Patient-specific computational modeling of keratoconus progression and differential responses to collagen cross-linking.
To model keratoconus (KC) progression and investigate the differential responses of central and eccentric cones to standard and alternative collagen cross-linking (CXL) patterns.



Three-dimensional finite element models (FEMs) were generated with clinical tomography and IOP measurements. Graded reductions in regional corneal hyperelastic properties and thickness were imposed separately in the less affected eye of a KC patient. Topographic results, including maximum curvature and first-surface, higher-order aberrations (HOAs), were compared to those of the more affected contralateral eye. In two eyes with central and eccentric cones, a standard broad-beam CXL protocol was simulated with 200- and 300-μm treatment depths and compared to spatially graded broad-beam and cone-centered CXL simulations.



In a model of KC progression, maximum curvature and HOA increased as regional corneal hyperelastic properties were decreased. A topographic cone could be generated without a reduction in corneal thickness. Simulation of standard 9-mm-diameter CXL produced decreases in corneal curvature comparable to clinical reports and affected cone location. A 100-μm increase in CXL depth enhanced flattening by 24% to 34% and decreased HOA by 22% to 31%. Topographic effects were greatest with cone-centered CXL simulations.



Progressive hyperelastic weakening of a cornea with subclinical KC produced topographic features of manifest KC. The clinical phenomenon of topographic flattening after CXL was replicated. The magnitude and higher-order optics of this response depended on IOP and the spatial distribution of stiffening relative to the cone location. Smaller diameter simulated treatments centered on the cone provided greater reductions in curvature and HOA than a standard broad-beam CXL pattern.
Cleveland Clinic Cole Eye Institute, 9500 Euclid Avenue, Cleveland, OH 44120, USA.
Abhijit
A
Sinha Roy
William J
WJ
Dupps
D003094:Collagen / Q000378:metabolism*; D003198:Computer Simulation; D003315:Cornea / Q000378:metabolism*; D019781:Corneal Topography; D003432:Cross-Linking Reagents / Q000627:therapeutic use*; D018450:Disease Progression; D004548:Elasticity / Q000502:physiology; D020342:Finite Element Analysis; D006801:Humans; D021621:Imaging, Three-Dimensional; D007429:Intraocular Pressure; D007640:Keratoconus / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D017319:Photosensitizing Agents / Q000627:therapeutic use; D012256:Riboflavin / Q000627:therapeutic use; D014466:Ultraviolet Rays
D003432:Cross-Linking Reagents; D017319:Photosensitizing Agents; D003094:Collagen; D012256:Riboflavin