Incidence Of Cytomegalovirus Retinitis Research Articles

Cytomegalovirus retinitis after allogeneic hematopoietic stem cell transplantation under cytomegalovirus antigenemia-guided active screening.

Although cytomegalovirus (CMV) remains a leading cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT), the incidence of CMV retinitis is considered to be lower than the incidence of CMV infection in other organs following allogeneic HSCT. In this study, the incidence and characteristics of CMV retinitis were retrospectively evaluated in recipients of allogeneic HSCT. Ophthalmological screening was performed at the development of ocular symptoms or positive CMV infection using peripheral blood evaluated by pp65 antigenemia or polymerase chain reaction. Of the 514 patients, 13 patients developed CMV retinitis. The median onset of CMV retinitis was day 34 (range, 21-118) post transplant, and the cumulative incidence was 2.5% (95% CI, 1.6-4.2) at 6 months after transplantation. Five patients presented ocular symptoms at the onset. In the remaining eight asymptomatic patients, the diagnosis of CMV retinitis was made by the screening guided by positive CMV infection. All evaluable patients responded to antiviral treatment but three showed incomplete improvement with ocular sequela. Our results suggest that the incidence of CMV retinitis after allogeneic HSCT is not negligible and active ophthalmological screening based not only on symptoms but also positive CMV infection monitoring contributes to the early diagnosis of CMV retinitis.

Cytomegalovirus Retinitis in HIV and Non-HIV Individuals.

Cytomegalovirus retinitis (CMVR) is a severe, vision-threatening disease that primarily affects immunosuppressed patients. CMVR is the most common ocular opportunistic infection in human immunodeficiency virus (HIV) infected patients and is the leading cause of blindness in this group; however, the incidence of CMVR in HIV patients has dramatically decreased with antiretroviral therapy. Other causes of immunosuppression, including organ transplantation, hematologic malignancies, and iatrogenic immunosuppression, can also lead to the development of CMVR. Herein, we describe the pathogenesis of CMVR and compare clinical features, epidemiology, and risk factors in HIV and non-HIV infected individuals with CMVR.

Opportunistic ocular infections in the setting of HIV.

The aim of this review is to highlight recent changes in opportunistic ocular infections (OOIs) in the era of modern combination antiretroviral therapy (cART), in the setting of HIV-infected patients. Improvements in modern cART has led to a progressive decline in the incidence of OOIs and mortality among patients with AIDS. Not only has there been a decreasing incidence of cytomegalovirus (CMV) retinitis, but there also has been a decline in progression of such retinitis when it does occur in AIDS patients, since the introduction of cART. Nevertheless, CMV retinitis remains the major cause of vision loss in AIDS patients. Although the incidence of CMV retinitis has declined overall, the incidence of ocular syphilis has increased during the cART era. Moreover, the impact of having HIV plays a role with respect to multidrug-resistant (MDR) tuberculosis and has resulted in a high prevalence of presumed ocular tuberculosis in HIV/MDR-TB co-infected patients. Although immune reconstitution uveitis (IRU) has been an important cause of visual deficits in developed countries, OOIs remain an important cause of blindness in the developing world. Reconstituting the immune system with effective cART while increasing accessibility of screening examinations is key to the success of blindness prevent in HIV-infected individuals, particularly in developing countries.

Cytomegalovirus Retinitis in Pediatric Stem Cell Transplants: Report of a Recent Cluster and the Development of a Screening Protocol

The incidence of cytomegalovirus (CMV) retinitis in the pediatric allogeneic hematopoietic stem cell transplant (HSCT) population is unknown. We report a cluster of 5 pediatric patients with CMV retinitis diagnosed in a 12-month period and compare this to the rate of CMV viremia and retinitis in the 4 years prior. Presented is the ophthalmic screening protocol developed in response to this experience. Retrospective cross-sectional study. A retrospective chart review was performed on patients at Children's Hospital of Colorado (CHCO) who received allogeneic HSCT between January 2010 and December 2014. Fisher exact test was used to compare the proportion of CMV viremia and CMV retinitis in patients transplanted between January 2010 and December 2013 with those transplanted in 2014. A total of 101 patients underwent allogeneic HSCT from January 2010 to December 2013; 32 (32%) tested positive for CMV viremia. No cases of CMV retinitis were identified. From January 2014 to December 2014, 28 patients underwent allogeneic HSCT; 13 patients (46%) had CMV viremia, not a statistically significant increase (P= .18). There were 5 cases of CMV retinitis diagnosed in those transplanted in 2014, a statistically significant increase compared with those transplanted in 2010-2013 (P= .0004). A multidisciplinary team was formed to review the literature and an ophthalmic screening protocol was developed. Our recent cluster of CMV retinitis in pediatric allogeneic HSCT patients may suggest a rise in incidence of CMV retinitis. We propose an ophthalmic screening protocol to diagnose retinitis in pediatric HSCT patients in the early, often asymptomatic stage.

Management of ganciclovir-resistant cytomegalovirus retinitis in HIV infection in the era of antiretroviral therapy

The incidence of cytomegalovirus retinitis has decreased significantly since the advent of antiretroviral therapy. However, it remains an important problem in both the developed and developing worlds. Furthermore, long-term antiviral suppression is associated with a significant increase in viral resistance. We present the case of a 46-year-old man who developed cytomegalovirus retinitis one year after being diagnosed with HIV. While he initially demonstrated an excellent clinical response to ganciclovir, his cytomegalovirus viral load remained persistently elevated. Over the subsequent years, his virus developed ganciclovir resistance with a concomitant deterioration in his visual acuity. He responded poorly to salvage therapy with foscarnet and cidofovir. This case highlights the ongoing difficulty of managing cytomegalovirus disease nearly two decades into the era of antiretroviral therapy and underlines the need to develop new treatment strategies.

A possible coincidence of cytomegalovirus retinitis and intraocular lymphoma in a patient with systemic non-Hodgkin’s lymphoma

PurposeTo present a possible coincidence of cytomegalovirus retinitis and intraocular lymphoma in a patient with systemic non-Hodgkin’s lymphoma.Case presentationA 47-year-old woman presented with decreased visual acuity associated with white retinal lesions in both eyes. A history of pneumonia of unknown aetiology closely preceded the deterioration of vision. Five years previously the patient was diagnosed with follicular non-Hodgkin’s lymphoma. She was treated with a chemotherapy regimen comprised of cyclophosphamide, adriamycin, vincristin, and prednisone with later addition of the anti-CD20 antibody rituximab. She experienced a relapse 19 months later with involvement of the retroperitoneal lymph nodes, and commenced treatment with rituximab and 90Y-ibritumomab tiuxetan. A second relapse occurred 22 months after radioimmunotherapy and was treated with a combination of fludarabine, cyclophosphamide, and mitoxantrone followed by rituximab. The patient experienced no further relapses until the current presentation (April, 2010).Pars plana vitrectomy with vitreous fluid analysis was performed in the right eye. PCR testing confirmed the presence of cytomegalovirus in the vitreous. Atypical lymphoid elements, highly suspicious of malignancy were also found on cytologic examination. Intravenous foscarnet was administered continually for three weeks, followed by oral valganciclovir given in a dose of 900 mg twice per day. In addition, the rituximab therapy continued at three monthly intervals. Nevertheless, cessation of foscarnet therapy was followed by a recurrence of retinitis on three separate occasions during a 3-month period instigating its reinduction to the treatment regime after each recurrence.ConclusionsCytomegalovirus retinitis is an opportunistic infection found in AIDS patients as well as in bone marrow and solid organ transplant recipients being treated with systemic immunosuppressive drugs. This case presents a less common incidence of cytomegalovirus retinitis occurring in a patient with non-Hodgkin’s lymphoma. We demonstrated a possible coexistence of cytomegalovirus retinitis and intraocular lymphoma in this particular patient. The final diagnosis was based on clinical manifestations together with the course of uveitis and its response to treatment alongside the results of vitreous fluid analysis. This report highlights the importance of intraocular fluid examination in cases with nonspecific clinical manifestations. Such an examination allows for the detection of simultaneously ongoing ocular diseases of differing aetiologies and enables the prompt initiation of effective treatment.

The Epidemiology and Incidence of Cytomegalovirus Retinitis in the HIV Population in Singapore over 6 Years

We report the epidemiologic trend of cytomegalovirus (CMV) retinitis among human immunodeficiency virus (HIV) patients in Singapore. Our study included a retrospective case series of HIV patients with newly diagnosed CMV retinitis (CMVR) at the Singapore CDC between 2005 and 2010. Demographics, symptoms, signs, and laboratory results, including CD4 counts, were collected. Prevalence and disease trends over time were measured. Of 224 new patients, 92.9% were male and 96.0% were on antiretroviral therapy (ART). Median age was 43.0 years, with a median CD4 count of 38.0 cells/μL at HIV diagnosis. There was a decline in CD4 counts at diagnosis, and median duration of ART initiation from HIV diagnosis generally was earlier. Overall incidence rate was 10.4 cases per 1000 person-years (PY) and the mortality rate was 19.4 per 1000 PY. Mean survival time was 160.2 months (95% confidence interval [CI] 150.3-170.2). The 25 patients who died during the study period were older at the time of CMVR diagnosis (P = 0.003) and had lower CD4 counts (P = 0.030). Worse prognoses were associated with older age (hazard ratio [HR] 1.06, 95% CI 1.02-1.10) and shorter time lag from HIV to CMVR diagnosis (HR 0.97, 95% CI 0.95-0.99). Patients who did not receive highly active antiretroviral treatment (HAART) had a higher mortality risk (HR 4.70, 95% CI 1.54-14.33). The incidence rate of CMVR was decreasing with earlier initiation of ART and lower CD4 counts at HIV diagnosis. Poor prognostic factors included older age, shorter time lag from HIV to CMVR diagnosis, and the absence of HAART. Constant ophthalmologic surveillance until immune reconstitution is recommended.

Incidence of Cytomegalovirus Retinitis in Patients With Human Immunodeficiency Virus Following Negative Initial Screening Examination Results

Incidence of Cytomegalovirus Retinitis in Patients With Human Immunodeficiency Virus Following Negative Initial Screening Examination Results

Incidence of Cytomegalovirus Retinitis in the Era of Highly Active Antiretroviral Therapy

To estimate the incidence of cytomegalovirus (CMV) retinitis in the era of highly active antiretroviral therapy (HAART) and to characterize the factors associated with increased risk of CMV retinitis. Prospective cohort study. A total of 1600 participants with acquired immunodeficiency syndrome (AIDS) but without CMV retinitis at enrollment who completed at least 1 follow-up visit in the Longitudinal Study of the Ocular Complications of AIDS (LSOCA) were seen every 6 months to obtain disease and treatment history, ophthalmic examination, and laboratory testing. Incidence of CMV retinitis and risk factors for incident CMV retinitis were assessed. The incidence rate of CMV retinitis in individuals with AIDS was 0.36/100 person-years (PY) based upon 29 incident cases during 8134 PY of follow-up. The rate was higher for those with a CD4+ T cell count at the immediately prior visit below 50 cells/μL (3.89/100 PY, P < .01), whereas only 1 individual with a CD4+ T cell count of 50 to 99 cells/μL and 2 individuals with a CD4+ T cell count >100 cells/μL developed CMV retinitis. Having a CD4+ T cell count below 50 cells/μL at the clinical visit prior to CMV retinitis evaluation was the single most important risk factor (HR: 136, 95% CI: 30 to 605, P < .0001) for developing retinitis. Patients with AIDS, especially those with severely compromised immune systems, remain at risk for developing CMV retinitis in the HAART era, although the incidence rate is reduced from that observed in the pre-HAART era.

Human immunodeficiency virus and its effects on the visual system

During the first 15 years of the AIDS epidemic patients experienced a high incidence of blindness due to cytomegalovirus (CMV) retinitis and other severe ocular opportunistic infections. Highly active anti-retroviral therapy, introduced in 1996, dramatically decreased the incidence of CMV retinitis. Though CMV retinitis still causes 40% of vision loss in AIDS patients, other conditions such as immune reconstitution uveitis, cataracts, and a significant othercategory -which most investigators believe is directly due to HIV - comprise the majority of cases. HIV causes vascular abnormalities of the conjunctiva and retina in the majority of AIDS patients, as well as retinitis, anterior and posterior uveitis and vasculitis. HIV frequently causes an optic neuropathy and is responsible for the majority of eye movement disorders among HIV patients. Physicians need to be aware that these problems may be the initial manifestation of HIV infections or a sign of highly active anti-retroviral therapy (HAART) failure. Therefore, patients with identifiable risk factors for AIDS who present with ophthalmologic conditions of unknown etiology should be considered for HIV testing. Finally, anti-retroviral therapy has been reported to cause asymptomatic deposits as well as degenerative conditions of both the anterior and posterior segments of the eye.

Cystoid macular edema secondary to immune recovery uveitis in a man with cytomegalovirus retinitis and AIDS

Cytomegalovirus (CMV) is the most common intraocular opportunistic infection in profoundly immunocompromised patients with AIDS. It is characterized by an acute, progressive, necrotizing retinitis in patients with a CD4 count of <50 cells/μL. Although the incidence of CMV retinitis has declined because of the introduction of antiretroviral therapy (ART), a new syndrome of intraocular inflammation has emerged in patients with rising CD4 lymphocyte counts following ART. This is called immune recovery uveitis (IRU). It is thought to occur as a result of restored immunity to various infectious agents, commonly mycobacterial, Cryptococcus, and herpes virus infections. We report a man who was treated for CMV retinitis and later developed IRU in the form of cystoid macular edema (CMO) even though his CMV retinitis remained inactive. His CMO resolved and visual acuity improved 2 years after the onset of CMO without any treatment interventions.

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.

Effect of highly active antiretroviral therapy on the incidence of HIV-related cytomegalovirus retinitis and retinal detachment.

Cytomegalovirus retinitis (CMVR) is the most common intraocular infection encountered in ophthalmic practices. To assess the impact of highly active antiretroviral therapy (HAART) on the incidence of CMVR and subsequent retinal detachments, a retrospective review of the HIV+ patients seen at a single university and community-based practice between 1992-1993 (group 1), before the advent of protease inhibitors, was compared with the data obtained from October 1996 to October 1997 (group 2) and October 1997-1998 (group 3), after the widespread use of HAART. The incidence of CMVR and retinal detachment rates for each group was calculated and compared. Twenty five (2.6%) of 974 HIV+ patients in group 1 developed CMVR. Of these, four patients developed retinal detachment (16%). Group 2 had a total of 1084 HIV+ patients, 18 (1.7%) of whom developed CMVR, which indicates a 35% decline of the incidence of CMV retinitis at our institution (p = 0.052, Odds ratio = 0.533, Confidence interval 0.28-1.01) and three patients (20%) developed retinal detachment. Only 1 patient (0.07%) of 1274 patients in group 3 developed CMVR, which represents a 99% reduction since 1993 (p = 0.0000000456). We conclude that the incidence of CMVR at this institution has decreased significantly with the recent use of HAART therapy. This effect may be related to the aggressive use of HAART and associated immune recovery in this population of AIDS patients. In this small series, however, the rate of retinal detachment appeared unchanged, but was only observed in those individuals who were not on HAART or who had just recently started.

Changes in the natural history of cytomegalovirus retinitis following the introduction of highly active antiretroviral therapy.

To determine the effect of highly active antiretroviral therapy (HAART) on the natural history of cytomegalovirus (CMV) retinitis. Retrospective analysis of 103 consecutive patients diagnosed with CMV retinitis between 1990 and 1998. Specialist HIV medicine department of a London hospital. Incidence of CMV retinitis, time to death following diagnosis, episodes of progression, incidence of inflammatory complications. The date of first use of HAART was January 1995. Data were censored on 30 June 1998. The incidence of CMV retinitis has declined dramatically following the introduction of HAART. Survival following CMV retinitis increased from a median of 0.65 years prior to 1995 to a median of 1.07 years after this date (P = 0.004). In multivariate analyses HAART was independently associated with improved survival (P = 0.02) and the association with year of diagnosis was no longer significant, suggesting that this effect is predominantly due to HAART. None of the patients receiving HAART experienced progression after 6 months of treatment. Complications of retinitis such as retinal detachment, uveitis and optic atrophy occurred in 39% of patients. The rare inflammatory complications of vitritis and cystoid macular oedema occurred only in recipients of HAART. The introduction of HAART has had a major impact on the natural history of CMV retinitis with improved survival time and decreased risk of progression following diagnosis. However, immune reconstitution may be associated with inflammatory complications which can result in significant visual loss in the absence of active CMV disease.

Oral Ganciclovir for the Prevention of Cytomegalovirus Disease in Persons with AIDS

In the advanced stages of the acquired immunodeficiency syndrome (AIDS), cytomegalovirus (CMV) disease, particularly vision-damaging retinitis due to CMV is common. We evaluated prophylactic treatment with orally administered ganciclovir as a way to prevent CMV disease. We conducted a prospective, randomized, double-blind, placebo-controlled study of CMV infected persons with AIDS with either CD4+ lymphocyte counts of < or = 50 per cubic millimeter or counts of < or = 100 per cubic millimeter in those with a history of an AIDS defining opportunistic infection. Patients were randomly assigned, in a 2:1 ratio, to receive either oral ganciclovir (1000 mg three times daily) or placebo. The study was stopped after a median 367 days of follow-up. In an intention-to-treat analysis, the twelve month cumulative rates of confirmed CMV disease were 26 percent in the placebo group (n = 239) and 14 percent in the ganciclovir group (n = 486), representing an overall reduction in risk of 49 percent in the ganciclovir group (P < 0.001). The incidence of CMV retinitis after 12 months was 24 percent in the placebo group and 12 percent in the ganciclovir group (P < 0.0001). The prevalence of CMV-positive urine cultures at base line was 42 percent; after two months it was 43 percent in the placebo group and 10 percent in the ganciclovir group (P < 0.0001). The one year mortality rate was 26 percent in the placebo group and 21 percent in the ganciclovir group (P = 0.14). Therapy with granulocyte colony stimulating factor was more frequent in the ganciclovir group (24 percent) than in the placebo group (9 percent). In persons with advanced AIDS, phophylactic oral ganciclovir significantly reduces the risk of CMV disease.

Cytomegalovirus retinitis in children following bone marrow transplantation

The authors describe three children, aged one, 13 and 24 months, who developed cytomegalovirus (CMV) retinitis seven to 18 months following allogeneic BMT. The underlying disease in two patients was severe combined immunodeficiency disease (SCID) and acute myeloid leukemia (AML) M5 in the third. All three patients developed chronic graft-versus-host-disease (GVHD) and received massive immunosuppressive therapy. The CMV retinitis was treated with ganciclovir. Clinical improvement was observed in the two SCID patients. The AML patient whose acute inflammatory retinitis was controlled, nevertheless developed optic atrophy in both eyes and VEP and ERG responses disappeared. The incidence of cytomegalovirus retinitis in our pediatric population of bone marrow transplant (BMT) recipients in the last three years was higher than expected: 3/85 (3.5%). Alertness to the possibility of intraocular complications is advocated. Early detection of CMV retinitis and intensive treatment with ganciclovir can save vision. It is therefore suggested to perform ocular examinations as part of the routine follow-up of BMT patients, especially in children with profound immune deficiency.