Glaucoma-related Changes in the Mechanical Properties and Collagen Micro-architecture of the Human Sclera

Abstract

ObjectiveThe biomechanical behavior of the sclera determines the level of mechanical insult from intraocular pressure to the axons and tissues of the optic nerve head, as is of interest in glaucoma. In this study, we measure the collagen fiber structure and the strain response, and estimate the material properties of glaucomatous and normal human donor scleras.MethodsTwenty-two posterior scleras from normal and diagnosed glaucoma donors were obtained from an eyebank. Optic nerve cross-sections were graded to determine the presence of axon loss. The specimens were subjected to pressure-controlled inflation testing. Full-field displacement maps were measured by digital image correlation (DIC) and spatially differentiated to compute surface strains. Maps of the collagen fiber structure across the posterior sclera of each inflated specimen were obtained using synchrotron wide-angle X-ray scattering (WAXS). Finite element (FE) models of the posterior scleras, incorporating a specimen-specific representation of the collagen structure, were constructed from the DIC-measured geometry. An inverse finite element analysis was developed to estimate the stiffness of the collagen fiber and inter-fiber matrix.ResultsThe differences between glaucoma and non-glaucoma eyes were small in magnitude. Sectorial variations of degree of fiber alignment and peripapillary scleral strain significantly differed between normal and diagnosed glaucoma specimens. Meridional strains were on average larger in diagnosed glaucoma eyes compared with normal specimens. Non-glaucoma specimens had on average the lowest matrix and fiber stiffness, followed by undamaged glaucoma eyes, and damaged glaucoma eyes but the differences in stiffness were not significant.ConclusionThe observed biomechanical and microstructural changes could be the result of tissue remodeling occuring in glaucoma and are likely to alter the mechanical environment of the optic nerve head and contribute to axonal damage.

Peripapillary sclera architecture revisited: A tangential fiber model and its biomechanical implications

“…We chose to simulate SALS and WAXS as they are two of the most common methods for quantitatively studying the fiber anisotropy of PPS tissues. [5, 7, 15, 16, 18, 19]…”

“…[5, 7, 13–17] Since collagen fibers stiffen when stretched, this ring would serve to restrict the opening of the canal that would be expected under elevated IOP. However, this current consensus is largely based on low-resolution, light scattering imaging techniques including small angle light scattering (SALS) and wide angle x-ray scattering (WAXS) [5, 7, 15, 16, 18, 19] or high resolution techniques such as second harmonic generation [17, 20] or electron microscopy [20–22] with excellent resolution but modest field of view. SALS and WAXS methods have been adopted in part due to their abilities to provide quantitative data that can be easily incorporated into mechanical models, however the resolution of these methods is on the order of 100–300 μm [5, 23], far below the resolution needed to observe individual collagen fibers or even bundles, on the order of 10–50 μm in width.…”

The connective tissue phenotype of glaucomatous cupping in the monkey eye - Clinical and research implications

“…While these concepts remain central to the discussion of ONH biomechanics in general, and the pathophysiology of glaucomatous damage to the ONH tissues specifically, a large group of investigators have expanded our understanding of glaucoma through the application of biomechanics and mechanobiology to the cornea (He and Liu, 2009, 2011; Liu and He, 2009; Liu and Roberts, 2005), trabecular meshwork (Braakman et al, 2014; Li et al, 2012; Overby et al, 2009; Stamer et al, 2014; Thomasy et al, 2012; Zhou et al, 2012), sclera (Coudrillier et al, 2013; Coudrillier et al, 2015a, b; Coudrillier et al, 2015c; Dastiridou et al, 2013; Fazio et al, 2014a; Fazio et al, 2014b; Girard et al, 2011b; Grytz et al, 2014; Nguyen and Ethier, 2015; Pijanka et al, 2012; Quigley et al, 2015) and ONH (Clark, 2012; Downs, 2015; Eilaghi et al, 2010; Girard et al, 2016; Girard et al, 2011a; Girard et al, 2013; Grytz et al, 2012a; Lei et al, 2011; Sigal et al, 2012; Sigal and Ethier, 2009; Sigal et al, 2005b, 2009a, b; Sigal and Grimm, 2012; Sigal et al, 2014; Stewart et al, 2014; Wang et al, 2016; Zhang et al, 2015) in health and disease. In sections 2.2 through 2.10, the details of these concepts are reviewed.…”

“…Computational models suggest that scleral stiffness (Sigal et al, 2011) and scleral collagen fiber organization (Girard et al, 2009b; Grytz et al, 2011) dictate the IOP-induced deformation exhibited by the ONH. Interestingly, the sclera exhibits significant biomechanical changes with age (Coudrillier et al, 2015a, b; Fazio et al, 2014a; Fazio et al, 2014b; Girard et al, 2009c), ethnicity (Fazio et al, 2014b), and following exposure to chronic IOP elevation (Coudrillier et al, 2015c; Downs et al, 2005; Girard et al, 2011b), both of which being major risk factors in human glaucoma.…”

Effects of collagen microstructure and material properties on the deformation of the neural tissues of the lamina cribrosa

“…We chose to use material properties for the connective tissues which were based on the properties of human scleral tissue obtained via inflation testing. Given that human scleral stiffness has been well characterized [15, 27, 28, 40, 41], we deemed this to be a reasonable assumption. More challenging was the choice of neural tissue properties.…”