Association Between Demyelinating Disease and Dry Eye Syndrome: A Matched Case-Control Study

Demyelinating disease has been associated with dry eye syndrome (DES). Current studies are limited by sample size and confounding autoimmune disorders. Neuromyelitis optica spectrum disorder (NMOSD) has not been associated with DES in a large-scale study to date.

This retrospective case-control study utilized data from the NIH's All of Us Research Database. Cases were patients with DES. Controls were identified with exact matching by birth year (±2 years), sex, race, and ethnicity. Patients with certain confounding diseases, including Sjögren's disease, were excluded. Patients with NMOSD and MS were identified, and aquaporin-4 (AQP4) testing was utilized to reclassify patients as NMOSD. Primary analysis was adjusted for exposure to DES-associated medications. A supplementary cross-sectional analysis was completed to evaluate the association in an unmatched cohort.

Cases (n = 25,789) and controls (n = 102,954) were successfully matched. After AQP4-based reclassification and exclusions, 1,065 MS patients (338 cases, 727 controls) and 36 NMOSD patients were analyzed for association with DES. MS was significantly associated with DES adjusted OR 1.61 (95% CI 1.41-1.85). Preliminary analysis also demonstrated NMOSD is associated with DES adjusted OR 3.43 (95% CI 1.74-6.77). Supplementary cross-sectional analysis supported these associations.

Both MS and NMOSD are significantly associated with DES, however the NMOSD effect size should be cautiously interpreted given the modest sample size. These findings represent the first moderate-scale epidemiological evidence linking NMOSD to DES. Our results support increased clinical awareness for DES in demyelinating disease patients. However, effect size validation is necessary in future, prospective studies.