Abstract

Antiretroviral therapy has revolutionized HIV treatment with didanosine (DDI) as a pioneering drug. However, DDI has been associated with retinal toxicity, characterized by peripheral chorioretinal degeneration with macular sparing. Despite its clinical recognition, the prevalence and risk factors for didanosine-induced retinopathy are not well described. This retrospective case series analyzed 127 DDI-treated patients at Weill Cornell Medicine Department of Ophthalmology. Inclusion criteria included at least 6 months of DDI use and available ultra-widefield imaging. Patients were categorized as affected or unaffected based on retinal imaging assessed by two reviewers. The affected group was further divided into "probable" or "possible" retinopathy. Patient demographics, DDI usage characteristics, and imaging findings were analyzed with statistical comparisons drawn between affected and unaffected cohorts. Of the 127 patients, 9 (7%) showed signs of didanosine-induced retinal toxicity. On average, the affected group was older compared with the unaffected group (65.1 vs. 56.5 years, P = 0.025), with lower BMI (23.2 vs. 27.4, P = 0.04), and older at the start of the treatment (51.6 vs. 40.8 years, P = 0.026). Mild phenotypes with peripheral pigmentary changes were also identified using ultra-widefield imaging. This pioneering academic study highlighted a notable prevalence of DDI-induced retinal toxicity. Statistical analysis demonstrated age, BMI, and age at treatment initiation as potential risk factors. Ultra-widefield autofluorescence emerged as a valuable tool in detecting and delineating findings. Follow-up studies are needed to determine the necessity of regular screening for individuals on or with a history of didanosine use.

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