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

Purpose To identify risk factors and effect modifiers associated with intraocular inflammation (IOI) following brolucizumab injection. Methods 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. Results 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) (p < 0.001). Regarding visual acuity, there was an improvement with a mean difference of 0.12 (95% CI = 0.18-0.07, z = 4.38, p < 0.0001, 2064 eyes). The most common reported complication is IOI (n = 196, 6%). IOI was observed more in the elderly (76.3 +/- 9.2 years), females (66%), and after the second injection. Conclusions 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.