The objective of this study is to investigate the role of the vascular risk factors in explaining why individuals of African descent (AD) are disproportionately affected by glaucoma compared to individuals of European descent (ED). Studies have suggested that ocular blood flow plays a significant role in the evolution of glaucomatous damage in some individuals. It is also well known that persons of AD have an increased prevalence of systemic and cerebral vascular diseases. Given these findings, this study is designed to investigate if abnormal ocular perfusion pressure and blood flow in persons of AD with glaucoma contribute to the differences observed in the prevalence and progression of glaucoma in the AD population. This investigation involves a carefully designed secondary analysis of the existing data from the Indianapolis Glaucoma Progression Study (IGPS). This study is unique in that it is the only long- term prospective observational study that investigates the relationship between ocular perfusion and blood flow and structural and functional glaucoma progression. The 113 open-angle glaucoma patients enrolled in the IGPS receive a comprehensive ocular blood flow and perfusion parameters assessment alongside comprehensive clinical markers of glaucoma progression. Extensive clinical and hemodynamic measures were identically assessed at two identical baseline visits one week apart followed by biannual visits over a 3 year period. At each visit, patients underwent comprehensive testing including: multiple measures of intraocular pressure (Goldmann and Psacal), visual acuity, contrast sensitivity, ultrasonic corneal pachymetry of central corneal thickness, height, weight, body mass index, blood pressure, heart rate, medical history, visual field testing (using standard automated perimetry), Fourier domain Doppler optical coherence tomography (FD-OCT) with total retinal blood flow assessment, Stratus optical coherence tomography (OCT) structural imaging, Heidelberg retina tomography III, color Doppler imaging of the retrobulbar blood vessels, confocal scanning laser Doppler flowmetry of retinal capillaries, ocular perfusion pressure calculations, refraction, Pascal applanation (ocular pulse amplitude) and medical questionnaires. The proposed secondary data analysis will analyze the relationship between structural and functional disease progression and ocular perfusion pressure and blood flow, and investigate the differences between AD and ED glaucoma populations. Identifying distinct differences in vascular parameters between individuals of AD and ED will provide valuable insight into determining the mechanisms of disparity in glaucoma prevalence and progression in persons of AD.

Public Health Relevance

The objective of this study is to explore the role of vascular risk factors in explaining the mechanisms behind the disparity of glaucoma in persons of African descent compared to those of European descent. The known increased prevalence of systemic vascular disease in the African descent population suggests that deficiencies in ocular perfusion pressure and blood flow may have a significant role in explaining these inequalities. Our unique secondary analysis of the Indianapolis Glaucoma Progression Study data which includes comprehensive ocular perfusion pressure, blood flow, retinal and optic nerve structure, visual function and their relationship to disease progression has the potential to elucidate, for the firs time, the reason for the disparity in glaucomatous disease between those of African descent and European descent.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21EY022101-02
Application #
8502507
Study Section
Special Emphasis Panel (ZEY1-VSN (10))
Program Officer
Wideroff, Louise
Project Start
2012-07-01
Project End
2014-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
2
Fiscal Year
2013
Total Cost
$185,250
Indirect Cost
$66,500
Name
Indiana University-Purdue University at Indianapolis
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
603007902
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
Causin, Paola; Guidoboni, Giovanna; Malgaroli, Francesca et al. (2016) Blood flow mechanics and oxygen transport and delivery in the retinal microcirculation: multiscale mathematical modeling and numerical simulation. Biomech Model Mechanobiol 15:525-42
Dziubek, Andrea; Guidoboni, Giovanna; Harris, Alon et al. (2016) Effect of ocular shape and vascular geometry on retinal hemodynamics: a computational model. Biomech Model Mechanobiol 15:893-907
Siesky, Brent; Harris, Alon; Carr, Joseph et al. (2016) Reductions in Retrobulbar and Retinal Capillary Blood Flow Strongly Correlate With Changes in Optic Nerve Head and Retinal Morphology Over 4 Years in Open-angle Glaucoma Patients of African Descent Compared With Patients of European Descent. J Glaucoma 25:750-7
Siesky, Brent; Harris, Alon; Racette, Lyne et al. (2015) Differences in ocular blood flow in glaucoma between patients of African and European descent. J Glaucoma 24:117-21
Causin, Paola; Guidoboni, Giovanna; Harris, Alon et al. (2014) A poroelastic model for the perfusion of the lamina cribrosa in the optic nerve head. Math Biosci 257:33-41
Guidoboni, Giovanna; Harris, Alon; Carichino, Lucia et al. (2014) Effect of intraocular pressure on the hemodynamics of the central retinal artery: a mathematical model. Math Biosci Eng 11:523-46
Guidoboni, Giovanna; Harris, Alon; Cassani, Simone et al. (2014) Intraocular pressure, blood pressure, and retinal blood flow autoregulation: a mathematical model to clarify their relationship and clinical relevance. Invest Ophthalmol Vis Sci 55:4105-18
Kanakamedala, Priyanka; Harris, Alon; Siesky, Brent et al. (2014) Optic nerve head morphology in glaucoma patients of African descent is strongly correlated to retinal blood flow. Br J Ophthalmol 98:1551-4
Huck, Andrew; Harris, Alon; Siesky, Brent et al. (2014) Vascular considerations in glaucoma patients of African and European descent. Acta Ophthalmol 92:e336-40
Harris, Alon; Siesky, Brent; Wirostko, Barbara (2013) Cerebral blood flow in glaucoma patients. J Glaucoma 22 Suppl 5:S46-8

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