The Role of Microvasculature in the Pathophysiology of Glaucoma
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.