Ocular adverse events associated with immune checkpoint inhibitors: a pharmacovigilance analysis of the FAERS database.

BACKGROUND

To systematically characterize ocular adverse events (oAEs) associated with immune checkpoint inhibitors (ICIs) and to quantify their disproportionality reporting signals using real-world pharmacovigilance data.

METHODS

This retrospective pharmacovigilance study analyzed oAE reports associated with four ICI treatment regimens-anti-CTLA-4 monotherapy, anti-PD-1/L1 monotherapy, nivolumab plus ipilimumab combination therapy, and the novel nivolumab plus relatlimab combination-using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database from the first quarter of 2011 through the second quarter of 2025. Disproportionality analyses were conducted to detect potential safety signals employing three complementary metrics: reporting odds ratio (ROR), proportional reporting ratio (PRR), and information component (IC). Additional analyses included ophthalmologist-reviewed clinical grouping of uveitis subtypes, stratification by underlying tumor indication, and temporal trend assessment.

RESULTS

A total of 5,244 oAE reports associated with ICIs were identified. At the preferred term (PT) level, the strongest overall signals were predominantly inflammatory ocular conditions, including uveitis (ROR 6.04, 95% CI 5.45-6.69), scleritis (ROR 4.85, 95% CI 3.20-7.36), and optic neuritis (ROR 4.59, 95% CI 3.91-5.39). Combination therapy was associated with markedly stronger disproportionality signals; notably, the ROR for uveitis with nivolumab plus ipilimumab reached 15.44 (95% CI 13.24 to 18.00), compared with 4.37 for anti-PD-1/L1 monotherapy. The nivolumab plus relatlimab regimen showed preliminary signals for keratitis (ROR 13.82, 95% CI 3.44 to 55.61) and diplopia (ROR 9.59, 95% CI 3.07 to 29.91), though based on a very small sample (N = 18). Melanoma was disproportionately represented among uveitis-spectrum cases (53.6%), and temporal analysis revealed a declining uveitis proportion paralleling the expansion of ICI use beyond melanoma.

CONCLUSION

ICIs are strongly associated with disproportionality signals for inflammatory ocular adverse events, with substantially higher signals observed for combination therapies compared with monotherapy. These hypothesis-generating findings highlight the need for prompt ophthalmologic assessment and individualized, multidisciplinary surveillance in patients receiving ICI treatment, particularly combined regimens.