REVIEW Determination of corneal biomechanical properties in vivo: a review Z. Gatzioufas 1 and B. Seitz* 2 Corneal biomechanical properties are essential for the early detection of corneal ectatic disease such as keratoconus, as well as for predicting and evaluating the visual outcome in corneal refractive surgery, the risk for corneal ectasia and the response to corneal collagen cross-linking. Advances in measurement of corneal biomechanical properties have the potential to enhance early keratoconus diagnosis, enable personalised, procedure specific ectasia risk assessment and optimise cross-linking treatment for stopping progression of corneal ectatic disease. Current corneal imaging technology provides an accurate anatomical and topographical analysis of the cornea, which is the ‘gold standard’ for the diagnosis of corneal ectatic disease and the preoperative screening in refractive surgery. Until recently, evaluation of corneal biomechanics was feasible only in vitro, since the technology required for in vivo analysis was not available. However, in the recent years, there have been developed methods that enable an accurate in vivo analysis of corneal biomechanics, thereby introducing a new era in corneal diagnostics and corneal refractive surgery. Keywords: Corneal biomechanics, Corneal hysteresis, Corneal resistance factor, Corneal viscoelasticity, Ocular Response Analyser, Corvis ST, Reviews This paper is part of a special issue on Biomaterial characterisation Introduction The cornea is a complex biomechanical composite, which behaviour depends on its structural subcompo- nents and their organisational patterns. The mechanical properties of the cornea and its constituent materials link the cornea’s morphology to its behaviour under the stress of surgery or disease. Analysis of the corneal biomechanical behaviour is therefore a major investiga- tional challenge due to the potential for identifying corneal ectatic disease, quantifying corneal ectasia risk in refractive surgery and designing predictive computa- tional models of corneal ectatic disease. Until recently, investigation of corneal biomechanics was feasible only in vitro, since the technology required for in vivo analysis was not available. However, in the recent years, there have emerged novel methods, which enable a real time analysis of corneal biomechanics in vivo, thereby increasing our understanding of corneal biomechanical properties in normal conditions as well as in disease. As a result of intensive and continuous research in the field of corneal biomechanics, there have been designed commercially available medical devices, which facilitate the real time biomechanical screening of the cornea in vivo. This review focuses on the clinical importance of investigating the corneal biomechanical properties in vivo, as well as on the available technology, which allows the determination of corneal biomechanics in vivo. Fundamentals of corneal biomechanics In the terminology of material science, the cornea is a complex anisotropic composite with non-linear elastic and viscoelastic properties. It is a composite because its proper- ties are determined by the interaction of disparate mate- rials like collagen and a polyanionic ground substance. It is anisotropic because its properties are not directionally uniform. The cornea is also highly structurally hetero- geneous when the centre is compared to the periphery and the anterior cornea is compared to posterior surface. The elastic (or Young’s) modulus is the most important material property for understanding and predicting overall corneal biomechanical behaviour in health and disease. 1 The elastic modulus is traditionally measured in excised corneal tissue by extensiometry, a technique that measures force generation during steady axial elongations of the sample in a manner similar to stretching a spring. The slope of stress (force per unit area) over strain (a dimen- sionless quantity defined by the current length of the sample divided by its starting length) is calculated for a representative portion of the curve. A high modulus indicates a stiff (low compliance) material. While most biological soft tissues approximate linear elastic behaviour when a small range of stresses is considered, their overall elastic behaviour is highly non-linear. Viscoelastic properties arise from the time dependent nature of biomechanical responses and are a feature of 1 Department of Ophthalmology, Geneva University Hospitals HUG, Geneva, Switzerland 2 Department of Ophthalmology, University Medical Center of Saarland, Homburg, Saar, Germany *Corresponding author, email berthold.seitz@uks.eu ß 2015 Institute of Materials, Minerals and Mining Published by Maney on behalf of the Institute Received 13 February 2014; accepted 11 July 2014 DOI 10.1179/1743284714Y.0000000612 Materials Science and Technology 2015 VOL 31 NO 2 188