Saturday, November 23, 2024
11/23/2024
DESCRIPTION Glaucoma is a group of diseases that results in a pathological loss of retinal ganglion cells (RGC) and irreversible vision loss. Increased intraocular pressure (IOP) is a major risk factor for glaucoma, but some individuals with elevated pressures never develop disease, and others with low pressures progress to blindness. Similarly, in the non-human primate experimental glaucoma model, animals with similar IOP profiles are shown to have significant differences in the extent and rate of retinal nerve fiber layer (RNFL) thickness loss. Both clinical and experimental models suggest that in addition to IOP, other factors need to be considered for glaucoma progression. We hypothesize the variability in disease progression can be explained by vascular factors. The retina is one of the most metabolic tissues in the body, and it is unknown if eyes with relatively lower vascular volume, or eyes that show greater change in perfusion with changes in IOP are at greater risk of pathology. Furthermore, although eyes with optic neuropathy have reduced vascular density, it remains unknown if there are changes in retinal vasculature that precede RGC loss. Optical coherence tomography angiography (OCTA) is a non-invasive method for three-dimensional vascular perfusion imaging. However, analysis of OCTA imaged vasculature is based on slab projections, where the three-dimensional nature of tissue is lost. In addition, OCTA vascular perfusion is often considered a static measure, but vascular flow velocity has temporal properties. For this project, we have optimized OCTA scans to quantify vascular volume and vascular volume density, and using sequential and registered scans, OCTA temporal variability. In the non-human primate experimental glaucoma model, we will determine; 1. if the rate of disease progression is related to baseline global and regional measures of vascular volume / volume density and regional OCTA temporal variability, 2. if there is loss of vascular volume prior to inner retinal thickness, 3. if the rate of structural and functional changes are is related to the extent to which vascular perfusion changes with IOP challenge, and 4. using post-mortem tissue, define vascular anatomy (pericyte coverage, endothelial cell density, capillary basement membrane thickness/integrity) in healthy and disease eyes and association with in vivo OCTA measures. Successful completion of these aims will establish if vascular measures as quantified using OCTA can be used to determine risk of pathology, and rate of glaucoma progression.
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