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.
