Development, Refinement, and Validation of Sensitive and Robust AO-OCT Glaucoma Biomarkers

About This Grant

PROJECT SUMMARY/ABSTRACT Glaucoma is a leading cause of irreversible blindness worldwide, resulting from progressive damage to retinal ganglion cells (RGCs). Current diagnostic methods detect disease only after significant structural and functional loss, and existing metrics for disease progression require extended monitoring periods, limiting the feasibility of clinical trials for neuroprotective therapies. There is an urgent need for robust, mechanistically relevant biomarkers to enable earlier detection of glaucoma progression and facilitate the development of novel therapeutics. This project aims to refine and validate advanced imaging biomarkers using Adaptive Optics-Optical Coherence Tomography (AO-OCT), a high-resolution imaging modality that permits direct visualization of RGC soma and vascular mural cells, including pericytes, in both animal models and human subjects. Preliminary data indicate that AO-OCT can detect early morphological changes in RGC soma and pericytes associated with glaucoma progression. However, further validation and improvement of these biomarkers are necessary before larger-scale clinical trials can be conducted. The proposed study consists of two specific aims. In Aim 1, we will utilize transgenic mouse models to confirm the specificity of AO-OCT biomarkers for RGCs and pericytes and to longitudinally assess cellular changes in two established glaucoma models. This work will provide critical validation of AO-OCT imaging against gold- standard histological techniques. In Aim 2, we will conduct a two-year longitudinal study of 50 human subjects with mild glaucoma to assess the relationship between AO-OCT biomarkers and conventional clinical measures of disease progression. Additionally, we will develop AI-based vessel segmentation techniques to enhance the precision of pericyte identification and characterization. This research will yield highly sensitive and specific biomarkers for glaucoma progression, enabling more efficient and cost-effective clinical trials for neuroprotective therapies. Ultimately, these advancements will improve early diagnosis, facilitate the development of novel treatments, and reduce the global burden of blindness due to glaucoma.