Biomechanics of Human Trabecular Meshwork in Healthy and Glaucoma Eyes via Dynamic Schlemm’s Canal Pressurization

Abstract

Purpose : To explore poorly understood mechanisms that maintain IOP within a normal range. The trabecular meshwork (TM) consists of ECM embedded with collagen and elastin fibers and studies have shown that TM stiffness is considerably higher in glaucoma eyes. Emerging data indicates that the TM moves dynamically with transient IOP fluctuations, resulting in dynamic aqueous outflow. Soft biological tissues exhibit time-dependent/viscoelastic behavior under dynamic loading, but little is known about time-dependent TM behavior. We calculated the viscoelastic mechanical properties of the TM in n=2 healthy and n=2 glaucoma eyes obtained within 72 hours postmortem.

Methods : A quadrant of the anterior segment was mounted and submerged in a saline bath inside a pressure chamber to maintain 4 mmHg simulated episcleral venous pressure. A cannula connected to an adjustable saline reservoir was inserted into one end of Schlemm’s canal (SC), with the other end open. A series of cross-sectional scans of the TM/SC complex were captured at 30 frames/second at two locations in each eye during pressure oscillation from 0 to 30 mmHg. A segmentation program delineated the TM boundaries in the OCT images to construct a 20-µm-thick volume finite element (FE) mesh of the TM/SC complex. Collagen and elastin fibrils were embedded in the model using our mesh-free penalty-based cable-in-solid algorithm (Fig). A pre-tension in the collagen and elastin fibrils and a pre-stress in the ECM of the TM were induced to mimic ciliary muscle contraction at the relaxed stage. The model was subjected to a normal optimized pressure function from 0 to 30 mmHg from the SC and the other boundaries were subjected to floating boundary conditions. An FE optimization algorithm was used to adjust the ECM/fiber mechanical properties such that TM/SC model and OCT imaging data best matched over time.

Results : Significantly higher short- and long-time ECM shear moduli, and collagen and elastin fibril elastic moduli, were present in the glaucoma eye TM compared to normal controls (p<0.05). The external region of the TM in glaucoma eyes (Fig) showed lower stresses versus the internal region.

Conclusions : Mechanical alterations are challenging to monitor clinically. We characterized the alterations in ex vivo healthy and glaucoma eyes. Our findings may contribute to enhanced understanding of glaucoma pathophysiology, diagnosis, and treatment.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.