Massimo A. Fazio

Material properties of the posterior human sclera

To characterize the material properties of posterior and peripapillary sclera from human donors, and to investigate the macro- and micro-scale strains as potential control mechanisms governing mechanical homeostasis. Posterior scleral shells from 9 human donors aged 57-90 years were subjected to IOP elevations from 5 to 45mmHg and the resulting full-field displacements were recorded using laser speckle interferometry. Eye-specific finite element models were generated based on experimentally measured scleral shell surface geometry and thickness. Inverse numerical analyses were performed to identify material parameters for each eye by matching experimental deformation measurements to model predictions using a microstructure-based constitutive formulation that incorporates the crimp response and anisotropic architecture of scleral collagen fibrils. The material property fitting produced models that fit both the overall and local deformation responses of posterior scleral shells very well. The nonlinear stiffening of the sclera with increasing IOP was well reproduced by the uncrimping of scleral collagen fibrils, and a circumferentially aligned ring of collagen fibrils around the scleral canal was predicted in all eyes. Macroscopic in-plane strains were significantly higher in peripapillary region then in the mid-periphery. In contrast, the meso- and micro-scale strains at the collagen network and collagen fibril level were not significantly different between regions. The elastic response of the posterior human sclera can be characterized by the anisotropic architecture and crimp response of scleral collagen fibrils. The similar collagen fibril strains in the peripapillary and mid-peripheral regions support the notion that the scleral collagen architecture including the circumpapillary ring of collagen fibrils evolved to establish optimal load bearing conditions at the collagen fibril level.

Variation of the Axial Location of Bruch's Membrane Opening With Age, Choroidal Thickness, and Race

PURPOSE This study explores variation in the axial location of Bruchs membrane opening (BMO) to determine if this reference plane varies with age and race. METHODS There were 168 spectral-domain optical coherence tomography (SDOCT) optic nerve head volumes that were obtained from healthy subjects and manually delineated within 24 axial slices to develop point clouds for Bruchs membrane and anterior scleral surfaces. A BMO-independent reference plane was generated based on the peripapillary sclera to measure BMO position. General estimating equations were used to determine the relationship of the axial position of BMO (BMO height) with choroidal thickness, age, and race (African Descent [AD] versus European Descent [ED]) controlling for variations in axial length. RESULTS The peripapillary choroid was thinner with increasing axial length (-14.9 μm/mm, P = 0.0096), advancing age (-1.1 μm/y, P = 0.00091), and in the ED group (20.2 μm, P = 0.019) in a multivariable model. Choroidal thickness was also strongly related to BMO height (P < 0.00001) independent of all covariates. Bruchs membrane opening position was more posterior relative to the sclera in older subjects (1.3 μm/y, P = 0.00017), independent of axial length and race. However, when choroidal thickness was included in the model, this association was lost (P = 0.225). There was no significant difference in BMO height between racial groups after adjustment for age and axial length. CONCLUSIONS Bruchs membrane opening is more posteriorly located in older individuals. These differences are largely due to differences in choroidal thickness and suggest that BMO migrates posteriorly with age due to age-related choroidal thinning. However, additional studies in longitudinal datasets are needed to validate these findings.

Age-related changes in human peripapillary scleral strain

To test the hypothesis that mechanical strain in the posterior human sclera is altered with age, 20 pairs of normal eyes from human donors aged 20 to 90 years old were inflation tested within 48-h postmortem. The intact posterior scleral shells were pressurized from 5 to 45 mmHg, while the full-field three-dimensional displacements of the scleral surface were measured using laser speckle interferometry. The full strain tensor of the outer scleral surface was calculated directly from the displacement field. Mean maximum principal (tensile) strain was computed for eight circumferential sectors (

Regional Variations in Mechanical Strain in the Posterior Human Sclera

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Peripapillary Choroidal Thickness Variation With Age and Race in Normal Eyes

45∘ wide) within the peripapillary and mid-peripheral regions surrounding the optic nerve head (ONH). To estimate the age-related changes in scleral strain, results were fit using a functional mixed effects model that accounts for intradonor variability and spatial autocorrelation. Mechanical tensile strain in the peripapillary sclera is significantly higher than the strain in the sclera farther away from the ONH. Overall, strains in the peripapillary sclera decrease significantly with age. Sectorially, peripapillary scleral tensile strains in the nasal sectors are significantly higher than the temporal sectors at younger ages, but the sectorial strain pattern reverses with age, and the temporal sectors exhibited the highest tensile strains in the elderly. Overall, peripapillary scleral structural stiffness increases significantly with age. The sectorial pattern of peripapillary scleral strain reverses with age, which may predispose adjacent regions of the lamina cribrosa to biomechanical insult. The pattern and age-related changes in sectorial peripapillary scleral strain closely match those seen in disk hemorrhages and neuroretinal rim area measurement change rates reported in previous studies of normal human subjects.

Variation of Laminar Depth in Normal Eyes With Age and Race

PURPOSE We tested the hypothesis that there are age- and race-related differences in posterior scleral material properties, using eyes from human donors of European (20-90 years old, n = 40 eyes) and African (23-74 years old, n = 22 eyes) descent. METHODS Inflation tests on posterior scleral shells were performed while full-field, three-dimensional displacements were recorded using laser speckle interferometry. Scleral material properties were fit to each eye using a microstructure-based constitutive formulation that incorporates the collagen fibril crimp and the local anisotropic collagen architecture. The effects of age and race were estimated using Generalized Estimating Equations, while accounting for intradonor correlations. RESULTS The shear modulus significantly increased (P = 0.038) and collagen fibril crimp angle significantly decreased with age (P = 0.002). Donors of African descent exhibited a significantly higher shear modulus (P = 0.019) and showed evidence of a smaller collagen fibril crimp angle (P = 0.057) compared to donors of European descent. The in-plane strains in the peripapillary sclera were significantly lower with age (P < 0.015) and African ancestry (P < 0.015). CONCLUSIONS The age- and race-related differences in scleral material properties result in a loss of scleral compliance due to a higher shear stiffness and a lower level of stretch at which the collagen fibrils uncrimp. The loss of compliance should lead to larger high frequency IOP fluctuations and changes in the optic nerve head (ONH) biomechanical response in the elderly and in persons of African ancestry, and may contribute to the higher susceptibility to glaucoma in these at-risk populations.

Displacement of the Lamina Cribrosa in Response to Acute Intraocular Pressure Elevation in Normal Individuals of African and European Descent

PURPOSE The goal of this study was to establish sectorial and regional variability in the mechanical strain of peripapillary and mid-peripheral sclera in normal eyes from elderly human donors. METHODS Ten pairs of normal eyes from human donors aged 57 to 90 years old were mechanically inflation-tested within 48 hours post mortem. The intact posterior scleral shells were pressurized from 5 to 45 mm Hg while the full-field three-dimensional displacements of the scleral surface were measured using laser speckle interferometry. The displacement field was fit to continuous and differentiable analytical functions, from which the full strain tensor of the outer scleral surface was calculated. Mean maximum principal (tensile) strain was computed for eight circumferential sectors (45° wide) within the peripapillary and mid-peripheral regions surrounding the optic nerve head (ONH). RESULTS Overall, the peripapillary sclera exhibited significantly higher tensile strain (1.2%) than mid-peripheral sclera (0.95%) for a 40 mm Hg IOP elevation (P < 0.00001). In the peripapillary region, the inferotemporal sector exhibited the highest tensile strain (1.45%) while the superior sector had the lowest (1.19%; P < 0.00001). Mid-peripheral scleral strains were lower but exhibited a similar sectorial pattern. CONCLUSIONS Human posterior sclera exhibits complex regional mechanical behavior in response to acute IOP elevations from 5 to 45 mm Hg. Results indicate 1) the peripapillary sclera is subjected to significantly higher tensile strain than the adjacent mid-peripheral sclera, and 2) strains are significantly higher in the temporal and inferior quadrants of the peripapillary sclera, which may contribute to the increased prevalence of glaucomatous damage associated with these regions of the ONH.

Compensation method for obtaining accurate, sub-micrometer displacement measurements of immersed specimens using electronic speckle interferometry

PURPOSE We tested the hypothesis that the variation of peripapillary scleral structural stiffness with age is different in donors of European (ED) and African (AD) descent. METHODS Posterior scleral shells from normal eyes from donors of European (n = 20 pairs; previously reported) and African (n = 9 pairs) descent aged 0 and 90 years old were inflation tested within 48 hours post mortem. Scleral shells were pressurized from 5 to 45 mm Hg and the full-field, 3-dimensional (3D) deformation of the outer surface was recorded at submicrometric accuracy using speckle interferometry (ESPI). Mean maximum principal (tensile) strain of the peripapillary and midperipheral regions surrounding the optic nerve head (ONH) were fit using a functional mixed effects model that accounts for intradonor variability, same-race correlation, and spatial autocorrelation to estimate the effect of race on the age-related changes in mechanical scleral strain. RESULTS Mechanical tensile strain significantly decreased with age in the peripapillary sclera in the African and European descent groups (P < 0.001), but the age-related stiffening was significantly greater in the African descent group (P < 0.05). Maximum principal strain in the peripapillary sclera was significantly higher than in the midperipheral sclera for both ethnic groups. CONCLUSIONS The sclera surrounding the ONH stiffens more rapidly with age in the African descent group compared to the European group. Stiffening of the peripapillary sclera with age may be related to the higher prevalence of glaucoma in the elderly and persons of African descent.