Collagen microstructural factors influencing optic nerve head biomechanics.

Abstract : Previous studies have suggested that the lamina cribrosa (LC) and its surrounding sclera are biomechanically important in the pathogenesis of glaucoma, but many were limited by assumptions of tissue isotropy and homogeneity. Here, we used an improved biomechanical model driven by experimental measurements of scleral and LC collagen fiber organization to more accurately evaluate optic nerve head (ONH) biomechanics. Collagen fiber organization was quantitatively mapped across human ONH cryosections (three normal and three glaucomatous) using small-angle light scattering (SALS) and fed into two-dimensional finite element models loaded under biaxial stress to simulate raised intraocular pressure. Effects of artificial variations in collagen fiber microstructure and stiffness on LC and scleral strains were also investigated. Scleral collagen fibers were circumferential and exhibited the highest alignment in a region not immediately adjacent to, but at a distance (400-500 μm) away from, the LC. In models, such a fiber arrangement yielded rings of low strain (second principal and effective) in the scleral region immediately adjacent to the LC. Further sensitivity analyses showed that scleral fiber alignment was crucial in determining LC strain levels. Moderate scleral anisotropy (as observed physiologically) was more effective than isotropy or high anisotropy in limiting LC and scleral strain magnitude. The presence of a heterogeneous collagen fiber organization in the peripapillary sclera appears effective in limiting LC strain and is able to reduce strain levels at the scleral canal boundary: a transition zone prone to LC disinsertion, focal lamina cribrosa defects, and optic disc hemorrhages in glaucoma.