Pharmacokinetics of the ganciclovir implant in the silicone-filled eye.

ABSTRACT

PURPOSE: Ganciclovir (GCV) implants are highly effective in delaying the progression of cytomegalovirus (CMV) retinitis. Rhegmatogenous retinal detachments can occur in untreated eyes with CMV retinitis or in eyes treated with anti-CMV therapy, which may include placement of a GCV implant. The clinical management of CMV retinitis and associated retinal detachment often involves the concurrent use of silicone oil and GCV implants. The authors investigated the effect of silicone oil tamponade on intravitreal drug levels achieved with the GCV implant. METHODS: The authors performed gas compression vitrectomy in the right eyes of 29 New Zealand white rabbits. They then inserted a 5-mg GCV implant into the vitreous cavity through an inferotemporal sclerotomy. Saline (1 cc), silicone oil 0.5 cc, or silicone oil 1.0 cc was then injected into the midvitreous cavity of 9, 8, and 12 rabbits, respectively. On postoperative days 21, 42, and 70, the rabbits were killed and the right eyes were immediately collected and stored at -70 degrees C until all samples were obtained. Vitreous was then isolated and drug levels were determined by high-pressure liquid chromatography. RESULTS: Vitreous GCV levels at days 21 and 42 were similar in both the saline-filled and silicone oil-filled eyes. At day 70, GCV levels in both the saline- and silicone-filled eyes were statistically significantly lower than at day 21 (P < 0.05 for all groups). In addition, at day 70, GCV levels in the saline-filled eyes were significantly lower than in silicone-filled eyes (saline versus 0.5 cc oil, P = 0.01; saline versus 1 cc oil, P = 0.09). CONCLUSIONS: Effective GCV levels are maintained in the aqueous phase of the vitreous cavity of eyes with silicone oil tamponade. Ganciclovir levels may be maintained longer in eyes with silicone oil tamponade than in those without. These results support the use of combined GCV implants and silicone oil tamponade in patients with CMV retinitis and associated retinal detachment.