CYTOMEGALOVIRUS RETINITIS AFTER AN INTRAVITREAL DEXAMETHASONE IMPLANT IN AN IMMUNOCOMPETENT PATIENT.

PURPOSE: To present the case of a 71-year-old woman who developed cytomegalovirus retinitis after the administration of an intravitreal dexamethasone implant in an immunocompetent patient. METHODS: Retrospective case report. PATIENTS: Single patient with a diagnosis of cytomegalovirus retinitis associated with the intravitreal dexamethasone implant. RESULTS: The patient developed cytomegalovirus retinitis three months after an intravitreal injection of a dexamethasone implant for macular edema. The patient had no history of poor immune function and was not taking immunosuppressive medications. CONCLUSION: Cytomegalovirus retinitis has been associated with local steroid therapy. This has been described in both immunocompromised and immunocompetent patients. The intravitreal dexamethasone implant may cause local immunosuppression and result in cytomegalovirus retinitis in immunocompetent patients.

A TNF Block Genotype may Influence CMV Retinitis in HIV Patients without Affecting Systemic Viral Replication.

BACKGROUND: A conserved TNF block haplotype marked by the minor alleles of rs1800629 (TNFA-308*A) and rs9281523 [BAT1(intron 10)*C] has been linked with several immunopathological conditions and with rapid progression of HIV disease. Reported associations with cytomegalovirus (CMV) retinitis in HIV patients before or during early antiretroviral therapy (ART) may therefore reflect greater replication of CMV in advanced HIV disease or an immunopathological response to CMV in the retina. OBJECTIVE: As all Indonesian HIV patients display high levels of CMV replication, we evaluated whether TNF block genotypes alter markers of their burden of CMV and/or associate with retinitis. METHODS: We assessed 79 consecutive HIV patients beginning ART, 25 HIV patients with a history of CMV-retinitis and 63 healthy adults. HIV RNA, CD4 T-cell counts, CMV-reactive antibody and CMV DNA were measured and alleles of TNFA-308, BAT1(intron 10) and TNFA-1031 (rs1799964) were determined. RESULTS: TNFA-308 and BAT1(intron 10) were in complete linkage disequilibrium. Patients carrying minor alleles at both loci had higher levels of CMV-reactive antibody after one month on ART (p=0.01), but not at other time points spanning 1 year on ART. 50% of patients had detectable CMV DNA before ART, irrespective of TNF block genotypes. However, the TNFA-308*A/- BAT1(intron 10)*C haplotype was more common in CMV-retinitis patients than other patients or healthy controls (p<0.01). CONCLUSION: The TNFA-308*A/BAT1(intron 10)*C haplotype appears to affect CMV-induced pathology rather than CMV replication.

Disseminated cytomegalovirus disease after bendamustine: a case report and analysis of circulating B- and T-cell subsets.

BACKGROUND: Bendamustine, used for the treatment of indolent B-cell non-Hodgkin lymphoma and chronic lymphocytic leukemia, is known to cause prolonged myelosuppression and lymphocytopenia and has been associated with the risk of developing serious and fatal infections. While reports of localized CMV infections in asymptomatic patients exist, disseminated CMV disease has not been described. CASE PRESENTATION: We report the first case of disseminated CMV infection in a 75-year-old male diagnosed with lymphoplasmacytic lymphoma/Waldenström macroglobulinemia with massive bone marrow infiltration. Despite 6-cycle R-bendamustine chemotherapy resulted in a good partial response, the patient developed persistent fever and severe weight loss. Analysis of cerebrospinal fluid and peripheral blood revealed the presence of CMV-DNA, while the fundus oculi examination revealed bilateral CMV retinitis. Treatment with induction and maintenance drugs was complicated by neutropenia and deterioration of renal function with electrolyte imbalance. From an immunological standpoint, we observed a profound imbalances in phenotype and function of B- and T-cell subsets, with a high proportion of circulating total, activated CD69+ and CD80+ B-cells, a low γ/δ T-cell frequency with a high proportion of CD69- and CD38-expressing cells, and hyperactivated/exhausted CD4+ and CD8+ T-cell phenotypes unable to face CMV challenge. CONCLUSIONS: We hereby describe a severe form of disseminated CMV disease after R-bendamustine treatment. Our observations strongly support the careful clinical monitoring of CMV reactivation/infection in oncologic patients undergoing this therapeutic regimen.

[Cytomegalovirus retinitis after an intravitreal dexamethasone implant].

In this case report an immunocompetent patient developed retinitis after implantation of an intravitreal dexamethasone implant following a primary infection with cytomegalovirus. The implant was prescribed due to a history following a central vein occlusion with macular oedema and loss of vision. Vision improved after implantation, however, due to retinitis a vitrectomy was performed proving infection with cytomegalovirus. This case and two other recent presen-tations warrant the consideration cytomegalovirus infection in even immunocompetent individuals showing signs of retinitis following dexamethasone implantation.

Macular cytomegalovirus retinitis following dexamethasone intravitreal implant combined with phacoemulsification.

A 60-year-old diabetic patient, who had undergone a renal transplant 2 years earlier, presented with sudden decrease in vision in his left eye (LE). He had undergone phacoemulsification combined with intravitreal dexamethasone implant injection in his LE 2 months earlier, for coexistent cataract and diabetic macular edema. Examination revealed necrotizing retinitis with hemorrhages in the macula. A diagnosis of cytomegalovirus retinitis was made, which was confirmed on vitreous polymerase chain reaction. Intravitreal and systemic ganciclovir led to the resolution of retinitis and improvement of visual acuity over a follow-up of 9 months.

Reduced frequency of murine cytomegalovirus retinitis in C57BL/6 mice correlates with low levels of suppressor of cytokine signaling (SOCS)1 and SOCS3 expression within the eye during corticosteroid-induced immunosuppression.

AIDS-related human cytomegalovirus retinitis remains a leading cause of blindness worldwide. We compared two C57BL/6 mouse models of experimental murine cytomegalovirus (MCMV) retinitis for intraocular expression of suppressors of cytokine signaling (SOCS)1 and SOCS3, host proteins that are inducible negative feedback regulators of cytokine signaling. These mouse models differed in method of immune suppression, one by retrovirus-induced immune suppression (MAIDS) and the other by corticosteroid-induced immune suppression. Following subretinal injection of MCMV to induce retinitis, intraocular SOCS1 and SOCS3 were only mildly stimulated, and often without significance, within MCMV-infected eyes during the progression of MCMV retinitis in corticosteroid-immunosuppressed mice, contrary to MCMV-infected eyes of mice with MAIDS that showed significant high stimulation of SOCS1 and SOCS3 expression in agreement with previous findings. Frequency and severity of retinitis as well as amounts of intraocular infectious MCMV in corticosteroid-immunosuppressed mice were also unexpectedly lower than values previously reported for MAIDS animals during MCMV retinitis. These data reveal a major difference between two mouse models of experimental MCMV retinitis and suggest a possible link between the amplitude of SOCS1 and SOCS3 stimulation and severity of disease in these models.

Cytomegalovirus retinitis complicating combination therapy with rituximab and fludarabine.

Cytomegalovirus (CMV) retinitis is exceptionally rare outside the clinical context of acquired immunodeficiency syndrome and organ allografting. In a population where seropositivity for past CMV infection exceeded 90 %, CMV retinitis was observed in five of 138 patients (3.6 %) receiving fludarabine-containing regimens together with rituximab, which was significantly more frequent than in 141 patients receiving fludarabine-containing regimens alone, where no case was observed (P = 0.029). Treatment of CMV retinitis comprised both intravitreal and systemic ganciclovir/foscarnet. Upon recovery, secondary retinal atrophy occurred in all patients, leading to blindness in 86 % of affected eyes. CMV retinitis is an important complication in patients receiving concomitant rituximab and fludarabine-containing regimens.

Cytomegalovirus retinitis diagnosed after completion of chemotherapy for acute lymphoblastic leukemia in an adolescent.

Although cytomegalovirus (CMV) retinitis is usually diagnosed in allogeneic hematopoietic cell transplantation recipients among patients with hematologic and oncologic disease, it can also occur in acute leukemia patients who have not received hematopoietic cell transplantation. However, CMV retinitis diagnosed after completion of chemotherapy for acute leukemia has not previously been reported. A 17-year-old boy was diagnosed with CMV retinitis 3 months after completion of chemotherapy for acute lymphoblastic leukemia, and his retinitis was assumed to be caused by a delayed immune reconstitution after chemotherapy. The patient was treated with intravenous and intravitreous ganciclovir therapy, and subsequently underwent surgery for retinal detachment.

Cytomegalovirus retinitis following intravitreal triamcinolone acetonide in a patient with chronic uveitis on systemic immunosuppression.

PURPOSE: To report a case of cytomegalovirus (CMV) retinitis in an HIV-negative, iatrogenically immunosuppressed patient with chronic uveitis following intravitreal triamcinolone acetonide (IVTA). DESIGN: Observational case report. METHODS: A 56-year-old female with chronic idiopathic panuveitis on azathioprine received a single 4-mg IVTA injection for macular edema and presented after 6 months with severe retinitis. RESULTS: CMV was confirmed by polymerase chain reaction of vitreous fluid. The retinitis responded well to intravitreal ganciclovir, but she developed a rhegmatogenous retinal detachment and underwent vitrectomy with silicone oil tamponade. CONCLUSIONS: Sight-threatening CMV retinitis may develop in HIV-negative, immunosuppressed individuals after IVTA. Regular fundoscopy for up to 9 months after IVTA is recommended.

Cytomegalovirus retinitis as an adverse immunological effect of pulses of vincristine and dexamethasone in maintenance therapy for childhood acute lymphoblastic leukemia.

We describe a 5-year-old female with acute lymphoblastic leukemia (ALL) who suffered from cytomegalovirus (CMV) retinitis during maintenance therapy consisting of 6-mercaptopurine (6-MP) and methotrexate (MTX) with pulses of vincristine (VCR) and dexamethasone (DEX). Administration of anticytomegaloviral drugs led to a complete regression of active retinitis. Her low CD4 positive T cells and serum immunoglobulin G (IgG) recovered when maintenance therapy was resumed without VCR and DEX. The patient has been in complete remission (CR) for more than 5 months after completion of maintenance therapy without recurrence of CMV retinitis.

Cytomegalovirus Retinitis in an ALL child on exclusive chemotherapy treated successfully with intravitreal ganciclovir alone.

A child suffering from acute lymphoblastic leukemia on treatment with exclusive chemotherapy presented with vision-threatening cytomegalovirus (CMV) retinitis in 1 eye. Prompt diagnosis and treatment with 3 weekly doses of 2 mg/0.1 mL intravitreal ganciclovir resulted in successful healing of CMV retinitis with restoration of visual acuity. In children with acute lymphoblastic leukemia on exclusive chemotherapy without hematopoietic stem cell transplantation, CMV retinitis has been reported in only 1 case in literature. This child was treated successfully with intravenous ganciclovir. This report highlights the use of successful intravitreal ganciclovir in pediatric age group to avoid side effects of systemic ganciclovir.

Tuberculoid leprosy and cytomegalovirus retinitis as immune restoration disease in a patient with AIDS.

Here we report a unique case of tuberculoid leprosy and cytomegalovirus retinitis in a 27-year-old female patient with AIDS, suggestive of highly active antiretroviral therapy (HAART)-induced immune restoration disease. After initiation of HAART, the patient presented with decreased visual acuity, hypoesthetic patch with local nerve thickening, and an increase in her CD4+ T cell count. On further investigations cytomegalovirus retinitis and tuberculoid leprosy were confirmed. To our knowledge no case with such a co-existence has previously been reported.

Cytomegalovirus retinitis after intravitreous triamcinolone in an immunocompetent patient.

PURPOSE: To report the case of a 75-year-old man with diabetes who developed cytomegalovirus (CMV) retinitis after intravitreous injection of triamcinolone acetonide (IVTA). DESIGN: Observational case report. METHODS: Review of medical records. RESULTS: A 75-year-old man with diabetic macular edema developed arcuate retinal whitening after IVTA. A presumptive diagnosis of viral retinitis was made, and a vitrectomy was performed. Polymerase chain reaction of the vitreous was positive for CMV DNA. An infectious disease consultant found no signs of systemic CMV infection, and laboratory examination revealed that the patient was HIV negative. The patient responded well to intravitreal ganciclovir and oral valganciclovir, but when therapy was discontinued, the retinitis recurred and CMV DNA was again detected in the vitreous. The retinitis once again responded to antiviral therapy. CONCLUSIONS: CMV retinitis can occur after local immunosuppression with IVTA. Clinicians should be aware of this rare complication of IVTA.

Cytomegalovirus retinitis in a patient treated with anti-tumor necrosis factor alpha antibody therapy for rheumatoid arthritis.

BACKGROUND: Anti-tumor necrosis factor alpha (anti-TNF- alpha ) antibodies have been used for the treatment of chronic inflammatory diseases such as rheumatoid arthritis (RA) and psoriasis arthritis. Such antibody therapies result in a severe interference with the patient's immune system. Increased rates of upper respiratory tract infection, reactivation of latent tuberculosis, and other systemic infectious diseases have been reported among patients receiving anti-TNF- alpha antibodies. METHODS: As a note of caution, we describe a 57-year-old woman who received therapy with anti-TNF- alpha antibodies for RA refractory to methotrexate. After almost 2 years of treatment, she developed a severe cytomegalovirus (CMV) retinitis of the right eye. RESULTS: Laboratory assays revealed an immune status with nearly total loss of the cellular immune response and partial reduction of the humoral immune response. Intravenous treatment with ganciclovir, followed by oral administration of valganciclovir, resulted in an ophthalmological remission. Cessation of immunosuppressive therapy led to partial immunological reconstitution in the patient. Six months after discontinuation of immunosuppressive therapy, CMV retinitis of the left eye occurred but was treated successfully with a second course of oral valganciclovir. CONCLUSION: In the light of this first reported case of a serious CMV infection following therapy with anti-TNF- alpha antibodies, CMV infection should be considered in symptomatic patients.

Bilateral cytomegalovirus retinitis in a patient with systemic lupus erythematosus and end-stage renal disease.

Rheumatic diseases are not commonly associated with cytomegalovirus (CMV) retinitis. We report a case of bilateral CMV retinitis in a human immunodeficiency virus-seronegative patient with systemic lupus erythematosus (SLE) who was undergoing hemodialysis for end-stage renal disease. The CMV retinitis in this patient was associated with combined azathioprine and low-dose corticosteroid therapy for lupus flare. This association may have important clinical implications because this drug combination is used routinely to treat active SLE. Our patient responded to discontinuation of azathioprine, reduction of the corticosteroid dose, and systemic administration of ganciclovir. We recommend that clinicians maintain heightened awareness of the possibility of CMV retinitis in patients with SLE and end-stage renal disease who are receiving azathioprine and low-dose corticosteroids.