Corneal cross-linking with riboflavin: entering a new era in ophthalmology


Keratoconus progression was halted in all 20 eyes treated at eight months postoperatively. In 75% of eyes we recorded a regression in pathology and an improvement in visual acuity was seen in 80% of eyes

The principle of cross-linking is not a new concept and it has long been known as an effective medical intervention, particularly in the field of orthopaedic and dental medicine. However, for the first time, Seiler was able to show the benefits of this technique in the treatment of ophthalmic conditions.

Initially, the main goal of Dr Seiler's studies was to obtain useful and reliable parameters, such as the riboflavin concentration, UV fluence for safety and depth of penetration, efficacy measurements with elastometry/extensiometry. Once those parameters had been established, Seiler went on to publish his first study in 1998, reporting on the benefits of cross-linking as a treatment of keratoconus.

Cross-linking: the mechanism

So how does this work? Why does the combined utilization of riboflavin and UVA irradiation bring about a modification in the biomechanics of corneal tissue?

The process can be explained chemically: the riboflavin is applied to the cornea and it penetrates for approximately

Is it safe?

Years of study by some key figures in the ophthalmic world (namely, Seiler and Spoerl), have been dedicated to verifying the safety of cross-linking, and recently an official document edited by the International Commission on Non-Ionizing Radiation Protection (ICNIRP) and the American Conference of Governmental Industrial Hygienists (ACGIH) support the absolute safety of this procedure. In fact, in their guidelines on limits of exposure to ultraviolet radiation of wavelengths between 180 nm and 400 nm, it is recommended that a limiting dose of 1 J/cm-2 should not be exceeded for longer UV irradiation times than 1,000 seconds. The radiant exposure of 5.4 J/cm-2 for 1,800 seconds applied during cross-linking, clearly exceeds both the ACGIH and ICNIRP guidelines. However, the absorption of riboflavin in a normal thickness cornea (>400 μm) ensures the corneal endothelium and lens are exposed to lower levels of radiation when compared with a non-riboflavin treated eye exposed to the recommended limit of radiation.

Tell me how I can do it

We began performing C3-R eight months ago at our institute [the Istituto Laser Microchirurgia Oculare (ILMO) in Brescia, Italy]. The therapy can be used to treat all diseases that require biomechanical stabilization of the cornea, in particular keratoconus, corneal melting and iatrogenic keratectasia. C3-R can also, potentially, be performed in combination with other surgical tools/procedures, such as intracorneal rings, conductive keratoplasty, LTK, ortho-keratoplasty, prevention of the central island, or following extended PRK, EpiLASIK or LASEK. Aphakic eyes and eyes with a pachymetry reading <400 μm, however, do not qualify for this procedure.

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