Project Summary This application is for a five-year extension of funding for the Pediatric Eye Disease Investigator Group (PEDIG) – an open collaborative network of over 100 sites and over 300 pediatric ophthalmologists and pediatric optometrists dedicated to conducting investigator-initiated clinical research in strabismus, amblyopia, and other childhood eye conditions. The organization of the PEDIG network enhances efficiency and quality while reducing costs by having a single infrastructure with the ability to conduct multiple concurrent and consecutive studies. Since its inception in 1997, PEDIG has published 130 manuscripts and conducted 46 randomized clinical trials or prospective observational studies on childhood eye conditions such as amblyopia, strabismus, nasolacrimal duct obstruction, refractive error, ROP, pediatric optic neuritis, and pediatric cataract. In the current grant cycle (2019-2023), the 8 protocols that were active at the beginning of the grant cycle will have been completed and 12 new protocols will have been initiated (3 will be completed during the current grant cycle and 9 will remain active). PEDIG studies have changed the practice standard of pediatric eye care and have become the foundation for the American Academy of Ophthalmology’s evidence-based Preferred Practice Pattern for amblyopia. The proposed studies in the current application would continue to advance the field in an evidence- based direction, improving care and quality of life for children. Despite these contributions, there remain important knowledge gaps. To address these gaps, PEDIG will continue to expand the evidence base for treating several pediatric eye conditions, including: (1) amblyopia, (2) strabismus, (3) myopia, (4) chalazia, (5) ROP, and (6) cerebral visual impairment (CVI). PEDIG will create an additional layer to its organizational structure to form 6 Disease-Area Working Groups that will provide support for development of investigator-initiated study ideas. PEDIG will also explore new methodologies to increase access to pediatric eye care by developing and implementing a novel, home-based visual acuity testing application, studying the use of ocular imaging in telehealth, and creating a comprehensive web- or phone application-based amblyopia treatment guide for general eye care providers that assimilates results from PEDIG and other amblyopia research, allowing for real-time decision making. PEDIG will continue to perform high-impact clinical studies to provide rigorous evidence for the optimal treatment of pediatric eye conditions. The network’s reach will also extend into new areas, in alignment with the NEI strategic plan, where the full breadth of the network’s size and expertise can be leveraged to create robust evidence as the basis for treatment of pediatric eye disease.