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      Structural and Functional Analyses of Retinal Ischemia in Eyes with Retinal Vein Occlusion: Relationship with Macular Edema or Microaneurysm Formation

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          Abstract

          Purpose: To study the structural and functional changes of retinal ischemia and investigate their association with macular edema (ME) or microaneurysm (MA) formation in eyes with retinal vein occlusion (RVO). Methods: Sixty eyes of 30 patients (27 eyes with branch [b]RVO, 3 with central RVO, and 30 fellow eyes) were retrospectively reviewed. Optical coherence tomography (OCT), OCT angiography (OCTA), and microperimetry were performed simultaneously to measure retinal thickness and sensitivity. The presence of ME or MA was also assessed using OCT and fluorescein angiography. Results: The mean retinal sensitivity in the nonperfused areas (NPAs) deteriorated, and this was significantly ( r = –0.379, p = 0.0391*) and inversely correlated with duration from disease onset. ME and MA were unlikely to be observed around the area where the retinal sensitivity decreased. In the NPAs, the mean retinal thickness of the superficial capillary plexus (SCP) ( p < 0.0001), deep capillary plexus (DCP) ( p = 0.0323), and outer retina ( p = 0.0008) were significantly thinner than those in the fellow eyes, respectively. Multivariate regression analysis revealed that the thicknesses of the DCP (β: 0.3107, p = 0.0007) and outer retina (β: 0.3482, p = 0.0001) were the independent correlative factors of the retinal sensitivity, but that SCP thickness was not. Conclusion: Deep retinal thinning in NPAs was correlated significantly with a decreased retinal sensitivity, which might be a negative predictor of ME and MA in eyes with RVO.

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          Sustained benefits from ranibizumab for macular edema following branch retinal vein occlusion: 12-month outcomes of a phase III study.

          David M Brown, Peter A Campochiaro, Robert Bhisitkul … (2011)
          Assess 12-month efficacy and safety of intraocular injections of 0.3 mg or 0.5 mg ranibizumab in patients with macular edema after branch retinal vein occlusion (BRVO). Prospective, randomized, sham injection-controlled, double-masked, multicenter trial. A total of 397 patients with macular edema after BRVO. Eligible patients were randomized 1:1:1 to 6 monthly injections of 0.3 mg or 0.5 mg ranibizumab or sham injections. After 6 months, all patients with study eye best-corrected visual acuity (BCVA) ≤20/40 or central subfield thickness ≥250 μm were to receive ranibizumab. Patients could receive rescue laser treatment once during the treatment period and once during the observation period if criteria were met. The main efficacy outcome reported is mean change from baseline BCVA letter score at month 12. Additional visual and anatomic parameters were assessed. Mean (95% confidence interval) change from baseline BCVA letter score at month 12 was 16.4 (14.5-18.4) and 18.3 (15.8-20.9) in the 0.3 mg and 0.5 mg groups, respectively, and 12.1 (9.6-14.6) in the sham/0.5 mg group (P<0.01, each ranibizumab group vs. sham/0.5 mg). The percentage of patients who gained ≥15 letters from baseline BCVA at month 12 was 56.0% and 60.3% in the 0.3 mg and 0.5 mg groups, respectively, and 43.9% in the sham/0.5 mg group. On average, there was a marked reduction in central foveal thickness (CFT) after the first as-needed injection of 0.5 mg ranibizumab in the sham/0.5 mg group, which was sustained through month 12. No new ocular or nonocular safety events were identified. At month 12, treatment with ranibizumab as needed during months 6-11 maintained, on average, the benefits achieved by 6 monthly ranibizumab injections in patients with macular edema after BRVO, with low rates of ocular and nonocular safety events. In the sham/0.5 mg group, treatment with ranibizumab as needed for 6 months resulted in rapid reduction in CFT to a similar level as that in the 0.3 mg ranibizumab treatment group and an improvement in BCVA, but not to the extent of that in the 2 ranibizumab groups. Intraocular injections of ranibizumab provide an effective treatment for macular edema after BRVO. Proprietary or commercial disclosure may be found after the references. Copyright © 2011 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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              Intravitreous injections of vascular endothelial growth factor produce retinal ischemia and microangiopathy in an adult primate.

              Michael Tolentino, Joan W. Miller, Evangelos Gragoudas … (1996)
              The purpose of the study is to determine the effect of exogenous vascular endothelial growth factor (VEGF) on the primate retina and its vasculature. Ten eyes of five animals were studied. Physiologically relevant amounts of the 165 amino acid isoform of human recombinant VEGF were injected into the vitreous of six healthy cynomolgus monkey eyes. Inactivated human recombinant VEGF or vehicle was injected into four contralateral control subject eyes. Eyes were assessed by slit-lamp biomicroscopy, tonometry, fundus color photography, fundus fluorescein angiography, light microscopy, and immunostaining with antibodies against proliferating cell nuclear antigen and factor VIII antigen. All six bioactive VEGF-injected eyes developed dilated, tortuous retinal vessels that leaked fluorescein. Eyes receiving multiple injections of VEGF developed progressively dilated and tortuous vessels, venous beading, edema, microaneurysms, intraretinal hemorrhages and capillary closure with ischemia. The severity of the retinopathy correlated with the number of VEGF injections. None of the four control eyes exhibited any abnormal retinal vascular changes. The endothelial cells of retinal blood vessels were proliferating cell nuclear antigen positive only in the bioactive VEGF-injected eyes. Vascular endothelial growth factor is sufficient to produce many of the vascular abnormalities common to diabetic retinopathy and other ischemic retinopathies, such as hemorrhage, edema, venous beading, capillary occlusion with ischemia, microaneurysm formation, and intraretinal vascular proliferation.
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                Author and article information

                Journal
                Journal ID (publisher-id): ORE
                Journal ID (nlm-ta): Ophthalmic Res
                Journal ID (doi): 10.1159/issn.0030-3747
                Title: Ophthalmic Research
                Publisher: S. Karger AG
                ISSN (Print): 0030-3747
                ISSN (Electronic): 1423-0259
                Publication date Subscription-year: 2019
                Publication date (Print): April 2019
                Publication date (Electronic): 25 October 2018
                Volume: 61
                Issue: 4
                Pages: 218-225
                Affiliations
                Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
                Author notes
                *Yoshio Hirano, MD, PhD, Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan), E-Mail yoshio.hirano@gmail.com
                Article
                Publisher ID: 493489 Other ID: Ophthalmic Res 2019;61:218–225
                DOI: 10.1159/000493489
                PubMed ID: 30359965
                SO-VID: 217cc4fe-bbfb-486f-91d1-ebd387205171
                Copyright © © 2018 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 : 04 July 2018
                Date accepted : 03 September 2018
                Page count
                Figures: 4, Tables: 2, Pages: 8
                Categories
                Subject: Research Article

                ScienceOpen disciplines: Vision sciences,Ophthalmology & Optometry,Pathology
                Keywords: Macular edema,Optical coherence tomography angiography,Retinal vein occlusion,Microaneurysm,Retinal thickness,Microperimetry
                Data availability:
                ScienceOpen disciplines: Vision sciences, Ophthalmology & Optometry, Pathology
                Keywords: Macular edema, Optical coherence tomography angiography, Retinal vein occlusion, Microaneurysm, Retinal thickness, Microperimetry

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