Laser Failure, the Steroid Paradox, and Surgical Potential: A Systematic Review Re-evaluating Adjunctive Therapies for Retinal Vein Occlusion

Efficacy and Safety of Adjunctive Therapies in Retinal Vein Occlusion: A Systematic Review and Clinical Synthesis of Laser, Corticosteroids, and Surgery | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Systematic Review Efficacy and Safety of Adjunctive Therapies in Retinal Vein Occlusion: A Systematic Review and Clinical Synthesis of Laser, Corticosteroids, and Surgery Vihaan Sahu, Dhaneesh Rucher Jetty, Tanmay Jape This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8682171/v3 This work is licensed under a CC BY 4.0 License Status: Posted Version 3 posted You are reading this latest preprint version Show more versions Abstract Objectives: The substantial treatment burden of anti-vascular endothelial growth factor (anti-VEGF) monotherapy for retinal vein occlusion (RVO) has driven the investigation of adjunctive laser, corticosteroids, and surgery. This systematic review evaluates the efficacy and safety of these combination therapies compared to anti-VEGF monotherapy. Methods: A comprehensive search of databases (2010–2025) identified 46 studies (RCTs and non-randomized studies). Due to substantial clinical heterogeneity and incomplete reporting of variance data, a quantitative meta-analysis was limited. A structured narrative synthesis following Cochrane guidelines, incorporating direction-of-effect plots and weighting by study sample size, was performed. Primary outcomes were Best-Corrected Visual Acuity (BCVA) and Central Retinal Thickness (CRT); injection burden was a key secondary outcome. Results: Anti-VEGF monotherapy was reaffirmed as the visual acuity standard. Adjunctive laser photocoagulation demonstrated no consistent visual benefit, with qualitative synthesis revealing more studies favoring monotherapy than combination and high-quality RCTs indicating a signal of potential visual inferiority with laser addition. Steroid adjuncts consistently reduced CRT and injection frequency but failed to provide superior long-term visual acuity compared to monotherapy. In contrast, surgical Laser-Induced Chorioretinal Anastomosis (L-CRA) showed promising visual superiority and significant treatment burden reduction in pilot studies, though these findings originate from a single research group and require external validation. Conclusion: Current evidence does not support the routine use of adjunctive laser for macular edema. Corticosteroids should be strategically deployed as a "burden management" tool rather than for vision enhancement. Surgical L-CRA shows potential as a hemodynamic intervention targeting the underlying venous obstruction and warrants further investigation in multicenter trials. Ophthalmology Retinal Vein Occlusion Anti-VEGF Combination Therapy Laser Photocoagulation Corticosteroids Laser-Induced Chorioretinal Anastomosis Systematic Review Treatment Burden Full Text Additional Declarations The authors declare no competing interests. Supplementary Files SuppFig1.png Supplementary Materials The following supplementary materials are provided: • Supplementary Figure 1: Sensitivity Analysis comparing the Primary Analysis (All Studies) versus the analysis excluding High Risk/Open-Label studies. SuppFig1.png Supplementary Materials The following supplementary materials are provided: • Supplementary Figure 1: Sensitivity Analysis comparing the Primary Analysis (All Studies) versus the analysis excluding High Risk/Open-Label studies. SuppFig3.png • Supplementary Figure 3: ROBINS-I Risk of Bias Assessment visualization for Non-randomized studies. SuppFig4.png • Supplementary Figure 4: Quantitative Meta-Analysis (Traditional forest plot) performed on the subset of studies with complete variance data. Cite Share Download PDF Status: Posted Version 3 posted You are reading this latest preprint version Show more versions Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8682171","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Systematic Review","associatedPublications":[],"authors":[{"id":585260017,"identity":"ddf5a17a-209c-4656-b7a8-8cfdb3fa1784","order_by":0,"name":"Vihaan 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This systematic review evaluates the efficacy and safety of these combination therapies compared to anti-VEGF monotherapy.\u003cbr\u003e\n\u003cbr\u003e\nMethods: A comprehensive search of databases (2010–2025) identified 46 studies (RCTs and non-randomized studies). Due to substantial clinical heterogeneity and incomplete reporting of variance data, a quantitative meta-analysis was limited. A structured narrative synthesis following Cochrane guidelines, incorporating direction-of-effect plots and weighting by study sample size, was performed. Primary outcomes were Best-Corrected Visual Acuity (BCVA) and Central Retinal Thickness (CRT); injection burden was a key secondary outcome. \u003cbr\u003e\n\u003cbr\u003e\nResults: Anti-VEGF monotherapy was reaffirmed as the visual acuity standard. 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