探讨法瑞西单抗治疗湿性年龄相关性黄斑变性（nAMD）合并视网膜色素上皮脱离（PED）的疗效及对血清miR-125b、HIF-1α的影响。方法：选取2024年1月～2024年12月我院收治的100例nAMD合并PED患者为研究对象进行单中心随机对照研究，通过随机数字表法将所有患者分为法瑞西单抗组（50例，50眼）和雷珠单抗组（50例，50眼）。雷珠单抗组采用标准3+PRN治疗方案，法瑞西单抗组采用6 mg 每4周共4次+延长治疗方案。随后记录治疗随访期间两组患者的药物注射频率、视力改善情况（BCVA）、视网膜厚度变化（CMT）、视觉电生理变化（FERG a波、b波）、眼压变化、血清miR-125b、HIF-1α表达及不良反应情况。结果：雷珠单抗组和法瑞西单抗组患者在核心治疗期内的注药次数分别固定为3.00和4.00次。延长治疗至9个月时雷珠单抗组和法瑞西单抗组患者的平均注药次数分别为6.35±1.75、5.12±1.03次，差异显著（t=4.283，P＜0.05）；两组患者注药前、注药1、3、6、9 mo时的BCVA在时间效应上显著，而在组间和交互效应上均不显著（F时间/组间/交互=71.47/0.700/0.160，P时间/组间/交互=0.001/0.403/0.959）；患者的CMT在时间、组间和交互效应均显著（F时间/组间/交互=115.865/13.322/2.824，P时间/组间/交=0.001/0.001/0.025）；患者眼压在时间和组间上的效应均显著，而交互效应不显著（F时间/组间/交互=11.784/15.176/1.824，P时间/组间/交互=0.001/0.001/0.123）；FERG a波、b波注药后的潜时均显著降低（P＜0.05），组间比较差异不显著（P＞0.05），FERG a波、b波注药后的振幅均显著升高（P＜0.05），组间比较差异均显著（P＜0.05）;两组患者注药前miR-125b和HIF-1α表达差异均不显著（P＞0.05），注药9 mo后miR-125b表达显著增加，HIF-1α表达显著降低（均P＜0.05），其中法瑞西单抗组较雷珠单抗组的增加或降低趋势更显著（P＜0.05）；随访期间两组患者不良反应情况比较，差异无统计学意义（χ2=0.444，P=0.505）。结论：与雷珠单抗3+PRN治疗方案对比，法瑞西单抗通过固定+延迟治疗方案能够在保持较高疗效的情况下减少药物的注射次数，显著改善PED解剖结构和视力预后，并能够影响缺氧信号通路miR-125b/HIF-1α轴的表达水平，为nAMD个体化治疗提供新的思路。

Objective: To explore the efficacy of faricimab in the treatment of Neovascular age-related macular degeneration (nAMD) complicated with pigment epithelial detachment (PED) and its effects on serum miR-125b and hypoxia-inducible factor-1α (HIF-1α). Methods: A total of 100 patients with nAMD complicated with PED admitted to our hospital from January 2024 to December 2024 were selected as the research subjects for a single-center randomized controlled study. All patients were divided into the faricimab group (50 cases, 50 eyes) and the ranibizumab group (50 cases, 50 eyes) by the random number table method. The ranibizumab group adopted the standard 3+PRN treatment regimen, and the faricimab group adopted the treatment regimen of 6 mg every 4 weeks for 4 times followed by an extended treatment. Subsequently, the drug injection frequency, visual acuity improvement (best corrected visual acuity, BCVA), changes in central macular thickness (CMT), changes in electroretinogram (FERG a-wave and b-wave), changes in intraocular pressure, expressions of serum miR-125b and HIF-1α, and adverse reactions of the two groups of patients during the treatment follow-up period were recorded. Results: The number of drug injections in the ranibizumab group and the faricimab group during the core treatment period was fixed at 3.00 and 4.00 times, respectively. When the treatment was extended to 9 months, the average number of drug injections in the ranibizumab group and the faricimab group was 6.35±1.75 and 5.12±1.03 times, respectively, with a significant difference (t= 4.283, P < 0.05). There was a significant time effect on BCVA of the two groups of patients before injection and at 1, 3, 6, and 9 months after injection, while there was no significant difference in the inter-group and interaction effects (Ftime/inter-group/interaction= 71.47/0.700/0.160, Ptime/inter-group/interaction= 0.001/0.403/0.959). There were significant effects of time, inter-group, and interaction on the CMT of patients (Ftime/inter-group/interaction = 115.865/13.322/2.824, Ptime/inter-group/interaction=0.001/0.001/0.025). There were significant effects of time and inter-group on the intraocular pressure of patients, while the interaction effect was not significant (Ftime/inter-group/interaction=11.784/15.176/1.824, Ptime/inter-group/interaction=0.001/0.001/0.123). The latencies of FERG a-wave and b-wave after injection were significantly decreased (P < 0.05), and there was no significant difference between the groups (P > 0.05). The amplitudes of FERG a-wave and b-wave after injection were significantly increased (P < 0.05), and there were significant differences between the groups (P < 0.05). There were no significant differences in the expressions of miR-125b and HIF-1α between the two groups of patients before injection (P > 0.05). The expression of miR-125b was significantly increased and the expression of HIF-1α was significantly decreased 9 months after injection (both P < 0.05), and the increasing or decreasing trend in the faricimab group was more significant than that in the ranibizumab group (P < 0.05). There was no significant difference in the adverse reactions between the two groups of patients during the follow-up period (χ2=0.444, P=0.505). Conclusion: Compared with the 3+PRN treatment regimen of ranibizumab, the fixed + delayed treatment regimen of faricimab can reduce the number of drug injections while maintaining high efficacy, significantly improve the anatomical structure of PED and visual prognosis, and affect the expression levels of the miR-125b/HIF-1α axis in the hypoxia signaling pathway, providing new ideas for the individualized treatment of nAMD.

2021年度黑龙江省省属高等学校基本科研业务费科研项目（2021-KYYWF-00492）