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A method motivated by the eye's aqueous veins is described for the imaging and strain calculation within soft biological tissues. A challenge to the investigation of the biomechanics of the aqueous vein-perilimbal sclera tissue complex is resolution of tissue deformations as a function of intraocular pressure and the subsequent calculation of strain (a normalized measure of deformation). The method involves perfusion of the eye with a contrast agent during conduction of non-invasive, optical resolution photoacoustic microscopy. This imaging technique permits three-dimensional displacement measurements of tracked points on the inner walls of the veins which are used in a finite element model to determine the corresponding strains. The methods are validated against two standard strain measurement methods. Representative porcine globe perfusion experiments are presented that demonstrate the power of the method to determine complex strain fields in the veins dependent on intraocular pressure as well as vein anatomy. In these cases, veins are observed to move radially outward during increases in intraocular pressure and to possess significant spatial strain variation, possibly influenced by their branching patterns. To the authors' knowledge, these are the only such quantitative, data driven, calculations of the aqueous vein strains available in the open literature., (© 2021. The Author(s).)

There is extensive knowledge on the relationship of posterior scleral biomechanics and intraocular pressure (IOP) load on glaucomatous optic neuropathy; however, the role for biomechanical influence of the perilimbal scleral tissue on the aqueous humor drainage pathway, including the distal venous outflow system, and IOP regulation is not fully understood. The purpose of this work is to study the outflow characteristics of perfused porcine eyes relative to the biomechanical properties of the perilimbal sclera, the posterior sclera and the cornea. Enucleated porcine eyes from eleven different animals were perfused with surrogate aqueous at two fixed flow rates while monitoring their IOP. After perfusion, mechanical stress-strain and relaxation tests were conducted on specimens of perilimbal sclera, posterior sclera, and cornea from the same perfused eyes. Statistical analysis of the data demonstrated a strong correlation between increased tangent modulus of the perilimbal sclera tissues and increased perfusion IOP (R2 = 0.74, p = 0.0006 at lower flow rate and R2 = 0.71, p = 0.0011 at higher flow rate). In contrast, there were no significant correlations between IOP and the tangent modulus of the other tissues (Posterior sclera: R2 = 0.17 at lower flow rate and R2 = 0.30 at higher flow rate; cornea: R2 = 0.02 at lower flow rate and R2<0.01 at higher flow rate) nor the viscoelastic properties of any tissue (R2 ≤ 0.08 in all cases). Additionally, the correlation occurred for IOP and not net outflow facility (R2 ≤ 0.12 in all cases). These results provide new evidence that IOP in perfused porcine eyes is strongly influenced by the tangent modulus, sometimes called the tissue stiffness, of the most anterior portion of the sclera, i.e. the limbus.

This work presents an optospectroscopic characterization technique for soft tissue microstructure using site-matched confocal Raman microspectroscopy and polarized light microscopy. Using the technique, the microstructure of soft tissue samples is directly observed by polarized light microscopy during loading while spatially correlated spectroscopic information is extracted from the same plane, verifying the orientation and arrangement of the collagen fibers. Results show the response and orientation of the collagen fiber arrangement in its native state as well as during tensile and compressive loadings in a porcine sclera model. An example is also given showing how the data can be used with a finite element program to estimate the strain in individual collagen fibers. The measurements demonstrate features that indicate microstructural reorganization and damage of the sclera's collagen fiber arrangement under loading. The site-matched confocal Raman microspectroscopic characterization of the tissue provides a qualitative measure to relate the change in fibrillar arrangement with possible chemical damage to the collagen microstructure. Tests and analyses presented here can potentially be used to determine the stress-strain behavior, and fiber reorganization of the collagen microstructure in soft tissue during viscoelastic response., Competing Interests: The authors have declared that no competing interests exist.

Ocular tissue properties have been widely studied in tension and compression for humans and a variety of animals. However, direct shear testing of the tissues of the sclera appear to be absent from the literature even though modeling, analyses, and anatomical studies have indicated that shear may play a role in the etiology of primary open angle glaucoma (POAG). In this work, the mechanical behavior of bovine scleral tissue in shear has been studied in both out-of-plane and in-plane modes of deformation. Stress-strain and relaxation tests were conducted on tissue specimens at controlled temperature and hydration focusing on trends related to specimen location and orientation. There was generally found to be no significant effect of specimen orientation and angular location in the globe on shear stiffness in both modes. The in-plane response, which is the primary load carrying mode, was found to be substantially stiffer than the out-of-plane mode. Also, within the in-plane studies, tissue further from the optic nerve was stiffer than the near tissue. The viscosity coefficient of the tissue varied insignificantly with distance from the optic nerve, but overall was much higher in-plane than out-of-plane.

The constitutive behavior of bovine scleral and corneal tissues is measured in tension and compression, at quasi-static and moderate strain rates. Experiments are conducted at strain rates up to about 50 strain per second by a pneumatic testing system developed to overcome noise and measurement difficulties associated with the time dependent test of low impedance materials. Results for the tissues at room and the natural bovine body temperatures are similar and indicate that ocular tissue exhibits nonlinear stiffening for increasing strain rates, a phenomena termed rate hardening. For example, at a tensile strain rate of 29/s, corneal tissue is found to develop 10 times the stress that it does quasi-statically at the same strain. Thus, conventional constitutive models will grossly underpredict stresses occurring in the corneo-scleral shell due to moderate dynamic events. This has implication to the accuracy of ocular injury models, the study of the stress field in the corneo-scleral shell for glaucoma research and tonometry measurements. The measured data at various strain rates is represented using the general framework of a constitutive model that has been used to represent biological tissue mechanical data. Here it is extended to represent the measured data of the ocular tissues over the range of tested strain rates. Its form allows for straightforward incorporation in various numerical codes. The experimental and analytical methods developed here are felt to be applicable to the test of human ocular tissue.

The mechanical properties of sclera play an important role in ocular functions, protection, and disease. Modulating the sclera's properties by exogenous crosslinking offers a way to expand the tissue's range of properties for study of the possible influences on the eye's behavior and diseases such as glaucoma and myopia. The focus of this work was to evaluate the effects of genipin crosslinking targeting the porcine perilimbal sclera (PLS) since the stiffness of this tissue was previously found in a number of studies to influence the eye's intraocular pressure (IOP). The work includes experiments on tensile test specimens and whole globes. The specimen tests showed decreased strain-rate dependence and increased relaxation stress due to the cross-linker. Whole globe perfusion experiments demonstrated that eyes treated with genipin in the perilimbal region had increased IOPs compared to the control globes. Migration of the cross-linker from the target tissue to other tissues is a confounding factor in whole globe, biomechanical measurements, with crosslinking. A novel quantitative genipin assay of the trabecular meshwork (TM) was developed to exclude globes where the TM was inadvertently crosslinked. The perfusion study, therefore, suggests that elevated stiffness of the PLS can significantly increase IOP apart from effects of the TM in the porcine eye. These results demonstrate the importance of PLS biomechanics in aqueous outflow regulation and support additional investigations into the distal outflow pathways as a key source of outflow resistance. [ABSTRACT FROM AUTHOR]