Is the corneal stromal demarcation line depth a true indicator of corneal collagen crosslinking efficacy?

Abstract

Moramarco et al.1 presented an interesting study comparing the corneal stromal demarcation line depth 1 month after corneal collagen crosslinking (CXL) using 2 CXL protocols. The authors discovered that using accelerated CXL, the corneal stromal demarcation line was significantly deeper using pulsed rather than continuous ultraviolet-A (UVA) light exposure and hypothesized that pulsed light–assisted accelerated CXL could be more effective clinically than standard continuous light–accelerated CXL. It would appear unreasonable to disagree with the authors’ interpretation of their results, which are based on the widely accepted clinical hypothesis that the depth of the corneal stromal demarcation line could reflect the efficacy of CXL. From their viewpoint, these findings also underscore at a clinical level the importance of corneal tissue oxygenation for effective CXL, as suggested by Richoz et al.2 However, the key question remains, and we believe the essential debate should focus on, whether the depth of the corneal stromal demarcation line is indeed a true indicator of CXL efficacy. In other words, does the “the deeper, the better” principle apply to CXL? Or do other confounding factors interfere with the clinical interpretation of the corneal demarcation line depth after CXL? There is evidence in the literature that the higher UVA light intensity used during accelerated CXL, the more superficial the corneal stromal demarcation line.1,3,4 Moreover, we would like to emphasize the lack of a standardized descriptive method of calculating the corneal stromal demarcation line. Considering there is a significant variation in axial resolution between different anterior segment optical coherence tomography devices, the difference in measured corneal stromal demarcation line depth could be substantial. On the other hand, there is no proportional decrease in CXL efficacy with increasing UVA light intensity.5,6 Therefore, we believe that the “the deeper, the better” principal is rather a simplistic approach of interpreting the clinical importance of the corneal stromal demarcation line. Considering that the elasticity of the anterior corneal stroma is significantly higher than that of the posterior corneal stroma and that each cornea has a different thickness, there should be a variable minimum corneal depth threshold of CXL treatment for biomechanical stabilization of the cornea that takes into account other factors influencing the measurement, such as intraocular pressure. We believe that studies with large numbers of eyes treated by different CXL modalities are required to correlate the corneal stromal demarcation line depth with the success–failure rate for each CXL modality and thereby extrapolate the critical minimum cutoff point of corneal depth for effective CXL, expressed as a percentage of the total corneal thickness. If it would be realistic to achieve biomechanical stability, crosslinking only the minimum amount of corneal tissue required, thereby using the minimum amount of energy and minimum time for treatment, might further improve the safety profile of the CXL treatment, reducing its potential complications. Until such studies have delivered further evidence, we believe that the clinical importance of the corneal stromal demarcation line depth is only relative and should be evaluated in this context.