ABCA4-associated retinopathy complicated by didanosine-associated retinal toxicity

ABCA4相关性视网膜病变并发地达诺辛相关性视网膜毒性

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Abstract

PURPOSE: To describe a rare case of severe central and peripheral chorioretinal atrophy in a patient with ABCA4-associated retinopathy and prior didanosine exposure. OBSERVATIONS: A 66-year-old man with a 20-year history of Stargardt disease and HIV/AIDS treated with didanosine for almost ten years in the late '90s presented with progressive bilateral visual loss and color desaturation. Best-corrected visual acuity was 20/400 in both eyes. Multimodal imaging revealed extensive retinal pigment epithelium and choroidal atrophy involving both the macula and mid-periphery, with macular thinning and structural damage confirmed on optical coherence tomography. The peripheral atrophy pattern was consistent with known didanosine toxicity, while the macular degeneration was typical of ABCA4-associated disease. Genetic testing identified three heterozygous ABCA4 variants: one pathogenic nonsense mutation, one likely pathogenic missense mutation, and one variant of uncertain significance. Segregation analysis was not possible due to lack of parental samples. CONCLUSIONS AND IMPORTANCE: This case suggests that prior mitochondrial-toxic drug exposure may exacerbate the course of inherited retinal dystrophies, producing unusually severe panretinal degeneration. Clinicians should review medication history in patients with inherited retinal diseases and consider long-term retinal monitoring even years after discontinuing potentially toxic agents.

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