The pressure-induced deformation response of the human lamina cribrosa: Analysis of regional variations

Midgett, Dan; Pease, Mary Ellen; Jefferys, Joan L.; Patel, Mohak; Franck, Christian; Quigley, Harry A.; Nguyen, Thao D.

doi:10.1016/j.actbio.2016.12.054

Cited by 71 publications

(100 citation statements)

References 66 publications

(71 reference statements)

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“…Accurate characterization of the effects of IOP on the neural tissues of the LC is critical to understanding the pathogenesis and progression of glaucoma as the LC neural tissues are hypothesized to be damaged by IOP-induced mechanical insult. Our conclusions are largely in agreement with recent experimental testing which has predicted similar behavior [18–20]. …”

Section: Discussionsupporting

confidence: 93%

“…Furthermore, our data suggested that the amount of stretch or compression varied largely from one pore to another. Peak strains exceeding 10% have been reported by Midgett and colleagues who also used second harmonic generation to measure the deformation of human LCs [20]. While both of these studies were done ex vivo, we have also recently measured strains in vivo in the LC of rhesus macaque monkeys under various levels of IOP and intracranial pressure using optical coherence tomography [19].…”

Section: Discussionmentioning

confidence: 88%

“…Not surprisingly, the models have been unable to reproduce the strain fields observed experimentally. Recent models predict tensile strains within the LC to be less than 5% under elevated levels of IOP [10, 13, 14, 16, 17], whereas experimental studies by us [18, 19] and others [20] have measured IOP-induced strains exceeding 10 and even 20% in some regions. Further, these experiments revealed highly heterogeneous deformation fields, with levels of stretch varying greatly from one LC pore to another.…”

Section: Introductionmentioning

confidence: 99%

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

2017

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It is widely considered that intraocular pressure (IOP)-induced deformation within the neural tissue pores of the lamina cribrosa (LC) contributes to neurodegeneration and glaucoma. Our goal was to study how the LC microstructure and mechanical properties determine the mechanical insult to the neural tissues within the pores of the LC. Polarized light microscopy was used to measure the collagen density and orientation in histology sections of three sheep optic nerve heads (ONH) at both mesoscale (4.4 µm) and microscale (0.73 µm) resolutions. Mesoscale fiber-aware FE models were first used to calculate ONH deformations at an IOP of 30 mmHg. The results were then used as boundary conditions for microscale models of LC regions. Models predicted large insult to the LC neural tissues, with 95th percentile 1st principal strains ranging from 7–12%. Pores near the scleral boundary suffered significantly higher stretch compared to pores in more central regions (10.0 ± 1.4% vs. 7.2 ± 0.4%; p=0.014; mean ± SD). Variations in material properties altered the minimum, median, and maximum levels of neural tissue insult but largely did not alter the patterns of pore-to-pore variation, suggesting these patterns are determined by the underlying structure and geometry of the LC beams and pores. To the best of our knowledge, this is the first computational model that reproduces the highly heterogeneous neural tissue strain fields observed experimentally.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

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

2017

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“…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][11][12][13][14] and nonhuman primate eyes. 15 Indeed, these regions contain the axons of the RGCs most susceptible to glaucoma injury.…”

mentioning

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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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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“…These incongruities could arise due to alteration in stiffness of the ocular tissues and their response to elevated IOP. These factors are material determinants of IOP-derived lamina strain which is related to glaucoma occurrence [6]. Elevated IOP induces distention of the sclera and lamina cribrosa and impose direct mechanical strain on the axons of the optic nerve damaging nerve fibers and potentially impairing the nerve’s blood supply.…”

Section: Introductionmentioning

confidence: 99%

Noninvasive measurement of wave speed of porcine cornea in ex vivo porcine eyes for various intraocular pressures

2017

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The objective of this study was to extend an ultrasound surface wave elastography (USWE) technique for noninvasive measurement of ocular tissue elastic properties. In particular, we aim to establish the relationship between the wave speed of cornea and the intraocular pressure (IOP). Normal ranges of IOP are between 12 and 22 mmHg. Ex vivo porcine eye balls were used in this research. The porcine eye ball was supported by the gelatin phantom in a testing container. Some water was pour into the container for the ultrasound measurement. A local harmonic vibration was generated on the side of the eye ball. An ultrasound probe was used to measure the wave propagation in the cornea noninvasively. A 25 gauge butterfly needle was inserted into the vitreous humor of the eye ball under the ultrasound imaging guidance. The needle was connected to a syringe. The IOP was obtained by the water height difference between the water level in the syringe and the water level in the testing container. The IOP was adjusted between 5 mmHg and 30 mmHg with a 5 mmHg interval. The wave speed was measured at each IOP for three frequencies of 100, 150 and 200 Hz. Finite element method (FEM) was used to simulate the wave propagation in the corneal according to our experimental setup. A linear viscoelastic FEM model was used to compare the experimental data. Both the experiments and the FEM analyses showed that the wave speed of cornea increased with IOP.

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The pressure-induced deformation response of the human lamina cribrosa: Analysis of regional variations

Cited by 71 publications

References 66 publications

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

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

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

Noninvasive measurement of wave speed of porcine cornea in ex vivo porcine eyes for various intraocular pressures

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