Development, validation and assessment of an automated, topographic structure-function approach to the detection of glaucoma and its progression

Project Summary / Abstract There is no single (litmus) test to confirm the presence or the progression of glaucoma, a group of optic neuropathies. Therefore, clinicians rely on characteristic changes on structural and functional tests to diagnose and monitor the disease. There is increasing evidence that challenge the old notion that “structure precedes function”. Research has shown that factors, such as baseline patient conditions, test paradigms, and test measures can affect the extent to which structural and functional glaucomatous damage agree. Studies have reported that functional damage, assessed by means of visual field (VF) testing, and structural loss, as evaluated by measures of optical coherence tomography (OCT) retinal nerve fiber layer (RNFL) thickness, typically coincide, often in a linear manner. As a matter of fact, recent work by Dr. Tsamis and his mentoring team (Prof Hood and Dr. De Moraes) provided evidence that a topographic approach of widefield OCT scans and 24-2 and 10-2 VFs, based on an R algorithm, can identify abnormal structure – abnormal function agreement in over 90% of eyes with early glaucomatous damage. The overarching goal of this proposal is to assess the capability of a topographic structure-function evaluation in glaucoma diagnosis and detection of progression. During the K99 phase, the tool-algorithm will be refined with the aim of improving its performance in the identification of early glaucomatous eyes. It will also be expanded to include other types of OCT scan protocols (e.g., circle scans), as well as scans from other manufacturers to extend the utility of this approach. At the same time, Dr. Tsamis will undergo extensive training in data science and statistics in order to enhance his skills, support his career development and provide a pathway towards research independency. He will use these skills during the R00 phase to develop a method of topographic assessment for detection of glaucoma progression in eyes with early and advanced glaucoma. The newly developed technique will be evaluated against a clinical reference standard as well as against other conventional methods, which are available in the glaucoma clinic. The proposed research has translational potential at multiple levels. First, the VF-OCT topographic assessment should provide a better balance between sensitivity and accuracy for the assessment of rates of progression than currently available methods. This should lead to reduced frequency of patient visits and testing. Second, the developed R algorithm has the potential to provide a standardized tool to further improve our understanding and assessment of glaucomatous phenotypes and their association with the structural status in a way less influenced by clinical subjectivity. Last, the proposed method could accelerate the design and conduction of clinical trials in glaucoma (e.g. neuroprotection) by demonstrating and establishing better structure-function endpoints, providing surrogate measures of the disease and its progression. This should lead to a reduction in study population size and duration of clinical trials, and thus their costs.