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

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.