Biomechanical assessment in models of glaucomatous optic neuropathy

Abstract

The biomechanical environment within the eye is of interest in both the regulation of intraocular pressure and the loss of retinal ganglion cell axons in glaucomatous optic neuropathy. Unfortunately, this environment is complex and difficult to determine. Here we provide a brief introduction to basic concepts of mechanics (stress, strain, constitutive relationships) as applied to the eye, and then describe a variety of experimental and computational approaches used to study ocular biomechanics. These include finite element modeling, direct experimental measurements of tissue displacements using optical and other techniques, direct experimental measurement of tissue microstructure, and combinations thereof. Thanks to notable technical and conceptual advances in all of these areas, we are slowly gaining a better understanding of how tissue biomechanical properties in both the anterior and posterior segments may influence the development of, and risk for, glaucomatous optic neuropathy. Although many challenging research questions remain unanswered, the potential of this body of work is exciting; projects underway include the coupling of clinical imaging with biomechanical modeling to create new diagnostic tools, development of IOP control strategies based on improved understanding the mechanobiology of the outflow tract, and attempts to develop novel biomechanically-based therapeutic strategies for preservation of vision in glaucoma.

The connective tissue phenotype of glaucomatous cupping in the monkey eye - Clinical and research implications

“…While these concepts remain central to the discussion of ONH biomechanics in general, and the pathophysiology of glaucomatous damage to the ONH tissues specifically, a large group of investigators have expanded our understanding of glaucoma through the application of biomechanics and mechanobiology to the cornea (He and Liu, 2009, 2011; Liu and He, 2009; Liu and Roberts, 2005), trabecular meshwork (Braakman et al, 2014; Li et al, 2012; Overby et al, 2009; Stamer et al, 2014; Thomasy et al, 2012; Zhou et al, 2012), sclera (Coudrillier et al, 2013; Coudrillier et al, 2015a, b; Coudrillier et al, 2015c; Dastiridou et al, 2013; Fazio et al, 2014a; Fazio et al, 2014b; Girard et al, 2011b; Grytz et al, 2014; Nguyen and Ethier, 2015; Pijanka et al, 2012; Quigley et al, 2015) and ONH (Clark, 2012; Downs, 2015; Eilaghi et al, 2010; Girard et al, 2016; Girard et al, 2011a; Girard et al, 2013; Grytz et al, 2012a; Lei et al, 2011; Sigal et al, 2012; Sigal and Ethier, 2009; Sigal et al, 2005b, 2009a, b; Sigal and Grimm, 2012; Sigal et al, 2014; Stewart et al, 2014; Wang et al, 2016; Zhang et al, 2015) in health and disease. In sections 2.2 through 2.10, the details of these concepts are reviewed.…”

OCT-Detected Optic Nerve Head Neural Canal Direction, Obliqueness, and Minimum Cross-Sectional Area in Healthy Eyes

“…Therefore, unlike BMO and ASCO, the NCMCA is not an actual opening, being instead an estimate of the smallest area through which the axons must pass. Although the size and shape of the NCMCA may influence axonal susceptibility within the ONH, incorporation of the NCMCA into biomechanical engineering models that predict IOP/CSF-related ONH connective tissue loading [57][58][59][60][61] should be undertaken with caution. We predict that neural canal direction and obliqueness contribute to RGC axonal susceptibility within the prescleral and scleral (lamina cribrosa) portions of the neural canal.…”

“…On the basis of ONH biomechanics literature that emphasizes the importance of the peripapillary sclera, as well as the size and shape of the scleral canal, to ONH susceptibility, [57][58][59][60][61] we suggest that ASCO size and shape as well as neural canal direction, obliqueness and NCMCA be incorporated into biomechanical models that attempt to predict individual eye susceptibility to glaucomatous damage. [57][58][59][60][61] Neural canal direction and ASCO/BMO offset direction are both defined by the vector that connects the ASCO and BMO centroids, and are therefore, by definition, the same ( Figure 3C). However, in this study, we address them individually in part because the phenomenon underlying the term ''ASCO/BMO offset'' is more clinically intuitive than the term ''neural canal direction'' and in part because it has been suggested that the relationship between the ASCO and BMO longitudinally changes as part of progressive myopia.…”

Non-invasive MRI Assessments of Tissue Microstructures and Macromolecules in the Eye upon Biomechanical or Biochemical Modulation

“…Although these ex vivo imaging techniques have provided fundamental information on the microarchitecture and biochemistry of the tissue microstructures and collagen across ocular tissues with excellent resolution and sensitivity7, most of these techniques require chemical tissue processing or tissue sectioning, which is highly invasive and can be destructive or affect the true morphology of the collagen (e.g. substantial tissue shrinkage during preparation for histological labeling).…”