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Updated: Jul 16, 2026
Induction of Ocular Surface Inflammation and Collection of Involved Tissues
Published on: August 4, 2022
Ophthalmic Immune-Related Adverse Events in Cancer Immunotherapy: Tissue-Specific Mechanisms, Clinical Phenotypes,
Yuan Zong1, Mingming Yang1, Jing Zhang1
1Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo 113-8510, Japan.
Immune checkpoint inhibitors (ICIs) have transformed cancer therapy by restoring anti-tumor immunity, but immune activation can disrupt ocular immune homeostasis and induce ophthalmic immune-related adverse events (OirAEs). Although uncommon, OirAEs may involve nearly all ocular compartments and can cause irreversible visual impairment or interruption of effective anticancer therapy. The 2025 international consensus criteria now provide a standardized framework for defining and classifying OirAEs. This review integrates current evidence on ICI-associated ocular toxicity, with emphasis on tissue-specific immune mechanisms and their clinical implications. Blockade of the PD-1/PD-L1 and CTLA-4 pathways may impair ocular immune privilege, expand autoreactive T-cell subsets, alter cytokine and chemokine networks, and amplify autoantibody-mediated retinal injury. These processes provide a plausible framework for understanding diverse phenotypes, including uveitis, ocular surface disease, optic neuritis, orbital inflammation, ocular myopathy, and retinopathy. We also outline a mechanism-informed management approach that balances visual preservation with maintenance of systemic anti-tumor immunity. Local corticosteroid therapy, cautious systemic immunosuppression, and selected steroid-sparing biologics should be individualized according to severity, anatomical involvement, and the oncologic context. Together, these insights support a consensus-based and mechanism-informed framework for recognizing and managing OirAEs while preserving systemic anti-tumor immunity.
Immune checkpoint inhibitors (ICIs) have transformed cancer therapy by restoring anti-tumor immunity, but immune activation can disrupt ocular immune homeostasis and induce ophthalmic immune-related adverse events (OirAEs). Although uncommon, OirAEs may involve nearly all ocular compartments and can cause irreversible visual impairment or interruption of effective anticancer therapy. The 2025 international consensus criteria now provide a standardized framework for defining and classifying OirAEs. This review integrates current evidence on ICI-associated ocular toxicity, with emphasis on tissue-specific immune mechanisms and their clinical implications. Blockade of the PD-1/PD-L1 and CTLA-4 pathways may impair ocular immune privilege, expand autoreactive T-cell subsets, alter cytokine and chemokine networks, and amplify autoantibody-mediated retinal injury. These processes provide a plausible framework for understanding diverse phenotypes, including uveitis, ocular surface disease, optic neuritis, orbital inflammation, ocular myopathy, and retinopathy. We also outline a mechanism-informed management approach that balances visual preservation with maintenance of systemic anti-tumor immunity. Local corticosteroid therapy, cautious systemic immunosuppression, and selected steroid-sparing biologics should be individualized according to severity, anatomical involvement, and the oncologic context. Together, these insights support a consensus-based and mechanism-informed framework for recognizing and managing OirAEs while preserving systemic anti-tumor immunity.
