Historically, management of corneal ectatic disorders involved attempts to delay keratoplasty—the only definitive treatment—for as long as possible by optimizing refractive correction. This paradigm has been transformed by the introduction of corneal collagen crosslinking (CXL) into clinical practice.1 This minimally invasive procedure effectively arrests, and sometimes reverses, ectasia progression.
Although CXL increases corneal stiffness (to strip extensiometry2-4) and resistance to enzymatic digestion5 and alters its behavior under thermal,6 hydrostatic,7 and electrophoretic stresses,8 the exact magnitude of its clinical effect cannot be quantified. The biomechanical information provided by these tests is either indirect or obtained using supraphysiologic forces.
Using the optical interferometric technique of radial shearing speckle pattern interferometry, our group has developed a nondestructive method of quantifying the biomechanical effect of physiologically relevant changes in corneal stress. We have investigated the variation in corneal stiffness with age and the effect of CXL as clinically practiced.
To determine the effect of age on corneal stiffness, 50 donor corneas from individuals between the ages of 24 and 102 years (Figure 1) were obtained and mounted in Barron artificial anterior chambers. Change in strain across the cornea was determined following an intraocular pressure increase (15–15.5 mm Hg). Strain maps were integrated to determine the increase in corneal apical displacement and Young's modulus, calculated by mathematical back analysis.
An identical approach was used to establish the effect of CXL on nine corneas that underwent epithelial debridement alone, epithelial debridement followed by riboflavin/UV-A CXL, or epithelial debridement followed by saturation with the histological fixative and powerful crosslinking agent 10% glutaraldehyde.
Corneal stiffness increased linearly with age, roughly doubling between the ages of 20 and 100 years. Following CXL with riboflavin/UV-A, corneal Young's modulus increased 4.3 times; after CXL with glutaraldehyde, the increase was 7.3-fold (Figure 2). If it were valid to extrapolate the linear relationship between stiffness and age indefinitely, this change is equivalent to CXL aging the cornea to just over 600 years. Glutaraldehyde CXL ages the cornea to about 1,000 years.
Such impressive changes are able to account for the clinical efficacy of CXL in arresting ectasia progression and, if capacity for corneal remodelling is speculated, also its regression. However, optimal corneal stiffness is unknown, and the mechanical changes that follow CXL are so substantial that it is possible they are excessive. It is important to develop means to target treatment to specific areas of the cornea and to modulate or even reverse the stiffening process.
John Marshall, PhD, FRCPath, FRCOphth(Hon), is the Frost Professor of Ophthalmology and Chairman of the Academic Department of Ophthalmology, Kings College London at Saint Thomas' Hospital. Dr. Marshall may be reached at e-mail: marshall-eye@kcl.ac.uk.
Nathaniel Knox-Cartwright, MA, MRCOphth, practices at St. Thomas Hospital at Kings College, London. Mr. Knox-Cartwright may be reached at e-mail: n.knoxcartwright@googlemail.com.
