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.

Visual acuity outcomes in cytomegalovirus retinitis: early versus late diagnosis.

AIMS: To determine if early dilated fundus examination for cytomegalovirus (CMV) retinitis leads to better visual outcomes in areas with limited HIV care, where patients may have long-standing retinitis before they are diagnosed with HIV. METHODS: Twenty-four eyes of 17 patients with CMV retinitis who were seen at an urban HIV clinic in Chiang Mai, Thailand, were included in this retrospective cohort study. Participants were divided into two groups based on the amount of time from the first documented CD4 count below 100 cells/mm3 to the first eye examination for CMV retinitis. Average visual acuity in each group was calculated at the time CMV retinitis was first detected, and then at 3, 6 and 12 months after diagnosis. RESULTS: The group of patients who received an eye examination within approximately 4 months of the initial low CD4 count measurement had better baseline visual acuity (median 20/30,IQR 20/20 to 20/60) compared with patients who presented later (median 20/80, 20/60 to hand motion); p=0.03). Visual acuity did not change significantly during the 12-month study period in either the early group (p=0.69) or late group (p=0.17). CONCLUSION: In this study, patients who were examined sooner after a low CD4 count had better vision than patients who were examined later. Routine early screening of patients with CD4 counts under below 100 cells/mm3 may detect earlier disease and prevent vision loss.

SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY FINDINGS IN MACULA-INVOLVING CYTOMEGALOVIRUS RETINITIS.

PURPOSE: To evaluate the microstructural features of cytomegalovirus (CMV) retinitis by spectral domain optical coherence tomography (OCT). METHODS: Subjects were patients with macula-involving CMV retinitis with OCT imaging. The leading edge of retinitis in the macula was identified based on fundus imaging, and OCT findings were longitudinally evaluated in three areas: within the area of active retinitis, at the leading edge of retinitis, and just beyond the leading edge of retinitis. RESULTS: Optical coherence tomography imaging of macular CMV retinitis identified vitreous cells in 10 eyes (100%), posterior vitreous detachment in four eyes (40%), broad-based vitreomacular traction in one eye (10%), epiretinal membrane in eight eyes (80%), and lamellar hole-associated epiretinal proliferation associated with an atrophic hole in one eye (10%). Retinal architectural disruption, disruption of inner retinal layers, disruption of the external limiting membrane, and ellipsoid zone abnormalities were noted within the area of retinitis in all eyes and decreased in frequency and severity at and beyond the leading edge of retinitis, although all 10 eyes (100%) exhibited one of these abnormalities, especially outer retinal microabnormalities, beyond the leading edge of retinitis. CONCLUSION: Microstructural abnormalities were frequently noted on OCT of CMV retinitis, including within the retina beyond the leading edge of retinitis identified by corresponding fundus imaging. Outer retinal abnormalities were noted more frequently than inner retinal abnormalities beyond the leading edge of retinitis. These findings provide insight into the effects of CMV retinitis on retinal microstructure and potentially on vision and highlight the potential utility of OCT for monitoring microprogression of macula-involving CMV retinitis.

COMPARISON OF VISUAL PROGNOSIS AND CLINICAL FEATURES OF CYTOMEGALOVIRUS RETINITIS IN HIV AND NON-HIV PATIENTS.

PURPOSE: To compare the visual prognosis and clinical features of cytomegalovirus (CMV) retinitis between HIV and non-HIV patients. METHODS: Retrospective cross-sectional study on patients diagnosed with CMV retinitis. Depending on the presence of HIV infection, best-corrected visual acuity (VA) and clinical feature of CMV retinitis were analyzed. The clinical characteristics associated with poor visual prognosis after antiviral treatment were also identified. RESULTS: A total of 78 eyes (58 patients) with CMV retinitis were included in this study: 21 eyes and 57 eyes in HIV and non-HIV patients, respectively. Best-corrected VA was not significantly different between HIV and non-HIV patients. The rate of foveal involvement, retinal detachment, involved zone, and mortality did not significantly differ between the two groups. Visual acuity after antiviral treatment was significantly worse (pretreatment logarithm of the minimal angle of resolution best-corrected VA, 0.54 ± 0.67 [Snellen VA, 20/63]; posttreatment logarithm of the minimal angle of resolution best-corrected VA, 0.77 ± 0.94 [Snellen VA, 20/125]; P = 0.014). Poor visual prognosis was significantly associated with Zone 1 involvement, retinal detachment, and a poor general condition. CONCLUSION: The overall visual prognosis and the clinical features of CMV retinitis do not differ between HIV and non-HIV patients. The visual prognosis of CMV retinitis still remains quite poor despite advancements in antiviral treatment. This poor prognosis after antiviral treatment is associated with retinal detachment during follow-up, Zone 1 involvement, and the poor general condition of the patient.

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.

Diagnostic Utility of Ocular Symptoms and Vision for Cytomegalovirus Retinitis.

PURPOSE: Cytomegalovirus (CMV) retinitis remains a leading cause of blindness in countries with a high burden of AIDS. Although dilated fundus examinations are recommended for those with CD4 counts below 100 cells/µL, in practice only those with poor vision and/or symptoms are routinely referred for screening. Therefore, the predictive value of this common practice should be assessed. METHODS: This is a prospective cross-sectional study. Patients with known HIV and a CD4 count of less than 100 cells/µL attending an HIV clinic in Chiang Mai, Thailand completed a standardized questionnaire about visual symptoms and underwent visual acuity testing and dilated fundus examination. Participants without CMV retinitis were invited for repeated examinations every 3 months until their CD4 count exceeded 100 cells/µL. Patient-level statistical analyses were conducted to calculate diagnostic test characteristics, with bootstrapping to account for correlated data. RESULTS: Of 103 study participants, 16 had CMV retinitis diagnosed at some point during the study. Participants with CMV retinitis were more likely to complain of visual symptoms compared to those without CMV retinitis (p = 0.01), including scotoma (p = 0.0002), itchy or watery eyes (p < 0.0001), and eye pain (p = 0.003); they were also more likely to have visual acuity worse than Counting Fingers (p = 0.0003). However, the absence of eye symptoms and the absence of poor vision did not strongly affect the probability that a patient did not have disease (negative likelihood ratio 0.56 and 0.76, respectively). CONCLUSIONS: Ocular symptoms and poor visual acuity were poor diagnostic indicators for the presence of CMV retinitis. Systematic screening of HIV patients with CD4 counts below 100 cells/µl should be carried out to detect disease at an early stage, when blindness can still be prevented.

Long-term Follow-up of Cytomegalovirus Retinitis in Non-HIV Immunocompromised Patients: Clinical Features and Visual Prognosis.

PURPOSE: To evaluate clinical features and long-term visual outcome of cytomegalovirus (CMV) retinitis in patients without human immunodeficiency virus (HIV) infection, and to determine factors that predict visual outcome. DESIGN: Retrospective cohort study. METHODS: Consecutive patients with CMV retinitis without HIV infection were reviewed. Main outcome measures included clinical features, proportion of eyes with 6-month and final visual acuity (VA) <20/70 and <20/400, and odds ratios of factors associated with poor visual outcome. RESULTS: A total of 20 eyes from 13 patients were included with a median follow-up time of 17 months. All had at least 6 months of follow-up except 1 patient who died from sepsis at 1 month. At presentation, 50% of eyes had VA <20/70 and 25% had VA <20/400. Zone 1 involvement occurred in 55% and vitreous haze ≥grade 2+ occurred in 25%. Recurrence occurred in 33.3% at a mean time of 6.4 ± 3.3 weeks after discontinuation of anti-CMV therapy. The retinal detachment rate was 21.7% per eye-year and mortality rate was 11.7% per person-year. At final visit, 60% had VA <20/70 and 35% had VA <20/400. Macular involvement was significantly associated with poor final VA <20/400 (odds ratio = 25.00, P = .016). CONCLUSIONS: CMV retinitis without HIV infection was often aggressive at presentation. Significant intraocular inflammation was not uncommon. The long-term visual outcome was poor, especially in those with macular involvement.

Retinal detachment associated with AIDS-related cytomegalovirus retinitis: risk factors in a resource-limited setting.

PURPOSE: To determine risk factors predictive of retinal detachment in patients with cytomegalovirus (CMV) retinitis in a setting with limited access to ophthalmic care. DESIGN: Case-control study. METHODS: Sixty-four patients with CMV retinitis and retinal detachment were identified from the Ocular Infectious Diseases and Retina Clinics at Chiang Mai University. Three control patients with CMV retinitis but no retinal detachment were selected for each case, matched by calendar date. The medical records of each patient were reviewed, with patient-level and eye-level features recorded for the clinic visit used to match cases and controls, and also for the initial clinic visit at which CMV retinitis was diagnosed. Risk factors for retinal detachment were assessed separately for each of these time points using multivariate conditional logistic regression models that included 1 eye from each patient. RESULTS: Patients with a retinal detachment were more likely than controls to have low visual acuity (odds ratio [OR], 1.24 per line of worse vision on the logMAR scale; 95% confidence interval [CI], 1.16-1.33) and bilateral disease (OR, 2.12; 95% CI, 0.92-4.90). Features present at the time of the initial diagnosis of CMV retinitis that predicted subsequent retinal detachment included bilateral disease (OR, 2.68; 95% CI, 1.18-6.08) and lesion size (OR, 2.64 per 10% increase in lesion size; 95% CI, 1.41-4.94). CONCLUSION: Bilateral CMV retinitis and larger lesion sizes, each of which is a marker of advanced disease, were associated with subsequent retinal detachment. Earlier detection and treatment may reduce the likelihood that patients with CMV retinitis develop a retinal detachment.

[Retinal detachment in HIV-infected patients with cytomegalovirus retinitis].

The authors present their own clinical experience in three HIV-infected patients with cytomegalovirus retinitis aged from 8 to 36 years. Detailed analysis of the results of physical and laboratory examinations is provided. Given short life expectancy for these patients, the authors pose a deontological question as to whether or not active treatment of retinal detachment in patients with AIDS and CMV retinitis is reasonable.

Outcome of cytomegalovirus retinitis in immunocompromised patients without Human Immunodeficiency Virus treated with intravitreal ganciclovir injection.

PURPOSE: To study the outcomes of treatment with intravitreal ganciclovir injection for cytomegalovirus (CMV) retinitis in patients without Human Immunodeficiency Virus (HIV) infection. METHODS: In this retrospective cohort study, demographic and clinical characteristics of patients with CMV retinitis without HIV were noted. Patients received intravitreal ganciclovir injection (2 mg/0.1 ml) alone until quiescence. The outcome measures were time taken for the lesions to heal, number of injections, change in best-corrected visual acuity (BCVA), recurrence of retinitis, occurrence of immune recovery uveitis (IRU) or injection-related complications and retinal detachment (RD). RESULTS: 18 eyes of ten patients (six males) with mean age of 33.7 years from June 2004 to March 2013 were included. Thirteen eyes with active lesions (mean BCVA of 0.51 ± 0.41) received 5.54 ± 3.36 intravitreal ganciclovir injections with complete healing within 1.81 ± 1.25 months. The final BCVA was 0.43 ± 0.52. IRU was observed in six eyes (33.33%) and RD developed in one eye. One eye had recurrence 1 month after stopping ganciclovir injections. The rest of the patients had recurrence-free follow-up at 9.46 ± 12.42 months. CONCLUSIONS: Non-HIV patients with CMV retinitis can be successfully treated with intravitreal ganciclovir injection alone, avoiding the systemic side effects of systemic anti-CMV therapy.

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.

Comparison of treatment regimens for cytomegalovirus retinitis in patients with AIDS in the era of highly active antiretroviral therapy.

PURPOSE: To describe the outcomes of different treatment approaches for cytomegalovirus (CMV) retinitis in the era of highly active antiretroviral therapy (HAART). DESIGN: Prospective cohort study, the Longitudinal Study of the Ocular Complications of AIDS. PARTICIPANTS: A total of 250 patients with CMV retinitis and a CD4+ T-cell count <100 cells/µl (n = 221) at enrollment or incident retinitis (n = 29) during cohort follow-up. METHODS: The effects of systemic therapy (vs. intraocular therapy only) on systemic outcomes and the effect of intraocular therapies (ganciclovir implants, intravitreal injections) on ocular outcomes were evaluated. MAIN OUTCOME MEASURES: Mortality, CMV dissemination, retinitis progression, and treatment side effects. RESULTS: Regimens containing systemic anti-CMV therapy were associated with a 50% reduction in mortality (adjusted hazard ratio [HR], 0.5; 95% confidence interval [CI], 0.3-0.7; P = 0.006), a 90% reduction in new visceral CMV disease (adjusted HR, 0.1; 95% CI, 0.04-0.4; P = 0.004), and among those with unilateral CMV retinitis at presentation, an 80% reduction in second eye disease (adjusted HR, 0.2; 95% CI, 0.1-0.5; P = 0.0005) when compared with those using only intraocular therapy (implants or injections). Compared with systemic treatment only, regimens containing intravitreal injections had greater rates of retinitis progression (adjusted HR, 3.4; P = 0.004) and greater visual field loss (for loss of one half of the normal field, adjusted HR, 5.5; P < 0.01). Intravitreal implants were not significantly better than systemic therapy (adjusted HR for progression, 0.5; P = 0.26; adjusted HR for loss of one half of the visual field, 0.5; P = 0.45), but the sample size was small. Hematologic and renal side effect rates were similar between those groups with and without systemic anti-CMV therapy. The rate of endophthalmitis was 0.017 per eye-year (EY) (95% CI, 0.006-0.05) among those treated with intravitreal injections and 0.01 per EY (95% CI, 0.002-0.04) among those treated with an implant. CONCLUSIONS: In the HAART era, systemic anti-CMV therapy, while there is immune compromise, seems to provide benefits in terms of longer survival and decreased CMV dissemination. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Visual function analysis in acute posterior vitreous detachment.

OBJECTIVE: To determine whether the visual function of patients with posterior vitreous detachment (PVD)changes between the initial visit and a 6-week follow-up visit, and to compare their visual function with that of patients with macular degeneration, cataract, glaucoma, low vision, cytomegalovirus (CMV) retinitis, or diabetic retinopathy and a reference population. DESIGN: Prospective cohort study. PARTICIPANTS: All patients presenting to the Hotel Dieu Hospital Emergency Eye Clinic between September 2008 and June 2009 who were diagnosed with acute PVD were offered enrollment in the study. METHODS: Patients were administered the National Eye Institute Visual Function Questionnaire NEI VFQ-25 at two points in time. The composite scores from the initial and the 6-week visits were compared. The scores were also compared with established normative data and 6 ophthalmologic diagnoses. RESULTS: The NEI VFQ-25 composite score for patients with acute PVD (n = 84) at baseline was 93.26 ± 5.59 (mean ± SD). After 6 weeks and a second ocular examination, there was no statistical difference in the composite score of 93.47 ± 6.20 (mean ± SD). (1-sided paired t-test, t = 0.57; P = 0.28). CONCLUSIONS: The visual function of patients with acute PVD remains stable over the first 6 weeks after diagnosis. It is significantly higher than that of patients with 6 other ophthalmologic conditions but comparable to that of a normal population.

[Severe case of cytomegalovirus-associated immune reconstitution syndrome in AIDS].

BACKGROUND: Immune reconstitution syndrome (IRS) is a complication caused by reactivation of the immune system that can occur after starting highly active antiretroviral therapy (HAART) in patients with acquired immunodeficiency syndrome (AIDS). Severe IRS associated with cytomegalovirus (CMV) in both eyes who had lost his left vision is reported. CASE: A 37-year-old man with AIDS who had started HAART discontinued his medication. Two weeks after the re-induction of HAART, he suffered CMV retinitis OU. Vitreous opacity OU appeared 3 days later, and optic neuritis OS appeared 6 days after the onset; and visual acuity OS decreased to 0.06. As the number of CD 4 positive T lymphocytes (CD 4) increased from 39 to 118/microl in both the pre- and- post HAART, we diagnosed IRS and started anti- CMV and systemic steroid therapy and discontinued the HAART. The focus of CMV retinitis was improved; however, visual acuity OS did not improve. CONCLUSION: Severe IRS with visual loss induced by CMV retinitis after HAART needs to be considered in low CD 4 level patients during the induction phase.

Cytomegalovirus retinitis and the acquired immunodeficiency syndrome--bench to bedside: LXVII Edward Jackson Memorial Lecture.

PURPOSE: To update information on cytomegalovirus (CMV) retinitis in patients with acquired immunodeficiency syndrome (AIDS) and to integrate information on its pathogenesis and clinical outcomes. DESIGN: Literature review. METHODS: Selected articles from the medical literature, particularly large epidemiologic studies, including the Johns Hopkins Cytomegalovirus Retinitis Cohort Study, the Longitudinal Study of the Ocular Complications of AIDS, and the Cytomegalovirus Retinitis and Viral Resistance Study, were reviewed. Clinical information is discussed in light of knowledge on CMV, its pathogenesis, and its interactions with human immunodeficiency virus (HIV). RESULTS: Cytomegalovirus uses several mechanisms to evade the immune system and establish latent infection in immunologically normal hosts. With immune deficiency, such as late-stage AIDS, CMV reactivates, is disseminated to the eye, and establishes a productive infection, resulting in retinal necrosis. HIV and CMV potentiate each other: CMV accelerates HIV disease, and CMV retinitis is associated with increased mortality. Randomized clinical trials have demonstrated the efficacy of treatments for CMV retinitis. Systemically administered treatment for CMV retinitis decreases AIDS mortality. Highly active antiretroviral therapy (HAART) effectively suppresses HIV replication, resulting in immune recovery, which, if sufficient, controls retinitis without anti-CMV therapy. Resistant CMV, detected in the blood, correlates with resistant virus in the eye and is associated with worse clinical outcomes, including mortality. Host factors, including host genetics and access to care, play a role in the development of CMV retinitis. CONCLUSIONS: Clinical outcomes of CMV retinitis in patients with AIDS are dependent on characteristics of the virus and host and on HIV-CMV interactions.

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.

Delayed presentation of cytomegalovirus retinitis in an infant with severe congenital cytomegalovirus infection.

PURPOSE: The purpose was to study the congenital cytomegalovirus (CMV), which is the most common cause for congenital infection in the United States, affecting nearly 40,000 infants per year. There is no widely accepted treatment protocol for congenital CMV infection despite recent clinical trials with antiviral medications ganciclovir and valganciclovir. METHODS: We present a case report of an infant with severe congenital CMV infection with presentation of chorioretinitis in both eyes at 5 months of age. RESULTS: The child did not receive treatment with ganciclovir during hospitalization after birth despite severe manifestations of CMV infection. Treatment was again withheld after diagnosis of retinitis because of immunocompetent status, potential side effects of ganciclovir treatment, and location of retinitis in the retinal periphery of both eyes. The retinitis resolved during a period of 3 months. CONCLUSION: This case shows that CMV retinitis in infants with congenital CMV infection can be delayed in presentation and can resolve without treatment. It shows the need for more consistent monitoring for chorioretinitis in infants with congenital CMV infection.

Juxtapapillary cytomegalovirus retinitis with optic neuritis.

A 49-year-old man with AIDS developed acute monocular visual loss and an ipsilateral swollen optic disc with a large right relative afferent pupillary defect, a nerve fiber bundle visual field defect, and a peripapillary retinal infiltrate. Lumbar puncture disclosed cytomegalovirus (CMV) DNA on polymerase chain reaction (PCR). Treatment with oral valganciclovir produced complete resolution of the visual deficits and the fundus abnormality. This case differs from previously reported cases of CMV optic neuritis in which visual function has been irreversibly lost.