Studying models and mechanisms of optic nerve diseases

? DESCRIPTION (provided by applicant): Glaucoma is the second leading cause of blindness in the world, but, with proper treatment, blindness can be avoided in the overwhelming majority of individuals. Our long-term goal is to improve the detection of early glaucomatous damage, as well as the detection of progression of such damage. We focus in large part on damage to the macula, the most important retinal region for everyday visual activities. The lack of knowledge about the nature and prevalence of glaucomatous damage of the macula is a major barrier to progress in this field. In Aim 1a,c, we test hypotheses about the nature of macular damage using a combination of visual field perimetry, optical coherence tomography (OCT), and a cutting-edge imaging technique, adaptive optics scanning laser ophthalmoscopy (AO-SLO). In both Aims 1b and 2a, we use AO-SLO to directly view the retinal nerve fiber (RNF) bundles so as to better understand glaucomatous damage and its progression at the level of individual RNF bundles. A second barrier to progress in the field is the sub-optimal clinical use of OCT. We attack this barrier in 4 ways. First, as part of Aim 1b, we compare AO-SLO images to OCT scans so as to improve the clinical utility of both spectral-domain (sd) and swept-source (ss) OCT, the widely available noninvasive, clinical techniques for assessing the integrity of the RNF layer. Our working hypothesis is that OCT scans contain information about local RNF bundle damage and that this information is currently going undetected. Second, in Aim 3c, we test the hypothesis that this damage can be better visualized with an en-face analysis of OCT scans than with the commonly used RNF layer thickness analyses. Third, in Aim 2b, we test the hypothesis that we can improve the detection of glaucomatous progression by focusing on local regions of damage, as seen on OCT scans of the optic disc. Finally, in Aim 3a, we test the hypothesis that the detection of glaucomatous damage can be improved if: 1. the OCT scans are carefully examined for local defects and algorithm failures; and 2. local thinning of both RNF and retinal ganglion cell layers, as seen with OCT cube scans, are topographically compared to local loss of visual field sensitivity, as seen with standard automated perimetry. In aim 3b, we compare this approach, which can be summarized in a single page, to other methods, including current clinical methods that use commercial reports and summary statistics.