The PI (Dr. Yanovitch) is currently funded by a K12 mechanism. This proposal outlines a 3 year, 3 month continuation of research, for a total of 6 years of career development funding, in order to continue mentored clinical research aims. Duke Eye Center and Duke University (sites of training) are outstanding training environments with numerous resources, interactions, facilities, and unique learning opportunities. Duke has made a strong commitment to training and supporting the next generation of clinician scientists. This research proposal involves the development of methods, such as statistical modeling, ocular imaging and genotyping, designed to predict refractory primary congenital glaucoma (PCG). The main project will be to test the hypothesis that phenotypes defined by baseline clinical characteristics and anatomic findings accurately predict prognosis and that these phenotypes positively correlate with genotypic findings. Over the next 31/4 years, we (the PI and her team) will accomplish the following objectives: 1) continue establishing a PCG cohort database and ascertaining DNA samples from PCG patients from multiple sites throughout the U.S., 2) develop and validate a prognostic model for refractory glaucoma in order to define phenotypes, 3) conduct a case-control trial comparing angle structures in normal, mild glaucoma, and refractory PCG subjects, and 4) perform genotype-phenotype correlations based upon previously defined phenotypes. We expect that these studies will confirm our proposed clinical classification system and imaging findings, as well as provide evidence to support genotype-phenotype correlations. The goal for this preliminary data is to justify a formal, prospective, multi-center study to validate our findings funded through an R01. The PI's long- term career goal is to apply the same analytic approach to other complex, pediatric eye diseases with a genetic component like retinopathy of prematurity and strabismus. The PI has committed her career to the treatment of genetic pediatric eye diseases and to the advancement of knowledge. As part of the K12 program, the PI has completed the course requirements for a Master's of Health Sciences in Clinical Research. In the short term, the PI hopes to continue to grow her basic sciences fund of knowledge, develop protocols for imaging and analyzing the anterior segment, and continue mentored research involving clinical genetics in order to obtain a solid foundation for independent research. PUBLIC HEALTH RELEVANCE: This study focuses on primary congenital glaucoma (PCG), a sight-threatening condition affecting infants and children from birth to 3 years of age. The specific structural and molecular mechanism behind PCG remains poorly understood. By combining precise clinical research methodology with cutting-edge diagnostic and genotyping techniques, this study will develop tools to help diagnose and treat PCG earlier with better targeted interventions.