Corneal cross-linking (CXL) with riboflavin (vitamin B₂) and

UV-A Ultraviolet (UV) is a form of electromagnetic radiation with wavelength from 10 nm (with a corresponding frequency around 30 PHz) to 400 nm (750 THz), shorter than that of visible light, but longer than X-rays. UV radiation i ...

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. In 2016, the

US Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

approved riboflavin ophthalmic solution crosslinking based on three 12-month clinical trials.

Medical uses

A 2015

Cochrane review Cochrane (previously known as the Cochrane Collaboration) is a British international charitable organisation formed to organise medical research findings to facilitate evidence-based choices about health interventions involving health profes ...

found that the evidence on corneal cross-linking was insufficient to determine if it is an effective procedure for the treatment of keratoconus.

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. 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.

Cautions

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

Procedure

Corneal cross-linking involves application of riboflavin solution to the eye that is activated by illumination with

light for approximately 30 or fewer minutes. The riboflavin causes new bonds to form across adjacent collagen strands and proteoglycans in the stromal layer of the

cornea The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Along with the anterior chamber and lens, the cornea refracts light, accounting for approximately two-thirds of the eye's total optical ...

, 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 Dresden protocol. People that are considered for treatment must undergo an extensive clinical workup, including corneal tomography, computerized

corneal topography Corneal topography, also known as photokeratoscopy or videokeratography, is a non-invasive medical imaging technique for mapping the anterior curvature of the cornea, the outer structure of the eye. Since the cornea is normally responsible for s ...

, endothelial microscopy, ultrasound pachymetry,

b-scan Medical ultrasound includes diagnostic techniques (mainly imaging techniques) using ultrasound, as well as therapeutic applications of ultrasound. In diagnosis, it is used to create an image of internal body structures such as tendons, musc ...

sonography Medical ultrasound includes diagnostic techniques (mainly imaging techniques) using ultrasound, as well as therapeutic applications of ultrasound. In diagnosis, it is used to create an image of internal body structures such as tendons, musc ...

, 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 TU Dresden (for german: Technische Universität Dresden, abbreviated as TUD and often wrongly translated as "Dresden University of Technology") is a public research university, the largest institute of higher education in the city of Dresden, th ...

Approvals and clinical trials

In Germany, CXL has been used in patients with keratoconus since 1998, and in Italy, routine interventions have been successfully performed since 2005. The standard (Dresden) CXL protocol 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

approved riboflavin ophthalmic solution and Avedro's KXL system for crosslinking on 18 April 2016, for the treatment of progressive keratoconus, and on 19 July 2016, for corneal ectasia after refractive surgery, making them the first FDA approved treatment for keratoconus and post-LASIK ectasia.

Research

Research studying the safety and efficacy of corneal cross-linking is ongoing. Transepithelial or epithelium-on (epi-on) cross-linking is a technique which was first performed in 2004 in the U.S., 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, and may be less effective, as keratoconus progression may be more likely in epi-on procedures. 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 Contact lenses, or simply contacts, are thin lenses placed directly on the surface of the eyes. Contact lenses are ocular prosthetic devices used by over 150 million people worldwide, and they can be worn to correct vision or for cosmetic ...

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. 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. Accelerated crosslinking allows a shorter treatment time by delivering the same energy more quickly, compared to the standard crosslinking procedure, which involves 3 mW of UV-A exposure for 30 minutes. Some hospitals are using this accelerated CXL technique delivering a similar amount of UV-A energy in eight to ten minutes, following research showing the cornea may better tolerate this shorter burst of UV-A.

References

External links

Corneal Collagen Cross-Linking
on National Keratoconus Foundation website.
Corneal Collagen Cross-Linking
on

EyeWiki This is a list of medical wikis, collaboratively-editable websites that focus on medical information. Many of the most popular medical wikis take the form of encyclopedias, with a separate article for each medical term. Some of these websites, such ...

from th
American Academy of Ophthalmology
{{Eye surgery Eye surgery