Toxicity of intravitreous ceftazidime in primate retina

Squirrel monkeys were anesthetized and given intravitreous injections of 0.1 mL of balanced salt solution containing 0 mg (two eyes), 1 mg (three eyes), 2.25 mg (three eyes), or 10 mg (three eyes) of ceftazidime, a third-generation cephalosporin that provides excellent coverage for gram-negative infections. Ophthalmoscopic examinations were performed 48 hours after the injections and results were completely normal in all eyes except for those that were injected with 10 mg of ceftazidime, all three of which showed the appearance of cystic change in the macula. The monkeys were killed and the eyes were removed and examined by light and electron microscopy. All eyes were normal by light microscopy except for those injected with 10 mg of ceftazidime, which showed disruption of photoreceptors (primarily outer segments) in the foveas with cystic changes in all three and macular holes in two of three. Electron microscopy showed mild swelling of mitochondria and perinuclear halos around photoreceptor nuclei in both control eyes and in eyes injected with 1 and 2.25 mg. An eye injected with 10 mg showed severe damage to central photoreceptor outer segments consisting of disruption of plasma membranes and accumulation of intracytoplasmic granular material. Inner segments showed mild changes and there was loss of apical microvilli of the retinal pigmented epithelium. The inner retina was normal. These data suggest that high doses of intravitreous ceftazidime show toxicity primarily to photoreceptor cells, but a dose of 2.25 mg is safe as studied in this model and can be used instead of intravitreous aminoglycosides that have a narrow therapeutic window.