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.