In Vivo Assessment of Lamina Cribrosa Microstructure in Glaucoma

Glaucoma is an optic neuropathy that is the second leading cause of blindness worldwide. The disease is characterized by damage to the retinal ganglion cells, resulting in irreversible vision loss. While the exact pathogenesis remains unclear, damage due to glaucoma is believed to first occur at the lamina cribrosa (LC), a collagenous meshwork in the optic nerve head through which all retinal ganglion cell axons pass on their way to the brain. \ud The mechanical theory of glaucoma postulates that elevated intraocular pressure deforms the LC, leading to a biological cascade resulting in retinal ganglion cell death. However, the interaction between intraocular pressure and glaucoma is complex; a substantial heterogeneity exists in the intraocular pressure at which a given patient experiences glaucoma. Recent studies have identified that perhaps intracranial pressure, which acts posterior to the LC, may play an important role in the disease process. \ud Given the complex 3D microstructure of the LC, in vivo studies thus far have been limited to assessment of changes in its surface. However, because the axons are traversing through the entire volume of the LC, the axonal damage can occur at any level of the LC, rather than only at its surface. Therefore, full understanding of the damage caused by glaucoma requires systematic characterization of the 3D LC microstructure. \ud In order to better characterize the 3D LC microstructure, we demonstrate here a novel automated 3D LC segmentation method that is reproducible and capable of accurately detecting the LC microstructural component. Using our segmentation analysis, we find in a primate model that the LC microstructure deforms according to both intraocular pressure as well as intracranial pressure, with significant interaction between the two. We then move to the translational aspect of our study to characterize the healthy LC in human eyes and identify a number of structural and biomechanical differences in the LC microstructure compared to glaucoma eyes. Our findings demonstrate that a novel automated 3D assessment of the LC microstructure is capable of 1) identifying in vivo difference in the LC microstructure and LC biomechanics in glaucoma eyes and 2) improving our understanding of glaucoma pathogenesis