Validation of New Glaucoma Diagnostic and Progression Prediction Method

This project aims to validate an OCT-based method that utilizes RGCs cellular dynamic scattering as a novel glaucoma biomarker by testing its predictive value in animal models of glaucoma. This proposal has two specific Aims. First Aim focuses on “ground truth” validation of novel cellular resolution OCT-based method, Temporal Speckle Analysis (TSA-OCT), allowing monitoring of the morphology and potentially function of individual RGC (somas and axons), against two gold standards of RGCs detection available in animal models: in vivo fluorescence SLO (FSLO) and the ex vivo flat-mounted histology. The second Aim focuses on validating the predictive value of the (RGCs) cellular dynamic scattering, measured by TSA-OCT, on individual RGCs fate in the Optic Nerve Crush model.

Glaucoma is a blinding disease that is mainly characterized by a progressive loss of retinal ganglion cells (RGCs), optic nerve defects, and atrophy, afflicting more than 60 million people worldwide. It is often developing slowly with symptoms and damages that are not noticed at an early stage. Novel treatments focused on restoring vision in Glaucoma, using Gene or Stem Cell therapies, would benefit from the development of cellular resolution in vivo imaging tools, that could offer sensitivity and specificity beyond current clinical tests. To achieve that we propose to develop and validate novel structural and functional extension of optical coherence tomography (OCT), so-called temporal speckle analysis OCT (TSA-OCT), for basic science research. The proposed TSA-OCT system employed with dedicated image analysis software will be used to acquire images of the RGC structures (somas and axons) with corresponding functional assessment in living mouse models over time. The structural information extracted using TSA-OCT will be validated using both in vivo and ex vivo imaging of fluorescently labeled RGCs in controls (Aim 1) and in glaucoma relevant mice models (Aim 2). The potential of functional assays of TSA-OCT will be evaluated using data from two previous Aims by assessing its predictive value of RGCs degeneration (Aim 3). If successful, it will provide a valuable tool that could speed up the testing of novel glaucoma therapeutic studies with experimental animals.

The proposed Temporal Speckle Analysis (TSA-OCT), allowing monitoring of the morphology and potentially a function of individual RGC (somas and axons), is very innovative. Proposed studies in animal models will allow its first-ever “Ground truth” validation against in vivo fluorescence SLO (FSLO) and the ex vivo images of the same retinas. Additionally, testing of the predictive value of changes in individual RGCs scattering in animal models of Glaucoma is also innovative. It will allow the first-ever evaluation of TSA-OCT as a potential clinical biomarker of Glaucoma and its progression.

Once the study is completed, there are several foreseeable benefits to the general public. First, this result will facilitate the implementation of TSA-OCT as a new biomarker in clinical glaucoma diagnostic, allowing earlier detection and better monitoring of treatment in individual patients. Second, its application to preclinical studies of novel glaucoma treatments will allow reduction of total animals needed for testing, considerably speeding up the validation period and shortening the time before new treatments become available to the general population.