This proposed project is motivated by the fact that comprehensive, broad-scale screening for eye diseases such as age-related macular degeneration (AMD) and diabetic retinopathy (DR) is economically prohibitive without the introduction of computer-assisted diagnosis of retinal images. According to the CDC approximately 80 million people in the U.S. have some form of eye disease, including 20 million diabetics at risk for retinopathy, 60 million at risk for glaucoma, and 13 million diagnosed with AMD. It is estimated that less than half of those individuals with diabetes are screened periodically for DR. Lack of medical coverage and access to healthcare providers imposes major obstacles for nearly 10 million diabetics. Creating an affordable and accessible solution to providing screening services to these diabetics presents a significant challenge to the healthcare community. A comprehensive screening program for U.S. citizens utilizing ophthalmologists, optometrists, or other trained specialists, "readers", to grade each case would be prohibitively expensive. The solution is to implement a computer-assisted technology similar to other medical applications, such as mammograms and Pap smears;that would provide comprehensive, periodic screening of our at-risk population. This grant will implement an automatic eye disease screening system (AEDSS) which will enable highly efficient screening at centers across the US and globally. This grant will conduct a comprehensive multi-site clinical study to implement a inter-connected regional system to evaluate the efficiency of computer-based algorithms. The study will be made possible through the implementation of the infrastructure for a reading center in South Texas where it is estimated that nearly 200,000 diabetics reside and over 50% do not receive annual examinations. The center will be a demonstration site where the efficacy of the software can be documented for submission to the FDA for pre-market approval (PMA). The goal is to show that a center's throughput, i.e. number of cases screened per time period, will increase five fold through the use of a hybrid (automation-human graders) approach with sensitivity that is comparable or better than solely human-based screening. The significance of this proposed research is two-fold. First, by increasing the productivity of reading centers through automation, a much larger population of at-risk diabetics will have access to this service, leading to improved productivity and quality of life through early detection and treatment. Second, by providing a FDA approved system for highly effective DR screening, the US healthcare system would benefit economically through the added efficiency of our system. Our system does not replace current human readers;it simply allows an increase of throughput of cases by factors of five or more without sacrificing sensitivity and specificity. The reduced cost of screening would lead to more reading centers and increased high-paying technical/medical jobs.