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.

引言：本研究直接对比了贝伐珠单抗（bevacizumab）、2mg剂量阿柏西普（aflibercept）以及雷珠单抗（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疗效。
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按需治疗并延长间隔方案管理的初治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）的变化情况；次要结局指标包括治疗负担（总注射次数与最终维持间隔时长）、无应答（经充分治疗后仍存在持续性/加重性渗出或功能下降）、未延长间隔（最终间隔为4周）以及无活动性渗出。
结果：本研究共纳入322只患眼，其中分别接受贝伐珠单抗（n=174）、阿柏西普（n=110）与雷珠单抗（n=38）治疗，平均随访时长为16.75±12.66个月。受试者平均接受10.5±6.3次注射后，平均VA从0.77±0.47 logMAR提升至0.60±0.45 logMAR。与贝伐珠单抗相比，阿柏西普可带来更显著的CRT降低（-51.94μm；p<0.001）、更少的注射次数（-2.35次；p=0.001）、更长的最终维持间隔（+2.14周；p<0.001），且无应答风险（调整后比值比（adjusted odds ratio, aOR）=0.016；p<0.001）与未延长间隔风险（aOR=0.128；p<0.001）均更低。阿柏西普的平均VA提升幅度最大，但在多变量分析中未达到统计学显著性（p=0.059）。与贝伐珠单抗相比，雷珠单抗可实现更显著的CRT降低（-44.53μm；p=0.012）且未延长间隔风险更低（aOR=0.079；p=0.001），但未显著降低治疗负担或改善VA。
结论：作为首个真实世界头对头对比研究，阿柏西普与雷珠单抗在关键解剖学指标与治疗效率结局方面均优于贝伐珠单抗，其中阿柏西普的优势最为持续一致。本研究结果揭示了抗血管内皮生长因子（anti-VEGF）类药物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。