Drug Rechallenge after Immune Checkpoint Inhibitor-Induced Inflammation and Optic Nerve Disorders

The aims of the study were to investigate clinical characteristics and spectrum of immune checkpoint inhibitor optic nerve disorders (ICI-OND), including ICI-optic neuritis (ICI-ON), ICI-optic disc edema (ICI-OE), ICI-optic perineuritis, and ICI-panuveitis; to understand the breadth of management options; to investigate long-term outcomes of these patients; and, importantly, to tackle the question of outcomes following rechallenge of these potentially life-preserving drug regimens.

Retrospective analysis, single-center tertiary cancer hospital. Thirty-seven eyes in twenty consecutive patients with ICI-OND treated at Memorial Sloan Kettering Cancer Center between June 16, 2019, and June 5, 2025, were included.

In 37 eyes with ICI-OND, the majority of patients had painless loss of vision (85%), bilateral involvement (70%), dyschromatopsia (59%), abnormal testing: visual field (79%), retinal nerve fiber layer optical coherence tomography (80%), and magnetic resonance imaging (56%). Time to diagnosis occurred following a median of 4.5 drug cycles and was shorter with combination ICI (two ICI's) versus monotherapy (one ICI). The 3 patients with pain all had concurrent intraocular inflammation. Following steroid treatment and ICI cessation, vision was improved in 84% of eyes, stable in 11%, and declined in 5%. Snellen lines regained was associated with baseline vision (p = 0.0002). Five patients were rechallenged, and we did not see nor detect recurrence of ICI-OND in 4 patients; 1 patient had recurrence which resolved with steroids and vision returned to baseline.

In the majority of cases, ICI-OND occurs bilaterally with painless vision decline and color vision deficits. Cessation of drug along with initiation of systemic steroids can improve vision to 20/40 or better in at least one involved eye, and although we included a smaller subset of patients, we found that ICI can be rechallenged after completion of steroids, without documented recurrence of ICI-OND in most patients.