Corneal collagen cross-linking

Corneal collagen cross-linking
Intervention
Cross-linking procedure, UV light source[1]
Synonyms	cross-linking, CXL, C3-R, CCL, KXL
CPT	0402T

Corneal collagen cross-linking with riboflavin (vitamin B₂) and UV-A light is a surgical treatment for corneal ectasia such as keratoconus, PMD, and post-LASIK ectasia.

It is used in an attempt to make the cornea stronger. According to a 2015 Cochrane review, there is insufficient evidence to determine if it is useful in keratoconus.^[2] In 2016, the US Food and Drug Administration approved riboflavin ophthalmic solution crosslinking based on three 12-month clinical trials.^[3]

Medical uses

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

Adverse effects

Among those with keratoconus who worsen CXL may be used. In this group the most common side effects are haziness of the cornea, punctate keratitis, corneal striae, corneal epithelium defect, and eye pain. In those who use it after post-LASIK ectasia, the most common side effects are haziness of the cornea, corneal epithelium defect, corneal striae, dry eye, eye pain, punctate keratitis, and sensitivity to bright lights.^[4]

There are no long term studies about crosslinking effect on pregnancy and lactation. According to a manufacturer crosslinking should not be performed on pregnant women.^[4]

Cautions

People undergoing crosslinking should not rub their eyes for the first five days after the procedure.^[4]

Procedure

Removed corneal epithelium during CCR operation on an eye with post-LASIK complication, from Kymionis et al., 2009^[5]

Corneal cross-linking involves 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.^[6]

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.

History

The technique was first developed in Germany in 1997 by Eberhard Spoerl and his team at the Dresden University of Technology.^[7][8]

Approvals and clinical trials

In Germany clinical trials have been in course since 1998.^[7] in Italy routine interventions have been successfully performed since 2005.^[9] The standard protocol of Corneal Collagen Cross-linking, with epithelium removal, is approved for use throughout Europe.

In the United States clinical trials commenced only in 2008. based on three 12-month clinical trials, the US Food and Drug Administration approved riboflavin ophthalmic solution and KXL system for crosslinking on April 18, 2016, for the treatment of progressive keratoconus, and on July 19, 2016, for corneal ectasia after refractive surgery, making them the first FDA approved treatment for keratoconus and post-LASIK ectasia.^{[3] [10]}

Research

As of 2016 research was ongoing.^[11]

Transepithelial or epithelium-on (epi-on) cross-linking is a technique which was first performed in 2004 in the U.S.,^[12] the corneal epithelium layer is left intact.^[13] in this technique, because the epithelium is not removed, riboflavin loading requires more time than with epi-off techniques, and may be less effective.^[14]

In a "pocket cross-linking" procedure, riboflavin is injected directly into the corneal stroma via a corneal pocket in order to bypass the epithelium, which is left intact.^[15][16]

Contact lens-assisted cross-linking (CACXL) may be performed for people 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.^[17][18]

Topography-guided crosslinking relies on an active eye tracker to allow a patterned delivery of UV light. Both the power and pattern can be programmed into the unit based on the topography of the individual's eyes.^[19]

Accelerated crosslinking would allow a shorter treatment time by delivering more energy, compared to the standard crosslinking procedure, which involves 3 mW of UVA exposure for 30 minutes.^[19]

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