Bioengineered corneal substitutes show promise in transplantations

The biosynthetic grafts can be tailored in shape, curvature, thickness and diameter.

Issue: November 2009

Bioengineered collagen-based corneal substitutes are showing to be fully compatible and to promote regeneration of corneal cells in patients with degenerative corneal disorders or post-traumatic damage, according to a study.

Per Fagerholm, MD, of Linköping University, Sweden, presented the preliminary results of a joint Swedish-Canadian study, in which this type of corneal substitute was effectively used for transplantation in 10 patients — nine with keratoconus and one with corneal scar.

“These biosynthetic grafts are composed of human recombinant collagen type III cross-linked with water-soluble carbodiimides,” Dr. Fagerholm said. “They are designed to mimic the extracellular matrix of the human corneal stroma to allow some regeneration of the host tissue. They can be tailored in the shape, curvature, thickness and diameter you want.”

Follow-up

In all of the patients enrolled in the study, a central, deep lamellar lenticule, 6 mm in diameter, was excised and replaced by a 6.25-mm, 500-µm thick construct. Three overlying sutures were used. Patients have now reached 1 year of follow-up.

“At 9 months, all patients had stably epithelialized, and implants were anchored by keratocyte ingrowth. Visual outcomes were satisfactory, with six patients achieving [best corrected visual acuity] of 20/40 or better,” Dr. Fagerholm said. “The mean central corneal thickness was unchanged between 3 and 12 months. Schirmer values were normal, and corneal sensitivity was the same as in the control fellow eye. In vivo confocal microscopy revealed a beginning ingrowth of corneal nerves and the presence of keratocytes in the constructs.”

Further improvements

This first experience, Dr. Fagerholm said, has been encouraging. More patients will be treated now and will benefit from further improvements in the biomaterial and implantation technique.

“We are going to increase the collagen content of the constructs and to try a better suture removal technique to promote faster re-epithelialization and corneal clarity,” he said.

Bioengineered corneal substitutes could be a breakthrough in corneal grafting. They could address the shortage of human donor tissues, as well as their clinical disadvantages, such as immune rejection and the risk of transmission of infectious diseases. At the same time, they would more naturally integrate in the host eye than artificial corneas, Dr. Fagerholm said. – by Michela Cimberle

Per Fagerholm, MD, can be reached at the Department of Ophthalmology, Linköping University Hospital, SE 581 85 Linköping, Sweden; +46-13222368; fax: +46-13223065; e-mail: perfa@inr.liu.se.

This technology may most benefit the regions of the world where cadaveric corneas are not readily available. This accounts for much of the developing world, where cornea blindness is also more common. Long-term studies will be needed to determine the overall retention and clarity of the implanted cornea substitutes. The patients selected in this study had ocular pathology that typically has the most favorable prognosis for penetrating keratoplasties. Therefore, it was a patient population with the best possibility for success and a good place to start. It will be interesting to see if the cornea substitute is also successful in less favorable prognostic categories, where cadaveric cornea transplants have less likelihood of success. This includes eyes that have had failed previous cadaveric cornea transplants or have autoimmune diseases.

– Joseph B. Ciolino, MD
Clinical Fellow, Massachusetts Eye and Ear Infirmary and Research Affiliate of the
Massachusetts Institute of Technology, U.S.A.