prospective comparative trials of anti-VEGF agents for BRVO.

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          Contributions of Inflammatory Processes to the Development of the Early Stages of Diabetic Retinopathy

          Timothy Kern (2007)
          Diabetes causes metabolic and physiologic abnormalities in the retina, and these changes suggest a role for inflammation in the development of diabetic retinopathy. These changes include upregulation of iNOS, COX-2, ICAM-1, caspase 1, VEGF, and NF- κ B, increased production of nitric oxide, prostaglandin E2, IL-1 β , and cytokines, as well as increased permeability and leukostasis. Using selective pharmacologic inhibitors or genetically modified animals, an increasing number of therapeutic approaches have been identified that significantly inhibit development of at least the early stages of diabetic retinopathy, especially occlusion and degeneration of retinal capillaries. A common feature of a number of these therapies is that they inhibit production of inflammatory mediators. The concept that localized inflammatory processes play a role in the development of diabetic retinopathy is relatively new, but evidence that supports the hypothesis is accumulating rapidly. This new hypothesis offers new insight into the pathogenesis of diabetic retinopathy, and offers novel targets to inhibit the ocular disease.
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            Natural history of branch retinal vein occlusion: an evidence-based systematic review.

            Sophie L. Rogers, Rachel McIntosh, Lyndell Lim … (2010)
            To describe the natural history of branch retinal vein occlusion (BRVO) based on the best available evidence from the literature. Branch retinal vein occlusion is the second most frequent major retinal vascular disease. Although several new treatments for BRVO are currently being introduced, data on its natural history are sparse. English language articles were retrieved using a keyword search of MEDLINE, EMBASE, Current Contents, and the Cochrane Library to November 13, 2008, supplemented by manually searching the references of review articles published within the last 5 years. All relevant observational studies evaluating the natural history of BRVO and all clinical trials evaluating BRVO interventions with an untreated control arm were independently identified by 2 investigators. Of a total of 5965 citations retrieved, 24 eligible studies were identified and reviewed, providing 1608 eyes with BRVO with data on natural history. Visual acuity (VA) was moderately poor at baseline (<20/40). Although VA generally improved, with mean improvement ranging from 1 letter at 6 weeks to 28 letters up to 24 months, few studies reported improvement beyond 20/40. Over a 1-year period, 5% to 15% of eyes developed macular edema (ME), but of those with ME at baseline, 18% to 41% resolved. At baseline, 5% to 6% of eyes had bilateral BRVO, with 10% developing fellow eye involvement over time. There were few high-quality studies on other outcomes, including development of new vessels. Visual acuity generally improved in eyes with BRVO without intervention, although clinically significant improvement beyond 20/40 was uncommon. Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
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              Pathogenesis of macular edema with branch retinal vein occlusion and intraocular levels of vascular endothelial growth factor and interleukin-6.

              Hidetoshi Yamashita, Reid Sakamoto, Hideharu Funatsu … (2005)
              To determine whether correlations between vascular endothelial growth factor (VEGF) or interleukin-6 (IL-6) contribute to the pathogenesis of macular edema in eyes of patients with branch retinal vein occlusion (BRVO). Retrospective case-control study. Nineteen patients with macular edema with BRVO and seven patients with non-ischemic ocular disease (control group) were studied. The degree of retinal ischemia was evaluated in terms of the area of capillary non-perfusion, and the severity of macular edema was examined by optical coherence tomography. Aqueous humor samples were obtained at the time of combined vitrectomy and cataract surgery, and VEGF and IL-6 levels in aqueous humor and plasma were determined by enzyme-linked immunosorbent assay. Aqueous levels of VEGF (351 +/- 273 pg/ml) and IL-6 (7.10 +/- 6.51 pg/ml) were significantly elevated in patients with BRVO compared with the control patients (119 +/- 38.7 pg/ml and 2.27 +/- 1.11 pg/ml, respectively) (P = .0017 and P = .0052, respectively). Aqueous level of VEGF was significantly correlated with that of IL-6 (P = .0396), and aqueous levels of VEGF and IL-6 were correlated with the size of the BRVO non-perfused area (P < .0001 and P = .0331, respectively). Aqueous level of VEGF was correlated with the severity of macular edema (P = .0306). VEGF and IL-6 may be involved in the pathogenesis of macular edema with BRVO. The increase in these cytokines might be used as a unique index of BRVO, through which we can determine the severity of the ischemic condition as being in a quiescent state or an exacerbation of macular edema.
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                Author and article information

                Journal
                Journal ID (publisher-id): OPH
                Journal ID (nlm-ta): Ophthalmologica
                Journal ID (doi): 10.1159/issn.0030-3755
                Title: Ophthalmologica
                Publisher: S. Karger AG
                ISSN (Print): 0030-3755
                ISSN (Electronic): 1423-0267
                Publication date Subscription-year: 2019
                Publication date (Print): September 2019
                Publication date (Electronic): 03 June 2019
                Volume: 242
                Issue: 3
                Pages: 163-177
                Affiliations
                [_a] aSydney Institute of Vision Science, Sydney Retina, Sydney, New South Wales, Australia
                [_b] bSave Sight Institute, University of Sydney, Sydney, New South Wales, Australia
                Author notes
                *Assoc. Prof Andrew Chang, Sydney Retina, Level 13, Park House, 187 Macquarie Street, Sydney, NSW 2000 (Australia), E-Mail achang@sydneyretina.com.au
                Article
                Publisher ID: 497492 Other ID: Ophthalmologica 2019;242:163–177
                DOI: 10.1159/000497492
                PubMed ID: 31158837
                SO-VID: bd83e482-cdee-4ef1-b8ad-fa4453752347
                Copyright © © 2019 S. Karger AG, Basel
                License:

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                Date received : 06 December 2018
                Date accepted : 01 February 2019
                Page count
                Figures: 4, Tables: 3, Pages: 15
                Categories
                Subject: Research Article

                ScienceOpen disciplines: Vision sciences,Ophthalmology & Optometry,Pathology
                Keywords: Meta-analysis,Retinal vein occlusion,Anti-VEGF,Macular oedema,VEGF
                Data availability:
                ScienceOpen disciplines: Vision sciences, Ophthalmology & Optometry, Pathology
                Keywords: Meta-analysis, Retinal vein occlusion, Anti-VEGF, Macular oedema, VEGF

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