Association between immune checkpoint inhibitors and the risk and prognosis of uveitis: a meta-analysis

Immune checkpoint inhibitors (ICIs) activate antitumor immunity by targeting immune checkpoint molecules such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed death receptor 1 (PD-1), and programmed death-ligand 1 (PD-L1). They have emerged as a key therapeutic modality for multiple malignancies. Nevertheless, excessive immune activation may trigger a spectrum of immune-related adverse events (irAEs). Though uncommon, uveitis is a sight-threatening irAEs that can result in permanent visual loss. The risk and prognostic outcomes of ICIs-associated uveitis remain poorly defined to date. Therefore, we performed this meta-analysis to systematically assess the correlation of ICIs therapy with uveitis risk and prognosis, with the goal of providing evidence-based recommendations for clinical identification and management of this ocular complication.

We searched PubMed, Embase and Web of Science for cohort studies investigating the association between ICIs therapy and uveitis risk as well as prognosis. The search period was from the database inception to March 2026. The risk of bias of the included studies was assessed with the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I). The meta-analysis was conducted using RevMan software.

In total, five studies comprising 277,790 participants were finally included. The meta-analysis revealed that ICIs therapy was associated with a significantly higher risk of uveitis (HR = 2.26, 95% CI: 1.46 - 3.51, P = 0.0003). However, no statistically significant association was observed between ICIs-associated uveitis and overall survival in the pooled analysis of two studies (HR = 0.69, 95% CI: 0.35 - 1.39, P = 0.30);this finding is based on limited evidence and should be interpreted with caution.

Current evidence indicates that ICIs therapy was associated with an increased risk of uveitis. However, existing evidence regarding the impact of ICIs-associated uveitis on overall survival is of very low certainty and associated with a high risk of bias, which precludes drawing reliable conclusions. Large-scale prospective multicenter real-world cohort studies are therefore warranted. Such studies should implement standardized ophthalmological assessments and uniform outcome definitions, systematically record anatomical subtypes and severity grades of uveitis, and clarify the relationships between these subtypes/grades and oncologic prognosis as well as systemic immune-related toxicity. Study outcomes should be reported stratified according to cancer type, and further research is required to explore biomarker-based risk prediction.

https://www.crd.york.ac.uk/PROSPERO/view/CRD420261341882, identifier CRD420261341882.