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Anterior Segment Cornea Vitamin B2 in Corneal Surgery—Riboflavin and Collagen Cross-Linking Spencer Thornton, MD, FACS Clinical Professor of Ophthalmology, University of Tennessee, Memphis, US Abstract Cross-linking of collagen refers to the ability of collagen fibrils to form strong chemical bonds with adjacent fibrils. Corneal collagen cross-linking (CXL) with vitamin B2 activated by ultraviolet offers a new method for stabilization of unstable or weakened corneal tissue in cases of ectasia, dystrophy and irregular post-surgical healing. Keywords Vitamin B2, corneal surgery, limbal thinning, Riboflavin CXL Disclosure: The author has no conflicts of interest to declare Received: July 19, 2012 Accepted: August 24, 2012 Citation: US Ophthalmic Review, 2012;5(2):105–6 Correspondence: Spencer P Thornton, MD, FACS, Clinical Professor of Ophthalmology at the University of Tennessee, Memphis, US. E: Support: The publication of this article was supported by Biosyntrx Because of increasing numbers of cases with corneal and limbal thinning, ways to stop or reverse the degenerative changes induced by corneal surgery (radial incisions, laser-assisted in situ keratomileusis (LASIK), lamellar keratoplasty) and degenerative diseases such as keratoconus have become imperative. These include several surgical and non-surgical modalities (vitamin therapy, ultraviolet (UV) light therapy and cross-linking). Originally developed as a new method to strengthen the weakened corneas of keratoconus, riboflavin CXL has been shown to strengthen the corneas in post-LASIK ectasias and in marginal corneal dystrophies. 1,2 Progressive irregular thinning (ectasia) is problematic and possible with any LASIK procedure. Cross-linking of collagen refers to the ability of collagen fibrils to form strong chemical bonds with adjacent fibrils. Some naturally occurs in the cornea with aging (as in other parts of the body), but for immediate therapeutic effect, chemical agents (UV-activated riboflavin) are used. In a number of studies, CXL has been shown to effectively stop the advancement of ectasia in eyes following excimer laser ablation. In an early German study with corneal cross-linking, the biomechanical status of the cornea was stabilized with a halting of the refractive and topographic progression of ectasia. 1 In practice, the cornea is saturated with riboflavin, then illuminated with UVA at a frequency of 365 nm, a wavelength which is strongly absorbed by the riboflavin. The riboflavin has a dual action of producing free radicals which cause cross-linking of the stromal collagen, creating stable bridges between collagen molecules, re-inforcing the corneal © TOUCH BRIEFINGS 2012 structure, strengthening the cornea, as well as acting as a shield to prevent significant levels of UV from penetrating deeper into the eye (see Figure 1). The photosensitizer riboflavin and UV irradiance lead to corneal tissue strengthening by increasing collagen covalent bonds, as in photopolymerization in polymers, leading to a significant increase in collagen fiber diameter and reduced elasticity. Immunofluorescent confocal microscopy has shown a pronounced compacting of collagen fibers in the anterior stroma after riboflavin and UVA exposure (see Figure 2). Cases of irregular astigmatism caused by ectasia have been treated by initial cross-linking followed by custom topography-guided surface ablation, with restoration of vision and stabilization of the ectasia, with improvement of patients' visual refractive and topographic outcomes. This method may eliminate the need for corneal transplantation. 3,4,6 Doyle Stulting, MD, states: “If cross-linking had been available in the US as it was in other parts of the world, 50 % of the corneal transplants could have been avoided.” 6,7 Joseph Colin, MD, has stated: “In theory, the UVA light could be damaging to the inner endothelial cell layer of the cornea, and this is why the corneal thickness of the stroma needs to be at least 350 µm if a standard CXL treatment is to be undertaken. Although UVA is potentially damaging to the lens and retina, it is believed that riboflavin soaking the stromal layer blocks the UVA transmission to an extent that no measurable damage will occur.” 6,8 105