Corneal Viscoelastic Properties from Finite-Element Analysis of In Vivo Air-Puff Deformation Sabine Kling, Nandor Bekesi, Carlos Dorronsoro, Daniel Pascual, Susana Marcos* Instituto de O ´ ptica ‘‘Daza de Valde ´s’’, Madrid, Spain Abstract Biomechanical properties are an excellent health marker of biological tissues, however they are challenging to be measured in-vivo. Non-invasive approaches to assess tissue biomechanics have been suggested, but there is a clear need for more accurate techniques for diagnosis, surgical guidance and treatment evaluation. Recently air-puff systems have been developed to study the dynamic tissue response, nevertheless the experimental geometrical observations lack from an analysis that addresses specifically the inherent dynamic properties. In this study a viscoelastic finite element model was built that predicts the experimental corneal deformation response to an air-puff for different conditions. A sensitivity analysis reveals significant contributions to corneal deformation of intraocular pressure and corneal thickness, besides corneal biomechanical properties. The results show the capability of dynamic imaging to reveal inherent biomechanical properties in vivo. Estimates of corneal biomechanical parameters will contribute to the basic understanding of corneal structure, shape and integrity and increase the predictability of corneal surgery. Citation: Kling S, Bekesi N, Dorronsoro C, Pascual D, Marcos S (2014) Corneal Viscoelastic Properties from Finite-Element Analysis of In Vivo Air-Puff Deformation. PLoS ONE 9(8): e104904. doi:10.1371/journal.pone.0104904 Editor: Craig Boote, Cardiff University, United Kingdom Received May 1, 2014; Accepted July 15, 2014; Published August 14, 2014 Copyright: © 2014 Kling et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability: The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper and its Supporting Information files. Funding: Spanish Government FIS2011-25637, European Research Council ERC-2011 AdG-294099 to SM. FPI-BES-2009-024560 Pre-doctoral Fellowship to SK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * Email: susana@io.cfmac.csic.es Introduction The demand for measuring biomechanical properties of biological tissue in-vivo and non-invasively is high, because abnormal tissue biomechanics play a key role in a wide range of diseases. The stress distribution [1] around and stiffness [2] of tumor tissue largely determine its progression. Biomechanical properties are also indicative of muscle function [3] and the effects of disease, wound healing [4], aging or cosmetics [5]. In ophthalmology, ocular biomechanics are essential for basic research, clinical evaluation, prognosis and treatment. Patholog- ical weakening of the cornea appears to be responsible for the corneal bulging, and dramatic visual degradation in keratoconus. Corneal collagen cross-linking is an emerging treatment to increase corneal stiffness in this disease [6]. Theoretical models that integrate individual mechanical, geometrical and structural patient data have the potential to improve clinical outcomes of eye surgery, but depend largely on the identification of pre-operative biomechanical parameters. Most frequently only the elastic tissue properties are evaluated, more specifically the elasticity modulus. However, also time-dependent mechanical properties are expected to matter, along with active remodeling processes. For example, the progressive deformation of the cornea (ectasia) occurring in keratoconus [17] and after some laser refractive procedures [18], may result from an altered stress distribution of the cornea inducing viscoelastic deformation until the new steady state is reached. Also certain treatments such as UV corneal collagen cross-linking (CXL) likely modify both elastic and viscoelastic properties. Changes in the degree of collagen interweaving, keratocyte density or the presence of hydrophilic proteoglycans may result in the viscoelastic failure or abnormal repair [19]. Today, most information regarding available corneal biome- chanical properties was assessed ex vivo [7,8,9,10], where changes in the hydration state [9] and other non-physiological conditions affect the measurement. In vivo approaches to measure corneal biomechanical proper- ties include stepwise indentation with a cantilever [11]; ultrasonic [12] and magnetic resonance [13] techniques; corneal optical coherence elastography [14]; phase-sensitive [15] Optical Coher- ence Tomography (OCT); and Brillouin microscopy [16]. Drawbacks of several of these techniques include that they only can be operated at low speed, have a low spatial resolution or require contact with the patient’s corneal surface. Studying the dynamic deformation following an air-puff has recently been proposed in different biomedical areas (skin [5], bacteria [20], cornea [21], soft tissue tumors [22]) to non- invasively assess biomechanical properties, but also in other fields to study chicken embryogenesis [23], fruit firmness [24] or meat tenderness [25]. In most cases the degree of deformation of the sample is empirically related to mechanical parameters, and the inherent mechanical parameters of the tissue were rarely retrieved. To our knowledge, only Boyer et al [5] proposed an analytical estimation of the ‘‘restricted Young’s modulus’’ from experimental deformation curves in skin. Air puff applanation of the cornea is a frequent technique in ophthalmology to measure intraocular pressure, yet requiring correction formulae to account for corneal thickness and stiffness. PLOS ONE | www.plosone.org 1 August 2014 | Volume 9 | Issue 8 | e104904