June 2015
Volume 56, Issue 7
ARVO Annual Meeting Abstract  |   June 2015
Photochemical kinetics model of corneal cross-linking with riboflavin
Author Affiliations & Notes
  • Pavel Kamaev
    Avedro, Inc, Waltham, MA
  • Mikhail Smirnov
    Avedro, Inc, Waltham, MA
  • Marc D Friedman
    Avedro, Inc, Waltham, MA
  • William A Eddington
    Avedro, Inc, Waltham, MA
  • Sarah Peterson
    Avedro, Inc, Waltham, MA
  • Evan A Sherr
    Avedro, Inc, Waltham, MA
  • David Muller
    Avedro, Inc, Waltham, MA
  • Footnotes
    Commercial Relationships Pavel Kamaev, Avedro (E); Mikhail Smirnov, Avedro (E); Marc Friedman, Avedro (E); William Eddington, Avedro (E); Sarah Peterson, Avedro (E); Evan Sherr, Avedro (E); David Muller, Avedro (E)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 3004. doi:
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      Pavel Kamaev, Mikhail Smirnov, Marc D Friedman, William A Eddington, Sarah Peterson, Evan A Sherr, David Muller, none; Photochemical kinetics model of corneal cross-linking with riboflavin. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3004.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: Corneal cross-linking (CXL) with riboflavin (Rf) for treatment of keratoconus has been performed for many years. The underlying photochemical kinetic mechanisms have been theorized, but not modeled or validated. The goal of this study was to develop and validate a sophisticated theoretical model for CXL with Rf.

Methods: A computer model of CXL was built (Comsol 5.0) as a matrix of partial differential equations representing CXL as a large set of photo-chemical reactions involving Rf, oxygen, and the corneal matrix. UVA irradiance, exposure time, and Rf concentration were parameterized. Oxygen partial pressure and pulsing light were also modulated to simulate various CXL treatments used in clinical practice. The model was validated against experiments with an oxygen sensor, and cross-linking of porcine corneas under several conditions (0.01-0.5% Rf, 3-30 mW/cm2 UVA at 365 nm, 20-100% O2) which were analyzed using papain digestion (1).

Results: The model accurately predicts oxygen behavior as well as the concentration of cross-links under various conditions of irradiance, dose and riboflavin concentration when compared to experimental results. The model also predicts the spatial profile of corneal cross-linking as well as riboflavin photo-chemical transformation from Rf to RfH2, and oxygen concentration.

Conclusions: A sophisticated theoretical model for CXL with Rf was developed and validated, elucidating underlying CXL mechanisms. The predictive capacity of this model allows study and optimization of CXL treatments, and predicting the behavior of treatment modifications and chemical additives to further improve CXL.<br /> (1) S. Rood-Ojalvo, P. Kamaev, M. Friedman, E. Sherr, D. Muller. Papain Digestion Method for Analysis of Cross-linking in Corneal Flaps. ARVO, Seattle 2013, poster C0199<br />


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