Good syndrome and cytomegalovirus retinitis: A literature review.

Good syndrome (GS) is a rare primary immunodeficiency in adults consisting of hypogammaglobulinemia and thymoma that affects both cellular and humoral immunity. It usually appears in patients between the 4th and 6th decade of life and affects both genders equally. Ophthalmological clinical presentation is highly variable; associations with herpetic keratitis, toxoplasmosis, and cytomegalovirus retinitis (CMVR) have been described. GS associated with CMVR is uncommon. Ophthalmologists may be the first to diagnose systemic disease and change the outcome. Only18 cases of CMVR have been described, most of them unilateral with poor visual outcomes. We discuss the clinical features of CMVR in patients with reported GS, pathogenesis, and outline a work-up for diagnosis. CMVR in an apparently healthy patient should encourage the clinician to search for human immunodeficiency virus (HIV) and non-HIV-associated immunosuppression.

Cytomegalovirus retinitis in hospitalized people living with HIV in the late antiretroviral therapy era in São Paulo, Brazil.

BACKGROUND: There is scarce information on AIDS-related cytomegalovirus (CMV) retinitis in middle-income countries. The objectives of this study were to identify the prevalence of active CMV retinitis in severely immunosuppressed people living with HIV (PLWHIV) and to describe its main features. METHODS: This retrospective cohort study was carried out at a tertiary center in São Paulo, Brazil. We included hospitalized adults PLWHIV with CD4 count ≤100 cells/µL, ≥ one quantitation of CMV DNA in plasma, and indirect ophthalmoscopy evaluation. RESULTS: Thirty-eight (21.6%) of 176 participants had at least an ophthalmoscopy diagnosis and only 3 (1.7%) individuals presented active CMV retinitis. All these participants were male, and retinitis was asymptomatic in 2 cases. Two participants had extraocular end-organ CMV disease and detectable CMV DNA in plasma. CONCLUSIONS: These results show a low prevalence of active CMV retinitis in the evaluated population. However, 2 of 3 participants had asymptomatic active CMV retinitis and a fifth of participants had at least one ophthalmoscopy diagnosis, suggesting the need for routine ophthalmologic evaluation in hospitalized severely immunosuppressed PLWHIV. The profile of participants with active CMV retinitis was similar to that described in the pre-ART era and quantitation of CMV DNA in plasma was variable.

Presumed cytomegalovirus retinitis late after kidney transplant.

Cytomegalovirus (CMV) retinitis is a rare manifestation of CMV invasive disease and potentially threatening to vision in immunocompromised individuals. Clinical suspicion is fundamental since it is an unusual entity with a progressive and often asymptomatic installation over a long period. The authors report a 70-year-old man with diabetic nephropathy who underwent a kidney transplant (KT) in August 2014 with good clinical evolution. No previous CMV infection or episodes of acute rejection were reported. Five years after transplant, he was admitted due to a reduced visual acuity of the left eye with seven days of evolution with associated hyperemia, without exudate. The ophthalmologic evaluation was compatible with acute necrosis of the retina and presumed associated with CMV infection. He had a progressive improvement after ganciclovir initiation. CMV retinitis is one of the most serious ocular complications in immune-suppressed individuals and can lead to irreversible blindness, and because of that, early diagnosis and treatment remains crucial in obtaining the best visual prognosis in affected patients. Secondary prophylaxis with ganciclovir is not consensual, neither is the safety of reintroducing the antimetabolite in these cases.

Retinite por citomegalovírus em paciente com Síndrome de Good / Cytomegalovirus retinitis in Good Syndrome

Resumo A Síndrome de Good é uma síndrome paraneoplásica caracterizada pela associação de timoma e hipogamaglobulinemia, cursando com imunossupressão. Relatamos um caso raro de retinite por citomegalovírus em paciente com esta síndrome.

Abstract Good syndrome is a paraneoplastic syndrome characterized by the association of thymoma and hypogammaglobulinemia, with immunosuppression. We report a rare case of cytomegalovirus retinitis in a patient with this syndrome.

Retinitis por citomegalovirus en un paciente con VIH / Cytomegalovirus retinitis in a HIV patient

La retinitis por citomegalovirus es la infección ocular más frecuente en pacientes con un recuento de linfocitos CD4 inferior a 200 por µL. El aspecto oftalmoscópico de las lesiones se caracteriza, en la mayoría de los casos, por infiltrados retinianos resultados de la necrosis retiniana producida por citomegalovirus y el edema en asociación con hemorragias. Estas lesiones se disponen, por lo general, siguiendo las arcadas vasculares temporales con invasión hacia la mácula. Se presentó una paciente de 24 años de edad, femenina, blanca, ama de casa, con antecedentes patológicos personales oculares sin datos de interés, y antecedentes patológicos personales generales de ser diagnosticadas con VIH. Hace cuatro años que comenzó con tratamiento antirretroviral, y tuvo cambios de tratamiento en dos ocasiones. El último fue impuesto en mayo del año 2011, con el cual presentó mala adherencia terapéutica, y comenzó desde entonces a presentar disminución de su peso corporal de forma marcada en breve período de tiempo. Refiere que desde hace unos meses comenzó a presentar una disminución progresiva de la agudeza visual en el ojo derecho, acompañado de visión borrosa. Adquiere gran importancia este caso, ya que ante la supervivencia de los pacientes con sida, va a ser cada vez más frecuente la aparición de las afecciones oculares relacionadas con esta enfermedad. Dentro de ellas se encuentran las infecciones oportunistas mayores como la retinitis por citomegalovirus(AU)

Retinitis caused by cytomegalovirus is the most frequent opportunistic infection in patients with a lymphocyte count CD4 less 200 µL. The ophthalmological aspect of the lesions in most of cases is characterized by retinal infiltrates derived from the retinal necrosis caused by cytomegalovirus and the edema associated to hemorrhages. In general, these lesions are arranged in the same form as the temporal vascular arcades and go into the macula. Here is a 24 years-old Caucasian female patient , housewife with a history of ocular problems with no interesting data and positive diagnosis of HIV, She began an antiretroviral treatment four your ago, which was changed twice. The last one was administered on May 2011 and the therapeutic adherence was inadequate. Since then, she began losing weight significantly in a short period of time. Some months ago, she reported a progressive reduction of the visual acuity in the right eye and blurred vision. This case is very important because, due to the survival rate of AIDS patients, the occurrence of ocular diseases related to it will become more frequent. One of them is major opportunistic infection such as cytomegalovirus retinitis(AU)

Immune recovery uveitis in a patient with previously undiagnosed cytomegalovirus retinitis.

A 40-year-old man presented to the emergency service of the Department of Ophthalmology, Fundación Oftalmológica de Santander, Floridablanca, Colombia, with blurred vision in his right eye. Anamnesis revealed that he also had newly diagnosed stage C HIV. He had recently started highly active antiretroviral therapy (HAART). Examination disclosed intraocular inflammation, along with plain white peripheral non-exudative lesions with sparse haemorrhaging. The differential diagnosis included cytomegalovirus (CMV) retinitis and immune recovery uveitis (IRU). On follow-up, the patient's left eye presented with decreased visual acuity and increased vitreous haze. A vitrectomy with vitreous tap was performed for microbiological studies. PCR for CMV in the vitreous sample was negative. The patient was discharged with the final diagnosis of IRU. In HIV patients with uveitis, the knowledge of characteristic signs and symptoms of particular entities such as opportunistic infections and IRU will enable the clinician to give the appropriate treatment.

Proposed clinical case definition for cytomegalovirus-immune recovery retinitis.

BACKGROUND: Cytomegalovirus (CMV) retinitis has been extensively described in patients with advanced or late human immunodeficiency virus (HIV) disease under ineffective treatment of opportunistic infection and antiretroviral therapy (ART) failure. However, there is limited information about patients who develop active cytomegalovirus retinitis as an immune reconstitution inflammatory syndrome (IRIS) after successful initiation of ART. Therefore, a case definition of cytomegalovirus-immune recovery retinitis (CMV-IRR) is proposed here. METHODS: We reviewed medical records of 116 HIV-infected patients with CMV retinitis attending our institution during January 2003-June 2012. We retrospectively studied HIV-infected patients who had CMV retinitis on ART initiation or during the subsequent 6 months. Clinical and immunological characteristics of patients with active CMV retinitis were described. RESULTS: Of the 75 patients under successful ART included in the study, 20 had improvement of CMV retinitis. The remaining 55 patients experienced CMV-IRR; 35 of those developed CMV-IRR after ART initiation (unmasking CMV-IRR) and 20 experienced paradoxical clinical worsening of retinitis (paradoxical CMV-IRR). Nineteen patients with CMV-IRR had a CD4 count of ≥50 cells/µL. Six patients with CMV-IRR subsequently developed immune recovery uveitis. CONCLUSIONS: There is no case definition for CMV-IRR, although this condition is likely to occur after successful initiation of ART, even in patients with high CD4 T-cell counts. By consequence, we propose the case definitions for paradoxical and unmasking CMV-IRR. We recommend close follow-up of HIV-infected patients following ART initiation.

Acometimento ocular em pacientes com AIDS e toxoplasmose do sistema nervoso central: antes e depois do HAART / Ocular involvement in AIDS patients with central nervous system toxoplasmosis: before and after HAART

OBJETIVO: Descrever o comprometimento ocular em pacientes com AIDS e toxoplasmose do sistema nervoso central, comparando os períodos pré e pós-terapia anti-retroviral (HAART). MÉTODOS: Em estudo retrospectivo, comparamos 118 pacientes com AIDS e toxoplasmose do sistema nervoso central que foram examinados em nossa instituição antes do pré e pós-terapia anti-retroviral (1994-1996) com 24 pacientes com AIDS e toxoplasmose do sistema nervoso central que foram tratados com pré e pós-terapia anti-retroviral (1996-1999). Todos os pacientes foram submetidos a exame oftalmológico completo e a testes específicos para confirmar o diagnóstico e não houve interseção entre os grupos. RESULTADOS: No grupo pré e pós-terapia anti-retroviral, foi encontrado 23 por cento de toxoplasmose ocular entre os pacientes com toxoplasmose do sistema nervoso central. O envolvimento ocular foi bilateral em 37 por cento dos casos. No grupo dos pacientes que receberam pré e pós-terapia anti-retroviral, que tinham CD4 médio de 256 cel/mm³ e carga viral média de 52.620 cópias, 16,6 por cento apresentaram concomitantemente toxoplasmose ocular e toxoplasmose do sistema nervoso central. O envolvimento ocular foi bilateral em 50 por cento dos casos. CONCLUSÃO: Pacientes com AIDS e toxoplasmose do sistema nervoso central apresentam freqüente associação com toxoplasmose ocular. Embora a incidência de infecções oportunistas tenha diminuído desde a introdução de pré e pós-terapia anti-retroviral, a toxoplasmose ocular continua sendo freqüente em pacientes com toxoplasmose do sistema nervoso central.

[Ocular involvement in AIDS patients with central nervous system toxoplasmosis: before and after HAART]. / Acometimento ocular em pacientes com AIDS e toxoplasmose do sistema nervoso central: antes e depois do HAART.

PURPOSE: To describe the ophthalmologic involvement in patients with Acquired Immunodeficiency Syndrome-AIDS and central nervous system toxoplasmosis comparing the period before and after highly active antiretroviral therapy (HAART). METHODS: In a retrospective study, we compared 118 Acquired Immunodeficiency Syndrome patients with central nervous system toxoplasmosis who were examined at our institution before highly active antiretroviral therapy (from 1994-1996) with 24 patients with Acquired Immunodeficiency Syndrome and central nervous system toxoplasmosis who were being treated with highly active antiretroviral therapy (from 1996-1999). All patients were submitted to a complete ophthalmological examination as well as specific tests to confirm the diagnosis and there was no intersection between the groups. RESULTS: In the pre-highly active antiretroviral therapy group, it was found that 23% of the patients with central nervous system toxoplasmosis had also ocular toxoplasmosis. Ocular involvement was bilateral in 37.2% of the cases. In the group of patients receiving highly active antiretroviral therapy, who had an average CD4 of 256 cells/mm(3) and average of viral load of 52,620 copies, 16.6% had concomitant ocular and central nervous system toxoplasmosis. Ocular involvement was bilateral in 50% of the cases. CONCLUSIONS: Acquired Immunodeficiency Syndrome patients with central nervous system toxoplasmosis have a frequent association with ocular toxoplasmosis. Although the incidence of opportunistic infections has decreased since the introduction of recent antiretroviral therapeutic strategies ocular toxoplasmosis continues to be frequent in patients with cen.ral nervous system toxoplasmosis.

Cytomegalovirus UL97 mutations associated with ganciclovir resistance in immunocompromised patients from Argentina.

BACKGROUND: Prolonged therapy with ganciclovir (GCV) can result in the development of GCV-resistant strains due to mutations in the viral phosphotransferase (UL97 gene) and/or in the viral DNA polymerase (UL54 gene). OBJECTIVES: The purpose of this study was to detect by molecular methods the most prevalent UL97 mutants which confer ganciclovir-resistance in immunocompromised populations. STUDY DESIGN: Patients from two populations were selected: (a) renal transplant patients with active cytomegalovirus (CMV) infection and more than one cycle of GCV; (b) HIV-infected patients with retinitis due to CMV, who were under GCV induction, maintenance therapy or withdrawal. Patients were followed up by pp65 antigenemia and by viral isolation from blood or/and urine samples. Two fragments (133 and 255pb) of the UL97 gene were amplified by polymerase chain reaction (PCR) from CMV isolates. RESULTS: Nine from 12 isolates obtained were sequenced, three from two renal transplant patients and six from five HIV-infected patients. A UL97 mutation, known to confer GCV resistance, was found in two isolates from a renal transplant patient. A methionine to valine mutation at codon 460 (M460V) was detected. These isolates exhibited another mutation at codon 605, whose amino acid changed from aspartic acid (D) to glutamic acid (E). These findings were observed after treatment with IV-GCV/ O-GCV/ IV-GCV for 151 days. The 605 mutation was also detected in leukocytes from the same patient previous to the beginning of the treatment with GCV. CONCLUSIONS: Although a known resistant mutation appeared in a renal transplant patient, it was not associated with CMV disease. We suggest that the D605E mutation could "partially or totally compensate" for the effect of GCV resistance conferred by the 460 mutation. Further studies should be performed to confirm this hypothesis.

Detection of herpesvirus DNA by the polymerase chain reaction (PCR) in vitreous samples from patients with necrotising retinitis.

AIMS: Viral uveitis and retinitis, usually caused by herpesviruses, are common in immunosuppressed patients. The diagnosis of viral anterior uveitis and retinitis is usually clinical. The polymerase chain reaction (PCR) has been used for the diagnosis of some viral infections, especially those caused by herpesviruses. This paper reports the use of PCR in the diagnosis of viral retinitis in vitreous samples from Brazilian patients. METHODS: PCR was used for the diagnosis of necrotising retinitis in vitreous samples from patients from the Hospital São Geraldo, Universidade Federal de Minas Gerais, Brazil. The vitreous samples were collected by paracentesis and stored until analysis. Samples were analysed by PCR using specific primers designed to amplify herpes simplex virus 1 (HSV-1), varicella zoster virus (VZV), or human cytomegalovirus (HCMV). In a case of anterior uveitis, PCR was performed with a sample from the anterior chamber. RESULTS: Herpesvirus DNA was amplified in 11 of 17 samples. HCVM DNA was detected in nine samples but DNA from HSV-1 and VZV were detected only once each. CONCLUSION: These results strongly suggest that PCR could be used for a rapid complementary diagnosis of viral uveitis and retinitis. A prospective study to evaluate the PCR results, clinical evolution, and treatment is imperative to corroborate the real value of PCR in diagnosis and how it could help the clinicians' approach.

Cytomegalovirus antigenemia in acquired immunodeficiency syndrome patients with untreated cytomegalovirus retinitis.

PURPOSE: To determine the frequency of cytomegalovirus (CMV) viremia in patients with acquired immunodeficiency syndrome (AIDS) and untreated CMV retinitis using conventional cell culture isolation and the sensitive CMV antigenemia assay. METHODS: We examined 24 AIDS patients with ophthalmologic diagnosis of untreated CMV retinitis and 24 AIDS patients without present or past retinitis (control patients) from three medical centers between September 1992 and March 1994. Cytomegalovirus antigenemia was detected by an indirect peroxidase staining in 300,000 cytocentrifuged neutrophils, using a mixture of murine monoclonal antibodies directed against the pp65 lower matrix protein of CMV. RESULTS: Positive antigenemia was demonstrated in eight (33.3%) of the 24 retinitis patients and in none of the 24 control patients (P < .001). Only two of the eight antigenemia-positive patients had a concurrent positive CMV isolation from blood leukocytes by conventional cell culture assay. CONCLUSIONS: These results emphasize the risk of extraocular disease in AIDS patients with CMV retinitis because the virus is often present in peripheral blood leukocytes. The CMV antigenemia assay may be a simple and rapid means of identifying those patients with unilateral retinitis at highest risk of developing CMV retinitis of the fellow eye or of visceral CMV disease if intravitreal injections or implants are used as sole treatment for CMV retinitis.

Cytomegalovirus Antigenemia in Acquired Immunodeficiency Syndrome Patients With Untreated Cytomegalovirus Retinitis

PURPOSE: To determine the frequency of cytomegalovirus (CMV) viremia in patients with acquired immunodeficiency syndrome (AIDS) and untreated CMV retinitis using conventional cell culture isolation and the sensitive CMV antigenemia assay. METHODS: We examined 24 AIDS patients with ophthalmologic diagnosis of untreated CMV retinitis and 24 AIDS patients without present or past retinitis (control patients) from three medical centers between September 1992 and March 1994. Cytomegalovirus antigenemia was detected by an indirect peroxidase staining in 300,000 cytocentrifuged neutrophils, using a mixture of murine monoclonal antibodies directed against the pp65 lower matrix protein of CMV. RESULTS: Positive antigenemia was demonstrated in eight (33.3 por cento) of the 24 retinitis patients and in none of the 24 control patients (P < .001). Only two of the eight antigenemia-positive patients had a concurrent positive CMV isolation from blood leukocytes by conventional cell culture assay. CONCLUSIONS: These results emphasize the risk of extraocular disease in AIDS patients with CMV retinitis because the virus is often present in peripheral blood leukocytes. The CMV antigenemia assay may be a simple and rapid means of identifying those patients with unilateral retinitis at highest risk of developing CMV retinitis of the fellow eye or of visceral CMV disease if intravitreal injections or implants are used as sole treatment for CMV retinitis

Periflebite retiniana aguda congelada: relato de um caso atípico / Acute frosted retinal periphebitis. Report of an atypical case

Os autores relatam um caso de vasculite retiniana aguda bilateral em uma paciente de 31 anos de idade, que apresentou, em um dos olhos acometidos, um aspecto fundoscópico semelhante ao quadro descrito na literatura como "periflebite retiniana aguda congelada" ou "angelite de ramos congelados".

Cytomegalovirus retinitis in AIDS patients: a clinical review

Cytomegalovirus (CMV) retinitis is an ocular condition previously seen in organ transplant recipients, patient on chemotherapy for malignancy, and in infants with congenital infections. As it present in immunocompromised, the AIDS patient has integrated this group of patients that can present with CMV retinitis. Moreover, it is the leading cause of opportunistic ocular infection in the AIDS patient, and the second most common ocular manifestation. As new drugs and modes of administration are studied that can effectively halt this progressively blinding condition, the awareness and recognition of CMV retinitis on AIDS patients has become increasingly important. This author will review the epidemiology, clinical presentation, and differential diagnosis of this condition. The current treatments being used and complications will also be discussed

Cytomegalovirus retinitis in AIDS patients: a clinical review.

Cytomegalovirus (CMV) retinitis is an ocular condition previously seen in organ transplant recipients, patient on chemotherapy for malignancy, and in infants with congenital infections. As it present in immunocompromised, the AIDS patient has integrated this group of patients that can present with CMV retinitis. Moreover, it is the leading cause of opportunistic ocular infection in the AIDS patient, and the second most common ocular manifestation. As new drugs and modes of administration are studied that can effectively halt this progressively blinding condition, the awareness and recognition of CMV retinitis on AIDS patients has become increasingly important. This author will review the epidemiology, clinical presentation, and differential diagnosis of this condition. The current treatments being used and complications will also be discussed.