Therapeutic options for resistant cytomegalovirus retinitis

Untreated cytomegalovirus (CMV) retinitis is progressive and generally leads to blindness within 6 months. Intravenous (i.v.) therapies such as foscarnet and ganciclovir, which were the first agents approved for the treatment of CMV retinitis, are effective in suppressing CMV replication, but they delay rather than prevent reactivation of CMV infection resulting in relapse of the disease. Furthermore, studies have shown that the time between subsequent reactivations becomes shorter, with each relapse producing more serious disease that may be more difficult to manage. This clinical failure may be caused in part by drug resistance; approximately 10% of all patients receiving systemic treatment with these agents may harbor drug-resistant viral strains. With three systemic therapies (ganciclovir, foscarnet, and cidofovir) now available for the treatment of CMV retinitis, several options exist for patients who have failed therapy with one of these drugs: reinduction with the same i.v. agent, switching therapies, or combining therapies. Resistant or relapsing CMV retinitis may also be treated by local therapies such as intraocular injections of ganciclovir and foscarnet or with a sustained-release ganciclovir implant. However, local therapy is ineffective in controlling extraocular or fellow eye CMV disease. It is likely that the integration of both local and systemic therapies will be required to halt the relentless progression of this debilitating disease, particularly when clinical resistance is encountered.