Accurate assessment of optic nerve and nerve fiber layer (NFL) structure is important to the early detection and timely treatment of glaucoma. The specific aims of this revised application are to: 1) develop novel structural measures of the optic nerve and NFL which are sensitive and specific for early and progressive glaucomatous optic nerve damage; 2) determine the diagnostic precision of existing and novel measures to detect the presence of early structural damage; 3) determine the diagnostic precision of existing and novel measures to detect the progression of structural damage; and 4) identify and validate methods that provide the most sensitive and specific measures of early glaucomatous structural damage. The techniques to be tested include but are not limited to: qualitative and quantitative assessment of color optic disc stereophotographs, qualitative and quantitative assessment of monochromatic NFL photographs, and scanning confocal laser image analysis of the optic nerve head and NFL. Cross-sectional analysis in age-matched normal and glaucomatous eyes will determine which techniques best detect the presence of glaucoma defined by early, reproducible visual field loss. A longitudinal study in progress will continue to follow normal subjects, ocular hypertensives and glaucoma patients to determine the sensitivity and specificity of various measures to identify change. Sensitivity and specificity will be determined for each measure and comparisons facilitated with receiver operating characteristic curves. Discriminant analysis and neural networks will be used to test the effectiveness of combined measures, and to estimate the probability that damage is present in individual eyes. Long-term follow-up of a well established cohort of subjects will enable early changes in structure to be validated by the subsequent development or worsening of visual field loss. This study will provide appropriately controlled, quantitative information to identify the most sensitive and specific methods to detect and monitor glaucoma damage in practice, and to define the most appropriate outcome measures for clinical trials and studies of glaucoma care.