Material properties of the posterior human sclera

PURPOSE. The purpose of this study was to measure change in anterior lamina cribrosa depth (ALD) globally and regionally in glaucoma eyes at different intraocular pressures (IOP).METHODS. Twenty-seven glaucoma patients were imaged before and after IOP-lowering procedures using optical coherence tomography. The anterior lamina was marked in approximately 25 locations in each of six radial scans to obtain global and regional estimates of ALD. ALD and its change with IOP were compared with optic disc damage, nerve fiber layer thickness, and visual field loss. RESULTS.Variables associated with deeper baseline ALD included larger cup/disc ratio, thinner rim area, larger cup volume, thinner central corneal thickness, and male sex (all P 0.02). When IOP was lowered, ALD position became more anterior, more posterior, or was unchanged. The mean ALD change after lowering was 27 6 142 lm (P ¼ 0.3). The mean absolute value of ALD change was 112 6 90 lm (P ¼ 0.002). Change in ALD was greater in eyes with lower IOP in paired comparisons (P ¼ 0.006) but was not associated with the magnitude of IOP lowering between imaging sessions (P ¼ 0.94). Eyes with no significant change in ALD tended to have more visual field loss than those with significant anterior ALD displacement (P ¼ 0.07). Areas within each optic nerve head that corresponded to zones with thicker nerve fiber layer had greater ALD positional change (P ¼ 0.0007).CONCLUSIONS. The lamina can move either anteriorly or posteriorly with IOP decrease, with greater displacement at lower IOP. Glaucoma eyes and regions within glaucoma eyes associated with greater glaucoma damage exhibited smaller responses.Keywords: glaucoma, lamina cribrosa, optic nerve head, optical coherence tomography, intraocular pressure, biomechanics, stress A major site of damage to retinal ganglion cell (RGC) axons in glaucoma is the optic nerve head (ONH), within the lamina cribrosa.1-3 The biomechanical transmission of stress from intraocular pressure (IOP) produces strain in both the sclera and the ONH, 4-6 generating detrimental effects on RGC axons, ONH astrocytes, and nutritional blood flow in the nerve head. 7 The IOP level that produces RGC loss can be variable among individuals; some eyes suffer damage at IOPs that would be considered normal based on population studies, whereas many eyes with elevated IOP suffer no detectable damage. This suggests that the short-and long-term responses of scleral and ONH connective tissues to changes in IOP represent possible biomarkers for glaucoma incidence and progression. Normal lamina cribrosa structure is remodeled in glaucoma eyes, becoming deeper and wider 8 under the influence of a variety of factors, notably the stress of IOP as delivered through the sclera. 9 The regional differences in connective tissue density and pore size within the lamina cribrosa and greater regional strains suggest that the upper and lower poles of the ONH are weaker at resisting the stress of IOP in both human 10-14 and nonhuman primate eyes. 15 Indeed, these regions contain...

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“…In engineering models, the behavior of both the peripapillary sclera and the lamina cribrosa determine the effect of IOP. [16][17][18] …”

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confidence: 99%

Biomechanical Responses of Lamina Cribrosa to Intraocular Pressure Change Assessed by Optical Coherence Tomography in Glaucoma Eyes

Quigley

Arora

Idrees

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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“…For example, scleral biomechanical properties may be altered by the initial IOP spike. 34,35 This effect may make the eye more vulnerable following insult. Further investigation is required to understand the role of the IOP spike in this model.…”

Section: Discussionmentioning

confidence: 99%

A Mouse Model of Chronic Ocular Hypertension Induced by Circumlimbal Suture

Liu

Flanagan

2017

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. To develop a chronic ocular hypertension mouse model by inducing intraocular pressure (IOP) elevation using a suture technique previously developed for rats.METHODS. C57BL/6 mice were given monocular circumlimbal suture (10/0) placement under anesthesia (ketamine/xylazine). The suture was left in place for 12 weeks (n ¼ 10). A control group had the same treatment while it was removed after day 1 (n ¼ 10). Intraocular pressure, electroretinogram (ERG), and optical coherence tomography (OCT) were measured in both groups for 12 weeks. At week 12, animals were euthanized and retina was harvested for histologic assessment.RESULTS. In the group with extended suture placement, IOP spiked from 14.3 6 0.9 to 48.4 6 4.8 mm Hg immediately after suture implantation. At day 1, it declined to 33.2 6 3.7 mm Hg and remained elevated for 12 weeks. In the suture removal group, IOP normalized to baseline within a day following suture removal. In the group with prolonged IOP elevation, the retinal ganglion cell (RGC) mediated ERG responses continued to exacerbate and were significantly reduced by week 12 (P < 0.001). Progressive loss of retinal nerve fiber layer was found and it became significant from week 4 (P < 0.001). At week 12, significant loss of RGCs (P < 0.001) was noted. In the IOP normalization group, no alteration in ERG, OCT, and RGC counting was observed.CONCLUSIONS. The circumlimbal suture approach produces a mild chronic IOP elevation in mice. Functional and structural changes under model induction are largely independent of the initial IOP spike.Keywords: glaucoma, intraocular pressure, electroretinogram, optical coherence tomography, ganglion cell G laucoma is a chronic ocular disease, which is characterized by selective retinal ganglion cell (RGC) degeneration and progressive visual field loss. Elevated intraocular pressure (IOP) is a critical risk factor for disease development, and IOP lowering is the mainstay of disease management. [1][2][3] Over the past few decades, a variety of rodent models have been developed to simulate human glaucoma. [4][5][6][7] These models aim to induce either acute or chronic ocular hypertension leading to glaucomatous-like changes. By using such models, investigators have made significant insights into understanding the pathogenesis of the disease.Previously, a rat model of chronic IOP elevation using conjunctival circumlimbal suture was developed. 8,9 This minimally invasive technique employed the concept of oculopression to produce elevated IOP. [10][11][12] An advantage of the suture compression model is that it is not associated with ocular tissue penetration or traumatization, and therefore relatively preserves the immune privilege of the eye. It was reported that a mild, chronic IOP elevation was induced for at least 15 weeks following an initial IOP spike that appeared immediately after suture placement. Progressive loss of RGC function, retinal nerve fiber layer (RNFL) defect, and eventual cell death in the ganglion cell layer were observed under model induction, ...

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“…Many studies have indicated that chronical IOP elevation induces significant structural changes in a thin porous tissue at the base of the optic nerve head called lamina cribrosa [2][3][4][5][6]. Elevated IOP may lead to vision loss by inducing mechanical damage on the retinal ganglion cells axons passing through the lamina (mechanical hypothesis) [7,8] and/or by altering the blood flow within the lamina's tissue (hemodynamical hypothesis) [9,10].…”

Section: Introductionmentioning

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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Material properties of the posterior human sclera

Cited by 113 publications

References 57 publications

Biomechanical Responses of Lamina Cribrosa to Intraocular Pressure Change Assessed by Optical Coherence Tomography in Glaucoma Eyes

Biomechanical Responses of Lamina Cribrosa to Intraocular Pressure Change Assessed by Optical Coherence Tomography in Glaucoma Eyes

A Mouse Model of Chronic Ocular Hypertension Induced by Circumlimbal Suture

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

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