Cytomegalovirus retinitis in diverse immunocompromised populations: clinical presentation, treatment outcomes, and prognostic factors

Background: Cytomegalovirus retinitis (CMVR) is a vision-threatening retinal infection that primarily affects severely immunocompromised individuals. Objectives: This study aimed to compare the clinical presentations, long-term visual outcomes, and predictors of visual prognosis in CMVR patients across different immunodeficiency subtypes. Design: Retrospective cohort study. Methods: This study analyzed 117 eyes from 91 patients with CMVR who were treated at a tertiary eye center between 2009 and 2024. Eyes were stratified by the underlying cause of immunosuppression into a human immunodeficiency virus (HIV)-positive group (71 eyes of 58 patients) and an HIV-negative group (46 eyes of 33 patients). The HIV-negative group included patients with hematologic malignancies, drug-induced immunosuppression (e.g., posttransplant or autoimmune therapy), solid organ transplantation, autoimmune disease, congenital immunodeficiency, and poorly controlled diabetes mellitus type 2 (DM2). Patient demographics and comprehensive ophthalmologic examination findings were recorded and compared across these subgroups. Results: The study included 91 patients (117 eyes) with a mean age of 40.1 ± 14.7 years; 62.6% were male. Of these, 58 patients (71 eyes) were HIV-positive (mean age 39.7 ± 10.9 years; 65.5% male) and 33 patients (46 eyes) were HIV-negative. Among HIV-negative patients, 19 eyes were in patients with hematologic malignancies (mean age 35.3 ± 21.1 years; 75% male), 20 eyes were in patients with drug-induced immunosuppression (mean age 38.6 ± 17.9 years; 40% male), and the remainder eyes were associated with solid organ transplant, autoimmune disease, congenital immunodeficiency, or poorly controlled DM (7 eyes). Eyes in HIV-negative patients exhibited more severe vitritis than those in HIV-positive patients (34.8% vs 19.7% with vitritis grade +2; p = 0.009). Conversely, HIV-positive patients presented with worse baseline visual acuity (mean 1.85 ± 1.14 logMAR vs 1.31 ± 1.17 logMAR; p = 0.045). Comparing the two main HIV-negative subgroups, the drug-induced immunosuppression group showed a significantly higher incidence of retinal vascular sheathing (30% vs 0% of eyes; p = 0.009), whereas the hematologic malignancy group demonstrated more cotton-wool spots (21.1% vs 0% of eyes; p = 0.030). Despite these phenotypic differences, long-term visual outcomes were similar across all groups. On multivariable regression, baseline best-corrected visual acuity (BCVA) (β = 0.527, p < 0.001) and retinal detachment (β = 0.254, p = 0.017) were independent predictors of poorer final visual acuity. Conclusion: CMV retinitis demonstrates distinct clinical phenotypes in different immunosuppressed populations. HIV-negative patients tend to show more pronounced vitritis and vasculopathic retinal features, whereas HIV-positive patients have worse baseline visual acuity. However, the long-term visual prognosis was not significantly influenced by the underlying cause of immunosuppression.