Translating ocular biomechanics into clinical practice: current state and future prospects

Abstract

Biomechanics is the study of the relationship between forces and function in living organisms and is thought to play a critical role in a significant number of ophthalmic disorders. This is not surprising, as the eye is a pressure vessel that requires a delicate balance of forces to maintain its homeostasis. Over the past few decades, basic science research in ophthalmology mostly confirmed that ocular biomechanics could explain in part the mechanisms involved in almost all major ophthalmic disorders such as optic nerve head neuropathies, angle closure, ametropia, presbyopia, cataract, corneal pathologies, retinal detachment and macular degeneration. Translational biomechanics in ophthalmology, however, is still in its infancy. It is believed that its use could make significant advances in diagnosis and treatment. Several translational biomechanics strategies are already emerging, such as corneal stiffening for the treatment of keratoconus, and more are likely to follow. This review aims to cultivate the idea that biomechanics plays a major role in ophthalmology and that the clinical translation, lead by collaborative teams of clinicians and biomedical engineers, will benefit our patients. Specifically, recent advances and future prospects in corneal, iris, trabecular meshwork, crystalline lens, scleral and lamina cribrosa biomechanics are discussed.

Keywords: Brillouin microscopy; intraocular pressure; ocular biomechanics; ophthalmic pathologies; optical coherence tomography; personalised medicine; translational biomechanics.

Figure 1

Optical coherence elastograms of control and crosslinked rabbit corneas. Cooler colors (blues) indicate lower strains and correspond to greater relative stiffness. The uncrosslinked cornea (bottom) demonstrates a depth-dependent gradient of properties with greatest stiffness in the anterior stroma. A cornea treated with transepithelial UVA-riboflavin crosslinking with tetracaine as an irritative adjunct (top) shows greater stiffness than the control (from experiments described in [39]).

Figure 2

Finite element analysis comparing the topographic effects of A) a standard 9mm collagen crosslinking treatment, B) a more graduated UV treatment profile with a smaller effective diameter, and C) a graduated treatment centered on the cone. Tangential curvature maps (D-F) show the change from pre-to-post crosslinking state. Topographic flattening was greatest with the cone-centered simulation.[29]

Figure 3

(a) Schematic of the eye during accommodation. (b) Scheimpflug images of 19-year-old (top) and 69-year-old (bottom) humans in unaccomodated (left, far vision) vs. accommodated (right, near vision) states. The stretching of the lens by the tension of the zonules is apparent in the young but not in the old lens. Images were reproduced and modified with permission from Koretz and Handelman, Sci. Am. 259, p.92, 1988. (c) MRI images of a 26-year-old vs. a 49-year-old subject in the unaccomodated state. The difference in size is apparent. Images were reproduced and modified with permission from Strenk et al., Progr. Eye Ret. Reas. 24, p.379, 2005. (d) The Brillouin frequency shift, which is directly related to the hypersonic longitudinal modulus, along the optics axis of a 60-year-old normal volunteer (measured at an optical wavelength of 780 nm).

Figure 4

Biomechanical effects on the LC of a 79 year old donor eye to an acute increase in IOP of 35 mmHg (from 10 to 45 mmHg). The effects were computed analyzing second harmonic generated images acquired ex-vivo.[195]

Figure 5

C-mode section at the level of the LC through an Adaptive optics OCT scan of a glaucomatous eye acquired in-vivo (left). The beams (blue) and pores (green) were identified using a semi-automated segmentation technique (middle). Beam thickness was then measured at every voxel, where hotter colors represent thicker beams (right). (Courtesy of the Glaucoma Imaging Group, University of Pittsburgh)[207]