Corneal collagen cross-linking

Cross-linking procedure, UV light source^[1]

Corneal collagen cross-linking with riboflavin (vitamin B₂) and UV-A light (also known as CXL, C3-R, CCL and KXL), better known as cross-linking, is a surgical treatment for corneal ectasia such as keratoconus.

It is used in an attempt to make the cornea stronger. According to a 2015 Cochrane review, as of 2015 there is insufficient evidence to determine if it is useful in keratoconus.^[2]

Medical uses

A 2015 Cochrane review that look at all high quality evidence on corneal collagen cross-linking found that it was insufficient to determine if it is useful in keratoconus.^[2]

Procedure

Removed corneal epithelium during CCR operation on an eye with post-LASIK complication, from Kymionis et al., 2009^[3]

Corneal cross-linking involves a one-time application of riboflavin solution to the eye that is activated by illumination with UV-A light for approximately 30 or less minutes. The riboflavin causes new bonds to form across adjacent collagen strands in the stromal layer of the cornea, which recovers and preserves some of the cornea's mechanical strength. The corneal epithelial layer is generally removed to increase penetration of the riboflavin into the stroma, a procedure known as the standard protocol.^[4]

People that are considered for treatment must undergo an extensive clinical workup, including corneal tomography, computerized corneal topography, endothelial microscopy, ultrasound pachymetry, b-scan sonography, keratometry and biomicroscopy.

Transepithelial cross-linking

In transepithelial or epithelium-on (epi-on) cross-linking technique which was first performed in 2004 in the U.S.,^[5] the corneal epithelium layer is left intact. in this technique, because the epithelium is not removed, riboflavin loading requires more time than with epi-off techniques.

Pocket cross-linking

In Pocket Cross-linking Riboflavin is injected directly into the target tissue (corneal stroma) via a corneal pocket in order to bypass the epithelium, which is left intact.^[6][7]

Contact lens-assisted collagen cross-linking

Contact lens-assisted cross-linking (CACXL) may be performed for patients with corneal stromal thickness between 350 µm to 400 µm after epithelial removal. in this method a pre-corneal riboflavin film, a riboflavin-soaked UV barrier-free soft contact lens of negligible power and a pre-contact lens riboflavin film are used to decrease UV irradiance to safe levels at the level of the endothelium.^[8][9]

Combination with refractive eye surgeries

Cross-linking is not intended to correct vision, thus it is usually combined with refractive eye surgeries such as photorefractive keratectomy, intrastromal corneal ring segments, and mini asymmetric radial keratotomy.^[10] Cross-linking can also be used to avoid post-LASIK ectasia and to improve refractive outcomes.^[11]

History

The technique was first developed in Germany in 1998 and clinical trials have been in course since the same year; in Italy routine interventions have been successfully performed since 2005, while in the USA clinical trials commenced only in 2008.

Approval

The standard protocol of Corneal Collagen Cross-linking, with epithelium removal, is approved for use throughout Europe.^[12] In the United States, amid concerns about study data and labeling,^[13] a FDA panel recommended approval of Avedro’s combined riboflavin ophthalmic solutions and ultraviolet light irradiation for corneal collagen cross-linking in February 2015.^[14] In March 2015, FDA decided not to approve the Avedro's new drug application, identifying areas of the application concerning the device which require additional information.^[15]

References

External links

Wikimedia Commons has media related to corneal collagen crosslinking.

• Corneal Collagen Cross-Linking on National Keratoconus Foundation website.
• Corneal Collagen Cross-Linking on EyeWiki from the American Academy of Ophthalmology