Glaucoma is the second leading cause of irreversible blindness in the world. It is characterized by the cupping of optic nerve head (ONH), loss of retinal ganglion cells and their axons resulting in loss of functional visual field. It is known that elevated intraocular pressure (IOP) is related to the disease, however the underlying pathophysiology of glaucoma in relation to IOP is not well understood and the factors contributing to disease progression are not well characterized.

The object of this work is to develop a three dimensional (3D) histomorphometry technique to study how the connective tissue and prelaminar neural tissue of the normal ONH respond to acute changes in IOP, and how these tissues response to long term IOP elevation in the early glaucoma (EG). The study of the ONH tissues is important because these tissues provide structural and nutritional support to the axons while they pass through the ONH. Furthermore, as the ONH is the primary site of axonal injury in glaucoma, investigation of its connective tissues provides may provide insight into the mechanism by which axons are damaged.

In this study, a 3D histomorphometry technique was introduced to reconstruct the ONH, delineate and quantify the major structures using customized software. Our major findings are:​ 1) Connective tissue and prelaminar neural tissue were permanently altered in EG. Lamina cribrosa permanently deformed in a posterior direction and thickened, accompanied by thickening of the prelaminar neural tissue. 2) The connective tissues deformed following acute IOP elevation characterized by thinning of the lamina, posterior bowing of the sclera and minimum anterior or posterior displacement of lamina. 3) Inter-eye physiologic differences of the normal ONH geometry were small enough to allow us to identify the effects of both acute and chronic IOP elevation to the ONH geometry. Finally new parameterized specimen-specific finite element models of the ONH and scleral shell were developed to study ONH biomechanics. Our study showed that the laminar elastic constant, scleral modulus, scleral thickness and laminar anisotropy were the most influential factors determining ONH biomechanics. In addition, the geometric and mechanical properties interacted to affect the ONH biomechanics.