The Role of Vascular Factors in Glaucoma

Linda Zangwill, PhD
University of California, San Diego
Year Awarded:
2017
Grant Duration:
July 1, 2017 to June 30, 2020
Disease:
Glaucoma
Award Amount:
$150,000
Grant Reference ID:
G2017122
Award Type:
Standard
Award Region:
US Southwestern
Linda Zangwill, PhD

The Role of Microvasculature in the Pathophysiology of Glaucoma

Summary

Numerous studies have suggested that vascular factors (blood supply) are involved in the development of glaucoma, but it is currently not known whether a reduction in blood supply to the eye is a cause or an effect of the glaucoma disease process.  Recent advances in imaging technology have made it possible to visualize and measure the retinal blood supply, as well as assess the deep layers of the optic nerve head, including the lamina cribrosa, during routine eye exams.  This prospective clinical research study will investigate whether changes in the retinal blood supply precede or follow other structural and mechanical changes in glaucoma.

Details

The goal of this prospective clinical research study is to utilize recent advances in retinal imaging technology to investigate whether changes in the retinal blood supply (microvasculature) precede or follow the death of cells in a layer of the optic nerve head (the retinal nerve fiber layer, or RNFL), as well as mechanical changes deep in the optic nerve head (lamina cribrosa) that can lead to glaucoma.

Numerous studies have suggested that vascular factors are involved in the development of glaucoma; however, it is not known whether reduced blood supply is a cause or an effect of that disease process. The overall goal of this longitudinal clinical research study is to investigate whether changes in the retinal blood supply precede or follow structural (RNFL) and mechanical (deep layer /lamina cribrosa) changes in glaucoma. Specifically, this study will elucidate the temporal and spatial relationship between changes in superficial and deep layer retinal blood supply, and also structural changes in the RNFL over time in eyes with and without focal lamina cribrosa defects.  We hypothesize that the loss of both superficial and deep layer microvasculature will be larger and/or faster in eyes with lamina cribrosa defects than in eyes without, particularly at the location of the lamina defect.  Moreover, we hypothesize that in eyes with focal lamina cribrosa defects, the loss of the microvasculature over time will be larger and/or faster than the loss of the RNFL.

Although there is clear evidence that both vascular and mechanical factors play a role in the pathophysiology of glaucoma, it is not clear whether retinal blood supply changes are primary or secondary events in the pathogenesis of the disease.  The study is innovative in that it utilizes a new retinal imaging technology, optical coherence tomography angiography (OCTA), to elucidate the temporal and spatial relationship between changes in the retinal microvasculature, retinal structure (RNFL) and mechanical factors in the deep layer/lamina cribrosa of the optic nerve head in glaucoma.  Moreover, we have already shown that there is microvascular dropout that corresponds to the location of lamina cribrosa damage without necessary loss of RNFL. This project will extend the follow-up of these patients over time to determine whether retinal microvascular dropout precedes or follows lamina cribrosa damage and when the loss of RNFL is detectable. To our knowledge, this would be the first clinical study to investigate the longitudinal relationship between retinal blood supply and mechanical aspects of the glaucomatous progression.

Currently, the only therapy available for glaucoma is based on lowering intraocular pressure (IOP).  Improving our understanding of the relationship between changes in the retinal microvasculature, RNFL and lamina cribrosa in the pathophysiology of glaucoma can inform the development of new therapeutic targets designed to slow the microvasculature changes as a new non-IOP lowering approach to glaucoma therapy. Moreover, this study will determine whether changes in retinal microvasculature can be used as a biomarker or clinical indicator for monitoring progression of glaucoma in clinical practice.

About the Researcher

Linda Zangwill, PhD is a professor of ophthalmology at the Shiley Eye Institute/ Department of Ophthalmology, University of California, San Diego. At the Hamilton Glaucoma Center, she serves as director of clinical research, director of the Diagnostic Imaging Laboratory, and director of the Imaging Data Evaluation and Analysis (IDEA) Reading Center. Dr. Zangwill completed her BS from UC Berkeley, MS from the Harvard School of Public Health, and PhD in epidemiology from Ben-Gurion University of the Negev, Beer-Sheva, Israel.   Dr. Zangwill’s research focuses on improving our understanding of the complex relationship between structural and functional change over time in the aging and glaucoma eye, developing computational and statistical techniques to improve glaucomatous change detection, and identifying risk factors that can predict rapidly progressing glaucoma. 

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