Herpesvirus Retinitis by Immune Status: Clinical Phenotypes and Predictors of Retinal Detachment and Severe Visual Impairment

Purpose To evaluate the clinical manifestations, retinal detachment (RD) patterns, treatment strategies, and visual outcomes in herpesvirus retinitis, and to identify predictors of RD and severe visual impairment. Design Retrospective longitudinal cohort study. Participants Among 1,175 patients screened for suspected viral retinitis (2013-2025), 120 patients (144 eyes) with acute retinal necrosis (ARN) or cytomegalovirus retinitis (CMVR) were included. Methods Demographic, clinical, imaging, and treatment data were reviewed. Diagnosis was based on the Standardization of Uveitis Nomenclature (SUN) classification criteria, irrespective of PCR status. Multivariable regression, generalized estimating equation modeling, Kaplan-Meier survival analysis, and Cox regression were performed to compare ARN and CMVR phenotypes and identify predictors of RD and severe visual impairment (< 20/200). PCR testing was recorded, and subgroup analyses were performed according to PCR status. Main Outcome Measures Ocular and systemic characteristics between CMVR and ARN, and risk factors for RD and severe visual impairment. Results Mean follow-up was 5.5 years. CMVR occurred mainly in patients with lymphoma (p = 0.022) and prior immunosuppressive therapy (p = 0.027), whereas ARN more commonly showed unilateral involvement (p = 0.012), peripheral necrosis (B = 1.91, p = 0.046), and a more fulminant course (B = -0.06, p < 0.001). RD developed earlier and more frequently in ARN (log-rank p < 0.001). In multivariable Cox analysis, ARN (HR 11.52, 95% CI 1.93,68.86, p = 0.007) and worse baseline visual acuity (HR 2.06, 95% CI 1.23, 3.44, p = 0.006) were independently associated with increased risk of RD. Surgical intervention (B = -2.50, 95% CI -4.72, -0.20, p = 0.033) and concurrent RD (B = -1.28, 95% CI -2.55, -0.02, p = 0.047) were independently associated with lower odds of severe visual impairment. PCR-based subgroup analyses showed broadly similar clinical and outcome patterns. Conclusions Host immune status was associated with distinct clinical phenotypes and outcome patterns in herpesvirus retinitis. CMVR occurred in immunocompromised patients and showed a more indolent course. ARN showed broader retinal involvement and earlier RD. RD timing, and surgical intervention were associated with visual outcomes. These findings highlight distinct disease patterns and may improve early recognition and management.