Quantitative Mapping of Collagen Fiber Orientation in Non - Glaucoma and 1 Glaucoma Posterior Human

1 Purpose: The posterior sclera has a major biomechanical influence on the optic nerve 2 head, and may therefore be important in glaucoma. Scleral material properties are 3 influenced significantly by collagen fiber architecture. Here we quantitatively map fiber 4 orientation in non-glaucoma and glaucoma posterior human scleras. 5 Methods: Wide-angle x-ray scattering quantified fiber orientation at 0.5mm intervals 6 across 7 non-glaucoma post-mortem human scleras, and 5 scleras with glaucoma history 7 and confirmed axon loss. Multiphoton microscopy provided semi-quantitative depth8 profiling in the peripapillary sclera. 9 Results: Mid-posterior fiber orientation was either uniaxial (one preferred direction) or 10 biaxial (two directions). The peripapillary sclera was characterized by a ring of fibers 11 located mainly in the mid/outer stromal depth and encompassing ~50% of the total 12 tissue thickness. Fiber anisotropy was 37% higher in the peripapillary sclera compared 13 to mid-posterior, varied up to four-fold with position around the scleral canal, and was 14 consistently lowest in the superior-nasal quadrant. Mean fiber anisotropy was 15 significantly lower in the superior-temporal (p < 0.01) and inferior-nasal (p < 0.05) 16 peripapillary scleral quadrants in glaucoma compared to non-glaucoma eyes. 17 Conclusions: The collagen fiber architecture of the posterior human sclera is highly 18 anisotropic and inhomogeneous. Regional differences in peripapillary fiber anisotropy 19 between non-glaucoma and glaucoma eyes may represent adaptive changes in response 20 to elevated IOP and/or glaucoma, or baseline structural properties that associate with 21 predisposition to glaucomatous axon damage. Quantitative fiber orientation data will 22