Development Of Cytomegalovirus Retinitis Research Articles

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.

Development of cytomegalovirus retinitis after negative conversion of cytomegalovirus antigenemia due to systemic antiviral therapy.

Cytomegalovirus (CMV) antigenemia assays have been widely used as adjunct tests to diagnose tissue invasive CMV diseases, including cytomegalovirus retinitis (CMVR). In this study, we examined CMVR cases to assess the presence of CMV in sera and aqueous humor and antiviral therapy received prior to the onset of CMVR. A total of 37 eyes from 26 different cases of CMVR in patients who visited Hokkaido University Hospital between 2007 and 2015 were enrolled. The diagnosis of CMVR was established based on characteristic ophthalmoscopic findings and the presence of local and/or systemic CMV infection. Among the 26 cases, 3 cases (12%) were HIV-positive, while the other 23 cases (88%) were HIV-negative. The records of clinical and laboratory results were reviewed from clinical charts retrospectively. CMV antigenemia was positive at the onset of CMVR in 14 cases (53.8%) and negative in the other 12 cases. In 9 cases among the antigenemia-negative cases (75.0%), the antigenemia had been previously positive and had turned negative before the onset of CMVR. In 12 of the 14 antigenemia-positive cases (85.7%) and in 8 of the 9 antigenemia-negative cases (88.9%) that were previously positive, systemic antiviral therapies had never been used or had been used before but had been discontinued prior to the onset of CMVR. Even if viremia turns negative, the risk of developing CMVR exists for more than several weeks after the completion of systemic therapy.

Abnormal levels of aqueous humor trace elements in patients with cytomegalovirus retinitis.

To investigate the alterations of trace elements levels in aqueous humor of patients with cytomegalovirus retinitis (CMVR). A total of 15 eyes of 11 patients with CMVR and 24 eyes of 24 patients with senile cataract as control group were enrolled. Aqueous humor samples were assessed for calcium (Ca), potassium (K), magnesium (Mg), sodium (Na), phosphorus (P), titanium (Ti), vanadium (V), chromium (Cr), manganese (Mn), iron (Fe), nickel (Ni), copper (Cu), zinc (Zn), selenium (Se), strontium (Sr), and lead (Pb) by using inductively coupled-plasma-mass-spectrometry. Meanwhile, we examined the concentration of the CMV DNA load by using PCR and the concentration of interleukin (IL)-8 by using a cytometric bead array. In patients with CMVR, the aqueous humor levels of P and Cu were significantly higher than those of controls (p < 0.001, p < 0.001, respectively). However, levels of K and Mg were significantly lower in patients with CMVR (p < 0.001, p < 0.001, respectively). The Spearman correlation test showed that the concentration of IL-8 in the aqueous humor was significantly associated with the aqueous level of Cu (p = 0.009, r = 0.646) and Se (p = 0.031, r = 0.558). In addition, the concentration of CMV DNA load in the aqueous humor was significantly associated with the aqueous level of Ca (p = 0.027, r = -0.568), Mn (p = 0.020, r = 0.593), and Cu (p = 0.043, r = 0.527). Our preliminary results demonstrated that the abnormal aqueous levels of trace elements (P and Cu) in CMVR patients. Thus, the roles of trace element changes in the development of CMVR and the influence of intraocular trace element for the prognosis of CMVR warrant further investigations.

Cytomegalovirus Retinitis in a Human Immunodeficiency Virus-negative Cohort: Long-term Management and Complications

Purpose: To examine the clinical outcomes achieved by using intravitreal ganciclovir injections combined with systemic anti-viral therapy in treating cytomegalovirus (CMV) retinitis in patients without human immunodeficiency virus (HIV) infection.Methods: Twenty-three eyes of 15 HIV-negative patients diagnosed with CMV retinitis were included in this retrospective study.Results: The median follow-up was 68 weeks (range, 12–156), and median number of injections was 10 (range, 2–22). The retinal lesions stopped progressing within 1–2 weeks following treatment. All of the eyes showed either unchanged or ≥2 line improvements of BCVA at last visit. There was no development of CMV retinitis in a fellow eye, or recurrence in a studied eye. Systemic complications such as neutropenia were not detected.Conclusions: Intravitreal ganciclovir injections combined with systemic anti-viral treatment is a good therapeutic option for treating CMV retinitis without HIV infection. Such treatment provided favorable visual outcomes, with minimal ocular and systemic complications.

Human leucocyte antigen profile in patients with aids and cytomegalovirus retinitis with and without macular involvement

Introduction: Cytomegalovirus retinitis is one of AIDS ocular manifestations. The objective of the present study was to determine possible associations between class I and II HLA antigens and alleles in patients with AIDS and cytomegalovirus retinitis (CMV-R) with macular involvement. Method: The study population consisted of 22 patients with AIDS and CMV-R with macular involvement (Group I), 19 patients with AIDS and CMV-R without macular involvement (Group II), and 202 individuals with negative serology for human immunodeficiency virus (Group III - control). Class I HLA antigens were typed by classical serology. Class II alleles were identified using sequence-specific oligonucleotide primers hybridized with amplified DNA. Results: HLA-DRB1*14 and HLA-DRB1*10 specificities were more frequent among patients with macular involvement, possibly indicating greater susceptibility to this condition. In contrast, the HLA-B35 antigen may be associated with protection against macular involvement since it was significantly more frequent among patients without this involvement. Conclusions: The HLA-DRB1*14 and HLA-DRB1*10 alleles may favor the development of CMV-R with macular involvement, whereas the HLA-B35 subtype may be associated with protection against macular involvement.

Effect of host genetics on the development of cytomegalovirus retinitis in patients with AIDS.

Cytomegalovirus (CMV) retinitis is a common opportunistic infection among patients with AIDS and still causes visual morbidity despite the wide spread usage of highly active antiretroviral therapy (HAART). The ubiquitous CMV pathogen contains a human interleukin-10 (IL-10) homolog in its genome and utilizes it to evade host immune reactions through an IL-10 receptor mediated immune-suppression pathway. Effects of IL-10R1, IL-10 and previously described AIDS restriction gene variants are investigated on the development of CMV retinitis in the Longitudinal Study of the Ocular Complications of AIDS (LSOCA) cohort (N = 1284). In European Americans (n = 750), a haplotype carrying an amino acid changing variation in the cytoplasmic domain (S420L) of IL-10R1 can be protective (OR, 0.14; 95% CI, 0.02-0.94; P = .04) against, whereas another haplotype carrying an amino acid changing variation in the extracellular domain (I224V) of IL-10R1 can be more susceptible (OR, 6.21; 95% CI, 1.22- 31.54; P = .03) to CMV retinitis. In African Americans (n = 534), potential effects of IL-10 variants are observed. Host genetics may have a role in the occurrence of CMV retinitis in patients infected with HIV.

Cytomegalovirus retinitis

Cytomegalovirus (CMV) retinitis is the most common ocular opportunistic infection affecting patients with AIDS, despite the fact that the use of highly active antiretroviral therapy (HAART) has reduced its incidence by 80%. Treatment with HAART has decreased the risk of retinitis progression, retinal detachment and visual loss in patients with CMV retinitis. HAART-induced immune recovery has been associated with an approximately 50% reduction in the risk of visual loss in eyes of patients with CMV retinitis. However, immune recovery uveitis, an ocular complication seen in the era of HAART, may increase the risk of visual loss. Furthermore, among patients with AIDS and without CMV retinitis followed in the era of HAART, the development of CMV retinitis over time has been reported to account for approximately 40% of incident vision loss and, thus, continues to be the leading cause of visual loss among patients with AIDS.

Effect of Cytomegalovirus Retinitis on the Risk of Visual Acuity Loss among Patients with AIDS

To describe the prevalence and incidence of reduced visual acuity in eyes of patients with AIDS and without cytomegalovirus (CMV) retinitis at enrollment and estimate the proportion of incident vision loss attributable to new-onset CMV retinitis in this cohort. Multicenter prospective observational study. Three thousand fourteen eyes of 1507 patients with AIDS and without CMV retinitis at enrollment. Medical history, ophthalmologic examination, and laboratory testing collected at enrollment and at follow-up visits every 6 months thereafter. Loss of visual acuity across the < or =20/50 and < or =20/200 thresholds and doubling of the visual angle; potential causes of this vision loss. For eyes of patients without CMV retinitis at enrollment, the proportions with best-corrected visual acuity of < or =20/50 and of < or =20/200 were 3.9% and 1.8%, respectively. The incidence rates of vision loss to < or =20/50, < or =20/200, and to a doubling of the visual angle were 1.5/100 eye-year (EY), 0.8/100 EY, and 2.1/100 EY, respectively. Approximately 40% of the incident vision loss was attributable to CMV retinitis diagnosed during the follow-up period, and approximately 25% was attributable to cataract. Although the development of CMV retinitis was the most common reason for visual acuity loss in eyes of our patients with AIDS, it accounted for less than half of the vision loss in our population (approximately 40%). Newly diagnosed cataract during the follow-up period accounted for a substantial amount of incident vision loss as well.

Incidence of Cytomegalovirus (CMV) Retinitis in Second Eyes of Patients With the Acquired Immune Deficiency Syndrome and Unilateral CMV Retinitis

To evaluate the risk and risk factors for developing cytomegalovirus (CMV) retinitis in previously uninvolved second eyes among patients with unilateral CMV retinitis. Cohort study. Single-center academic AIDS ophthalmology practice. Three hundred seventy-six consecutive patients with AIDS and unilateral CMV retinitis were followed from the time of CMV retinitis diagnosis for the development of second-eye retinitis. Demographic and clinical characteristics were noted at baseline. Use of highly active antiretroviral therapy (HAART) and immune recovery in response to HAART were noted prospectively. Development of CMV retinitis in a previously uninvolved eye. Ninety-one percent of subjects received systemic anti-CMV treatment. Second-eye retinitis occurred in 26.1%/person-year (19.6% within the first 6 months), less than half the rate previously reported in untreated groups. Initial CD4+ T cell count >12 cells/microl, use of HAART, and initial posterior pole involvement were associated with 64%, 46%, and 41% reductions in incidence vis-à-vis comparison groups. Benefit from HAART was limited to that subset who developed immune recovery of a degree expected to restore innate control of CMV (a rise in the CD4+ T cell count by >50 cells/microl to a level >100 cells/microl). The risk of second-eye retinitis is substantial in patients with unilateral CMV retinitis but appears to be reduced by anti-CMV therapy and by HAART-induced immune recovery. Patients are at highest risk when CD4+ T cell counts are very low and in the months immediately after CMV retinitis diagnosis.

Association between cytomegalovirus-specific reactivity of T cell subsets and development of cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome.

The association between cytomegalovirus (CMV)-specific reactivity of T cell subsets and development of CMV retinitis (CMV-R) was prospectively studied in 50 CMV-seropositive AIDS patients. The frequency of CMV-specific CD69 expression on CD8 T cells was similar in patients with and patients without CMV-R (median, 1.0% vs. 1.2%; P=.14). However, the frequency of CMV-specific CD69 expression on CD4 T cells was significantly lower in patients with CMV-R than in those without CMV-R (median, 0.4% vs. 2.25%; P<.001). CMV-specific CD4 T cell reactivity in patients who developed CMV-R shortly after starting highly active antiretroviral therapy (HAART) remained low, although the CD4 cell counts increased markedly. Therefore, development of CMV-R is associated with a poor CMV-specific reactivity of CD4 T cells but not with poor reactivity of CD8 T cells. Development of CMV-R after initiation of HAART is associated with a poor reconstitution of CMV-specific immune response, rather than with immune rebound.

Retrospective study of CMV retinitis in patients with AIDS

To study the characteristics of clinical presentations and treatment outcome of patients with HIV infection who developed cytomegalovirus(CMV) retinitis. A retrospective study for the period 1986-97 at the regional Unit of Infectious Diseases, Newcastle General Hospital; a teaching hospital in the north-east of England. Twenty-seven patients with advanced HIV disease and clinically confirmed CMV retinitis were studied. The mean age was 40.8 years, standard deviation +/-6.3 years. The male : female ratio was 25 : 2. Twenty-six of the patients were white Caucasians and one was of Afro-Caribbean origin. The median time between the first AIDS-defining diagnosis and development of CMV retinitis was 1.5 years and the CD4+ cell count at the time of diagnosis of CMV retinitis was 7/mm3. After 14 months of treatment. 80% of patients on mono antiretroviral therapy had impairment of sight (visual acuity 3/60) versus 30% for those on triple antiretroviral therapy. In the same period, the survival rate was 18 versus 70% for mono versus triple antiretroviral therapy, respectively. The outcome for patients with CMV retinitis was significantly better for those who were on triple than for those on mono antiretroviral therapy.

Quantitative cytomegalovirus DNA level in the blood and its relationship to cytomegalovirus retinitis in patients with acquired immune deficiency syndrome

Objective A pilot study was performed to determine whether relationships exist between changes in a quantitative solution hybridization assay for cytomegalovirus (CMV) DNA in the blood and development of CMV retinitis, development of nonocular CMV disease, or reactivation of pre-existing CMV retinitis lesions. Design Observational case series. Participants Two groups of human immunodeficiency virus-infected patients: 10 CMV antibody-positive patients with CD4+ T-lymphocyte counts of less than 50 ml and no CMV disease at baseline and 11 patients with CMV retinitis but no extraocular CMV disease at baseline. Intervention Quantitative changes in leukocyte-associated CMV DNA levels were observed over time. Anti-CMV therapies were based on clinical findings only. Main outcome measures Development of CMV end-organ disease or change in activity of pre-existing CMV retinitis lesions was measured. Results Among patients with no CMV disease at baseline, four had CMV disease develop during follow-up (three cases of CMV retinitis, one case of presumed CMV esophagitis); all had CMV DNA levels greater than 5000 genomes/ml before the onset of CMV disease. The remaining six patients had levels less than 5000 genomes/ml throughout follow-up ( P = 0.05). Among patients with CMV retinitis at baseline, all whose CMV DNA blood levels rose more than tenfold had extraocular CMV disease or reactivation of CMV retinitis develop. Raised CMV DNA blood levels were not seen in every patient with clinical reactivation of CMV retinitis. Conclusion Elevated or rising CMV DNA blood levels appear to be associated with the development of CMV disease in individuals with low CD4+ T-lymphocyte counts. In patients with CMV retinitis, rising levels appear to be associated with the development of extraocular CMV disease or reactivation of CMV retinitis. Conversely, reactivation of CMV retinitis also may occur in the absence of changes in CMV DNA blood levels. Further studies are warranted to determine whether changes in CMV blood levels can be used as a guide for preemptive therapy to prevent reactivation of CMV retinitis lesions or to help choose between local and systemic therapy for management of reactivations.

Cytomegalovirus glycoprotein B groups associated with retinitis in AIDS.

To determine if cytomegalovirus (CMV) retinitis occurs more frequently in patients infected with certain strains CMV isolates from the blood of 44 patients with advanced human immunodeficiency virus disease were grouped by the DNA sequence or the restriction endonuclease digest pattern of a portion of the glycoprotein B (gB) gene. Forty-two patients (95%) were followed clinically until the development of CMV retinitis or death. Fourteen (78%; 95% confidence interval, 7%-39%) of 26 with isolates belonging to other gB groups developed CMV retinitis (P = .002). Viremia caused by gB group 2 CMV strains is associated with higher risk of CMV retinitis than viremia due to other CMV gB groups. The association of CMV gB gene with retinitis suggests this gene, or one linked to it, is a virulence factor for CMV strains causing infection in AIDS patients.