Comparative ocular adverse events across immune checkpoint and targeted therapies in melanoma: A FAERS-based pharmacovigilance analysis
Hadassah Som-Pimpong, Ronny Amamoo, Zane Wilson, Aleah J. Brokemond, Amadou Gaye, Ravirajsinh N. Jadeja, Pamela M. Martin, Menaka C. ThounaojamBackground
Immune checkpoint inhibitors (ICIs) and targeted therapies like BRAF and MEK inhibitors have improved advanced melanoma outcomes but can cause ocular adverse events that threaten vision if not caught early. While such eye issues have been noted for specific therapies, comparisons across these treatments in real-world populations are limited.
Objectives
To compare ocular adverse-event phenotypes and associated serious outcomes among ICIs, BRAF inhibitors, and MEK inhibitors in patients with melanoma using a real-world pharmacovigilance database.
Design
Retrospective pharmacovigilance study utilizing the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS).
Methods
FAERS reports from January 2018 to September 2025 analyzed for melanoma-related reports with ocular adverse events. Reports were filtered by indication and deduplicated. Drug exposures grouped into ICIs, BRAF inhibitors, and MEK inhibitors. The main analysis classified reports by the primary suspect drug, with a sensitivity analysis excluding reports with multiple agents. Ocular phenotypes and serious outcomes were assessed using reporting odds ratios (RORs), with p-values adjusted via the Benjamini-Hochberg method.
Results
A total of 31,482 melanoma-related adverse-event reports were identified, with 2,633 (8.4%) containing at least one ocular adverse event. The primary class-specific cohort included 2,463 reports, and the single-agent cohort included 705 reports. ICIs showed higher reporting of inflammatory and optic nerve events, BRAF inhibitors reported more retinal, choroid, vitreous, and visual disturbances, and MEK inhibitors reported more visual disturbances with fewer inflammatory and optic nerve events. ICIs also showed higher serious outcomes and hospitalization, while BRAF and MEK inhibitors had lower reporting of serious outcomes. The strict analysis confirmed several class-specific patterns while reducing others after excluding reports with multiple agents.
Conclusions
Ocular adverse events associated with systemic melanoma therapies demonstrate distinct and comparatively different toxicity patterns across therapeutic classes in real-world data. By directly comparing ICIs, BRAF inhibitors, and MEK inhibitors within a unified pharmacovigilance framework, this study highlights class-specific differences in both phenotype and severity, providing a foundation for mechanism-informed monitoring strategies and multidisciplinary care.