OBJECTIVE To examine rates of submacular hemorrhage in patients undergoing anti-VEGF injections, comparing rates between specific anti-VEGF agents. DESIGN Retrospective clinical cohort study. PARTICIPANTS All patients in the database from January 2015-November 2023 with a diagnosis of neovascular age-related macular degeneration (nAMD) and accompanying submacular hemorrhage (SMH). METHODS SMH prevalence and associated anti-VEGF injection type were analyzed in 140,915 eyes (of which 9,107 had SMH) in a nationwide aggregated electronic health care database using chi-square test of proportion. Visual acuity (VA) data was assessed using 2-sample independent t-tests. The primary outcome was rate of SMH per injection type. Secondary datapoints examined were time between SMH diagnosis and last anti-VEGF injection, number of injections before SMH, treatment interval at time of SMH, VA before and at 12 months after SMH, eyes undergoing pars plana vitrectomy (PPV) within 30 days of SMH, and VA before PPV and at 12 months after PPV. RESULTS The last injection type in eyes with SMH was bevacizumab in 3,439 (37.8%) eyes, brolucizumab-dbII in 46 (0.51%) eyes, aflibercept in 3,221 (35.4%) eyes, ranibizumab in 2,246 (24.7%) eyes, and faricimab-svoa in 155 (1.7%) eyes. Rates of SMH were significantly higher (p≤0.001) for last injection with bevacizumab compared to every other injection type. Rates of SMH were significantly lower (p=0.0004) for last injection with faricimab-svoa compared to every other injection type. Patients receiving either faricimab-svoa or ranibizumab injections each had significantly shorter (mean and standard deviation (SD) 48.9 (27.9), p<0.02; mean and standard deviation (SD) 59.6 (38.2), p=0.003, respectively) mean time between SMH diagnosis and last injection than did patients undergoing any other injection. Mean VA before SMH and at 12 months after SMH did not significantly differ by injection type among all patients. The number of patients who underwent PPV were 52 (1.51%) for bevacizumab, 4 (8.7%) for brolucizumab-dbII, 58 (1.8%) for aflibercept, 41 (1.8%) for ranibizumab, and 3 (1.9%) for faricimab-svoa. Mean VA before SMH and at 12 months after SMH did not significantly differ by injection type in patients undergoing PPV. CONCLUSIONS Faricimab may be more protective than other anti-VEGF injections against SMH in patients with nAMD.

中文翻译：

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渗出性年龄相关性黄斑变性抗血管内皮生长因子注射后的黄斑下出血率。


目的 检查接受抗 VEGF 注射的患者黄斑下出血率，比较特定抗 VEGF 药物之间的发生率。设计 回顾性临床队列研究。参与者 2015 年 1 月至 2023 年 11 月数据库中的所有诊断为新生血管性年龄相关性黄斑变性 （nAMD） 和伴随黄斑下出血 （SMH） 的患者。方法 使用卡方比例检验分析全国聚合电子医疗保健数据库中 140,915 只眼睛（其中 9,107 只患有 SMH）的 SMH 患病率和相关的抗 VEGF 注射类型。使用 2 样本独立 t 检验评估视力 （VA） 数据。主要结局是每种注射类型的 SMH 发生率。检查的次要数据点是 SMH 诊断和最后一次抗 VEGF 注射之间的时间、SMH 前的注射次数、SMH 时的治疗间隔、SMH 前后 12 个月的 VA、SMH 后 30 天内接受睫状体玻璃体切除术 （PPV） 的眼睛，以及 PPV 前和 PPV 后 12 个月的 VA。结果 SMH 眼的最后注射类型是 3,439 只 （37.8%） 眼的贝伐珠单抗，46 只 （0.51%） 的眼睛使用 brolucizumab-dbII，3,221 只 （35.4%） 的眼睛使用阿柏西普，2,246 只 （24.7%） 的眼睛使用雷珠单抗，155 只 （1.7%） 的眼睛使用 faricimab-svoa。与其他注射类型相比，最后一次注射贝伐珠单抗的 SMH 发生率 （p≤0.001） 显著升高。与其他注射类型相比，最后一次 faricimab-svoa 注射的 SMH 发生率显著降低 （p=0.0004）。接受 faricimab-svoa 或雷珠单抗注射的患者均显著缩短 （平均值和标准差 （SD） 48.9 （27.9），p<0.02;平均值和标准差 （SD） 59.6 （38.2），p=0。003）SMH 诊断和最后一次注射之间的平均时间比接受任何其他注射的患者都要短。SMH 前和 SMH 后 12 个月的平均 VA 因注射类型而异，所有患者均无显著差异。接受 PPV 的患者人数为贝伐珠单抗 52 例 （1.51%），brolucizumab-dbII 4 例 （8.7%），阿柏西普 58 例 （1.8%），雷珠单抗 41 例 （1.8%），法瑞单抗-svoa 3 例 （1.9%）。在 PPV 患者中，SMH 前和 SMH 后 12 个月的平均 VA 因注射类型而异。结论 Faricimab 可能比其他抗 VEGF 注射液对 nAMD 患者 SMH 更具保护作用。