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Can we safely cross-link thinner corneas? Pathways for optimized CXL treatment planning

Poster Details

First Author: M.Friedman USA

Co Author(s):    M. Smirnov   P. Kamaev   M. Mrochen   G. Lytle   D. Muller        

Abstract Details

Purpose:

Treatment parameters that may contribute to safety and efficacy margins for corneal cross-linking (CXL) were investigated. CXL with riboflavin (Rf) is a well-established procedure for treatment of keratoconus. 1-3 months after cross-linking, a “line of demarcation,” which is thought to be a measure of cross-linking depth, is commonly observed on Optical Coherence Tomography (OCT) and has been corroborated in the literature by confocal microscopy. A photochemical kinetics model of CXL with Rf was developed to determine underlying mechanisms of the cross-linking process, with theoretical outcomes correlated against the clinical data.

Setting:

Research Laboratory at Avedro Inc, Waltham MA USA

Methods:

Clinical literature was reviewed to correlate CXL protocols with observed depth of demarcation lines, as reported with OCT. Protocols ranged from irradiances of 3mW/cm2–30mW/cm2. These protocols were analyzed using a photochemical kinetics model formulated as a set of partial differential equations in 1D space and solved with finite-element software (Comsol 5.0) for the theoretical concentration of cross-links as a function of depth. A threshold number of cross-links per volume was set (5mol/m3) and the corresponding depth values were recorded for all protocols. The distribution of the cross-linking was also analyzed. The theoretical values were compared to the clinical values.

Results:

Analysis of the published clinical data alone revealed a decrease in the depth of the line of demarcation with increasing irradiance. Correlation of the measured depth of the line of demarcation versus the calculated depth of the line of demarcation using the model was plotted for each of the published protocols. The linear fit was y = 1.1065x - 28.743 with R² = 0.9825. It was also noted that the shape of the distribution of the cross-linking as a function of depth had a gradual slope for 3mW/cm2 and increasingly higher slopes for higher irradiances.

Conclusions:

After review of the clinical literature and validation through theoretical modeling, the depth of CXL may be accurately predicted for various CXL clinical protocols. The transition between cross-linked and uncross-linked stroma became more sharply defined with increasing irradiance. With lower irradiance, the transition was more gradual. With this knowledge it is believed that thinner corneas may be safely and effectively cross-linked by precisely tailoring the protocol to cross-link to a prescribed safety margin from the endothelium. Furthermore, this concept may be applied to tailoring treatment protocols for CXL for infectious keratitis to target the specific depth of infection.

Financial Disclosure:

One or more of the authors gains financially from product or procedure presented, One or more of the authors travel has been funded, fully or partially, by a company producing, developing or supplying the product or procedure presented, One or more of the authors research is funded, fully or partially, by a company producing, developing or supplying the product or procedure presented, One or more of the authors receives consulting fees, retainer, or contract payments from a competing company, One or more of the authors receives consulting fees, retainer, or contract payments from a company producing, developing or supplying the product or procedure presented, One or more of the authors is employed by a for-profit company with an interest in the subject of the presentation, One or more of the authors has significant investment interest in a company producing, developing or supplying product or procedure presented

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