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Ke Wang, Murray A Johnstone, Chen Xin, Steven Padilla, Ruikang K Wang, C Ross Ethier; Estimating human trabecular meshwork stiffness by numerical modeling and advanced OCT imaging. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3543.
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© ARVO (1962-2015); The Authors (2016-present)
The cause of increased outflow resistance leading to ocular hypertension in glaucoma remains unknown. Human trabecular meshwork (hTM) stiffness, measured by AFM, was markedly elevated in glaucomatous vs. normal eyes (Last et al., 2011). However, in that study, the TM was dissected free from its physiological environment and mechanically loaded differently than in vivo. Our goal was to estimate hTM stiffness using an alternate approach, based on advanced OCT imaging and numerical biomechanical modeling.
Anterior regions of normal post mortem human eyes (n=2; ages: 74, 79 years; post mortem time: 24, 9 hours; Sightlife Eyebank) were dissected into corneoscleral wedges. A cannula was inserted into Schlemm’s canal (SC) to allow SC luminal pressure to be controlled by a variable height reservoir. Tissue displacements were captured by OCT in a series of cross-sections through the TM/SC at each reservoir pressure. Based on the observed anatomy in one cross-section at low SC pressure, a quasi-3D specimen-specific finite element model (FEM) was created (Fig. 1). Loading and boundary conditions were applied to the model as delivered experimentally. Tissues were treated as isotropic and hyperelastic. FEM simulations were carried out using a range of stiffness values for TM while other tissues were assigned a stiffness based on literature or best estimates. TM stiffness was varied until the L2-norm difference between OCT-observed and computed SC displacement was minimized. A sensitivity analysis was performed to investigate the influence of surrounding tissue stiffness and ciliary body (CB) boundary delineation on TM stiffness estimation.
Estimated hTM stiffnesses were 114 and 159 kPa, with an unambiguous “best match” value for each of the 2 eyes examined to date. Sensitivity analysis suggested that predicted TM stiffness was insensitive to CB boundary delineation and stiffness of CB, scleral and cornea.
Estimated hTM stiffness in normal eyes is c. 20x greater than reported by Last et al. Combining FEM and OCT has the potential to provide an alternative approach to assess hTM stiffness in a physiologically relevant manner. Future work will improve FEM geometry to better depict local structures, thus obtaining a more accurate estimate of outflow tissue stiffnesses.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
Figure 1: Representative finite element mesh of a cross-section from one corneoscleral wedge.
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