Emerging Role of Letermovir, a CMV DNA Terminase Inhibitor, in the Management of Cytomegalovirus Retinitis: Efficacy, Safety, and Treatment Outcomes

Abstract

Cytomegalovirus retinitis (CMVR), an eye infection that attacks the retina and, if untreated, can lead to irreversible vision loss. In healthy individuals with a robust immune system, CMV is often asymptomatic; 60% of the immunocompromised population in developed countries are affected while 90% of the immunocompromised population in developing countries are affected. CMVR is a sight-threatening condition resulting from CMV reactivation in immunocompromised individuals, including those with HIV/AIDS and transplant recipients. Conventional antivirals such as ganciclovir, valganciclovir, foscarnet, and cidofovir effectively control CMVR but are limited by toxicities such as myelosuppression and nephrotoxicity, as well as emerging drug resistance. Letermovir, a CMV terminase complex inhibitor, has emerged as a targeted alternative with a favorable safety profile and potential for prophylaxis and treatment. This review examines CMVR epidemiology, risk factors, diagnostic approaches, and current therapeutic strategies, with emphasis on letermovir. Analysis of 23 published case reports shows that combination systemic and intravitreal therapy is the standard of care, with patient outcomes varying from vision improvement to irreversible loss and complications including immune recovery uveitis and retinal detachment. Integrating letermovir into combination regimens represents a promising approach to reduce treatment-related toxicity and resistance. Further clinical trials and long-term follow-up are needed to clarify its role as a therapeutic agent.