Characteristics of untreated AIDS-related cytomegalovirus retinitis. II. Findings in the era of highly active antiretroviral therapy (1997 to 2000)

PURPOSE: To describe host characteristics (use of highly active antiretroviral therapy [HAART]; CD4+ T-lymphocyte count; HIV ribonucleic acid [RNA] blood level) of people who were diagnosed with AIDS-related cytomegalovirus (CMV) retinitis after HAART became available and to investigate effects of HAART on ophthalmic findings. DESIGN: Retrospective, observational case series. METHODS: We collected demographic, medical, laboratory, and ophthalmic data for all patients with AIDS and newly diagnosed, untreated CMV retinitis from January 1997 through December 2000 at 10 sites in Los Angeles and Orange Counties, California. RESULTS: The proportions of Hispanic and African-American patients were equivalent to or greater than their prevalences in the AIDS and general populations of Los Angeles County. Most patients (n = 80; 63.5%) were known to be receiving HAART at the time of CMV retinitis diagnosis; only 22 patients (17.5%) were HAART-na?ve. Median CD4+ T-lymphocyte count was 15 cells/microl and median HIV RNA blood level was 103,000 copies/ml for all patients, but in 10 patients, CMV retinitis developed despite good immunologic and virologic responses to HAART. When compared with HAART-na?ve patients, HAART-failure patients with CMV retinitis had more asymptomatic disease (P = .073), better visual acuity in the better eye (P = .003), more bilateral disease (P = .007), less zone 1 involvement (P = .042), and lower lesion border opacity scores (P = .054). CONCLUSIONS: Most patients with AIDS and newly diagnosed CMV retinitis in an urban setting are HAART-experienced. HAART may influence characteristics of new CMV retinitis lesions at presentation, despite laboratory evidence of treatment failure, possibly because of residual CMV-specific immunity.     

Immune recovery uveitis in AIDS patients with cytomegalovirus retinitis treated with highly active antiretroviral therapy in Venezuela

PURPOSE: To determine the characteristics of immune recovery uveitis (IRU) in acquired immunodeficiency syndrome (AIDS) patients with inactive cytomegalovirus (CMV) retinitis who responded to highly active antiretroviral therapy (HAART) in a Venezuelan population. METHODS: We examined 34 patients (50 eyes) with AIDS (HAART responders) and healed CMV retinitis. Patients were observed for a median of 19.3 months following an increase in the CD4 cell count. Ten eyes were treated with sub-Tenon space corticosteroid injections. An age-matched control group of patients with healed CMV retinitis who did not have IRU (30 eyes of 20 patients) was included to compare CMV surface area and complications. RESULTS: We found that 12 (37.5%) of 32 HAART responders developed IRU (18 eyes). The clinical findings of these 18 eyes with IRU are presented. The clinical spectrum of inflammation included vitritis, macular edema, epiretinal membranes, anterior uveitis, macular hole, retinal detachment with proliferative vitreoretinopathy, and cataract. Eyes with IRU had a mean CMV surface area of 31.7%. However, eyes without IRU (control group) had a mean CMV surface area of 35% (P = 0.41). Periocular treatment resulted in vision improvement (in 90% of eyes) without reactivation of retinitis. CONCLUSIONS: Symptomatic IRU developed in a significant number of patients with CMV retinitis following successful HAART in a Venezuelan population. CMV surface area does not seem to be a risk factor for the development of IRU. Eyes with IRU respond favorably to antiinflammatory therapy without reactivation of retinitis.     

Immune recovery vitritis and uveitis in AIDS: clinical predictors, sequelae, and treatment outcomes

PURPOSE: To determine 1) clinical predictors of an inflammatory syndrome associated with cytomegalovirus (CMV) retinitis (immune recovery vitritis or uveitis [IRV or IRU]); 2) clinical sequelae of IRV; and 3) the effect of corticosteroid treatment on visual acuity. METHODS: A cohort study from the AIDS Ocular Research Unit of the University of California, San Diego, and a case series from the Cleveland Clinic consisted of patients who had acquired immunodeficiency syndrome and inactive CMV retinitis who responded to highly active antiretroviral therapy (HAART) with CD4 T-lymphocyte levels >60 cells/mm3. The cohort was followed for a median of 13.5 months following increase in CD4 count. The authors studied the occurrence of IRV, defined as symptomatic (vision decrease and/or floaters) vitritis of 1+ or greater severity associated with inactive CMV retinitis. Macular edema or epiretinal membrane formation was determined by clinical examination and fluorescein angiography. Five eyes were treated with sub-Tenon corticosteroid injections. RESULTS: In the cohort study, 19 (63%) of 30 HAART responders developed IRV (26 eyes). The clinical spectrum of inflammation included vitritis, papillitis, macular edema, and epiretinal membranes. Eyes with CMV surface area >30% of the retina were at the highest risk (relative risk = 4.5) of developing IRV (P = 0.03). During follow-up, inflammation persisted without treatment for a median of 20 weeks and 14 patients (16 eyes) developed macular changes. Treatment resulted in vision improvement without reactivation of retinitis. Histology and immunohistochemistry of associated epiretinal membranes showed evidence of chronic inflammation with a predominant T-lymphocyte cell population. In the case series, 3 (38%) of 8 HAART responders developed IRV (4 eyes). All four eyes were treated and resulted in visual acuity improvement of one line. CONCLUSIONS: Symptomatic IRV or IRU develops in a significant number of patients with CMV retinitis following successful HAART. Eyes with CMV surface area >30% of the retina are at the greatest risk. Eyes with IRV respond favorably to antiinflammatory therapy without reactivation of retinitis. Immune recovery vitritis may be the result of an immunologic reaction to latent CMV antigens in the eye in which T-lymphocytes play a role.     

Long term visual outcome of patients with cytomegalovirus retinitis treated with highly active antiretroviral therapy

BACKGROUND: Healed cytomegalovirus (CMV) retinitis in the setting of highly active antiretroviral therapy (HAART) is complicated by inflammatory sequelae and vision loss. AIM: To determine the long term visual outcome of AIDS patients with CMV retinitis who received HAART. METHODS: 90 eyes of 63 consecutive AIDS patients with extramacular CMV retinitis were studied prospectively. RESULTS: Immune recovery status was related to time to onset of epiretinal membrane (p=0.05) and cystoid macular oedema (p=0.06) as well as to the incidence of cataract (p=0.001) and moderate vision loss (p<0.0001). Severe vision loss was associated with retinal detachment (p<0.001). CONCLUSION: AIDS patients with extramacular CMV retinitis lose vision while on HAART. HAART related immune recovery is associated with increased frequencies of epiretinal membrane, cystoid macular oedema, cataract, and retinal detachment with resultant vision loss in AIDS patients with healed CMV retinitis.     

Cytomegalovirus retinitis after initiation of highly active antiretroviral therapy in HIV infected patients: natural history and clinical predictors

PURPOSE: To characterize the natural course and clinical predictors of cytomegalovirus (CMV) retinitis in human immunodeficiency virus (HIV)-infected patients after initiation of highly active antiretroviral therapy (HAART). METHODS: Retrospective analysis of 53 HIV-positive patients (73 eyes with CMV retinitis) treated with and without HAART. All participants continued to take anti-CMV therapy. Survival analysis was used to characterize the natural course of CMV retinitis. Proportional hazards analysis was performed to assess the correlation of the nine potential clinical predictors (baseline CD4 count, post-HAART CD4 count, post-HAART rise in CD4 count, baseline weight, post-HAART rise in weight, post-HAART percentage rise in weight, log of baseline HIV viral load, log of minimum post-HAART HIV viral load, and post-HAART log unit reduction in HIV viral load) with the duration of CMV retinitis remission. RESULTS: Patients receiving HAART had a median CMV retinitis remission duration of 574 days (95% confidence interval, 336-NA) whereas those not receiving HAART had a median remission duration of 80.5 days (95% confidence interval, 28-NA; P < 0.001). Within the HAART-treated population, the minimal viral load reached after HAART was the only clinical predictor to demonstrate significance (P = 0.0075). Several other clinical predictors demonstrated borderline significance; however, this was most likely due to the high correlation of these variables with the minimum post-HAART viral load. A potential secondary clinical predictor identified was the post-HAART rise in CD4 count (P = 0.085). CONCLUSION: With the introduction of HAART, HIV-infected patients have much longer remission durations from recurrent CMV retinitis. The minimum HIV viral load level reached after the initiation of HAART treatment appears to be more important than other clinical variables in the prediction of favorable CMV retinitis remission status. Furthermore, a rise in CD4 T-lymphocyte count by itself appears to be a less significant clinical predictor but may be useful in combination with the HIV viral load data. Selective discontinuation of anti-CMV therapy may be considered in patients with a favorable set of clinical predictors.     

High-dose (5000-microg) intravitreal ganciclovir combined with highly active antiretroviral therapy for cytomegalovirus retinitis in HIV-infected patients in Venezuela

PURPOSE: To describe the use of high doses of intravitreal ganciclovir combined with highly active antiretroviral therapy (HAART) for the treatment of cytomegalovirus (CMV) retinitis in human immunodeficiency virus (HIV)-infected patients. METHODS: Thirteen HIV-infected patients (18 eyes) with active CMV retinitis (83.3% in zone 1 and 38.4% resistant) participated in this prospective interventional case series. Patients were treated with high dose intravitreal ganciclovir (5.0 mg/0.1 mL once a week) in combination with HAART therapy. Intravitreal injections were discontinued once CMV retinitis healed if there was a significant increase in CD4+ count (any increase of > or 50 cells/microL to levels over 100 cells/microL sustained for at least 3 months). Mean follow-up was 15.6 months. Main outcome measures included assessment of visual acuity and retinal inflammation (CMV retinitis activity). A matched historical control group of 20 eyes (15 patients) with CMV retinitis treated with systemic ganciclovir (intravenous [induction] and oral [maintenance]) was included. RESULTS: Complete regression of the retinitis was obtained with high doses of intravitreal ganciclovir in 88.8% of eyes (two patients died during follow-up) at a mean of 4.5 weeks (2 to 8 weeks). Visual acuity improved two or more lines in 61.1% of eyes. No ganciclovir retinal toxicity was identified. Three eyes presented CMV retinitis reactivation at a mean of 25.6 days after their last injection. Complications (33.3%) included retinal detachment (RD; 3 eyes), immune recovery uveitis (IRU; 2 eyes), and endophthalmitis (1 eye). In our control group complete regression of the retinitis was obtained in 100% of eyes at a mean of 4 weeks (3 to 7 weeks). However, 12 eyes (60%) presented with CMV retinitis relapse at a mean of 29 days (21 to 32 days) after initiating oral ganciclovir (maintenance). Complications included RD (7 eyes, 35%) and IRU (3 eyes, 15%). Severe neutropenia occurred in 2 patients (13%). CONCLUSIONS: High doses of intravitreal ganciclovir (5.0 mg) once a week in combination with HAART therapy is effective to control CMV retinitis, and may be discontinued after CMV retinitis has healed if immune reconstitution with a significant increase in CD4+ count has occurred.     

Incidence of cytomegalovirus (CMV) retinitis in second eyes of patients with the acquired immune deficiency syndrome and unilateral CMV retinitis

PURPOSE: To evaluate the risk and risk factors for developing cytomegalovirus (CMV) retinitis in previously uninvolved second eyes among patients with unilateral CMV retinitis. DESIGN: Cohort study. METHODS: SETTINGS: Single-center academic AIDS ophthalmology practice. PATIENT POPULATION: Three hundred seventy-six consecutive patients with AIDS and unilateral CMV retinitis were followed from the time of CMV retinitis diagnosis for the development of second-eye retinitis. EXPERIMENTAL PROCEDURES: Demographic and clinical characteristics were noted at baseline. Use of highly active antiretroviral therapy (HAART) and immune recovery in response to HAART were noted prospectively. MAIN OUTCOME MEASURE: Development of CMV retinitis in a previously uninvolved eye. RESULTS: Ninety-one percent of subjects received systemic anti-CMV treatment. Second-eye retinitis occurred in 26.1%/person-year (19.6% within the first 6 months), less than half the rate previously reported in untreated groups. Initial CD4+ T cell count >12 cells/microl, use of HAART, and initial posterior pole involvement were associated with 64%, 46%, and 41% reductions in incidence vis-à-vis comparison groups. Benefit from HAART was limited to that subset who developed immune recovery of a degree expected to restore innate control of CMV (a rise in the CD4+ T cell count by >50 cells/microl to a level >100 cells/microl). CONCLUSIONS: The risk of second-eye retinitis is substantial in patients with unilateral CMV retinitis but appears to be reduced by anti-CMV therapy and by HAART-induced immune recovery. Patients are at highest risk when CD4+ T cell counts are very low and in the months immediately after CMV retinitis diagnosis.     

Regression der Zytomegalievirus-Retinitis bei AIDS-Patienten ohne systemische Anti-Zytomegalievirus-Erhaltungstherapie unter hochaktiver antiretroviraler Therapie (HAART)

BACKGROUND: The purpose of this study was to evaluate the course of CMV retinitis after initiation of highly active antiretroviral therapy (HAART) and discontinuation of systemic anti-CMV maintenance therapy. PATIENTS AND METHODS: Case reports are presented for two AIDS patients (2 eyes, ages 34, 43, male) with CMV retinitis. The CD4 count at the time of CMV retinitis was 20/microliter (patient 1) and 35/microliter (patient 2). Under HAART the CD4 count rose up to 202/microliter (patient 1) and 350/microliter (patient 2); the viral load was under detection limit in both patients. At that time systemic maintenance therapy was discontinued in both patients. RESULTS: There was no progression of retinitis during the observation period of 21 months (patient 1) and 24 months (patient 2). CONCLUSIONS: In selected patients with immune recovery under HAART it is possible to discontinue systemic anti-CMV maintenance therapy.     

人类免疫缺陷病毒感染及获得性免疫缺陷综合征患者眼部病变的诊断与治疗

目的 探讨人类免疫缺陷病毒(HIV)感染及获得性免疫缺陷综合征(AIDS)患者的眼部病变特点、临床症状及治疗原则.方法 回顾性系列病例研究.回顾性分析110例(220只眼)HIV感染和AIDS患者的临床资料,包括患者视力、眼前节、眼底检查和荧光素眼底血管造影及外周血CD_4~+T淋巴细胞检测结果,其中2例(4只眼)AIDS合并巨细胞病毒(CMV)性视网膜炎患者施行了更昔洛韦玻璃体腔注药治疗.患者年龄、HIV感染时间与HIV视网膜病变及CMV性视网膜炎的相关性采用Pearson相关分析法,性别与HIV视网膜病变及CMV性视网膜炎的相关性采用Pearson ChiSquare分析法,正常眼底组、HIV视网膜病变组、CMV性视网膜炎组间CD_4~+T淋巴细胞计数比较采用多个独立样本的秩和检验.结果 患者初诊视力为无光感者5只眼,光感至0.04者10只眼,0.05～0.2者14只眼,0.3～0.7者62只眼,0.8及以上者129只眼.110例(220只眼)HIV感染和AIDS患者中,有25只眼角膜后有灰白色细小或色素性沉着物.22只眼房水闪光(+)或(++).4只眼虹膜后粘连.28只眼晶状体混浊.34只眼确诊为HIV视网膜病变,眼底表现为棉絮斑、视网膜出血及微血管瘤.32只眼确诊为AIDS合并CMV性视网膜炎,26只眼的眼底表现为沿血管分布的浓厚黄白色病损区,其上片状出血,边缘有不规则黄白色颗粒.3只眼为眼底病变晚期,表现为视网膜萎缩、视网膜血管硬化和狭窄、视神经萎缩.3只眼合并视网膜脱离.正常眼底的HIV感染者及AIDS患者CD_4~+T淋巴细胞计数中位数为100.0个/mm~3,HIV视网膜病变患者CD_4~+T淋巴细胞计数中位数为41.0个/mm~3,CMV性视网膜炎患者CD_4~+T淋巴细胞计数中位数为18.0个/mm~3.CD_4~+T淋巴细胞计数比较,正常眼底组与HIV视网膜病变组相比,差异有统计学意义(x~2=4.848,P=0.028);正常眼底组与CMV性视网膜炎组相比,差异有统计学意义(x~2=15.696,P=0.000);HIV视网膜病变组与CMV性视网膜炎组相比,差异有统计学意义(x~2=4.860,P=0.027).2例(4只眼)CMV性视网膜炎患者行更昔洛韦(400 μg)玻璃体腔注药后,视力提高,眼底病变明显消退.结论 视网膜微血管病变是HIV感染及AIDS常见的眼部并发症,CMV性视网膜炎是AIDS晚期最严重的眼部并发症.高效抗逆转录病毒治疗可重建患者的免疫功能,更昔洛韦玻璃体腔注药可有效治疗CMV性视网膜炎并挽救患者视力.     

Characterization of reactivation of cytomegalovirus retinitis in patients healed after treatment with highly active antiretroviral therapy

PURPOSE: To delineate the immune parameters associated with reactivation of cytomegalovirus (CMV) retinitis in patients for whom highly active antiretroviral therapy (HAART) was not successful. METHODS: Prospective, longitudinal observational study of a cohort of 102 patients with CMV retinitis treated with HAART and being followed up at the AIDS Ocular Research Unit of the University of California, San Diego from November 1995 to November 1998. The study included serial clinical and fundus photographic examinations with CD4 T-lymphocyte counts and HIV viral load measurements. RESULTS: Forty-seven of the 102 patients with CMV retinitis responded to HAART. Thirty-five of the patients were successfully withdrawn from anti-CMV therapy. During a median follow-up of 74.71 weeks (range, 4.86-144 weeks) after discontinuation of anti-CMV therapy, four patients experienced a reactivation of CMV retinitis. In each case, the CD4 count decreased before reactivation to a median of 31.5 cells/mm3 (mean, 31.25 cells/mm3; range, 23-39 cells/mm3). The association between the CD4 count decreasing to less than 50 cells/mm3 and reactivation of CMV retinitis was statistically significant (P < 0.0003). CONCLUSION: Four patients treated with HAART experienced reactivation of CMV retinitis as their CD4 count decreased. The threshold CD4 count below which reactivation of CMV retinitis occurred in patients for whom HAART was not successful appeared to be 50 cells/mm3. Despite an initial response to HAART, patients are still at risk for reactivation of CMV retinitis if their CD4 count decreases to less than 50 cells/mm3. The HIV viral load did not appear to predict CMV reactivation.     

Paradoxical activity of CMV retinitis in patients receiving highly active antiretroviral therapy

PURPOSE: To report two types of atypical behaviors of cytomegalovirus (CMV) retinitis in the highly active antiretroviral therapy (HAART) era, including active CMV retinitis in the presence of persistently high CD4 cell counts during HAART and CMV retinitis that has not reactivated despite persistently low CD4 cell counts. METHODS: Prospective, longitudinal, observational study of a cohort of 116 patients with acquired immunodeficiency syndrome who had a history of CMV retinitis during the HAART era. RESULTS: Sixty (52%) of the 116 patients with acquired immunodeficiency syndrome and CMV retinitis were HAART responders. Subsequently, HAART failed for 9 of the 60 patients with low CD4 cell counts. Of these 9 patients, 5 developed reactivation of CMV retinitis, and 4 remained free of CMV retinitis despite CD4 cell counts of <50/microL and lack of anti-CMV therapy. Paradoxically, there was a patient with a documented median CD4 cell count of 204/microL for 19 months who had newly diagnosed active CMV retinitis. CONCLUSION: In the HAART era, CMV retinitis may remain quiescent despite extremely low CD4 cell counts, and rarely, CMV retinitis may become active in the setting of persistently high CD4 cell counts in a subset of HAART responders.     

Highly active antiretroviral therapy-associated regression of cytomegalovirus retinitis: long-Term results in a small case series

PURPOSE: To report the stability of acquired immunodeficiency syndrome (AIDS)-associated cytomegalovirus (CMV) retinitis lesions that have undergone regression in the absence of specific anti-CMV medications owing to highly active antiretroviral therapy (HAART)-generated immune recovery. METHODS: The initial examination revealed HAART-associated regression of CMV retinitis lesions in eight subjects at two institutions. Patients were monitored for recurrences of CMV activity. CD4+ T-lymphocyte counts and human immunodeficiency virus (HIV) loads were measured. RESULTS: All patients had positive initial responses to HAART with an average HIV load decrease of 2.26 log units (range 0.3-5.57). Mean CD4+ T-lymphocyte count at baseline was 45.6 (range 4-107) and increased by an average of 132.5 (range 7-266) within the first 2 to 4 months of HAART. Patients were observed for an average of 15.5 months (range 11-20 months). Six subjects had a vigorous and sustained response to therapy, achieving an average HIV load of 9,400 copies/mL (3.32 log10 decrease) and CD4+ T-lymphocyte count of 158.2 cells/microL. These patients had no CMV retinitis progression. By contrast, two others who attained an average log10 decrease of only 0.48 had modest and short-lived increases in the CD4+ T-lymphocyte count. These patients experienced reactivation of CMV retinitis after 5 and 7 months, respectively. CONCLUSIONS: Regressed CMV retinitis may remain healed for long periods. However, failure of HAART to induce substantial decreases in HIV load may predict poor or unsustainable rises in the CD4+ T-lymphocyte count and presage recurrence of CMV retinitis. Vigilance in ophthalmic examinations is especially mandatory in these subjects.     

Effect of potent antiretroviral therapy on recurrent cytomegalovirus retinitis treated with the ganciclovir implant

PURPOSE: To determine the effect of highly active antiretroviral therapy on cytomegalovirus (CMV) retinitis treated with ganciclovir implants. METHODS: A retrospective cohort study was performed of 15 patients with recurrent CMV retinitis treated with the ganciclovir implant and highly active antiretroviral therapy (cases) and 38 patients with recurrent retinitis treated with ganciclovir implants before availability of improved antiretroviral therapy (controls). Progression was defined as occurrence of new lesions in the treated eye or advancement of the retinitis border by more than 750 microm. RESULTS: Cases and controls were statistically similar in age, ethnicity, and duration of acquired immunodeficiency syndrome (AIDS). Controls had received intravenous ganciclovir for 9.5 +/- 9.5 months vs 3.5 +/- 4.6 months in cases (P = .003). The mean (+/- SE) time to progression of retinitis after implantation of the device was 26.7 +/- 2.4 months (95% confidence interval, 22.1 to 31.3) in the cases receiving highly active antiretroviral therapy vs 6.2 +/- 0.9 months (95% confidence interval, 4.5 to 7.9) in the controls (P = .001). Multivariate analysis, adjusted for preoperative variables, confirmed a significantly prolonged time to progression in patients receiving highly active antiretroviral therapy (P = .0003). The odds ratio for progression in the cases vs controls was 0.034 (95% confidence interval, 0.003 to 0.350). Cases had higher CD4+ T-lymphocyte counts (P = .004) and longer survival (P < .001) than controls. CONCLUSION: Highly active antiretroviral therapy is associated with improved outcomes in patients with AIDS and recurrent CMV retinitis treated with the ganciclovir implant.     

Atypical healing of cytomegalovirus retinitis. Significance of persistent border opacification.

PURPOSE: To analyze a phenomenon seen in patients with acquired immune deficiency syndrome (AIDS) with cytomegalovirus (CMV) retinitis undergoing systemic antiviral treatment: a persistent white border opacification on the edge of healed CMV retinitis. PATIENTS AND METHODS: The authors prospectively evaluated a population of 137 patients with AIDS and CMV retinitis during a 44-month period. Eleven patients (12 eyes) who were undergoing maintenance antiviral treatment were identified with an atypical healing response--the persistence of a white flat border opacification that did not advance for many weeks to months. Patient records and photographs were reviewed. Results of one autopsy were analyzed with histopathology and special stains. RESULTS: The persistent white edge maintained (without advancement or smoldering) for an average of 11.6 weeks (range, 4 to 41 weeks). This border opacification was not affected by reinduction treatment in the six patients to whom reinduction was given. Results from histopathologic examination of one patient with a persistent white border are presented: these results show that dead cytomegalic cells formed stable structures within the retina, causing white opacification that could be confused with active lesions. Immunoperoxidase stains identified CMV antigens. CONCLUSION: This persistent white border opacification, which does not advance or smolder, represents an important clinical entity that should be recognized during antiviral treatment for CMV retinitis. It can often be observed. If it is not recognized as a stable configuration, patients may undergo unnecessary reinductions with potentially toxic doses of antiviral medications.     

Effect of anti-cytomegalovirus therapy on the incidence of immune recovery uveitis in AIDS patients with healed cytomegalovirus retinitis

PURPOSE: To determine the association between anticytomegalovirus (CMV) maintenance therapy after immune recovery and immune recovery uveitis in acquired immunodeficiency syndrome (AIDS) patients on highly active antiretroviral therapy (HAART). DESIGN: Observational cohort study. METHODS: Data were obtained on AIDS patients with CMV retinitis followed up at the AIDS Ocular Research Unit of University of California San Diego from November 1995 to October 1999. Immune recovery was defined as CD4 count greater than 50 cells/microl for more than 3 months. Patients with immune recovery uveitis presented with vitritis, cystoid macular edema, or epiretinal membrane. Statistical analyses were conducted to determine the risk of continued use of anti-CMV therapy after immune recovery and the relationship of developing immune recovery uveitis with the type of anti-CMV therapy. RESULTS: Forty-three patients (64 eyes) had healed CMV retinitis and had achieved immune recovery. Thirty-one patients (48 eyes) received anti-CMV therapy after immune recovery, and 20 patients (29 eyes) developed immune recovery uveitis. Per-eye analyses revealed a 3.8-fold increase in the odds of developing immune recovery uveitis with anti-CMV therapy compared with no treatment (P =.02). If treated with cidofovir the odds were 3.3 greater than if treated with an alternative regimen (P =.04), 4.1 greater if treated intravenously (P =.01), and 5.2 greater than if not treated (P =.004). If not treated with cidofovir, a nonsignificant increase in the risk (2.4) of immune recovery uveitis was found (P =.15). Neither the potency nor the use of implants for noncidofovir treatment was related to the risk of recovery uveitis (P >.62). CONCLUSIONS: The use of cidofovir is a primary risk factor in the subsequent development of immune recovery uveitis. Ongoing treatment of healed CMV retinitis after immune recovery does not appear to protect against the development of immune recovery uveitis.     

An analysis of lesion size and location in newly diagnosed cytomegalovirus retinitis.

OBJECTIVE: To investigate the size and distribution of lesions in newly diagnosed cytomegalovirus retinitis (CMVR). DESIGN: Retrospective, observational case series. PARTICIPANTS: Fundus photographs of 252 newly diagnosed CMVR lesions in 173 eyes of 130 patients (123 male, 7 female). METHODS: Thirty-five millimeter (60 degrees ) color transparencies were digitized. A montage of the retina was assembled for each involved eye and was superimposed on a specially designed map of the postequatorial retina. Cytomegalovius retinitis lesions were delineated, and the size and location of each lesion was measured. The size of newly diagnosed CMVR lesions was computed in terms of percent postequatorial retinal surface area (PERSA), and the location of lesions was plotted on a polar coordinate system. MAIN OUTCOME MEASURES: Size and location of patches of newly diagnosed CMVR. RESULTS: The median lesion size was 3% PERSA. Peripheral CMVR lesions were larger than posterior ones (P < 0.001). The mean number of lesions was 1.6 per eye. The total area of CMVR involvement ranged from 1% to 76% PERSA, with a median of 5% PERSA. There was no difference between left and right eyes in the distribution of lesion centers (P = 0.27). The concentric distribution of lesion centers appeared to be homogeneous, except for fewer centers in the most peripheral 14 degrees (P < 0.001), and a greater than expected number of lesion centers in the macula (central 11.6 degrees, P < 0.001). Eyes of patients with unilateral retinitis had 1.3 lesions per involved eye compared with eyes of patients with bilateral retinitis, which had 1.6 lesions per eye (P = 0.003). CONCLUSIONS: Most newly diagnosed CMVR lesions were small. Peripheral lesions were larger than more posterior lesions. Variations from a homogeneous distribution of lesions were noted only at the extreme peripheral and central locations and are probably explained by ascertainment bias. The macula was not spared from new CMVR lesions in this patient population.     

Cytomegalovirus Retinitis and Immune Recovery Uveitis in AIDS Patients Treated with Highly Active Antiretroviral Therapy in Taiwanese

Purpose: To determine the characteristics of cytomegalovirus (CMV) retinitis and immune recovery uveitis (IRU) in the era of highly active antiretroviral therapy (HAART). Methods: We reviewed data from 47 of 79 consecutive patients with acquired immunodeficiency syndrome (AIDS) and CMV retinitis. Results: The incidence of CMV retinitis in AIDS patients has markedly decreased over the recent 10 years. The characteristics of CMV retinitis have changed. Development of IRU occurred in 24.4%. Conclusions: Symptomatic IRU develops in a significant number of patients with inactive CMV retinitis following successful HAART. Eyes with IRU respond favorably to antiinflammatory therapy without reactivation of retinitis.     

Bilateral cystoid macular edema following successful treatment of AIDS-associated CMV retinitis

Background: Cystoid macular edema (CME) in AIDS patients with inactive cytomegalovirus (CMV) retinitis is an uncommon but potentially sight-threatening complication. The pathogenesis of CME in these patients is unclear. This study tries to identify possible risk factors by analyzing the charts of five patients. Methods: Ten eyes of 5 patients that finally developed CME were followed for an average of 18 months. The initial retinal lesions, their response to antiviral treatment, the development of CME, and the patients' immune status were prospectively monitored. Results: CMV retinitis was diagnosed at a median CD4+ count of 3 cells/mm³ (range 0–11). All eyes responded to the initial systemic anti-viral treatment. At the onset of CME, CMV retinitis was controlled by antiviral maintenance therapy in all patients [ganciclovir (n = 2), cidofovir (n = 2), foscarnet (n = 1)]. The median time between diagnosis of CMV retinitis and onset of CME was 11.5 months (range 5–24). Development of CME was associated with significant visual loss: acuity ranged from 0.05 to 0.7 when CME was first noticed, compared to 0.8–1.25 at diagnosis of CMV retinitis. Duration of inflammation, size or zone of retinal necrosis did not favor the development of CME, neither did the antiviral therapy. A weak correlation of CME development and immune status (expressed as increase of CD4+ cells) was found. Due to systemic corticosteroids CME resolved. Conclusions: CME is a new visual threat to AIDS-patients with CMV retinitis whose immune status improved under the latest combined antiretroviral therapy. Therapy with oral corticosteroids may positively influence this condition.      

巨细胞病毒性视网膜炎与获得性免疫缺陷综合征

目的 探讨巨细胞病毒性视网膜炎与获得性免疫缺陷综合征的关系、临床表现及诊断、治疗。 方法 观察分析56例巨细胞病毒(cytomeglovirus,CMV)性视网膜炎合并获得性免疫缺陷综合征(acquired immunodeficiency syndrome,AIDS)患者95只眼，对其眼底、视力、T辅助细胞的细胞受体4（CD4 ＋）计数及预后进行观察随访2周～18个月。 结果 56例患者在诊断为巨细胞病毒性视网膜炎之前AIDS病程为4～26个月。95只眼56例患者中，眼底病灶表现为颗粒型者55只眼，其中46只眼位于周边部；爆发型者25只眼，均位于后极部，视网膜坏死灶致密伴斑片状出血和血管炎；颗粒型与爆发型病灶混合存在者15只眼；其中7只眼合并有视神经乳头炎；患者就诊时视力为眼前数指至0.5，病变广泛者及病变位于后极部者视力下降尤为严重。30例患者CD4 ＋细胞计数为0～30 个/μl,平均(15±9) 个/μl。患者存活时间为3～18个月。接受更昔洛韦(ganciclovir)治疗组患者视力多数提高，CD4 ＋T细胞计数明显升高，未治疗组患者92%病变呈进行性发展，视力显著下降。 结论 CMV性视网膜炎是AIDS病的主要眼部并发症，临床上以坏死性视网膜炎伴出血及血管炎为特征，目前治疗主要用更昔洛韦。 (中华眼底病杂志, 2002, 18: 89-91)