BackgroundImmune checkpoint inhibitors (ICIs) can cause rare but potentially vision-threatening optic nerve toxicity. This study aimed to characterize ICI-associated optic nerve toxicity using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS).MethodsFAERS reports from the first quarter of 2004 to the second quarter of 2025 were screened for optic nerve toxicity associated with five ICIs: pembrolizumab, nivolumab, atezolizumab, durvalumab, and ipilimumab. Baseline characteristics, temporal trends, disproportionality signals, time-to-onset patterns, and potential associated factors were analyzed.ResultsA total of 53,522 pembrolizumab-related, 67,178 nivolumab-related, 23,394 atezolizumab-related, 13,246 durvalumab-related, and 18,488 ipilimumab-related reports were included. Optic nerve toxicity was reported mainly in middle-aged and older adults, with the United States contributing most reports. In recent years, the number of relevant reports showed an increasing trend. Disproportionality analysis detected significant signals for optic nerve toxicity and related optic nerve events. Time-to-onset analysis revealed that all five ICIs exhibited a “wear-out failure” pattern, suggesting that the reporting probability of optic nerve-related adverse events might increase gradually with prolonged exposure. Age was the most important feature, followed by sex. Among concomitant medications, gabapentin showed a relatively strong association; among comorbidities, erosive gastritis and hypophysitis were more commonly reported.ConclusionThis FAERS-based pharmacovigilance study identified optic nerve toxicity as a clinically relevant adverse event associated with five ICIs. Age and sex were key associated factors. These findings support closer ophthalmic monitoring during ICI therapy.