PROJECT SUMMARY/ABSTRACT Among working-age U.S. adults, diabetic retinopathy remains the leading cause of blindness despite landmark National Eye Institute (NEI) clinical trials showing that early detection and treatment reduce the risk of severe vision loss by over 90%. Yet adherence with yearly diabetic retinopathy screening in the U.S remains below half of patients in rural communities. Ocular telemedicine (i.e. teleophthalmology) can substantially increase diabetic retinopathy screening rates and prevent blindness. However, there is often very limited use of this technology even after a teleophthalmology program is established in multi-payer health systems, where the majority of Americans receive their care. To overcome major barriers identified for teleophthalmology use in rural multi-payer primary care clinics, the PI developed and piloted Implementation to Sustain Impact in Teleophthalmology (I-SITE) in a NEI K23 Career Development Award. I-SITE is the first implementation program specifically designed to overcome barriers to teleophthalmology use by tailoring its integration into rural primary care clinic workflows. The proposed study is a multi-center randomized controlled trial aiming to: (1) test the effectiveness of I-SITE, (2) identify explanatory factors and implementation components that distinguish high and low teleophthalmology use in rural health systems following I-SITE implementation, and (3) evaluate implementation costs. We hypothesize that I-SITE will sustain significant diabetic eye screening rate increases at 18 months compared to usual care teleophthalmology. This UG1 proposal directly responds to multiple elements of the NEI Strategic Plan, including areas of emphasis in telemedicine, diabetic retinopathy, and expanding access to eye care in rural populations. This research will facilitate the effective translation of telemedicine technology in rural multi-payer primary care clinics to improve diabetic retinopathy screening rates. The effective integration and scale-up of ocular telemedicine would greatly expand eye care access for millions of rural Americans. This will be critical for preventing avoidable blindness by overcoming the shortage of eye care providers and meeting the increased demand for eye screening resulting from major projected increases in diabetes prevalence. As we face unprecedented challenges to our nation's health systems, never before in our history has the need for a rapid transition to telehealth been more acute. Our study will provide vital knowledge regarding the methods and factors needed to successfully translate telehealth technology into widespread clinical practice for improving public health nationwide.