The focus of this grant is to develop reliable quantitative and qualitative topographic criteria for detecting subclinical forms of keratoconus in order to conduct critical pedigree analyses of families with isolated keratoconus to delineate the modes of inheritance for future gene linkage analysis. The study will recruit 200 normal subjects, 300 subjects with keratoconus, and 500 family members of keratoconus patients and follow them annually for 3 years with a keratometer, CorneoscopeTM and computer- assisted videophotokeratoscope. Its aims are to identify the relationship of the videokeratography variables to biomicroscopic indicators of disease status, develop criteria for "mildly affected" or subclinically affected individuals, construct accurate keratoconus pedigrees, and identify predictors of progression to keratoconus in family members. The family data will be analyzed by qualitative and quantitative segregation analysis techniques to determine the mode(s) of inheritance of the various definitions of the keratoconus phenotype, as well as any subgroups. Identification of mildly affected and/or subclinical keratoconus patients is crucial to constructing accurate pedigrees. With the accurately constructed pedigrees and the understanding of the mode of inheritance of keratoconus, we will be able to subsequently design genetic linkage studies to identify the genes contributing to the disease process. Identification of such genes may provide insights into devising medical therapy to arrest the progression of keratoconus and prevent the need for multiple contact lens changes and/or cornea transplantation in affected individuals.