The meaning of the demarcation line after riboflavin-UVA corneal collagen crosslinking

ABSTRACT

Introduction: The demarcation line (DL) observed since the pioneering crosslink (CLX) protocol at the posterior edge of the cross-linked stroma has been universally accepted as a therapeutic milestone of treatment. Numerous laboratory and clinical CXL studies demonstrate that a deeper DL is associated with a higher amount and saturation level of crosslinks, a more pronounced stiffening effect, and a more durable ectasia stability.

Areas covered: A critical revision of laboratory, clinical, and analytical studies on the DL depth supports the significance of the DL as an evaluator of the performance of CLX procedures in terms of biomechanical efficacy and safety avoiding extensive experiments. A mechanical approach based on experimental data shows that the DL depth obtained with different CXL protocols relates with an asymptotic non-linear increasing function to the modified biomechanical corneal stiffness (elastic modulus).

Expert opinion: The strong connection between the depth of the DL and the increase of the biomechanical efficacy can be explained by means of UV cross-linking chemical investigations demonstrating that only a limited amount of free reactive collagen residues is involved in the short-wave UV-mediated CXL. Thus, the CXL density can rise only up to an upper boundary value, i.e. the saturation value.

KEYWORDS:

• Confocal microscopy
• cornea
• cross-linking
• demarcation line
• keratoconus
• riboflavin
• UVA
• Young´s modulus

Article highlights

• The article provides a critical review of the clinical and mechanical significance of the demarcation line depth in crosslink procedures.

• The DL depth is related to the UV-A exposure times and to the power supplied to the radiation in a nonlinear way.

• The same nonlinearity is observed between the UV-A exposure times and power supplied and an increase in the mechanical stiffness of the cornea in terms of elastic modulus.

• The lack of a linear relationship between irradiation times and power and biomechanical improvement is due to the saturation of the free reactive collagen residues involved in the short wave UV-mediated CXL.

• The DL depth can be considered as a sound evaluator of the performance of CLX procedures in terms of biomechanical efficacy and safety.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.