Supplementary Material for: Comparative Real-World Efficacy of Anti-VEGF Agents in Neovascular AMD: 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).
Methods: 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.
Results: 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 to 0.60 ± 0.45 logMAR 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 (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.
Conclusion: 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-VEGF agents and underscore the importance of real-world data to guide nvAMD management.

研究简介：本研究头对头比较了贝伐单抗（bevacizumab）、阿柏西普2mg（aflibercept 2 mg）与雷珠单抗（ranibizumab）作为新生血管性年龄相关性黄斑变性（neovascular age-related macular degeneration, nvAMD）一线治疗方案的真实世界临床疗效。

研究方法：本研究为多中心回顾性队列研究，纳入以色列与加拿大境内接受治疗-延长方案（treat-and-extend）管理的初治nvAMD患眼。主要结局指标为视力（visual acuity, VA）与中心视网膜厚度（central retinal thickness, CRT）的变化；次要结局指标包括治疗负担（总注射次数与最终维持注射间隔）、治疗无应答（足量治疗后仍存在持续性/加重性渗出或视力功能下降）、无法延长注射间隔（最终注射间隔仍为4周）以及无活动性渗出。

研究结果：共计322只患眼分别接受贝伐单抗（n=174）、阿柏西普（n=110）或雷珠单抗（n=38）治疗，平均随访时长为16.75±12.66个月。受试者平均视力从基线的0.77±0.47 logMAR提升至随访末的0.60±0.45 logMAR，平均注射次数为10.5±6.3次。与贝伐单抗相比，阿柏西普可使中心视网膜厚度降低更显著（-51.94μm；p<0.001），注射次数减少更多（-2.35次；p=0.001），最终维持注射间隔更长（+2.14周；p<0.001），且治疗无应答（调整后优势比adjusted odds ratio, aOR=0.016；p<0.001）与无法延长注射间隔（aOR=0.128；p<0.001）的发生风险更低。阿柏西普在视力提升幅度上最大，但在多变量分析中仅接近统计学显著性（p=0.059）。与贝伐单抗相比，雷珠单抗可使中心视网膜厚度降低更显著（-44.53μm；p=0.012），且无法延长注射间隔的发生风险更低（aOR=0.079；p=0.001），但未显著降低治疗负担或改善视力。

研究结论：在这项首个真实世界头对头对照研究中，阿柏西普与雷珠单抗在关键解剖学与治疗效率结局上均优于贝伐单抗，其中阿柏西普的优势最为一致。本研究结果凸显了抗血管内皮生长因子（anti-vascular endothelial growth factor, anti-VEGF）类药物之间存在具有临床意义的差异，同时强调了真实世界数据在指导nvAMD临床管理中的重要价值。