Association Between Systemic TNF-α Inhibitor Use and Risk of Primary Open-Angle Glaucoma

To evaluate the association between systemic tumor necrosis factor-alpha (TNF-α) inhibitor use and the long-term risk of primary open angle glaucoma (POAG), and to compare glaucoma risk among users of different TNF-α inhibitors.

Retrospective, multicenter clinical cohort study.

This retrospective, multicenter cohort study compared patients ≥40 years with and without TNF-α inhibitor use (2006-2026) using data from aggregated, de-identified electronic health records across 70 U.S. health care organizations. Patients prescribed TNF-α inhibitors (adalimumab, infliximab, etanercept, certolizumab pegol, or golimumab) were propensity matched (1:1) to controls without TNF-α inhibitor exposure based on demographics and systemic indications for TNF-a. Patients with a history of uveitis and related sequelae were excluded. New POAG diagnosis, identified by ICD-10 codes within 10 years of follow-up, was assessed using Cox proportional hazards models.

Among 12,227 TNF-α inhibitor users and 1,354,651 controls, 11,915 matched pairs were analyzed (mean [SD] age 59 [10] years; 68% female). At 10 years, TNF-α inhibitor users were associated with a lower risk of POAG diagnosis compared to controls (2.0% vs. 3.3%; HR 0.70 [95% CI 0.59-0.82]; P<.001) In agent-specific analysis, adalimumab-users (n=4,962 per cohort) (HR 0.74 [0.57-0.96]) and infliximab users (n=2,134 per cohort; HR 0.68 [95% CI 0.47-0.97) were associated with a lower risk of POAG diagnosis compared to matched controls. No significant differences were observed in pairwise comparisons amongst TNF-α inhibitors.

Systemic TNF-α inhibitor use, particularly adalimumab and infliximab, was associated with a modest but significant reduction in long-term POAG risk. These findings support a potential role of TNF-α-mediated inflammation in glaucomatous neurodegeneration.