Ganciclovir resistance has been associated with mutations in the UL97 gene, which is responsible for the first phosphorylation step of ganciclovir to the active drug ganciclovir triphosphate. We are currently engaged in a prospective epidemiologic trial to determine the frequency and clinical correlations of antiviral resistance in patients with CMV retinitis. The device consists of a 6 mg pellet of ganciclovir encased within a plastic strut which is sutured to the inside of the eye. The device permits a steady-state level of intravitreous ganciclovir to be achieved which is above the ID50 for most CMV isolates. It is designed to last for six months, at which time it can be replaced or a second device can be implanted in the eye.
Most patients tolerate the surgery well under local anesthesia.
There is a temporary reduction in vision as a result of surgically induced astigmatism, which typically resolves over 4 weeks. Most importantly, the median time to relapse in a national Eye Institute sponsored trial of newly diagnosed CMV retinitis was 209 days in eyes receiving the GIOD, compared to 13 days for deferred-treatment eyes. A study sponsored by the manufacturer showed a time to relapse of 201 days, compared to 72 days in eyes of patients receiving conventional intravenous ganciclovir. Issues that remain undecided at this point include the efficacy of the GIOD in eyes in which the retinitis has already relapsed in which silicone oil has been used as part of retinal detachment repair, the long-term risks of surgical complications such as retinal detachment and infection, and cost. As with all local therapy, the GIOD works only in the eye in which it is used.