Developing an experimental-computational workflow to study the biomechanics of the human conventional aqueous outflow pathway

Abstract

The aqueous humor actively interacts with the trabecular meshwork (TM), juxtacanalicular tissue (JCT), and Schlemm's canal (SC) through a dynamic fluid-structure interaction (FSI) coupling. Despite the fact that intraocular pressure (IOP) undergoes significant fluctuations, our understanding of the hyperviscoelastic biomechanical properties of the aqueous outflow tissues is limited. In this study, a quadrant of the anterior segment from a normal human donor eye was dynamically pressurized in the SC lumen, and imaged using a customized optical coherence tomography (OCT). The TM/JCT/SC complex finite element (FE) with embedded collagen fibrils was reconstructed based on the segmented boundary nodes in the OCT images. The hyperviscoelastic mechanical properties of the outflow tissues' extracellular matrix with embedded viscoelastic collagen fibrils were calculated using an inverse FE-optimization method. Thereafter, the 3D microstructural FE model of the TM, with adjacent JCT and SC inner wall, from the same donor eye was constructed using optical coherence microscopy and subjected to a flow load-boundary from the SC lumen. The resultant deformation/strain in the outflow tissues was calculated using the FSI method, and compared to the digital volume correlation (DVC) data. TM showed larger shear modulus (0.92 MPa) compared to the JCT (0.47 MPa) and SC inner wall (0.85 MPa). Shear modulus (viscoelastic) was larger in the SC inner wall (97.65 MPa) compared to the TM (84.38 MPa) and JCT (56.30 MPa). The conventional aqueous outflow pathway is subjected to a rate-dependent IOP load-boundary with large fluctuations. This necessitates addressing the biomechanics of the outflow tissues using hyperviscoelastic material-model. STATEMENT OF SIGNIFICANCE: While the human conventional aqueous outflow pathway is subjected to a large-deformation and time-dependent IOP load-boundary, we are not aware of any studies that have calculated the hyperviscoelastic mechanical properties of the outflow tissues with embedded viscoelastic collagen fibrils. A quadrant of the anterior segment of a normal humor donor eye was dynamically pressurized from the SC lumen with relatively large fluctuations. The TM/JCT/SC complex were OCT imaged and the mechanical properties of the tissues with embedded collagen fibrils were calculated using the inverse FE-optimization algorithm. The resultant displacement/strain in the FSI outflow model was validated versus the DVC data. The proposed experimental-computational workflow may significantly contribute to understanding of the effects of different drugs on the biomechanics of the conventional aqueous outflow pathway.

Keywords: Finite element method; Hyperviscoelastic; Juxtacanalicular tissue; Optimization algorithm; Schlemm's canal; Trabecular meshwork.

Fig. 1.

Aqueous humor is secreted into the posterior chamber at a nearly constant rate, enters the anterior chamber through the pupil (blue arrows) and then drains through one of two outflow pathways. The conventional outflow pathway (green arrow) includes the trabecular meshwork (TM), juxtacanalicular tissue (JCT), Schlemm’s canal (SC) and distal vessels (DV), comprising collector channels and intrascleral vessels, leading to episcleral vessels (EV). The unconventional pathway includes flow through the iris root (red arrow) and is believed to be relatively pressure-independent. The circled numbers in the inset refer to the location of the anterior chamber and collector channels. This figure is gotten from Sherwood et al., [110] under CC BY 4.0 license.

Fig. 2.

The schematic representation of the experimental setup, including the short-distance OCT and reservoirs to control the pressure in the SC lumen through cannulation from one end of the SC. A quadrant of the donor eye pinned in a petri dish as shown in the inset. This figure is gotten from [10, 35, 111] under CC BY 4.0 license.

Fig. 3.

(a) The OCT images of the TM/JCT/SC complex at different cross-section. The SC inner wall, SC-JCT, JCT-TM, and TM nodes are shown in this panel. (b) The finite element models of the TM/JCT/SC complex at different cross-section. The SC inner wall, JCT, and TM are shown in this panel. (c) The finite element model of the TM/JCT/SC complex with embedded collagen fibrils. The ECM of the sclera was modeled as hyperelastic neo-Hookean with embedded elastic collagen fibrils. The ECM of the TM and JCT was modeled as hyperviscoelastic with embedded viscoelastic collagen fibrils.

Fig. 4.

(a) The TM finite element model. The ECM of the TM was modeled as hyperviscoelastic with embedded viscoelastic collagen fibrils. The displacement boundary condition was applied on one end of the TM FE model and the other end was fixed. (b) The experimental stress-strain data versus finite element model for the healthy human TM.

Fig. 5.

Flow-chart of the imaging, segmentation, finite element model reconstruction, and inverse finite element coupled with an optimization algorithm.

Fig. 6.

(a) The original grayscale and (b) binary OCT image of the TM/JCT/SC complex. The volume mesh of the TM/JCT/SC complex from the (c) front and (d) isometric views. Element edge length of ~1μm.

Fig. 7.

(a) The finite element model of the TM/JCT/SC complex (b) with embedded collagen fibrils. The ECM of the sclera was modeled as hyperelastic neo-Hookean with embedded elastic collagen fibrils. The ECM of the TM and JCT was modeled as hyperviscoelastic with embedded viscoelastic collagen fibrils.

Fig. 8.

The pressure load-boundary applied on the SC inner wall.

Fig. 9.

(a) Original OCT image was (b) median filtered for better pixel detection in the DVC code. (c) The DVC code detected the TM/JCT/SC complex based on the filtered data and the region of interest is defined with higher color bar magnitude.

Fig. 10.

Comparison between the SC inner wall, SC-JCT, JCT-TM, and TM nodes from the OCT imaging data and the inverse finite element-optimization algorithm results at (a) cross-section #1, (b) cross-section #2, (c) cross-section #3, and (d) cross-section #4.

Fig. 11.

Comparison between the (a) resultant displacement, (b) maximum shear strain, and (c) 1^st principal strain between the FSI simulation results and DVC data at the SC lumen pressure of 17.6mmHg.