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.

Estimated Utility of the Short-term Assessment of Glaucoma Progression Model in Clinical Practice.

IMPORTANCE: Clinical trials of glaucoma therapies focused on protecting the optic nerve have required large sample sizes and lengthy follow-up to detect clinically relevant change due to its slow rate of progression. Whether shorter trials may be possible with more frequent testing and use of rate of change as the end point warrants further investigation. OBJECTIVE: To describe the design for the Short-term Assessment of Glaucoma Progression (STAGE) model and provide guidance on sample size and power calculations for shorter clinical trials. DESIGN, SETTING, AND PARTICIPANTS: A cohort study of patients with mild, moderate, or advanced open-angle glaucoma recruited from the Diagnostic Innovations in Glaucoma Study at the University of California, San Diego. Enrollment began in May 2012 with follow-up for every 3 months for 2 years after baseline examination. Follow-up was concluded in September 2016. Data were analyzed from July 2019 to January 2021. Visual fields (VF) and optic coherence tomography (OCT) scans were obtained at baseline and for 2 years with visits every 3 months. EXPOSURES: Glaucoma was defined as glaucomatous appearing optic discs classified by disc photographs in at least 1 eye and/or repeatable VF damage at baseline. MAIN OUTCOMES AND MEASURES: Longitudinal rates of change in retinal nerve fiber layer (RNFL) thickness and VF mean deviation (MD) are estimated in study designs of varying length and observation frequency. Power calculations as functions of study length, observation frequency, and sample size were performed. RESULTS: In a total referred sample of 97 patients with mild, moderate, or advanced glaucoma (mean [SD] age, 69 [11.4] years; 50 [51.5%] were female; 19 [19.6%]), over the 2-year follow-up, the mean VF 24-2 MD slope was -0.32 dB/y (95% CI, -0.43 to -0.21 dB/y) and the mean RNFL thickness slope was -0.54 µm/y (95% CI, -0.75 to -0.32 µm/y). Sufficient power (80%) to detect similar group differences in the rate of change in both outcomes was attained with total follow-up between 18 months and 2 years and fewer than 300 total participants. CONCLUSIONS AND RELEVANCE: In this cohort study, results from the STAGE model with reduction of the rate of progression as the end point, frequent testing, and a moderate effect size, suggest that clinical trials to test efficacy of glaucoma therapy can be completed within 18 months of follow-up and with fewer than 300 participants.