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

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 in vivo 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 in vivo 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.

Corneal cross-linking

“…Computer simulation modeling may provide insight into the biomechanical changes following cross-linking and provide better clinical metrics to follow. 126,135 …”

Slowing the Progression of Keratoconus - Turning to Corneal Crosslinking

“…[40] More topographic flattening occurs in eyes with centrally located cones and the least flattening effect of the cone occurs when the cone is located peripherally. [9][10][11] A great challenge today is the management of the keratoconus in patients with more advanced or decentered ectasia, intolerant to rigid gas permeable contact lenses and poor spectacles corrected visual acuity. [40,41] The refraction of these patient is always difficult because spectacle correction is unable to correct HOA and irregular astigmatism, especially in peripheral cones, and a comfortable contact lens fitting sometimes is hard to reach or not possible at all and could cause corneal scarring or infection.…”

“…[4,5] Since its introduction, the CXL technique was developed and evolved in order to shorten the treatment time and to extend the indication to thin corneas (Raiskup-Spoerl-Hafezi hypotonic solution CXL, Mazzotta's epithelial island CXL, Jacob's contact-lens-assisted CXL), to the more advanced and decentered cones, alone or in combination with excimer laser photo-ablation, intra-corneal rings segments (ICRS) and phakic intraocular lenses (CXL plus). [6][7][8][9][10][11][12][13][14] According to current evidences of CXL safety and efficacy, the National Institute for Health and Care Excellence in the UK, since September 2013, recommended only the cross-linking with epithelium removal as a benchmark for this conservative treatment of progressive ectasia.…”

“…The protocol showed in Table 1 is based on patient-specific computational modeling of keratoconus progression and differential responses to CXL. [9][10][11] According to computational analysis, smaller-diameter-simulated CXL treatments centered on the cone provided greater reductions in corneal curvatures and HOA than conventional broad-beam CXL patterns. [9] In our experience, by using energy doses higher than standard 5.4 J/cm 2 (7.2, 10 and 15 J/cm 2 ), the keratocytes apoptosis was detected between 250 and 300 µm.…”

“…[9][10][11][12][13] Many authors described several approaches combining different CXL and refractive surgery protocols performed at the same time (same-day) or in two surgical steps. [9][10][11][12][13] The thinnest corneal thickness (measured with epithelium) considered for residual stromal bed in these papers varied from 300 to 450 µm. The common opinion is to consider 50 µm as maximum stromal ablation depth.…”