Association between circadian rhythm sleep disorders and dry eye disease: a retrospective cohort study

To evaluate the association between Circadian Rhythm Sleep Disorders (CRSD) and the risk of developing dry eye disease (DED). Retrospective cohort study using real-world clinical data. A total of 48,356 patients aged ≥ 18 years with a diagnosis of CRSD and 24,185 controls who underwent polysomnography and were not diagnosed with CRSD were identified. Electronic health records from the TriNetX U.S. Collaborative Network were accessed in March 2025. CRSD was identified using International Classification of Diseases-10 codes (G47.2), and patients with prior DED diagnoses were excluded. Propensity score matching (PSM) was conducted to control demographic, clinical, and pharmacologic confounders. The primary outcome was the risk of DED at 1-, 3-, and 5-year post-index date. Adjusted hazard ratios (aHR) and Kaplan-Meier survival analyses were used to evaluate the associations. Following 1:1 PSM, 19,877 patients were included in each cohort. Dry eye disease alone was significantly more frequent in the CRSD group at 1 year (0.58% vs. 0.22%; adjusted hazard ratio [aHR], 2.31; 95% CI, 1.85-2.87; p < 0.001), 3 years (1.25% vs. 0.61%; aHR, 2.12; 95% CI, 1.82-2.47; p < 0.001), and 5 years (1.58% vs. 0.89%; aHR, 2.04; 95% CI, 1.78-2.33; p < 0.001). The cumulative incidence of DED or initiation of DED medication was also elevated at 1 year (1.61% vs. 1.15%; aHR, 1.36; 95% CI, 1.22-1.53, p < 0.001), 3 years (3.15% vs. 2.65%; aHR 1.19; 95% CI, 1.1-1.29; p = 0.004), and 5 years (4.11% vs. 3.43%; aHR, 1.16; 95% CI, 1.08-1.25, p < 0.001). CRSD was associated with an increased risk of DED across all time points. These findings suggest a potential link between circadian disruption and ocular surface health, but should be interpreted with caution given the observational design.