Corneal cross-linking (CXL) with

riboflavin Riboflavin, also known as vitamin B2, is a vitamin found in food and sold as a dietary supplement. It is essential to the formation of two major coenzymes, flavin mononucleotide and flavin adenine dinucleotide. These coenzymes are involved in ...

(vitamin B₂) and UV-A light is a surgical treatment for corneal ectasia such as

keratoconus Keratoconus (KC) is a disorder of the eye that results in progressive thinning of the cornea. This may result in blurry vision, double vision, nearsightedness, irregular astigmatism, and light sensitivity leading to poor quality-of-life. Usu ...

PMD PMD may refer to: In government and diplomacy: * Pakistan Meteorological Department * Performance Management Division, of the Cabinet Office, Government of India * Possible Military Dimensions of a nuclear program (specifically that of Iran) In ...

, and

post-LASIK ectasia Post-LASIK ectasia is a condition similar to keratoconus where the cornea starts to bulge forwards at a variable time after LASIK, PRK, or SMILE corneal laser eye surgery. However, the physiological processes of post-LASIK ectasia seem to be diff ...

. 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

. In 2016, the US Food and Drug Administration approved riboflavin ophthalmic solution crosslinking based on three 12-month clinical trials.

Medical uses

A 2015 Cochrane review found that the evidence on corneal cross-linking was insufficient to determine if it is an effective procedure for the treatment of

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

, 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

solution to the eye that is activated by illumination with UV-A 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, 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 so ...

, endothelial

microscopy Microscopy is the technical field of using microscopes to view objects and areas of objects that cannot be seen with the naked eye (objects that are not within the resolution range of the normal eye). There are three well-known branches of micr ...

, ultrasound

pachymetry Corneal pachymetry is the process of measuring the thickness of the cornea. A pachymeter is a medical device used to measure the thickness of the eye's cornea. It is used to perform corneal pachymetry prior to refractive surgery, for Keratoconu ...

, b-scan sonography,

keratometry A keratometer, also known as an ophthalmometer, is a diagnostic instrument for measuring the curvature of the anterior surface of the cornea, particularly for assessing the extent and axis of astigmatism. It was invented by the German physiologi ...

and biomicroscopy.

History

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

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 Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellul ...

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