Efficacy and Safety of Adjunctive Therapies in Retinal Vein Occlusion: A Systematic Review and Clinical Synthesis of Laser, Corticosteroids, and Surgery

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.