The African Descent and Glaucoma Evaluation Study (ADAGES) III: Contribution of Genotype to Glaucoma Phenotype in African Americans: Study Design and Baseline Data.

PURPOSE: To describe the study protocol and baseline characteristics of the African Descent and Glaucoma Evaluation Study (ADAGES) III. DESIGN: Cross-sectional, case-control study. PARTICIPANTS: Three 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. METHODS: Individuals 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 MEASURES: Participant 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. RESULTS: The 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. CONCLUSIONS: With 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.

Genetic Architecture of Primary Open-Angle Glaucoma in Individuals of African Descent: The African Descent and Glaucoma Evaluation Study III.

PURPOSE: To find genetic contributions to glaucoma in African Americans. DESIGN: Cross-sectional, case-control study. PARTICIPANTS: One 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. METHODS: MegaChip 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 MEASURES: Primary 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). RESULTS: Eighteen 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 ß, 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. CONCLUSIONS: A 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.

Clinical outcomes of Ahmed Glaucoma valve in posterior segment versus anterior chamber.

PURPOSE: To compare the intermediate-term intraocular pressure (IOP) control and complication profile of the Ahmed Glaucoma Valve (AGV) implanted posteriorly through the pars plana in eyes undergoing concurrent pars plana vitrectomy (PPV) with device implantation in the anterior chamber (AC) in nonvitrectomized eyes. METHODS: : We retrospectively reviewed the medical records of 31 case eyes (30 patients) with refractory glaucoma that underwent posterior implantation of AGV after complete PPV and compared them to 31 control eyes (31 patients) with refractory glaucoma that underwent implantation of AGV in the AC. Case-control patients were matched one-to-one on the basis of principal glaucoma diagnosis. All surgeries were performed at 1 institution using a silicone-plate device. Success was defined as intraocular pressure (IOP)≥ 5 mm Hg and ≤ 21 mm Hg with or without glaucoma medications at final follow-up, no additional glaucoma surgery, no removal of the implant, and no loss of light perception. RESULTS: The average follow-up was 20.9 months (range, 6 to 54 mo) for the posterior group and 20.5 months (range, 4 to 48 mo) for the anterior group. The reduction in IOP was similar in both groups at all postoperative time points. The number of postoperative glaucoma medications in both groups was not statistically different at final follow-up. Success rates at final follow-up were identical, 83.9% in both groups, and Kaplan-Meier survival curve analysis showed no significant difference between the 2 groups (P=0.96). Postoperative complications were similar between the 2 groups, except there were more instances of early postoperative flat AC in the anterior group than the posterior group (P=0.01). CONCLUSIONS: The AGV can similarly control IOP in the majority of cases, whether the tube is placed in the posterior segment after PPV or in the AC of nonvitrectomized eyes.

Corneal graft survival and intraocular pressure control in coexisting penetrating keratoplasty and pars plana Ahmed Glaucoma Valves.

PURPOSE: To evaluate corneal graft survival and intraocular pressure (IOP) control after penetrating keratoplasty (PK) and pars plana Ahmed Glaucoma Valve (AGV) implantation among patients with coexisting glaucoma and corneal disease. METHODS: Retrospective chart review at an institution of 25 eyes (24 patients) that received PK and pars plana AGV. RESULTS: The mean postoperative follow-up was 23 months (range, 2-106 months). Survival of the grafts was 89% (16 of 18 eyes) at 1 year and 63% (5 of 8) at 2 years. IOP control was 78% (15 of 19) at 1 year and 44% (4 of 9) at 2 years. By Kaplan-Meier analysis, the 50% probability of sustained graft clarity occurred at 28 months and that of sustained IOP control at 24 months. By last follow-up, best-corrected visual acuity had improved by at least 1 line in 52% (13 of 25) of eyes compared with preoperative values. Preoperative factors, including peripheral anterior synechiae, were not found to be associated with graft survival, IOP control, or visual acuity at 1 year. CONCLUSION: Pars plana AGV can successfully control IOP in PK patients in the short and intermediate terms, but graft clarity and IOP control diminish over time. Graft decompensation, when it did occur, likely reflects the associated ocular morbidity and clinical complexity of this circumscribed cohort of eyes.