Longitudinal Association of Systemic Autoimmune Disease and Infection in Undifferentiated Uveitis: A Large Multicenter Cohort Study from the United States

PURPOSE: To determine the long-term association of systemic autoimmune disease, infection, and vitreoretinal lymphoma in patients initially diagnosed with undifferentiated uveitis, stratified by anatomical location. METHODS: Retrospective cohort study using a multicenter electronic health records database. We identified patients ≥18 years with the index diagnosis of undifferentiated uveitis. We excluded patients if they had an autoimmune, infectious, adverse drug reaction, or positive autoimmune serologic markers at baseline. We stratified patients by time (6 months, 5 years, and 15 years) and anatomical location (anterior, intermediate, and posterior/panuveitis). We estimated survival probabilities and reported cumulative incidence using a time-to-first event analysis. RESULTS: We analyzed 39 703 patients with undifferentiated uveitis at baseline. Mean age was 51 years. The cohort was predominantly female (21,894, 57%), non-Hispanic (27,915, 72%), and White (20,467, 53%). Systemic autoimmune disease demonstrated the highest cumulative incidence at 15 years (25.93%), with infectious disease being 11.61% and lymphoma approximating between 0.12% and 2.78%. Inflammatory spondyloarthropathy (SpA) showed the greatest systemic diagnosis outcome (8.62%) while herpes viruses were the predominate infectious etiologic diagnosis (8.02%). Etiologies varied by anatomy with inflammatory SpA demonstrating the greatest cumulative incidence among anterior uveitis (34.14%), multiple sclerosis displaying a high cumulative incidence among intermediate uveitis (7.23%), and lymphoma concentrating in posterior/panuveitis (0.35%-5.22%). CONCLUSION: Undifferentiated uveitis potentially carries a risk of association with systemic autoimmune disease compared to other etiologies over time. Although less frequent, infectious etiologies remain a significant presence in later diagnoses. Longitudinal monitoring is critical for the correct etiological diagnosis of uveitis.