The long-term objective of the proposed research is to advance the diagnosis, treatment planning, and treatment monitoring of ocular diseases that threaten life and sight. To achieve these goals, interwoven engineering efforts (at RRI) and clinical studies (at CUMC) will build upon previous methods that have successfully diagnosed and subclassified ocular tumors. The research will shift its focus to improve the management of glaucoma, a major cause of blindness, and corneal disorders and diseases where laser treatments may become the most common ocular surgery. New methods will use very-high frequency ultrasound to improve B-mode and spectral resolution by more than an order of magnitude. Well defined tissues will be studied with three dimensional biometry. Complex stochastic tissues will be studied with spectrum analysis and characterized in terms of the effective sizes, concentrations, and mechanical properties of their sub-resolution constituents. A theoretical model will address different classes of stochastic tissues, and 3-D evaluations will delineate the microstructural perturbations induced by diseases. Special 2-D spectral methods will assess additional features and enhance the detection of particular tissue types. The methods and models will be validated with test targets and correlations with light and electron microscopy. Clinical studies will use data-base techniques to address specific diseases. Glaucoma studies will assay ciliary body morphology and response to drugs. Corneal diseases and disorders will be evaluated by 3-D biometry and delineation of scars for planning procedures including excimer laser photorefractive surgery. Traumatic injuries will be evaluated in terms of induced injury and status of anterior chamber blood. Tumor lethality studies, examining sub-resolution vascular loops, will be completed. Ancillary studies will employ light and acoustic microscopy to relate measured tissue features to actual tissue microstructure.