A Review of Structural and Biomechanical Changes in the Cornea in Aging, Disease, and Photochemical Crosslinking

Abstract

The study of corneal biomechanics is motivated by the tight relationship between biomechanical properties and visual function within the ocular system. For instance, variation in collagen fibril alignment and non-enzymatic crosslinks rank high among structural factors which give rise to the cornea's particular shape and ability to properly focus light. Gradation in these and other factors engender biomechanical changes which can be quantified by a wide variety of techniques. This review summarizes what is known about both the changes in corneal structure and associated changes in corneal biomechanical properties in aging, keratoconic, and photochemically crosslinked corneas. In addition, methods for measuring corneal biomechanics are discussed and the topics are related to both clinical studies and biomechanical modeling simulations.

Keywords: aging; cornea; cornea biomechanical properties; crosslinking; crosslinking (CXL) corneal collagen; keratoconus.

Figure 1

Structural anatomy of human cornea. From left to right: (1) A diagram of human cornea structure. (2) The mean alignment of collagen fibrils with depth in human cornea is shown (Cheng et al., 2015) as well as the mean fibril diameter with depth in porcine cornea (Chang et al., 2018).

Figure 2

Images of lateral fiber alignment. Left: Figure reprinted with permission from reference Abahussin et al. (2009) published by The Association for Research in Vision and Technology (ARVO). Polar plot maps showing collagen fibril orientation at 0.5-mm intervals across varying depth: the anterior third (A) and middle 200 μm region (B) of a human cornea (P2). The posterior 200 μm of the cornea (with a full thickness scleral rim) (C), is shown after removal of the anterior (red dotted line) and middle (black dotted line) layers from the central 8- to 9-mm region. Polar plots have been scaled down to fit onto the grid as indicated in the color key. In this key, lower numbers (red and green) indicate less fibrillar alignment than higher numbers (white and gray). Right: Figure reprinted with permission from reference Boote et al. (2006), published by The ARVO. (A) Contour maps of aligned collagen X-ray scatter from a left/right pair of normal human corneas. Scatter from only preferentially aligned collagen fibrils. Dotted circle is the limbus. Scatter listed in arbitrary units. (B) Theoretical model of fibrillar arrangement based on (A). Inner solid circle is the limbus.

Figure 3

A visual representation of various method of measuring corneal biomechanics, plotted by spatial regime (x-axis, log-scale) and temporal regime (y-axis, log-scale). Numbers correspond to each method listed in Table 2.

Figure 4

Illustrative plots of depth-dependent corneal properties as measured by various methods. From left to right: the depth-dependent mechanical properties of porcine cornea measured by AFM (Seifert et al., 2014), Brillouin microscopy of human cornea (Scarcelli et al., 2014), shear rheometry of human cornea (Sloan et al., 2014), and extensiometry of human cornea (Randleman et al., 2008b).

Figure 5

Lateral mechanical anisotropy of the porcine cornea Left: Supersonic shear wave imaging of in vivo porcine cornea demonstrating corneal anisotropy. Figure reprinted with permission from reference Nguyen et al. (2014), published by The ARVO. Right: Shear Wave OCE detection of porcine corneal anisotropy at 20 mmHg intraocular pressure. Figure reprinted with permission from reference Singh et al. (2017), published by The Optical Society (OSA).