Keratoconic corneas generate interest among researchers and surgeons

While researchers look for the keys to keratoconus, surgeons are trying quicker, safer refractive alternatives to cornea transplant.

NEW YORK — Keratoconus, a genetic disease that is characterized by abnormal corneal growth where the cornea gradually becomes thinned and conical, reportedly affects up to as many as one in 1,000 people in the United States annually. The disease generally starts in puberty and progresses with increasing myopia and distortion of vision. Hard contact lenses improve vision in the early stages and corneal transplants are generally successful later on; however, tissue supply is limited, recovery is slow and additional vision correction is still necessary.

For all of these reasons, researchers are looking for answers. New York City cornea specialist Sandra C. Belmont, MD, explains the basis for much of the research this way: “They’re trying to ascertain why corneas start to stretch out and become ectatic. What they’re finding is that there’s a decrease in the total protein of a keratoconic cornea. They’re trying to come up with a biochemical explanation for it and what they’re finding is that there is an increase in the degradative protein enzymes in the keratoconus cornea, so essentially there is an increase in the enzymes that break down protein.” Dr. Belmont is associate professor of clinical ophthalmology at Weill Cornell University, Weill Medical College.

The hope, Dr. Belmont said, is that eventually researchers will identify pathways that lead to the cornea becoming very irregular and ectatic, which will then lead to a medication that will block that pathway. “These are just the beginning steps to analyzing a biochemical explanation for the clinical changes we see, and possibly one day they’ll come up with a medication that can cure it.”

Until then, Dr. Belmont recommends contact lenses for as long as the patient can tolerate them and has useful vision. “Once their cornea becomes steep enough that their contact lens tolerance decreases and it interferes with their lifestyle, then my treatment of choice is a corneal transplant,” she said.

Refractive surgery

Other surgeons are experimenting with different modalities such as using photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK) to try to treat the patient’s myopic astigmatism. “What they’re trying to do is delay a corneal transplant for as long as they can by reshaping the cornea. Hopefully the patient can see a little bit better and perhaps tolerate their contact lenses a little better,” Dr. Belmont said. “But as these patients are followed out over the next 5 to 10 years, I believe they are going to end up with corneal transplants anyway and probably sooner than later because of the fact that these refractive procedures are thinning an already thin cornea.

“I was trained that with a thin irregular cornea, you shouldn’t do anything to make it any weaker. You should replace it with a cornea that has a normal shape, that has normal thickness and that gives the patient their very best chance at very good visual acuity,” Dr. Belmont said. Most of these post-PRK patients see 20/20 with correction.

Dr. Belmont, agrees that LASIK can play a role in the treatment of keratoconus, but in her opinion, it should be employed post-PRK. “After the transplant, the cornea has normal thickness, normal shape and you end up with just some myopic regular astigmatism — not the irregular astigmatism that is associated with the keratoconus — and you can safely perform LASIK,” she said. “What is exciting is that by doing LASIK after PRK, I can offer these patients the chance to see well, which is something that keratoconus patients never really had before. Now with the advent of LASIK after their transplant, they have the same opportunity as a myope to be able to see without glasses or contacts.”

Dr. Belmont did a study comparing the outcomes of keratoconus patients who received cornea transplants early in the progression of the disease and those who waited until the cornea was very distorted. She found that patients who had PRK sooner had less postoperative astigmatism.

Another interesting finding that has been reported is that 30 years after having a cornea transplant, keratoconus patients sometimes start to show signs of irregular astigmatism or recurrence. Analyses of the graft tissue indicates that the transplanted cornea shows signs of the same biochemical changes that they saw in keratoconus patients prior to the transplant three decades earlier. “This is leading to two possible explanations,” Dr. Belmont said. “It could be that the remaining keratocytes in the peripheral cornea migrate to the new cornea or that the rim itself, after many years, continues to become more ectatic and, therefore, doesn’t hold the transplant.”

Other options

French ophthalmologist Joseph Colin, MD, is using Intacs micro-thin prescription inserts (KeraVision Inc., Fremont, Calif.) to delay PRK in cases of keratoconus where the patient is very young. In his first series of 10 patients, he reported that irregular astigmatism had been reduced and best corrected and uncorrected visual acuities were increasing in every case.

Brian S. Boxer Wachler, MD, is implanting Intacs inserts in keratoconus patients in the United States at the University of California Los Angeles, Jules Stein Eye Institute. He reported that his first patient was seeing better than he had in years in less than 24 hours after the treatment. The Intacs procedure involves the insertion of tiny pieces of plastic between layers of the cornea to flatten it back to its natural prolate shape. A special Intacs technique has been developed that can decrease the corneal apex in keratoconus. This can lead to improved natural vision, as well as improved vision with glasses. Unlike corneal transplants, the Intacs immediately correct the near-sightedness and sharpen vision of the patient with keratoconus. Other benefits of the Intacs procedure over a corneal transplant are that patients can return to work and function normally within a few days of the procedure, and no anti-rejection medication is needed.

Clinical Research and Statistics (CRS), a Scottsdale, Ariz.-based physician research group, is expected to file an investigational device exemption with the Food and Drug Administration (FDA) within the next 45 days. CRS plans to seek FDA permission to study six potential new indications for the Intacs technology. Study Arm 1 of the CRS clinical trial will focus on the use of Intacs for the treatment of keratoconus.

CRS wants to assess whether Intacs can be used to build up and restore the natural prolate shape of a cornea that has been thinned and weakened by keratoconus. This might delay or eliminate the need for corneal transplants for many keratoconus patients.

The future

Dr. Colin also is considering revisiting epikeratoplasty for keratoconus patients. In previously published reports, he has stated that he handled many cases of keratoconus with epikeratoplasty a decade ago and most cases did not progress much after the procedure. Daniel S. Durrie, MD, looks at deep lamellar transplants as a preferable alternative to PRK for correction of keratoconus because while PRK offers excellent corrected visual acuity, deep lamellar transplants offer the added perk of improved uncorrected visual acuity.

For Your Information:

Sandra C. Belmont, MD, can be reached at 525 E. 68th St., New York, NY 10021; (212) 746-0224; fax: (212) 746-3002.

Brian S. Boxer Wachler, MD, can be reached at Jules Stein Eye Institute – UCLA Laser Refractive Center, 100 Stein Plaza, Los Angeles, CA 90095; (310) 794-7216; fax: (310) 794-7906. Dr. Boxer Wachler has no direct financial interest in any of the products mentioned in this article, nor is he a paid consultant for any companies mentioned.

Joseph Colin, MD, can be reached at CHU de Bordeaux, Hôpital Pellegrin, Place Amélia Raba Léon, 33076 Bordeaux, France; (33) 055-679-5608; fax: (33) 055-679-5909. Dr. Colin has no direct financial interest in any of the products mentioned in this article, nor is he a paid consultant for any companies mentioned.

Daniel S. Durrie, MD, can be reached at Hunkeler Eye Centers, 5520 College Blvd., Ste. 201, Overland Park, KS 66211; (913) 491-3737; fax: (913) 491-9650. Dr. Durrie has no direct financial interest in any of the products mentioned in this article, nor is he a paid consultant for any companies mentioned.