Prevalence and Long-Term Incidence of Ocular Manifestations in Sarcoidosis: A Large Nationwide Population-Based Study

Abstract

Purpose Ocular involvement causes major vision-threatening morbidity in sarcoidosis. Population-based evidence on the full ocular spectrum, long-term incidence, and organ-specific patterns remains limited.Methods Nationwide 1:1 matched case-control study with a longitudinal retrospective cohort component, using the electronic health record (EHR) database of Clalit Health Services (CHS; Israel’s largest health organization), comprising 12 076 adults matched on age and sex. We examined prevalence and post-diagnosis incidence of all five principal ocular manifestations (uveitis, optic neuritis, glaucoma, retinitis, scleritis) using multivariable logistic and Cox regression, adjusted for demographics, lifestyle, and 8 comorbidities.Results All five ocular phenotypes were significantly more prevalent in sarcoidosis, most strikingly optic neuritis (adjusted odds ratio [aOR] 10.46, 95% confidence interval [CI] 2.44–44.88, p = 0.002) and uveitis (aOR 7.15, 95% CI 5.54–9.22, p < 0.001); any ocular manifestation aOR 3.03 (p < 0.001). Over a median 11.3-year follow-up, sarcoidosis was associated with increased risk of any ocular manifestation (adjusted hazard ratio [aHR] 2.44, 95% CI 2.00–2.97) and uveitis (aHR 6.65, 95% CI 4.72–9.38, p < 0.001). Incident glaucoma was not elevated (aHR 0.90, p = 0.472), suggesting that the cross-sectional excess largely reflects prevalent disease. In an exploratory within-case analysis, cardiac involvement was associated with retinitis (adjusted OR 4.35, 95% CI 1.50–12.66, p = 0.007), based on few events (37 retinitis cases) and requiring prospective validation. This pairing was the strongest organ-ocular signal observed. Conclusion Sarcoidosis was associated with elevated prevalence of all five ocular outcomes and increased incident uveitis risk; retinitis showed a directionally elevated but imprecise estimate, whereas glaucoma risk was not increased. The exploratory cardiac-retinitis association warrants prospective evaluation.