Controversies in Corneal Collagen Cross-linking

Abstract

Cross-linking of collagen refers to the ability of collagen fibrils to form strong chemical bonds with adjacent fibrils. 1 In the cornea, collagen cross-linking occurs naturally with aging due to an oxidative deamination reaction that takes place within the end chains of collagen. 2 Collagen cross-linking in the cornea is also observed in patients with diabetes due to glycation resulting in additional bonds between collagen fibrils. 2 The original method of therapeutic corneal cross-linking was developed in Germany by researchers at the University of Dresden in 1998. 3 The process, later called the Dresden protocol, involves the use of UVA light and riboflavin to form bonds between collagen fibrils. Although the exact mechanism is unknown, it is believed that riboflavin causes the release of oxygen radicals that in turn induces an oxidation reaction to create new cross-linking bonds between collagen molecules. 3 The Dresden protocol involves the removal of the epithelium from the central 9.0 mm of the cornea (epithelial-off cross-linking), application of riboflavin in 20% dextrane for 30 minutes, and irradiation of the area with 3 mW/cm 2 of ultraviolet light at a wavelength of 365 nm for 30 minutes. 4 Multiple studies of porcine and rabbit corneas treated in this manner demonstrated that the resultant corneas were stiffer and more resistant to enzymatic digestion. 4 Safety studies showed that the endothelium was not damaged by the treatment if proper UV irradiance was maintained and if the corneal thickness exceeded 400 mm. 5 Clinical trials in human subjects with corneal cross-linking began in 2003 at the University of Dresden. The initial pilot study enrolled 22 patients (23 eyes) with moderate or advanced progressive keratoconus who were treated with the Dresden protocol. 6 Results showed that 16 eyes (70%) had a reduction of the maximal keratometry readings by 2 diopters and

Efficacy of pulsed-light accelerated crosslinking in the treatment of progressive keratoconus: Two-year results

“…On the contrary, the presence of oxygen is required for CXL, but high-exposure doses of UVA light cause a rapid decrease in the oxygen concentration. 14,15 In order to increase the efficacy of CXL treatment by replenishing the consumed oxygen, research has focused on pulsing the UVA light with “on” and “off” periods. Studies show increased efficacy of pulsed-light accelerated corneal collagen crosslinking (PLA-CXL) treatment in comparison with continuous-light accelerated corneal collagen crosslinking (CLA-CXL) treatment.…”

Keratoconus Treatment Toolbox: An Update

“…Due to the presence of oxygen is required for CXL, but high-exposure doses of UVA light cause a decrease in the oxygen concentration rapidly [45]. The recent technique has focused on pulsing the UVA light with "on" and "off " periods to increase the efficacy of CXL treatment by replenishing the consumed oxygen [46].…”