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Association of Ocular Inflammation and Rubella Virus Persistence. Importance: Metagenomic deep sequencing (MDS) demonstrates that persistent and active rubella virus (RV) infection is associated with Fuchs heterochromic iridocyclitis (FHI). Objective: To assess the utility of MDS in identifying RV infection in patients with uveitis. Design, Setting, and Participants: This case series assessed 6 patients diagnosed by MDS with RV-associated uveitis at a tertiary uveitis referral center in the United States. Exposures: Prior RV infection. Main Outcomes and Measures: Clinical examination findings, slitlamp photography, corneal confocal imaging, and infectious pathogen genome obtained from RNA sequencing. Results: Six white men (age range, 36-61 years) were diagnosed with RV-associated uveitis by MDS. Three patients exhibited iris heterochromia associated with their uveitis in classic FHI fashion. The other 3 patients had less classic FHI features and exhibited anterior vitritis. Three patients had in vivo corneal confocal microscopy, with 2 demonstrating stellate keratic precipitates in addition to endothelial infiltration, spotlike holes, and enlarged intercellular boundaries. Of these 3 patients, 1 patient exhibited polymorphism and polymegathism of the endothelial cells. Conclusions and Relevance: These findings suggest that persistent RV infection is associated with recurrent or chronic anterior or anterior-intermediate uveitis as well as corneal endothelial cell damage. Ophthalmologists should consider RV infection as a potential cause of hypertensive anterior and intermediate uveitis.