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Technological innovations in corneal collagen cross-linking
Improving the outcomes of progressive keratoconus therapy


Ophthalmology Times Europe
Volume 3, Issue 7

Corneal collagen cross-linking represents a new therapeutic option for delaying or halting keratoectasia in progressive keratoconus and post-LASIK ectasia. The basic technique was developed in Dresden in 1998 by Wollensak, Spoerl and Seiler, however, it wasn't until 2003 that the first clinical trial data in 22 patients was published by the same authors.1

We introduced corneal collagen cross-linking in Italy for the first time in 2004 at Siena University in the form of the Siena Eye Cross Project, which was awarded "Best Ophthalmological Research of the Year in Italy" by the Italian Society of Ophthalmology. We, along with some other colleagues published the preliminary report of the first 10 cases treated in Italy in 2006,2 and the final report of 44 patients was presented in June 2007 at the local Ethical Committee of Siena University.

The Italian Eye Cross Study, which was conducted by Caporossi and co-workers, represents the first international in vivo analysis of the human cornea by scanning laser in vivo confocal microscopy, performed by Mazzotta,3,4 and strongly supports the safety and efficacy of the Riboflavin UV-A collagen cross-linking technique. The first international confocal results in humans were published in the European Journal of Ophthalmology in 20063 and, more recently, in the journal Cornea in May 2007.4

The basics of collagen cross-linking

The technique of Riboflavin UV-A collagen cross-linking1,2 involves the photo-polymerization of corneal collagen by increasing chemical inter- and intra-helical bond formation. This mechanism of molecular cross-linking allows the cornea to build strength and a resistance to ectasia. The mechanism of hardening and thickening the cornea is mediated by a photodynamic reaction between the photosensitizer Riboflavin 0.1 % / Dextrane 20% solution (Ricrolin; Sooft, Italy) and low-dose UV-A irradiation (3 mW/cm2 ) with a total exposure time of 30 minutes. The release of reactive oxygen species (ROS) during the reaction stimulates covalent bond formation between collagen fibres.

At our clinic, the UV-A irradiation is delivered by a solid state UV-A illuminator named C.B.M. (Caporossi-Baiocchi-Mazzotta) X-Linker VEGA, which is CE-marked and was developed by us in collaboration with the Italian firm C.S.O. (Costruzione Strumenti Oftalmici, Badia a Settimo, Florence, Italy).3,5 The clinical experience that we have now achieved at Siena University has enabled us to develop a UV-A source that optimizes the surgical technique and postsurgical outcomes of corneal cross-linking.2,3,4,5

What is different about our technology?

The first Italian prototype was developed in 2004 at Siena University by Caporossi and Mazzotta2,6 in collaboration with the National Research Council of Florence. It consisted of a dual LED UV-A illuminator similar to the first instrument used in Dresden Technical University for the cross-linking pilot study.1 The only difference between the two illuminators was in the energy stabilizing system (CM controller). The new prototype was designed to obtain a timely, homogeneous irradiation, thus avoiding the emission peak and energy decrease related to battery pack systems.2 The first spot diameter was 6 mm and the UV-A source was focused at a distance of 1 cm from the corneal apex.

In 2005 we, in collaboration with C.S.O., went on to create the "CBM X linker" (Caporossi-Baiocchi-Mazzotta cross-linker).3,5 Learning from our experience with the previous system,2 the aim of this new technology was to obtain the most circular illumination spot and the biggest and most constant in its diameter. In order to do this, we increased the cross-linkable area to 9 mm, by using an illuminator made of a five UV-A LED array (370-10), mounted on a heat sink system in the source head of the equipment and powered by a stabilized circuit to provide an energy equal to a safe and efficient value (5.4 J/cm2 , thus 3.0 mW/cm2 as power density).


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