Accomplishments: Over the course of this proposal we have made accomplishments on all of our computational and experimental approaches. Specifically, we have developed 3 lumped parameter models: one each of the cardiovascular system, central nervous system, and eye. We have also further developed our FEM of the posterior eye and optic nerve head (ONH). We have worked towards integrating these lumped parameter models with our ocular biomechanics finite element code to understand how different environment conditions impact the deformation at the posterior eye. We have also made direct measurements of the tissue mechanical properties of the optic nerve sheath and collagen structure. Lastly, we have taken clinical imaging of patients with elevated intracranial pressure.

Before undertaking finite element modeling, it was necessary to carry out experiments to measure relevant parameters of the optic nerve sheath (dura mater). Specifically, we characterized the mechanical behavior (stiffness) and fluid permeability of the dura mater, and determined its collagen orientation. Stiffness measurements showed significant hysteresis, typical of soft tissues, and strain-induced stiffening. From measured pressure-diameter curves we derived stress-strain relationship for the sheath and calculated the tangent modulus at various levels of intracranial ICP. At ICP = 7 mmHg, the tangent modulus was approximately 400 kPa, increasing to c. 2 MPa at ICP = 30 mmHg. The measured fluid permeability of the dura was approximately 0.8 µL/min/cm2/mmHg (n=17), which in turn predicts that a significant volume of CSF crosses the dura each day. Microscopy showed that the collagen fibers in the dura mater have an initial crimp, or wave-like, pattern when unloaded but become elongated and straighten as ICP is increased.

We then created a finite element model of the posterior eye. This model includes the posterior sclera, peripapillary sclera, optic nerve, lamina cribrosa, dura mater, pia mater, and a simplified central retinal vessel. In this initial model we treated all the constituent tissues as linearly elastic and isotropic, simplifications which we will shortly relax. Utilizing this model we examined the effect of increasing intracranial pressure from 0 to 30 mmHg, based on the CSF pressures at the posterior eye expected in upright posture (walking and standing, 0 mmHg) to those in space flight (30 mmHg). For these simulations we held intraocular and retinal vessel pressures constant at normal values (15 mmHg and 55 mmHg, respectively) to isolate the effects of increasing ICP. A significant finding from these results was that strains within the lamina cribrosa and post-laminar neural tissue change as ICP increases. This is important because changes in strains have been hypothesized to play a role in other visual diseases (e.g. glaucoma) and may explain some of the connective tissue changes observed in VIIP.