Glaucoma is the second leading cause of irreversible blindness in the world with a higher prevalence in those of African Descent (AD) and Hispanic Ethnicity (HE) than in those of European Descent (ED). The objective of this study was to investigate the pressure dependent biomechanical response of the lamina cribrosa (LC) in normal human donor tissues from these racioethnic backgrounds. Pressure inflation tests were performed on 24 human LCs (n=9 AD, n=6 ED, and n=9 HE) capturing the second harmonic generation (SHG) signal of collagen at 5, 15, 30, and 45 mmHg from an anterior view. A non-rigid image registration technique was utilized to determine the 3D displacement field in each LC from which 3D Green strains were calculated.

Purpose The lamina cribrosa (LC) is a leading target for initial glaucomatous damage. We investigated the in vivo microstructural deformation within the LC volume in response to acute IOP modulation while maintaining fixed intracranial pressure (ICP). Methods In vivo optic nerve head (ONH) spectral-domain optical coherence tomography (OCT) scans (Leica, Chicago, IL, USA) were obtained from eight eyes of healthy adult rhesus macaques (7 animals; ages = 7.9–14.4 years) in different IOP settings and fixed ICP (8–12 mm Hg). IOP and ICP were controlled by cannulation of the anterior chamber and the lateral ventricle of the brain, respectively, connected to a gravity-controlled reservoir. ONH images were acquired at baseline IOP, 30 mm Hg (H1-IOP), and 40 to 50 mm Hg (H2-IOP). Scans were registered in 3D, and LC microstructure measurements were obtained from shared regions and depths. Results Only half of the eyes exhibited LC beam-to-pore ratio (BPR) and microstructure deformations. The maximal BPR change location within the LC volume varied between eyes. BPR deformer eyes had a significantly higher baseline connective tissue volume fraction (CTVF) and lower pore aspect ratio ( P = 0.03 and P = 0.04, respectively) compared to BPR non-deformer. In all eyes, the magnitude of BPR changes in the anterior surface was significantly different (either larger or smaller) from the maximal change within the LC (H1-IOP: P = 0.02 and H2-IOP: P = 0.004). Conclusions The LC deforms unevenly throughout its depth in response to IOP modulation at fixed ICP. Therefore, analysis of merely the anterior LC surface microstructure will not fully capture the microstructure deformations within the LC. BPR deformer eyes have higher CTVF than BPR non-deformer eyes.

Although strongly correlated with elevated intraocular pressure, primary open-angle glaucoma (POAG) occurs in normotensive eyes. Mechanical properties of the sclera around the optic nerve head (ONH) may play a role in this disparity. The purpose of this study is to present an automated inverse mechanics based approach to determine the distribution of heterogeneous mechanical properties of the human sclera as derived from its surface deformations arising from pressure inflation experiments. The scleral shell of a 78 year old European Descent male donor eye was utilized to demonstrate the method; the sclera was coated with a speckle pattern on the outer surface and was subjected to inflation pressures of 5, 15, 30, and 45 mmHg. The speckle pattern was imaged at each pressure, and a displacement field was calculated for each pressure step using a previously described sequential digital image correlation (S-DIC) technique. The fiber splay and fiber orientation of the sclera collagen were determined experimentally, and the thickness across the scleral globe was determined using micro CT images. The displacement field from the inflation test was used to calculate the strain and also used as an input for inverse mechanics to determine the heterogeneity of material properties. The scleral geometry was divided into subdomains using the first principal strain. The Holzapfel anisotropic material parameters of matrix and fiber stiffness were estimated within each individual subdomain using an inverse mechanics approach by minimizing the sum of the square of the residuals between the computational and experimental displacement fields. The mean and maximum error in displacement across all subdomains were 8.9 ± 3.0 μm and 13.2 μm, respectively. The full pressure-inflation forward mechanics experiment was done using subdomain-specific mechanical properties on the entire scleral surface. The proposed approach is effective in determining the distribution of heterogeneous mechanical properties of the human sclera in a user-independent manner. Our research group is currently utilizing this approach to better elucidate how scleral stiffness influences those at high risk for POAG.

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