Optic Nerve Head Biomechanics Research Articles

Comparing continuum and direct fiber models of soft tissues: An ocular biomechanics example reveals that continuum models may artificially disrupt the strains at both the tissue and fiber levels

Collagen fibers are the main load-bearing component of soft tissues but difficult to incorporate into models. Whilst simplified homogenization models suffice for some applications, a thorough mechanistic understanding requires accurate prediction of fiber behavior, including both detailed fiber-level strains and long-distance transmission. Our goal was to compare the performance of a continuum model of the optic nerve head (ONH) built using conventional techniques with a fiber model we recently introduced which explicitly incorporates the complex 3D organization and interaction of collagen fiber bundles [1]. To ensure a fair comparison, we constructed the continuum model with identical geometrical, structural, and boundary specifications as for the fiber model. We found that: 1) although both models accurately matched the intraocular pressure (IOP)-induced globally averaged displacement responses observed in experiments, they diverged significantly in their ability to replicate specific 3D tissue-level strain patterns. Notably, the fiber model faithfully replicated the experimentally observed depth-dependent variability of radial strain, the ring-like pattern of meridional strain, and the radial pattern of circumferential strain, whereas the continuum model failed to do so; 2) the continuum model disrupted the strain transmission along each fiber, a feature captured well by the fiber model. These results demonstrate limitations of the conventional continuum models that rely on homogenization and affine deformation assumptions, which render them incapable of capturing some complex tissue-level and fiber-level deformations. Our results show that the strengths of explicit fiber modeling help capture intricate ONH biomechanics. They potentially also help modeling other fibrous tissues. Statement of SignificanceUnderstanding the mechanics of fibrous tissues is crucial for advancing knowledge of various diseases. This study uses the ONH as a test case to compare conventional continuum models with fiber models that explicitly account for the complex fiber structure. We found that the fiber model captured better the biomechanical behaviors at both the tissue level and the fiber level. The insights gained from this study demonstrate the significant potential of fiber models to advance our understanding of not only glaucoma pathophysiology but also other conditions involving fibrous soft tissues. This can contribute to the development of therapeutic strategies across a wide range of applications.

Comparing continuum and direct fiber models of soft tissues. An ocular biomechanics example reveals that continuum models may artificially disrupt the strains at both the tissue and fiber levels.

Collagen fibers are the main load-bearing component of soft tissues but difficult to incorporate into models. Whilst simplified homogenization models suffice for some applications, a thorough mechanistic understanding requires accurate prediction of fiber behavior, including both detailed fiber-level strains and long-distance transmission. Our goal was to compare the performance of a continuum model of the optic nerve head (ONH) built using conventional techniques with a fiber model we recently introduced which explicitly incorporates the complex 3D organization and interaction of collagen fiber bundles [1]. To ensure a fair comparison, we constructed the continuum model with identical geometrical, structural, and boundary specifications as for the fiber model. We found that: 1) although both models accurately matched the intraocular pressure (IOP)-induced globally averaged displacement responses observed in experiments, they diverged significantly in their ability to replicate specific 3D tissue-level strain patterns. Notably, the fiber model faithfully replicated the experimentally observed depth-dependent variability of radial strain, the ring-like pattern of meridional strain, and the radial pattern of circumferential strain, whereas the continuum model failed to do so; 2) the continuum model disrupted the strain transmission along each fiber, a feature captured well by the fiber model. These results demonstrate limitations of the conventional continuum models that rely on homogenization and affine deformation assumptions, which render them incapable of capturing some complex tissue-level and fiber-level deformations. Our results show that the strengths of explicit fiber modeling help capture intricate ONH biomechanics. They potentially also help modeling other fibrous tissues.

Fibrous finite element modeling of the optic nerve head region

The optic nerve head (ONH) region at the posterior pole of the eye is supported by a fibrous structure of collagen fiber bundles. Discerning how the fibrous structure determines the region biomechanics is crucial to understand normal physiology, and the roles of biomechanics on vision loss. The fiber bundles within the ONH structure exhibit complex three-dimensional (3D) organization and continuity across the various tissue components. Computational models of the ONH, however, usually represent collagen fibers in a homogenized fashion without accounting for their continuity across tissues, fibers interacting with each other and other fiber-specific effects in a fibrous structure. We present a fibrous finite element (FFE) model of the ONH that incorporates discrete collagen fiber bundles and their histology-based 3D organization to study ONH biomechanics as a fibrous structure. The FFE model was constructed using polarized light microscopy data of porcine ONH cryosections, representing individual fiber bundles in the sclera, dura and pia maters with beam elements and canal tissues as continuum structures. The FFE model mimics the histological in-plane orientation and width distributions of collagen bundles as well as their continuity across different tissues. Modeling the fiber bundles as linear materials, the FFE model predicts the nonlinear ONH response observed in an inflation experiment from the literature. The model also captures important microstructural mechanisms including fiber interactions and long-range strain transmission among bundles that have not been considered before. The FFE model presented here advances our understanding of the role of fibrous collagen structure in the ONH biomechanics. Statement of SignificanceThe microstructure and mechanics of the optic nerve head (ONH) are central to ocular physiology. Histologically, the ONH region exhibits a complex continuous fibrous structure of collagen bundles. Understanding the role of the fibrous collagen structure on ONH biomechanics requires high-fidelity computational models previously unavailable. We present a computational model of the ONH that incorporates histology-based fibrous collagen structure derived from polarized light microscopy images. The model predictions agree with experiments in the literature, and provide insight into important microstructural mechanisms of fibrous tissue biomechanics, such as long-range strain transmission along fiber bundles. Our model can be used to study the microstructural basis of biomechanical damage and the effects of collagen remodeling in glaucoma.

Computational study on the effects of central retinal blood vessels with asymmetric geometries on optic nerve head biomechanics

Optic nerve head (ONH) biomechanics are associated with glaucoma progression and have received considerable attention. Central retinal vessels (CRVs) oriented asymmetrically in the ONH are the single blood supply source to the retina and are believed to act as mechanically stable elements in the ONH in response to intraocular pressure (IOP). However, these mechanical effects are considered negligible in ONH biomechanical studies and received less attention. This study investigated the effects of CRVs on ONH biomechanics taking into consideration three-dimensional asymmetric CRV geometries. A CRV geometry was constructed based on CRV centerlines extracted from optical coherence tomography ONH images in eight healthy subjects and superimposed in the idealized ONH geometry established in previous studies. Mechanical analyses of the ONH in response to the IOP were conducted in the cases with and without CRVs for comparison. Obtained results demonstrated that the CRVs induced anisotropic ONH deformation, particularly in the lamina cribrosa and the associated upper neural tissues (prelamina) with wide ranges of spatial strain distributions. These results indicated that the CRVs result in anisotropic deformation with local strain concentration, rather than function to mechanically support in response to the IOP as in the conventional thinking in ophthalmology.

The impact of horizontal eye movements versus intraocular pressure on optic nerve head biomechanics: A tridimensional finite element analysis study

It has been proposed that eye movements could be related to glaucoma development. This research aimed to compare the impact of intraocular pressure (IOP) versus horizontal duction on optic nerve head (ONH) strains. Thus, a tridimensional finite element model of the eye including the three tunics of the eye, all of the meninges, and the subarachnoid space (SAS) was developed using a series of medical tests and anatomical data. The ONH was divided into 22 subregions, and the model was subjected to 21 different eye pressures, as well as 24 different degrees of adduction and abduction ranging from 0.5° to 12°. Mean deformations were documented along anatomical axes and in principal directions. Additionally, the impact of tissue stiffness was assessed. The results show no statistically significant differences between the lamina cribrosa (LC) strains due to eye rotation and IOP variation. However, when assessing LC regions some experienced a reduction in principal strains following a 12° duction, while after the IOP reached 12 mmHg, all LC subzones showed an increase in strains. From an anatomical perspective, the effect on the ONH following 12° duction was opposite to that observed after a rise in IOP. Moreover, high strain dispersion inside the ONH subregions was obtained with lateral eye movements, which was not observed with increased IOP and variation. Finally, SAS and orbital fat stiffness strongly influenced ONH strains during eye movements, while SAS stiffness was also influential under ocular hypertension. Even if horizontal eye movements cause large ONH deformations, their biomechanical effect would be markedly distinct from that induced by IOP. It could be predicted that, at least in physiological conditions, their potential to cause axonal injury would not be so relevant. Thus, a causative role in glaucoma does not appear likely. By contrast, an important role of SAS would be expectable.

Relative Contributions of Intraocular and Cerebrospinal Fluid Pressures to the Biomechanics of the Lamina Cribrosa and Laminar Neural Tissues.

PurposeThe laminar region of the optic nerve head (ONH), thought to be the site of damage to the retinal ganglion cell axons in glaucoma, is continuously loaded on its anterior and posterior surfaces by dynamic intraocular pressure (IOP) and orbital cerebrospinal fluid pressure (CSFP), respectively. Thus, translaminar pressure (TLP; TLP = IOP-CSFP) has been proposed as a glaucoma risk factor.MethodsThree eye-specific finite element models of the posterior human eye were constructed, including full 3D microstructures of the load-bearing lamina cribrosa (LC) with interspersed laminar neural tissues (NTs), and heterogeneous, anisotropic, hyperelastic material formulations for the surrounding peripapillary sclera and adjacent pia. ONH biomechanical responses were simulated using three combinations of IOP and CSFP loadings consistent with posture change from sitting to supine.ResultsResults show that tensile, compressive, and shear stresses and strains in the ONH were higher in the supine position compared to the sitting position (P < 0.05). In addition, LC beams bear three to five times more TLP-driven stress than interspersed laminar NT, whereas laminar NT exhibit three to five times greater strain than supporting LC (P < 0.05). Compared with CSFP, IOP drove approximately four times greater stress and strain in the LC, NT, and peripapillary sclera, normalized per mm Hg pressure change. In addition, IOP drove approximately three-fold greater scleral canal expansion and anterior-posterior laminar deformation than CSFP per mm Hg (P < 0.05).ConclusionsWhereas TLP has been hypothesized to play a prominent role in ONH biomechanics, the IOP and CSFP effects are not equivalent, as IOP-driven stress, strain, and deformation play a more dominant role than CSFP effects.

Society Awards 2021.

Society Awards 2021.

A high-accuracy and high-efficiency digital volume correlation method to characterize in-vivo optic nerve head biomechanics from optical coherence tomography

In-vivo optic nerve head (ONH) biomechanics characterization is emerging as a promising way to study eye physiology and pathology. We propose a high-accuracy and high-efficiency digital volume correlation (DVC) method to characterize the in-vivo ONH deformation from optical coherence tomography (OCT) volumes. Using a combination of synthetic tests and analysis of OCTs from monkey ONHs subjected to acutely elevated intraocular pressure, we demonstrate that our proposed methodology overcame several challenges for conventional DVC methods: First, a pre-registration technique was used to remove large ONH rigid body motion in OCT volumes which could lead to analysis failure; second, a modified 3D inverse-compositional Gaussian Newton method was used to ensure sub-voxel accuracy of displacement calculations despite high noise and low image contrast of some OCT volumes; third, a tricubic B-spline interpolation method was applied to improve computational efficiency; fourth, a confidence parameter was introduced to guide the searching path in the displacement calculation; fifth, a confidence-weighted strain calculation method was applied to further improve the accuracy. The proposed DVC method had displacement errors smaller than 0.037 and 0.028 voxels with Gaussian and speckle noises, respectively. The strain errors in the three directions were less than 0.0045 and 0.0018 with Gaussian and speckle noises, respectively. Compared with the conventional DVC method, the proposed method reduced the errors of displacement and strain calculations by up to 70% under large body motions, with 75% lower computation time, while saving about 30% memory. Our study demonstrates the potential of the proposed technique to investigate ONH biomechanics. Statement of significanceThe biomechanics of the optic nerve head (ONH) in the posterior pole of the globe play a central role in eye physiology and pathology. The application of digital volume correlation (DVC) to the analysis of optical coherence tomography (OCT) images of the ONH has emerged as a promising way to quantify ONH biomechanics. Conventional DVC methods, however, face several important challenges when analyzing OCT images of the ONH. We introduce a high-accuracy and high-efficiency DVC method to characterize in vivo ONH deformations from OCT volumes. We demonstrate the new method using synthetic tests and actual OCT data from monkey ONHs. The new method also has the potential to be used to study other tissues, as OCT applications continue to expand.

Real-time imaging of optic nerve head collagen microstructure and biomechanics using instant polarized light microscopy

Current tools lack the temporal or spatial resolution necessary to image many important aspects of the architecture and dynamics of the optic nerve head (ONH). We evaluated the potential of instant polarized light microscopy (IPOL) to overcome these limitations by leveraging the ability to capture collagen fiber orientation and density in a single image. Coronal sections through the ONH of fresh normal sheep eyes were imaged using IPOL while they were stretched using custom uniaxial or biaxial micro-stretch devices. IPOL allows identifying ONH collagen architectural details, such as fiber interweaving and crimp, and has high temporal resolution, limited only by the frame rate of the camera. Local collagen fiber orientations and deformations were quantified using color analysis and image tracking techniques. We quantified stretch-induced collagen uncrimping of lamina cribrosa (LC) and peripapillary sclera (PPS), and changes in LC pore size (area) and shape (convexity and aspect ratio). The simultaneous high spatial and temporal resolutions of IPOL revealed complex ONH biomechanics: i) stretch-induced local deformation of the PPS was nonlinear and nonaffine. ii) under load the crimped collagen fibers in the PPS and LC straightened, without torsion and with only small rotations. iii) stretch-induced LC pore deformation was anisotropic and heterogeneous among pores. Overall, with stretch the pores were became larger, more convex, and more circular. We have demonstrated that IPOL reveals details of collagen morphology and mechanics under dynamic loading previously out of reach. IPOL can detect stretch-induced collagen uncrimping and other elements of the tissue nonlinear mechanical behavior. IPOL showed changes in pore morphology and collagen architecture that will help improve understanding of how LC tissue responds to load.

Assessment of the viscoelastic mechanical properties of the porcine optic nerve head using micromechanical testing and finite element modeling

Optic nerve head (ONH) biomechanics is centrally involved in the pathogenesis of glaucoma, a blinding ocular condition often characterized by elevation and fluctuation of the intraocular pressure and resulting loads on the ONH. Further, tissue viscoelasticity is expected to strongly influence the mechanical response of the ONH to mechanical loading, yet the viscoelastic mechanical properties of the ONH remain unknown. To determine these properties, we conducted micromechanical testing on porcine ONH tissue samples, coupled with finite element modeling based on a mixture model consisting of a biphasic material with a viscoelastic solid matrix. Our results provide a detailed description of the viscoelastic properties of the porcine ONH at each of its four anatomical quadrants (i.e., nasal, superior, temporal, and inferior). We showed that the ONH's viscoelastic mechanical response can be explained by a dual mechanism of fluid flow and solid matrix viscoelasticity, as is common in other soft tissues. We obtained porcine ONH properties as follows: matrix Young's modulus E=1.895[1.056,2.391] kPa (median [min., max.]), Poisson's ratio ν=0.142[0.060,0.312], kinetic time-constant τ=214[89,921] sec, and hydraulic permeability k=3.854×10−1[3.457×10−2,9.994×10−1] mm4/(N.sec). These values can be used to design and fabricate physiologically appropriate ex vivo test environments (e.g., 3D cell culture) to further understand glaucoma pathophysiology. Statement of significanceOptic nerve head (ONH) biomechanics is an important aspect of the pathogenesis of glaucoma, the leading cause of irreversible blindness. The ONH experiences time-varying loads, yet the viscoelastic behavior of this tissue has not been characterized. Here, we measure the time-dependent response of the ONH in porcine eyes and use mechanical modeling to provide time-dependent mechanical properties of the ONH. This information allows us to identify time-varying stimuli in vivo which have timescales matching the characteristic response times of the ONH, and can also be used to design and fabricate ex vivo 3D cultures to study glaucoma pathophysiology in a physiologically relevant environment, enabling the discovery of new generations of glaucoma medications focusing on neuroprotection.

Effects of glaucoma and central corneal thickness on optic nerve head biomechanics.

To evaluate effects of glaucoma and central corneal thickness (CCT) on optic nerve head biomechanics. Four groups were formed according to CCT measurements and the presence of glaucoma. Glaucomatous patients with thin (< 510µ) and thick (> 570µ) corneas composed groups 1 and 3, respectively. Nonglaucomatous patients with thin and thick corneas composed groups 2 and 4, respectively. Real-time elastography (RTE) was performed on all groups, and optic nerve strain rate (ONSR), orbital fat strain rate (OFSR), and strain ratio of orbital fat to the optic nerve and medial and lateral parts of the optic nerve (SROFON, SROFMON, SROFLON, respectively) were obtained and compared between groups. The correlations between CCT and these parameters were also investigated. Statistically significant difference was not found between groups in terms of strain rate of optic nerve and orbital fat, SRFON, SROFMON and SROFLON. There was a positive correlation between ONSR and OFSR and mean CCT in patients with CCT thinner than 510µ (p: 0.03 r: 0.26, p: 0.01 r: 0.32 respectively). SROFON, SROFLON and SROFMON values did not differ between glaucomatous and nonglaucomatous patients with thin or thick CCTs. The correlations between CCT and OFSR and ONSR were found to be statistically significant in patients with thin CCT.

Individual-Specific Modeling of Rat Optic Nerve Head Biomechanics in Glaucoma.

Glaucoma is the second leading cause of blindness worldwide and is characterized by the death of retinal ganglion cells (RGCs), the cells that send vision information to the brain. Their axons exit the eye at the optic nerve head (ONH), the main site of damage in glaucoma. The importance of biomechanics in glaucoma is indicated by the fact that elevated intraocular pressure (IOP) is a causative risk factor for the disease. However, exactly how biomechanical insult leads to RGC death is not understood. Although rat models are widely used to study glaucoma, their ONH biomechanics have not been characterized in depth. Therefore, we aimed to do so through finite element (FE) modeling. Utilizing our previously described method, we constructed and analyzed ONH models with individual-specific geometry in which the sclera was modeled as a matrix reinforced with collagen fibers. We developed eight sets of scleral material parameters based on results from our previous inverse FE study and used them to simulate the effects of elevated IOP in eight model variants of each of seven rat ONHs. Within the optic nerve, highest strains were seen inferiorly, a pattern that was consistent across model geometries and model variants. In addition, changing the collagen fiber direction to be circumferential within the peripapillary sclera resulted in more pronounced decreases in strain than changing scleral stiffness. The results from this study can be used to interpret data from rat glaucoma studies to learn more about how biomechanics affects RGC pathogenesis in glaucoma.

Role of radially aligned scleral collagen fibers in optic nerve head biomechanics

Collagen fibers organized circumferentially around the canal in the peripapillary sclera are thought to provide biomechanical support to the sensitive tissues within the optic nerve head (ONH). Recent studies have demonstrated the existence of a family of fibers in the innermost sclera organized radially from the scleral canal. Our goal was to determine the role of these radial fibers in the sensitivity of scleral canal biomechanics to acute increases in intraocular pressure (IOP). Following the same general approach of previous parametric sensitivity studies, we created nonlinear generic finite element models of a posterior pole with various combinations of radial and circumferential fibers at an IOP of 0 mmHg. We then simulated the effects of normal and elevated IOP levels (15 and 30 mmHg). We monitored four IOP-induced geometric changes: peripapillary sclera stretch, scleral canal displacement, lamina cribrosa displacement, and scleral canal expansion. In addition, we examined the radial (maximum tension) and through-thickness (maximum compression) strains within the ONH tissues. Our models predicted that: 1) radial fibers reduced the posterior displacement of the lamina, especially at elevated IOP; 2) radial fibers reduced IOP-induced radial strain within the peripapillary sclera and retinal tissue; and 3) a combination of radial and circumferential fibers maintained strains within the ONH at a level similar to those conferred by circumferential fibers alone. In conclusion, radial fibers provide support for the posterior globe, additional to that provided by circumferential fibers. Most importantly, a combination of both fiber families can better protect ONH tissues from excessive IOP-induced deformation than either alone.

Finite element analysis of trans-lamina cribrosa pressure difference on optic nerve head biomechanics: the Beijing Intracranial and Intraocular Pressure Study.

The present study aims to assess the potential difference of biomechanical response of the optic nerve head to the same level of trans-lamina cribrosa pressure difference (TLCPD) induced by a reduced cerebrospinal fluid pressure (CSFP) or an elevated intraocular pressure (IOP). A finite element model of optic nerve head tissue (pre- and post-laminar neural tissue, lamina cribrosa, sclera, and pia mater) was constructed. Computed stresses, deformations, and strains were compared at each TLCPD step caused by reduced CSFP or elevated IOP. The results showed that elevating TLCPD increased the strain in optic nerve head, with the largest strains occurring in the neural tissue around the sclera ring. Relative to a baseline TLCPD of 10 mmHg, at a same TLCPD of 18 mmHg, the pre-laminar neural tissue experienced 11.10% first principal strain by reduced CSFP and 13.66% by elevated IOP, respectively. The corresponding values for lamina cribrosa were 6.09% and 6.91%. In conclusion, TLCPD has a significant biomechanical impact on optic nerve head tissue and, more prominently, within the pre-laminar neural tissue and lamina cribrosa. Comparatively, reducing CSFP showed smaller strain than elevating IOP even at a same level of TLCPD on ONH tissue, indicating a different potential role of low CSFP in the pathogenesis of glaucoma.

Factors affecting optic nerve head biomechanics in a rat model of glaucoma.

Glaucoma is the leading cause of irreversible blindness and is characterized by the death of retinal ganglion cells, which carry vision information from the retina to the brain. Although it is well accepted that biomechanics is an important part of the glaucomatous disease process, the mechanisms by which biomechanical insult, usually due to elevated intraocular pressure (IOP), leads to retinal ganglion cell death are not understood. Rat models of glaucoma afford an opportunity for learning more about these mechanisms, but the biomechanics of the rat optic nerve head (ONH), a primary region of damage in glaucoma, are only just beginning to be characterized. In a previous study, we built finite-element models with individual-specific rat ONH geometries. Here, we developed a parametrized model of the rat ONH and used it to perform a sensitivity study to determine the influence that six geometric parameters and 13 tissue material properties have on rat optic nerve biomechanical strains due to IOP elevation. Strain magnitudes and patterns in the parametrized model generally matched those from individual-specific models, suggesting that the parametrized model sufficiently approximated rat ONH anatomy. Similar to previous studies in human eyes, we found that scleral properties were highly influential: the six parameters with highest influence on optic nerve strains were optic nerve stiffness, IOP, scleral thickness, the degree of alignment of scleral collagen fibres, scleral ground substance stiffness and the scleral collagen fibre uncrimping coefficient. We conclude that a parametrized modelling strategy is an efficient approach that allows insight into rat ONH biomechanics. Further, scleral properties are important influences on rat ONH biomechanics, and additional efforts should be made to better characterize rat scleral collagen fibre organization.

Intracranial pressure modulates aqueous humour dynamics of the eye.

An elevation in intracranial pressure (ICP) lowers conventional outflow facility (increases aqueous outflow resistance) of rat eyes. The reduction in outflow facility correlates with an increase in intraocular pressure (IOP). The effect of ICP elevation on outflow facility and IOP is blocked by TTX. The results indicate that aqueous humour dynamics is modulated by ICP-driven neural feedback from the brain. This feedback mechanism may act to stabilize translaminar pressure across the optic nerve head and may provide a new avenue for glaucoma therapy. While intraocular pressure (IOP) is a well-known risk factor for glaucoma, intracranial pressure (ICP) is attracting heightened interest because of its influence on optic nerve head biomechanics. Studies have shown that ICP can have marked impacts on posterior eye health by modifying the translaminar pressure gradient across the optic nerve. There is also growing evidence that IOP and ICP may be interconnected, although the mechanism of their putative interaction is unknown. We sought to test the hypothesis that ICP modulates IOP by altering aqueous humour dynamics. The anterior chamber and lateral ventricle of anaesthetized Brown-Norway rats were cannulated with fine-gauge needles connected to a programmable pump and saline reservoir, respectively. ICP was manipulated by varying reservoir height, and eye outflow facility (C) was determined from the pump flow rate required to hold IOP at different levels. C was 22±4nl/min/mmHg at resting ICP and 13±3nl/min/mmHg when ICP was raised 15mmHg, a reduction of 41±13% (n=18). The decrease in outflow facility was independent of blood pressure, reversible, scaled with ICP elevation and correlated with increases in resting IOP. It was physiological in origin because C returned to baseline values after the rats were killed and corneal application of TTX though ICP remained elevated. These results indicate that a neural feedback mechanism driven by ICP regulates conventional outflow facility in rats. The mechanism may protect the eye from translaminar pressure swings and may offer a new target for glaucoma treatment.

Quantitative confocal optical coherence elastography for evaluating biomechanics of optic nerve head using Lamb wave model.

.The mechanosensitivity of the optic nerve head (ONH) plays a pivotal role in the pathogenesis of glaucoma. Characterizing elasticity of the ONH over changing physiological pressure may provide a better understanding of how changes in intraocular pressure (IOP) lead to changes in the mechanical environment of the ONH. Optical coherence elastography (OCE) is an emerging technique that can detect tissue biomechanics noninvasively with both high temporal and spatial resolution compared with conventional ultrasonic elastography. We describe a confocal OCE system in measuring ONH elasticity in vitro, utilizing a pressure inflation setup in which IOP is controlled precisely. We further utilize the Lamb wave model to fit the phase dispersion curve during data postprocessing. We present a reconstruction of Young’s modulus of the ONH by combining our OCE system with a Lamb wave model for the first time. This approach enables the quantification of Young’s modulus of the ONH, which can be fit using a piecewise polynomial to the corresponding IOP.

Peripapillary border tissue of the choroid and peripapillary scleral flange in human eyes.

To assess dimensions and associations of the peripapillary border tissue of the choroid (PBT-C) and peripapillary scleral flange (PBT-S). The histomorphometric investigation included histological sections of enucleated eyes of Caucasian patients. Using light microscopy, the PBT dimensions were measured. The study included 85 eyes (85 patients) with an age of 62.0years (14.1years) (mean (SD)) (range:37-87years) and mean axial length of 26.7mm (3.5mm) (range:21.0-37.0mm). Thicker PBT-C thickness (mean: 68.8μm (35.7μm)) was associated with shorter axial length (p<0.001; standardized regression coefficient beta: -0.50), and longer PBT-C length (mean: 531μm (802μm)) was correlated with longer axial length (p<0.001;beta:0.66). PBT-C cross-sectional area (mean 17050μm2 (10420μm2 )) was not significantly associated with axial length (p=0.37). Decreasing with longer axial length (p<0.001;beta:0.64), the angle between PBT-C and Bruch's membrane was approximately 90° in non-highly myopic eyes without overhanging Bruch's membrane (BM), it ranged between 100° and 180° in eyes with BM overhanging into the intrapapillary region, and it was close to 0° in eyes with parapapillary gamma zone. Thicker thickness of PBT-S (mean:83μm (21μm)) was correlated with presence of glaucoma (p=0.02). Optic nerve pia mater thickness (mean:109μm (44μm)) increased with glaucoma presence (p=0.046;beta:0.31) but not with axial length (p=0.34). Peripapillary border tissue of the choroid (PBT-C) and PBT-S as continuation of the optic nerve pia mater are distinct structures, with PBT-C remodelling during myopic axial elongation and PBT-S being mostly independent of axial elongation. PBT-C and PBT-S may be of importance for the optic nerve head biomechanics and PBT-C for separation of the choroidal space from the intrapapillary compartment.

Investigation of the Optic Nerve Head Morphology Influence to the Optic Nerve Head Biomechanics - Patient Specific Model.

Glaucoma is associated with damage and death of optic nerve fibers within the Lamina Cribrosa (LC) region of the Optic Nerve Head. The pathogenesis of the disease is unclear, and the anterior LC surface morphology of different individuals can be one of the possible contributor of glaucoma development and progression. The current study evaluates the relationship between the LC surface curvature and distribution of shear stresses on the LC surface. The patient-specific reconstructed ocular model was developed and analyzed in a finite element analysis software. In addition, the effect of elastic modulus of both sclera and LC on the shear stress was examined. Results showed that there is a correlation between the shear stress distribution and the curvature of the anterior LC surface. This finding highlights the potential significance of the LC morphology on the distribution of LC shear stress and require further investigation.

Investigation of the Optic Nerve Head Morphology Influence to the Optic Nerve Head Biomechanics - Population Specific Model.

Glaucoma is an eye disorder potentially leading to permanent blindness through the damage of optic nerves at the optic nerve head (ONH). As a critical region of optic nerve damage, the porous Lamina Cribrosa (LC) in the ONH plays a critical role in determining whether optic nerves passing through will experience apoptosis in response to shear stress. The primary cause of shear stress to the LC is the increase in intraocular pressure (IOP). Since morphology governs how mechanical stresses distributes, LC morphology could be an important factor in determining the risks of glaucoma development and progression. The current project aims at investigating how anterior LC surface morphology impacts its response to shear stress caused by IOP. Results of the current study show that steeper LC morphologies could be associated with increased average shear stress on the anterior LC surface. The effect of LC morphology was comparable to that of IOP. This highlights the potential significance of LC morphology on the distribution of IOP-induced shear stress and calls for further investigation in this area.