Corneal collagen cross linking (CXL) was developed in 1998 by Theo Seiler, MD, and has been shown in numerous clinical trials to strengthen the eye’s clear surface (cornea) through the application of riboflavin, a form of vitamin-B2, followed by treatment with ultraviolet A (UV-A) light.
The two basic types of corneal cross linking are:
Epithelium off, which means the thin layer covering the eye’s surface is removed, allowing for faster penetration with liquid riboflavin.
Transepithelial corneal cross linking (epithelium on) is where the corneal epithelial surface is left intact, which requires a longer riboflavin loading time.
Cross linking with riboflavin and UV-A light has proven to be a first-line treatment for people with eye conditions such as keratoconus, pellucid marginal degeneration and corneal weakness (ectasia) after LASIK.
While cross linking is used in virtually every country around the world, it is still in the FDA approval process in the United States. Both Avedro and Topcon are working to get their brands of riboflavin drops and UV light sources approved by the FDA. As well, many other single-center and multi-center clinical trials are evaluating CXL in the U.S.
Corneal cross linking can also be used in combination with other technologies, with the goal of improving the visual results more rapidly. Tiny plastic inserts known as Intacs, which are surgically implanted within the cornea, have been shown to work well with cross linking. Surface laser vision correction guided by corneal topography has also proven to be a useful technology.
Another technology, currently under development, uses microwave energy to flatten the cornea, and this may one day prove to be effective when combined with cross linking.
Who Are the Best Candidates for Corneal Cross linking?
Multiple systems for corneal cross linking have received approval in Europe. Since these systems are widely available there, the goal is to identify patients with corneal ectactic disorders such as keratoconus or pellucid marginal degeneration early in the disease process and treat them before they develop significant vision loss from ectasia.
Once they have received cross linking, in most cases their corneal shape will either remain stable or actually improve. This can provide patients with improved visual acuity and improved ability to wear contact lenses.
Other potential applications of corneal cross linking include the treatment of corneal ulcers that are non-responsive to topical antibiotics. Studies have found that the combination of riboflavin plus the UV light can be effective for eradicating a variety of corneal infections.
Some surgeons have also reported reasonable results in improving the stability of the cornea in people who have undergone radial keratotomy, an incisional refractive procedure from the 1980s and 1990s. Crosslinking appears to work best for those who are experiencing daily fluctuations in their vision.
People who are considering vision correction procedures such as LASIK also might eventually be pre-treated with corneal cross linking to strengthen the eye’s surface before undergoing an excimer laser ablation that reshapes the cornea.
What To Expect During and After a Corneal Cross linking Procedure
During preliminary examinations, your eye doctor will measure the thickness of your cornea and make sure you are a good candidate for the procedure. You also will need to have a routine eye exam to assess your visual acuity and general eye health. And your doctor will perform mapping of your cornea (called corneal topography) to determine the level of your eye condition.
magnified section of the cornea showing all layers of the cornea in cross-section.
Corneal cross linking strengthens bonds in the stroma of the cornea, which is the layer from which tissue is removed during LASIK surgery.
The cross linking procedure takes 60 to 90 minutes in most cases. If you are receiving epithelial-off cross linking, your surgeon will place you in a reclining position and remove the epithelial layer from your cornea. Riboflavin eye drops will then be placed.
If you are receiving epithelial-on cross linking, you are placed in a reclining position, and riboflavin drops are started. After enough time has passed (depending on the technique), the surgeon will evaluate your eye to ensure that the cornea has sufficient riboflavin present.
The corneal thickness will be checked, and then the UV light will be applied for up to 30 minutes.
In some cases, a bandage contact lens will be placed. Topical antibiotic and anti-inflammatory drops will be prescribed.
With both epithelial-off and epithelial-on CXL, studies have found that 99 percent of patients will remain stable or achieve improvement in the corneal shape, which is highly significant for people with progressive keratoconus that otherwise might lead to blindness.
Epithelium-Off Vs. Transepithelial Corneal Cross linking
One of the big questions that some clinicians are researching is whether transepithelial CXL can provide similar results to procedures where the epithelium has been removed.
In Europe, a special riboflavin formulation has been developed that helps facilitate transepithelial CXL, called Ricolin TE. In the United States, investigators are evaluating the effectiveness of transepithelial CXL, and to date these researchers have reported visual results that are similar to those of epithelial-off CXL.*
The advantages of transepithelial CXL are reduced risks of infection, corneal haze and delays in epithelial healing. While outcomes with epithelial-off CXL tend to be significantly better in younger candidates than in people older than 35**, this difference does not appear to be an issue with transepithelial CXL.*** Transepithelial CXL also allows for quicker visual recovery and less discomfort.