A new large-scale study has found a significant association between the use of immune checkpoint inhibitors (ICIs) – a class of immunotherapy drugs used to treat cancer – and an increased risk of uveitis.
Published in the Canadian Journal of Ophthalmology and using data taken from a large Japanese administrative claims database, the research analyzed over 26,000 patients diagnosed with lung cancer, renal cell carcinoma, or malignant melanoma who began treatment with either ICIs or traditional chemotherapy between 2014 and 2022. The team then compared rates of uveitis and other ocular inflammatory diseases between the two groups.
The findings revealed that patients receiving ICIs had a 49 percent higher risk of developing uveitis than those treated with chemotherapy alone. The incidence rate of uveitis was 85.1 per 10,000 person-years in the ICI group, compared to 55.9 in the non-ICI group. Additionally, a composite measure including uveitis, scleritis, and optic neuropathy also trended higher in the ICI group. Notably, the increased risk was more pronounced in patients under the age of 75.
ICIs work by reactivating the body’s immune system to attack cancer cells, but this can sometimes lead to unintended inflammation in healthy tissues, including the eyes. The researchers suggest that this immune activation may interfere with the eye’s natural immune-privileged state, particularly through mechanisms involving the PD-1/PD-L1 pathway.
This study is one of the largest to date examining the ocular side effects of ICIs and provides robust, real-world evidence of their link to uveitis. While the exact mechanisms remain to be fully understood, the findings highlight the need for increased vigilance among oncologists and ophthalmologists. Patients undergoing immunotherapy should be counseled about potential eye symptoms and referred for prompt ophthalmologic evaluation if issues arise.
