OCULAR TOXICITY OF 2',3'-DIDEOXYINOSINE

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This project, "Ocular toxicity of 2',3'-Dideoxyinosine (ddI)", was previous listed in the Laboratory of Immunology but is now a project in the Clinical Branch. ddI is a purine analog with antiretroviral activity currently used to treat patients with the acquired immunodeficiency syndrome (AIDS), both adults and children, in clinical protocols at the NIH. The purpose of this study is to prospectively follow patients treated with ddI for the development of ocular complications secondary to drug toxicity. Ninety-fiv children with symptomatic (CDC class P-2) HIV infection were enrolled in a Phase I-II study to assess the safety and antiretroviral activity of ddI. More than 100 children treated with ddI have been examined, and 6 children have developed peripheral atrophy of the retinal pigment epithelium during ddI therapy. Eyes with ddI-associated retinal lesions have now been examined histologically. Microscopic examination of these lesions revealed multiple areas of retinal pigment epithelial (RPE) loss, some surrounded by areas of hypertrophy or hypopigmentation of the RPE. Partial loss of the choriocapillaris and neurosensory retina were also noted in areas of diseas RPE. Transmission electron microscopy showed numerous membranous lamellar inclusions and cytoplasmic bodies in the RPE cells. These data sh that didanosine primarily affects the RPE and that the choriocapillaris and overlying neurosensory retina are also dystrophic in areas of RPE loss. We also continue to follow a group of 75 adults treated with ddI with periodic fundus examinations and electrooculograms. One adult previously developed retinal lesions while treated with ddI, but no additional adult patients ha developed retinal lesions.