Dataset Information

The African Descent and Glaucoma Evaluation Study (ADAGES): predictors of visual field damage in glaucoma suspects.

ABSTRACT: To evaluate racial differences in the development of visual field (VF) damage in glaucoma suspects.Prospective, observational cohort study.Six hundred thirty-six eyes from 357 glaucoma suspects with normal VF at baseline were included from the multicenter African Descent and Glaucoma Evaluation Study (ADAGES). Racial differences in the development of VF damage were examined using multivariable Cox proportional hazard models.Thirty one of 122 African-descent participants (25.4%) and 47 of 235 European-descent participants (20.0%) developed VF damage (P = .078). In multivariable analysis, worse baseline VF mean deviation, higher mean arterial pressure during follow-up, and a race ? mean intraocular pressure (IOP) interaction term were significantly associated with the development of VF damage, suggesting that racial differences in the risk of VF damage varied by IOP. At higher mean IOP levels, race was predictive of the development of VF damage even after adjusting for potentially confounding factors. At mean IOPs during follow-up of 22, 24, and 26 mm Hg, multivariable hazard ratios (95% confidence intervals) for the development of VF damage in African-descent compared to European-descent subjects were 2.03 (1.15-3.57), 2.71 (1.39-5.29), and 3.61 (1.61-8.08), respectively. However, at lower mean IOP levels (below 22 mm Hg) during follow-up, African descent was not predictive of the development of VF damage.In this cohort of glaucoma suspects with similar access to treatment, multivariate analysis revealed that at higher mean IOP during follow-up, individuals of African descent were more likely to develop VF damage than individuals of European descent.

SUBMITTER: Khachatryan N

PROVIDER: S-EPMC4361282 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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The African Descent and Glaucoma Evaluation Study (ADAGES): predictors of visual field damage in glaucoma suspects.

Khachatryan Naira N Medeiros Felipe A FA Sharpsten Lucie L Bowd Christopher C Sample Pamela A PA Liebmann Jeffrey M JM Girkin Christopher A CA Weinreb Robert N RN Miki Atsuya A Hammel Na'ama N Zangwill Linda M LM

American journal of ophthalmology 20150115 4

<h4>Purpose</h4>To evaluate racial differences in the development of visual field (VF) damage in glaucoma suspects.<h4>Design</h4>Prospective, observational cohort study.<h4>Methods</h4>Six hundred thirty-six eyes from 357 glaucoma suspects with normal VF at baseline were included from the multicenter African Descent and Glaucoma Evaluation Study (ADAGES). Racial differences in the development of VF damage were examined using multivariable Cox proportional hazard models.<h4>Results</h4>Thirty on ...[more]

PMID: 25597839

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Project description:PurposeTo describe the study protocol and baseline characteristics of the African Descent and Glaucoma Evaluation Study (ADAGES) III.DesignCross-sectional, case-control study.ParticipantsThree thousand two hundred sixty-six glaucoma patients and control participants without glaucoma of African or European descent were recruited from 5 study centers in different regions of the United States.MethodsIndividuals of African descent (AD) and European descent (ED) with primary open-angle glaucoma (POAG) and control participants completed a detailed demographic and medical history interview. Standardized height, weight, and blood pressure measurements were obtained. Saliva and blood samples to provide serum, plasma, DNA, and RNA were collected for standardized processing. Visual fields, stereoscopic disc photographs, and details of the ophthalmic examination were obtained and transferred to the University of California, San Diego, Data Coordinating Center for standardized processing and quality review.Main outcome measuresParticipant gender, age, race, body mass index, blood pressure, history of smoking and alcohol use in POAG patients and control participants were described. Ophthalmic measures included intraocular pressure, visual field mean deviation, central corneal thickness, glaucoma medication use, or past glaucoma surgery. Ocular conditions, including diabetic retinopathy, age-related macular degeneration, and past cataract surgery, were recorded.ResultsThe 3266 ADAGES III study participants in this report include 2146 AD POAG patients, 695 ED POAG patients, 198 AD control participants, and 227 ED control participants. The AD POAG patients and control participants were significantly younger (both, 67.4 years) than ED POAG patients and control participants (73.4 and 70.2 years, respectively). After adjusting for age, AD POAG patients had different phenotypic characteristics compared with ED POAG patients, including higher intraocular pressure, worse visual acuity and visual field mean deviation, and thinner corneas (all P < 0.001). Family history of glaucoma did not differ between AD and ED POAG patients.ConclusionsWith its large sample size, extensive specimen collection, and deep phenotyping of AD and ED glaucoma patients and control participants from different regions in the United States, the ADAGES III genomics study will address gaps in our knowledge of the genetics of POAG in this high-risk population.

Project description:Importance:?-zone parapapillary atrophy (?PPA) has been reported as a risk factor for glaucoma onset and progression. Previous studies have shown that the prevalence of ?PPA differs between individuals of African descent (AD) and European descent (ED). Objective:To test whether the association between the presence and progression of ?PPA vs visual field progression of glaucoma differs between these 2 ancestry groups. Design, Setting, and Participants:In a prospective, multicenter, longitudinal cohort study, 634 individuals (1090 eyes) enrolled in the African Descent and Evaluation Study (ADAGES) with a diagnosis of glaucomatous optic neuropathy (GON) or ocular hypertension (OHT) and at least 2 disc stereophotographs were included. Two graders masked to clinical and ancestry data reviewed and graded the baseline and last disc stereophotographs for the presence of ?PPA at baseline and ?PPA progression (development or enlargement). Mixed-effects linear models were tested with visual field mean deviation as a dependent variable and time (alone and with interaction terms) as independent variables. ADAGES enrollment began in January 2003 and ended in July 2006; follow-up ended in 2016. Exposures:Disc stereophotographs. Main Outcomes and Measures:Progression of ?PPA in AD and ED individuals. Results:In 634 patients, a total of 814 eyes of AD (395 eyes) and ED (419) patients with GON and 276 eyes of AD (106) and ED (170) patients with OHT who were enrolled in ADAGES were analyzed. There were 336 (53.0%) women in the study; mean (SD) age was 61.9 (12.7) years. In the OHT group, the association between ?PPA at baseline and visual field progression was not significantly different between AD and ED eyes (??=?0.071; 95% CI, -0.016 to 0.158; P?=?.11), nor was the association between ?PPA progression and visual field progression (??=?0.020; 95% CI, -0.465 to 0.506; P?=?.93). In the GON group, ED eyes with baseline ?PPA progressed faster than did AD eyes with baseline ?PPA (??=?-0.124; 95% CI, -0.241 to -0.007; P?=?.04), although the association between ?PPA progression and visual field progression did not differ significantly between race groups (??=?-0.101; 95% CI, -0.323 to 0.119; P?=?.37). Conclusions and Relevance:Race had a significant effect on the association between baseline ?PPA and rates of visual field progression in eyes with GON. Progression of ?PPA was not associated with faster visual field progression in either racial group.

Project description:PurposeTo investigate the differences in the frequency of optic disc hemorrhage (DH) and prevalence of beta-zone parapapillary atrophy (βPPA) between individuals of African descent (AD) and European descent (ED).DesignProspective, multicenter, observational cohort.ParticipantsA total of 1950 eyes of 1172 participants of the African Descent and Glaucoma Evaluation Study (ADAGES).MethodsStereoscopic disc photographs of subjects with and without glaucomatous optic neuropathy (GON) followed during the first 13 years of the ADAGES underwent masked review searching for DH and βPPA. A total of 928 eyes (non-GON, 581; GON, 347) of 551 AD patients (non-GON, 334; GON, 217) and 1022 eyes (non-GON, 568; GON, 454) of 611 ED patients (non-GON, 334; GON, 277) were included. We compared the number of eyes with detected DH at any time during follow-up and eyes with βPPA between the AD and ED groups. The analyses were then adjusted for clinical parameters using multivariable logistic regression.Main outcome measuresDifferences in frequency of DH and prevalence of βPPA.ResultsA total of 9395 stereoscopic disc photographs were reviewed. More ED eyes experience DH than AD eyes (49/1022 [4.8%] vs. 10/928 eyes [1.1%], respectively; P < 0.001), whereas βPPA had higher prevalence in AD eyes (675 eyes [72%] vs. 659 eyes [64%]; P < 0.001). In the final multivariable model, after controlling for confounders, AD eyes were less likely to have at least 1 detected DH than ED eyes (odds ratio [OR], 0.21; 95% CI, 0.10-0.45; P < 0.001) but were more likely to have βPPA than ED eyes (OR, 1.55; 95% CI, 1.12-2.14; P = 0.008).ConclusionsSubjects of ED are at higher risk for developing DH compared with AD subjects, whereas AD subjects have greater prevalence of βPPA. These findings suggest that there are structural differences within the optic nerve complex between these groups. Further research is needed to determine whether racial differences in the frequency of DH and prevalence of βPPA affect the likelihood of glaucomatous progression.

Project description:PurposeTo find genetic contributions to glaucoma in African Americans.DesignCross-sectional, case-control study.ParticipantsOne thousand eight hundred seventy-five primary open-angle glaucoma (POAG) patients and 1709 controls, self-identified as being of African descent (AD), from the African Descent and Glaucoma Evaluation Study (ADAGES) III and Wake Forest School of Medicine.MethodsMegaChip genotypes were imputed to Thousand Genomes data. Association of single nucleotide polymorphisms (SNPs) with POAG and advanced POAG was tested by linear mixed model correcting for relatedness and population stratification. Genetic risk scores were tested by receiver operator characteristic curves (ROC-AUCs).Main outcome measuresPrimary open-angle glaucoma defined by visual field loss without other nonocular conditions (n = 1875). Advanced POAG was defined by age-based mean deviation of visual field (n = 946).ResultsEighteen million two hundred eighty-one thousand nine hundred twenty SNPs met imputation quality of r2 > 0.7 and minor allele frequency > 0.005. Association of a novel locus, EN04, was observed for advanced POAG (rs185815146 β, 0.36; standard error, 0.065; P < 3×10-8). For POAG, an AD signal was observed at the 9p21 European descent (ED) POAG signal (rs79721419; P < 6.5×10-5) independent of the previously observed 9p21 ED signal (rs2383204; P < 2.3×10-5) by conditional analyses. An association with POAG in FNDC3B (rs111698934; P < 3.9×10-5) was observed, not in linkage disequilibrium (LD) with the previously reported ED SNP. Additional previously identified loci associated with POAG in persons of AD were: 8q22, AFAP1, and TMC01. An AUC of 0.62 was observed with an unweighted genetic risk score comprising 11 SNPs in candidate genes. Two additional risk scores were studied by using a penalized matrix decomposition with cross-validation; risk scores of 50 and 400 SNPs were identified with ROC of AUC = 0.74 and AUC = 0.94, respectively.ConclusionsA novel association with advanced POAG in the EN04 locus was identified putatively in persons of AD. In addition to this finding, this genome-wide association study in POAG patients of AD contributes to POAG genetics by identification of novel signals in prior loci (9p21), as well as advancing the fine mapping of regions because of shorter average LD (FNDC3B). Although not useful without confirmation and clinical trials, the use of genetic risk scores demonstrated that considerable AD-specific genetic information remains in these data.

Project description:PurposeIdentify factors predicting worse or better than expected visual field (VF) performance.MethodsA total of 10,262 VFs from 1538 eyes of 909 subjects with manifest or suspected glaucoma were analyzed. Linear mixed-effects models predicted mean deviation (MD) at each timepoint. Differences between observed and predicted MD (?MD) were calculated and logistic regression identified factors predicting lower than expected (?MD <-1 dB) or higher than expected (?MD >1 dB) sensitivity.ResultsBoth higher and lower than expected sensitivity were more likely in VFs with severe compared with mild damage (relative risk [RR] >1.3, P < 0.05). Higher than expected sensitivity was more likely in VFs with moderate damage (RR = 2.57, P < 0.001). False-positive (FP) errors increased the likelihood of higher than expected sensitivity at all disease stages (RR >2.1 per 10% increase, P < 0.001), whereas false-negative (FN) errors increased the likelihood of lower than expected sensitivity in mild and moderate disease (RR >1.19 per 10% increase, P < 0.05). Fixation loss errors slightly increased the likelihood of higher than expected VF sensitivity in moderate and severe disease (RR >1.1 per 10% increase, P < 0.01). Longer test duration increased likelihood of lower than expected sensitivity at all disease stages (RR >1.36 per minute increase, P < 0.001). Lower than expected sensitivity was more likely in late afternoon tests (RR = 1.27, P < 0.01). A total of 26.6% of VFs had higher or lower than expected sensitivity in the absence of FPs, FNs, or fixation losses.ConclusionsFPs, test duration, and FNs are the primary measures predicting if a VF is likely to be reliable, although tests with normal reliability measures may still be unreliable. Our results help clinicians judge VF reliability and highlight the need to integrate reliability measures with other clinical data when making treatment decisions.Translational relevanceThis likelihood model derived from a large dataset helps clinicians identify VFs that may either falsely suggest disease progression or mask true worsening, thereby improving the utility of VFs in clinical practice.

Dataset Information

The African Descent and Glaucoma Evaluation Study (ADAGES): predictors of visual field damage in glaucoma suspects.

Publications

The African Descent and Glaucoma Evaluation Study (ADAGES): predictors of visual field damage in glaucoma suspects.

Similar Datasets

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