Foscarnet-Ganciclovir Cytomegalovirus Retinitis Trial: 5. Clinical Features of Cytomegalovirus Retinitis at Diagnosis

To examine associations of systemic and ocular characteristics with severity of cytomegalovirus (CMV) retinitis at time of diagnosis and to compare ocular characteristics of eyes with and without CMV retinitis. Eleven clinical centers, a data coordinating center, and a fundus photograph reading center participated in a randomized, controlled, multicenter clinical trial comparing foscarnet and ganciclovir as primary therapy for previously untreated CMV retinitis in 240 patients with AIDS. The systemic characteristics marginally associated with the percentage of retina affected by CMV in a patient's worse eye at diagnosis were chronic fever, weight loss, and number of HIV-related illnesses. A positive CMV blood culture at diagnosis was similarly associated with bilateral disease. Laboratory measures of disease did not correlate well with measures of CMV retinitis severity. Many eyes with CMV retinitis had no or minimal lesion hemorrhage, but most had signs of inflammation. Patients often reported visual symptoms for involved eyes. The worse eyes (the eye with lesions covering the most retinal area) of patients with bilateral disease had greater retinal involvement, more lesions, and fewer degrees of visual field than did involved eyes of patients with unilateral disease. Visual symptoms, inflammation, indolent retinitis, and hemorrhagic lesions were associated with a greater percentage of retina affected by CMV. The findings support viremia as a mechanism of spread for untreated disease. Visual symptoms and signs of ocular inflammation were indicators both of the presence of CMV retinitis and of greater extent of retinal area covered by CMV retinitis lesions

Rhegmatogenous Retinal Detachment in Patients With Cytomegalovirus Retinitis: The Foscarnet-Ganciclovir Cytomegalovirus Retinitis Trial

To determine the incidence and risk factors for rhegmatogenous retinal detachment in a population of patients with newly diagnosed cytomegalovirus retinitis. Analysis of selected baseline and time-dependent data on patients enrolled in a multicenter, prospective, randomized, controlled clinical trial of therapy with foscarnet vs ganciclovir. In 316 eyes with cytomegalovirus retinitis at baseline, the risk of rhegmatogenous retinal detachment in an eye involved by cytomegalovirus retinitis was 18.9% at 6 months (95% confidence interval [CI], 14.0% to 23.8%) and 37.9% at 1 year (95% CI, 30.5% to 45.3%). Retinal detachment was not associated with the type of anticytomegalovirus therapy (intravenous foscarnet or ganciclovir) to which the patient was assigned. Extent of retinal involvement by cytomegalovirus retinitis, higher patient age, and lower CD4+ T-cell counts were associated with an increased risk of retinal detachment; myopia was not. Retinal detachment in patients with cytomegalovirus retinitis is unrelated to the type of intravenous therapy used or to refractive error. The median time to retinal detachment in an involved eye with cytomegalovirus retinitis and free of retinal detachment at baseline was 18.2 months. Strategies to reduce the extent of retinitis and possibly the number of reactivations may reduce the incidence of retinal detachment

Incidence of cytomegalovirus retinitis in the era of highly active antiretroviral therapy

PURPOSE: To estimate the incidence of cytomegalovirus (CMV) retinitis in the era of highly active antiretroviral therapy (HAART) and to characterize the factors associated with increased risk of CMV retinitis. DESIGN: Prospective cohort study METHODS: 1600 participants with acquired immune deficiency syndrome (AIDS) but without CMV retinitis at enrollment who completed at least one follow-up visit in the Longitudinal Study of the Ocular Complications of AIDS (LSOCA) were seen every 6 months to obtain disease and treatment history, ophthalmic examination, and laboratory testing. Incidence of CMV retinitis and risk factors for incident CMV retinitis were assessed. RESULTS: The incidence rate of CMV retinitis in individuals with AIDS was 0.36/100 person years (PY) based upon 29 incident cases during 8,134 person-years of follow-up. The rate was higher for those with a CD4+ T cell count at the immediately prior visit below 50 cells/μL (3.89/100 PY, p < 0.01), whereas only one individual with a CD4+ T cell count of 50–99 cells/μL and two individuals with a CD4+ T cell count > 100 cells/μL developed CMV retinitis. Having a CD4+ T cell count below 50 cells/μL at the clinical visit prior to CMV retinitis evaluation was the single most important risk factor (HR: 136, 95% CI: 30 to 605, p < 0.0001) for developing retinitis. CONCLUSIONS: Patients with AIDS, especially those with severely compromised immune systems, remain at risk for developing CMV retinitis in the HAART era, although the incidence rate is reduced from that observed in the pre-HAART era

Association of Host Genetic Risk Factors with the Course of Cytomegalovirus Retinitis in Patients Infected with Human Immunodeficiency Virus

PURPOSE: To evaluate the effects of previously reported host genetics factors that influence cytomegalovirus (CMV) retinitis incidence, progression to acquired immune deficiency syndrome (AIDS), and efficacy of highly active antiretroviral therapy (HAART) for mortality, retinitis progression, and retinal detachment in patients with CMV retinitis and AIDS in the era of HAART. DESIGN: Prospective, multicenter, observational study. METHODS: Cox proportional hazards model based genetic association tests examined the influence of IL-10R1_S420L, CCR5-Δ32, CCR2-V64I, CCR5 promoter, and SDF-3′A polymorphisms among patients with mortality, retinitis progression, and retinal detachment. Participants were 203 European-American and 117 African-American patients with AIDS and CMV retinitis. RESULTS: European-American patients with the CCR5 +.P1.+ promoter haplotype showed increased risk for mortality (hazard ratio [HR] = 1.83; 95% confidence interval [CI]: 1.00-3.40; P = .05). Although the same haplotype also trended for increased risk for mortality in African-American patients, the result was not significant (HR = 2.28; 95% CI: 0.93-5.60; P = .07). However, this haplotype was associated with faster retinitis progression in African Americans (HR = 5.22; 95% CI: 1.54-17.71; P = .007). Increased risk of retinitis progression was also evident for African-American patients with the SDF1-3′A variant (HR = 3.89; 95% CI: 1.42-10.60; P = .008). In addition, the SDF1-3′A variant increased the retinal detachment risk in this patient group (HR = 3.05; 95% CI: 1.01-9.16; P = .05). CONCLUSION: Besides overall immune health, host genetic factors influence mortality, retinitis progression, and retinal detachment in patients with AIDS and CMV retinitis that are receiving HAART