PROJECT SUMMARY: Glaucoma is the leading cause of irreversible blindness worldwide. There are significant disparities in glaucoma prevalence, presentation, and treatment in the United States (US) by race and ethnicity, English proficiency, and health insurance status. However, many published glaucoma clinical trials have not reflected the level of diversity in the US population by race/ethnicity or socioeconomic disadvantage. Broad patient representation in clinical trials is necessary to ensure that research conclusions are more generalizable to actual patient populations in the US. Pragmatic registry-based randomized controlled trials (RRCT) are a low- cost strategy to evaluate glaucoma intervention efficacy in routine settings and to more efficiently recruit diverse patient populations that have not been well-represented in prior traditional randomized controlled trials (RCTs). This study proposes a future pragmatic RRCT to obtain high-quality evidence comparing selective laser trabeculoplasty (SLT) and medications in heterogenous, real-world populations, and with less cost and complexity than conducting a traditional RCT. More evidence is needed to determine how first-line SLT compares to medications in US patients with more advanced open-angle glaucoma, and in a more diverse patient population with respect to race/ethnicity, English proficiency, and ocular comorbidities. The proposed RRCT will include patients with newly diagnosed open-angle glaucoma, who are treatment-naïve, with any level of English proficiency, and with active ocular comorbidities. This future trial will leverage the Intelligent Research in Sight (IRIS) Registry® to identify patients for enrollment. Using a pragmatic approach, follow-up care will closely mirror usual care. This R34 planning grant will lay the necessary foundation for this future RRCT and determine its acceptability, methodology, and feasibility. The specific aims are: (1) to determine the beliefs and attitudes of US glaucoma specialists and patients toward SLT versus medications using a mixed- methods approach; (2) to refine the enrollment criteria, sample size and trial endpoint for the future RRCT using retrospective data from the IRIS Registry; and (3) to develop and refine the study protocol, and to evaluate the operational feasibility of the future RRCT by conducting a non-randomized feasibility study. This planning grant will help prepare for a future pragmatic RRCT through the IRIS Registry and a UG1 submission. In addition to answering questions crucial to the care of diverse patient populations, this future trial will establish infrastructure vital to support additional pragmatic RRCTs in ophthalmology.