FDA approves first corneal cross-linking system for treatment

July 12, 2016
Scope of treatment expanded for patients with keratoconus.

Tested and approved. Doctors of optometry have been waiting to see those three words.

Finally, in April 2016, the U.S. Food and Drug Administration (FDA) gave approval to Avedro Inc.'s corneal cross-linking system to treat patients with progressive keratoconus and post-LASIK ectasia.

Studies on corneal cross-linking go back more than a decade, and countries in Europe have offered their approved treatment for years. In the U.S., some doctors of optometry have been co-managing patients with cross-linking for years, informing them that it was "off label" and had not yet been approved in this country. But that approval has come, and it was worth the wait for the good it will do patients, says Andrew Morgenstern, O.D., AOA clinical consultant who practices at Walter Reed National Military Medical Center in Bethesda, Maryland.

The Avedro system is the first corneal cross-linking treatment ever approved in this country.

"Quite frankly, the U.S. was lagging behind the rest of the world, so I'm very happy about its approval," Dr. Morgenstern says.

He adds, "It is really a significant increase in scope of treatment for patients with keratoconus. It has been proven through study on top of study on top of study."

Keratoconus is a progressive eye disease in which the cornea thins and bulges out to form a cone shape. This is due to a breakdown of the tiny fibers in the eye (collagen) that normally help the cornea hold its shape. But when the collagen fibers weaken the cornea bulges.

Based on a 1998 study, the prevalence of keratoconus was 1 in 2,000 people. However, other estimates put the prevalence at 1 in 750 people. This makes keratoconus one of the most common corneal disorders in the U.S.

How does corneal cross-linking work?

Cross-linking involves applying liquid riboflavin (Vitamin B2) to the cornea and exposing it to ultraviolet light. The treatment strengthens and stiffens the cornea's structure and can slow and halt the progression of keratoconus. It is theorized that the existing collagen is strengthened. Ultimately, cross-linking can prevent the necessity for corneal transplants in a majority of keratoconus patients.

Avedro received approval for Photrexa and Photrexa Viscous in Dextrose 20% plus its KXL System (UV light source). Avedro, a private pharmaceutical and medical device manufacturing company in Waltham, Massachusetts, is ramping up production on Photrexa and taking orders now for the KXL system.

What should doctors of optometry know about the FDA-approved cross-linking?

According to Dr. Morgenstern, doctors of optometry should:

  1. Learn about this new treatment option and inform patients as well. Be prepared to make a referral. Develop relationships with doctors who can treat patients with the cross-linking drugs and device.
  2. Review the prescribing information.
  3. Know the law in your own state and whether you can undertake the procedure associated with the new drugs and device. Some state laws are more restrictive than others, he says.
  4. Expect that eventually a Current Procedural Terminology code will be created for this service, Dr. Morgenstern says.
  5. Invest in the proper technology that is capable of detecting, monitoring and evaluating pre- and post-treatment corneas if they intend to perform corneal cross-linking. The industry standard of care is anterior and posterior corneal elevation mapping with Scheimpflug-style camera.

Epi-on versus epi-off debate

Over the years, doctors of optometry have engaged in a lively debate over how to best apply cross-linking to keratoconus patients—using the "epi-on" or "epi-off" methods. In the less-invasive epi-on treatment, the cornea's epithelial layer is left intact. Patients experience less pain and recover faster.

By contrast, in epi-off, the epithelium is removed to get a quicker, deeper saturation of the riboflavin, Dr. Morgenstern says.

"There are some people who believe you get a better cross-linking effect from epi-off," he says, "because you have a higher concentration of riboflavin and the light can reach deeper."

However, Dr. Morgenstern says, if the epithelial layer is removed (epi-off), patients sustain a corneal abrasion on the front surface of the eye. Recovery takes longer, is painful and there is a significantly higher risk of infection versus the epi-on method.

That debate has been settled, provided doctors of optometry will be treating patients with the Avedro drugs and device. Other non-approved cross-linking drugs and devices, such as CXLUSA, are undergoing clinical study using epi-on cross-linking.

"The FDA approved the Avedro drugs and device for epi-off cross-linking," Dr. Morgenstern says.

The comments and opinions expressed above are those of Dr. Andrew Morgenstern and do not represent the U.S. government.

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