Diffuse retinal dysfunction following immune reconstitution uveitis in patients with prior cytomegalovirus retinitis: a novel observation.

PURPOSE: To report continuing diffuse retinal dysfunction following resolution of immune reconstitution uveitis (IRU) in patients with cytomegalovirus retinitis (CMVR). METHODS: Retrospective case series describing two patients with IRU following CMVR who underwent serial fundus photography and macular optical coherence tomography. One patient had serial electrophysiology. RESULTS: Both patients had CMVR successfully treated with antiviral medication. The affected eyes later developed IRU that resolved with steroids. However, following resolution, chronic retinal damage was evidenced by ellipsoid line loss in one case and gradual optic disc cupping in the other. Electrophysiology in both cases revealed generalized retinal dysfunction worse in the eye with more severe IRU and demonstrated objectively the efficacy of treatment intervention in the patient with serial recordings. CONCLUSIONS: Patients with IRU following CMV retinitis may have continuing diffuse retinal dysfunction despite apparent recovery and normal visual acuity. An aggressive approach to inflammation control may be warranted in such patients.

Cytomegalovirus immunoglobulin therapy for CMV retinitis post hematopoietic stem cell transplantation.

PURPOSE: To report a case of cytomegalovirus (CMV) retinitis complicated with ganciclovir-related myelosuppression, which was successfully managed with intravenous (IV) ganciclovir and CMV immunoglobulin (CMVIG) therapy. METHODS: Observational case report. RESULTS: A 51-year-old male with follicular type non-Hodgkin lymphoma post hematopoietic stem cell transplantation (HSCT) developed vision-threatening retinitis. polymerase chain reaction (PCR) of the aqueous humour showed positive for CMV. Despite myelosuppression occurred during IV ganciclovir therapy, the retinitis resolved and intraocular CMV viral load significantly improved after CMVIG therapy. CONCLUSION: Combined IV ganciclovir treatment and CMVIG therapy can significantly improve visual outcome and reduce intraocular CMV viral load in vision-threatening CMV retinitis.

CMV Retinitis in Wiskott Aldrich Syndrome.

PURPOSE: Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disease whose optimal curative treatment is hematopoietic stem cell transplantation (HSCT). Patients with WAS may suffer from cytomegalovirus retinitis (CMVR) which can cause vision loss. This study is to report the progression and prognosis of patients with WAS and CMVR. METHODS: A retrospective case series of ten patients with WAS and CMVR before and after HSCT who were referred to the Ophthalmology Department of Xinhua Hospital from June 2018 to February 2021. Progression and prognosis were recorded. RESULTS: Five patients were diagnosed with CMVR before receiving HSCT at a median age of 10.5 months (range: 4-23 months). Eight patients developed CMVR post-transplantation with a median interval from HSCT of 3.5 months (range: 1-9 months). CONCLUSION: Regular fundus examinations and prompt treatments in patients with WAS are therefore crucial before they receiving HSCT or approximately 3.5 months after HSCT until complete reconstitution of immune function.

Cytomegalovirus-Specific T Cells from Third-Party Donors Successfully Treated Refractory Cytomegalovirus Retinitis after Unrelated Umbilical Cord Blood Transplantation.

Umbilical cord blood (UCB) transplants (UCBTs) are becoming increasingly common in the treatment of a variety of hematologic and nonhematologic conditions. The T cells from UCB are naïve T cells, which have not yet been exposed to antigens and therefore do not contain T cells with specific immune functions against viruses. Cytomegalovirus (CMV) infections occur in more than 80% of patients after UCBT compared to other types of transplantation. Anti-CMV medications are currently restricted, with ganciclovir, foscarnet, and valganciclovir being the most common in China; however, with limited efficacy and considerable side effects, all these drugs are susceptible to viral resistance. In recent years, cytomegalovirus-specific T cells (CMVST) have advanced the treatment of viral infections in immunodeficient patients. CMVST usually uses the same donor as hematopoietic stem cell transplantation. CMVST should be administered to UCBT patients because of the absence of donors after UCBT. In China, there is no report on the use of CMVST to treat CMV infection after UCBT, and foreign reports are also limited. This paper reported a 20-year-old male patient with acute myeloid leukemia who developed cytomegalovirus retinitis (CMVR) after umbilical cord blood transplantation. After ineffective viral treatment, he was treated with a third-party donor CMVST and was successfully transformed into CMV nucleic acid negative.

Cytomegalovirus Retinitis and Retinal Detachment following Chimeric Antigen Receptor T Cell Therapy for Relapsed/Refractory Multiple Myeloma.

Cytomegalovirus (CMV) retinitis is a rare end-organ disease of CMV infection and is a marker of severe immunosuppression, especially in human immunodeficiency virus (HIV)-positive patients. In multiple myeloma (MM) patients, CMV retinitis has been reported in the post-transplant setting, with an incidence lower than 0.2%, and in patients receiving lenalidomide. Here, we describe the first case of CMV retinitis in myeloma patients following B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor T (BCMA CAR-T) cell therapy. In addition to CMV, the patient developed multiple infections including a mouth ulcer, pneumonia, and fungal enteritis. While the complete remission (CR) status of MM was maintained, he regained a visual acuity of 20/1000 after appropriate ophthalmologic treatment. This single case illustrates the potential of BCMA CAR-T therapy to induce profound humoral immunosuppression, and demonstrates an imperative need for an established standard of monitoring and prophylaxis of post-CAR-T infections.

Efficacy and Safety of Aqueous Interleukin-8-Guided Treatment in Cytomegalovirus Retinitis after Bone Marrow Hematopoietic Stem Cell Transplantation.

PURPOSE: To explore the optimal treatment for cytomegalovirus retinitis (CMVR) in patients status-post Allogeneic bone marrow hematopoietic stem cell transplantation (Allo-HSCT), based on aqueous humor indicators. METHODS: A randomized controlled study with 35 eyes. Eyes were randomized with a 1:1 ratio to standard treatment group (Group 1, with treatment endpoint as aqueous CMV-DNA load＜103 copy/ml), and interleukin (IL)-8 group (Group 2, with treatment endpoint as aqueous IL-8 level ＜30 pg/ml or CMV-DNA load＜103 copy/ml) to receive antiviral intravitreal injections. Number of injections, CMVR recurrence rate, complication rate, and vision changes were analyzed and compared. RESULTS: The mean number of injections in group 2 was less than in group 1 (6 vs 8 respectively, p<0.05). There were no significant differences in CMVR recurrence, complication and vision recovery rate. CONCLUSION: Incorporating aqueous humor IL-8 level into the criteria of CMVR treatment decision can safely and effectively reduce the number of intravitreal injections needed and can be used as important indicators to assess treatment endpoint.

The Predictive Value of Interleukin-8 in the Development of Cytomegalovirus Retinitis in HIV-Negative Patients.

INTRODUCTION: The aim of this study was to evaluate the value of interleukin (IL)-8 in the development and management of cytomegalovirus retinitis (CMVR) in HIV-negative patients. METHODS: A retrospective case series from January 2014 to May 2018 was conducted. Forty patients (40 eyes) received intravitreal injection of ganciclovir (IVG). The aqueous levels of the cytomegalovirus (CMV) DNA and IL-8 in each follow-up visit were tested. The initial and final best-corrected visual acuity (BCVA), the course of treatment, the recurrence rate, and the occurrence of complications were recorded and analyzed. RESULTS: The aqueous value of IL-8 was significantly correlated with the aqueous level of the CMV DNA during treatment but was not associated with the BCVA or the number of IVG. No recurrence occurred in the condition in which a low aqueous IL-8 level was set as the endpoint of the treatment. CONCLUSION: In HIV-negative patients with CMVR, IL-8 was closely associated with CMV DNA concentration in the aqueous humor. The real-time aqueous level of IL-8 could be used as one of the evidences of disease recovery.

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.

An Uncommon Concurrence of Cytomegalovirus Retinitis and Corneal Endotheliitis in an Immunocompromised HIV-Negative Patient.

Purpose: To describe a case of Cytomegalovirus (CMV) retinitis in both eyes complicated with unilateral corneal endotheliitis in an iatrogenic immunocompromised patient.Methods: A retrospective case report.Result: A 58-year-old male, on long-term immunosuppressive treatment for chronic glomerulonephritis and nephrotic syndrome. Ocular examination revealed bilateral vitritis and necrotizing retinitis and concurrent corneal endotheliitis with ocular hypertension in his left eye. The PCR result showed positivity for CMV infection by diagnostic aqueous aspiration. Vitritis/retinitis in both eyes resolved gradually after systemic valganciclovir use, and the endotheliitis in the left eye regressed after topical antiviral treatment. There was no recurrence of retinitis/endotheliitis with a maintenance dose of oral valganciclovir. Unfortunately, tractional macular hole developed in the left eye and complicated the visual outcome.Conclusion: CMV retinitis may occur in HIV-negative immunocompromised individuals, but CMV endotheliitis generally appears in the immunocompetent. It is a rare combination of CMV retinitis and endotheliitis in this patient.

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.

Prognostic factors of cytomegalovirus retinitis after hematopoietic stem cell transplantation.

PURPOSE: To identify the visual prognostic factors in patients with cytomegalovirus (CMV) retinitis after hematopoietic stem cell transplantation (HSCT). METHODS: This retrospective cohort study included 4241 patients who underwent HSCT from April 1, 2010 to March 31, 2019 at Seoul St. Mary's Hospital. Of them, 1063 patients presented CMV viremia, and 67 patients (93 eyes) were diagnosed with CMV retinitis. We enrolled 66 patients (91 eyes). The main outcomes included the initial best-corrected visual acuity (BCVA), BCVA at the diagnosis of retinitis and last visit, involved retinal zone, peak CMV DNA levels in the peripheral blood and aqueous humor, time between HSCT and the diagnosis of retinitis, time between the diagnosis of viremia and retinitis, complications, recurrence, survival, and so on. RESULTS: The mean BCVA (logarithm of the minimum angle of resolution) values before HSCT, at the time of retinitis diagnosis, and at the last visit were 0.041 ± 0.076, 0.262 ± 0.529, and 0.309 ± 0.547, respectively. Multiple regression analysis revealed that the involved zone (P = 0.001), time between HSCT and retinitis diagnosis (P = 0.019), and survival status (P = 0.001) were associated with the final visual acuity. CONCLUSIONS: The final visual prognosis was worse in patients with greater invasion of the central retinal zone, those with a longer interval between HSCT and the diagnosis of retinitis, and those who died. Prompt diagnosis of CMV retinitis through periodic fundus examinations of patients with CMV viremia can prevent severe vision loss. Once CMV viremia is confirmed, we recommend fundus examinations to be immediately performed and repeated every 2 weeks for at least 2 months, even if the CMV DNA titer in the peripheral blood becomes negative.

Incidence, risk factors, and outcomes of cytomegalovirus retinitis after haploidentical hematopoietic stem cell transplantation.

This study investigated the epidemiological characteristics of cytomegalovirus retinitis (CMVR) after haploidentical hematopoietic stem cell transplantation (HSCT). We studied a cohort of 1466 consecutive patients who had undergone haploidentical HSCT between 2013 and 2017. We documented 34 episodes of CMVR in 31 patients, with a median onset of 167 days after the transplant. The cumulative incidence of CMVR was 2.3% 1 year after the transplant. Multivariate analysis suggested that platelet engraft failure at 100 days, EBV DNAemia, refractory or recurrent CMV DNAemia, and acute graft-versus-host disease were related to the development of CMVR in patients with CMV DNAemia. Patients with ≥3 risk factors (high risk) had a higher 1-year incidence of CMVR than patients with ≤2 risk factors (low risk) (26.2% vs. 0.6%, P < 0.001). In patients with CMVR, visual acuity (VA) improved in 16 episodes, remained stable in 10 episodes, and worsened in 8 episodes. The variable related to the improvement of VA was VA ≥ 0.1 at time of CMVR diagnosis. Our study showed that CMVR was a rare complication after haploidentical HSCT but that the risk was greater in patients with multiple risk factors.

Cytomegalovirus retinitis in children and adolescents with acute leukemia following allogeneic hematopoietic stem cell transplantation.

Cytomegalovirus retinitis (CMVR) may occur after allogeneic hematopoietic stem cell transplantation (HSCT). However, little is known about its incidence, strategies for ophthalmic surveillance, and timely implementation of adequate antiviral treatment in pediatric allogeneic HSCT recipients. We provide a retrospective analysis of the epidemiology and clinical features of CMVR in pediatric allogeneic HSCT patients transplanted at our center over a 16-year period. Two patients of this cohort with leukemia are presented. Our analysis is supplemented by a systematic review on pediatric patients with leukemia and CMVR in the setting of allogeneic HSCT. The overall incidence of CMVR in our cohort was 1% (4/338) and 14.2% (3/21) in leukemic patients. In published cases, CMVR occurred at a median of 143 days after transplantation, and, in the majority of patients, was preceded by CMV detection in blood by a median of 93 days. Continued immune suppression following engraftment likely triggers CMVR. Preemptive treatment with ganciclovir as standard is usually successful. Foscarnet is used in case of resistance to ganciclovir or drug-induced granulocytopenia. Overall, CMVR after HSCT in pediatric leukemic patients is rare, but a potentially higher vulnerability of this population for involvement of the eye warrants a standardized ophthalmological examination plan.

Cytomegalovirus retinitis, in a diabetic immunocompetent patient, after intravitreal ranibizumab injection.

We here report a case of cytomegalovirus retinitis in a diabetic patient that occurred after intravitreal ranibizumab injection. A 75-year-old woman was treated with intravitreal ranibizumab injections for diabetic macular edema. During this period, a retinitis occurred in her left eye along with increased IgG and later IgM cytomegalovirus antibody titers. Ocular and intravenous ganciclovir was administered. Cytomegalovirus retinitis subsided post treatment with residual areas of retinal atrophy. Ophthalmologists should be aware of the incidence of cytomegalovirus retinitis, in diabetic patients, after ranibizumab injection.

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.

[Influent factors for treating procedure of cytomegalovirus retinitis after allogeneic bone marrow hematopoietic stem cell transplantation].

Objective: To explore clinical and laboratory factors that influencing treating procedure of cytomegalovirus retinitis (CMVR) after allogeneic bone marrow hematopoietic stem cell transplantation (HSCT). Methods: This is a retrospective case series study. A total of 9 CMVR patients (15 eyes) between January 2016 and March 2017 were included in this study. All patients received intravenous or oral ganciclovir, together with intravitreous injection of ganciclovir alone or combined with foscanet sodium. One day before the first injection, aqueous humor samples from the affected eyes were collected, and CMV-DNA and interleukin-8 (IL-8) level were examined. Blood samples were acquired and CMV-DNA was examined too. Best corrected visual acuity, intraocular pressure (Goldmann), slit-lamp and fundus examination, ultra-wide fundus photography were performed before the first injection and every visit since then. Fifty eyes were divided into stop treating group (Group A) and continue-to-treat group (Group B) according to whether local treatment could be seized after loading phase. Image-Pro plus 6.0 was exploited to determine the area of CMVR in the retina, together with number of quadrants involved and whether macular was involved.Then the clinical and laboratory data were compared between two groups. ROC curve was used to calculate the cutoff values for quantitative factors that showed significant differences between two groups. Results: The interval time between HSCT and diagnosis of CMVR, visual acuity and CMV-DNA in the blood at baseline, area of CMVR and number of quadrants involved and whether macular was involved didn't show any difference between two groups. But the intraocular pressure (Z=-2.488, P=0.017), CMV-DNA (Z=-2.239, P=0.013) and IL-8 level (Z=-2.475, P=0.012) in aqueous humor at baseline, proportion of eyes with active inflammation in anterior (P=0.003) and proportion of eyes with ocular hypertension (P=0.021) in group B were significantly higher than those in group A. The cutoff values of intraocular pressure, CMV-DNA and IL-8 level in aqueous humor at baseline were 14.5 mmHg (P=0.013), 2.99×10(5) copy/ml (P=0.025) and 447.8 pg/ml (P=0.013), respectively. Conclusion: Higher intraocular pressure, CMV-DNA and IL-8 in aqueous humor at baseline, especially combined with active inflammation in anterior segment and ocular hypertension suggest longer treating period and more times of intravitreous injections. (Chin J Ophthalmol, 2017, 53: 740-745).

[Specific immunoglobulins G and M in blood serum in retinoblastoma and 'pseudoretinoblastoma']. / Spetsificheskie immunoglobuliny G i M v syvorotke krovi pri retinoblastome i 'psevdoretinoblastomakh'.

Perinatal inflammatory retinal diseases and intrauterine retinal maldevelopments are mistaken for retinoblastoma as often as in 8-16% of cases. AIM: To analyze the infectious status in children with retinoblastoma and pseudoretinoblastoma at different ages. MATERIAL AND METHODS: A total of 47 retinoblastoma suspects aged 4-69 months were enrolled. Pseudoretinoblastoma (inflammatory retinal diseases and intrauterine maldevelopments of the retina) was detected in 14 children (group 1), retinoblastoma - in 33 children (group 2). In each group, two subgroups were identified: 'a' - children under 12 months of age (1a - 5 patients, 2a - 10 patients) and 'b'- children over 12 months of age (1b - 9 patients, 2b - 23 patients). Their blood sera were examined for antibodies to herpes simplex virus types 1 and 2, cytomegalovirus, Epstein-Barr virus, toxoplasma, toxocara, chlamydia, and mycoplasma (enzyme-linked immunosorbent assay). RESULTS: According to serological screening, all patients from group 1a (children under 12 months of age with pseudoretinoblastoma), in contrast to other groups, were infected perinatally with cytomegalovirus infection. All 47 patients were seronegative to toxoplasma. Toxocara infection was identified in children over 12 months of age: in 3 out of 9 patients with pseudoretinoblastoma and in 2 out of 23 patients with retinoblastoma (p>0.05). Markers of Epstein-Barr viral activity were detected only in 3 retinoblastoma children over 12 months of age. CONCLUSION: The results suggest that cytomegalovirus infection plays the leading role in the development of perinatal eye pathology, which, in infants, is clinically similar to retinoblastoma. In children over 12 months of age we found no serological signs that could be regarded as specific of either retinoblastoma, or pseudoretinoblastoma. The only thing worth paying attention to is the activation of Epstein-Barr virus infection in children over 12 months of age with retinoblastoma.

Cytomegalovirus retinitis followed by immune recovery uveitis in an elderly patient with rheumatoid arthritis undergoing administration of methotrexate and tofacitinib combination therapy.

Cytomegalovirus (CMV) retinitis is an opportunistic ocular infection most commonly observed in patients infected with human immunodeficiency virus (HIV). We present a rare case of CMV retinitis that developed in a non-HIV patient with rheumatoid arthritis (RA). Over the preceding 5 months, a family doctor had been treating the 78-year-old male patient with a combination therapy of methotrexate (MTX) and tofacitinib (TOF). CMV retinitis occurred when the patient's CD4+ T cells were low (196 cells/µl), and preceded the onset of Pneumocystis pneumonia. MTX and TOF were stopped after the diagnosis of CMV retinitis. While intravenous and intravitreal ganciclovir administration significantly improved the CMV retinitis, uveitis developed 3 months later during the maintenance therapy with oral valganciclovir, concomitantly with the recovery of the CD4+ T cell counts. As we believed this uveitis was caused by the immune reconstitution mechanism, we treated the patient with a retrobulbar injection of corticosteroids. During the 6 months following the cessation of MTX and TOF, there was no flare-up of the RA. Cases of CMV retinitis and immune recovery uveitis in RA patients have been rarely reported in the literature. In the current case, the intensive immunosuppressive therapy in this elderly patient might have been the cause of this unusual opportunistic complication of RA.