Association Between Circadian Rhythm Sleep Disorder and Noninfectious Uveitis: A Retrospective Cohort Study

PURPOSE: Circadian misalignment influences ocular immune homeostasis, inflammatory signaling, and blood-retinal barrier integrity, each implicated in the pathogenesis of noninfectious uveitis (NIU). Whether clinically diagnosed circadian rhythm sleep-wake disorder (CRSD) is associated with incident NIU is unknown. This study examined that association in a large multicenter cohort. METHODS: This retrospective cohort study used the TriNetX federated network. Adults with CRSD (ICD-10 G47.2) were compared with adults who underwent polysomnography without a sleep disorder. Patients with uveitis before the index date or with causes of infectious or secondary intraocular inflammation were excluded. Multivariable Cox proportional hazards regression estimated adjusted hazard ratios (aHR) for incident anterior and composite NIU, adjusting for demographics, systemic comorbidities, corticosteroid exposure, and prior ophthalmology encounters. Major depressive disorder and appendicitis served as positive and negative control outcomes. RESULTS: The CRSD cohort included 47 323 adults and the comparator cohort 22 241 adults. CRSD was independently associated with an increased hazard of incident anterior NIU (aHR, 1.70; 95% CI, 1.11-2.61) and composite NIU (aHR, 1.84; 95% CI, 1.21-2.79). Control outcomes performed as expected, with a strong association for major depressive disorder (aHR, 2.19; 95% CI, 2.10-2.29) and no association for appendicitis (aHR, 1.12; 95% CI, 0.87-1.45). CONCLUSION: Clinically diagnosed CRSD was independently associated with an increased risk of incident NIU. These findings support a potential role for circadian dysregulation in ocular inflammatory disease and warrant prospective confirmation.