Factors Influencing Lamina Cribrosa Microcapillary Hemodynamics and Oxygen Concentrations

Abstract

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.

Photoacoustic imaging of lamina cribrosa microcapillaries in porcine eyes

“…3(b) and 4(a)], which were similar to the morphology of porcine LC collagenous beams observed from micro-computed tomography [34]. The similarity of LC microcapillaries and LC beams' morphology may prove that each LC beam contains a microcapillary, validating an important assumption used in computational hemodynamics study of the LC [7].…”

“…It has been speculated that several loads (IOP, the cerebrospinal fluid pressure [2], and optic nerve traction forces [3]) can cause RGC axonal death by inducing biomechanical insult to the ONH tissue, causing direct mechanical damage to the RGC and disrupting axonal transport of essential trophic factors [4][5][6]. Another possible pathway for RGC damage relates to the vascular deficiency-alterations in the structures of the ONH due to a modified biomechanical environment or poor ocular hemodynamics could predispose a person to ischemic RGC death [7][8][9][10].…”

Morphometric, Hemodynamic, and Biomechanical Factors Influencing Blood Flow and Oxygen Concentration in the Human Lamina Cribrosa

“…The methods used to generate the network and descriptions of the parameters were described in our previous work. 18 So, for each eye model we varied eight unique parameters (excluding the IOP) simultaneously by randomly assigning a value to each parameter based on a predefined normal distribution (described in Table 1). The IOP was varied from 10 mm Hg to 55 mm Hg in increments of 5 mm Hg, and 500 models were built for each IOP value.…”

“…[6][7][8] Another possible pathway for RGC damage is vascular deficiency, and it is speculated that alterations in the structures of the optic nerve head (ONH), due to a modified biomechanical environment or poor ocular hemodynamics, could lead to ischemic RGC death. [9][10][11][12] To date, both mechanical and vascular factors have been assumed to be involved in glaucoma pathogenesis, but the relationship between these factors remains unclear. In our previous work, we investigated the hemodynamical aspects of OAG by developing computational fluid dynamics (CFD) models of the lamina cribrosa (LC), a sieve-like network of collagenous connective tissue and microcapillaries that mechanically supports and nourishes the RGCs.…”

“…13 We found that morphological parameters of the LC, particularly the increase in LC radius, had an adverse impact on LC blood flow and could lead to ischemia. 12 Given the technical limitations involved in experimentally characterizing blood flow in the LC microcapillary network, our computational model represented a powerful alternative to study the involvement of blood flow in glaucoma pathogenesis. However, in our previous study we did not include the elasticity of tissues, IOP and CSFP loads, or their potential impacts on blood flow.…”