Peripapillary Sclera Research Articles

Effects of Peripapillary Scleral Stiffening on the Deformation of the Lamina Cribrosa.

PurposeScleral stiffening has been proposed as a treatment for glaucoma to protect the lamina cribrosa (LC) from excessive intraocular pressure–induced deformation. Here we experimentally evaluated the effects of moderate stiffening of the peripapillary sclera on the deformation of the LC.MethodsAn annular sponge, saturated with 1.25% glutaraldehyde, was applied to the external surface of the peripapillary sclera for 5 minutes to stiffen the sclera. Tissue deformation was quantified in two groups of porcine eyes, using digital image correlation (DIC) or computed tomography imaging and digital volume correlation (DVC). In group A (n = 14), eyes were subjected to inflation testing before and after scleral stiffening. Digital image correlation was used to measure scleral deformation and quantify the magnitude of scleral stiffening. In group B (n = 5), the optic nerve head region was imaged using synchrotron radiation phase-contrast microcomputed tomography (PC μCT) at an isotropic spatial resolution of 3.2 μm. Digital volume correlation was used to compute the full-field three-dimensional deformation within the LC and evaluate the effects of peripapillary scleral cross-linking on LC biomechanics.ResultsOn average, scleral treatment with glutaraldehyde caused a 34 ± 14% stiffening of the peripapillary sclera measured at 17 mm Hg and a 47 ± 12% decrease in the maximum tensile strain in the LC measured at 15 mm Hg. The reduction in LC strains was not due to cross-linking of the LC.ConclusionsPeripapillary scleral stiffening is effective at reducing the magnitude of biomechanical strains within the LC. Its potential and future utilization in glaucoma axonal neuroprotection requires further investigation.

Measuring Mean Cup Depth in the Optic Nerve Head.

Since the deformation of structures in the optic nerve head (ONH) is associated with glaucoma and other diseases of the optic nerve, measurement of this deformation is of current research interest. This paper considers the computation of cup depth, a measurement of the depth of the internal limiting membrane (ILM). The computation of cup depth requires a reference structure against which to measure the ILM, and the construction of two reference structures is discussed, one based on Bruch's membrane opening (BMO) and the other based on the anterior surface of the peripapillary sclera (AS). A main focus of the paper is the robust computation of mean cup depth, which requires a good sampling of a reconstruction of the ILM surface. To evaluate our algorithm, the construction of synthetic datasets is considered.

Three-Dimensional Strains in Human Posterior Sclera Using Ultrasound Speckle Tracking.

Intraocular pressure (IOP) induced strains in the peripapillary sclera may play a role in glaucoma progression. Using inflation testing and ultrasound speckle tracking, the 3D strains in the peripapillary sclera were measured in nine human donor globes. Our results showed that the peripapillary sclera experienced through-thickness compression and meridional stretch during inflation, while minimal circumferential dilation was observed when IOP was increased from 10 to 19 mmHg. The maximum shear was primarily oriented in the through-thickness, meridional cross sections and had a magnitude slightly larger than the first principal strain. The tissue volume had minimal overall change, confirming near-incompressibility of the sclera. Substantial strain heterogeneity was present in the peripapillary region, with local high strain areas likely corresponding to structural heterogeneity caused by traversing blood vessels. These 3D strain characteristics provide new insights into the biomechanical responses of the peripapillary sclera during physiological increases of IOP. Future studies are needed to confirm these findings and investigate the role of these biomechanical characteristics in ocular diseases.

High-Magnitude and/or High-Frequency Mechanical Strain Promotes Peripapillary Scleral Myofibroblast Differentiation.

To determine the effects of altered mechanical strain on human peripapillary scleral (ppSc) fibroblast-to-myofibroblast differentiation. Eight human ppSc fibroblast cultures were isolated from three paired eyes and two unilateral eyes of five donors using an explant approach. Human ppSc fibroblast isolates were subjected to 1% and 4% cyclic strain at 0.05 to 5 Hz for 24 hours. Levels of α smooth muscle actin (αSMA) mRNA and protein were determined by real-time PCR and immunoblot. Incorporation of αSMA into actin stress fibers was evaluated by confocal immunofluorescent microscopy. Myofibroblast contractility was measured by fibroblast-populated three-dimensional collagen gel contraction assay and phosphorylation of myosin light chain (MLC20). Human ppSc fibroblasts contained 6% to 47% fully differentiated myofibroblasts before strain application; 4% cyclic strain increased αSMA mRNA and protein expression in ppSc fibroblasts compared with 1% strain applied at 5 Hz, but not at lower frequencies. Seven of eight ppSc fibroblast isolates responded to high-magnitude and high-frequency strain with increased cellular contractility and increased MLC20 phosphorylation. In addition, increasing strain frequency promoted αSMA expression in ppSc fibroblasts under both 1% and 4% strain conditions. High-magnitude and/or high-frequency mechanical strain promotes differentiation of human ppSc fibroblasts into contractile myofibroblasts, a fibroblast phenotypic change known to be key to tissue injury-repair responses. These findings suggest that the cellular constituent of ppSc may play an important role in the regulation of optic nerve head biomechanics in response to injurious IOP fluctuations.

Expansions of the neurovascular scleral canal and contained optic nerve occur early in the hypertonic saline rat experimental glaucoma model

PurposeTo characterize early optic nerve head (ONH) structural change in rat experimental glaucoma (EG). MethodsUnilateral intraocular pressure (IOP) elevation was induced in Brown Norway rats by hypertonic saline injection into the episcleral veins and animals were sacrificed 4 weeks later by perfusion fixation. Optic nerve cross-sections were graded from 1 (normal) to 5 (extensive injury) by 5 masked observers. ONHs with peripapillary retina and sclera were embedded, serial sectioned, 3-D reconstructed, delineated, and quantified. Overall and animal-specific EG versus Control eye ONH parameter differences were assessed globally and regionally by linear mixed effect models with significance criteria adjusted for multiple comparisons. ResultsExpansions of the optic nerve and surrounding anterior scleral canal opening achieved statistical significance overall (p < 0.0022), and in 7 of 8 EG eyes (p < 0.005). In at least 5 EG eyes, significant expansions (p < 0.005) in Bruch's membrane opening (BMO) (range 3–10%), the anterior and posterior scleral canal openings (8–21% and 5–21%, respectively), and the optic nerve at the anterior and posterior scleral canal openings (11–30% and 8–41%, respectively) were detected. Optic nerve expansion was greatest within the superior and inferior quadrants. Optic nerve expansion at the posterior scleral canal opening was significantly correlated to optic nerve damage (R = 0.768, p = 0.042). ConclusionIn the rat ONH, the optic nerve and surrounding BMO and neurovascular scleral canal expand early in their response to chronic experimental IOP elevation. These findings provide phenotypic landmarks and imaging targets for detecting the development of experimental glaucomatous optic neuropathy in the rat eye.

Quantitative analysis of three-dimensional fibrillar collagen microstructure within the normal, aged and glaucomatous human optic nerve head.

The aim of this study was to quantify connective tissue fibre orientation and alignment in young, old and glaucomatous human optic nerve heads (ONH) to understand ONH microstructure and predisposition to glaucomatous optic neuropathy. Transverse (seven healthy, three glaucomatous) and longitudinal (14 healthy) human ONH cryosections were imaged by both second harmonic generation microscopy and small angle light scattering (SALS) in order to quantify preferred fibre orientation (PFO) and degree of fibre alignment (DOFA). DOFA was highest within the peripapillary sclera (ppsclera), with relatively low values in the lamina cribrosa (LC). Elderly ppsclera DOFA was higher than that in young ppsclera (p < 0.00007), and generally higher than in glaucoma ppsclera. In all LCs, a majority of fibres had preferential orientation horizontally across the nasal–temporal axis. In all glaucomatous LCs, PFO was significantly different from controls in a minimum of seven out of 12 LC regions (p < 0.05). Additionally, higher fibre alignment was observed in the glaucomatous inferior–temporal LC (p < 0.017). The differences between young and elderly ONH fibre alignment within regions suggest that age-related microstructural changes occur within the structure. The additional differences in fibre alignment observed within the glaucomatous LC may reflect an inherent susceptibility to glaucomatous optic neuropathy, or may be a consequence of ONH remodelling and/or collapse.

A Novel Mgp-Cre Knock-In Mouse Reveals an Anticalcification/Antistiffness Candidate Gene in the Trabecular Meshwork and Peripapillary Scleral Region.

Soft tissue calcification is a pathological condition. Matrix Gla (MGP) is a potent mineralization inhibitor secreted by cartilage chondrocytes and arteries' vascular smooth muscle cells. Mgp knock-out mice die at 6 weeks due to massive arterial calcification. Arterial calcification results in arterial stiffness and higher systolic blood pressure. Intriguingly, MGP was highly abundant in trabecular meshwork (TM). Because tissue stiffness is relevant to glaucoma, we investigated which additional eye tissues use Mgp's function using knock-in mice. An Mgp-Cre-recombinase coding sequence (Cre) knock-in mouse, containing Mgp DNA plus an internal ribosomal entry site (IRES)-Cre-cassette was generated by homologous recombination. Founders were crossed with Cre-mediated reporter mouse R26R-lacZ. Their offspring expresses lacZ where Mgp is transcribed. Eyes from MgpCre/+;R26RlacZ/+ (Mgp-lacZ knock-in) and controls, 1 to 8 months were assayed for β-gal enzyme histochemistry. As expected, Mgp-lacZ knock-in's TM was intensely blue. In addition, this mouse revealed high specific expression in the sclera, particularly in the peripapillary scleral region (ppSC). Ciliary muscle and sclera above the TM were also positive. Scleral staining was located immediately underneath the choroid (chondrocyte layer), began midsclera and was remarkably high in the ppSC. Cornea, iris, lens, ciliary body, and retina were negative. All mice exhibited similar staining patterns. All controls were negative. Matrix Gla's restricted expression to glaucoma-associated tissues from anterior and posterior segments suggests its involvement in the development of the disease. Matrix Gla's anticalcification/antistiffness properties in the vascular tissue, together with its high TM and ppCS expression, place this gene as a strong candidate for TM's softness and sclera's stiffness regulation in glaucoma.

Collagen microstructural factors influencing optic nerve head biomechanics.

Previous studies have suggested that the lamina cribrosa (LC) and its surrounding sclera are biomechanically important in the pathogenesis of glaucoma, but many were limited by assumptions of tissue isotropy and homogeneity. Here, we used an improved biomechanical model driven by experimental measurements of scleral and LC collagen fiber organization to more accurately evaluate optic nerve head (ONH) biomechanics. Collagen fiber organization was quantitatively mapped across human ONH cryosections (three normal and three glaucomatous) using small-angle light scattering (SALS) and fed into two-dimensional finite element models loaded under biaxial stress to simulate raised intraocular pressure. Effects of artificial variations in collagen fiber microstructure and stiffness on LC and scleral strains were also investigated. Scleral collagen fibers were circumferential and exhibited the highest alignment in a region not immediately adjacent to, but at a distance (400-500 μm) away from, the LC. In models, such a fiber arrangement yielded rings of low strain (second principal and effective) in the scleral region immediately adjacent to the LC. Further sensitivity analyses showed that scleral fiber alignment was crucial in determining LC strain levels. Moderate scleral anisotropy (as observed physiologically) was more effective than isotropy or high anisotropy in limiting LC and scleral strain magnitude. The presence of a heterogeneous collagen fiber organization in the peripapillary sclera appears effective in limiting LC strain and is able to reduce strain levels at the scleral canal boundary: a transition zone prone to LC disinsertion, focal lamina cribrosa defects, and optic disc hemorrhages in glaucoma.

Depth-dependent changes in collagen organization in the human peripapillary sclera.

PurposeThe collagen structure of the human peripapillary sclera plays a significant role in determining optic nerve head (ONH) biomechanics, and is therefore of interest in the study of glaucoma. The aim of the current work was to map the anisotropic collagen structure of the normal human peripapillary sclera as a function of tissue depth.MethodsWide-angle x-ray scattering was used to quantify collagen fibril orientation at 0.5mm intervals across six 150μm-thick serial sections through the peripapillary sclera of eight normal European-derived human eyes. Two structural parameters were measured: 1) the relative number of fibrils preferentially aligned at a given angle within the tissue plane, 2) the degree of collagen alignment (anisotropy).ResultsThe inner-most one-third of the peripapillary scleral stroma (nearest to the choroid) was characterised by collagen fibrils either randomly arranged or preferentially aligned radially with respect to the ONH. In contrast, the outer two-thirds of the tissue was dominated by a circumferential arrangement of collagen encircling the ONH. In all tissue regions the degree of collagen anisotropy peaked in the mid-stroma and progressively decreased towards the tissue surfaces, with the largest depth variations occurring in the inferior-nasal quadrant, and the smallest occurring in the superior-nasal quadrant.ConclusionsSignificant, region-specific variations in collagen structure are present in the human peripapillary sclera as a function of depth. In normal eyes, the circumferential collagen fibril architecture is most prominent in the outer two-thirds of the stroma, possibly as a mechanical adaption to more effectively support the lamina cribrosa at the level of its insertion into the scleral canal wall.

Collagen structure and mechanical properties of the human sclera: analysis for the effects of age.

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).

A Novel Mgp -Cre Knock-In Mouse Reveals an Anticalcification/Antistiffness Candidate Gene in the Trabecular Meshwork and Peripapillary Scleral Region

A Novel Mgp -Cre Knock-In Mouse Reveals an Anticalcification/Antistiffness Candidate Gene in the Trabecular Meshwork and Peripapillary Scleral Region

Age- and race-related differences in human scleral material properties.

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. 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. 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). 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.

Peripapillary Rat Sclera Investigated In Vivo With Polarization-Sensitive Optical Coherence Tomography

To demonstrate polarization-sensitive (PS) optical coherence tomography (OCT) for noninvasive, volumetric, and quantitative imaging of the birefringent properties of the peripapillary rat sclera; to compare the findings from PS-OCT images to state-of-the-art histomorphometric analysis of the same tissues. A high-speed PS-OCT prototype operating at 840 nm was modified for imaging the rat eye. Densely sampled PS-OCT raster scans covering an area of ~1.5 × 1.5 mm centered at the papilla were acquired in the eyes of anesthetized male Sprague-Dawley rats. Cross-sectional PS-OCT images were computed, and fundus maps displaying the birefringent properties of the sclera were analyzed. Postmortem histomorphologic analysis was performed. Polarization-sensitive OCT enables visualization of the polarization properties of ocular tissues in vivo. The birefringent characteristics of the rat sclera were quantitatively assessed. Scleral birefringence formed a donut-shaped pattern around the papilla with significantly increased values of 0.703 ± 0.089°/μm (i.e., 1.64 × 10(-3) ± 0.2 × 10(-3); mean ± standard deviation) and 0.721 ± 0.084°/μm (i.e., 1.68 × 10(-3) ± 0.2 × 10(-3)) at an eccentricity of 0.4 mm for the left and right eyes, respectively. Birefringent axis orientation maps revealed a ring-shaped distribution around the optic nerve. Postmortem PS-OCT micrographs provided access to retinal and scleral microstructure and were compared to standard histomorphologic analysis. Polarization-sensitive OCT enables quantitative imaging of tissue polarization properties in addition to conventional OCT imaging based on reflectivity. In the rat sclera, in vivo PS-OCT provides access to volumetric mapping of birefringence. Scleral birefringence is associated with microstructural tissue organization. Therefore, PS-OCT should prove a valuable tool for the in vivo investigation of peripapillary sclera in glaucoma.

Changes in scleral collagen organization in murine chronic experimental glaucoma.

The organization of scleral collagen helps to determine the eye's biomechanical response to intraocular pressure (IOP), and may therefore be important in glaucoma. This study provides a quantitative assessment of changes in scleral collagen fibril organization in bead-induced murine experimental glaucoma. Wide-angle X-ray scattering was used to study the effect of bead-induced glaucoma on posterior scleral collagen organization in one eye of 12 CD1 mice, with untreated fellow eyes serving as controls. Three collagen parameters were measured: the local preferred fibril directions, the degree of collagen anisotropy, and the total fibrillar collagen content. The mouse sclera featured a largely circumferential orientation of fibrillar collagen with respect to the optic nerve head canal. Localized alteration to fibril orientations was evident in the inferior peripapillary sclera of bead-treated eyes. Collagen anisotropy was significantly (P<0.05) reduced in bead-treated eyes in the superior peripapillary (Treated: 43±8%; 49±6%) and midposterior (Treated: 39±4%; 43±4%) sclera, and in the peripapillary region overall (Treated: 43±6%; 47±3%). No significant differences in total collagen content were found between groups. Spatial changes in collagen fibril anisotropy occur in the posterior sclera of mice with bead-induced chronic IOP elevation and axonal damage. These results support the idea that dynamic changes in scleral form and structure play a role in the development of experimental glaucoma in mice, and potentially in human glaucoma.

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

This study explores variation in the axial location of Bruch's membrane opening (BMO) to determine if this reference plane varies with age and race. 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 Bruch's 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. 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. Bruch's 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. Bruch's 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.

Sequential-Digital Image Correlation for Mapping Human Posterior Sclera and Optic Nerve Head Deformation

Optic nerve head (ONH) deformations may be involved in the onset or further development of glaucoma, including in patients with relatively normal intraocular pressures (IOPs). Characterizing posterior scleral deformations over physiological pressures may provide a better understanding of how changes in IOP lead to changes in the mechanical environment of the ONH and possibly retinal ganglion cell death. Pressure inflation measurement test protocols are commonly used to measure deformation of the peripapillary sclera with full-field noncontact optical methods. The purpose of this work was to develop and validate a new sequential 3D digital image correlation (S-DIC) approach for quantification of posterior scleral pressure induced deformation that improves z (in-depth) resolution of the DIC measurement without losing in-plane sensitivity, while also being able to contour and map deformations of the complex-shaped ONH. Our approach combines two orthogonal axes of parallax with standard 3D DIC methods using a single high-resolution camera. The enhanced capabilities of S-DIC with respect to standard 3D DIC has been demonstrated by carrying out a complete benchmark for shape, deformation, and strain measurement on an object of known complex geometry. Our S-DIC method provided a reconstruction accuracy of 0.17% and an uncertainty in z-position measurement of 8 μm. The developed methodology has also been applied to a human posterior scleral shell, including the full peripapillary sclera and optic nerve. The relatively inexpensive S-DIC approach may provide new information on the biomechanical deformations of the optic nerve head and, thus, the death of retinal ganglion cells in primary open angle glaucoma.

Evaluation of Congenital Optic Disc Pits and Optic Disc Colobomas by Swept-Source Optical Coherence Tomography

To investigate the structural abnormalities of optic disc pits and colobomas by swept-source optical coherence tomography (OCT). Sixteen eyes with congenital optic disc pits, and seven eyes with optic disc colobomas were studied. Papillary and peripapillary areas were examined with swept-source OCT. The entire course of the pit or cavity and the spatial relationship between pits and retrobulbar subarachnoid space (SAS) were examined. Optical coherence tomography images showed the entire course of the pits from their openings to the bottom in 12 eyes. Shape of optic disc pits varied from sharp triangular cavities to longitudinally oval according to the depth of the pits. In the other four eyes, the pit narrowed into a tunnel along the optic nerve. The entire area of the optic disc was observed in three of seven eyes with disc coloboma by OCT. In all of the eyes with optic disc pits, the lamina cribrosa was torn off of the peripapillary sclera at the site of the pits. In two cases with optic disc pits and one case with optic disc coloboma, Optical coherence tomography showed SAS immediately posterior to the highly reflective tissue lining the bottom of the excavation. The distance between the intraocular cavity and SAS in these three cases were 88, 126, and 133 μm. Swept-source OCT is able to detect different kinds of abnormalities including shape of cavities, defect of lamina cribrosa, or distance to SAS in the excavated optic discs anomalies.

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 (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.

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.

Peripapillary Scleral Deformation and Retinal Nerve Fiber Damage in High Myopia Assessed With Swept-Source Optical Coherence Tomography

To study peripapillary morphologic changes in highly myopic eyes using swept-source optical coherence tomography at a longer wavelength. Prospective cross-sectional study. Peripapillary regions of 196 eyes of 107 patients with high myopia (refractive error, <-8.0 diopters or axial length, >26.0 mm) were analyzed quantitatively and qualitatively with an swept-source optical coherence tomography prototype system that uses a tunable laser light source operated at a 100,000-Hz A-scan repetition rate in the 1-μm wavelength region. The visual field was evaluated by standard automated perimetry. Area of peripapillary atrophy β and presence of scleral protrusion temporal to the optic disc were assessed. Peripapillary atrophy β area, but not disc area, was significantly larger in eyes with visual field defect (3.16 ± 2.70 mm(2); range, 0.00 to 12.85 mm(2)) than those without visual field defect (2.31 ± 2.83 mm(2); range, 0.00 to 17.70 mm(2)). Temporal scleral protrusion was detected by color stereo disc photography in 22 (19.5%) of 113 eyes with visual field defect and in 4 (4.8%) of 83 eyes without visual field defect. Scleral bending demonstrated a wide range of angles (mean, 31.0 ± 21.1 degrees; range, 2 to 80 degrees). The angle of scleral bending, but not the distances from scleral bend to disc margin or foveal center, correlated significantly with retinal nerve fiber layer thickness above the bend (r = -0.557, P = .007) and visual field defect severity (r = -0.445, P = .038). Swept-source optical coherence tomography visualizes peripapillary deep structures in high myopia. Some cases of high myopia may be affected by direct scleral compression or stretching at the peripapillary region.