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Anterior Segment Cornea/External Disorders Collagen Crosslinking—An Evolving Procedure Spencer P Thornton, MD, FACS Clinical Professor of Ophthalmology, Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, Tennessee, US Abstract Vitamin therapy combined with minimally invasive corneal surgery appears to be safe and effective in treating ectasias of varied etiology. Keratoconus, laser-assisted in situ keratomileusis (LASIK), radial keratotomy (RK), and marginal dystrophies have presented significant challenges in ophthalmic surgery. Ectasia resulting from progressive keratoconus, marginal degeneration, or any of several corneal surgical procedures has been successfully treated with riboflavin-activated ultraviolet light. These minimal surgical modalities are a major advance, and are discussed in this article. Keywords Cornea, ectasia, keratoconus, collagen crosslinking, riboflavin, UV Disclosure: The author has no conflicts of interests to declare. Received: July 17, 2013 Accepted: August 12, 2013 Citation: US Ophthalmic Review, 2014;7(1):16–9 Correspondence: Spencer P Thornton, MD, FACS, 5031 Hillsboro Pike, Suite 314, Nashville, Tennessee 37215, US E: sthornton@biosyntrx.com “Look… Up in the sky… It’s a bird… It’s a plane… No, it’s supertechnology.” Commonly performed in Europe, South Africa, Canada, and China, corneal collagen crosslinking (CXL) is still off-label in the US. Why? Despite the proven effectiveness and safety of the procedure in many countries around the world, many feel that the lack of approval in the US is because of US Food and Drug Administration (FDA) bureaucracy and suppression of innovation. Femtosecond Laser for Corneal Eye Surgery Clinical Perspective Progressive irregular corneal thinning is problematic with any LASIK procedure. Developed as a method of strengthening weakened corneas of keratoconus, CXL has been shown to strengthen the corneas in post- LASIK ectasias and in marginal corneal dystrophies. 2 Developed in response to the need for a treatment for the ectasia of ketatoconus, Seiler et al., in the 1990s, introduced a procedure that was a fusion of vitamin therapy with corneal epithelial surgery. 1 The procedure has been shown to virtually stop the advancement of ectasia in keratoconus and that following excimer laser ablation. In their reported series, the biomechanical status of the cornea was stabilized, with minimal side effects and few complications. Crosslinking of collagen refers to the capacity of collagen fibers to form strong chemical bonds with adjacent fibrils. Some crosslinking naturally occurs in the cornea with aging, but for therapeutic effect under precise control, chemical agents (ultraviolet [UV]-activated riboflavin [RF]) are used. While there is no doubt that the microkeratome is a great tool for surgeons performing laser eye surgery, the femtosecond laser appears to be more accurate. But complications (transient light sensitivity, irregular flap with induced astigmatism, and ectasias) still occur. Dry eye syndrome is also a problem. The search for effective treatment continues (see Figures 2 and 3). Immunofluorescent confocal microscopy has shown a pronounced compacting of collagen fibers in the anterior stroma after RF and UVA exposure (see Figures 4–5). How it works. The photosensitizer RF and UV irradiance lead to corneal tissue strengthening by increasing collagen covalent bonds, as in photopolymerization in polymers. The crosslinking leads to a significant increase in collagen fiber diameter. Method In addition to the progressive degenerative condition keratoconus, corneal ectasia can occur following any type of corneal surgery, such as laser- assisted in situ keratomileusis (LASIK) procedures and radial keratotomy (RK), and in pathologic peripheral degeneration (marginal corneal dystrophy) (see Figure 1). 16 The cornea is saturated with RF, then illuminated with UVA at a frequency of 365  nm, a wavelength that is strongly absorbed by the RF. The RF has a dual action of producing free radicals that cause crosslinking of the stromal collagen, creating new, stable bridges between collagen molecules, reinforcing the corneal structure, strengthening the cornea, © TOU C H M E D ICA L ME D IA 2014