Supplementary Material for: Anti-vascular endothelial growth factor therapy regimens for polypoidal choroidal vasculopathy: a systematic review

Introduction: There are no guidelines on the optimal anti-vascular endothelial growth factor (anti-VEGF) monotherapy regimen for patients with polypoidal choroidal vasculopathy (PCV). In this study, we aimed to assess the comparative safety and efficacy of different treatment regimens of anti-VEGF monotherapy for PCV. Methods: We conducted a systematic literature search on Ovid MEDLINE, EMBASE, and Cochrane Library from January 2000 to May 2023 for comparative articles reporting on different treatment regimens of anti-VEGF agents in PCV. Our primary outcomes were the final best-corrected visual acuity (BCVA) and the change in BCVA from baseline. Secondary outcomes were the final retinal thickness (RT), the change in RT from baseline, the rate of polyp closure, and the incidence of adverse events. Results: A total of 10,440 studies were screened and seven studies reporting on 636 eyes with PCV at baseline were included in this systematic review. One RCT of 53 eyes found a similar final BCVA, change in BCVA from baseline, final RT, and complete polyp closure rate between a T&E regimen and a bimonthly fixed dosing regimen of aflibercept. This trial also found superiority of T&E for change in RT from baseline. One observational study of 33 eyes found a similar BCVA at last study observation between a pro-re-nata (PRN) regimen and bimonthly fixed dosing regimen of aflibercept. One observational study of 42 eyes found a similar change in BCVA from baseline and complete polyp closure rate between a PRN regimen and bimonthly fixed dosing regimen of aflibercept. One RCT of 249 eyes found a similar change in BCVA and RT from baseline, as well as polyp closure, between a T&E regimen and fixed 12-week dosing regimen of conbercept. One observational study of 30 eyes found a superiority of T&E aflibercept for change in BCVA and risk of polyp recurrence, compared to a PRN regimen. Discussion/Conclusion: Overall, there is a paucity of evidence comparing various treatment regimens of anti-VEGF therapy in patients with PCV. This limited evidence suggests that current treatment regimens are similarly efficacious, though T&E aflibercept achieved superior outcomes when compared to bimonthly dosing or PRN in some individual studies. Further trials are needed to confirm or refute these findings.

引言：目前尚无针对息肉样脉络膜血管病变（polypoidal choroidal vasculopathy, PCV）患者的最优抗血管内皮生长因子（anti-vascular endothelial growth factor, anti-VEGF）单药治疗方案的相关指南。本研究旨在评估不同抗VEGF单药治疗方案用于PCV患者的安全性与疗效差异。
方法：本研究于2000年1月至2023年5月期间，在Ovid MEDLINE、EMBASE及Cochrane图书馆数据库中开展系统性文献检索，筛选报道PCV患者接受不同抗VEGF药物治疗方案的对比性研究。本研究的主要结局指标为最终最佳矫正视力（best-corrected visual acuity, BCVA）及基线至末次随访的BCVA变化量；次要结局指标包括末次随访视网膜厚度（retinal thickness, RT）、基线至末次随访的RT变化量、息肉闭合率及不良事件发生率。
结果：本研究共筛选出10440篇文献，最终纳入7项研究，共包含636例基线PCV患眼。其中1项纳入53只患眼的随机对照试验（randomized controlled trial, RCT）显示，阿柏西普（aflibercept）的治疗-延长（Treat-and-Extend, T&E）方案与双月固定给药方案在最终BCVA、基线至末次随访的BCVA变化量、最终RT及完全息肉闭合率方面无显著差异；该试验同时发现，T&E方案在基线至末次随访的RT变化量上更具优势。1项纳入33只患眼的观察性研究显示，阿柏西普的按需给药（pro-re-nata, PRN）方案与双月固定给药方案在末次随访时的BCVA无显著差异。1项纳入42只患眼的观察性研究显示，阿柏西普的PRN方案与双月固定给药方案在基线至末次随访的BCVA变化量及完全息肉闭合率方面无显著差异。1项纳入249只患眼的RCT显示，康柏西普（conbercept）的T&E方案与12周固定给药方案在BCVA变化量、RT变化量及息肉闭合率方面无显著差异。1项纳入30只患眼的观察性研究显示，相较于PRN方案，阿柏西普的T&E方案在BCVA变化量及息肉复发风险方面更具优势。
讨论/结论：总体而言，目前针对PCV患者的抗VEGF治疗方案对比研究证据较为匮乏。现有有限证据表明，当前主流治疗方案的疗效总体相近，但部分单项研究显示，阿柏西普T&E方案相较于双月给药或PRN方案可获得更优结局。未来需开展更多临床试验以验证或推翻上述结论。