Comparative Real-World Efficacy of Anti-Vascular Endothelial Growth Factor Agents in Neovascular Age-Related Macular Degeneration: A Multicenter Retrospective Study

Introduction: This study directly compared the real-world effectiveness of bevacizumab, aflibercept 2 mg, and ranibizumab as first-line treatments for neovascular age-related macular degeneration (nvAMD).

A multicenter retrospective cohort of treatment-naïve nvAMD eyes managed with a treat-and-extend regimen in Israel and Canada. Primary outcomes were changes in visual acuity (VA) and central retinal thickness (CRT). Secondary outcomes included treatment burden (total injections and final maintained interval), non-response (persistent/worsening exudation or functional decline despite adequate treatment), non-extension (final interval of 4 weeks), and absence of active exudation.

A total of 322 eyes received bevacizumab (n = 174), aflibercept (n = 110), or ranibizumab (n = 38) over a mean follow-up of 16.75 ± 12.66 months. Mean VA improved from 0.77 ± 0.47-0.60 ± 0.45 logarithm of the minimum angle of resolution following an average of 10.5 ± 6.3 injections. Aflibercept produced greater CRT reduction (-51.94 μm; p < 0.001), fewer injections (-2.35; p = 0.001), longer final intervals (+2.14 weeks; p < 0.001), and lower odds of non-response (adjusted odds ratio [aOR] 0.016; p < 0.001) and non-extension (aOR 0.128, p < 0.001) versus bevacizumab. It showed the largest mean VA gain, just short of significance on multivariable analysis (p = 0.059). Ranibizumab showed greater CRT reduction (-44.53 μm; p = 0.012) and lower non-extension odds (aOR 0.079; p = 0.001) than bevacizumab but did not significantly reduce treatment burden or improve VA.

In this first real-world, head-to-head comparison, aflibercept and ranibizumab outperformed bevacizumab in key anatomic and treatment-efficiency outcomes, with aflibercept showing the most consistent advantages. These findings highlight clinically relevant differences among anti-vascular endothelial growth factor agents and underscore the importance of real-world data to guide nvAMD management.