The Etiological Spectrum of Uveitis in the United States: A Systematic Review and Meta-Analysis.

PURPOSE: To characterize the etiologic distribution of uveitis in the United States through a systematic review and meta-analysis. METHODS: A systematic search of PubMed, Scopus, PubMed Central, and Web of Science identified U.S.-based cohort and cross-sectional studies reporting uveitis etiology. Random-effects meta-analyses pooled proportional estimates. Study quality was assessed using Newcastle-Ottawa-based tools. Included studies spanned 1987-2023, encompassing 11,146 patients across 11 tertiary referral centers and one population-based registry. RESULTS: Twelve studies were included. Undifferentiated uveitis was the most common etiology, accounting for 42.18% (95% CI 32.68-52.29%). Among non-infectious causes, HLA-B27-associated uveitis (5.65%) and sarcoidosis (4.98%) were most prevalent. Toxoplasmosis was the leading infectious cause (4.07%), followed by HSV (3.70%) and CMV (3.14%). Heterogeneity was observed, partly explained by publication era. Sensitivity analyses confirmed a significant temporal trend for undifferentiated uveitis and identified the pre-HAART era as a driver of heterogeneity in infectious etiologies. CONCLUSIONS: Undifferentiated uveitis remains the predominant diagnosis in the U.S. with HLA-B27, sarcoidosis, and toxoplasmosis representing key defined etiologies. Because these pooled estimates were derived predominantly from tertiary referral centers and a single population-based cohort, they primarily reflect the included U.S. cohorts and should be extrapolated to the general U.S. population with caution. Regional, temporal, and methodological differences contribute to heterogeneity and should be considered in clinical evaluation and research.