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Purpose: To evaluate depth-resolved changes of corneal biomechanical properties in eyes with corneal ectasia after corneal crosslinking (CXL) using optical coherence elastography., Methods: In a prospective pilot series of eyes with corneal ectasia, a custom high-speed swept source optical coherence tomography system was used to image the cornea before and 3 months after CXL during a low-speed applanating deformation while monitoring applanation force. Cross-correlation was applied to track frame-by-frame two-dimensional optical coherence tomography speckle displacements, and the slope of force versus local axial displacement behavior during the deformation was used to produce a two-dimensional array of axial stiffness (k). These values were averaged for anterior (ka) and posterior (kp) stromal regions and expressed as a ratio (ka/kp) to assess depth-dependent differences in stiffness. CXL was performed according to the Dresden protocol with a system approved by the U.S. Food and Drug Administration., Results: Four eyes from four patients with keratoconus (n = 3) or post-LASIK ectasia (n = 1) underwent optical coherence elastography before and 3 months after CXL. The mean ka/kp was 1.03 ± 0.07 before CXL compared with 1.34 ± 0.17 after the CXL procedure. All four eyes demonstrated at least a 20% increase in the ka/kp., Conclusions: Preferential stiffening of the anterior stroma with the standard CXL protocol was demonstrated with optical coherence elastography in live human subjects., Translational Relevance: Although ex vivo studies have demonstrated anterior stiffening effects after CXL using various destructive and nondestructive methods, this report presents the first evidence of such changes in serial live human measurements.

Purpose: Compare depth-resolved biomechanical properties in normal and keratoconic corneas in live human subjects using optical coherence elastography (OCE)., Methods: In a prospective series of normal and keratoconus (KC) eyes, a corneal perturbation was applied by a custom swept-source OCE system using a transparent flat lens coupled to force transducers. Cross-correlation was applied to track frame-by-frame OCT speckle displacement. Regional displacements for the anterior and posterior stroma were plotted in force versus displacement ( k ) graphs. A spatial biomechanical property ratio ( k a /k p ) was defined by dividing the maximum total displacement by the maximum force for the anterior ( k a ) and posterior cornea ( k p ) and was compared between normal and KC groups with the Mann-Whitney U test. Area under the receiver operating characteristics curve (AUROC) for differentiating normal and KC eyes was calculated for k a /k p , k max , and thinnest point of corneal thickness (TPCT)., Results: Thirty-six eyes were analyzed (21 eyes of 12 normal subjects and 15 KC eyes of 12 subjects). The k a /k p for the normal group was 1.135 ± 0.07 (mean ± standard deviation) and 1.02 ± 0.08 for the KC group ( P < 0.001), indicating a relative deficit in anterior stromal stiffness in KC eyes. AUROC was 0.91 for k a / k p , 0.95 for k max , and 1 for TPCT., Conclusions: Significant differences in depth-dependent corneal biomechanical properties were observed between normal and KC subjects., Translational Relevance: OCE was applied for the first time to human KC subjects and revealed alterations in the normal anterior-to-posterior stromal stiffness gradient, a novel and clinically accessible disease biomarker., Competing Interests: Disclosure: V.S. De Stefano, None; M.R. Ford, Cleveland Clinic (P); I. Seven, None; W.J. Dupps, Cleveland Clinic (P), Alcon (C), Zeiss (C), Glaukos (C), (Copyright 2020 The Authors.)