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Corneal cross-linking treatment for keratoconus

cross-section of cornea
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Corneal cross-linking is a minimally invasive outpatient procedure designed to treat progressive keratoconus (and, sometimes, other conditions that cause a similar weakening of the cornea).

The corneal cross-linking procedure strengthens and stabilizes the cornea by creating new links between collagen fibers within the cornea. The two-step procedure applies liquid riboflavin (vitamin B2) to the surface of the eye immediately followed by a controlled exposure of the eye to ultraviolet light.

The two basic types of corneal cross-linking are:

  • Epithelium-off cross-linking. In this procedure, the thin outer layer (epithelium) of the cornea is removed to allow the liquid riboflavin to more easily penetrate the deeper corneal tissue.
  • Epithelium-on cross-linking. In this procedure (also called transepithelial cross-linking), the protective corneal epithelium is left intact, making it a less invasive procedure than cross-linking with epithelium removal.

Corneal cross-linking can be combined with other procedures for keratoconus treatment. For example, it can be performed along with implantation of tiny arc-shaped corneal inserts called Intacs to reshape and stabilize the cornea in more advanced cases of keratoconus.

Currently, the only corneal cross-linking platform that is FDA-approved for the treatment of progressive keratoconus in the U.S. is Avedro's KXL System, which includes the company's proprietary Photrexa and Photrexa Viscous riboflavin solutions.

The FDA approves medications and treatments for a specific use. Avedro's KXL System has FDA approval for epithelium-off cross-linking only. However, a doctor in the United States can legally use FDA-approved medications and treatments in another reasonable way that he or she considers appropriate. This is called an "off-label" use, and it's a common way to expand the use of an FDA-approved medication or procedure without having to undergo the often long and very expensive FDA approval process.

Corneal cross-linking

Corneal cross-linking (CXL) strengthens a weak or thin cornea with a combination of riboflavin solution and controlled UV light. (Image: Avedro, Inc.)

So, though Avedro's KXL System is FDA-approved only for epithelium-off cross-linking, eye surgeons can lawfully use riboflavin solutions, other proprietary formulations and UV light to perform less invasive, epithelium-on cross-linking for keratoconus.

Holcomb C3-R cross-linking

One of the pioneers in the development of corneal cross-linking treatment for keratoconus is Brian Boxer Wachler, MD, an eye surgeon who founded the Boxer Wachler Vision Institute in Beverly Hills, California. Dr. Boxer Wachler also is an AllAboutVision.com Editorial Advisory Board member.

In 2007, Boxer Wachler was visited by U.S. Olympic bobsledding champion Steve Holcomb. Holcomb was suffering from progressive keratoconus that was degrading his vision to the point of legal blindness and was about to end his bobsledding career.

Boxer Wachler performed an epithelium-on cross-linking procedure to reshape and stabilize Holcomb's misshapen cornea, combined with implantation of a phakic IOL to further improve the athlete's vision.

The procedures were a huge success, and in February 2010 at the Winter Olympics in Vancouver, Holcomb and his teammates won an Olympic gold medal — the first in bobsledding for the United States in 62 years.

To honor the athlete, Boxer Wachler named his transepithelial cross-linking procedure the Holcomb C3-R and continues to perform the off-label procedure with excellent results. ( Watch Dr. Boxer Wachler's appearance on The Doctors, where he describes the Holcomb C3-R cross-linking procedure .)

Best candidates for corneal cross-linking

Corneal cross-linking is most effective if it can be performed before the cornea has become too irregular in shape or there is significant vision loss from keratoconus. If applied early, cross-linking typically will stabilize or even improve the shape of the cornea, resulting in better visual acuity and an improved ability to wear contact lenses.

Other potential applications of cross-linking include the treatment of corneal ulcers that are unresponsive to treatment with topical antibiotics. Studies also have found that corneal cross-linking can be effective for eradicating a variety of corneal infections.

SEE ALSO: Answers from an eye doctor about keratoconus

Some surgeons have also reported reasonable results in improving the stability of the cornea in people who have undergone radial keratotomy (RK), an incisional refractive procedure from the 1980s and 1990s. Cross-linking appears to work best for those who are experiencing daily fluctuations as a result of their RK procedures.

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

that reshapes the cornea.

What to expect during and after corneal cross-linking

During a preliminary evaluation, 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 vision and general eye health.

Detailed mapping of the shape of your cornea (called corneal topography) will also be performed.

Diagram showing layers of the cornea

Layers of the cornea. 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 30 to 90 minutes in most cases, depending on the technique used.

If you are undergoing an epithelium-off ("epi-off") procedure, your surgeon will place you in a reclining position and remove the epithelial layer from your cornea. Riboflavin eye drops will then be placed on your eye.

If you undergo an epithelium-on ("epi-on") procedure, you are placed in a reclining position, and riboflavin drops are applied. After enough time has passed (depending on the technique), the surgeon may evaluate your eye to ensure that the cornea has absorbed a sufficient amount of riboflavin.

Corneal thickness may be checked, and then the UV light will be applied for up to 30 minutes.

After epi-off cross-linking, a bandage contact lens will be placed on your eye to reduce discomfort and facilitate healing. Topical antibiotic and anti-inflammatory drops will be prescribed.

You can expect discomfort to range from minor to significant after epi-off cross-linking, and it can take weeks to months for your cornea for a full recovery. With an epi-on procedure, on the other hand, there typically is no pain following the procedure and recovery is one day, according to Boxer Wachler.

With both epi-off and epi-on cross-linking, studies have found that most keratoconus 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 severe vision loss.

Cost of corneal cross-linking

The cost of corneal cross-linking for the treatment of progressive keratoconus typically ranges from $2,500 to $4,000 per eye.

Some of this cost may be covered by your health insurance policy. Ask your eye doctor or insurance company for assistance in determining what your total out-of-pocket expense for the procedure will be.

Marilyn Haddrill also contributed to this article.

Page updated June 2019

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