Dataset Information

Relationship Between Opacity of Cytomegalovirus Retinitis Lesion Borders and Severity of Immunodeficiency Among People With AIDS.

ABSTRACT: Purpose:To evaluate risk factors for severity of cytomegalovirus (CMV) retinitis lesion whitening (opacity), using a standardized scoring system. Methods:We performed a cross-sectional, observational investigation of all individuals with newly diagnosed AIDS-related CMV retinitis in three randomized clinical trials and one prospective observational study. Opacity was scored by masked readers, using a prospectively defined ordinal 6-point scale. Demographic factors, laboratory data (CD4+, CD8+ T-lymphocyte counts, human immunodeficiency virus [HIV] blood levels), and lesion characteristics (location, size) were compared to the highest opacity score assigned to either eye. Among eyes with active lesions (scores ?3), factors associated with severe opacity (scores 5, 6) were identified. Results:There were 299 participants (401 eyes with CMV retinitis). In one or more comparisons, increased opacity was associated with lower CD4+ and lower CD8+ T-lymphocyte counts, higher HIV blood level, lack of antiretroviral therapy, male sex, race/ethnicity, and bilateral disease. In eyes with active disease, severe opacity was associated with lower CD4+ T-lymphocyte count, higher HIV blood level, older age, Karnofsky score, lesion size, and bilateral disease. No relationship was identified between opacity and lesion location. Conclusions:Lesion border opacity (resulting from CMV activity) reflects level of immune function; as immunodeficiency becomes worse, CMV activity (and opacity) increases. The positive relationship between opacity and HIV blood level may reflect both immunodeficiency and increased CMV activity caused by transactivation of CMV by HIV. Scoring of opacity may be a useful, standard measure for continued study of CMV retinitis across different settings and populations. (Clinicaltrials.gov number for the HPMPC CMV Retinitis Trial: NCT00000142; Clinicaltrials.gov number for the Monoclonal Antibody CMV Retinitis Trial: NCT00000135; Clinicaltrials.gov number for the Ganciclovir-Cidofovir CMV Retinitis Trial: NCT0000014; Clinicaltrials.gov number for the Longitudinal Study of the Ocular Complications of AIDS: NCT00000168.).

SUBMITTER: Holland GN

PROVIDER: S-EPMC6890425 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Relationship Between Opacity of Cytomegalovirus Retinitis Lesion Borders and Severity of Immunodeficiency Among People With AIDS.

Holland Gary N GN Van Natta Mark L ML Goldenberg David T DT Ritts Rory R Danis Ronald P RP Jabs Douglas A DA

Investigative ophthalmology & visual science 20190501 6

<h4>Purpose</h4>To evaluate risk factors for severity of cytomegalovirus (CMV) retinitis lesion whitening (opacity), using a standardized scoring system.<h4>Methods</h4>We performed a cross-sectional, observational investigation of all individuals with newly diagnosed AIDS-related CMV retinitis in three randomized clinical trials and one prospective observational study. Opacity was scored by masked readers, using a prospectively defined ordinal 6-point scale. Demographic factors, laboratory data ...[more]

PMID: 31042791

Similar Datasets

Project description:Background: Cytomegalovirus retinitis (CMVR) is a crucial blind-causing disease of AIDS-related ocular opportunistic infection. The CMVR lesions produced retinal necrosis. It is not entirely clear whether CMVR eyes without macular-involved necrotic lesions may have subtle macular damage. In this study, we conducted a cross-sectional study using optical coherence tomography angiography (OCTA) to evaluate macular microvasculature and structure in eyes with AIDS-related CMVR. Methods: Acquired immune deficiency syndrome (AIDS)-related CMVR patients (active and inactive CMVR) and healthy controls treated in the Department of Ophthalmology, Beijing Youan Hospital, Capital Medical University between August 25, 2019, and October 18, 2019, were recruited. All OCTA parameters, including the foveal avascular zone (FAZ), retinal vessel density (VD), choroidal vascularity index (CVI), retinal thickness, and choroidal thickness, were compared between groups after the signal strength was corrected. Results: Signal strength in the 3 × 3 and 6 × 6 mm scan patterns was significantly weaker in the inactive CMVR group than in the control group (both p < 0.001). After adjusting for signal strength, heterogeneity in the central fovea and parafoveal quadrants was present with a shift toward lower macular chorioretinal vasculature, decreased full choroidal thickness, and thicker retinal thickness in the active and inactive CMVR groups. The retinal nerve fiber layer (RNFL) and inner nuclear layer (INL) were significantly thicker in the active and inactive CMVR groups than in the control group (all p < 0.05). For photoreceptor-retinal pigment epithelium (PR-RPE) thickness, no significant differences were found in any quadrant between groups. Foveal avascular zone areas were not significantly different among the three groups (p = 0.053). Conclusions: Subtle macular structure and microvasculature damage still existed in CMVR eyes without macular-involved necrotic lesions. The results of our study are helpful for a deep understanding of the damage caused by CMVR.

Project description:BackgroundCytomegalovirus retinitis (CMVR) is the most common and sight-threatening opportunistic retinal infection in patients with acquired immunodeficiency syndrome (AIDS) and several controversies remain to be settled. We aimed to summarize the current evidence and clarify the clinical features and prognosis of CMVR in AIDS patients.MethodsThe databases PubMed, EMBASE, and Ovid from inception to April 2022 were searched to identify the relevant studies. R software version 3.6.3 was used to perform the statistical analyses. Results in proportion with 95% confidence interval (CI) were calculated using the Freeman-Tukey variant of arcsine square transformation.ResultsWe finally included 236 studies comprising 20,214 patients. CMVR in AIDS was male-dominated (88%, 95%CI 86%-89%), with 57% (95%CI 55%-60%) aged <41 years and 44% (95%CI 41%-47%) being bilaterally involved. CMVR was preponderant in AIDS patients with the following characteristics: white and non-Hispanic, homosexual, HIV RNA load ≥ 400 copies/mL, and CD4+ T-cells <50 cells/μL. The positivity of CMV-DNA in blood, aqueous humor, and vitreous humor was 66% (95%CI 52%-79%), 87% (95%CI 76%-96%), and 95% (95%CI 85%-100%), respectively. The most common symptoms were blurred vision (55%, 95%CI 46%-65%), followed by asymptomatic, visual field defect, and floaters. CMVR was first diagnosed and regarded as the clue to AIDS diagnosis in 9% (95%CI 6%-13%) of CMVR patients. Approximately 85% (95%CI 76%-93%) of the CMVR patients have received cART. CMVR remission was observed in 72%-92% of patients depending on the specific category of anti-CMV therapy. The general incidence of CMVR-related RD in the entire course was 24% (95%CI 18%-29%), of which most patients received PPV with SO or gas tamponade and the rate of anatomic success was 89% (95%CI 85%-93%).ConclusionCMVR is a common opportunistic infection with diverse clinical features in AIDS patients, preponderant in those who are male, homosexual, or with CD4+ T-cells <50 cells/μL. Current therapies for CMVR and CMVR-related RD were shown to be effective. Early detection and routine ophthalmic screening should be promoted in AIDS patients.Systematic review registrationPROSPERO, identifier CRD42022363105.

Project description:PurposeTo describe the outcomes of different treatment approaches for cytomegalovirus (CMV) retinitis in the era of highly active antiretroviral therapy (HAART).DesignProspective cohort study, the Longitudinal Study of the Ocular Complications of AIDS.ParticipantsA total of 250 patients with CMV retinitis and a CD4+ T-cell count <100 cells/μl (n = 221) at enrollment or incident retinitis (n = 29) during cohort follow-up.MethodsThe effects of systemic therapy (vs. intraocular therapy only) on systemic outcomes and the effect of intraocular therapies (ganciclovir implants, intravitreal injections) on ocular outcomes were evaluated.Main outcome measuresMortality, CMV dissemination, retinitis progression, and treatment side effects.ResultsRegimens containing systemic anti-CMV therapy were associated with a 50% reduction in mortality (adjusted hazard ratio [HR], 0.5; 95% confidence interval [CI], 0.3-0.7; P = 0.006), a 90% reduction in new visceral CMV disease (adjusted HR, 0.1; 95% CI, 0.04-0.4; P = 0.004), and among those with unilateral CMV retinitis at presentation, an 80% reduction in second eye disease (adjusted HR, 0.2; 95% CI, 0.1-0.5; P = 0.0005) when compared with those using only intraocular therapy (implants or injections). Compared with systemic treatment only, regimens containing intravitreal injections had greater rates of retinitis progression (adjusted HR, 3.4; P = 0.004) and greater visual field loss (for loss of one half of the normal field, adjusted HR, 5.5; P < 0.01). Intravitreal implants were not significantly better than systemic therapy (adjusted HR for progression, 0.5; P = 0.26; adjusted HR for loss of one half of the visual field, 0.5; P = 0.45), but the sample size was small. Hematologic and renal side effect rates were similar between those groups with and without systemic anti-CMV therapy. The rate of endophthalmitis was 0.017 per eye-year (EY) (95% CI, 0.006-0.05) among those treated with intravitreal injections and 0.01 per EY (95% CI, 0.002-0.04) among those treated with an implant.ConclusionsIn the HAART era, systemic anti-CMV therapy, while there is immune compromise, seems to provide benefits in terms of longer survival and decreased CMV dissemination.Financial disclosure(s)Proprietary or commercial disclosure may be found after the references.

Project description:Human cytomegalovirus (HCMV) is an opportunistic human herpesvirus that causes a sight-threatening retinitis in immunosuppressed patients, especially those with AIDS. Using an established model of experimental murine cytomegalovirus (MCMV) retinitis in mice with retrovirus-induced immunodeficiency (MAIDS), we have been attempting to define with greater clarity the immunologic mechanisms that contribute to the progression of AIDS-related HCMV retinitis in the unique immunosuppressive setting of HIV infection. Toward this end, we provide herein a comprehensive assessment of immune response gene expression during the onset and development of MAIDS-related MCMV retinitis employing NanoString nCounter. In so doing, we analyzed and compared the intraocular expressions of 561 immune response genes within MCMV-infected eyes of groups of healthy mice, MCMV-infected mice with MAIDS of 4 weeks' (MAIDS-4) duration, and MCMV-infected eyes of mice with MAIDS of 10 weeks' (MAIDS-10) duration. These animal groups show a progression of retinal disease from absolute resistance to retinitis development in healthy mice to the development of classic full-thickness retinal necrosis in MAIDS-10 mice but through an intermediate stage of retinal disease development in MAIDS-4 mice. Our findings showed that increased susceptibility to MCMV retinitis during the progression of MAIDS is associated with robust upregulation or downregulation of a surprisingly large number of immune response genes that operate within several immune response pathways often unique to each animal group. Analysis of 14 additional immune response genes associated with programmed cell death pathways suggested involvement of necroptosis and pyroptosis during MAIDS-related MCMV retinitis pathogenesis. Use of the NanoString nCounter technology provided new and unexpected information on the immunopathogenesis of retinitis within MCMV-infected eyes of mice with retrovirus-induced immunosuppression. Our findings may provide new insights into the immunologic events that operate during the pathogenesis of AIDS-related HCMV retinitis.

Dataset Information

Relationship Between Opacity of Cytomegalovirus Retinitis Lesion Borders and Severity of Immunodeficiency Among People With AIDS.

Publications

Relationship Between Opacity of Cytomegalovirus Retinitis Lesion Borders and Severity of Immunodeficiency Among People With AIDS.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets