Systemic manifestations of microvascular disease in primary open-angle glaucoma


Nicholas M. Pfahler

Michael M. Miazga

Indre Bielskus

Elani Kaufman

Jack G. McGuire

Thomas Cronin

James Haney

Ryan McCarty

Michael Giovingo

Nicholas J. Volpe

Angelo P. Tanna

Paul Knepper

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Purpose: Primary open-angle glaucoma (POAG) is clinically characterized by increased intraocular pressure, increased cup-to-disc ratio, retinal ganglion cell degeneration, and corresponding visual field loss. Intraocular pressure remains the only treatable risk factor for POAG and can be well-controlled in a majority of patients, although some are unresponsive to treatment. The purpose of this chapter is to examine systemic manifestations of POAG to better understand the disease pathophysiology and identify treatable systemic risk factors.
Methods: In cohorts of POAG patients and aged control subjects, we used nailfold capillary microscopy to
analyze capillary abnormalities, flow cytometry to measure platelet subtype levels, spectrophotometry to measure procoagulant activity, and a cone-plate rheometer to measure a series of viscosity parameters. Additionally, we reviewed the literature for visual and non-visual central nervous system changes associated with POAG.
Results: POAG patients exhibited increased nailfold capillary hemorrhages, increased production of
superactivated platelets and transglutaminase-active platelets, increased platelet procoagulant activity, and
increased clotting sensitivity to low shear stress and to thrombin. Additionally, POAG is accompanied by widespread neurodegenerative changes throughout the visual pathway and central nervous system including white matter changes characteristic of cerebrovascular disease.
Conclusions: Multiple lines of evidence suggest that POAG is associated with systemic microvascular
pathologies that influence the progression of glaucomatous retinal ganglion cell degeneration and visual field loss. Platelet dysfunction in particular represents a promising therapeutic target in POAG. These systemic findings may help to elucidate the cause of POAG, identify early diagnostic markers, and increase the amount of available treatment options.

Glaucoma Research 2018-2020, pp. 151-167 #11
Edited by: John R. Samples and Paul A. Knepper
© Kugler Publications, Amsterdam, The Netherlands

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