The optic nerve head as a biomechanical structure: a new paradigm for understanding the role of IOP-related stress and strain in the pathophysiology of glaucomatous optic nerve head damage.

We propose here a conceptual framework for understanding the optic nerve head (ONH) as a biomechanical structure. Basic principles of biomechanical engineering are used to propose a central role for intraocular pressure (IOP)-related stress and strain in the physiology of ONH aging and the pathophysiology of glaucomatous damage. Our paradigm suggests that IOP-related stress and strain (1) are substantial within the load-bearing connective tissues of the ONH even at low levels of IOP and (2) underlie both ONH aging and the two central pathophysiologies of glaucomatous damage--mechanical failure of the connective tissues of the lamina cribrosa, scleral canal wall, and peripapillary sclera, and axonal compromise within the lamina cribrosa by a variety of mechanisms. Modeling the ONH as a biomechanical structure generates a group of testable hypotheses regarding the central mechanisms of glaucomatous damage and provides a logic for classifying the principal components of the susceptibility of an individual ONH to a given level of IOP.

Viscoelastic material properties of the peripapillary sclera in normal and early-glaucoma monkey eyes.

PURPOSE: To test the hypothesis that changes in the viscoelastic material properties of peripapillary sclera are present within monkey eyes at the onset of early experimental glaucoma detected by confocal scanning laser tomography (CSLT). METHODS: Short-term (3-9 weeks), moderate (< or =44 mm Hg) intraocular pressure (IOP) elevation was induced in one eye of each of eight male monkeys by lasering the trabecular meshwork. This procedure generated early experimental glaucoma, defined as the onset of CSLT-detected optic nerve head (ONH) surface change, in the treated eye. Scleral tensile specimens from the superior and inferior quadrants of the eight early-glaucoma eyes were subjected to uniaxial stress relaxation and tensile tests to failure and the results compared with similar data obtained in a previous study of 12 normal (nonglaucomatous) eyes. Linear viscoelastic theory was used to characterize viscoelastic material property parameters for each specimen. Differences in each parameter due to quadrant and treatment were assessed by analysis of variance (ANOVA). RESULTS: Peripapillary sclera from the early-glaucoma eyes exhibited an equilibrium modulus (7.46 +/- 1.58 MPa) that was significantly greater than that measured in normal eyes (4.94 +/- 1.22 MPa; mean +/- 95% confidence interval, P < 0.01, ANOVA). Quadrant differences were not significant for the viscoelastic parameters within each treatment group. CONCLUSIONS: The long-term viscoelastic material properties of monkey peripapillary sclera are altered by exposure to moderate, short-term, chronic IOP elevations and these alterations are present at the onset of CSLT-detected glaucomatous damage to the ONH. Damage to and/or remodeling of the extracellular matrix of these tissues may underlie these changes in scleral material properties.

Biomechanical changes in the sclera of monkey eyes exposed to chronic IOP elevations.

PURPOSE: To characterize scleral biomechanics in both eyes of eight monkeys in which chronic intraocular pressure (IOP) elevation was induced in one eye. METHODS: Each posterior sclera was mounted on a pressurization apparatus, IOP was elevated from 5 to 45 mm Hg while the 3D displacements of the scleral surface were measured by speckle interferometry. Finite element (FE) models of each scleral shell were constructed that incorporated stretch-induced stiffening and multidirectionality of the collagen fibers. FE model predictions were then iteratively matched to experimental displacements to extract unique sets of scleral biomechanical properties. RESULTS: For all eyes, the posterior sclera exhibited inhomogeneous, anisotropic, nonlinear biomechanical behavior. Biomechanical changes caused by chronic IOP elevation were complex and specific to each subject. Specifically: (1) Glaucomatous eyes in which the contralateral normal eyes displayed large modulus or thickness were less prone to biomechanical changes; (2) glaucomatous scleral modulus associated with an IOP of 10 mm Hg decreased (when compared with that of the contralateral normal) after minimal chronic IOP elevation; (3) glaucomatous scleral modulus associated with IOPs of 30 and 45 mm Hg increased (when compared with that of the contralateral normal) after moderate IOP elevation; and (4) FE-based estimates of collagen fiber orientation demonstrated no change in the glaucomatous eyes. CONCLUSIONS: Significant stiffening of the sclera follows exposure to moderate IOP elevations in most eyes. Scleral hypercompliance may precede stiffening or be a unique response to minimal chronic IOP elevation in some eyes. These biomechanical changes are likely to be the result of scleral extracellular matrix remodeling.

Scleral biomechanics in the aging monkey eye.

PURPOSE: To investigate the age-related differences in the inhomogeneous, anisotropic, nonlinear biomechanical properties of posterior sclera from old (22.9 +/- 5.3 years) and young (1.5 +/- 0.7 years) rhesus monkeys. METHODS: The posterior scleral shell of each eye was mounted on a custom-built pressurization apparatus, then intraocular pressure (IOP) was elevated from 5 to 45 mm Hg while the 3D displacements of the scleral surface were measured with speckle interferometry. Each scleral shell's geometry was digitally reconstructed from data generated by a 3-D digitizer (topography) and 20-MHz ultrasound (thickness). An inverse finite element (FE) method incorporating a fiber-reinforced constitutive model was used to extract a unique set of biomechanical properties for each eye. Displacements, thickness, stress, strain, tangent modulus, structural stiffness, and preferred collagen fiber orientation were mapped for each posterior sclera. RESULTS: The model yielded 3-D deformations of posterior sclera that matched well with those observed experimentally. The posterior sclera exhibited inhomogeneous, anisotropic, nonlinear mechanical behavior. The sclera was significantly thinner (P = 0.038) and tangent modulus and structural stiffness were significantly higher in old monkeys (P < 0.0001). On average, scleral collagen fibers were circumferentially oriented around the optic nerve head (ONH). No difference was found in the preferred collagen fiber orientation and fiber concentration factor between age groups. CONCLUSIONS: Posterior sclera of old monkeys is significantly stiffer than that of young monkeys and is therefore subject to higher stresses but lower strains at all levels of IOP. Age-related stiffening of the sclera may significantly influence ONH biomechanics and potentially contribute to age-related susceptibility to glaucomatous vision loss.

Peripapillary and posterior scleral mechanics--part I: development of an anisotropic hyperelastic constitutive model.

The sclera is the white outer shell and principal load-bearing tissue of the eye as it sustains the intraocular pressure. We have hypothesized that the mechanical properties of the posterior sclera play a significant role in and are altered by the development of glaucoma-an ocular disease manifested by structural damage to the optic nerve head. An anisotropic hyperelastic constitutive model is presented to simulate the mechanical behavior of the posterior sclera under acute elevations of intraocular pressure. The constitutive model is derived from fiber-reinforced composite theory, and incorporates stretch-induced stiffening of the reinforcing collagen fibers. Collagen fiber alignment was assumed to be multidirectional at local material points, confined within the plane tangent to the scleral surface, and described by the semicircular von Mises distribution. The introduction of a model parameter, namely, the fiber concentration factor, was used to control collagen fiber alignment along a preferred fiber orientation. To investigate the effects of scleral collagen fiber alignment on the overall behaviors of the posterior sclera and optic nerve head, finite element simulations of an idealized eye were performed. The four output quantities analyzed were the scleral canal expansion, the scleral canal twist, the posterior scleral canal deformation, and the posterior laminar deformation. A circumferential fiber organization in the sclera restrained scleral canal expansion but created posterior laminar deformation, whereas the opposite was observed with a meridional fiber organization. Additionally, the fiber concentration factor acted as an amplifying parameter on the considered outputs. The present model simulation suggests that the posterior sclera has a large impact on the overall behavior of the optic nerve head. It is therefore primordial to provide accurate mechanical properties for this tissue. In a companion paper (Girard, Downs, Bottlang, Burgoyne, and Suh, 2009, "Peripapillary and Posterior Scleral Mechanics--Part II: Experimental and Inverse Finite Element Characterization," ASME J. Biomech. Eng., 131, p. 051012), we present a method to measure the 3D deformations of monkey posterior sclera and extract mechanical properties based on the proposed constitutive model with an inverse finite element method.

Peripapillary and posterior scleral mechanics--part II: experimental and inverse finite element characterization.

The posterior sclera likely plays an important role in the development of glaucoma, and accurate characterization of its mechanical properties is needed to understand its impact on the more delicate optic nerve head--the primary site of damage in the disease. The posterior scleral shells from both eyes of one rhesus monkey were individually mounted on a custom-built pressurization apparatus. Intraocular pressure was incrementally increased from 5 mm Hg to 45 mm Hg, and the 3D displacements were measured using electronic speckle pattern interferometry. Finite element meshes of each posterior scleral shell were reconstructed from data generated by a 3D digitizer arm (shape) and a 20 MHz ultrasound transducer (thickness). An anisotropic hyperelastic constitutive model described in a companion paper (Girard, Downs, Burgoyne, and Suh, 2009, "Peripapillary and Posterior Scleral Mechanics--Part I: Development of an Anisotropic Hyperelastic Constitutive Model," ASME J. Biomech. Eng., 131, p. 051011), which includes stretch-induced stiffening and multidirectional alignment of the collagen fibers, was applied to each reconstructed mesh. Surface node displacements of each model were fitted to the experimental displacements using an inverse finite element method, which estimated a unique set of 13 model parameters. The predictions of the proposed constitutive model matched the 3D experimental displacements well. In both eyes, the tangent modulus increased dramatically with IOP, which indicates that the sclera is mechanically nonlinear. The sclera adjacent to the optic nerve head, known as the peripapillary sclera, was thickest and exhibited the lowest tangent modulus, which might have contributed to the uniform distribution of the structural stiffness for each entire scleral shell. Posterior scleral deformation following acute IOP elevations appears to be nonlinear and governed by the underlying scleral collagen microstructure as predicted by finite element modeling. The method is currently being used to characterize posterior scleral mechanics in normal (young and old), early, and moderately glaucomatous monkey eyes.

Experimental surface strain mapping of porcine peripapillary sclera due to elevations of intraocular pressure.

To experimentally characterize 2D surface mapping of the deformation pattern of porcine peripapillary sclera following acute elevations of intraocular pressure (IOP) from 5 mm Hg to 45 mm Hg. Four porcine eyes were obtained within 48 h postmortem and dissected to the sclera. After the anterior chamber was removed, each posterior scleral shell was individually mounted at the equator on a custom-built pressurization device, which internally pressurized the scleral samples with isotonic saline at 22 degrees C. Black polystyrene microspheres (10 microm in diameter) were randomly scattered and attached to the scleral surface. IOP was incrementally increased from 5 mm Hg to 45 mm Hg (+/-0.15 mm Hg), and the surface deformation of the peripapillary sclera immediately adjacent to the dural insertion was optically tracked at a resolution of 2 micrompixel one quadrant at a time, for each of four quadrants (superior, nasal, inferior, and temporal). The 2D displacement data of the microsphere markers were extracted using the optical flow equation, smoothed by weighting function interpolation, and converted to the corresponding Lagrangian finite surface strain. In all four quadrants of each eye, the principal strain was highest and primarily circumferential immediately adjacent to the scleral canal. Average maximum Lagrangian strain across all quadrants for all eyes was 0.013+/-0.005 from 5 mm Hg to 10 mm Hg, 0.014+/-0.004 from 10 mm Hg to 30 mm Hg and 0.004+/-0.001 from 30 mm Hg to 45 mm Hg, demonstrating the nonlinearity in the IOP-strain relationship. For each scleral shell, the observed surface strain mapping implied that the scleral stiffness was relatively low between 5 mm Hg and 10 mm Hg, but dramatically increased for each IOP elevation increment beyond 10 mm Hg. Peripapillary deformation following an acute IOP elevation may be governed by the underlying scleral collagen microstructure and is likely in the high-stiffness region of the scleral stress-strain curve when IOP is above 10 mm Hg.

Periosteal augmentation of a tendon graft improves tendon healing in the bone tunnel.

Secure fixation of tendon or ligament to bone has been a challenging problem. The periosteum is an osteogenic organ that regulates bone growth and remodeling at the outer surface of cortical bone and also is known to play an important role in forming a tendon insertion site to bone. Therefore, we hypothesized that a freshly harvested periosteum can be used as a stimulative scaffold to biologically reinforce the attachment of tendon graft to bone. Using a rabbit hallucis longus tendon and calcaneus process model, we found that a periosteal augmentation of a tendon graft could enhance the structural integrity of the tendon-bone interface, when the periosteum is placed between the tendon and bone interface with the cambium layer facing toward the bone. Clinically, the use of an autogenous periosteum patch would be an optimal choice for biologic augmentation of the tendon graft in the bone tunnel, because the tissue is readily available for harvest from the patient's body.

Viscoelastic characterization of peripapillary sclera: material properties by quadrant in rabbit and monkey eyes.

In this report we characterize the viscoelastic material properties of peripapillary sclera from the four quadrants surrounding the optic nerve head in both rabbit and monkey eyes. Scleral tensile specimens harvested from each quadrant were subjected to uniaxial stress relaxation and tensile ramp to failure tests. Linear viscoelastic theory, coupled with a spectral reduced relaxation function, was employed to characterize the viscoelastic properties of the tissues. We detected no differences in the stress-strain curves of specimens from the four quadrants surrounding the optic nerve head (ONH) below a strain of 4 percent in either the rabbit or monkey. While the peripapillary sclera from monkey eyes is significantly stiffer (both instantaneously and in equilibrium) and relaxes more slowly than that from rabbits, we detected no differences in the viscoelastic material properties (tested at strains of 0-1 percent) of sclera from the four quadrants surrounding the ONH within either species group.