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Purpose: To demonstrate cases of anterior uveitis requiring more than one anterior chamber paracenesis to elucidate CMV as the causative etiology., Design: Retrospective chart review., Methods: Patients were seen at the Francis I. Proctor Foundation at the University of California, San Francisco between 2013 and 2024. Patients who required more than one anterior chamber paracentesis to detect CMV as the etiologic agent of their anterior uveitis were included. Number of anterior chamber paracenteses required to detect CMV, demographic and clinical features, viral load at time of positive anterior chamber paracentesis and association between topical corticosteroid use and viral load at time of positive anterior chamber paracentesis., Results: Fourteen patients required a median of 2 (range 2-4) anterior chamber paracenteses to detect CMV. Mean age was 48.2 years, and 57.1% were male. Most patients (64.3%) were born in East and Southeast Asia. All affected eyes featured ocular hypertension. Five patients (35.7%) were initially treated with systemic immunosuppression before CMV was detected. Increasing frequency of topical corticosteroid use was significantly associated with higher CMV viral loads (P < .001). Five patients (35.7%) required glaucoma surgery. In 13 patients with available data, uveitis was present for an average of 2776 days (range 23-7889 days) prior to CMV detection. Once diagnosed, most patients were treated with oral valganciclovir, with one patient transitioning to letermovir due to side effects., Conclusions: CMV anterior uveitis may be more prevalent than previously recognized and often requires multiple anterior chamber paracenteses for diagnosis. Reliance on a signle negative test may lead to misdiagnosis and inappropriate treatment. Clinicians should maintain a high index of suspicion for CMV in cases of recurrent anterior uveitis, particularly in patients of East and Southeast Asian descent. This study highlights the importance of repeated testing and appropriate antiviral treatment to prevent complications such as glaucoma., (Copyright © 2024 Elsevier Inc. All rights reserved.)