Bowman layer transplantation effective in advanced keratoconus

Isolated Bowman layer transplantation can reduce and stabilize corneal ectasia in eyes with progressive advanced keratoconus, researchers said. “It flattens the cornea into a more normal position,” said Jack Parker, MD, a researcher at the Netherlands Institute for Innovative Ocular Surgery (NIIOS) in Rotterdam, The Netherlands. “It doesn’t give them perfect vision, but it keeps them from getting worse. It lets them to continue wearing their contact lenses.”

Reviewed by Jack Parker, MD

Isolated Bowman layer transplantation can reduce and stabilize corneal ectasia in eyes with progressive advanced keratoconus, researchers said.

“It flattens the cornea into a more normal position,” said Jack Parker, MD, a researcher at the Netherlands Institute for Innovative Ocular Surgery (NIIOS) in Rotterdam, The Netherlands. “It doesn’t give them perfect vision, but it keeps them from getting worse. It lets them to continue wearing their contact lenses.”

In a recently published study (van Dijk et al. Ophthalmology. 2015 May. 122:5;909-917) , the procedure produced an average flattening of about 8 D in 20 eyes, and a stabilization after that. There were two complications.

In keratoconus, the cornea gradually bulges outward in the shape of a cone, distorting the patient's vision.

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Glasses and contact lenses can correct mild cases, and hard contact lenses as well as implantation of intracorneal ring segments can help in moderate cases. However, in severe cases the distortion of the cornea may progress to the point that the contact lenses become too uncomfortable to wear.

Alternative to PK, DALK

“The problem with patients who have keratoconus is that the cornea is changing shape,” said Dr. Parker. “A lot of times you can help them with contact lenses, but if the cornea is getting worse they’ll outgrow their lenses.”

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At that point, penetrating keratoplasty (PK) or deep anterior lamellar keratoplasty (DALK) may restore some vision, but these procedures come with the risk for infection and other complications, may not halt the progress of the disease, and can make the cornea vulnerable to injury, said Dr. Parker.

More recently, surgeons have used ultraviolet A radiation to induce collagen cross-linking in patients with mild to moderate keratoconus. This procedure can halt the progression of the disease, but patients with advanced keratoconus are not eligible for the treatment, Dr. Parker said. He and colleagues are proposing Bowman layer grafts as an alternative.

A smooth, acellular, nonregenerating membrane composed of collagen fibrils, the Bowman layer lies between the superficial epithelium and the stroma in the cornea. Because it has no cells, the layer does not provoke a graft rejection when transplanted, Dr. Parker said.

Coauthor Gerrit R.J. Melles, MD, PhD, came up with the idea of transplanting it into eyes with keratoconus, Dr. Parker said. Dr. Melles, an ophthalmologist at the Netherlands Institute for Innovative Ocular Surgery in Rotterdam, has a reputation for pioneering new cornea surgeries.

About the study

For the current study, the researchers operated on 22 eyes in 19 patients with progressive, advanced keratoconus.

Ten of the patients were male and nine were female, ranging in ages from 17 to 72 years, with keratoconus stages III to IV.

At baseline, their eyes had a K_max of more than 67.5 D and a best spectacle-corrected visual acuity (BSCVA) of worse than 20/60.

All the eyes had documented evidence of keratoconus progression, defined as ≥1 D change in simulated keratometery (SimK) values, ≥ 2 D change in K_max, or both, and a history of subjective decline in visual acuity.

The surgeons removed the Bowman layers from donor corneas and created mid-stromal pockets up to the limbus over 360° under air using manual dissection. This procedure was similar to the procedure used to create a lamellar dissection plane in DALK, except that the dissection went to the mid-stroma.

The surgeons inserted the donor Bowman layer into the stromal pocket, then unfolded and centered it using a cannula and balanced salt solutions to manipulate the tissue.

The procedure is less invasive than PK or DALK “because you are doing no cutting or sewing,” Dr. Parker said.

Although it is technically feasible to place a donor Bowman layer in its true anatomic position in a keratoconic cornea, it cannot be fixated with currently available sutures or glues, making it difficult to obtain sufficient traction force across the cornea to flatten the central cone.

As the corneas healed, the donor Bowman layers attached to the patients' corneas, and the incisions closed without sutures.

“We’re not really sure why it works,” said Dr. Parker. “It seems to provoke a healing response in the cornea.”

Complications, results

Out of the 22 transplantations, two resulted in complications. In both of these, the Descemet membrane was perforated during manual dissection. Both patients declined PK, preferring to wait for corneal clearance after re-endothelialization for the perforation.

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After initial clearance, one eye showed progressive corneal decompensation for which PK has been scheduled. The cornea of the other eye cleared slowly and BSCVA improved during the first postoperative six months. The researchers excluded the two eyes from postoperative evaluation.

Of the remaining 20 eyes, a mean follow-up of 20 months (range 12-36 months) showed a flattening effect in 18.

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On average, maximum keratometry (K_max) decreased from 77.2 D to 69.2 D a month after the surgery. Anterior SimK decreased from 64.0 before surgery to 58.9 at 1 month after surgery. Posterior mean keratometry decreased from -10.1 to -9.0 D. The changes were statistically significant (p < 0.001).

After the first postoperative month, K_max stabilized. SimK and posterior keratometry showed a small regression from 1 to 6 months after surgery (p < 0.028), then also stabilized. In two eyes, the corneal curvature continued steepening for reasons that were not clear.

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One eye had low visual potential because of a cataract, and another had preoperative visual acuity measured only with a contact lens.

BSCVA changes

In the remaining 18 eyes, BSCVA changed from 1.27 logarithm of the minimum angle of resolution (LOGMAR) before surgery to 0.90 LOGMAR 12 months after the transplantation, a statistically significant different (p < 0.001). After that, no change in BSCVA was observed.

Average best contact lens-corrected visual acuity (BCLVA) showed no change from before surgery to any time point after.

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The transplantation caused the most flattening in corneas with a relatively steep K_max, combined with a flatter SimK and a small corenal apex-to- K_max distance. This means the procedure worked best in the most advanced cases with the most central cones, the researchers said.

Because the procedure resulted in stabilization, it might be useful in managing keratoconus cases ineligible for ultraviolet cross-linking, Dr. Parker said.

The main value of the procedure may be that it preserved an acceptable contact lens corrected vision while stabilizing the cornea, he said.

Researchers have continued to transplant Bowman layers into patients with advanced keratoconus and now have follow-up data on 65 or more, said Dr. Parker.

This article was adapted from Dr. Parker’s presentation of the Howard Lieberman Memorial Paper at the 2016 meeting of the American Society of Cataract and Refractive Surgery. Dr. Parker has no financial interest relevant to the subject matter.