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

Abstract

Since at least two decades, corneal cross-linking by riboflavin and UV-A irradiation stands as an established treatment option of progressive corneal ectasia. More than ten years ago, the histological evaluation of animal corneas and later of human corneas by means of in vivo biomicroscopy and scanning laser confocal microscopy demonstrated in corneas treated with cross-linking procedure the occurrence of a demarcation line running almost parallel to the corneal surface. The feature is a direct consequence of the cross-linking-induced photooxidative modification of the stromal tissue due to riboflavin stromal concentration, light distribution within the corneal stroma, riboflavin activation, oxygen availability and diffusion in the corneal stroma, radicals release, and UV-A exposure time. In this study, the general role of the demarcation line observed after a corneal cross-linking process, in particular its mechanical relevance, clinical consequences, and other various findings in the numerous nowadays available modalities of this treatment, are reviewed objectively.

Study of Demarcation Line Depth in Transepithelial versus Epithelium-Off Accelerated Cross-Linking (AXL) in Keratoconus

“…Both transepithelial and epi-off AXL have been shown to be biomechanically less efficacious than standard CXL [5]. The weaker effect is also reflected by the present study with the difference in the DL depth and the often patchy and irregular configuration or even absence of the DL in transepithelial AXL probably due to an inhomogenous distribution of the photosensitizer riboflavin [18].…”

“…Our results on AXL were markedly different from Yam et al who used a classic protocol of 3.0 mW/cm 2 for 30 minutes (surface dose 5.4 J/cm 2 ). The median CXL demarcation line depth at the central cornea was 323.0 ± 48.6, suggesting a significantly weaker cross-linking effect of AXL compared to standard CXL [5].…”

“…So-called accelerated cross-linking (AXL) has been proposed to shorten the duration of the procedure. It is based on the Bunsen-Roscoe law of reciprocity increasing the UVA irradiance and significantly reducing the irradiation time resulting in a similar overall UVA dose [5]. Transepithelial cross-linking, gained ground by leaving epithelium intact, improving patient comfort and minimizing the risk of infection associated with epithelial removal.…”

“…Studies have shown that the effective depth of standard CXL is confined to the anterior 300 um of the cornea as demonstrated by the depth of the keratocyte apoptosis with lacunar edema on histology and the clinical demarcation line [5].…”

Standard cross‐linking protocol versus accelerated and transepithelial cross‐linking protocols for treatment of paediatric keratoconus: a 2‐year comparative study

“…Mazzotta et al. () confirmed a strong relationship between DL and improvement in corneal biomechanical efficacy, thus achieving more efficient functioning of CXL with better stability. They considered that CXL involves limited amounts of collagen residues with the ability to attract free radicals.…”