Clinical Features and Prognostic Factors of Acute Retinal Necrosis Secondary to Varicella Zoster Virus versus Herpes Simplex Virus: A Comparative Retrospective Cohort Study

<title>Abstract</title> <p>Background To compare the demographic characteristics, clinical presentation, management, visual outcomes, and complications of polymerase chain reaction (PCR)-confirmed acute retinal necrosis (ARN) caused by varicella zoster virus (VZV) and herpes simplex virus (HSV), and to identify prognostic factors associated with retinal detachment (RD) and poor visual outcome. Design: Retrospective multicenter comparative cohort study. Methods Adult patients (≥ 18 years) with PCR-confirmed ARN caused by VZV, HSV-1, or HSV-2 who presented to two tertiary ophthalmic referral centers in Saudi Arabia between January 2015 and June 2025 were included. Demographic characteristics, clinical presentation, treatment, visual outcomes, and ocular complications were compared between the VZV and HSV groups. Multivariable logistic regression was performed to identify independent predictors of RD and poor final visual outcome. Results Twenty-seven patients with PCR-confirmed ARN were included, comprising 12 patients with VZV and 15 with HSV infection. Compared with patients who had VZV-associated ARN, those with HSV-associated disease presented with significantly worse visual acuity (1.52 ± 1.00 vs. 0.67 ± 0.68 LogMAR; P = 0.027) and a higher incidence of RD (80.0% vs. 33.3%; P = 0.022). Visual acuity remained significantly poorer in the HSV group during the first three months of follow-up. Mutton-fat keratic precipitates and cystoid macular edema were more common in VZV-associated disease, whereas rapid retinal lesion progression occurred more frequently in HSV-associated ARN. On multivariable analysis, greater retinitis extent was the only independent predictor of RD (OR 4.87; 95% CI 1.49–37.26; P = 0.043), while poorer presenting visual acuity (OR 7.00; 95% CI 1.48–78.16; P = 0.043) and RD (OR 25.14; 95% CI 2.39–721.24; P = 0.019) independently predicted poor final visual outcome. Conclusions HSV-associated ARN presented with poorer visual acuity and a substantially higher incidence of RD than VZV-associated disease. However, retinitis extent, rather than viral subtype, was the only independent predictor of RD, while presenting visual acuity and RD independently predicted poor final visual outcome. These findings suggest that disease severity at presentation, rather than viral etiology alone, is the principal determinant of prognosis and underscore the importance of early diagnosis, careful assessment of retinitis extent, and close surveillance of patients at high risk for RD.</p>