Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Up-Dated the Critical Issues of Corneal Cross-Linking (Type-I and II): Safety Dose for Ultra-Thin Cornea, Role of Oxygen and Initiator Regeneration

Version 1 : Received: 10 July 2021 / Approved: 13 July 2021 / Online: 13 July 2021 (11:19:16 CEST)

How to cite: Lin, J. Up-Dated the Critical Issues of Corneal Cross-Linking (Type-I and II): Safety Dose for Ultra-Thin Cornea, Role of Oxygen and Initiator Regeneration . Preprints 2021, 2021070296 (doi: 10.20944/preprints202107.0296.v1). Lin, J. Up-Dated the Critical Issues of Corneal Cross-Linking (Type-I and II): Safety Dose for Ultra-Thin Cornea, Role of Oxygen and Initiator Regeneration . Preprints 2021, 2021070296 (doi: 10.20944/preprints202107.0296.v1).

Abstract

Aims:To update analytic formulas for the overall efficacy of corneal collagen crosslinking (CXL) including both type-I and oxygen-mediated type-II mechanisms, the role of oxygen and the initiator regeneration. Study Design:modeling the kinetics of CXL in UV light and using riboflavin as the photosensitizer.Place and Duration of Study:New Taipei City, Taiwan, between June, 2021 and July, 2021.Methodology:Coupled kinetic equations are derived under the quasi-steady state condition for the 2-pathway mechanisms of CXL. For type-I CXL, the riboflavin (RF) triplet state [T] may interact directly with the stroma collagen substrate [A] to form radical (R) and regenerate initiator. For type-II process, [T] interacts with oxygen to form a singlet oxygen [1O2]. Both reactive radical (R) and [1O2], can relax to their ground state, or interact with the substrate [A]) for crosslinking. Based on a safety dose, the minimum corneal thickness formula is derived. Results:Our updated theory/modeling showed that oxygen plays a limited and transient role in the process, in consistent with that of Kamave [2]. In contrary, Kling et al [3] believed that type-II is the predominant mechanism, which however conflicting with the epi-on CXL results. For both type-I and type-II, a transient state conversion (crosslink) efficacy in an increasing function of light intensity (or dose), whereas, its steady state efficacy is a deceasing function of light intensity. RF depletion in type-I is compensated by the RF regeneration term (RGE) which is a decreasing function of oxygen. For the case of perfect regeneration case (or when oxygen=0), RF is a constant due to the catalytic cycle. Unlike the conventional Dresden rule of 400 um thickness, thin cornea CXL is still safe as far as the dose is under a threshold dose (E*), based on our minimum thickness formula (Z*). Our formula for thin cornea is also clinically shown by Hafez et al forultra thin (214 nm) CXL. Conclusion: For both type-I and type-II, a transient state conversion (crosslink) efficacy in an increasing function of light intensity (or dose), whereas, its steady state efficacy is a deceasing function of light intensity. Ultra thin cornea is still safe as far as it is under a threshold dose (E*), based on our minimum thickness formula.

Subject Areas

Corneal crosslinking; efficacy; kinetic modeling; oxygen; riboflavin; ultraviolet light; safety dose; minimum thickness.

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