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Updated: Apr 21, 2026

Three Different Protocols of Corneal Collagen Crosslinking in Keratoconus: Conventional, Accelerated and Iontophoresis
Published on: November 12, 2015
Effects of corneal cross-linking on ocular response analyzer waveform-derived variables in keratoconus and
Katie M Hallahan1, Karolinne Rocha, Abhijit S Roy
1Cole Eye Institute (K.M.H., K.R., A.S.R., W.J.D.), Cleveland Clinic, Cleveland, OH; Storm Eye Institute (K.R.), Medical University of South Carolina, Charleston, SC; Narayana Nethralaya Eye Hospital (A.S.R.), Bengaluru, India; Emory Eye Center (J.B.R.), Atlanta, GA; Stulting Research Center (R.D.S.), Woolfson Eye Institute, Atlanta, GA; and Biomedical Engineering (W.J.D.), Cleveland Clinic Lerner Research Institute, Cleveland, OH.
Purpose:
To assess changes in Ocular Response Analyzer (ORA) waveforms after UVA/riboflavin corneal collagen cross-linking (CXL) using investigator-derived and manufacturer-supplied morphometric variables in patients with keratoconus (KC) and postrefractive surgery ectasia.
Design:
Prospective randomized trial of a standard epithelium-off CXL protocol.
Participants:
Patients with progressive KC (24 eyes of 21 patients) or postrefractive surgery ectasia (27 eyes of 23 patients) were enrolled.
Methods:
Replicate ORA measurements were obtained before and 3 months after CXL. Pretreatment and posttreatment waveform variables were analyzed for differences by paired Student t tests using measurements with the highest waveform scores.
Main Outcome Measures:
Corneal hysteresis, corneal resistance factor, 37-s generation manufacturer-supplied ORA variables, and 15 investigator-derived ORA variables.
Results:
No variables were significantly different 3 months after CXL in the KC group, and no manufacturer-supplied variables changed significantly in the postrefractive surgery ectasia group. Four custom variables (ApplanationOnsetTime, P1P2avg, Impulse, and Pmax) increased by small but statistically significant margins after CXL in the postrefractive surgery ectasia group.
Conclusions:
Changes in a small subset of investigator-derived variables suggested an increase in corneal bending resistance after CXL. However, the magnitudes of these changes were low and not commensurate with the degree of clinical improvement or prior computational estimates of corneal stiffening in the same cohort over the same period. Available air-puff-derived measures of the corneal deformation response underestimate the biomechanical changes produced by CXL.
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