Relative Contributions of Intraocular and Cerebrospinal Fluid Pressures to the Biomechanics of the Lamina Cribrosa and Laminar Neural Tissues

Abstract

Purpose The laminar region of the optic nerve head (ONH), thought to be the site of damage to the retinal ganglion cell axons in glaucoma, is continuously loaded on its anterior and posterior surfaces by dynamic intraocular pressure (IOP) and orbital cerebrospinal fluid pressure (CSFP), respectively. Thus, translaminar pressure (TLP; TLP = IOP-CSFP) has been proposed as a glaucoma risk factor. Methods Three eye-specific finite element models of the posterior human eye were constructed, including full 3D microstructures of the load-bearing lamina cribrosa (LC) with interspersed laminar neural tissues (NTs), and heterogeneous, anisotropic, hyperelastic material formulations for the surrounding peripapillary sclera and adjacent pia. ONH biomechanical responses were simulated using three combinations of IOP and CSFP loadings consistent with posture change from sitting to supine. Results Results show that tensile, compressive, and shear stresses and strains in the ONH were higher in the supine position compared to the sitting position ( P < 0.05). In addition, LC beams bear three to five times more TLP-driven stress than interspersed laminar NT, whereas laminar NT exhibit three to five times greater strain than supporting LC ( P < 0.05). Compared with CSFP, IOP drove approximately four times greater stress and strain in the LC, NT, and peripapillary sclera, normalized per mm Hg pressure change. In addition, IOP drove approximately three-fold greater scleral canal expansion and anterior-posterior laminar deformation than CSFP per mm Hg ( P < 0.05). Conclusions Whereas TLP has been hypothesized to play a prominent role in ONH biomechanics, the IOP and CSFP effects are not equivalent, as IOP-driven stress, strain, and deformation play a more dominant role than CSFP effects.

In vivo Modulation of Intraocular and Intracranial Pressures Causes Nonlinear and Non-monotonic Deformations of the Lamina Cribrosa and Scleral Canal

“…An alternative is to enrich the statistical model fitting using mechanistic relationships that can be derived from computational models. 17,18,27…”

“…An alternative is to enrich the statistical model fitting using mechanistic relationships that can be derived from computational models. 17,18,27 In conclusion, we aimed to explore patterns of interaction between IOP and ICP in a monkey model. We demonstrate that IOP-ICP interaction significantly affects ONH feature morphology.…”

“…This previous preliminary study evidenced the existence of IOP-ICP interaction. Computational modeling studies from us 17 and others 18 suggest that there are rich and complex effects of both IOP and ICP on the ONH, including nonlinear responses. Such effects cannot be determined from binary pressure conditions.…”

Modeling the Endothelial Glycocalyx Layer in the Human Conventional Aqueous Outflow Pathway

“…The 3D FE model of the TM/JCT/SC complex of a normal human donor of European descent was constructed [ 52 ]. The descriptions in regard to the imaging, segmentation, and volume meshing of the TM/JCT/SC complex FE model were fully explained in our prior publications [ 46 , 47 , 49 , 50 , 53 ].…”

Biomechanical homeostasis in ocular diseases: A mini-review

“…The increased TLCPD may contribute to the LC deformation involving astrocyte migration, axonal bundle disorganization and extracellular matrix alternation ( 54 , 55 ). Specifically, the individual role of these two forming ingredients is not equivalent, IOP-driven biomechanical effects display a more dominant role than CSFP ( 56 ). Multiple mechanosensitive channels such as Piezo, TRPV4, and TREK-1 are proven to have biomechanical effects in glaucoma on an experimental basis.…”