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Cytomegalovirus retinitis in immunosuppressed hosts. II. Ocular manifestations.

We observed the course of cytomegalovirus (CMV) retinitis in 21 eyes of 14 immunosuppressed patients. In two patients, other organisms, specifically Toxoplasma and Candida, also appeared to be causing retinal disease simultaneously. Post-mortem examination was done on 10 eyes from seven patients. At initial presentation, the retinitis was often asymptomatic and diagnosed during routine examination. The ophthalmoscopic picture was characteristic of cytomegalovirus; the early lesion was a small opaque, white granular area of retinal necrosis that spread in a centrifugal, brush-fire-like manner over 1 to 8 months. Vessel sheating and hemorrhages appeared as the disease progressed. In two patients new foci of retinitis developed remote from the original lesion. Four weeks to 4 months (average, 10 weeks) elapsed from the most extensive disease to total resolution. Resolution of active disease left a subtle retinal scar, and final visual acuity was reduced in one half the eyes. Repeated ophthalmoscopic examinations can aid in early diagnosis of CMV retinitis and in ascertaining which persons are most at risk for visual loss.

Candidiasis↗

Increased presence of Epstein-Barr virus DNA in ocular fluid samples from HIV negative immunocompromised patients with uveitis.

AIMS: To investigate whether routine testing for Epstein-Barr virus (EBV) is necessary in the examination of a patient with uveitis. METHODS: Intraocular EBV DNA was determined in 183 ocular fluid samples taken from patients with AIDS and uveitis, HIV negative immunocompromised uveitis, acute retinal necrosis, toxoplasma chorioretinitis, intraocular lymphoma, anterior uveitis, and miscellaneous uveitis of unknown cause. In 82 samples from this group of patients paired serum/ocular fluid analysis was performed to detect local antibody production against EBV. Controls (n = 46) included ocular fluid samples taken during surgery for diabetic retinopathy, macular pucker, or cataract. RESULTS: Serum antibody titres to EBV capsid antigen proved to be significantly increased in HIV negative immunocompromised patients with uveitis (p < 0.01) compared with controls. Local antibody production revealed only three positive cases out of 82 patients tested, two results were borderline positive and one patient had uveitis caused by VZV. EBV DNA was detected in three out of 46 control ocular fluid samples. In the different uveitis groups EBV DNA was noted, but was not significantly higher than in the controls, except in six out of 11 HIV negative immunocompromised patients (p = 0.0008). In four out of these six cases another infectious agent (VZV, HSV, CMV, or Toxoplasma gondii) had previously been identified as the cause of the uveitis. CONCLUSIONS: When comparing various groups of uveitis patients, EBV DNA was found more often in HIV negative immunocompromised patients with uveitis. Testing for EBV does not have to be included in the routine management of patients with uveitis, since indications for an important role of this virus were not found in the pathogenesis of intraocular inflammation.

AIDS-Related Opportunistic Infections↗

Recurrent choroidal neovascularization after argon laser photocoagulation for neovascular maculopathy. Macular Photocoagulation Study Group.

Results from the Macular Photocoagulation Study Group have shown that argon laser photocoagulation is beneficial in reducing the risk of severe visual loss in eyes with extrafoveal choroidal neovascular membranes secondary to senile macular degeneration (Senile Macular Degeneration Study or SMDS), ocular histoplasmosis (Ocular Histoplasmosis Study or OHS), or idiopathic neovascularization (Idiopathic Neovascularization Study or INVS). However, argon laser treatment has not been entirely successful in permanently eradicating active neovascularization from those eyes. Recurrent neovascularization in the form of either neovascularization contiguous with the treatment scar or independent neovascular membranes have been observed in 70 (59%) of the 119 SMDS eyes originally assigned to treatment, 40 (30%) of the 132 OHS eyes, and 11 (33%) of the 33 INVS eyes. Recurrence was accompanied by an increased frequency of severe visual loss. Characteristics of the patient, original lesion, and treatment were examined for their ability to predict recurrence. Cigarette smoking was related to the rate of recurrence in the SMDS (P = .02) and the INVS (P = .09). Younger age and female gender were associated with an increased frequency of recurrence in the OHS. Predictions of which eyes will suffer recurrence, however, cannot be made accurately. Therefore, careful follow-up of all treated eyes is indicated, particularly within the first year after initial argon photocoagulation.

Adult↗

Laboratory passage and characterization of an isolate of Toxoplasma gondii from an ocular patient in Korea.

Toxoplasma gondii tachyzoites were isolated from the blood of an ocular patient, and have been successfully passaged in the laboratory, for over a year, by peritoneal inoculation in mice. The isolated parasite was designated the Korean Isolate-1 (KI-1) and its characteristics were compared with those of the RH strain, a wellknown virulent strain originating from a child who suffered from encephalitis. The morphology, pathogenicity, infectivity and cell culture characteristics of the KI-1 were similar to those of the RH strain. Both RH and KI-1 antigens were detected by an anti-T. gondii monoclonal antibody (mAb), Tg563, against the major surface protein SAG1 (30 kDa), whereas no reaction was observed against an anti-Neospora caninum mAb, 12B4. The KI-1 was confirmed as an isolate of T. gondii. A long-term laboratory maintenance and characterization of a local T. gondii isolate is reported for the first time in the Republic of Korea.

Animals↗

Incidence of symptomatic toxoplasma eye disease: aetiology and public health implications.

Ocular disease is the commonest disabling consequence of toxoplasma infection. Incidence and lifetime risk of ocular symptoms were determined by ascertaining affected patients in a population-based, active reporting study involving ophthalmologists serving a population of 7.4 million. Eighty-seven symptomatic episodes were attributed to toxoplasma infection. Bilateral visual acuity of 6/12 or less was found in seven episodes (8%) and was likely to have been transient in most cases. Black people born in West Africa had a 100-fold higher incidence of symptoms than white people born in Britain. Only two patients reported symptoms before 10 years of age. The estimated lifetime risk of symptoms in British born individuals (52% of all episodes) was 18/100000 (95% confidence interval: 10.8-25.2). The low risk and mild symptoms in an unscreened British population indicate limited potential benefits of prenatal or postnatal screening. The late age at presentation suggests a mixed aetiology of postnatally acquired and congenital infection for which primary prevention may be appropriate, particularly among West Africans.

Adolescent↗

The HIV RNA Levels of Plasma and Ocular Fluids in AIDS Patients with Ophthalmic Infections.

The aim of the present study was to evaluate the impact of highly active antiretroviral therapy (HAART) on HIV viral load of plasma and intraocular fluids in AIDS patients with ophthalmic opportunistic infections. We further compared the treatment effect of HAART on these patients. From June 1997 to July 2003, we examined and followed up the ophthalmic conditions of 49 patients receiving HAART with ophthalmic diseases during this period. The method of reverse-transcriptase polymerase chain reaction was used to detect and monitor HIV load in plasma and/or aqueous humor of AIDS patients. Before HAART, the HIV levels in the plasma and aqueous humor in 8 AIDS patients with ophthalmic opportunistic infections were significantly higher than those in 6 patients with HIV-related retinopathy (p < 0.05). Compared to the eye findings and clinical improvement, HIV loads of aqueous humor in 10 of 14 AIDS patients (6 with HIV-related retinopathy, 5 with cytomegalovirus retinitis, 2 with toxoplasmic retinitis and 1 with cryptococcal chorioretinitis) declined to undetectable levels (< 400 copies/ml) after 4-8 months of HAART. HIV virus levels in the plasma of AIDS patients were significantly decreased, and the CD4 counts of these patients were significantly increased (Wilcoxon test) after initiation of HAART.

AIDS-Related Opportunistic Infections↗

Serologic and polymerase chain reaction analysis of intraocular fluids in the diagnosis of infectious uveitis.

PURPOSE: Infectious uveitis entities are usually rapidly progressive blinding diseases that can be prevented by prompt administration of specific antimicrobial therapy. With the aim of improving early diagnosis in patients with infectious uveitis, intraocular fluid samples from patients with sight-threatening posterior uveitis were investigated to determine the causative agent. METHODS: Thirty-eight patients with acquired immunodeficiency syndrome (AIDS) and retinitis, eight immunosuppressed patients with retinitis, 16 immunocompetent patients with acute retinal necrosis, and 22 immunocompetent patients with toxoplasmic retinochoroiditis were analyzed by polymerase chain reaction for the presence of herpesviruses and Toxoplasma gondii DNA and for local antibody production against these microorganisms. RESULTS: In patients with AIDS and retinitis, polymerase chain reaction was positive for cytomegalovirus DNA in 21 (91%) of the 23 ocular fluid samples obtained during active cytomegalovirus retinitis, whereas local antibody production analysis was negative in all cases. In acute retinal necrosis, varicella-zoster virus or herpes simplex virus could be established as the inciting agent in 81% of the cases, using the combination of both techniques. Polymerase chain reaction was positive in all samples obtained within two weeks after the onset of disease. Toxoplasma gondii DNA was detected in 4 of 13 samples (31%) from immuno-competent patients with active toxoplasmic retinochoroiditis; in each case, local antibody production was also detected. In contrast, no local antibody production was observed in two of three samples from transplant recipients that were positive for T. gondii DNA. All the control samples tested were negative for the above-mentioned tests. CONCLUSIONS: In patients with AIDS, polymerase chain reaction analysis is preferable above local antibody production in detecting the inciting agent of retinitis. In other cases, the combination of both techniques can make a valuable contribution to the diagnosis.

AIDS-Related Opportunistic Infections↗

The importance of specific IgG and IgE autoantibodies to retinal S antigen, total serum IgE, and sCD23 levels in autoimmune and infectious uveitis.

Autoimmunity plays an important role in the development of uveitis. The uveitis are linked to Th1 or Th2 lymphocyte activation. We studied 41 patients with uveitis, divided into autoimmune uveitis (n = 32) and infectious uveitis (n = 9), 30 normal controls, and 20 asthmatic atopic without ocular diseases. The infectious uveitis patients were separated into bacterial (n = 6) and toxoplasmic (n = 3) retinochoroiditis. We measured IgE and sCD23 serum levels and specific IgG and IgE to retinal S antigen by ELISA tests. The IgE levels were 500 +/- 325 kU/L in autoimmune uveitis, 57 +/- 35 kU/L in bacterial uveitis, 280 +/- 38 kU/L in toxoplasmic retinochoroiditis, 75 +/- 32 kU/L in the controls, and 557 +/- 243 kU/L in atopics (P < 0.0005). The sCD23 levels were 10.4 +/- 5.4 ng/ml in autoimmune uveitis, 3.7 +/- 1.17 ng/ml in bacterial uveitis, 6.76 +/- 1.36 ng/ml in toxoplasmic retinochoroiditis, 3.4 +/- 1 ng/ml in controls, and 8.35 +/- 2.2 ng/ml in atopic patients (P < 0.005). The specific IgG to retinal S antigen was positive in 27 of 32 cases, and the specific IgE to retinal S antigen was positive in 22 of 32 autoimmune uveitis. The bacterial uveitis patients as well as the controls were negative for both autoantibodies to retinal S antigen. The toxoplasmic retinochoroiditis patients presented specific IgG and IgE to retinal S antigen in two of three cases, respectively, one of them with overlap of both antibodies. These results suggest the importance of specific IgG and IgE to retinal S antigen in autoimmune uveitis, which, along with higher IgE and sCD23 levels, reveal Th2 activation.

Adult↗

Local production of IgG and IgG subclasses in the aqueous humor of patients with Fuchs heterochromic cyclitis, herpetic uveitis and toxoplasmic chorioretinitis.

Changes in local immunity are important when considering the physiopathology of uveitis. The aim of this study was to measure IgG and IgG subclass concentrations in the serum and the AH of patients with three different types of uveitis and to determine for each of them the presence of a local production of IgG in the intra-ocular compartment. This investigation was extended to IgG subclasses. Serum and AH of 46 patients, including 11 with Fuchs heterochromic cyclitis (FHC), 13 with toxoplasmic chorioretinitis, 11 with herpetic uveitis and 11 with senile cataract (taken as controls) were analyzed by ELISA for IgG and IgG subclasses. Three quotients (r1, IgG/albumin in serum; r2, IgG/albumin in AH; and R, r2/r1) were calculated in order to estimate the local synthesis (LS) of IgG and each IgG subclass. In AH of patients with herpetic uveitis, a concomitant and significant increase of all IgG subclasses as well as albumin (with no significant increase of r2 or R) was observed. This finding was interpreted as an indirect consequence of major damage to the blood-aqueous barrier. In patients with FHC, a significant increase of r2 and R involving only the IgG1 subclass was observed, indicating the existence of LS of IgG1 in the majority of these patients. In the AH of patients with toxoplasmic chorioretinitis, no significant modification of IgG subclass or albumin concentrations was observed when compared to controls. In conclusion, it would seem interesting to consider measurement of IgG and IgG subclasses and calculation of the coefficients r1, r2 and R for a better evaluation of the local immunological processes observed in different types of uveitis.

Adolescent↗

Cultured embryonic retina systems as a model for the study of underlying mechanisms of Toxoplasma gondii infection.

PURPOSE: Toxoplasma gondii, the most common cause of retinochoroiditis in humans, is an obligate intracellular protozoan parasite that depends on te host cell's microenvironment to proliferate. Because congenital infection is associated with a higher risk of ocular involvement than a postnatally acquired infection, this study was conducted to investigate the ability of Toxoplasma gondii to infect retinal tissue during development, when cellular environmental changes normally occur. METHODS: Retinas from 5- to 9-day-old chick embryos were used. Stationary cultures were prepared in 24-well cell culture dishes and maintained at 37 degrees C in DMEM plus 5% fetal bovine serum for 2 to 6 days. Then the wells were infected with 4 x 10(5) tachyzoites. Retina explants and aggregate cell cultures were maintained in DMEM under rotation at 37 degrees C. T. gondii proliferation was measured using [(3)H]-thymidine incorporation after 72 hours. Ornithine and arginine decarboxylase (ODC and ADC) activities were determined by measuring CO(2) production from [1-(14)C]-ornithine and [1-(14)C]-arginine, respectively. RESULTS: The proliferation of tachyzoites was high in dense, stationary cultures expressing elevated ODC and ADC activity. The addition of ODC or ADC inhibitors reduced T. gondii proliferation by approximately 20% to 40%. As for cultured retina cells, retina explants also allowed T. gondii proliferation whenever ODC activity was high. CONCLUSIONS: The data suggest a direct correlation between retinal polyamine biosynthesis and the proliferation of T. gondii, in agreement with the observation that individuals infected congenitally have a greater risk of development of toxoplasmic retinochoroiditis.

Animals↗

Antibiotics versus control for toxoplasma retinochoroiditis.

BACKGROUND: Acute toxoplasma retinochoroiditis causes transient symptoms of ocular discomfort and may lead to permanent visual loss. Antibiotic treatment primarily aims to reduce the risk of permanent visual loss, recurrent retinochoroiditis, and the severity and duration of acute symptoms. There is uncertainty about the effectiveness of antibiotic treatment. OBJECTIVES: The objective of this review was to compare the effects of antibiotics versus placebo or no treatment for toxoplasma retinochoroiditis. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register - CENTRAL/CCTR, which contains the Cochrane Eyes and Vision Group Specialised Register (Cochrane Library Issue 2, 2001), MEDLINE (1966 to August 2001), EMBASE (1980 to September 2001), Dissertation Abstracts (1861 to June 2001), LILACS (1982 to 1998), Pascal (1984 to March 2000), proceedings of the Association for Research in Vision and Ophthalmology (1980 to 2001), international symposia on uveitis, and reference lists of review articles. Pharmaceutical companies were contacted for unpublished trials. SELECTION CRITERIA: We included randomised controlled trials that compared any systemic antibiotic treatment against placebo or no treatment. Trials that included immunocompromised patients were excluded. DATA COLLECTION AND ANALYSIS: The primary outcomes for this review were visual acuity at least three months after treatment and risk of recurrent retinochoroiditis. Secondary outcomes were improvement in symptoms and signs of intraocular inflammation, size of lesion and adverse events. Effect measures were pooled using a random effects model. MAIN RESULTS: Three trials, which randomised a total of 173 participants, met the inclusion criteria. All trials were methodologically poor. None reported the effect of treatment on visual acuity. Two studies reported results for recurrent retinochoroiditis: one (124 participants) found a significant reduction in participants with chronic recurrent disease who were treated for 14 months: relative risk 0.28 (95% confidence interval 0.10 to 0.78); the other (20 participants) found no evidence of an effect in participants with acute toxoplasma retinochoroiditis (relative risk 1.00, 95% confidence interval 0.07 to 13.87). Two studies reported an improvement in intraocular inflammation in treated compared with untreated participants and one study reported no difference. Two studies found an increased risk of adverse events in treated participants. REVIEWER'S CONCLUSIONS: There is a lack of evidence to support routine antibiotic treatment for acute toxoplasma retinochoroiditis. There is weak evidence to suggest that long-term treatment of patients with chronic recurrent toxoplasma retinochoroiditis may reduce recurrence. Placebo controlled trials of patients with acute and chronic toxoplasma retinochoroiditis affecting any part of the retina are required to determine the effectiveness of antibiotic treatment.

Anti-Bacterial Agents↗