Ophthalmic Immune-Related Adverse Events in Cancer Immunotherapy: Tissue-Specific Mechanisms, Clinical Phenotypes, and Consensus-Based Management

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Authors: Yuan Zong, Mingming Yang, Jing Zhang, Yaru Zou, Zizhen Ye, Jie Deng, Wendong Gu, Kyoko Ohno‐Matsui, Koju Kamoi
Cited by: 1
References: 82

Abstract

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.

Fields of Study & Subjects

Cancer Immunotherapy and Biomarkers Ocular Oncology and Treatments Autoimmune Neurological Disorders and Treatments

Publication details

Journal / source
International Journal of Molecular Sciences
Publisher
MDPI AG
Volume
27
Issue
13
Pages
5944–5944
Publication date
1 July 2026
Language
EN