Therapeutic cross-linking of the cornea using Riboflavin/UVA

Background: The method of cross-linking of the cornea using riboflavin and ultraviolet light (UV) has recently entered the phase of clinical evaluation. The purpose of this paper is to review the current knowledge about corneal cross-linking. Methods: A literature research (medline) using the key words "cross-linking" and "cornea" revealed 99 citations. Thirty-four of the 99 articles dealt with the topic and were used for this review. Some of our own as yet unpublished data were also included. Results: In a first phase (until 2003) different methods of cross-linking were experimentally compared regarding efficacy and safety. As the most promising compromise the use of UVA (370 nm) and riboflavin as a photomediator was tested in pilot studies on human eyes with progressive keratoconus. In 2003, the first results of such pilot studies were published. Surprisingly, not only a halt in progression was found but in more than half of the eyes treated a regression towards a more regular cornea took place. So far, no complications have been reported. Keratocytes are killed up to 320 microns deep in the stroma and the endothelium appears unaffected. Nine cases of therapy-refractory corneal melting were treated by means of UVA/riboflavin cross-linking and in 8 of the 9 cases the melting process was stopped. Conclusions: In the current situation, we can state only that UVA/riboflavin cross-linking of the keratoconus cornea leads in the majority of the cases to a halt of the progression and complications seem to be rare. There are not yet enough data available to establish a list of indications and contraindications. A potential clinical acceptance of the procedure requires the results of prospective controlled studies that are currently under-way.