Background: Psoriasis is a chronic systemic inflammatory disease with established extra-cutaneous manifestations. While the association between uveitis and spondyloarthritis (SpA)-related disorders is well recognized, the incident risk of uveitis among broader psoriasis populations remains inadequately defined due to methodological limitations and inconsistent findings across previous studies. We aimed to estimate the incidence of uveitis in a large, nationwide population-based cohort and identify specific clinical and treatment-related predictors of ocular inflammation. Methods: This retrospective cohort study utilised electronic health records from Clalit Health Services, Israel's largest health maintenance organization (2002-2024). We identified 157,360 patients with dermatologist-confirmed psoriasis and 156,927 age- and sex-matched controls. The primary outcome was incident uveitis, with risk estimated using Cox proportional hazards models. Within the psoriasis cohort, multivariable logistic regression was employed to identify predictors of uveitis, ensuring appropriate temporal sequencing between psoriasis treatment exposure and outcome. Results: Over a median follow-up of 12.6 years, psoriasis was associated with a significantly higher risk of incident uveitis (adjusted Hazard Ratio [aHR] 1.80; 95% CI, 1.50-2.15). Stratified analysis revealed a graded risk pattern: mild psoriasis showed no increased risk (aHR 1.01; 95% CI, 0.91-1.13), whereas severe disease (aHR 1.59; 95% CI, 1.25-2.03) and concomitant SpA (aHR 2.21; 95% CI, 1.87-2.61) demonstrated markedly elevated risks. Within the psoriasis cohort, independent predictors included SpA, diabetes mellitus, systemic lupus erythematosus, and sarcoidosis. Exposure to biologics, particularly etanercept (OR 3.37; 95% CI, 2.42-4.54), was associated with higher odds of uveitis, potentially reflecting higher disease severity. Conclusions: Incident uveitis risk in psoriasis is primarily driven by the magnitude of systemic inflammatory burden, with the highest risk observed in severe disease and those with concomitant SpA. Clinicians should maintain heightened vigilance for ocular symptoms in these high-risk subgroups to ensure timely intervention.
