Alopecia areata patients are associated with increased risk of glaucoma: a multicenter, retrospective cohort study.

Background: Alopecia areata (AA) is a T cell-mediated autoimmune disease characterized by systemic immune activation that may extend to ocular tissues. However, whether AA increases the long-term risk of glaucoma remains unclear. Methods: We conducted a multicenter retrospective cohort study using the TriNetX Global Collaborative Network, comprising over 144 million patients across 147 healthcare organizations. For cross-database validation, we additionally performed a parallel analysis in another dataset, the US collaborative network, restricting the population to patients from healthcare organizations in the United States. Adults (≥18 years) with at least two visit records and a diagnosis of AA between 2005 and 2023 were included and matched 1:1 with individuals undergoing general health examinations without an AA diagnosis. Exclusion criteria included prior glaucoma, malignancy, or death before the index date. Propensity score matching incorporated demographic, socioeconomic, and clinical factors, including hypertension, diabetes, conjunctivitis, and Sjögren syndrome. The primary endpoint was new-onset glaucoma, with additional assessment of subtypes. Stratified analyses were performed by age and sex, and sensitivity analyses applied alternative definitions, matching models, and washout periods. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated. Results: The final matched cohort included 28,966 patients with AA and 28,966 controls. During a 15-year follow-up, AA was associated with a higher risk of glaucoma (HR = 1.89; 95% CI, 1.51-2.38), consistent across models and sensitivity analyses. The risk was elevated for primary glaucoma (HR = 1.99; 95% CI, 1.10-3.62) and glaucoma-suspect states. Stratified analyses revealed stronger associations in females (HR = 1.78; 95% CI, 1.36-2.33) and older adults (≥65 years; HR = 2.76; 95% CI, 1.95-3.89). For the cross-database validation, the association remained significant in the US collaborative network, with a hazard ratio of 2.11 (95% CI, 1.72-2.59). Conclusions: AA was associated with a higher long-term risk of glaucoma across the primary, sensitivity, and cross-database analyses. However, this observational study establishes an epidemiologic association only and does not demonstrate a direct biological or immune-mediated link. Further prospective studies incorporating detailed ophthalmic examinations, longitudinal intraocular pressure measurements, retinal imaging, and systemic or ocular immune biomarkers are needed to determine whether shared inflammatory pathways contribute to this association.