Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Analysis of Dynamic Efficacy Profile of Corneal Cross-Linking: Role of Oxygen and Rate Constants

Version 1 : Received: 15 November 2021 / Approved: 17 November 2021 / Online: 17 November 2021 (10:39:32 CET)

How to cite: Lin, J.; Lee, Y. Analysis of Dynamic Efficacy Profile of Corneal Cross-Linking: Role of Oxygen and Rate Constants. Preprints 2021, 2021110298 (doi: 10.20944/preprints202111.0298.v1). Lin, J.; Lee, Y. Analysis of Dynamic Efficacy Profile of Corneal Cross-Linking: Role of Oxygen and Rate Constants. Preprints 2021, 2021110298 (doi: 10.20944/preprints202111.0298.v1).

Abstract

Purpose:To explore (theoretically) the key parameters and their influence on the time profiles of photosensitizer (riboflavin), free radicals, singlet oxygen, oxygen and the efficacy of corneal collagen crosslinking (CXL)in both type-I and oxygen-mediated type-II mechanisms, specially the role of oxygen and the initiator regeneration. Methodology:Coupled kinetic equations are derived and numerically solved under the quasi-steady state condition for the 2-pathway mechanisms of CXL. The key parameters explored include (bI, V, Q', K, K',Q,P) and their influence on the time profiles of photosensitizer (riboflavin, C), radicals (R), singlet oxygen(S), oxygen (X) and efficacy (E), parameters of (K,K',Q) define the relative strength of type-I and type-II process. The oxygen depletion profile, X(t), and the associated singlet oxygen, S(t), depend on the parameters of V, Q' and the initial value of oxygen. The coupling strength given by (bI) governs almost all profiles, where b is an effective absorption parameter and I is the UV light intensity.Results:Our numerical method for CXL dynamic profiles demonstrated the following important features: (i) Type-I and type-II coexit in CXL, in the presence of oxygen. However, there is no type-II when oxygen is depleted or in a condition without oxygen. (ii) Type-I with bimolecular termination, the radical R(t) is a function of [K'(bIgC)]0.5, leading to the steady-state efficacy given by a scaling law of 1/(bI)0.5, in contract to that of type-II which is almost independent to the light intensity. (iii) The depletion rate (2 to 5 minutes) of X(t) is much faster than that of C(t) (10 to 20 minutes), (iv) Thepure type-II profile, has a transition point from straight line to saturating curve and matches the depletion point of singlet oxygen S(t). (v) Improved CXL efficacy of type-I and type-II may be achieved by external supply of photoinitiator (riboflavin) and oxygen, respectively.

Keywords

Corneal crosslinking; efficacy; kinetic modeling; oxygen; riboflavin; ultraviolet light

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