Abstract

Purpose: To evaluate whether immune checkpoint inhibitors (ICIs), which modulate T-cell activity in cancer therapy, influence the risk of developing age-related macular degeneration (AMD).

Design: Retrospective cohort study.

Participants: Adults aged ≥60 years with a history of cancer, identified from the TriNetX Global Collaborative Network. Only patients who remained alive throughout the follow-up period were included.

Methods: Two cohorts were constructed: patients who received ICIs and those who did not. Sub-analyses were conducted for patients with melanoma and for those with metastatic disease. Propensity score matching (1:1) was performed using demographic and clinical covariates. Kaplan-Meier estimates and Cox proportional hazards models assessed the association between ICI exposure and AMD incidence over 5 years.

Main outcome measures: Incidence of non-neovascular and neovascular AMD after ICI therapy.

Results: After matching, 36,037 patients were included in each cohort. ICI-treated patients had a significantly lower risk of developing non-neovascular AMD (hazard ratio [HR], 0.77; 95% CI, [0.63, 0.93]; log-rank P = .0084) over a 5-year follow-up. No significant association was observed between ICI exposure and neovascular AMD. The protective association persisted in melanoma and metastatic subgroups.

Conclusions: In this large, multicenter cohort, ICI therapy was associated with a reduced risk of non-neovascular AMD in older adults with cancer. These findings suggest a potential protective role of T-cell modulation in AMD pathogenesis and highlight the need for further research into the retinal effects of ICIs.