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      PCR with the Aqueous Humor, Blood Leukocytes and Vitreous of Patients Affected by Cytomegalovirus Retinitis and Immune Recovery Uveitis

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          Purpose: To detect the cytomegalovirus (CMV) genome by PCR in the aqueous humor, blood leukocytes and vitreous of patients affected by retinitis and immune recovery uveitis (IRU). Methods: A PCR for CMV genome detection was carried out with the aqueous humor, vitreous and blood leukocytes of 54 patients with retinitis, including 25 HIV-infected patients presenting CMV retinitis in different stages (active lesion 6 cases, healed lesion 14 cases and IRU 5 cases), and 29 non-HIV-infected patients (retinitis unrelated to CMV) as negative controls. Results: The CMV genome was detected in the vitreous, aqueous humor and blood leukocytes of 3 out of 6 HIV-infected patients, presenting active lesions in the retina. No CMV genome was detected in the vitreous, aqueous humor and blood leukocytes of the 5 HIV-infected patients presenting IRU. Conclusions: CMV genome detection by PCR in aqueous humor could be used as a specific and highly predictive technique for confirmation of this infection in the retina. The absence of CMV, based on the results of PCR done in clinical samples of the 5 IRU cases, does not confirm the hypothesis of a viral replication in the vitreous body and aqueous humor of these patients.

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          Cytomegalovirus (CMV) viraemia detected by polymerase chain reaction identifies a group of HIV-positive patients at high risk of CMV disease.

          Cytomegalovirus (CMV) disease is a major cause of morbidity in patients with HIV infection. Despite treatment, CMV retinitis causes substantial visual loss, especially in patients with CD4 cell counts below 50 x 10(6)/l. Although routine ophthalmological screening of these patients has been recommended, no controlled trials have evaluated how frequently it should be performed. The aim of this study was to assess whether CMV polymerase chain reaction (PCR) results could direct ophthalmological screening to patients at high risk of CMV retinitis. In a prospective study of HIV-positive patients with CD4 cell counts below 50 x 10(6)/l, CMV viraemia was detected by qualitative PCR of whole blood. Patients who were CMV PCR-viraemic were allocated to monthly virological and ophthalmological follow-up; patients who were PCR-negative received 3-monthly virological and ophthalmological follow-up. CMV viral load was determined in all CMV-positive samples using a quantitative competitive PCR. Nineteen out of 97 patients developed CMV disease over the first 12 months of the study. Sixteen (59%) out of 27 patients who were CMV-positive developed disease compared with three (4%) out of 70 of patients who were PCR-negative (P = 0.0001). A positive CMV PCR result was significantly associated with the development of disease (P = 0.0001), with a relative hazard of 20.15 [95% confidence interval (CI), 5.80-69.98]. Median CMV viral load was significantly higher in those individuals who went on to develop CMV disease (P = 0.02). In PCR-positive patients, each 0.25 log10 increase in viral load increased the risk of disease (relative hazard, 1.37; 95% CI, 1.15-1.63; P = 0.0004). CMV PCR predicts the development of CMV disease and can be used to target ophthalmological resources to those patients at highest risk of retinitis. Asymptomatic patients who are PCR-positive represent a high-risk group in whom controlled trials of pre-emptive therapy could be conducted.
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            Long-term posterior and anterior segment complications of immune recovery uveitis associated with cytomegalovirus retinitis.

            To identify and describe long-term posterior and anterior segment complications of immune recovery uveitis in patients with inactive cytomegalovirus retinitis who are undergoing highly active antiretroviral therapy-mediated recovery of immune function. A prospective cohort study at a university medical center. Twenty-nine eyes of 21 patients with immune recovery uveitis and inactive cytomegalovirus retinitis were followed for 14.5 to 116 weeks (median, 43 weeks) after diagnosis of immune recovery uveitis. Nine eyes of nine patients developed visually important complications involving the posterior segment, anterior segment, or a combination of both. Posterior segment complications included severe proliferative vitreoretinopathy in three eyes and spontaneous vitreous hemorrhage from avulsion of a blood vessel secondary to contraction of the inflamed vitreous in one eye. Proliferative vitreoretinopathy recurred in all cases after surgery, severely compromising the visual outcome. Anterior segment complications included posterior subcapsular cataracts with vision decrease in five eyes and persistent anterior chamber inflammation after cataract extraction, resulting in posterior synechiae and large visually important lens deposits in three eyes. Persistent inflammation in immune recovery uveitis may lead to vision-threatening complications, such as proliferative vitreoretinopathy, posterior subcapsular cataracts, and severe postoperative inflammation. Immune recovery uveitis is a chronic inflammatory syndrome that may result in complications months to years after the onset of inflammation.
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              Characteristics of patients with cytomegalovirus retinitis in the era of highly active antiretroviral therapy21For the Studies of Ocular Complications of AIDS Research Group.22Conflict of interest: Statements on file with the SOCA Coordinating Center, The Johns Hopkins University School of Hygiene and Public Health.


                Author and article information

                S. Karger AG
                February 2004
                22 December 2003
                : 218
                : 1
                : 43-48
                Departments of aOphthalmology and bVirology, São Paulo University, Ribeirão Preto, and cDepartment of Uveitis, Minas Gerais Federal University, Belo Horizonte, Brazil
                74566 Ophthalmologica 2004;218:43–48
                © 2004 S. Karger AG, Basel

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                Figures: 1, Tables: 4, References: 16, Pages: 6
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