Cytomegalovirus Retinitis Research Articles

Bilateral Cytomegalovirus Retinitis in a Child with Rhabdomyosarcoma

Bilateral Cytomegalovirus Retinitis in a Child with Rhabdomyosarcoma

Foscarnet calcium microcrystals as the intravitreal drug depot.

Foscarnet sodium is an antiviral drug for the treatment of CMV retinitis, currently in the form of twice-weekly intravitreal injection. Here we developed foscarnet calcium microcrystals as the drug depot, and using the rabbit model we demonstrated that the injected microcrystals maintained a therapeutically relevant drug concentration in the vitreous for more than 3 months.

From Petunias to the Present- A Review of Oligonucleotide Therapy

Oligonucleotide therapy has come a long way since the early days. Ongoing research is finding more and more applications for this therapeutic tool. At present there are six FDA approved drugs based on oligonucleotide therapy. These are fomivirsen for treatment of CMV retinitis in AIDS patients, mipomersen for treatment of familial hypercholesterolemia, defibrotide for treatment of venoocclusive disease in liver, eteplirsen for treatment of Duchene Muscular Dystrophy, pegaptanib for treatment of neovascular age related macular degeneration and nusinersen for management of spinal muscular atrophy.

When Dermatomyositis Patient Has Blurring of Vision – What Goes Wrong?

Cytomegalovirus (CMV) retinitis occurs predominantly in Human Immunodeficiency Virus (HIV) -infected patients. It was also reported in HIV-seronegative patients with systemic autoimmune disorder requiring systemic immunosuppression, organ or bone marrow transplantation, haematological or breast malignancy receiving chemotherapy, ocular diseases following intraocular or periocular corticosteroid injection, diabetes mellitus and Good syndrome. However, CMV retinitis in patients with concurrent dermatomyositis and malignancy has not been previously reported. It has not been reported in cancer other than haematological or breast malignancy, or in cancer patient prior to chemotherapy. We report a case of 40-year-old HIV-seronegative woman with underlying dermatomyositis and lung malignancy who developed right CMV retinitis which relapsed after recommencement of immunosuppressant. Both episodes of CMV retinitis were successfully treated after taken her immunocompromised state into consideration.

Safety and Preliminary Efficacy of "Ready to Administer" Cytomegalovirus (CMV)-Specific T Cells for the Treatment of Patients with Refractory CMV Infection

Despite advances in antiviral drugs, Cytomegalovirus (CMV) infections remain a significant cause of morbidity and mortality in immunocompromised individuals. We have recently demonstrated in hematopoietic stem cell transplant (HSCT) recipients that adoptively-transferred virus-specific T cells, generated from healthy 3rd party donors and administered as an "ready to administer" product, can be curative, even in patients with drug-refractory CMV infections. However, broader implementation has been hindered by the postulated need for extensive panels of T cell lines representing a diverse HLA profile, as well as the complexities of large scale manufacturing for widespread clinical application. To address these potential issues, we have developed a decision tool that identified a short list of donors who provide HLA coverage for >90% of the stem cell transplant population. Furthermore, to generate banks of CMV-specific T cells from these donors, we have created a simple, robust, and linearly scalable manufacturing process. To determine whether these advances would enable the widespread application of "ready to administer" T cells, we generated CMV cell banks (Viralym-C™) from 9 healthy donors selected by our decision tool, and initiated a fixed-dose (2x107 cells/m2) Phase I clinical trial for the treatment of drug-refractory CMV infections in pediatric and adult HSCT recipients.To generate the Viralym-C™ banks, we stimulated donor peripheral blood mononuclear cells (PBMCs) with overlapping peptide libraries spanning the immunodominant CMV antigens pp65 and IE1. Cells were subsequently expanded in a G-Rex device, resulting in a mean fold expansion of 103±12. The lines were polyclonal, comprising both CD4+ (21.3±6.7%) and CD8+ (74.8±6.9%) T cells, and expressed central CD45RO+/CD62L+ (58.5±4.2%) and effector memory markers CD45RO+/CD62L- (35.3±12.2%). Furthermore, the lines generated were specific for the target antigens (IE1: 419±100; pp65 1070±31 SFC/2x105, n=9).To date, we have screened 12 patients for study participation, and from our bank of just 9 lines we have successfully identified a suitable line for all patients within 24 hours. Of these, 6 patients have been infused; 5 received a single infusion and 1 patient required 2 infusions for sustained benefit. There were no immediate infusion-related toxicities; and despite the HLA disparity between the Viralym-C lines and the patients infused, there were no cases of de novo or recurrent graft versus host disease (GvHD). One patient developed a transient fever a few hours post-infusion, which spontaneously resolved. Based on viral load, measured by quantitative PCR, or symptom resolution (in patients with disease), Viralym-C™ cells controlled active infections in all 5 evaluable patients; 4 patients had complete responses, and 1 patient had a partial response within 4 weeks of cell infusion. One patient with CMV retinitis had complete resolution of symptoms following Viralym-C™ infusion.In conclusion, our results demonstrate the feasibility, preliminary safety and efficacy of "ready to administer" Viralym-C™ cells that have been generated from a small panel of healthy, eligible CMV seropositive donors identified by our decision support tool. These data suggest that cost-effective, broadly applicable T cell anti-viral therapy may be feasible for patients following HSCT and potentially other conditions. DisclosuresTzannou:ViraCyte LLC: Consultancy. Leen:ViraCyte LLC: Equity Ownership, Patents & Royalties. Kakarla:ViraCyte LLC: Employment.

Most Closely HLA-Matched Third Party Allogeneic CMV Specific T-Cells Generated Using the Cytokine Capture System for the Treatment of CMV Infections after Allogeneic Stem Cell Transplantation

Adoptive immunotherapy with ex vivo expanded virus-specific T-cell lines from transplant donors has emerged as a potentially curative approach for the treatment of drug-refractory viral infections complicating allogeneic hematopoietic cell transplants (HSCT). In these studies, viral-specific T cells are generated in compliance with current good manufacturing practice (cGMP) following repeated rounds of antigen-driven stimulation over a number of weeks. Such protocols are logistically and technically demanding, requiring access to specialized GMP units and are difficult to apply in urgent clinical settings.The cytokine-capture (gamma-catch) procedure is a fast and simple method that takes <30 hours to isolate polyclonal IFN-gamma-secreting CD8+ and CD4+ viral-specific T cells and can be performed outside a dedicated GMP facility. The cells are directly transfused to the patient without the requirement for ex vivo expansion. The use of allogeneic third party T-cell donors offers the option of selecting donors with high viral-specific T cell precursor frequencies and may serve as an alternative for patients receiving an allogeneic cord blood transplant or a transplant from a virus-seronegative donor.Here, we report the interim results of a Phase 2 study in 11 patients with persistent CMV infection after HSCT, despite optimum anti-viral therapy for at least 14 days. We established a bank of cryopreserved peripheral blood mononuclear cells (PBMCs) from 36 healthy donors. Eligible patients were treated with small numbers of CMV-specific T cells selected by cytokine capture from the most closely HLA-matched third party donor. Manufacture of third party derived CMV specific CTLs was performed at the MDACC Core Facility. Cryopreserved PBMCs were thawed, washed and diluted at 1 × 109 cells in 100 mL MACS GMP TexMACS Reagent (Miltenyi Biotec) for approximately 16 hours at 37°C. The product was stimulated with MACS® GMP Peptivator® HCMV pp65 for approximately 4 hours at 37°C, CO2. Enrichment of cytokine-secreting cells was performed using the cytokine secretion system and the CliniMACS device for immunomagnetic separation. CMV-specific T cells were transfused directly after isolation without any further in vitro expansion.To date, 11 HSCT recipients have received CMV-specific T-cells generated by gamma-catch. Of 11 patients, 2 had failed to respond to foscarnet, 12 to ganciclovir and 8 to both agents. One patient who had a complete response (CR) to his first CMV-specific T-cell infusion received a second infusion 166 days after the first dose for the treatment of CMV retinitis. The median number of infused CD3+IFN-gamma+ T-cells was 2598/kg (range, 61/kg-12717/kg). There were no immediate infusion-related adverse events. CMV-specific CTLs controlled infection in 9 of 11 evaluable infusions; 6 CR and 3 partial response (PR). The overall response and CR rates at 4 weeks were 77% (95%CI; 51%, 95%) and 54.5% (95%CI; 25.4%, 78.6%). Interestingly, the success of adoptive T-cell transfer was not related to the dose of infused T-cells. The median ratio of CD8+ IFN-gamma+ to CD4+ IFN-gamma+ T-cells was 2.7 (range, 0.17-13.4). Among 6 CR patients, 4 had a second episode of CMV infection at a median of 71 days (range, 61-355 days) after the first CTL infusion. Following infusion, there was expansion of both CD8+ and/or CD4+ CMV-specific T-cells, which persisted for a minimum of 1 month following infusion. Recurrence of CMV PCR after CTL infusion was associated with loss of CMV CTL response.Despite the use of third-party donors with HLA disparity, only one patient developed de novo graft versus host disease (GVHD) of the gastrointestinal tract (grade 1) 3 months after CTL infusion. Three patients with a history of acute GVHD prior to CTL infusion had flares 5-6 months after CTL infusions and responded to systemic steroid use.In summary, these interim results demonstrate the safety, feasibility and efficacy of immunotherapy with the most closely HLA-matched CMV specific CTLs generated by cytokine capture for the treatment of drug resistant CMV infection after HSCT patients. The clinical trial continues to enroll and an updated report of the study will be presented at the meeting. DisclosuresCiurea:Spectrum Pharmaceuticals: Other: Advisory Board; Cyto-Sen Therapeutics: Equity Ownership.

Long-Term Follow up of Patients with HIV-Associated Non-Hodgkin Lymphoma (NHL) after Autologous Stem Cell Transplantation (ASCT)

Background:The Blood and Marrow Transplant Clinical Trials Network 0803 study confirmed the safety and efficacy of ASCT in HIV-infected patients with lymphoma. Short term toxicity and transplant related mortality was low (5.2%) and engraftment, treatment-related mortality and survival outcomes were not statistically significantly different from that of age and diagnosis matched CIBMTR controls. However, median follow up in that trial was 24 months after ASCT, and the questions of second cancer incidence and other infections in a this population remain (Alvarnas et al, ASH 2014). Herein we report the long term outcomes of ASCT in HIV-infected patients.Methods: Retrospective cohort trial of 52 HIV-infected patients who underwent ASCT for high-risk NHL at City of Hope from January 1, 1998 to December 31, 2011. Two patients were excluded from the analysis due to early post-transplant mortality: one patient died at day 22 due to multiorgan failure, and another died at day 72 due to relapsed lymphoma. Fifty patients with a minimum survival of 100-days post ASCT were evaluated for long-term outcomes. Estimation of event-free survival (EFS) and overall survival (OS) was computed using Kaplan-Meier curves and the cumulative incidence of relapse was estimated with competing risk of mortality.Results: Median follow up was 5.43 years (range 0.30-14.96 years). Median age at the time of transplantation was 45 years (range 26-64 years of age). Prior to transplant, 23 patients (46%) were in complete remission and 27 (54%) were in partial remission. Most patients had aggressive NHL, with diffuse large B-cell lymphoma (48%) and Burkitt lymphoma (24%) being most common histologies. Other subtypes included Burkitt-like (10%), plasmablastic (10%), follicular lymphoma (2%), and T-cell lymphomas (6%). Nine patients relapsed (18%), at a median time of 97 days (range 54-253 days) post ASCT. Fifteen patients (30%) died; 8 out of 15 (53%) died due to relapse. Opportunistic infections (OI) occurred in 8 patients (16%) at a median of 0.68 years (range 0.17-10.82 years). Types of OI included CMV retinitis (1), HSV/Zoster (1), HPV (1), Candida esophagitis (1) and PJP (3). One patient died from OI (PJP). Seven patients (14%) developed a second primary malignancy (SPM) at median time to SPM of 5.63 years (range 1.02-14.35 years). Type of SPM included treatment-related myelodysplastic syndrome (t-MDS) with progression to acute myelogenous leukemia (AML) (2) observed at 3.2 years and 12.6 years, respectively, after ASCT; squamous cell carcinoma of the tongue (1), and skin cancers, including melanoma (1) at 14.3 years post ASCT, basal cell carcinoma (2) at 5.5 and 5.6 years post ASCT, and squamous cell carcinoma in situ (1) at 1.0 year post ASCT. Two patients died from the t-MDS.Conclusions: Thirty-five of 50 patients (70%) were alive at the time of analysis confirming the efficacy of this procedure. EFS/OS at 1 year and 5 years post ASCT was 78% (95% CI:67.3%-90.4%)/82% (95% CI: 71.9%-93.4%) and 71.4% (95% CI:59.8%-85.3%)/73.3% (95% CI: 61.8%-86.9%), respectively. Relapse of NHL tended to occur early post-transplant. Cumulative incidence of relapse was 18% at 1 year post ASCT (95% CI: 8.8%-29.8%). Development of OI was also seen early post-ASCT. While SPM appeared as late as 14.35 years following ASCT, it was no higher than that seen in the non-HIV ASCT setting. This is the largest single institution study reporting long-term follow up of HIV-positive patients post ASCT for NHL and demonstrating that while SPM remain a long term concern neither SPM, OI or HIV infection were major factors in mortality. DisclosuresNo relevant conflicts of interest to declare.

Immune recovery uveitis in HIV patients with cytomegalovirus retinitis in the era of HAART therapy-a 5-year study from Singapore.

BackgroundThe aim of this study is to analyse the clinical features of HIV patients with cytomegalovirus retinitis (CMVR) developing immune recovery uveitis (IRU) while on highly active antiretroviral therapy (HAART) and to identify the risk factors, visual outcomes and complications of IRU.ResultsMajority (n = 26, 86.7 %) of patients were male, with 76.7 % (n = 23) of patients having bilateral disease. Twenty-seven eyes (50.9 %) had both anterior uveitis and vitritis. The median CD4 at IRU was 210 cells/μL (IQR 140–279), with 86.7 % having CD4 >100 cells/μL. The median duration from initiation of HAART to IRU was significantly different between those <50 years old (median 763 days, IQR 174–1872 days) and those ≥50 years old (median 161 days, IQR 84.5–278 days). Fourteen eyes (26.4 %) had loss of one or more Snellen lines visual acuity at 6 months while the rest maintained or improved vision. Complications developed in 21 eyes, with cataract (66.7 %), glaucoma and ocular hypertension (33.3 %) being the most common. The risk of complications was associated with the absolute difference in CD4 counts at IRU and at HAART commencement (p = 0.041). Age was also negatively associated with the duration from HAART to IRU (p = 0.005, Spearman’s rho coefficient = −0.503).ConclusionsIt is common to have both anterior uveitis and vitritis in IRU. There was a positive association between the increase in CD4 from HIV to IRU diagnoses and the risk of developing complications. Younger patients appeared to develop IRU later than older patients after HAART, suggesting that long-term follow-ups are essential for these patients.

English

Cytomegalovirus (CMV) retinitis is an ocular manifestation of human immunodeficiency virus (HIV) infection especially in individual with low CD4 cells count. In Ghana, a country where CMV infection is hyperendemic, there is no data of CMV retinitis among HIV positive persons. This work was conducted to evaluate the prevalence of CMV retinitis among HIV positive persons attending eye clinic in Korle-Bu Teaching Hospital. Eye swab and vitreous samples were collected from HIV positive patients with retinal inflammation. The samples were assayed for DNA of Herpes Simplex Virus, Varicella Zoster, Cytomegalovirus and Epstein - Barr virus by using qualitative polymerase chain reaction (PCR) (multiplex PCR) to detect the presence or absence of herpes viruses. Sixty-two patients had retinal inflammation from ophthalmoscopy out of the total 404 that came into the clinic during the study period from July, 2010 to April, 2011. Forty six of these were HIV positive. Only 3 (6.5%) HIV positive patients had their swab or vitreous humour samples yielding DNA of CMV virus. These patients had their CD4 cell counts above 25 cells/&micro;l. This is the first study to show the prevalence of CMV retinitis among HIV patients in Korle-Bu Teaching Hospital, Ghana. It is necessary for more comprehensive longitudinal study to evaluate incidence and cumulative risk of CMV retinitis among HIV positive individual. Key words: Cytomegalovirus, human immunodeficiency virus, Ghana, Korle-Bu, retinitis, CD4, ophthalmoscopy.

Cytomegalovirus Retinitis in Patients With Acquired Immunodeficiency Syndrome After Initiating Antiretroviral Therapy

To evaluate the rates of new-onset cytomegalovirus (CMV) retinitis and worsening existing CMV retinitis in patients with AIDS after initiating combination antiretroviral therapy (cART) and the role of an immune recovery inflammatory syndrome (IRIS). Cohort study. Immune recovery was defined as an increase in CD4+ Tcells to ≥100 cells/μL; rates of new-onset CMV retinitis and of worsening of CMV retinitis (either increasing border activity or retinitis progression) were compared between those with and without immune recovery. Among patients without CMV retinitis, 1 of 75 patients with immune recovery developed CMV retinitis in the first 6months after initiating cART vs 1 of 31 without immune recovery (P= .14). Among patients with CMV retinitis, the rates of retinitis progression and increasing retinitis border activity among patients during the first 6months after initiating cART in those with immune recovery were 0.11 per person-year (PY; 95% confidence interval [CI] 0-0.62) and 0.11 per PY (95% CI 0-0.62), respectively, vs 0.67 per PY (95% CI 0.22-1.56) and 0.40 per PY (95% CI 0.08-1.17), respectively, for those without immune recovery (P= .11 and .47). Among persons with AIDS who experience immune recovery, there was neither an increased rate of new-onset CMV retinitis nor worsening of existing CMV retinitis in the first 6months after initiating cART vs those without immune recovery. These data are consistent with the known 3- to 6-month lag in recovery of specific immunity to CMV after initiating cART and suggest that "immune recovery retinitis," a proposed immune recovery inflammatory syndrome phenomenon, is rare.

Diagnostic Utility of Ocular Symptoms and Vision for Cytomegalovirus Retinitis.

PurposeCytomegalovirus (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.MethodsThis 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.ResultsOf 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).ConclusionsOcular 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.

Cytomegalovirus Retinitis in Pediatric Stem Cell Transplants: Report of a Recent Cluster and the Development of a Screening Protocol

The incidence of cytomegalovirus (CMV) retinitis in the pediatric allogeneic hematopoietic stem cell transplant (HSCT) population is unknown. We report a cluster of 5 pediatric patients with CMV retinitis diagnosed in a 12-month period and compare this to the rate of CMV viremia and retinitis in the 4 years prior. Presented is the ophthalmic screening protocol developed in response to this experience. Retrospective cross-sectional study. A retrospective chart review was performed on patients at Children's Hospital of Colorado (CHCO) who received allogeneic HSCT between January 2010 and December 2014. Fisher exact test was used to compare the proportion of CMV viremia and CMV retinitis in patients transplanted between January 2010 and December 2013 with those transplanted in 2014. A total of 101 patients underwent allogeneic HSCT from January 2010 to December 2013; 32 (32%) tested positive for CMV viremia. No cases of CMV retinitis were identified. From January 2014 to December 2014, 28 patients underwent allogeneic HSCT; 13 patients (46%) had CMV viremia, not a statistically significant increase (P= .18). There were 5 cases of CMV retinitis diagnosed in those transplanted in 2014, a statistically significant increase compared with those transplanted in 2010-2013 (P= .0004). A multidisciplinary team was formed to review the literature and an ophthalmic screening protocol was developed. Our recent cluster of CMV retinitis in pediatric allogeneic HSCT patients may suggest a rise in incidence of CMV retinitis. We propose an ophthalmic screening protocol to diagnose retinitis in pediatric HSCT patients in the early, often asymptomatic stage.

A rare case of cytomegalovirus papillitis in patient with immunodeficiency

A 26-year-old male diagnosed with AIDS came with sudden blurred vision and central sco-toma in left eye since 2 weeks before admission. His visual acuity was counting finger at 5 meters with normal IOP and anterior segment. The posterior segment revealed edematous optic nerve covered by exudates and hemorrhages. Due to low CD4+ count and serological test result, we considered a HIV-related opportunistic ocular infection, specifically HSV infection. As visual acuity worsened during treatment with acyclovir, we performed PCR ex-amination from aqueous tap which revealed positive CMV DNA. Unfortunately, the visual acuity had worsened to no light perception before he received any specific anti-CMV agent. CMV papillitis is an unusual presentation of CMV retinitis. PCR examination from aqueous or vitreous tap should be performed while waiting for serological test result, especially in doubtful cases. Therefore, appropriate diagnosis and management can be established early to prevent irreversible visual loss.

Review of cytomegalovirus coinfection in HIV-infected individuals in Africa

Cytomegalovirus (CMV) infection among HIV-infected individuals may cause end-organ disease, which is an AIDS-defining condition. Evidence from high-income countries suggests that CMV may alter the outcome of HIV infection, other than causing end-organ diseases. We reviewed literature on HIV and CMV coinfection in Africa. Systematic review of published studies on HIV and CMV coinfection in Africa using the PubMed database. High CMV seroprevalence was found throughout Africa, exceeding 90% in most populations. Retinitis, pneumonia, and colitis were the most commonly reported CMV manifestations in HIV-infected individuals. Among patients with pulmonary symptoms, the prevalence of CMV pneumonitis varied from 20% to over 60%, whereas CMV was found in 0% to 14% of patients with gastrointestinal manifestations. Cytomegalovirus retinitis was found in 0% to 2.6% of examined HIV-infected individuals. The diagnostics of CMV end-organ diseases were found complex and difficult to interpret in African settings. Cytomegalovirus viremia was correlated with significantly lower CD4 cell count and increase in activated and apoptosis vulnerable T-lymphocytes. Also, CMV coinfection was found to be associated with increased transmission and progression of HIV infection. Moreover, detectable CMV DNA was an independent predictor of HIV transmission and mortality among HIV-infected individuals. Cytomegalovirus is highly prevalent in Africa and a common cause of disease manifestations in HIV-infected individuals among all age groups. Cytomegalovirus coinfection in HIV-infected individuals in Africa is associated with increased transmission and mortality of HIV, but it is a neglected area of research.

Lenalidomide-bendamustine-rituximab in patients older than 65 years with untreated mantle cell lymphoma

AbstractFor elderly patients with mantle cell lymphoma (MCL), there is no defined standard therapy. In this multicenter, open-label phase 1/2 trial, we evaluated the addition of lenalidomide (LEN) to rituximab-bendamustine (R-B) as first-line treatment for elderly patients with MCL. Patients >65 years with untreated MCL, stages II-IV were eligible for inclusion. Primary end points were maximally tolerable dose (MTD) of LEN and progression-free survival (PFS). Patients received 6 cycles every four weeks of L-B-R (L D1-14, B 90 mg/m2 IV, days 1-2 and R 375 mg/m2 IV, day 1) followed by single LEN (days 1-21, every four weeks, cycles 7-13). Fifty-one patients (median age 71 years) were enrolled from 2009 to 2013. In phase 1, the MTD of LEN was defined as 10 mg in cycles 2 through 6, and omitted in cycle 1. After 6 cycles, the complete remission rate (CRR) was 64%, and 36% were MRD negative. At a median follow-up time of 31 months, median PFS was 42 months and 3-year overall survival was 73%. Infection was the most common nonhematologic grade 3 to 5 event and occurred in 21 (42%) patients. Opportunistic infections occurred in 3 patients: 2 Pneumocystis carinii pneumonia and 1 cytomegalovirus retinitis. Second primary malignancies (SPM) were observed in 8 patients (16%). LEN could safely be combined with R-B when added from the second cycle in patients with MCL, and was associated with a high rate of CR and molecular remission. However, we observed a high degree of severe infections and an unexpected high number of SPMs, which may limit its use. This trial is registered at www.Clinicaltrials.gov as #NCT00963534.

Frosted branch angiitis in an AIDS patient with cytomegalovirus retinitis

A case of frosted branch angiitis in an AIDS patient with cytomegalovirus (CMV) retinitis is reported. The use of PCR techniques for CMV DNA detection in intraocular fluid was helpful in this situation. The appropriate therapy was given promptly due to the timely diagnosis based on this assay.

Presentation and management of cytomegalovirus retinitis in immunocompromised children

PurposeCytomegalovirus retinitis in children is poor known and his management remains controversial. The objective of this study is to provide a precise clinical description and set a treatment protocol for a better management of these patients.MethodsRetrospective study including all children's eyes with primary immune deficiency (PID) patients with CMV retinitis confirmed by PCR on aqueous humor. The treatment protocol consisted of: an anti‐viral treatment with intravitreal injection (IVT) associated with general treatment. The primary endpoint was the good response to treatment defined by a quantifiable vision at the end of treatment.ResultsFifteen eyes of 8 children aged 6 months to 10 years were included, of 156 children transplanted for PID. Each eye received 4.7 ± 2.5 IVT of Gancyclovir (12/15) or Foscarnet (3/15). The time between IVT was 4, 8 ± 2 days. A systemic treatment was initiated. Eight eyes were placed in the ‘good recovery’ group (BR) and seven eyes of four patients in the ‘poor recovery’ group (MR). In the BR group's initial involvement was peripheral or sectorial, while in the MR group achievement was broadcast for four eyes or sectoral reached the posterior pole for three eyes. The number of IVT by eye and the time between IVT were not different between the groups as well as systemic therapy. At the end of treatment in the BR group the posterior pole was normal for five eyes or showed a para‐macular scar for three eyes. In the MR group, five eyes showed diffuse fibrosis and two macular scar.ConclusionsVisual prognosis seems related to the extent of the initial damage, the need for regular checks of the FO in children at risk is paramount. Regarding the treatment protocol, an average of four ganciclovir IVT to two per week without exceeding six IVT, combined with the general treatment appears to be an effective protocol.

Efficacy of the Janus kinase 1/2 inhibitor ruxolitinib in the treatment of vasculopathy associated with TMEM173-activating mutations in 3 children

Efficacy of the Janus kinase 1/2 inhibitor ruxolitinib in the treatment of vasculopathy associated with TMEM173-activating mutations in 3 children

Risk factors for cytomegalovirus retinitis among individuals with HIV and low CD4 count in northern Thailand

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Incidence and risk factors of cytomegalovirus (CMV) retinitis: implications for screening

Incidence and risk factors of cytomegalovirus (CMV) retinitis: implications for screening