Vitamin D Deficiency and Dry Eye Disease: A Retrospective Cohort Study.

Abstract

Dry eye disease (DED) is a common ocular surface disorder associated with ocular discomfort, visual disturbance, and reduced quality of life. Vitamin D has anti-inflammatory and immunomodulatory properties, and deficiency may predispose individuals to ocular surface disease. This study evaluated the association between vitamin D deficiency and incident DED. Retrospective cohort study. Adults aged ≥18 years identified from the TriNetX U.S. Collaborative Network. After 1:1 propensity score matching, 6,047,502 patients with vitamin D deficiency were compared with 6,047,502 matched controls without vitamin D deficiency. De-identified electronic health records with up to 20 years of follow-up were analyzed. Vitamin D deficiency was defined using ICD-10 code E55. Controls were patients undergoing routine medical examinations without abnormal findings (ICD-10: Z00.00). Propensity score matching was performed for age, sex, and relevant comorbidities. Time-to-event analyses were conducted using Cox proportional hazards models. Kaplan-Meier curves and log-rank tests compared cumulative incidence between cohorts. Risk ratios (RRs) and odds ratios (ORs) were calculated from end-of-follow-up incidence proportions. Incident dry eye disease, defined by ICD-10 code H04.12. DED developed in 196,639 patients (3.3%) with vitamin D deficiency and 160,141 patients (2.7%) without deficiency. Vitamin D deficiency was associated with a significantly increased risk of DED (hazard ratio [HR], 1.286; 95% CI, 1.277-1.294; p < .001). Kaplan-Meier curves demonstrated a higher cumulative incidence in the vitamin D-deficient cohort (log-rank χ² = 5590.618; p < .001). The risk ratio was 1.242 (95% CI, 1.234-1.250; p < .001), and the odds ratio was 1.250 (95% CI, 1.242-1.259; p < .001). Limitations include reliance on diagnostic coding and lack of serum vitamin D level data. Vitamin D deficiency was significantly associated with an increased risk of developing DED, with a 28.6% higher hazard compared with matched controls. These findings suggest that vitamin D deficiency may represent a modifiable risk factor for DED and support further prospective studies to evaluate the role of vitamin D supplementation in prevention and management.