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C Ross Ethier, Guorong Li, Chanyoung Lee, Ke Wang, Iris D Navarro, Joseph M Sherwood, Karen Crews, Sina Farsiu, Cheng-Wen Lin, W Daniel Stamer; In vivo measurement of TM stiffness: proof-of-principle in mice. Invest. Ophthalmol. Vis. Sci. 2019;60(9):5213.
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Outflow facility and trabecular meshwork (TM) stiffness are correlated (Wang, IOVS, 2017), implying that TM stiffness may be a useful indirect measure of TM function. However, most previous work used invasive techniques on post mortem eyes to determine TM stiffness. Here we: (i) describe a technique for OCT-based measurements of TM stiffness that overcomes many previous simplifying assumptions, and (ii) apply it to a mouse ocular hypertension model.
The iridocorneal angle was imaged in C57BL/6 mice by SD-OCT (Envisu R2200, Bioptigen) in eyes receiving nanoparticles loaded with dexamethasone or vehicle. Images were acquired at intraocular pressure (IOP) steps of 10-20 mmHg, set by cannulation. A finite element model of a typical angle cross-section simulated expansion of TM/collapse of Schlemm’s canal (SC) as IOP was varied, which was compared to experimental measurements of SC cross-sectional area from OCT (Fig 1A). Within the model, pressure loads were applied to surfaces exposed to aqueous humor, including an estimated pressure within SC. The effects of the iris and cornea were modeled by forces and moments at the virtual cut plane corresponding to the edge of the OCT image (Fig 1B).
Simulations predicted significant iris deformations, matching the OCT images (Fig 1C). However, if iridial forces and moments at the virtual cut plane were omitted, predicted iris deformations did not agree well with OCT images, emphasizing the importance of properly accounting for complex iris mechanics in the mouse eye. We ran multiple simulations with TM stiffness in the range 20-240 kPa, and used the best match between OCT and model results (Fig 1D) to estimate TM stiffness. TM in dexamethasone-treated eyes was approximately 2x stiffer than controls (69 kPa vs. 29 kPa), qualitatively consistent with reported effects of dexamethasone on TM from ex vivo measurements.
Determining TM stiffness in mice is feasible using OCT imaging + engineering modeling. Technical issues include the small size of the outflow tissues in the mouse and the deformation delivered to the TM/SC by iris displacement as IOP changes. Such effects will be less influential in human eyes, and thus this non-destructive approach to monitoring TM stiffness in vivo shows potential for both mouse and human studies. Further studies in mice and humans are indicated to compare directly measured TM stiffness vs. stiffness determined as described above.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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