Estimating Human Trabecular Meshwork Stiffness by Numerical Modeling and Advanced OCT Imaging (original) (raw)
Related papers
Elastic Modulus Determination of Normal and Glaucomatous Human Trabecular Meshwork
Investigative Ophthalmology & Visual Science, 2011
PURPOSE. Elevated intraocular pressure (IOP) is a risk factor for glaucoma. The principal outflow pathway for aqueous humor in the human eye is through the trabecular meshwork (HTM) and Schlemm's canal (SC). The junction between the HTM and SC is thought to have a significant role in the regulation of IOP. A possible mechanism for the increased resistance to flow in glaucomatous eyes is an increase in stiffness (increased elastic modulus) of the HTM. In this study, the stiffness of the HTM in normal and glaucomatous tissue was compared, and a mathematical model was developed to predict the impact of changes in stiffness of the juxtacanalicular layer of HTM on flow dynamics through this region. METHODS. Atomic force microscopy (AFM) was used to measure the elastic modulus of normal and glaucomatous HTM. According to these results, a model was developed that simulated the juxtacanalicular layer of the HTM as a flexible membrane with embedded pores. RESULTS. The mean elastic modulus increased substantially in the glaucomatous HTM (mean ϭ 80.8 kPa) compared with that in the normal HTM (mean ϭ 4.0 kPa). Regional variation was identified across the glaucomatous HTM, possibly corresponding to the disease state. Mathematical modeling suggested an increased flow resistance with increasing HTM modulus. CONCLUSIONS. The data indicate that the stiffness of glaucomatous HTM is significantly increased compared with that of normal HTM. Modeling exercises support substantial impairment in outflow facility with increased HTM stiffness. Alterations in the bio-physical attributes of the HTM may participate directly in the onset and progression of glaucoma. (Invest Ophthalmol Vis Sci.
Circumferential Tensile Stiffness of Glaucomatous Trabecular Meshwork
Investigative Ophthalmology & Visual Science, 2014
PURPOSE. Our previous work indicated that a larger circumferential Young's modulus (E) of trabecular meshwork (TM) correlated with a higher outflow facility (C) in normal human donor eyes. The current study investigated the influence of glaucomatous TM stiffness and cellularity on C.
We report the use of a high-resolution optical coherence tomography (OCT) imaging platform to identify and quantify pressure-dependent aqueous outflow system (AOS) tissue relationships and to infer mechanical stiffness through examination of tissue properties in ex vivo human eyes. Five enucleated human eyes are included in this study, with each eye prepared with four equal-sized quadrants, each encompassing 90 degrees of the limbal circumference. In radial limbal segments perfusion pressure within Schlemm's canal (SC) is controlled by means of a perfusion cannula inserted into the canal lumen, while the other end of the cannula leads to a reservoir at a height that can control the pressure in the can-nula. The OCT system images the sample with a spatial resolution of about 5 μm from the trabecular meshwork (TM) surface. Geometric parameters are quantified from the 2D OCT images acquired from the sample subjected to controlled changes in perfusion pressures; parameters include area and height of the lumen of SC, collector channel entrances (CCE) and intrascleral collector channels (ISCC). We show that 3D OCT imaging permits the identification of 3-D relationships of the SC, CCE and ISCC lumen dimensions. Collagen flaps or leaflets are found at CCE that are attached or hinged at only one end, whilst the flaps are connected to the TM by cylindrical structures spanning SC. Increasing static SC pressures resulted in SC lumen enlargement with corresponding enlargement of the CCE and ISCC lumen. Pressure-dependent SC lumen area and height changes are significant at the 0.01 levels for ANOVA, and at the 0.05 for both polynomial curves and Tukey paired comparisons. Dynamic measurements demonstrate a synchronous increase in SC, CCE and ISCC lumen height in response to pressure changes from 0 to 10, 30 or 50 mm Hg, respectively, and the response time is within the 50-millisecond range. From the measured SC volume and corresponding IOP values, we demonstrate that an elastance curve can be developed to infer the mechanical stiffness of the TM by means of quantifying pressure-dependent SC volume changes over a 2 mm radial region of SC. Our study finds pressure-dependent motion of the TM that corresponds to collagen leaflet configuration motion at CCE
Journal of Clinical Medicine
Background: Although the tissues comprising the ocular conventional outflow pathway have shown strong viscoelastic mechanical response to aqueous humor pressure dynamics, the viscoelastic mechanical properties of the trabecular meshwork (TM), juxtacanalicular connective tissue (JCT), and Schlemm’s canal (SC) inner wall are largely unknown. Methods: A quadrant of the anterior segment from two human donor eyes at low- and high-flow (LF and HF) outflow regions was pressurized and imaged using optical coherence tomography (OCT). A finite element (FE) model of the TM, the adjacent JCT, and the SC inner wall was constructed and viscoelastic beam elements were distributed in the extracellular matrix (ECM) of the TM and JCT to represent anisotropic collagen. An inverse FE-optimization algorithm was used to calculate the viscoelastic properties of the ECM/beam elements such that the TM/JCT/SC model and OCT imaging data best matched over time. Results: The ECM of the glaucoma tissues showed s...
IEEE Transactions on Medical Imaging, 2014
Optic nerve head (ONH) tissue properties and biomechanics remain mostly unmeasurable in the experiment. We hypothesized that these can be estimated numerically from ocular parameters measurable in vivo with optical coherence tomography (OCT). Using parametric models representing human ONHs we simulated acute intraocular pressure (IOP) increases (10 mmHg). Statistical models were fit to predict, from OCT-measurable parameters, 15 outputs, including ONH tissue properties, stresses, and deformations. The calculations were repeated adding parameters that have recently been proposed as potentially measurable with OCT. We evaluated the sensitivity of the predictions to variations in the experimental parameters. Excellent fits were obtained to predict all outputs from the experimental parameters, with cross-validated R2s between 0.957 and 0.998. Incorporating the potentially measurable parameters improved fits significantly. Predictions of tissue stiffness were accurate to within 0.66 MPa for the sclera and 0.24 MPa for the lamina cribrosa. Predictions of strains and stresses were accurate to within 0.62% and 4.9 kPa, respectively. Estimates of ONH biomechanics and tissue properties can be obtained quickly from OCT measurements using an applet that we make freely available. These estimates may improve understanding of the eye sensitivity to IOP and assessment of patient risk for development or progression of glaucoma.
Purpose: To investigate differences in biomechanical properties focusing on stiffness parameters between normal, treatment-naïve primary open-angle glaucoma (POAG), and treated POAG eyes.Design: Retrospective case-control studyMethods: This study included 46 treatment-naïve POAG eyes, 46 POAG eyes treated with prostaglandin analogues, and 49 normal eyes used as controls; matched in terms of age and axial length. Corneal hysteresis (CH) and corneal resistance factor (CRF) were measured using an ocular response analyzer (ORA). Fifteen biomechanical parameters were obtained with the Corneal Visualization Scheimpflug Technology (Corvis ST), including biomechanical glaucoma factor (BGF) and two stiffness parameters of ‘SP A1’ and ‘stress-strain index (SSI)’, which were compared among the three groups. Additionally, the area under the curve (AUC) values of the receiver-operating curve, to discriminate control and treatment-naïve POAG eyes were calculated and compared between CH and BGF.Re...
Bioengineering, 2021
Glaucoma is a leading cause of irreversible blindness globally, with primary open angle glaucoma (POAG) being the most common subset. Raised intraocular pressure is an important risk factor for POAG and is caused by a reduction in aqueous humour (AqH) outflow due to dysfunctional cellular and matrix dynamics in the eye’s main drainage site, the trabecular meshwork (TM) and Schlemm’s canal (SC). The TM/SC are highly specialised tissues that regulate AqH outflow; however, their exact mechanisms of AqH outflow control are still not fully understood. Emulating physiologically relevant 3D TM/S in vitro models poses challenges to accurately mimic the complex biophysical and biochemical cues that take place in healthy and glaucomatous TM/SC in vivo. With development of such models still in its infancy, there is a clear need for more well-defined approaches that will accurately contrast the two central regions that become dysfunctional in POAG; the juxtacanalicular tissue (JCT) region of th...
PloS one, 2015
The biomechanical behavior of the sclera determines the level of mechanical insult from intraocular pressure to the axons and tissues of the optic nerve head, as is of interest in glaucoma. In this study, we measure the collagen fiber structure and the strain response, and estimate the material properties of glaucomatous and normal human donor scleras. Twenty-two posterior scleras from normal and diagnosed glaucoma donors were obtained from an eyebank. Optic nerve cross-sections were graded to determine the presence of axon loss. The specimens were subjected to pressure-controlled inflation testing. Full-field displacement maps were measured by digital image correlation (DIC) and spatially differentiated to compute surface strains. Maps of the collagen fiber structure across the posterior sclera of each inflated specimen were obtained using synchrotron wide-angle X-ray scattering (WAXS). Finite element (FE) models of the posterior scleras, incorporating a specimen-specific represent...
Investigative ophthalmology & visual science, 2018
The extracellular matrix (ECM) of the trabecular meshwork (TM) modulates resistance to aqueous humor outflow, thereby regulating IOP. Glaucoma, a leading cause of irreversible blindness worldwide, is associated with changes in the ECM of the TM. The elastic modulus of glaucomatous TM is larger than age-matched normal TM; however, the biomechanical properties of segmental low (LF) and high flow (HF) TM regions and their response to elevated pressure, are unknown. We perfused human anterior segments at two pressures using an ex vivo organ culture system. After extraction, we measured the elastic modulus of HF and LF TM regions by atomic force microscopy and quantitated protein differences by proteomics analyses. The elastic modulus of LF regions was 2.3-fold larger than HF regions at physiological (1×) pressure, and 7.4-fold or 3.5-fold larger than HF regions at elevated (2×) pressure after 24 or 72 hours, respectively. Using quantitative proteomics, comparisons were made between HF a...