Effect Modifiers and Risk Factors of Intraocular Inflammation Following Brolucizumab: A Systematic Review and Meta-analysis

To identify risk factors and effect modifiers associated with intraocular inflammation (IOI) following brolucizumab injection. Our protocol was registered on PROSPERO (CRD42022382645). We searched six electronic databases (PubMed, Scopus, Web of Science, CENTRAL, EMBASE, and Google Scholar) to retrieve all studies that reported the occurrence of IOI following brolucizumab. Data are reported as mean difference with their corresponding 95% confidence intervals. All analyses were conducted per eye, and the risk of bias was assessed using the National Health Institute tool. Our analysis included 3527 eyes of 3469 patients of 33 papers. The mean age of the patients was 74 years (SD = 10.9, Range = 62.3–80.9). There were 1793 male patients (51.7%) and 1719 female patients (49.6%). The average follow-up period was 13.9 months (SD = 9.4). The mean number of injections was 4.5 (SD = 2.9) injections per eye; 1315 (37.3%) eyes had neovascular AMD, 189 (5.4%) had diabetic macular edema, and 129 (3.7%) eyes had polypoidal choroidal vasculopathy. Post-intervention, subretinal fluid, intraretinal fluid, and pigment epithelial detachment were significantly improved (46.5–11.3% of patients, 55.7–11.3% of patients, 24.7–7.1% of patients, respectively) (<i>p</i> &lt; 0.001). Regarding visual acuity, there was an improvement with a mean difference of 0.12 (95% CI = 0.18–0.07, <i>z</i> = 4.38, <i>p</i> &lt; 0.0001, 2064 eyes). The most common reported complication is IOI (<i>n</i> = 196, 6%). IOI was observed more in the elderly (76.3 ± 9.2 years), females (66%), and after the second injection. This systematic review provides valuable insights into risk factors and effect modifiers for IOI associated with brolucizumab treatment, aiding clinicians in optimizing patient care. Future studies should prioritize prospective, long-term investigations to further elucidate the safety profile of brolucizumab and refine its use in the management of retinal and choroidal vascular diseases.

本研究旨在明确布罗利珠单抗（brolucizumab）注射后相关的眼内炎症（intraocular inflammation, IOI）危险因素及效应调节因素。本研究方案已在PROSPERO平台注册（注册号：CRD42022382645）。本研究检索了6个电子数据库（PubMed、Scopus、Web of Science、CENTRAL、EMBASE及Google Scholar），以获取所有报道布罗利珠单抗注射后眼内炎症发生情况的研究。数据以均数差及其对应的95%置信区间（95% confidence interval, 95%CI）进行汇报。所有分析均以眼为单位开展，并采用美国国立卫生研究院（National Health Institute, NHI）偏倚风险评估工具进行偏倚风险评价。本研究最终纳入33篇文献，涉及3469例患者的3527只眼。受试者平均年龄为74岁（标准差SD=10.9，年龄范围62.3~80.9岁），其中男性患者1793例（占比51.7%），女性患者1719例（占比49.6%）。平均随访时长为13.9个月（SD=9.4）。每眼平均注射次数为4.5次（SD=2.9）；1315只眼（37.3%）为新生血管性年龄相关性黄斑变性（neovascular AMD, nAMD），189只眼（5.4%）为糖尿病性黄斑水肿，129只眼（3.7%）为息肉状脉络膜血管病变。干预后，视网膜下液、视网膜内液及色素上皮脱离均得到显著改善（对应患者占比分别为46.5%~11.3%、55.7%~11.3%、24.7%~7.1%，*p*<0.001）。就视力而言，视力得到显著提升，均数差为0.12（95%CI=0.18~0.07，*z*=4.38，*p*<0.0001，纳入2064只眼）。最常见的报道并发症为眼内炎症（IOI），共196例，占比6%。眼内炎症更多见于老年患者（年龄76.3±9.2岁）、女性患者（占比66%），且多发生于第二次注射后。本系统综述明确了布罗利珠单抗治疗相关眼内炎症的危险因素及效应调节因素，可为临床医师优化患者诊疗方案提供参考。未来研究应优先开展前瞻性长期随访研究，以进一步阐明布罗利珠单抗的安全性特征，并优化其在视网膜及脉络膜血管性疾病治疗中的应用。