Ocular toxicity of multiple intravitreal DHPG injections

Intravitreal 9-[2-hydroxy-1-(hydroxymethyl) ethoxymethyl] guanine (DHPG) has been advocated as an alternative mode of therapy in cytomegalovirus (CMV) retinitis in the acquired immunodeficiency syndrome (AIDS) because of toxic neutropenia which is a complication of systemic intravenous DHPG. The recommended regimen requires injection of 200 micrograms DHPG intravitreally twice a week for a period of several weeks to months to control the progression of CMV retinitis. A previous study performed to determine the safe dose of intravitreal DHPG was based on a single intravitreal dose study; it does not consider the toxicity which may arise from multiple intravitreal injections of DHPG as it is utilized in the treatment of patients with CMV retinitis. In our study, intravitreal injections of 1000, 400, 200, 100, 50, and 25 micrograms DHPG were administered weekly for a period of 5 weeks in rabbit eyes. Ocular toxicity was monitored using slit-lamp biomicroscopy, indirect ophthalmoscopy, electroretinography, and light and electron microscopy. Electroretinographic evidence of retinal toxicity was found with doses as low as 100 micrograms. Electron-micrographic studies of retinal tissue from the eyes injected with even lower doses (as low as 25 micrograms) also showed evidence of toxic vacuolization in the inner segments of the photoreceptor.