FDA Approved Corneal Cross-Linking For Keratoconus

This recently approved procedure will help many patients with this progressive disease. Corneal collagen cross-linking is a treatment for keratoconus that was approved in the United States in April 2016. The procedure has long been available in Europe, and Avedro’s approval of Photrexa brings it to many more patients in need in the USA. Our office has the Avedro unit and treats keratoconus with collagen cross linking.

Let’s first understand the condition of keratoconus.

Understanding Keratoconus

Keratoconus is a progressive, degeneration of the cornea which often begins in teenagers and slowly progresses at a variable rate for the rest of the patient’s life. It is estimated that the incidence of keratoconus in the United States is about one in 2000 patients, but that number may be much higher if calculated using modern screening strategies. In some countries, keratoconus is much more common, affecting as many as one patient in 500.

Because the cornea is the primary focusing lens of the eye, even mild cases of keratoconus have an effect on the quality of the patient’s vision. The most common early symptom of keratoconus is blurred vision caused by astigmatism. Keratoconus is almost always bilateral, but it can be more advanced in one eye than the other.

At first, glasses can adequately correct the vision; however, the amount of the astigmatism in keratoconus changes frequently, and in many patients, glasses no longer provide clear vision and special contact lenses are required. Most patients can function for years with special contact lenses, however, in a little less than 10% of patients the degeneration becomes severe enough to require corneal transplantation.

Diagnosing and Treating Keratoconus

Frequent changes in a patient’s prescription may be an early sign of keratoconus. Keratoconus can start as early as 12-14 years of age when puberty occurs. The definitive diagnosis is made with a corneal topography map.

The corneal topographic map shows the shape of the cornea, much like a topographic map of the earth in which red and yellow colors indicate a steep curve (mountains) and blue and green colors indicate a flat curve (oceans and plains). Typically, the inferior part of the cornea in keratoconus becomes steeper; so the map shows a red spot(cone) in the lower portion of the cornea. As the cone progresses, the steep area becomes steeper(more red) and larger, and the astigmatism increases. The cornea under the area of the cone also becomes thinner than the surrounding area.

The pathology of keratoconus is often due to an inherited weakness of the millions of collagen fibers that make up the structure of the cornea. Until recently, keratoconus was treated with glasses, contact lenses, and, in a small percentage of patients, with corneal transplant (penetrating keratoplasty) surgery when the keratoconus progresses to the point that contact lenses were no longer adequate.

Now, a procedure called corneal cross-linking can halt keratoconus progression in most patients and may even cause some regression of keratoconus. This procedure will dramatically reduce the number of patients who will require corneal transplants during their lifetimes. It is truly a game changer!

Collagen Cross-Linking Therapy

A focal weakening of the collagen fibers leads to bulging of the cornea (ectasia). More than 15 years ago, Prof. Theo Seiler learned about collagen cross-liking during a visit to his dentist. The dentist was performing a procedure to strengthen Dr. Seiler’s gums. Intrigued by this process, Professor Seiler performed experiments on rabbit corneas and found that the treated corneas were more rigid after cross-linking than the control corneas. Corneal collagen fibers span the cornea in horizontal plane, and the new crosslinks created bond to hold the fibers together, acting like struts between groups of collagen fibers. Corneal collagen fibers are then stronger following crosslinking.

Crosslinking is indicated in all cases of keratoconus that are not so severe that corneal transplantation is necessary. In younger patients (< 18 years of age), treatment at the time of initial diagnosis is very important because these patients are very likely to progress over their lifetimes.

Currently, the FDA-approved cross-linking protocol is the epi-off technique using the Avedro system. This is the technique that we use at the Braverman Eye Center. First the corneal epithelium (skin) is manually removed, and then the cornea is soaked with riboflavin drops for about 30 minutes. Next, the cornea is exposed to a special ultraviolet light for 30 minutes. A contact lens is then placed for comfort and removed when the skin has re-healed in 4-5 days.

Cross-linking Results and Complications

The first human study of cross-linking for keratoconus was published in 2003 by Drs. Wollensak, Spoerl and Seiler in 23 eyes of 22 patients with follow-up from three months to four years. In all treated eyes, the progression of keratoconus was halted. In 16 eyes (70 percent), regression with a reduction of maximal keratometry readings by 2.01 D and a reduction of the refraction error by 1.14 D was found. Wollensak provided a long-term follow-up review of cross-linking using their protocol. The three and five year results of their clinical study have shown that in 60 treated eyes, the progression of keratoconus was halted in all 60 eyes. In 31 of the eyes, there was also a reversal and flattening of the steep corneal reading by up to 2.87 D. In essence, the mountain was made less steep!

Because cross-linking involves removal of the epithelium and four to five days of healing with a bandage contact lens, complications are always possible, just like those that might be expected from a photorefractive keratectomy (PRK) or prolonged wearing of soft contact lenses. Please see our informed consent for a more detailed discussion of complications.

Wrapping up

Corneal collagen cross-linking is a major advance and for the first time allows patients an opportunity to stabilize and at times partially reverse the progressive changes usually observed over their lifetime. Because keratoconus is a worldwide problem affecting millions of patients, the necessity of corneal transplants and frequent changes in the prescription for glasses and contact lenses will be dramatically reduced if all keratoconus patients have this treatment done.