Risk of Incident Dry Eye Disease Among Patients With Chronic Pain Conditions

To evaluate whether chronic pain conditions (CPCs) are associated with increased risk of incident dry eye disease (DED) and prescription-requiring DED in a large electronic health record network.

Retrospective cohort study.

Adults aged 18 years or older in the TriNetX Analytics Network (2005-2025) with a qualifying ophthalmology examination and no prior DED diagnosis. The exposure cohort included patients with at least one CPC diagnosis before the index visit; controls had no CPC diagnoses before or after the index visit. After 1:1 propensity score-matching, 538 364 patients were included per cohort. A validation cohort restricted to patients with age-related cataract included 506 763 matched patients per group.

Patients were identified using ICD-10-CM, SNOMED, and CPT codes. Propensity score matching balanced demographics and comorbidities. Two outcomes were assessed at 1, 2, and 3 years after the index visit: incident DED, defined by a new diagnosis of dry eye syndrome or keratoconjunctivitis sicca not specified as Sjögren's, and prescription-requiring DED, defined by initiation of topical cyclosporine or lifitegrast. Risk ratios with 95% confidence intervals were calculated. Time-to-event analyses used Kaplan-Meier curves and multivariable Cox proportional hazards models.

Incident DED and prescription-requiring DED.

Patients with at least one CPC diagnosis had significantly higher risk of incident DED compared with controls at all follow-up intervals. At 1 year, incident DED occurred in 3.34% of the CPC cohort versus 0.72% (RR 4.64; 95% CI, 4.49-4.81; P < .0001). At 3 years, cumulative incidence increased to 7.16% versus 1.50% (RR 4.78; 95% CI, 4.66-4.89; P < .0001). Prescription-requiring DED was also more common in the CPC cohort at 3 years (0.79% vs 0.30%; RR 2.60; 95% CI, 2.45-2.75). In multivariable Cox regression, CPCs were independently associated with increased hazard of incident DED (hazard ratio 4.85; 95% CI, 4.76-4.94; P < .0001). Findings were consistent in the validation cohort.

CPCs are strongly associated with an increased risk of incident and prescription-requiring DED. These findings support consideration of CPCs as risk factors in the evaluation and management of DED and suggest that a subset of patients with DED may reflect broader pain-processing abnormalities.