Recent Advances in Corneal Collagen Cross Linking in Corneal and Refractive Surgeries

Abstract

Cross-linking of collagen refers to the ability of collagen fibrils to form strong chemical bonds with adjacent fibrils. In the cornea, collagen cross-linking occurs naturally with aging due to an oxidative deamination reaction that takes place within the end chains of the collagen. The basis for the currently employed corneal collagen cross-linking techniques were developed in Europe by researchers at the University of Dresden in the late 1990's. UV light was used to induce collagen cross-linking in riboflavin soaked porcine and rabbit corneas via the oxidation pathway. The resultant corneas were shown to be stiffer and more resistant to enzymatic digestion. Investigation also proved that the treated corneas contained higher molecular weight polymers of collagen due to fibril crosslinking. 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 microns.

Methods: 1. Standard Procedure After the application of topical anesthesia, the central epithelium with a diameter of 8-9 mm is removed with a blade. Then 0.1% riboflavin solution containing 20% dextran is dropped every 5 minutes for 30 minutes until the stroma is saturated with riboflavin. The cornea is then exposed to UVA (370 nm) for 30 minutes (energy density 3 mW/cm2). 2. 2. CXL with Hypoosmolar Riboflavin Solution Using hypoosmolar riboflavin solution (0.1% riboflavin in 0.9% saline instead of dextran) as an alternative treatment protocol to increase the corneal thickness. 3. “Epithelium-On” CXL Epithelial debridement in “Dresden protocol” may cause severe pain to the patient and may increase the risk of infection and stromal haze. Ophthalmologists attempted to find a modified CXL procedure without epithelium debridement, “epithelium-on” CXL procedure. “Epithelium-on” CXL was performed by applying an enhanced riboflavin solution with benzalkonium chloride, EDTA, and gentamicin which can help riboflavin penetrate into the corneal stroma through an intact epithelium.