The Orinda Longitudinal Study of Myopia (OLSM) was started in 1989 and has investigated normal eye growth and the development =of myopia in over 1,200 school-aged children to date. In the next five years of this project, we propose to conduct three parallel study phases. Phase I will investigate additional factors that may predict the onset of juvenile myopia (accommodative function, peripheral refractive error, intraocular pressure, and school achievement). Phase 2 will compare and contrast the optical ocular components and refractive error profiles of other ethnic groups with the predominantly Caucasian Orinda database. Phase 3 will initiate DNA- based studies on the prevalent OLSM myopes and their families to use these phenotypically well-characterized children and a panel of candidate genes to look for evidence of genetic factors. In parallel with the candidate gene association, family material will be used in an allele sharing approach to identify loci using highly variable, PCR-based markers. In Phase 1 we will continue to examine Orinda Union School District children in grades 1 through 8 (ages 6 through 14 years) annually. The measurement of accommodative response, accommodative lag, phoria, response AC/A ratio, peripheral refractive error, pushup accommodative amplitude, and intraocular pressure will be added to the existing protocol. Parents of children in the study will be contacted for their permission to release school achievement data (Iowa Test of Basic Skills). Phase 2 will add a major component to assess the influence of ethnicity on normal ocular and refractive error development. We propose to identify three participating sites with access to their local school districts that are predominantly African-American, Hispanic, and Asian, Children in the school districts associated with these sites will be examined annually with initial enrollment in all grades from 1 through 8 using the revised OLSM protocol as described above. Increased prevalence of myopia among children of myopic parents, twin studies, segregation analysis, and our own preliminary analyses from OLSM support a genetic etiologic component for myopia. In phase 3, we will use the phenotypic characterization of children in the Orinda Longitudinal Study of Myopia to identify prevalent cases of myopia and their families. These well-defined phenotypic myopes and non-myopic siblings and their parents will be explored, seeking to develop a panel of candidate genes for myopia and to conduct an allele sharing analysis in these families.
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