Direct randomized evidence comparing ranibizumab and bevacizumab for macular edema secondary to retinal vein occlusion: a systematic review and meta-analysis

Background Intravitreal anti–vascular endothelial growth factor therapy is the first-line treatment for macular edema secondary to retinal vein occlusion. However, direct comparative evidence between ranibizumab and bevacizumab from randomized controlled trials remains limited. This study aimed to compare the efficacy and safety of these two agents using evidence from randomized controlled trials. Methods We systematically searched PubMed, Embase, the Cochrane Library, and Web of Science from database inception to February 11, 2026. Eligible studies were published randomized controlled trials directly comparing intravitreal ranibizumab and bevacizumab monotherapy in adults with RVO-ME. Nonrandomized and noncomparative studies were excluded. Results Four randomized controlled trials involving 759 participants were included. At 6 months, no significant difference was observed in mean best-corrected visual acuity (BCVA) change (MD 0.61 letters, 95% CI −1.95 to 3.18). The pooled mean difference in central macular thickness (CMT) change was 1.52 μm (95% CI −237.41 to 240.46). The proportion of eyes gaining ≥ 15 ETDRS letters was comparable (RR 0.97, 95% CI 0.82 to 1.14). Safety profiles were broadly similar. Rare systemic events were infrequent and associated with considerable statistical uncertainty. Certainty of evidence was moderate for visual outcomes and low to very low for rare adverse events. Conclusion Ranibizumab and bevacizumab show comparable short-term efficacy and safety for macular edema secondary to retinal vein occlusion, although evidence for rare systemic events remains uncertain. Clinical trial number Not applicable. Trial registration PROSPERO CRD420251172336.