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Douglas A. Jabs - One of the best experts on this subject based on the ideXlab platform.
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visual field loss in patients with Cytomegalovirus Retinitis
Ophthalmology, 2011Co-Authors: Douglas A. Jabs, Jennifer E Thorne, Mark L Van Natta, Jacque L Duncan, Sunil K SrivastavaAbstract:Purpose To describe visual field (VF) loss among patients with Cytomegalovirus (CMV) Retinitis and the risk factors for such loss. Design Multicenter, prospective, observational study. Participants A total of 476 patients with AIDS and CMV Retinitis, and VF data. Methods Follow-up every 3 months with medical history, ophthalmologic examination, Goldmann visual fields, and laboratory testing. Main Outcome Measures Incidence of VF loss in eyes affected with CMV Retinitis and characteristics associated with such VF loss. Results Over a median follow-up of 4 years (range, 0.5–9 years), the incidence rates of VF loss to 75% and 50% of normal were 0.22/eye-year (EY, 95% confidence interval [CI], 0.20–0.25) and 0.08/EY (95% CI, 0.06–0.10), respectively. The observed rates were 6- to 7-fold less than those observed rates of VF loss in the era before highly active antiretroviral therapy (HAART). Decreased CD4+ T-cell count, whether measured at enrollment or over follow-up time, was associated with increased rates of VF loss for all VF outcomes in a dose-dependent fashion. Risk factors for VF loss included lower CD4+ T-cell count, CMV lesion size >25% of the total retinal area, and active CMV Retinitis after controlling for potential confounding. Highly active antiretroviral therapy use and immune recovery (CD4+ T-cell count >100 cells/μL) were associated with reduced risk of VF loss in multiple regression models. Immune recovery was statistically significantly associated with a lower risk of VF loss to 75% of normal (relative risk [RR] = 0.63; 95% CI, 0.49–0.86; P = 0.003) and to 50% of normal (RR = 0.60; 95% CI, 0.44–0.82; P = 0.001) after controlling for demographic characteristics, HIV viral load, HAART use, CMV lesion location and size, and Retinitis activity. Conclusions Cytomegalovirus Retinitis was associated with a substantial risk of incident VF loss, but the incidence is approximately 6-fold lower than that observed in the pre-HAART era. Those who have HAART-induced immune recovery have approximately 40% lower risk of VF loss for both outcomes after controlling for confounding. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.
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Cytomegalovirus Retinitis and the acquired immunodeficiency syndrome bench to bedside lxvii edward jackson memorial lecture
American Journal of Ophthalmology, 2011Co-Authors: Douglas A. JabsAbstract:Purpose To update information on Cytomegalovirus (CMV) Retinitis in patients with acquired immunodeficiency syndrome (AIDS) and to integrate information on its pathogenesis and clinical outcomes. Design Literature review. Methods Selected articles from the medical literature, particularly large epidemiologic studies, including the Johns Hopkins Cytomegalovirus Retinitis Cohort Study, the Longitudinal Study of the Ocular Complications of AIDS, and the Cytomegalovirus Retinitis and Viral Resistance Study, were reviewed. Clinical information is discussed in light of knowledge on CMV, its pathogenesis, and its interactions with human immunodeficiency virus (HIV). Results Cytomegalovirus uses several mechanisms to evade the immune system and establish latent infection in immunologically normal hosts. With immune deficiency, such as late-stage AIDS, CMV reactivates, is disseminated to the eye, and establishes a productive infection, resulting in retinal necrosis. HIV and CMV potentiate each other: CMV accelerates HIV disease, and CMV Retinitis is associated with increased mortality. Randomized clinical trials have demonstrated the efficacy of treatments for CMV Retinitis. Systemically administered treatment for CMV Retinitis decreases AIDS mortality. Highly active antiretroviral therapy (HAART) effectively suppresses HIV replication, resulting in immune recovery, which, if sufficient, controls Retinitis without anti-CMV therapy. Resistant CMV, detected in the blood, correlates with resistant virus in the eye and is associated with worse clinical outcomes, including mortality. Host factors, including host genetics and access to care, play a role in the development of CMV Retinitis. Conclusions Clinical outcomes of CMV Retinitis in patients with AIDS are dependent on characteristics of the virus and host and on HIV-CMV interactions.
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incidence of and risk factors for visual acuity loss among patients with aids and Cytomegalovirus Retinitis in the era of highly active antiretroviral therapy
Ophthalmology, 2006Co-Authors: Jennifer E Thorne, Douglas A. Jabs, John H. Kempen, Janet T Holbrook, Charles W Nichols, Curtis L MeinertAbstract:Purpose To describe the incidence of and risk factors for visual acuity loss among patients with AIDS and Cytomegalovirus (CMV) Retinitis in the era of highly active antiretroviral therapy (HAART). Design Multicenter prospective observational study. Participants Three hundred seventy-nine patients with AIDS and CMV Retinitis (494 eyes). Methods Follow-up every 3 months with medical history, ophthalmologic examination, and laboratory testing. Main Outcome Measures Incidence of visual acuity loss to 20/50 or worse, to 20/200 or worse, and of doubling of the visual angle in eyes affected with CMV Retinitis. Results Among the 494 eyes with CMV Retinitis, the baseline frequencies of visual acuity loss to 20/50 or worse and to 20/200 or worse were 29% and 15%, respectively. Over a median follow-up period of 3.1 years, the incidences of visual acuity loss to 20/50 or worse, to 20/200 or worse, and of doubling of the visual angle were 0.10/eye-year (EY), 0.06/EY, and 0.13/EY, respectively. Immune recovery was associated with a 42% reduction in vision loss to 20/50 or worse and with a 61% reduction in vision loss to 20/200 or worse after adjusting for confounding. Of the patients with immune recovery at baseline, 17% had immune recovery uveitis (IRU). In these patients, the incidence rate of 20/50 or worse vision was similar to that observed in patients without immune recovery (0.17/EY vs. 0.16/EY), but the incidence of 20/200 or worse vision was similar to that observed among patients with immune recovery (0.04/EY vs. 0.04/EY). Conclusions Cytomegalovirus Retinitis is associated with a substantial risk of incident vision loss in the era of HAART. Those who have HAART-induced immune recovery have approximately 50% lower risk of visual acuity loss. Presence of IRU at baseline attenuated the protective effect of immune recovery for moderate vision loss but not for blindness.
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hiv and Cytomegalovirus viral load and clinical outcomes in aids and Cytomegalovirus Retinitis patients monoclonal antibody Cytomegalovirus Retinitis trial
AIDS, 2002Co-Authors: Douglas A. Jabs, John H. Kempen, Adele Kaplan M Gilpin, Yuan I Min, Alejo Erice, Thomas C QuinnAbstract:Objective To determine the association of Cytomegalovirus (CMV) viremia with mortality and CMV Retinitis progression in newly diagnosed and relapsed CMV Retinitis. Design Ancillary study of a randomized, placebo-controlled, phase III clinical trial. Patients A total of 83 patients with AIDS and CMV Retinitis, enrolled during the first phase of the Monoclonal Antibody Cytomegalovirus Retinitis Trial, were administered MSL-109 or placebo as adjuvant therapy for CMV Retinitis. Main outcome measure(s) Mortality and CMV Retinitis progression. Results Treatment with MSL-109 did not predict either progression of CMV Retinitis or mortality. Detection in plasma CMV DNA at baseline predicted mortality, but CMV antigenemia did not. CMV DNA was a better predictor of mortality than a high HIV viral load. Neither CMV DNA nor antigenemia predicted the progression of CMV Retinitis. Among newly diagnosed patients, there was a decline in the proportion with detectable CMV viral load and CMV antigenemia in response to anti-CMV therapy. However, there was a rebound in CMV viral load to 25% and CMV antigenemia to 54.6% at 6 months. In relapsed patients, anti-CMV therapy was not associated with a change in the percentage with detectable CMV-DNA or CMV antigenemia over time. Conclusion In patients with AIDS and CMV Retinitis, the detection of plasma CMV DNA was associated with a higher risk of mortality than was a high HIV viral load. Anti-CMV therapy provided a transient reduction in CMV viremia in newly diagnosed but not relapsed patients with CMV Retinitis. Adjuvant therapy with MSL-109 was ineffective in clearing CMV-DNA and CMV antigen from the plasma.
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immune recovery uveitis in patients with aids and Cytomegalovirus Retinitis after highly active antiretroviral therapy
American Journal of Ophthalmology, 2000Co-Authors: Quan Dong Nguyen, John H. Kempen, James P. Dunn, Stephen G Bolton, Douglas A. JabsAbstract:Abstract PURPOSE: To estimate the incidence and describe the characteristics of immune recovery uveitis in patients with acquired immunodeficiency syndrome (AIDS) and Cytomegalovirus Retinitis treated with highly active antiretroviral therapy. METHODS: The records of all patients with AIDS and Cytomegalovirus Retinitis from 1995 to 1998 seen at the AIDS Ophthalmology Service of the Johns Hopkins Medical Institutions were reviewed. Eighty-two patients with Cytomegalovirus Retinitis treated with highly active antiretroviral therapy were identified. Thirty-three patients (40.2%) were classified as responders to highly active antiretroviral therapy, defined as an increase in CD4+ T-cell count by 50 cells/μL or more to a level of 100 cells/μL or more. RESULTS: Immune recovery uveitis occurred in six patients. Among the 33 patients with an immunologic response to highly active antiretroviral therapy, the incidence rate of immune recovery uveitis was 0.109/person-year. Ocular complications associated with immune recovery uveitis included cystoid macular edema (four patients), epiretinal membranes (two patients), and optic disk neovascularization (one patient). CONCLUSIONS: Immune recovery uveitis was uncommon in our population but may have vision-impairing complications.
William R. Freeman - One of the best experts on this subject based on the ideXlab platform.
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Immune Recovery Vitritis Associated With Inactive Cytomegalovirus Retinitis
2017Co-Authors: Marietta P. Karavellas, Careen Y. Lowder, J. Christopher Macdonald, Cesar P. Avila, William R. FreemanAbstract:Objective: To describe a syndrome of posterior segment intraocular inflammation that causes visual loss in patients with acquired immunodeficiency syndrome and Cytomegalovirus Retinitis. This syndrome was associated with immune recovery mediated by combination antiretroviral treatment including protease inhibitors. Design: A case-control study at 2 university medical centers. Participants: One hundred thirty patients with acquired immunodeficiency syndrome and Cytomegalovirus Retinitis were examined at 2 medical centers for 15 months. In addition, the medical records of 509 patients examined at 1 center for 11 years before the initiation of protease inhibitor therapy were analyzed retrospectively. Results: Five patients with symptomatic vitritis and papillitis with cystoid macular edema or epiretinal membrane formation were documented. In each patient there was inactive Cytomegalovirus Retinitis that had not caused visual decrease before the onset of inflammation. All patients had elevated CD4 + T lymphocyte levels (median increase, 86310 6 /L [86 cells/mm 3 ]) after combination treatment including protease inhibitors. Two patients with cystoid macular edema were treated with corticosteroids and had resolution of the cystoid macular edema and an increase in visual acuity without reactivation of the Retinitis. Retrospective analysis failed to disclose similar patients with intraocular inflammation in the era before the introduction of protease inhibitors. Conclusions: This newly described syndrome of posterior segment inflammation related to Cytomegalovirus Retinitis is a cause of visual morbidity in patients with acquired immunodeficiency syndrome. It is associated with increased immune competence as a result of combined antiretroviral treatment with protease inhibitors and may be amenable to corticosteroid therapy without reactivation of Retinitis. Arch Ophthalmol. 1998;116:169-175
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Immune Recovery Vitritis Associated With Inactive Cytomegalovirus Retinitis: A New Syndrome
Archives of Ophthalmology, 1998Co-Authors: Marietta P. Karavellas, Careen Y. Lowder, J. Christopher Macdonald, Cesar P. Avila, William R. FreemanAbstract:Objective To describe a syndrome of posterior segment intraocular inflammation that causes visual loss in patients with acquired immunodeficiency syndrome and Cytomegalovirus Retinitis. This syndrome was associated with immune recovery mediated by combination antiretroviral treatment including protease inhibitors. Design A case-control study at 2 university medical centers. Participants One hundred thirty patients with acquired immunodeficiency syndrome and Cytomegalovirus Retinitis were examined at 2 medical centers for 15 months. In addition, the medical records of 509 patients examined at 1 center for 11 years before the initiation of protease inhibitor therapy were analyzed retrospectively. Results Five patients with symptomatic vitritis and papillitis with cystoid macular edema or epiretinal membrane formation were documented. In each patient there was inactive Cytomegalovirus Retinitis that had not caused visual decrease before the onset of inflammation. All patients had elevated CD4 + T lymphocyte levels (median increase, 86×10 6 /L [86 cells/mm 3 ]) after combination treatment including protease inhibitors. Two patients with cystoid macular edema were treated with corticosteroids and had resolution of the cystoid macular edema and an increase in visual acuity without reactivation of the Retinitis. Retrospective analysis failed to disclose similar patients with intraocular inflammation in the era before the introduction of protease inhibitors. Conclusions This newly described syndrome of posterior segment inflammation related to Cytomegalovirus Retinitis is a cause of visual morbidity in patients with acquired immunodeficiency syndrome. It is associated with increased immune competence as a result of combined antiretroviral treatment with protease inhibitors and may be amenable to corticosteroid therapy without reactivation of Retinitis.
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intraocular pressure and aqueous humor dynamics in patients with aids treated with intravitreal cidofovir hpmpc for Cytomegalovirus Retinitis
American Journal of Ophthalmology, 1997Co-Authors: Alay S Banker, Ibrahim Taskintuna, Fernando J Arevalo, David Munguia, Firas M Rahhal, Bruce Ishimoto, Charles C Berry, Erik De Clercq, Renata Ochabski, William R. FreemanAbstract:Purpose To evaluate the decrease in intraocular pressure associated with cidofovir (1-[( S )-3-hydroxy-2-(phosphonomethoxy)propyl]cytosine dihydrate; HPMPC) intravitreal injections. Methods We followed up 97 eyes of 63 patients with acquired immunodeficiency syndrome (AIDS) who had Cytomegalovirus Retinitis and had been treated with up to nine 20-μg intravitreal cidofovir injections. Measurements were taken at baseline, between 2 and 3 weeks, and at 5 to 6 weeks after injections. Anterior chamber fluorophotometry was studied in seven eyes (four patients) before and after injections. Ciliary body anatomy was evaluated in two patients. Results After the first intravitreal injection, mean intraocular pressure was 2.2 mm Hg lower than that at baseline at 2 to 3 weeks ( P P = .0025). After the second injection, mean pressure was 2.6 mm Hg lower at 2 to 3 weeks ( P = .0013) and 1.5 mm Hg lower at 5 to 6 weeks ( P = .043). After subsequent injections, however, the decrease was less than 1 mm Hg, suggesting that a plateau had been reached. Pressure in eyes with anterior uveitis after the first injection was lower than that in eyes without anterior uveitis ( P P Conclusions Intraocular pressure decreases after the initial 20-μg cidofovir intravitreal injection. However, eyes stabilize (pressure plateaus) after three injections. Effects on the ciliary body are the main cause of the decrease after cidofovir injections.
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iritis and hypotony after treatment with intravenous cidofovir for Cytomegalovirus Retinitis
Archives of Ophthalmology, 1997Co-Authors: Janet L Davis, William R. Freeman, Ibrahim Taskintuna, David V Weinberg, William J Feuer, Robert E LeonardAbstract:Objective: To describe intraocular inflammation due to treatment with intravenous cidofovir dihydrate for Cytomegalovirus Retinitis. Design: Retrospective cohort. Setting: Three university outpatient ophthalmology clinics. Patients: All patients treated with intravenous cidofovir therapy before October 31, 1996. Intervention: Treatment with intravenous cidofovir was given according to standardized protocols. Intraocular inflammation was treated according to the best medical judgment. Main Outcome Measures: The presence of new intraocular inflammation, the severity of inflammation, visual acuity, and intraocular pressure. Results: Eleven cases of iritis (26%) occurred among 43 patients. In 6 cases, the iritis was bilateral. Patients who experienced iritis were more likely to have been previously treated for Cytomegalovirus Retinitis ( P =.03), to be diabetic ( P =.05), or to be receiving protease inhibitors ( P P =.70). The onset of iritis occurred at a mean (±SD) of 4.9±1.8 days after a cidofovir dose and after a mean (±SD) of 4.2±1.6 doses of cidofovir. Six eyes of 4 patients had hypotony. Five eyes of 5 patients had a persistent decrease in visual acuity of at least 2 Snellen lines. Conclusions: Acute intraocular inflammation may occur with or without hypotony after intravenous cidofovir therapy, similar to the reactions seen after intravitreous administration. Although the manifestations may be severe, they are manageable with topical corticosteroid therapy in most cases. Cidofovir therapy can be continued in some patients if medical necessity warrants, but recurrent inflammation or permanent hypotony may occur.
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Correlation Between CD4+ Counts and Prevalence of Cytomegalovirus Retinitis and Human Immunodeficiency Virus--related Noninfectious Retinal Vasculopathy in Patients With Acquired Immunodeficiency Syndrome
American Journal of Ophthalmology, 1993Co-Authors: Baruch D. Kuppermann, John G. Petty, Douglas D. Richman, W. Christopher Mathews, Steven C. Fullerton, Leland S. Rickman, William R. FreemanAbstract:We prospectively studied 132 patients with acquired immunodeficiency syndrome (AIDS) to determine the cross-sectional prevalence of Cytomegalovirus Retinitis. All patients had serum CD4+ lymphocyte counts to determine the degree of immune dysfunction. Correlations between CD4+ counts, the presence of Cytomegalovirus Retinitis or human immunodeficiency virus (HIV)--related noninfectious retinal vasculopathy, and ocular symptoms were made. The study disclosed that 26 of 132 patients with AIDS (20%) had Cytomegalovirus Retinitis. However, subset analysis according to CD4+ count disclosed that in patients with CD4+ counts of 50 cells/mm 3 or less, 26 of 87 (30%) had Cytomegalovirus Retinitis, whereas in patients with CD4+ counts of 50 cells/mm 3 or more, none of 45 was noted to have Cytomegalovirus Retinitis. Similarly, 46 of 132 patients (35%) were noted to have HIV-related noninfectious retinal vasculopathy, with a trend toward increasing prevalence associated with declining CD4+ count. In patients with CD4+ counts of 50 cells/mm 3 or less, 39 of 87 (45%) had HIV-related noninfectious retinal vasculopathy, whereas seven of 45 patients (16%) with CD4+ counts of 50 cells/mm 3 or more were noted to have these changes. We confirmed the clinical impression that Cytomegalovirus Retinitis and HIV-related noninfectious retinal vasculopathy are late manifestations of AIDS, demonstrated an increased risk for patients with low CD4+ counts, and suggested a basis for coherent chemoprophylaxis and screening strategies for Cytomegalovirus Retinitis.
Scott M. Whitcup - One of the best experts on this subject based on the ideXlab platform.
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High-dose intravitreal ganciclovir and foscarnet for Cytomegalovirus Retinitis.
American Journal of Ophthalmology, 2001Co-Authors: Gisela Velez, Chichao Chan, Scott M. Whitcup, Chandra Roy, Michael R RobinsonAbstract:Abstract PURPOSE: To describe the chronic use of high doses of intravitreal ganciclovir, in combination with foscarnet, for the treatment of Cytomegalovirus Retinitis. METHODS: A 31-year-old man with human immunodeficiency virus (HIV) infection and unilateral active Cytomegalovirus Retinitis was treated with escalating intravitreal injections of ganciclovir (up to 3.0 mg twice a week) in combination with foscarnet (up to 2.4 mg twice a week) over the course of approximately 1 year. RESULTS: Complete regression of the Retinitis was obtained with high doses of intravitreal ganciclovir and foscarnet. Visual acuity in the affected eye remained 20/20 throughout the course of therapy. No ganciclovir retinal toxicity was identified. CONCLUSION: High doses of intravitreal ganciclovir in combination with foscarnet can be well tolerated and may be required to successfully control Cytomegalovirus Retinitis in some patients.
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immune recovery uveitis in patients with Cytomegalovirus Retinitis taking highly active antiretroviral therapy
American Journal of Ophthalmology, 2000Co-Authors: George W Reed, Karl G Csaky, Michael A Polis, Scott M. WhitcupAbstract:Abstract PURPOSE: To investigate the clinical features associated with immune recovery in human immunodeficiency virus (HIV)–infected patients with Cytomegalovirus Retinitis who are taking highly active antiretroviral therapy. METHODS: Sixteen patients were evaluated prospectively at the National Eye Institute, Bethesda, Maryland. Evaluation included a medical history and a complete ophthalmologic examination. The examination included best-corrected visual acuity score measured by means of logarithmic charts, slit-lamp biomicroscopy, dilated retinal examination, retinal photography, and fluorescein angiography. Immune-recovery uveitis was defined as the ocular inflammation associated with clinical immune recovery in patients taking potent antiretroviral regimens. The ophthalmic characteristics of immune-recovery uveitis were identified, and their effect on visual acuity was statistically analyzed. RESULTS: The mean CD4+ T-lymphocyte count for the 16 patients taking highly active antiretroviral therapy at the time of evaluation was 393 cells/μl (range, 97–1,338 cells/μl). Immune-recovery uveitis was characterized by vitreitis and optic disk and macular edema. Clinically important complications of immune-recovery uveitis included cataract and epiretinal membrane formation. The visual acuity scores were significantly worse in the 23 eyes with Cytomegalovirus Retinitis (mean, 67.2 letters, 20/50) than in the nine eyes without Cytomegalovirus Retinitis (mean, 89.8 letters, 20/16) ( P P ≤ .001). CONCLUSIONS: Immune-recovery uveitis is an important cause of visual morbidity in HIV-infected patients with Cytomegalovirus Retinitis in the era of highly active antiretroviral therapy. Although immune recovery associated with highly active antiretroviral therapy has allowed some patients to discontinue specific antiCytomegalovirus therapy, the rejuvenated immune response can be associated with sight-threatening inflammation.
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discontinuation of maintenance therapy in patients with quiescent Cytomegalovirus Retinitis and elevated cd4 counts
Ophthalmology, 1998Co-Authors: Tamara R Vrabec, Vincent F Baldassano, Scott M. WhitcupAbstract:Abstract Objective To determine whether maintenance therapy can be discontinued safely in patients with quiescent Cytomegalovirus Retinitis (CMVR) and increased CD4+ counts after treatment with highly active antiretroviral therapy (HAART). Design A prospective observational case series. Participants Eight human immunodeficiency virus (HIV)-positive patients with quiescent CMVR who were taking HAART and had CD4+ counts above 100 cells/μl elected to discontinue anti-CMV maintenance treatment. Intervention Biweekly-to-monthly indirect ophthalmoscopy and fundus photographs, monthly-to-quarterly CD4+ counts, and quarterly HIV viral loads were ordered. Main outcome measures Twelve previously affected eyes were examined for evidence of recurrent Retinitis, which was defined as any retinal whitening, border opacification, or expansion of areas of retinal pigment epithelial (RPE) atrophy greater than 750 μm. Four previously unaffected fellow eyes were observed for new CMVR. Results There was no reactivation or progression of Retinitis in any patient during the mean follow-up interval of 11.4 months (range, 3–16 months). No previously unaffected eye developed CMVR. CD4+ remained elevated in all patients (range, 70–725; mean, 255). The HIV viral load ranged from undetectable to 139,000 copies. Conclusion Discontinuation of maintenance therapy may be considered in patients with HAART-induced elevated CD4+ counts above 100 cells/μl, prolonged relapse-free intervals during the reconstitution period before CD4+ counts rise above 100 cells/μl, and completely quiescent Retinitis characterized by RPE scarring only. Reduced risks of drug toxicity and drug-resistant organisms are potential benefits. Close observation for evidence of recurrent Retinitis is indicated.
James P. Dunn - One of the best experts on this subject based on the ideXlab platform.
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immune recovery uveitis in patients with aids and Cytomegalovirus Retinitis after highly active antiretroviral therapy
American Journal of Ophthalmology, 2000Co-Authors: Quan Dong Nguyen, John H. Kempen, James P. Dunn, Stephen G Bolton, Douglas A. JabsAbstract:Abstract PURPOSE: To estimate the incidence and describe the characteristics of immune recovery uveitis in patients with acquired immunodeficiency syndrome (AIDS) and Cytomegalovirus Retinitis treated with highly active antiretroviral therapy. METHODS: The records of all patients with AIDS and Cytomegalovirus Retinitis from 1995 to 1998 seen at the AIDS Ophthalmology Service of the Johns Hopkins Medical Institutions were reviewed. Eighty-two patients with Cytomegalovirus Retinitis treated with highly active antiretroviral therapy were identified. Thirty-three patients (40.2%) were classified as responders to highly active antiretroviral therapy, defined as an increase in CD4+ T-cell count by 50 cells/μL or more to a level of 100 cells/μL or more. RESULTS: Immune recovery uveitis occurred in six patients. Among the 33 patients with an immunologic response to highly active antiretroviral therapy, the incidence rate of immune recovery uveitis was 0.109/person-year. Ocular complications associated with immune recovery uveitis included cystoid macular edema (four patients), epiretinal membranes (two patients), and optic disk neovascularization (one patient). CONCLUSIONS: Immune recovery uveitis was uncommon in our population but may have vision-impairing complications.
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incidence of foscarnet resistance and cidofovir resistance in patients treated for Cytomegalovirus Retinitis
Antimicrobial Agents and Chemotherapy, 1998Co-Authors: Douglas A. Jabs, Michael Forman, Cheryl Enger, James P. DunnAbstract:Cytomegalovirus (CMV) Retinitis is a common opportunistic infection in patients with AIDS. With long-term therapy for CMV Retinitis, resistant CMV may develop. In a prospective study of 122 patients with CMV Retinitis, 2.4 and 0.8% of patients had foscarnet-resistant blood culture isolates (50% inhibitory concentration [IC50], >400 mM) and urine culture isolates, respectively, at diagnosis of CMV Retinitis prior to treatment, whereas 4.1 and 6.6% had cidofovir-resistant (IC50 ,> 2mM) blood and urine culture isolates, respectively. Patients were treated according to best medical judgement. Of 44 foscarnet-treated patients, 26% had a resistant blood or urine culture isolate by 6 months of treatment and 37% had a resistant isolate by 9 months; of 13 cidofovir-treated patients, 29% had a resistant blood or urine culture isolate by 3 months of therapy. The probabilities of developing foscarnet resistance while on foscarnet and developing cidofovir resistance while on cidofovir were not significantly different from that for developing ganciclovir resistance while on ganciclovir (odds ratios, 1.87 [P 5 0.19] and 2.28 [P 5 0.15], respectively). Cytomegalovirus (CMV) Retinitis is the most common intraocular infection in patients with AIDS and has been reported to affect approximately 30% of patients with AIDS (9, 10, 12). Left untreated, CMV Retinitis is a progressive disease, which spreads throughout the retina, causing total retinal destruction and blindness (12). As of November 1997, three drugs were approved by the United States Food and Drug Administration for the treatment of CMV Retinitis: ganciclovir, foscarnet, and cidofovir. All are effective, but none eliminates virus from the retina, and chronic suppressive therapy is required (10, 15, 17). The use of chronic suppressive antiviral therapy is associated with the development of resistant virus (5, 7, 13), and resistant CMV is associated with a poor response to therapy (7, 13, 14). The Cytomegalovirus Retinitis and Viral Resistance Study (8, 11, 13) is a prospective study of CMV resistance to antiviral agents. Herein we report results on the incidence of resistance to foscarnet and to cidofovir.
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immune recovery vitritis in hiv infection
JAMA, 1998Co-Authors: James P. DunnAbstract:ObjectiveTo describe a syndrome of posterior segment intraocular inflammation that causes visual loss in patients with acquired immunodeficiency syndrome and Cytomegalovirus Retinitis. This syndrome was associated with immune recovery mediated by combination antiretroviral treatment including protease inhibitors.DesignA case-control study at 2 university medical centers.ParticipantsOne hundred thirty patients with acquired immunodeficiency syndrome and Cytomegalovirus Retinitis were examined at 2 medical centers for 15 months. In addition, the medical records of 509 patients examined at 1 center for 11 years before the initiation of protease inhibitor therapy were analyzed retrospectively.ResultsFive patients with symptomatic vitritis and papillitis with cystoid macular edema or epiretinal membrane formation were documented. In each patient there was inactive Cytomegalovirus Retinitis that had not caused visual decrease before the onset of inflammation. All patients had elevated CD4+ T lymphocyte levels (median increase, 86 × 106/L [86 cells/mm3]) after combination treatment including protease inhibitors. Two patients with cystoid macular edema were treated with corticosteroids and had resolution of the cystoid macular edema and an increase in visual acuity without reactivation of the Retinitis. Retrospective analysis failed to disclose similar patients with intraocular inflammation in the era before the introduction of protease inhibitors.ConclusionsThis newly described syndrome of posterior segment inflammation related to Cytomegalovirus Retinitis is a cause of visual morbidity in patients with acquired immunodeficiency syndrome. It is associated with increased immune competence as a result of combined antiretroviral treatment with protease inhibitors and may be amenable to corticosteroid therapy without reactivation of Retinitis.
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Cytomegalovirus Retinitis and viral resistance ganciclovir resistance
The Journal of Infectious Diseases, 1998Co-Authors: Douglas A. Jabs, James P. Dunn, Cheryl Enger, Michael FormanAbstract:Cytomegalovirus (CMV) Retinitis is among the most common opportunistic infections in patients with AIDS and a substantial cause of visual loss. With long-term therapy, resistant CMV may develop. In a prospective study of 108 patients with CMV Retinitis, 80.6% of patients were found to have either a positive blood culture or positive urine culture for CMV at the diagnosis of Retinitis. At diagnosis of Retinitis, 0.9% and 2.7% of patients had a ganciclovir-resistant blood culture isolate and urine culture isolate, respectively. Of 76 patients initially treated with ganciclovir, 11.4% had a resistant blood or urine culture isolate by 6 months of treatment and 27.5% by 9 months. The development of ganciclovir resistance during follow-up correlated with the occurrence of CMV Retinitis in the contralateral eye (odds ratio = 9.06, P = .003).
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Viral Sensitivity Testing in Patients With Cytomegalovirus Retinitis Clinically Resistant to Foscarnet or Ganciclovir
American Journal of Ophthalmology, 1995Co-Authors: James P. Dunn, Michael Forman, Mathew W. Maccumber, Patricia Charache, Linda G. Apuzzo, Douglas A. JabsAbstract:Purpose Resistance to antiviral therapy is a potential cause of progression of Cytomegalovirus Retinitis in patients with the acquired immunodeficiency syndrome. We investigated the results of viral sensitivity testing in a series of patients with clinically resistant Retinitis who had positive results of blood or urine Cytomegalovirus cultures. Methods All patients with newly diagnosed Cytomegalovirus Retinitis between January 1990 and December 1991 were prospectively studied. Blood and urine cultures for Cytomegalovirus were obtained in a nonrandomized subgroup of this group. The results of in vitro sensitivity to foscarnet and ganciclovir, determined by a DNA hybridization assay, were then analyzed in seven patients with clinically resistant Cytomegalovirus Retinitis and whose blood or urine culture results, or both, were positive for Cytomegalovirus while on a treatment regimen. Results Foscarnet-resistant Cytomegalovirus (ID 50 > 300 μM) was isolated from two patients, one of whom was being treated with foscarnet. Ganciclovir-resistant Cytomegalovirus (ID 50 > 6.0 μM) was isolated from four patients, three of whom were being treated with ganciclovir. Foscarnet- and ganciclovir-resistant Cytomegalovirus occurred with previous ganciclovir therapy in one patient. Clinical improvement occurred in three patients whose change in therapy was based on viral sensitivity testing. In general, prolonged therapy with one drug was associated with a progressive increase in the ID 50 for that drug. Conclusions Viral resistance to foscarnet or ganciclovir may explain refractory Cytomegalovirus Retinitis in some patients.
John H. Kempen - One of the best experts on this subject based on the ideXlab platform.
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incidence of and risk factors for visual acuity loss among patients with aids and Cytomegalovirus Retinitis in the era of highly active antiretroviral therapy
Ophthalmology, 2006Co-Authors: Jennifer E Thorne, Douglas A. Jabs, John H. Kempen, Janet T Holbrook, Charles W Nichols, Curtis L MeinertAbstract:Purpose To describe the incidence of and risk factors for visual acuity loss among patients with AIDS and Cytomegalovirus (CMV) Retinitis in the era of highly active antiretroviral therapy (HAART). Design Multicenter prospective observational study. Participants Three hundred seventy-nine patients with AIDS and CMV Retinitis (494 eyes). Methods Follow-up every 3 months with medical history, ophthalmologic examination, and laboratory testing. Main Outcome Measures Incidence of visual acuity loss to 20/50 or worse, to 20/200 or worse, and of doubling of the visual angle in eyes affected with CMV Retinitis. Results Among the 494 eyes with CMV Retinitis, the baseline frequencies of visual acuity loss to 20/50 or worse and to 20/200 or worse were 29% and 15%, respectively. Over a median follow-up period of 3.1 years, the incidences of visual acuity loss to 20/50 or worse, to 20/200 or worse, and of doubling of the visual angle were 0.10/eye-year (EY), 0.06/EY, and 0.13/EY, respectively. Immune recovery was associated with a 42% reduction in vision loss to 20/50 or worse and with a 61% reduction in vision loss to 20/200 or worse after adjusting for confounding. Of the patients with immune recovery at baseline, 17% had immune recovery uveitis (IRU). In these patients, the incidence rate of 20/50 or worse vision was similar to that observed in patients without immune recovery (0.17/EY vs. 0.16/EY), but the incidence of 20/200 or worse vision was similar to that observed among patients with immune recovery (0.04/EY vs. 0.04/EY). Conclusions Cytomegalovirus Retinitis is associated with a substantial risk of incident vision loss in the era of HAART. Those who have HAART-induced immune recovery have approximately 50% lower risk of visual acuity loss. Presence of IRU at baseline attenuated the protective effect of immune recovery for moderate vision loss but not for blindness.
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hiv and Cytomegalovirus viral load and clinical outcomes in aids and Cytomegalovirus Retinitis patients monoclonal antibody Cytomegalovirus Retinitis trial
AIDS, 2002Co-Authors: Douglas A. Jabs, John H. Kempen, Adele Kaplan M Gilpin, Yuan I Min, Alejo Erice, Thomas C QuinnAbstract:Objective To determine the association of Cytomegalovirus (CMV) viremia with mortality and CMV Retinitis progression in newly diagnosed and relapsed CMV Retinitis. Design Ancillary study of a randomized, placebo-controlled, phase III clinical trial. Patients A total of 83 patients with AIDS and CMV Retinitis, enrolled during the first phase of the Monoclonal Antibody Cytomegalovirus Retinitis Trial, were administered MSL-109 or placebo as adjuvant therapy for CMV Retinitis. Main outcome measure(s) Mortality and CMV Retinitis progression. Results Treatment with MSL-109 did not predict either progression of CMV Retinitis or mortality. Detection in plasma CMV DNA at baseline predicted mortality, but CMV antigenemia did not. CMV DNA was a better predictor of mortality than a high HIV viral load. Neither CMV DNA nor antigenemia predicted the progression of CMV Retinitis. Among newly diagnosed patients, there was a decline in the proportion with detectable CMV viral load and CMV antigenemia in response to anti-CMV therapy. However, there was a rebound in CMV viral load to 25% and CMV antigenemia to 54.6% at 6 months. In relapsed patients, anti-CMV therapy was not associated with a change in the percentage with detectable CMV-DNA or CMV antigenemia over time. Conclusion In patients with AIDS and CMV Retinitis, the detection of plasma CMV DNA was associated with a higher risk of mortality than was a high HIV viral load. Anti-CMV therapy provided a transient reduction in CMV viremia in newly diagnosed but not relapsed patients with CMV Retinitis. Adjuvant therapy with MSL-109 was ineffective in clearing CMV-DNA and CMV antigen from the plasma.
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immune recovery uveitis in patients with aids and Cytomegalovirus Retinitis after highly active antiretroviral therapy
American Journal of Ophthalmology, 2000Co-Authors: Quan Dong Nguyen, John H. Kempen, James P. Dunn, Stephen G Bolton, Douglas A. JabsAbstract:Abstract PURPOSE: To estimate the incidence and describe the characteristics of immune recovery uveitis in patients with acquired immunodeficiency syndrome (AIDS) and Cytomegalovirus Retinitis treated with highly active antiretroviral therapy. METHODS: The records of all patients with AIDS and Cytomegalovirus Retinitis from 1995 to 1998 seen at the AIDS Ophthalmology Service of the Johns Hopkins Medical Institutions were reviewed. Eighty-two patients with Cytomegalovirus Retinitis treated with highly active antiretroviral therapy were identified. Thirty-three patients (40.2%) were classified as responders to highly active antiretroviral therapy, defined as an increase in CD4+ T-cell count by 50 cells/μL or more to a level of 100 cells/μL or more. RESULTS: Immune recovery uveitis occurred in six patients. Among the 33 patients with an immunologic response to highly active antiretroviral therapy, the incidence rate of immune recovery uveitis was 0.109/person-year. Ocular complications associated with immune recovery uveitis included cystoid macular edema (four patients), epiretinal membranes (two patients), and optic disk neovascularization (one patient). CONCLUSIONS: Immune recovery uveitis was uncommon in our population but may have vision-impairing complications.
