BIOMECHANICS and GLAUCOMA

 

Biomechanics is a newly developed interdisciplinary subject which applies mechanical principles and technology to biological systems.

The normal human sclera is composed from the outside to the inside of episclera, scleral stroma and lamina fascia. The episclera contains an irregular arrangement of interwoven small collagen fibers. The scleral stroma is composed of dense collagen fiber bundles containing many collagenous fibrils which lie parallel to each other on the outer surface, and which interlace and fuse together on the inner surface. The lamina fascia is composed of smaller collagen fiber bundles. Thus, collagen plays a major role in maintaining the structure, function and the biomechanical properties of the sclera.

The biomechanical theory of glaucoma proposes that optic nerve head (ONH) biomechanics may explain how IOP-induced stress and strain (a measure of tissue deformation) of the load bearing tissues of the ONH (sclera and lamina cribrosa/LC) influence their physiology and pathophysiology, and of the adjunctive tissues (astrocytes, glia, endothelial cells, vascular pericytes and their basement membranes) and the retinal ganglion cell (RGC) axons.

The biomechanical model of the disease proposes that IOP-induced mechanical strain on the ONH leads to a cascade of events eventually culminating in RGC dysfunction and apoptosis.

The ‘compliance’ (the inverse of stiffness) of the normal ONH in response to an acute elevation of IOP have been studied using techniques of increasing complexity. These include: X-ray photography of cadaveric non-human primate eyes with fine platinum wires inserted into the peripapillary sclera and optic disc, laser doppler velocimetry of normal human autopsy eyes, conventional histology of human eyes, 2D- and 3D-histo-morphometric reconstructions of post mortem normal monkey eyes. These reports were all consistent (to a greater or lesser degree) in finding a posterior movement of the optic disc surface in response to an acute elevation of IOP.

Finite element modeling is a computational tool for predicting how a complex biological tissue will behave under varying levels of load. Finite element modeling in monkey and human cadaver eyes have been used to study the mechanical response of the sclera to different levels of IOP.

The biomechanical model suggests that a given level of IOP-related stress may be physiologic or pathophysiologic depending on the individual ONH experiencing the stress.

Physiologic levels of IOP-related stress are assumed to be capable of inducing a broad spectrum of acute and chronic changes in all three ONH tissue types.

Pathophysiologic levels of IOP-related stress are assumed to induce pathologic changes in cell synthesis and tissue microarchitecture.

Scleral material properties, geometry, and thickness have significant effects on the biomechanical environment of the ONH.

There may be significant inter-individual differences in biomechanical behavior stemming from differences in the anatomy of the sclera.

The biomechanical environment within the ONH may play a role in RGC loss in glaucomatous optic neuropathy.

Biomechanically, it is hypothesized that IOP-induced mechanical strain on glial cells supporting ganglion cell axons eventually leads to apoptosis of the RGCs and the consequent loss of vision.

The “safe” level of IOP is patient specific, a difference that is likely due, at least in part, to differences in ONH geometry and biomechanical properties.

Strain represents the amount of stretching that a tissue undergoes, and stress is the force within the tissue per unit of tissue area. Strain is important since most research in mechanobiology suggests that cells respond to strain (deformation) rather than directly to stress. Stress is important because it determines the tendency of extracellular materials to fail (tear) as occurs at the periphery of the glaucomatous LC.