Cornea and Cataract TOUCH MEDICAL MEDIA 115 Corneal Collagen Cross-linking for Keratoconus Daniel Herbert, 1 Vito Romano, 2 Oliver Baylis, 2 Natasha Spiteri, 2 Stephen B Kaye 2,3 and Sajjad Ahmad 2,3 1. School of Medicine, University of Liverpool, Liverpool, UK; 2. Department of Corneal and External Eye Diseases, St Paul’s Eye Unit, Royal Liverpool University Hospital, Liverpool, UK; 3. Department of Eye and Vision Science, University of Liverpool, Liverpool, UK Abstract Corneal collagen cross-linking (CXL) is a successful technique used to slow the progression of corneal ectatic disease, mainly keratoconus. It is able to achieve this aim with a single application of vitamin B2 (riboflavin) and ultraviolet-A light to the corneal stroma where it results in cross- links to form between the collagen fibres, resulting in corneal stiffening. We describe the different protocols, results and complications reported. Keywords Corneal collagen cross-linking, keratoconus Disclosure: Daniel Herbert, Vito Romano, Oliver Baylis, Natasha Spiteri, Stephen B Kaye and Sajjad Ahmad have nothing to disclose in relation to this article. No funding was received in the publication of this article. Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any non-commercial use, distribution, adaptation and reproduction provided the original author(s) and source are given appropriate credit. Received: 29 October 2015 Accepted: 9 December 2015 Citation: European Ophthalmic Review, 2015;9(2):115–20 Correspondence: Sajjad Ahmad, St Paul’s Eye Unit, Royal Liverpool University Hospital, 8Z Link, Prescot Street, Liverpool L7 8XP, UK. E: Sajjad.Ahmad@liverpool.ac.uk Cross-linking (CXL) is a technique originating from the synthetic polymer field that can be used to alter a polymer’s physical and mechanical properties. It was first proposed for corneal use by Theo Seiler from Germany in 1995 and was later applied clinically in 1998. 1 A corneal ‘cross- link’ is a bond between natural polymer chains such as collagen fibrils and proteoglycan core proteins. The induction of a photochemical reaction using riboflavin (vitamin B2) and ultraviolet A (UV-A) light (370 nm) produces these cross-links, which have been proved to generate free radicals that can strengthen and rigidify the cornea. This idea was conceived after observing the CXL of proteins that occurs naturally with ageing. 2 Keratoconus is a common bilateral disorder that causes progressive thinning of the cornea, transforming the normally regular dome-shaped cornea into a more irregular conical profile. 3 A defect in collagen allowing enzymatic degradation and fibrillary slippage is believed to be the cause of the weakened cornea. The resulting irregular astigmatism and corneal opacities lead to visual impairment. CXL can be used to treat keratoconus by stiffening the cornea, thus preventing the progressive change in shape. Keratoconus typically presents during adolescence; it normally progresses until approximately 40 years old, by which time natural cross-links within the cornea have become established. Keratoconus staging can be performed using the Amsler-Krumeich classification that contains four stages, ranging from mild (grade I) to severe (grade IV). 3 CXL offers the opportunity to change the natural history/evolution of the disease. The aim of the procedure is to slow the progression of this disease thus maintaining vision, and to prevent advanced changes that require more invasive therapy. Keratoconus is one of several non-inflammatory conditions that cause thinning of the cornea, termed ectasias. Corneal ectasia can also result as a rare yet serious complication of laser-assisted in situ keratomileusis (LASIK) surgery. Progressive post-LASIK ectasia can weaken the cornea’s structure causing astigmatism that is difficult to correct with lenses or further LASIK surgery. Thus, CXL may be beneficial to slow this process. 4 Techniques Used for Corneal CXL Current techniques for CXL involve the use of riboflavin drops and UV-A light exposure to the cornea. The several methods used are described in detail below. Epithelium-Off CXL The first attempt to cease the progression of keratoconus by using photochemical CXL was reported by Wollensak and co-workers in 2003. 4 The treatment technique used has become known as the Dresden protocol (named after the founding university in Germany). 5 The first step in this protocol is to remove the central 9 mm of corneal epithelium. The corneal surface is then saturated with 0.1 % riboflavin solution for 30 minutes, after which the eye is exposed to 370 nm of UV-A with an irradiance of 3 mW/cm 2 over an 8 mm diameter for a further 30 minutes. Additional riboflavin drops are given every 5 minutes during UV-A exposure. Essentially, the riboflavin within the corneal stroma is activated by UV-A to produce a photochemical reaction that creates collagen and proteoglycan cross-links. The original Dresden protocol takes approximately an hour and is usually performed under topical anaesthesia. Following treatment, a short course of topical antibiotics and vitamin A eye ointment is prescribed, with further antibiotics and fluorometholone drops as necessary. Different methods of disrupting the corneal epithelium for epi-off CXL have also been described, including the use of corneal disruptor devices 6 and chemical disruption using benzalkonium chloride. 7 Epithelium-On CXL Removal of the corneal epithelium in epithelium-off CXL (epi-off CXL) results in an iatrogenic corneal abrasion, causing post-operative discomfort that may last around 5 days. During this period there is an DOI: http://doi.org/10.17925/EOR.2015.09.02.115