Didanosine-Associated Retinal Toxicity in a Patient With a Mutation in the CRB1 Gene

Abstract

Purpose: This article describes a case of didanosine (DDI)-associated retinal toxicity in a patient with a heterozygous pathogenic variant in the CRB1 gene.

Methods: Case report.

Results: A middle-aged patient with HIV controlled on HAART therapy, and a remote 10-year year history of treatment with DDI and tenofivir, presented with external ophthalmoplegia and well-circumscribed, midperipheral patterns of bilateral pigmentary retinopathy and chorioretinal atrophy in both eyes. Genetic testing revealed a heterozygous pathogenic variant in the CRB1 gene that encodes a protein (Crumbs homolog 1) involved in regulation of cell polarity and junctions and is localized adjacent to mitochondria in the ellipsoid and myoid area.

Conclusions: This case highlights a potential role for genetic susceptibility to retinal toxicity in DDI-associated retinal toxicity. Large, prospective pharmacogenomics studies may be informative to further elucidate the role of genetic risk factors in drug-induced retinal toxicity.

Keywords: CRB1; didanosine; toxicity.

Figure 1.

Widefield color fundus photography of the (A) right and (B) left eye shows characteristic midperipheral and peripheral chorioretinal degeneration in a well-circumscribed pattern. Widefield fundus autofluorescence of the (C) right and (D) left eye shows corresponding patches of hypoautofluorescent atrophy interspersed in a diffuse pattern of mottled autofluorescence. Optical coherence tomography images of the (E) right and (F) left eye shows grade 1 epiretinal membranes in both eyes and (F) cystoid macular edema in the left eye.