• Biotherapeutics

    Regenerative approaches to improving corneal transplantation

Mayo Clinic is refining corneal transplantation surgery nearly a century after it first pioneered this groundbreaking procedure to restore vision.

Corneal transplants, which were among the first successful organ transplants, are considered one of the earliest forms of regenerative medicine. Mayo Clinic's Center for Regenerative Medicine is a catalyst for advancing regenerative procedures like corneal transplants that deliver new options for healing.

The cornea is the transparent, curved surface that lies in front of the iris. Like any transparent smoothly curved surface, it acts as a lens and provides two-thirds of the focusing power of the human eye. When the cornea becomes swollen or scarred, it can no longer focus well, and a corneal transplant is needed to restore corneal clarity and normal vision.

Leo Maguire, M.D.

"Until 2005, the only way to perform a corneal transplant was to remove the entire thickness of the central 7–8 millimeters of the 12-millimiter cornea and replace it with a similar size, full-thickness donor cornea. Since over 90% of the corneal thickness is collagen, and collagen is the slowest healing material in the body, most patients required sutures to be present for a year before removal," says Leo Maguire, M.D., a Mayo Clinic ophthalmologist and corneal surgeon. "Besides the long healing time, this type of transplant often caused unpredictable glasses prescriptions that could be quite different from the prescription in the unoperated eye."

Beginning in 2005, researchers began working on a new approach to corneal transplant that allowed for much faster visual recovery and much more predictable spectacle correction for patients who need corneal transplant because of swelling of the cornea. Corneal swelling triggers the need for transplant 65% of the time.

What part of the cornea usually prevents swelling?

The endothelium is a sheet of cells that line the back of the cornea. These cells act as pumper cells to pump water out of the stroma, which makes up 90% of the thickness of the cornea. When the endothelial cells don't properly pump moisture from the corneal chamber, fluid builds up, leading to swelling, clouding, blurry vision, sensitivity to light or a nagging feeling that is something in the eye.

The endothelium cell layer is depicted as the back lining of the yellow thickness of the cornea

Endothelial cells do not replicate, but they also do not decrease in number for people with normal, healthy eyes. However, in corneal diseases such as Fuchs' dystrophy, patients lose cells at an accelerated pace. People with some types of glaucoma also may rapidly lose endothelial cells.

"Over time, if you lose enough of the endothelial pumper cells, it's like not having enough fingers to plug the dike and hold back a surge of fluid. The cornea swells and loses its transparency and uniformity of the corneal curvature on top. That leads to problems with eyesight," says Dr. Maguire.

Upward of 45,000 people in the U.S. need corneal transplants every year to restore corneal function. Advancements in transplantation surgery make it possible to replace only the diseased cell line and improve eyesight without removing the full thickness of the cornea.

"Endothelial transplant researchers started to say, 'If the only issue is with the posterior 2% of the cornea, why not replace the damaged sheet of endothelium across the cornea's back surface with cells from a donor, but leave the rest of the patient's natural cornea alone?' Replacing cell layers is so much easier for us to do than a full-thickness transplant," says Dr. Maguire. "More importantly, it's much easier for the patient. It's much less painful and results in fewer postoperative visits."

Mayo Clinic offers two partial-thickness corneal transplants for patients with diseased endothelial cells:

Descemet's stripping with endothelial keratoplasty

This procedure preserves the healthy part of the cornea, and transplants only a layer of donor endothelial cells along with a small amount of collagen. The cells are implanted through small self-sealing incisions that do not require stiches. The transplanted cell line is put in place with a burst of air where it attaches to the cornea and restores pumper cell function.

"It's much less invasive. It doesn't affect as much the front curvature of the native cornea at all. Within a few months, the patient has recovered enough that the glasses prescription is close to what is was before the surgery," says Dr. Maguire.

Descemet's membrane endothelial keratoplasty (DMEK)

In this surgery, a layer of endothelial cell without the collagen is inserted into the cornea through small self-sealing incisions. This surgery has the potential for quickest recovery time and lowest risk of rejection.

"People who have the DMEK surgery recover really fast. I've had some people's vision restored to 20/20 or 20/25, with spectacle correction, a week after surgery. However, others may take a month or a little longer to get to that point," says Dr. Maguire.

Full thickness corneal transplant

Full-thickness corneal transplantation surgery is still performed for some corneal diseases. Keratoconus, a disorder that occurs when the cornea thins and gradually bulges, is an example of a condition that still requires full-thickness corneal transplantation.

Just as Mayo Clinic pioneered the first full-thickness corneal transplants, Mayo Clinic is performing research to improve partial-thickness transplants. For example, Mayo Clinic research contributed to the discovery of the genetic mutation linked to Fuchs' dystrophy. Over time, better understanding of genetic and environmental factures may help researchers find new therapeutic options for patients with corneal diseases.