Age- and Race-Related Differences in Human Scleral Material Properties

Grytz, Rafael; Fazio, Massimo A.; Libertiaux, Vincent; Bruno, Luigi; Gardiner, Stuart K.; Girkin, Christopher A.; Downs, J. Crawford

doi:10.1167/iovs.14-14029

Cited by 121 publications

(103 citation statements)

References 67 publications

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“…Other recent scleral mechanics studies have uti lized laser speckle interferometer (ESPI) to measure surface dis placement [17,24,25,51]. ESPI was shown to have an unmatched 16nm accuracy in displacement calculation [63], Using ESPI, Girard et al [17] in monkeys and Fazio et al [24] in humans detected an age-related stiffening of scleral tissue, which is con sistent with what we observed using DIC [18], A similar inverse finite element optimization method was applied to match ESPImeasured displacement fields obtained in an inflation test to model-predicted displacement fields and calculate the anisotropic hyperelastic material properties of the monkey [17,51] and human [22,52] sclera. Although ESPI has a noticeably better displace ment resolution than DIC, the quality of the fit in our study is comparable to if not improved over those studies.…”

Section: Adjustmentsupporting

confidence: 74%

“…Age-related accu mulation of nonenzymatic cross-links has been reported in various tissues [20] and has commonly been associated with a stiffening of the tissue. Increased mechanical stiffness was measured in the aging human [18,21,22], monkey [17], and mouse [23] sclera. More recently, Fazio et al [24,25] showed that the strains in the peripapillary sclera were significantly lower in older human speci mens.…”

Section: Introductionmentioning

confidence: 99%

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Collagen Structure and Mechanical Properties of the Human Sclera: Analysis for the Effects of Age

Coudrillier

Pijanka

Jefferys

et al. 2015

Journal of Biomechanical Engineering

104

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The objective of this study was to measure the collagen fiber structure and estimate the material properties of 7 human donor scleras, from age 53 to 91. The specimens were subjected to inflation testing, and the full-field displacement maps were measured by digital image correlation. After testing, the collagen fiber structure was mapped using wide-angle X-ray scattering. A specimen-specific inverse finite element method was applied to calculate the material properties of the collagen fibers and interfiber matrix by minimizing the difference between the experimental displacements and model predictions. Age effects on the fiber structure and material properties were estimated using multivariate models accounting for spatial autocorrelation. Older age was associated with a larger matrix stiffness (p = 0.001), a lower degree of fiber alignment in the peripapillary sclera (p = 0.01), and a lower mechanical anisotropy in the peripapillary sclera (p = 0.03).

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Section: Adjustmentsupporting

confidence: 74%

Section: Introductionmentioning

confidence: 99%

Collagen Structure and Mechanical Properties of the Human Sclera: Analysis for the Effects of Age

Coudrillier

Pijanka

Jefferys

et al. 2015

Journal of Biomechanical Engineering

104

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“…Raising the steady-state IOP effectively increased the stiffness of the entire corneoscleral shell, whereas chemical crosslinking treatment only alters a small region. This suggests that ubiquitous alterations in corneoscleral stiffness due to aging (Coudrillier et al, 2015; Coudrillier et al, 2012; Fazio et al, 2014) or race/genetics (Grytz et al, 2014) could have a much stronger impact on IOP spikes and glaucoma risk than localized treatment such as corneal or scleral crosslinking.…”

Section: Discussionmentioning

confidence: 99%

Corneoscleral stiffening increases IOP spike magnitudes during rapid microvolumetric change in the eye

Clayson

Pan

Pavlatos

et al. 2017

Experimental Eye Research

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Factors governing the steady-state IOP have been extensively studied; however, the dynamic aspects of IOP are less understood. Clinical studies have suggested that intraocular pressure (IOP) fluctuation may be associated with glaucoma risk. This study aims to investigate how stiffening of corneoscleral biomechanical properties affects IOP spikes induced by rapid microvolumetric change. Porcine eyes (n = 25 in total) were subjected to volumetric infusions before and after external treatment of a circular area (11 mm diameter) in either the central cornea or posterior sclera. The treated area in the control group was immersed in phosphate-buffered saline (PBS) for 40 min, while the treated area of the chemical crosslinking group was immersed in 4% glutaraldehyde/PBS for 40 min. A subset of the sham-treated eyes was also subjected to volumetric infusions at a raised steady-state IOP. The magnitude of IOP spikes increased after localized chemical crosslinking of either the cornea (27.5% increase, p < 0.001) or the sclera (14.3% increase, p < 0.001) with corneal crosslinking having a stronger effect than scleral crosslinking (p = 0.018). We also observed that raising the steady-state IOP from 15 to 25 mmHg resulted in marked increase in IOP spike magnitudes by 63.9% (p < 0.001). These results suggested that an increased corneoscleral stiffness could significantly increase IOP spike magnitudes at the same volumetric change. Corneal stiffness appeared to have a strong impact on the IOP spike magnitude and may play a major role in regulating rapid volume-pressure dynamics. An increase in steady-state IOP also resulted in larger IOP fluctuations due to the increased “apparent” stiffness of the ocular shell, suggesting a potential interaction between the magnitude of IOP and its fluctuations. Corneoscleral properties may represent additional pathways for understanding and managing glaucoma risk and warrant future investigation.

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“…ONH connective tissues stiffen with age (Fazio et al, 2014a; Fazio et al, 2014b; Grytz et al, 2014), although it is not clear if the individual components of those tissues stiffen at different rates. The process may not progress at comparable rates in all humans, as there is strong evidence that it is influenced by genetic factors (Fazio et al, 2014b).…”

Section: Questions Related To Onh Structure and Glaucoma Susceptibmentioning

confidence: 99%

Biomechanical aspects of axonal damage in glaucoma: A brief review

Tamm

Ethier

Dowling

et al. 2017

Experimental Eye Research

100

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The biomechanical environment within the optic nerve head (ONH) is complex and is likely directly involved in the loss of retinal ganglion cells (RGCs) in glaucoma. Unfortunately, our understanding of this process is poor. Here we describe factors that influence ONH biomechanics, including ONH connective tissue microarchitecture and anatomy; intraocular pressure (IOP); and cerebrospinal fluid pressure (CSFp). We note that connective tissue factors can vary significantly from one individual to the next, as well as regionally within an eye, and that the understanding of ONH biomechanics is hindered by anatomical differences between small-animal models of glaucoma (rats and mice) and humans. Other challenges of using animal models of glaucoma to study the role of biomechanics include the complexity of assessing the degree of glaucomatous progression; and inadequate tools for monitoring and consistently elevating IOP in animal models. We conclude with a consideration of important open research questions/challenges in this area, including: (i) Creating a systems biology description of the ONH; (ii) addressing the role of astrocyte connective tissue remodeling and reactivity in glaucoma; (iii) providing a better characterization of ONH astrocytes and non-astrocytic constituent cells; (iv) better understanding the role of ONH astrocyte phagocytosis, proliferation and death; (v) collecting gene expression and phenotype data on a larger, more coordinated scale; and (vi) developing an implantable IOP sensor.

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Age- and Race-Related Differences in Human Scleral Material Properties

Cited by 121 publications

References 67 publications

Collagen Structure and Mechanical Properties of the Human Sclera: Analysis for the Effects of Age

Collagen Structure and Mechanical Properties of the Human Sclera: Analysis for the Effects of Age

Corneoscleral stiffening increases IOP spike magnitudes during rapid microvolumetric change in the eye

Biomechanical aspects of axonal damage in glaucoma: A brief review

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