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.

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.

[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.

[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).

Leukaemic infiltration and cytomegalovirus retinitis in a patient with acute T-cell lymphoblastic leukaemia in complete remission. / Infiltración leucémica y retinitis por citomegalovirus en paciente con leucemia linfoblástica aguda tipo T en remisión completa.

CLINICAL CASE: A 43-year-old woman in remission from T- cell acute lymphoblastic leukaemia was referred to our hospital with suspected leukaemic retinitis. The funduscopic examination of her left eye revealed multifocal yellow-white peripheral retinitis and retinal haemorrhage. The patient was treated for cytomegalovirus retinitis after an extended haematological investigation showed no abnormalities. Initial improvement was followed by papillitis in the left eye and motility restriction in the right eye. Magnetic resonance and lumbar puncture confirmed leukaemia relapse. Specific treatment was initiated with complete resolution. DISCUSSION: Ocular involvement may precede haematological leukaemia relapse. Physicians should be alerted when ocular symptoms appear in these cases.

POSTERIOR EYE SEGMENT COMPLICATIONS RELATED TO ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION.

PURPOSE: To identify complications in the posterior eye segment in patients who have undergone allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: This retrospective cohort study enrolled 747 patients with hematologic disease who had undergone allogeneic HSCT at Seoul St. Mary's Hospital from January 2009 to December 2012. The posterior eye segment complications were evaluated by reviewing information in medical records at the Department of Hematology and Ophthalmology, including the types, onset times, locations, and resolution times of the complications according to the treatment periods for HSCT; in addition, a subgroup analysis was performed. RESULTS: Among the 635 included patients, 48 (7.6%) experienced complications related to HSCT in the posterior eye segment. Twenty patients were diagnosed with retinal hemorrhage, 16 with cytomegalovirus (CMV) retinitis, and 5 with uveitis. Six patients (37.5%) with retinal hemorrhage had a lesion in Zone 1 and took more time to recover from this complication. Retinal tear (1/16, 6.3%) and rhegmatogenous retinal detachment (2/16, 12.5%) were observed in the patients with CMV retinitis. Among the 20 patients with retinal hemorrhage, 18 (90.0%) had thrombocytopenia, 14 (70.0%) had pancytopenia, and 7 (35.0%) had profound cytopenia. Cytomegalovirus viremia was detected in 16 (72.7%) of the 22 patients with inflammation-associated complications. CONCLUSION: Understanding of each patient's general condition, which is affected by the specific procedures used for HSCT, is important for the diagnosis and management of transplantation-related complications in the posterior eye segment.

Necrotizing retinitis of multifactorial etiology.

Introduction. We present the case of a 73-year-old woman with osteoporosis, who presented to the emergency room with a sudden vision loss and ocular pain in the right eye, which appeared two days before. The patient mentioned loss of appetite, weight loss for three months and low fever for two weeks. Materials and methods. Among the ophthalmological findings, the most important were panuveitis, and large confluent necrotic areas in the peripheral retina. The patient was diagnosed with RE Panuveitis and acute necrotizing retinitis. Results. Blood exams showed leukocytosis and monocytosis, thrombocytosis and anemia. Further investigations showed high levels of Cytomegalovirus (CMV) anti IgG and Herpes Simplex (HS) type 1 virus anti IgM, urinary infection, and secondary hepatic cytolysis. The CT and MRI of the thorax and abdomen showed no sign of neoplastic disease, and no explanation for the CMV infection was found. The patient received general corticotherapy and antiviral therapy, and, after one month, RE BCVA was 20/ 30. Particularity of the case. Acute necrotizing retinitis in an old patient with CMV and HSV type 1, associated with secondary hepatic cytolysis, without any other immunosuppressive disease and very good outcome.

Differences of cytomegalovirus diseases between kidney and hematopoietic stem cell transplant recipients during preemptive therapy.

BACKGROUND/AIMS: Cytomegalovirus (CMV) surveillance and preemptive therapy is a widely-used strategy for preventing CMV disease in transplant recipients. However, there are limited data on the incidence and patterns of CMV disease during the preemptive period. Thus, we investigated the incidence and pattern of tissue-invasive CMV disease in CMV seropositive kidney transplantation (KT) and hematopoietic stem cell transplantation (HCT) recipients during preemptive therapy. METHODS: We prospectively identified patients with tissue-invasive CMV disease among 664 KT (90%) and 496 HCT (96%) recipients who were D+/R+ (both donor and recipient seropositive) during a 4-year period. RESULTS: The incidence rates of CMV disease were 4.1/100 person-years (4%, 27/664) in KT recipients and 5.0/100 person-years (4%, 21/496) in HCT recipients. Twenty-six (96%) of the KT recipients with CMV disease had gastrointestinal CMV, whereas 17 (81%) of the HCT recipients had gastrointestinal CMV and 4 (19%) had CMV retinitis. Thus, CMV retinitis was more common among HCT recipients (p = 0.03). All 27 KT recipients with CMV disease suffered abrupt onset of CMV disease before or during preemptive therapy; 10 (48%) of the 21 HCT recipients with CMV disease were also classified in this way but the other 11 (52%) were classified as CMV disease following successful ganciclovir preemptive therapy (p < 0.001). CONCLUSIONS: The incidence of CMV disease was about 4% in both KT and HCT recipients during preemptive therapy. However, CMV retinitis and CMV disease as a relapsed infection were more frequently found among HCT recipients.