Inverse computational analysis of in vivo corneal elastic modulus change after collagen crosslinking for keratoconus

• Type of Material: Article
• Authors: Abhijit Sinha Roy, Cleveland Clinic; Karol M. Rocha, Cleveland Clinic; J. Bradley Randleman, Emory University; R. Doyle Stulting, Emory University; William J. Dupps, Cleveland Clinic
• Language: English
• Date: 2013-08-01
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 Elsevier Ltd.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.exer.2013.04.010
• Title of Journal or Parent Work: Experimental Eye Research
• ISSN: 0014-4835
• Volume: 113
• Start Page: 92
• End Page: 104
• Grant/Funding Information: Supported in part by NIH K12RR023264/1KL2RR024990, RPB Challenge and Unrestricted Grants from Research to Prevent Blindness to the Department of Ophthalmology of the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, a Cleveland Clinic Innovations Product Development Award, and a grant from the National Keratoconus Foundation/Discovery Eye Foundation.; Also Supported in part by NIH NEI P30EY06360 and an unrestricted departmental grant from Research to Prevent Blindness to Emory University.; The computational analysis presented here involved no corporate funding.; William Dupps, Jr. is a recipient of a Research to Prevent Blindness Career Development Award.; Intellectual property related to corneal computational modeling through Cleveland Clinic Innovations, sponsored research with Avedro, Topcon, and Zeiss (Dr.s Dupps and Sinha Roy).
• Keywords: RIBOFLAVIN; biomechanics; RIBOFLAVIN/ULTRAVIOLET; Science & Technology; inverse finite element analysis; PORCINE; BIOMECHANICAL PROPERTIES; elastic modulus; ECTASIA; modeling; ABSORPTION; TOPOGRAPHY; ORIENTATION; collagen crosslinking; Life Sciences & Biomedicine; RESPONSES; ULTRAVIOLET; Ophthalmology; cornea; keratoconus
• Research Categories: Health Sciences, Opthamology; Engineering, Biomedical

Abstract

Corneal collagen crosslinking with riboflavin photosensitization and ultraviolet irradiation is a novel approach to limiting the progression of keratoconus in patients by increasing the elastic modulus of the degenerate cornea. Beneficial reductions in corneal steepness and aberrations after crosslinking also frequently occur. In a previous study, we described a computational modeling approach to simulating topographic progression in keratoconus and regression of disease with corneal collagen crosslinking. In the current study, this model has been expanded and applied to the inverse problem of estimating longitudinal time-dependent changes in the corneal elastic modulus after crosslinking using invivo measurements from 16 human eyes. Topography measured before crosslinking was used to construct a patient-specific finite element model with assumed hyperelastic properties. Then the properties of the cornea were altered using an inverse optimization method to minimize the difference between the model-predicted and invivo corneal shape after crosslinking. Effects of assumptions regarding sclera-to-cornea elastic modulus ratio and spatial attenuation of treatment effect due to ultraviolet beam characteristics on the predicted change in elastic modulus were also investigated. Corneal property changes computed by inverse finite element analysis provided excellent geometric agreement with clinical topography measurements in patient eyes post-crosslinking. Over all post-treatment time points, the estimated increase in corneal elastic modulus was 110.8±48.1%, and slightly less stiffening was required to produce the same amount of corneal topographic regression of disease when the sclera-to-cornea modulus ratio was increased. Including the effect of beam attenuation resulted in greater estimates of stiffening in the anterior cornea. Corneal shape responses to crosslinking varied considerably and emphasize the importance of a patient-specific approach.