Association of Anti-VEGF Therapy with Reported Ocular Adverse Events: A Global Pharmacovigilance Analysis.

Objective: Anti-vascular endothelial growth factor (VEGF) therapies have transformed the management of neovascular age-related macular degeneration, diabetic macular edema, and macular edema secondary to retinal vein occlusion (RVO). This class-wide pharmacovigilance study evaluated the disproportionality of reported ocular adverse events (AEs) among anti-VEGF agents using real-world data.

Design: A population-based, observational pharmacovigilance study.

Participants: Reports from the FDA Adverse Event Reporting System (FAERS) database (January 2004-September 2024) for individuals treated with anti-VEGF agents.

Methods: Ocular AEs were identified from FAERS, and disproportionality was assessed by comparing each anti-VEGF agent to background reporting using reporting odds ratios (RORs, 95% CI); signals were considered significant if IC₀₂₅>0. Ranibizumab, aflibercept, brolucizumab, and faricimab were evaluated to compare ocular AE profiles amongst agents.

Main outcome measures: Disproportionality of reported ocular AEs among anti-VEGF agents.

Results: Across included patients receiving anti-VEGF agents with ocular AEs, most were female and aged 65-85 years. When comparing intraocular inflammation (IOI) signals across anti-VEGF agents, the strongest association was observed with brolucizumab (ROR=633.32), followed by faricimab (ROR=156.44), aflibercept (ROR=51.29), and ranibizumab (ROR=16.90). Faricimab was notably associated with elevated disproportionality signals for reports of anterior segment inflammation, including anterior chamber flare (ROR=270.95), unspecified anterior chamber inflammation (ROR=226.28), iridocyclitis (ROR=214.60), and iritis (ROR=88.90). For posterior segment involvement, increased reporting of vitritis was observed with brolucizumab (ROR=1769.33), faricimab (ROR=466.99), aflibercept (ROR=165.31), and ranibizumab (ROR=56.67), Rare but clinically significant complications were reported across all agents, including for reports of endophthalmitis (aflibercept ROR=208.88, ranibizumab ROR=114.69, faricimab ROR=99.75, brolucizumab ROR=56.15), non-infectious endophthalmitis (aflibercept, ROR=846.11, 244.42 for brolucizumab, 65.45 for ranibizumab, and 59.08 for faricimab), and pseudoendophthalmitis, which showed the strongest signal with faricimab (ROR=262.31; all 95%CI=29.37-649.50, P<0.0001, IC₀₂₅>0). Faricimab also demonstrated increased reporting of retinal vascular inflammation but showed comparatively lower signals for non-inflammatory occlusive events and other serious ocular complications relative to other anti-VEGF agents.

Conclusions: This global pharmacovigilance study revealed variability in ocular AE reporting across anti-VEGF agents. Brolucizumab showed the strongest signal for intraocular inflammation, while aflibercept showed the highest signal for endophthalmitis. Continued real-world monitoring is warranted to define evolving safety profiles across anti-VEGF agents.