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Keratoconus is a condition in which the biomechanical strength of the cornea's collagen fibres is reduced to about half their normal strength, causing the cornea to bulge forward in a conical shape, with an off-centre apex.
This change in shape of the cornea results in high levels of irregular astigmatism, which is initially corrected with spectacles but, as the disease progresses, the astigmatism increases and requires correction with specialist contact lenses. Eventually, if the keratoconus becomes very advanced, some patients will require a corneal graft.
A new procedure aims to halt the progression of keratoconus, before it reaches the stage where a graft is required. This procedure is based on increasing the tensile strength of the cornea by cross-linking. Until recently cross-linking was not widely known in ophthalmology, but it is a standard technique used in polymer science, for increasing the mechanical strength of a material.
Professor Theo Seiler, of the Institute for Refractive and Ophthalmic Surgery, Zurich, Switzerland, first described a method of increasing the strength of the cornea using cross-linking, in 1998.1 Before undertaking a feasibility study in keratoconus patients, he and his colleagues used in vitro and animal models, to evaluate the efficacy and safety of different methods, for inducing corneal cross-linking.2,3,4 The treatment technique they devised, involves abrasion of the central corneal epithelium and application of photosensitising riboflavin 0.1 per cent eye drops in dextrane solution to the denuded cornea, followed five minutes later by irradiation with 365nm UVA light for 30 minutes.
The ultraviolet light causes the riboflavin to release oxygen radicals, which in turn create new cross-linking bonds between collagen lamellar fibres and within the collagen molecules. This causes an increase in corneal rigidity, similar to that which occurs naturally as a result of ageing or diabetes.
To date the longest Prof Seiler's patients have been followed up is five years post-operatively. All eyes have shown no further progression of the keratoconus and in 65 per cent of eyes the keratoconic corneas have assumed a more normal shape, with consequent improvements in visual acuity.5 The procedure has now been adopted by various ophthalmologists, in different countries, with all of them reporting similar results.6 Moreover, no adverse effects have occurred during follow-up and safety evaluations show no apoptosis of endothelial cells, if the corneal thickness is at least 400 microns pre-treatment and there has been no change in the clarity of the cornea or the lens.7 Professor Seiler has, however, reported that the long-term data available in rabbits treated with the riboflavin/UV light cross-linking technique, show that keratoconus eventually begins to progress again.
The future for collagen cross-linking is a very exciting one. It may also be used to treat other ectatic disorders - pellucid marginal degeneration, post-Lasik keratectasia - and because of its low cost, it may have applications in developing countries, where corneal grafts are not readily available. ?
References
1 Spoerl E, Huhle M, Seiler T. Induction of cross-links in corneal tissue. Exp Eye Res, 199866:97-103.
2 Wollensak, G, Spoerl E, Wilsch M, Seiler T. Endothelial cell damage after riboflavin-ultraviolet-A-treatment in the rabbit. J Cataract Refract Surg, 200329:1786-1790.
3 Wollensak G, Wilsch M, Spoerl E, Seiler T. Collagen fiber diameter in the rabbit cornea after collagen-crosslinking. Cornea, 200423:503-507
4 Spoerl E, Wollensak G, Dittert DD, Seiler T. Thermomechanical behaviour of collagen cross-linked porcine cornea. Ophthalmologica, 2004218:136-140.
5 Spoerl E, Seiler T. Techniques for stiffening the cornea. J Refract Surg, 199915:711-713
6 Hagele G, Boxer Wachler BS. Corneal collagen crosslinking with riboflavin (C3-R) for corneal stabilization. Presented at the international congress of corneal cross linking (CCL). December 9-10, 2005. Zurich, Switzerland.
7 Wollensak G, Spoerl E, Reber F, Seiler T. Keratocyte cytotoxicity of riboflavin/UVA treatment in vitro. Eye, 200418:718-722.
? Clare McDonnell is an optometrist working in the refractive surgery sector