Mortality of cytomegalovirus infection among people living with HIV: A retrospective study from a tertiary hospital in Indonesia.

BACKGROUND: There are still many patients newly diagnosed with HIV at an advanced stage in Indonesia. We aimed to identify factors associated with 1-year mortality among cytomegalovirus (CMV)-infected people living with HIV (PLHIV). METHODS: This retrospective cohort study was carried out at a tertiary-care hospital in Jakarta, Indonesia (January 2017 to December 2022). We included PLHIV with CMV end-organ disease (EOD) and CMV syndrome. The presence of CMV infection was confirmed by fulfilling one of the following criteria: (1) positive PCR from plasma, urine, cerebrospinal fluid, or other body fluids, or associated tissue for CMV EOD; (2) positive immunoglobulin M (IgM); or (3) consistent symptoms and signs of CMV retinitis. RESULTS: Out of 1737 PLHIV, 147 (8.5%, 95% CI: 7.2 to 9.9%) were diagnosed with CMV infection. Forty (27.2%, 95% CI: 20.6 to 35.1%) patients died within 1 year of being diagnosed. Only anti-retroviral therapy (ART) defaulting (aHR 3.31, 95% CI: 1.12 to 9.73) was found to be significantly associated with 1-year mortality in multivariate analysis. CONCLUSION: Defaulted ART status is significantly associated with reduced 1-year survival after CMV infection diagnosis. Patients with low CD4 counts, especially those with <50 cells/µL, should be assessed for CMV infection, monitored, and treated accordingly.

Clinical manifestations and immune markers of non-HIV-related CMV retinitis.

BACKGROUND: Since the HIV epidemic in the 1980s, CMV retinitis has been mainly reported in this context. CMV retinitis in persons living with HIV is usually observed when CD4 + cells are below 50 cells/mm3. This study aims to describe the immune markers of non-HIV-related CMV retinitis as well as to describe its clinical manifestations and outcomes. METHODS: Retrospective chart review of consecutive patients with CMV retinitis not related to HIV seen at the uveitis clinic of Jules Gonin Eye Hospital between 2000 and 2023. We reported the clinical manifestations and outcomes of the patients. We additionally assessed immune markers during CMV retinitis (leukocyte, lymphocyte, CD4 + cell and CD8 + cell counts as well as immunoglobulin levels). RESULTS: Fifteen patients (22 eyes) were included. Underlying disease was hematologic malignancy in 9 patients, solid organ transplant in 3 patients, rheumatic disease in 2 patients and thymoma in one patient. The median time between the onset of underlying disease and the diagnosis of retinitis was 4.8 years. Lymphopenia was observed in 8/15 patients (mild = 3, moderate = 4, severe = 1), and low CD4 counts were observed in 9/12 patients, with less than 100 cells/mm3 in 4 patients. Hypogammaglobulinemia was detected in 7/11 patients. Retinitis was bilateral in 7/15 patients, and severe visual loss was frequent (5/19 eyes). Disease recurrence was seen in 7/13 patients at a median time of 6 months after initial diagnosis. No differences in immune markers were observed in patients with vs. without recurrence. CONCLUSION: CMV retinitis is a rare disorder that can affect patients suffering any kind of immunodeficiency. It is associated with a high visual morbidity despite adequate treatment. CD4 + cell counts are usually higher than those in HIV patients, but B-cell dysfunction is common.

GOOD SYNDROME: CYTOMEGALOVIRUS RETINITIS CASE CHALLENGE.

PURPOSE: To describe cytomegalovirus retinitis in a patient with Good syndrome (hypogammaglobulinemia and thymoma), ocular progression despite treatment and fatal outcome. METHODS: A 71-year-old woman with unilateral panuveitis of unknown cause and a history of thymoma resection was referred to the clinic. Visual acuity was 20/100 in her right eye and light perception in her left eye. In slit-lamp examination, the right eye had inferior, fine, pigmented keratic precipitates, 2+ anterior chamber cells, cataract, and 2+ vitreous cells, with no fundus detail and normal ocular ultrasound results. Left eye presented a white cataract, chronic hypotony, and increased choroidal thickness with calcifications. Laboratory evaluations showed normal or negative results for common causes of infection and inflammation. Prednisolone acetate eye drops were started, with improvement of AC inflammation. Cataract surgery was performed, reaching visual acuity of 20/30. Two years later, visual acuity had decreased and 2+ vitritis and retinitis were found. On clinical suspicion of masquerade syndrome, a vitrectomy biopsy was performed; pathologic assessments reported no data on ocular lymphoma. Leukopenia and lymphopenia were found: immunoglobulin levels, CD4 count, and viral load revealed systemic immunosuppression. The aqueous tap was positive for cytomegalovirus. Oral valganciclovir and intravitreal ganciclovir were initiated. RESULTS: In a patient with previous resection of thymoma and hypogammaglobulinemia, final diagnosis was Good syndrome, with cytomegalovirus retinitis being secondary to immunosuppression. Despite treatment, cytomegalovirus retinitis progressed and systemic deterioration resulted in mortal outcome. CONCLUSION: Good syndrome is an extremely rare disease, and association with cytomegalovirus retinitis is uncommon. To the authors' knowledge, only 14 cases exist in the literature.

Comparison of two different intravitreal treatment regimens combined with systemic antiviral therapy for cytomegalovirus retinitis in patients with AIDS.

PURPOSE: To compare the efficacy and injection frequency of intravitreal low-dose vs. intermediate-dose ganciclovir therapy in acquired immune deficiency syndrome (AIDS) patients exhibiting cytomegalovirus retinitis (CMVR). METHODS: A prospective, single-centre, double-blinded, randomized controlled interventional study was conducted. Fifty patients with a total of 67 included eyes were randomly divided into low-dose (0.4 mg ganciclovir per week) and intermediate-dose (1.0 mg ganciclovir per week) groups. The primary clinical outcomes were the changes in best corrected visual acuity (BCVA) from baseline to the end of treatment and the 12-month follow-up visit as well as the number of intravitreal injections. RESULTS: In both groups, the median BCVA, expressed as the logarithm of the minimum angle of resolution (logMAR), improved significantly from baseline to the end of treatment (both p < 0.001), while vision loss from CMVR continued to occur at the 12-month visit. The mean number of injections was 5.8 in the low-dose group and 5.4 in the intermediate-dose group. No significant differences were detected between the two groups (p > 0.05). Regarding the location of CMVR, we found that Zone I lesions led to a worse visual outcome, more injections and a higher occurrence rate of complications than lesions in other zones (p < 0.05). CONCLUSIONS: The efficacy and frequency of injections to treat CMVR in AIDS patients were not significantly different between low and intermediate doses. Zone I lesions were associated with a worse visual outcome, more injections and a higher occurrence rate of CMVR-related complications than lesions in other zones.

Human immunodeficiency virus retinopathy with presumed cytomegalovirus retinitis with macular oedema in a diabetic.

A man in his early 50s on regular follow-up for a stable non-proliferative diabetic retinopathy (NPDR) presented with decreased vision, worsening of retinal pathology and macular oedema in both eyes. His corrected distance visual acuity (CDVA) was 6/9 in the right eye and 6/15 in the left eye and fundus examination showed multiple intraretinal haemorrhages in all quadrants. His systemic workup revealed a severe thrombocytopaenia, which prompted a further detailed systemic evaluation revealing him to be positive for HIV with retinopathy complicating the pre-existing NPDR. Given the significant inflammation and macular oedema, a cocktail of intravitreal bevacizumab, ganciclovir and dexamethasone was administered. The retinopathy and macular oedema resolved and the CDVA improved to 6/6 in both eyes over a 6-month follow-up period. Any sudden worsening of fundus findings in a patient with diabetes necessitates immediate and detailed ocular and systemic evaluation, especially when the immune status is unknown.

A Case of Good Visual Outcome following Retinal Ganciclovir Toxicity.

We present a case of CMV retinitis with retinal toxicity secondary to inadvertent overdose of intravitreal ganciclovir. To our knowledge, this is the first case published with good visual outcome from timely intervention.

Clinical characteristics in the misdiagnosis of cytomegalovirus retinitis: A retrospective analysis of eight patients.

Purpose: To highlight characteristics in the misdiagnosis of cytomegalovirus retinitis (CMVR). Methods: Misdiagnosed cases related to CMVR were analyzed retrospectively at the Department of Ophthalmology, Beijing Youan Hospital, from July 2017 to October 2019. The medical records were reviewed by two independent senior ophthalmologists and the patients' clinical characteristics were analyzed. Results: Eight patients (16 eyes) were identified with misdiagnoses related to CMVR. Six of the patients with CMVR were previously unaware of their human immunodeficiency virus (HIV) infection; one patient with CMVR concealed their history of HIV infection. The cases were initially misdiagnosed as diabetic retinopathy (1/7, 14.3%), branch retinal vein occlusion (1/7, 14.3%), ischemic optic neuropathy (1/7, 14.3%), Behçet's disease (1/7, 14.3%), iridocyclitis (2/7, 28.6%), and progressive outer retinal necrosis (1/7, 14.3%). One patient with binocular renal retinopathy and chronic renal insufficiency was misdiagnosed with CMVR. Four eyes (4/16, 25%) presented with pan-retinal involvement. Fourteen eyes (14/16, 87.5%) had optic disc or macular area involvement. At the final diagnosis, one patient was blind, and two patients had low vision. Seven AIDS patients showed an extremely low level of CD4+ T lymphocytes (median of 5 cells/µl; range 1-9 cells/µl). Conclusion: CMVR may be misdiagnosed in the absence of known immune suppression. CMVR and HIV screening cannot be overlooked if a young male patient presents with yellowish-white retinal lesions. These misdiagnosed patients had severe retinitis associated with poor vision.

Pre-Transplant Platelet Refractoriness and Alternative Donors Are Associated With Cytomegalovirus Retinitis in Hematopoietic Stem Cell Transplantation for Severe Aplastic Anemia.

Background: Cytomegalovirus retinitis is a severe, vision-threatening opportunistic infection in an immunodeficient population. Reports on cytomegalovirus retinitis in hematopoietic stem cell transplant recipients due to severe aplastic anemia have been scant. This study assessed the risk of cytomegalovirus retinitis in relation to the pre-transplant status of severe aplastic anemia patients. Methods: We conducted a retrospective nested case-control study of cytomegalovirus retinitis among severe aplastic anemia patients receiving allogeneic hematopoietic stem cell transplants in a tertiary care institution that attends severe aplastic anemia patients from southern China from January 1, 2013 to December 31, 2018. Each cytomegalovirus retinitis case was matched with four controls without cytomegalovirus retinitis by age and gender. Thirteen pre-transplant parameters were chosen to compare the risk factor levels between the cases and controls. Multivariable logistic regressions were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). Results: A total of 361 severe aplastic anemia patients received hematopoietic stem cell transplants in the study period 2013-2018 in our medical institution, and 31 (8.58%) developed cytomegalovirus retinitis. Cytomegalovirus retinitis was diagnosed in the median of 148 days after transplantation. We confirmed platelet refractoriness more frequently in cases than in controls (p = 0.0005). Compared with human leukocyte antigen-matched sibling donors, alternative donors were significantly more prone to cytomegalovirus retinitis (p = 0.0009). After stepwise selection in multivariate logistic regression, platelet refractoriness (OR 5.41, 95% CI 1.98-15.39), haploidentical donor (OR 7.46, 95% CI 2.19-34.87), and unrelated donor (OR 8.38, 95% CI 2.30-41.34) were associated with an increased risk of cytomegalovirus retinitis. Conclusions: Pre-transplant platelet refractoriness and alternative donors were significant predictors of cytomegalovirus retinitis in severe aplastic anemia recipients. These results highlight the importance of accounting for existing risks while developing prevention strategies and preemptive treatment for severe aplastic anemia recipients. We recommend that the platelet count be closely monitored and thrombopoietin be properly applied during the period when cytomegalovirus retinitis is prone to occur.

Granulocyte Colony Stimulating Factor-induced Immune Recovery Uveitis Associated with Cytomegalovirus Retinitis in the Setting of Good Syndrome.

PURPOSE: To report a case of immune recovery uveitis (IRU) secondary to cytomegalovirus (CMV) retinitis in a patient with Good syndrome treated with granulocyte colony stimulating factor (GCSF). METHODS: A case report. CASE: A 54-year-old woman with a history of Good syndrome for 2 years presented with chronic panuveitis in her right eye for 6 months. She had received multiple doses of GCSF for a pulmonary infection. Her visual acuity was hand movement in the right eye. Few anterior chamber cells, dense vitreous haze, and chorioretinal lesions were noted. Granular retinal atrophic lesions without obvious infiltration were observed during diagnostic vitrectomy. Polymerase chain reaction of the vitreous sample was positive for CMV DNA. A diagnosis of IRU secondary to CMV retinitis was made. The inflammation was controlled with topical steroids after surgery. SUMMARY: In this report, we present a patient with Good syndrome who developed IRU secondary to CMV retinitis.

Clinical Features and CD4+ T Cells Count in AIDS Patients with CMV Retinitis: Correlation with Mortality.

PURPOSE: To explore the all-cause mortality in patients with acquired immune deficiency syndrome (AIDS) and Cytomegalovirus (CMV) retinitis. METHODS: A retrospective cohort study of patients with CMV retinitis (CMVR) presented to a tertiary referral center in Singapore from January 1, 2004, through December 31, 2015. RESULTS: A total of 144 patients were studied (87 survived, 11 lost to follow up, 46 died). Patients with bilateral CMVR and six-month follow up CD4 + T cell count < 50 cells/mm3 have shorter time to mortality, compared to patients with CD4 + T cell count > 50 cells/mm3 (p < .001) and unilateral disease (p = .043). Baseline CD4 + T cell count, size and zone of initial primary retinitis lesions, recurrences of retinitis, and timing of combined antiretroviral therapy (cART) are not significantly associated with mortality. CONCLUSION: Bilateral ocular involvement and lack of immune recovery in patients with AIDS and CMVR are associated with shorter survival time.

Outcomes of 25-gauge pars plana vitrectomy for cytomegalovirus retinitis-related retinal detachment.

PURPOSE: The purpose of this study is to evaluate the anatomical and functional outcomes of 25-gauge (G) pars plana vitrectomy (PPV) in patients with cytomegalovirus retinitis (CMVR)-related rhegmatogenous retinal detachment (RRD). METHODS: Single-center retrospective consecutive case series of patients who underwent 25-G PPV for CMVR-related RRD repair with a minimum follow-up of 3 months. Complete anatomic success was defined as the complete attachment of retina including the periphery. Best-corrected visual acuity (BCVA) of ≥20/400 was defined as functional success. RESULTS: Sixteen eyes of 15 patients were included in the study. Eleven patients were human immunodeficiency virus positive, three patients had hematological malignancies, and one patient suffered from dyskeratosis congenita. The mean follow-up was 20.5 ± 17.4 months (range 3-60 months). Complete anatomical success was seen in 15 eyes (93.75%). One eye had a residual inferior detachment with attached macula. Silicone oil was used as tamponade in 15 eyes and C3F8 gas in one eye. The mean change in BCVA was statistically significant, preoperative LogMAR BCVA was 2.05 ± 0.94 while the final follow-up postoperative LogMAR BCVA was 1.03 ± 0.61 (P < 0.001). Thirteen eyes (81.25%) had final BCVA ≥20/400. CONCLUSION: Microincision vitrectomy surgery can achieve excellent retinal reattachment rates in post-CMVR RRDs without significant intraoperative and postoperative complications. The visual outcome varies depending on the status of the optic disc and macula. Majority of the patients maintained functional vision.

Frosted branch angiitis due to cytomegalovirus-associated unmasking immune reconstitution inflammatory syndrome: a case report and literature review.

BACKGROUND: Cytomegalovirus (CMV) retinitis is a common opportunistic infection in patients with acquired immunodeficiency syndrome. The common funduscopic manifestations are haemorrhagic necrotising variety and granular variety. Frosted branch angiitis (FBA), as a special form, when it occurred after antiretroviral therapy(ART), could possibly be associated with immune reconstitution. We report a case of FBA secondary to CMV infection-associated unmasking immune reconstitution inflammatory syndrome (IRIS). CASE PRESENTATION: A 27-year-old man with human immunodeficiency virus infection developed FBA after 35 days of ART. The left Aqueous humour (AqH) tested positive for CMV DNA, and the patient was diagnosed with CMV retinitis. The degree of intraocular inflammation was reflected by increased levels of interleukin (IL)-6 and IL-8 in AqH. After anti-CMV treatment and continuous ART for several months, his FBA and vision significantly improved. CMV DNA became undetectable in the left AqH, and the IL-6 and IL-8 levels in AqH decreased. CONCLUSION: FBA could be a sign of CMV-associated unmasking IRIS. Anti-CMV treatment alone or combination with steroid treatment may be administered, depending on the changes in CMV DNA load and immunologic profile of AqH.