Experience with corneal collagen cross-linking finds new indication, safety criteria

February 22, 2006

Increasing clinical experience with corneal collagen cross-linking using combined topical riboflavin application and ultraviolet-A (UVA) irradiation indicates this simple, nonsurgical intervention may be an effective treatment for keratoconus and iatrogenic keratectasia. However, its safety may depend on respecting a minimum corneal thickness threshold of 400 microns as a criterion for candidate selection, said Theo Seiler, MD, at the World Ophthalmology Congress.

Increasing clinical experience with corneal collagen cross-linking using combined topical riboflavin application and ultraviolet-A (UVA) irradiation indicates this simple, nonsurgical intervention may be an effective treatment for keratoconus and iatrogenic keratectasia. However, its safety may depend on respecting a minimum corneal thickness threshold of 400 microns as a criterion for candidate selection, said Theo Seiler, MD, at the World Ophthalmology Congress.

Dr. Seiler of the Institute for Refractive and Ophthalmic Surgery, Switzerland, explained Wednesday that the procedure aims to increase the stiffness of the cornea and its mechanical and biochemical resistance by inducing additional chemical bonds within the connective tissue. Initial preclinical experiments in which animal eyes underwent corneal abrasion, followed by 30 minutes of application of 0.1% riboflavin and irradiation with a UVA light source (365-nm, 3 mW/cm2) demonstrated that corneal biomechanical strength increased 1.5-fold.

The technique was first performed clinically in patients with keratoconus, and those studies showed it could convert progressive disease into forme fruste keratoconus without causing any complications or evidence of toxicity to the cornea, lens or iris. More recent experience in eyes with iatrogenic keratectasia has also produced exciting results, as the procedure was associated with a reduction in keratometry readings rather than just stabilization.

However, in an eye with iatrogenic kerectasis, an adverse endothelial reaction occurred as the first complication of the cross-linking procedure. That experience led to further research on keratocyte cytotoxicity of the riboflavin/UVA treatment and the recommendation for the corneal thickness rule.

"Studies in cell cultures and animal eyes show there is a very sharp endothelial damage threshold for this treatment at an irradiance level of 0.3 mW/cm2, and while the intensity of radiation delivered decreases with increasing corneal depth, there appears to be a risk for endothelial damage in thinner corneas where the endothelium is closer to the surface," said Dr. Seiler.