Development, refinement, and validation of sensitive and robust AO-OCT glaucoma biomarkers

The National Eye Institute of the Department of Health and Human Services awarded $571,206 to the University of Maryland, Baltimore on May 1, 2026, under the Vision Research program (CFDA 93.867) to develop, refine, and validate sensitive and robust adaptive optics-optical coherence tomography (AO-OCT) biomarkers for glaucoma detection and progression monitoring.

The project addresses the need for earlier detection of glaucoma progression and mechanistically relevant biomarkers to support neuroprotective therapeutic development. Glaucoma causes irreversible blindness through progressive retinal ganglion cell damage, but current diagnostic methods detect disease only after significant structural and functional loss. The research uses AO-OCT imaging to visualize retinal ganglion cell soma and vascular pericytes in animal models and human subjects, with preliminary evidence that the technology can detect early morphological changes associated with glaucoma progression.

The award funds two specific aims. Aim 1 uses transgenic mouse glaucoma models to confirm the specificity of AO-OCT biomarkers for retinal ganglion cells and pericytes through longitudinal assessment validated against histological techniques. Aim 2 conducts a two-year longitudinal study of 50 human subjects with mild glaucoma to assess the relationship between AO-OCT biomarkers and conventional clinical disease progression measures, including development of artificial intelligence-based vessel segmentation techniques to enhance pericyte identification precision.

Work is performed in Baltimore, Maryland with a period of performance from May 1, 2026, through March 31, 2030.

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.