Ophthalmic Immune-Related Adverse Events after Anti-CTLA-4 or PD-1 Therapy Recorded in the American Academy of Ophthalmology Intelligent Research in Sight Registry

Purpose Detailed study of ophthalmic immune-related adverse events (AEs), including determination of incidence and recurrence rates, is of integral importance in cancer immunotherapy to inform management and treatment guidelines. Design Retrospective registry study. Participants Patients newly diagnosed with ophthalmic immune-related AEs between January 1, 2013, and December 31, 2017, in the American Academy of Ophthalmology’s Intelligent Research in Sight (IRIS®) Registry. Methods Data were collected from electronic health records of IRIS® Registry participating ophthalmology practices. Patients with select ophthalmic immune-related AEs were identified by International Classification of Diseases diagnosis codes. The primary exposure of interest was prior initiation of immune checkpoint inhibitors (ICIs). Main Outcome Measures Incidence of ophthalmic immune-related AEs within 1 year after initiation of ICI therapy was determined. Incidence rate ratios (IRRs) were derived by comparing incidence of ophthalmic immune-related AEs after ICIs versus rates of the same ocular complications in patients not taking ICIs in the entire registry population. Rates of ophthalmic immune-related AEs in patients with a past history of ocular inflammation or other specific ophthalmic condition before initiation of ICIs were examined further. Results A total of 3123 patients who received anti-CTLA-4 or anti-programmed cell death 1 (PD-1) therapy were identified, 112 of whom demonstrated an ophthalmic immune-related AE. Incidence rates for anterior uveitis, the most common ophthalmic immune-related AE, were 8209 per 100 000 for ipilimumab (anti-CTLA-4), 2542 per 100 000 for nivolumab (anti-PD-1), 2451 per 100 000 for pembrolizumab (anti-PD-1), 5556 per 100 000 for ipilimumab plus nivolumab, and 3740 per 100 000 among all ICIs. Rates of ophthalmic immune-related AEs among patients receiving ICI therapy were higher compared with baseline rates in the general registry population (anterior uveitis IRR, 13.9; other uveitis IRR, 43.0; papilledema IRR, 38.3). Patients with a history of uveitis or other ocular inflammatory condition demonstrated high recurrence rates of ophthalmic immune-related AEs after initiating ICIs (up to 51.1%). Conclusions For patients initiating ICI therapy, early coordination with ophthalmic subspecialist care is important because rates of ophthalmic immune-related AEs are elevated compared with ocular complication rates in the entire registry population and patients with a history of prior autoimmune ocular disease are at high risk of recurrence of ocular complications.