Mathematical modeling approaches in the study of glaucoma disparities among people of African and European descents

Guidoboni, Giovanna; Harris, Alon; Arciero, Julia; Siesky, Brent; Amireskandari, Annahita; Gerber, Austin; Huck, Andrew; Kim, Nathaniel J.; Cassani, Simone; Carichino, Lucia

doi:10.1166/jcsmd.2013.1004

Cited by 26 publications

(15 citation statements)

References 125 publications

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“…As a first approximation, we assumed that blood was an incompressible Newtonian fluid, 34 whose flow behavior can be described with the HagenPoiseuille equation:…”

Section: Governing Equations For Lc Blood Flow Simulationmentioning

confidence: 99%

Factors Influencing Lamina Cribrosa Microcapillary Hemodynamics and Oxygen Concentrations

Chuangsuwanich

Birgersson

Thiéry

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. To identify and rank the lamina cribrosa (LC) morphologic factors that influence LC microcapillary hemodynamics and oxygen concentrations using computational fluid dynamics (CFD).METHODS. We generated 12,000 'artificial' LC microcapillary networks and predicted blood flow velocities and oxygen concentrations within the microcapillaries using CFD. Across models, we varied the average pore size of the LC (5500 6 2400 lm 2 ), the microcapillary arrangement (radial, isotropic, or circumferential), the LC diameter (1.9 6 0.3 mm), the inferior-superior curvature (340 6 116 m À1 ), and the nasal-temporal curvature (À78 6 130 m À1 ). We assumed that blood flow originated from the Circle of Zinn-Haller, fed the LC uniformly at its periphery, and was drained into the central retinal vein. Arterial (50 6 6 mm Hg) and venous (17.7 6 6 mm Hg) pressures were applied as boundary conditions and were also varied within our simulations. Finally, we performed linear regression analysis to rank the influence of each factor on LC hemodynamics and oxygen concentrations. RESULTS.The factors influencing LC hemodynamics and oxygen concentrations the most were: LC diameter, arterial pressure, and venous pressure, and to a lesser extent: the microcapillary arrangement (anisotropy) and nasal-temporal curvature. Lamina cribrosa pore size and superior-inferior curvature had almost no impact. Specifically, we found that LCs with a smaller diameter, a radial arrangement of the microcapillaries, an elevated arterial pressure and a decreased venous pressure had higher oxygen concentrations across their networks.CONCLUSION. This study described LC hemodynamics using a computational modeling approach. Our study may provide clinically relevant information for the understanding of ischemia-induced neuronal cell death in optic neuropathies.

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“…As a first approximation, we assumed that blood was an incompressible Newtonian fluid, 34 whose flow behavior can be described with the HagenPoiseuille equation:…”

Section: Governing Equations For Lc Blood Flow Simulationmentioning

confidence: 99%

Factors Influencing Lamina Cribrosa Microcapillary Hemodynamics and Oxygen Concentrations

Chuangsuwanich

Birgersson

Thiéry

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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“…Many factors influence the properties of the scleral insertion of the lamina cribrosa, such as ethnicity [42] and age 43]. In addition, these properties have observed to change within the same individual as glaucoma progresses [44].…”

Section: Discussionmentioning

confidence: 99%

A poroelastic model for the perfusion of the lamina cribrosa in the optic nerve head

Causin

Guidoboni

Harris

et al. 2014

Mathematical Biosciences

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In this work we present a mathematical model for the coupling between biomechanics and hemodynamics in the lamina cribrosa, a thin porous tissue at the base of the optic nerve head which is thought to be the site of injury in ocular neurodegenerative diseases such as glaucoma. In this exploratory two-dimensional investigation, the lamina cribrosa is modeled as a poroelastic material where blood vessels are viewed as pores in a solid elastic matrix. The model is used to investigate the influence on the distributions of stress, blood volume fraction (or vascular porosity) and blood velocity within the lamina cribrosa due to the application of different levels of the intraocular pressure (IOP) and the enforcement of different mechanical constraints at the lamina's boundary. The model simulations suggest that the degree of fixity of the boundary constraint strongly influences the lamina's response to IOP elevation. Specifically, when the boundary is mechanically clamped, IOP elevation leads to an increase in stress close to the lamina's boundary, making it more susceptible to tissue damage. On the other hand, when rotations are allowed at the boundary, the most vulnerable region appears to be located at the lamina's central axis, in proximity of the eye globe, where increased stress and reduced vascular porosity and blood velocity are predicted for increased levels of IOP.

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“…The pathogeny of glaucoma is considered multifactorial [15], obscure [16], or unknown [17]. Theories abound.…”

Section: Glaucoma: How Many Different Diseases?mentioning

confidence: 99%

“…Apart from the difficulty of answering some of the questions asked of other models, clinically neuroprotection at the eye level has been deemed useless and even dangerous [23]. However, protection of the CNS neurons has recently been proposed as an adjunct therapy with less inherent risks [17].…”

Section: Glaucoma and The Brainmentioning

confidence: 99%

Glaucoma as a Tax on Hominid Evolution. Constraints of the Experimental Animal Models of Glaucoma

Carreras¹

2016

J Clin Exp Ophthalmol

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Glaucoma continues to be a mysterious disease. High intraocular pressure (IOP), once the landmark of the disease, has been relegated to the humble role of risk factor, despite the fact that lowering IOP continues to be the only partially successful treatment. Even with an IOP successfully controlled to statistical standards, many patients still mysteriously continue to progressively lose neural tissue. A novel pathogenetical mechanism has recently been put forward as the main agent of the disease. In this new light, some structural details of the human eye, the result of the peculiar evolutionary development, take on an unexpected role in the presentation of the disease. As results of cladistics analysis, the human eye appears as particularly prone to suffering glaucoma as a consequence of the evolutionary path taken. That makes glaucoma essentially a human (and related hominid) scourge. Exclusive features of the human eye compared to other vertebrates involve both the anterior and posterior segment. Those features that facilitate glaucoma in humans are absent in many of the purported animal models for the disease, and this inadequacy further convolutes the mystery of glaucoma. This suggests the division of the animal models into those that mimic the whole disease and those that only reproduce a pertinent histological feature. Unfortunately most animal models are based on high intraocular pressure which excludes most cases of low or moderate pressure. For any animal model, it is important the researcher accurately establishes the constraints of the model in order to avoid jumping to conclusions.

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Mathematical modeling approaches in the study of glaucoma disparities among people of African and European descents

Cited by 26 publications

References 125 publications

Factors Influencing Lamina Cribrosa Microcapillary Hemodynamics and Oxygen Concentrations

Factors Influencing Lamina Cribrosa Microcapillary Hemodynamics and Oxygen Concentrations

A poroelastic model for the perfusion of the lamina cribrosa in the optic nerve head

Glaucoma as a Tax on Hominid Evolution. Constraints of the Experimental Animal Models of Glaucoma

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