Visual prognosis, clinical features, and predisposing factors in non-HIV patients with cytomegalovirus retinitis.

PURPOSE: To study the characteristics and visual outcome of cytomegalovirus retinitis in patients of a tertiary referral ophthalmology center. METHODS: This retrospective cross-sectional study included 16 patients who presented with CMV retinitis between February 2014 and January 2017. Demographics, clinical signs, course of treatment, and visual and anatomical results were analyzed. RESULTS: Twenty five eyes of 16 patients were included. Eleven (68.8%) were females. The mean age was 29.37 ± 17.12 (range 11-73) years. Involvement was bilateral in 9 (56.2%) cases. HIV serology was negative in all patients. Best-corrected visual acuity was 0.57 ± 0.55 logarithm of the minimal angle of resolution (LogMAR) at the time of presentation and decreased to 0.69 ± 0.55 LogMAR on final visit (P = 0.332). None of the patients participating in this study was HIV-positive. CONCLUSION: CMV retinitis is a devastating complication in immunosuppressed. The visual acuity usually decreases despite aggressive appropriate treatment. This observation supports the increasing incidence of CMV infection in non-HIV patients.

Analysis and Outcomes of Cataract Surgery in Patients with Acquired Immunodeficiency Syndrome.

PURPOSE: To investigate the surgical outcomes, complications and postoperative progression in HIV patients undergoing cataract surgery in a teaching hospital. METHODS: A retrospective cohort study of patients with HIV/AIDS who had cataract surgery from January 2000 until December 2011 at a tertiary referral multidisciplinary hospital in Singapore. RESULTS: We identified 44 eyes from 29 patients. Preoperatively, 41.3% had no ophthalmic manifestations of HIV/AIDS, while 16 eyes had quiescent cytomegalovirus retinitis (CMVR). Postoperatively, 1 eye developed new CMVR, while 1 eye had reactivation of previous CMVR. Of eyes with new or previous CMVR, 1 eye developed rhegmatogenous retinal detachment (RD) postoperatively. Only 3 eyes had prolonged postoperative inflammation. There were no cases of endophthalmitis or cystoid macular edema. Postoperative improvement of at least two Snellen lines was achieved in 86.6% of eyes. CONCLUSIONS: Cataract surgery in HIV patients is generally safe, regardless of CD4 count, but their general and ocular health should be optimized preoperatively.

Multiple intravitreal injections of ganciclovir for cytomegalovirus retinitis after stem-cell transplantation.

BACKGROUND: Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality in patients after hematopoietic stem cell transplantation (HSCT). Although much effort has been put into dealing with CMV retinitis secondary to acquired immunodeficiency syndrome (AIDS), the few reports which have been published have mainly focused on treatment of CMVR after HSCT. METHODS: This clinical interventional retrospective study included 14 patients (eight men; mean age 23.89 ± 12.09; 23 eyes) who suffered from CMV retinitis after stem-cell transplantation, in order to evaluate the efficacy and safety of multiple intravitreal injections of ganciclovir (IVG) for patients with CMV retinitis. All patients received 4 injections of IVG of 1 mg at 1 week intervals, and were followed up weekly for at least 2 months with measurement of best-corrected visual acuity (BCVA) and CMV levels in anterior aqueous humor with real-time polymerase chain reaction. Anterior aqueous humor was obtained before each injection. RESULTS: The levels of CMV in anterior aqueous humor showed significant decrease from (6.34 ± 15.78) × 10(5) copies/ml at baseline to (5.22 ± 12.15) × 10(3) copies/ml at 1 month (P < 0.001, Mann-Whitney U test). CMV couldn't be detected in 11 eyes (47.8 %) after two injections, and this rose to 18 eyes (78.3 %) at 1 month. The mean logMAR BCVA was 0.659 ± 0.572 at baseline and 0.680 ± 0.527 at 2 months, which suggested no significant improvement (P = 0.736, Mann-Whitney U test) during the procedure. All patients experienced improved vitreous opacity and diminished area of the lesion under funduscopy after 4 injections of IVG. No severe complications developed. CONCLUSIONS: Multiple IVG seemed to be beneficial for patients with CMV retinitis after stem-cell transplantation, in reducing CMV levels in aqueous humor. Further study to optimize the dose of ganciclovir is needed in order to achieve better treatment outcomes.

Human immunodeficiency virus-associated cytomegalovirus infection with multiple small vessel cerebral infarcts in the setting of early immune reconstitution.

Cytomegalovirus (CMV) infection is an important cause of neurologic disease in the context of advanced human immunodeficiency virus (HIV) infection and is recognized as a cause of immune reconstitution inflammatory syndrome (IRIS) after initiation of highly active antiretroviral therapy (HAART). Central nervous system vasculitis secondary to CMV has only rarely been described in the context of HIV, despite the established ability of CMV to infect microvascular endothelial cells in the brain. However, we report a case that demonstrates the association between CMV and multiple small vessel cerebral infarct lesions after initiation of HAART.

Clinical features and outcomes of cytomegalovirus retinitis after transplantation.

Cytomegalovirus (CMV) infection of the retina is a rarely encountered end-organ disease after transplantation. In order to describe the clinical characteristics and outcomes of CMV retinitis after hematopoietic stem cell and solid organ transplantation, we performed a retrospective review of all cases of CMV retinitis at the Mayo Clinic (Rochester, Minnesota) during 1990-2004. During this 15-year period, CMV retinitis was diagnosed in 14 eyes of 9 patients who had received kidney (n=5), liver (n=2), heart (n=1), and autologous hematopoietic stem cell transplant (n=1). The mean age of the patients was 58 (standard deviation+/-11) years; 6 were male. The median time to diagnosis of CMV retinitis was 9 months (range, 4 months to 13 years) after transplantation. Four (44%) patients had concomitant pneumonitis or hepatitis. Five (55%) patients had bilateral retinitis. Retinal involvement was 10% but 50% in 2 eyes. All patients received induction therapy with intravenous ganciclovir (n=8) or foscarnet (n=1) for a median of 43 days (range, 14-100 days) followed by maintenance therapy with intravenous or oral ganciclovir for a median of 88 days (range, 36-943 days) in 6 (67%) patients. One patient developed bilateral immune recovery uveitis during treatment, and later on progressed to develop rhegmatogenous retinal detachment. During the mean follow-up period of 20 months, visual acuity improved in 4 (28.5%), was stable in 4 (28.5%), and worsened in 6 (43%) eyes. CMV retinitis recurred in 2 patients. In conclusion, CMV retinitis is a rare, progressive, and highly morbid infectious complication of transplantation. The severity of clinical disease at the time of diagnosis may predict poor outcome. Hence, early intervention may be crucial to prevent its progression to irreversible visual loss.

Cytomegalovirus ventriculoencephalitis in a bone marrow transplant recipient receiving antiviral maintenance: clinical and molecular evidence of drug resistance.

We describe a case of CMV ventriculoencephalitis in a severely immunocompromised bone marrow transplant recipient who was receiving combination therapy with ganciclovir and foscarnet for treatment of viremia and retinitis. Analysis of sequential viral isolates recovered from the patient's cerebrospinal fluid suggested that disease developed because of the presence of viral resistance and, possibly, low tissue penetration of antiviral agents.

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

OBJECTIVE: To determine the effect of highly active antiretroviral therapy (HAART) on the natural history of cytomegalovirus (CMV) retinitis. DESIGN AND PARTICIPANTS: Retrospective analysis of 103 consecutive patients diagnosed with CMV retinitis between 1990 and 1998. SETTING: Specialist HIV medicine department of a London hospital. MAIN OUTCOME MEASURES: 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. RESULTS: 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. CONCLUSIONS: 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.

Identifying the content area for the 51-item National Eye Institute Visual Function Questionnaire: results from focus groups with visually impaired persons.

OBJECTIVE: To identify the content area for a questionnaire designed to measure vision-targeted health-related quality of life and to determine whether problems with vision-related functioning are qualitatively similar across different common eye diseases. DESIGN: Twenty-six condition-specific focus groups were conducted with 246 patients from 5 geographic regions to identify the content area for a questionnaire for use among persons with diabetic retinopathy, glaucoma, macular degeneration, cytomegalovirus retinitis, and cataract. A standard protocol was used to structure each focus group discussion. Sessions were audiotaped, transcribed, and coded in preparation for a content analysis. SETTINGS: Five university-based ophthalmology practices and 1 nonprofit eye care foundation. PARTICIPANTS: Eligible participants had to have 1 of the following eye conditions: age-related cataracts, age-related macular degeneration, diabetic retinopathy, primary open angle glaucoma, cytomegalovirus retinitis, or low vision from any cause. All eligible persons were older than 21 years, spoke English, and had sufficient cognitive function to provide informed consent. RESULTS: Among the 246 participants, 2623 problems with vision-related functioning were mentioned. The mean number of problems per person ranged from 13.5 for those with diabetic retinopathy to 7.9 for persons with glaucoma. For the sample overall, reading problems were mentioned most frequently, followed by driving, general problems with seeing clearly, and mental health complaints caused by vision. Although the proportion of persons who reported each problem varied by condition, at least some persons with each eye disease reported each problem. The 3 most common descriptors associated with each problem were difficulty or ease of performance (13%), psychological distress associated with performance of the activity (11%), and complete inability to participate in a visual activity (11%). CONCLUSION: An item-generation strategy for a new questionnaire using a standardized focus group method identified content areas and aspects of visual disability that are not included in currently available vision-specific instruments that assess the impact of common eye diseases on visual functioning in every-day life. Although participants mentioned problems that were unique to their disease, across conditions the problems mentioned were similar. These findings provide empirical evidence of content validity for a vision-targeted, health-related quality-of-life survey designed for use across conditions.

MSL-109 adjuvant therapy for cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome: the Monoclonal Antibody Cytomegalovirus Retinitis Trial. The Studies of Ocular Complications of AIDS Research Group. AIDS Clinical Trials Group.

OBJECTIVE: To evaluate the efficacy and safety of an intravenous human monoclonal antibody to cytomegalovirus (CMV), MSL-109, as adjuvant treatment for CMV retinitis. METHODS: Two hundred nine patients with acquired immunodeficiency syndrome and active CMV retinitis were enrolled in a multicenter, phase 2/3, randomized, placebo-controlled clinical trial. Patients received adjuvant treatment with MSL-109, 60 mg intravenously every 2 weeks, or placebo. Randomization was stratified on the basis of whether patients had untreated or relapsed retinitis. Primary drug therapy for CMV retinitis was determined by the treating physician. RESULTS: The rates of retinitis progression, as evaluated in a masked fashion, were 3.04/person-year in the MSL-109-treated group and 3.05/person-year in the placebo-treated group (P=.98; Wald test); the median times to progression were 67 days in the MSL-109-treated group and 65 days in the placebo-treated group. No differences between the 2 groups were noted in the rates of increase in retinal area involved by CMV, visual field loss, or visual acuity outcomes. The mortality rate in the MSL-109-treated group was 0.68/person-year, and in the placebo-treated group, 0.31/person-year (P=.01). The mortality difference was not explained by differences in baseline variables or in concurrent antiretroviral therapy. Among patients with newly diagnosed retinitis, mortality rates were similar (MSL-109, 0.41/person-year; placebo, 0.42/person-year; P=.95), whereas among patients with relapsed retinitis the MSL-109-treated group had a greater mortality rate (MSL-109, 0.83/person-year; placebo, 0.24/person-year; P=.003). However, the mortality rate in the placebo-treated patients with relapsed CMV retinitis was lower than that in the placebo-treated patients with newly diagnosed CMV retinitis and lower than that in other trials of patients with relapsed CMV retinitis. CONCLUSIONS: Intravenous MSL-109, 60 mg every 2 weeks, appeared to be ineffective adjuvant therapy for CMV retinitis. The mortality rate was higher in the MSL-109-treated group, but the reasons for this difference remain uncertain.

Ganciclovir implant exchange. Timing, surgical procedure, and complications.

BACKGROUND: The ganciclovir implant is effective for the treatment of cytomegalovirus (CMV) retinitis. The device eventually runs out of drug, however, and must be replaced. We report our experience with exchanging ganciclovir implants during the course of a randomized clinical trial. METHODS: During our study, patients with newly diagnosed peripheral CMV retinitis were treated with a ganciclovir implant. The implant was scheduled for exchange at 32 weeks. It was exchanged earlier if progression of CMV retinitis occurred. Patient examinations and standard fundus photography were performed at 2-week intervals after the exchange procedure. RESULTS: Twenty-six exchange procedures were performed. Twenty-two eyes in 15 patients received a second implant and 4 eyes in 4 patients later received a third implant. Cytomegalovirus retinitis was rendered or maintained inactive in 22 of 23 cases with more than 1 month of follow-up after the second or third implants. Complications after the second implant procedure included transient vitreous hemorrhage in 5 eyes, postoperative inflammation in 1 eye, and retinal detachment in 1 eye. Median visual acuity returned to 20/25 by 28 days and to 20/20 by 42 days. Complications after the third implant procedure included dense vitreous hemorrhage in 3 of 4 eyes. Median survival time after a second implant procedure was 89 days. CONCLUSIONS: The initial ganciclovir implant exchange procedure is well tolerated with continued long-term control of CMV retinitis. Multiple reentries through the same wound may be associated with an increased risk for vitreous hemorrhage.

Detecting CMV retinitis: know what to look for. Treatment is effective but not pleasant.

AIDS: Approximately one-third of all AIDS patients develop cytomegalovirus (CMV) retinitis. Symptoms begin with blurred vision, loss of peripheral vision, and dark spots in the eye that obstruct vision. HIV-infected persons with CD4 counts below 100 should be tested twice a year for CMV. Oral ganciclovir (Cytovene) is a preventive option approved by the Food and Drug Administration (FDA). If diagnosed with CMV, a regimen of the antiviral drugs foscarnet and ganciclovir is initiated either as monotherapy or in combination. Side effects of combination therapy are greater than monotherapy and the treatment takes longer. Direct ganciclovir injections into the eye and ganciclovir implants are other options but are not FDA-approved. Other eye diseases can also occur, such as tumors, infections, and neuro-ophthalmic disorders.^ieng

Deletion mutants in human cytomegalovirus glycoprotein US9 are impaired in cell-cell transmission and in altering tight junctions of polarized human retinal pigment epithelial cells.

Retinal cytomegalovirus (CMV) disease is one of the major manifestations of viral pathogenesis in immunosuppressed patients with the acquired immunodeficiency syndrome (AIDS). CMV infection of the retina causes directional destruction which begins at the optic nerve head adjacent to the retinal capillaries and progresses, if untreated, to retinal detachment and blindness. Infection does not occur across the basal membrane of the retinal pigment epithelium (RPE), adjacent to the highly vascularized choroid. CMV replicates in polarized RPE cells, and progeny virions cross apical and lateral membranes of RPE cells grown on permeable filter supports, but not basal membranes. Cell-cell junctions of CMV-infected RPE cells are permeabilized, and the tight junction protein zonula occludens (ZO-1) is disassembled; progeny virions then spread to neighboring cells through the lateral cell membranes, which in polarized cells differ significantly in lipid and protein composition from the apical cell membranes. We found that CMV mutants with deletions in US9 and US8/US9 failed to spread from cell to cell, exhibiting a small-plaque phenotype in polarized RPE cells. Immunofluorescence confocal microscopy staining of ZO-1 protein revealed that RPE cells infected with CMV deletion mutants RV35, RV80, and RV61 did not exhibit altered tight junctions, in contrast to RPE cells infected with wild-type strain AD169 virus. Our findings indicate that US9, which is an accessory glycoprotein in infected foreskin fibroblasts, is required for transmission of virus across cell-cell junctions of polarized RPE cells. The relationship between US9 expression and virus transmission across cell-cell boundaries suggests that US9 may directly or indirectly permeabilize tight junction complexes of polarized RPE cells.

Improved visual results after surgical repair of cytomegalovirus-related retinal detachments.

PURPOSE: This study was conducted to determine whether visual outcomes have improved after repair of retinal detachments (RDs) associated with cytomegalovirus (CMV) retinitis, and, if so, whether factors such as earlier intervention and changes in surgical technique have led to these results. METHODS: The authors performed a retrospective review of 35 eyes in 30 immunocompromised patients with CMV retinitis and RD who underwent pars plana vitrectomy with the use of silicone oil injection. Visual and anatomic results in eyes treated between January 1991 and April 1992 (group 1) were compared with eyes treated before January 1991 (group 2). Follow-up was limited due to patient mortality; median follow-up was 4.1 months in group 1 and 2.5 months in group 2. RESULTS: Best-attained postoperative visual acuities were better for group 1 than group 2 eyes, with 71% of group 1 eyes attaining visual acuity of 20/200 or better compared with 17% of group 2 eyes (chi-square1 trend = 12.3; P < 0.001). A similar result was found among eyes with macula-off detachments. Ambulatory visual acuity of 5/200 or better was achieved in 86% of group 1 versus 33% of group 2 eyes. There was a longer interval between diagnosis and surgery in group 2 compared with group 1 (7 versus 3 days); scleral buckling in conjunction with pars plana vitrectomy and silicone oil injection was used in more group 1 eyes. CONCLUSION: Earlier intervention, absence of preoperative optic atrophy, and macular CMV correlate with better postoperative visual acuity results. Pars plana vitrectomy combined with silicone oil for eyes with macula-off RDs can result in improved visual acuity.