Project title:

Computational modeling of the posterior eye to study ocular biomechanics under cerebrospinal fluid and
intracranial pressures

Project description:

Glaucoma is the second leading cause of blindness worldwide [1]. The optic nerve head (ONH) at the back of
the eyes is a critical site where nerve damage often starts in early glaucoma. The ONH region is
biomechanically protected in a healthy eye by its collagenous tissues. The protection becomes insufficient with
glaucoma development due to elevated intraocular pressure (IOP). Several works have extensively studied the
effects of IOP on the ONH biomechanics to understand glaucoma biomechanics [2-3]. However, the ONH is
also exposed to other biomechanical loads such as cerebrospinal fluid pressure (CSFP) and intracranial
pressure (ICP), but their effects on the ONH biomechanics remain elusive [4]. More importantly, it is not well-
understood how the collagen fibers of the ONH region support the combined loads from various pressures and
prevent nerve damage.

Figure 1. (a) Schematic of eye cross-section with the ONH highlighted and (b) enlarged view of the
ONH with boundary conditions. (c) PLM images of coronal sections were used to determine fiber
location and orientation. Shown is an example image with in-plane fiber orientation in color. (d)
Example sagittal section of another eye corresponding to the region shown in (b). (e) Isometric and (f)
sagittal perspective views of the fiber-based computational model. (e) shows full bundle widths. (f)
shows only bundle centerlines. Longitudinal fiber bundles of the pia and dura are continuous with
fibers of the sclera. The colors in (e) and (f) are intended to help compare with conventional tissue
definitions.

The overarching goal of this project is to understand the effects of various pressures and the associated
collagen fiber mechanics that may alter the ONH biomechanics and susceptibility to glaucoma development.
This project will focus on implementing fiber-based computational models of the ONH to simulate IOP, CSFP,
and ICP effects on the ONH biomechanics.
The specific research tasks will include but not limited to:
I. Post-processing of microscopy images to extract collagen fiber organization information.
II. Development of efficient computational algorithms to generate the fibrous geometry of the ONH.
III. Fibrous finite element modeling of the ONH.
IV. Simulation of the ONH model under various IOP, CSFP, and ICP boundary conditions.
V. Model validation with respect to experimental tests and parametric study.

The student responsible for this project will receive training on polarized light microscopy imaging, image
processing, and finite element modeling. The student will receive opportunities to present research work at
national conferences and publish peer-reviewed journal articles. The student will work physically on site and
will have weekly meetings with the supervisor (Dr. Ian Sigal). The supervisor will review the research progress
of the student and provide feedback on performance and areas of improvement.

References:

[1] Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J
Ophthalmol. 2006; 90: 262– 267.

[2] Sigal IA, Flanagan JG, Tertinegg I, Ethier CR. . Predicted extension, compression and shearing of
optic nerve head tissues. Exp Eye Res. 2007; 85: 312– 322.

[3] Strouthidis NG, Fortune B, Yang H, Sigal IA, Burgoyne CF. . Effect of acute intraocular pressure
elevation on the monkey optic nerve head as detected by spectral domain optical coherence
tomography. Invest Ophthalmol Vis Sci. 2011; 52: 9431– 9437.

[4] Hua Y, Voorhees AP, Sigal IA. Cerebrospinal Fluid Pressure: Revisiting Factors Influencing Optic
Nerve Head Biomechanics. Invest Ophthalmol Vis Sci. 2018 Jan 1;59(1):154-16.