Ocular Surface Disease as an Immune-related Adverse Event of Immune Checkpoint Inhibitor Therapy.

PURPOSE: Ocular surface disease, encompassing scleritis, episcleritis, keratitis, and sicca syndrome, is an increasingly recognized immune-related adverse event of immune checkpoint inhibitors (ICIs), yet its pharmacovigilance profile has not been systematically characterized across all approved ICI classes. We conducted a disproportionality analysis of the FDA Adverse Event Reporting System to quantify reporting odds ratios (RORs) for ocular surface end points across the PD-1, PD-L1, CTLA-4, and LAG-3 inhibitor classes. METHODS: Adverse event reports were extracted from FDA Adverse Event Reporting System using OpenVigil 2.1 from database inception through March 2026. Disproportionality was assessed using the ROR with 95% confidence intervals for FDA-approved ICI agents. Primary end points were immune-mediated scleritis, episcleritis, sicca syndrome, and keratitis. Secondary end points included scleritis (NOS, not otherwise specified), ulcerative keratitis, dry eye, and superior limbic keratoconjunctivitis. RESULTS: The most notable signals were for immune-mediated scleritis: pembrolizumab generated an ROR of 353.57 (95% CI: 114.03-1096.33, n = 6) and nivolumab an ROR of 120.84 (95% CI: 32.71-446.40, n = 3). Sicca syndrome signals were significant for nivolumab, atezolizumab, durvalumab, and ipilimumab. Keratitis signals were significant for nivolumab, pembrolizumab, and relatlimab. Ulcerative keratitis was disproportionately reported for nivolumab and pembrolizumab. CONCLUSION: Immune-mediated scleritis generated the strongest disproportionality signal in this analysis among PD-1 inhibitors, although these estimates are based on small case counts and wide confidence intervals and should be regarded as hypothesis-generating. Sicca syndrome and keratitis were reported across multiple ICI classes, with the keratitis signals for nivolumab and pembrolizumab supported by the largest case counts. As a disproportionality analysis, this study cannot establish incidence, comparative risk, or causality; the findings support clinical vigilance and further epidemiologic study rather than definitive causal conclusions. Physicians managing ICI-treated patients should have a low threshold for ophthalmological referral when ocular symptoms arise.