Scientists have successfully implanted a biosynthetic alternative to the human cornea in the first clinical study of it’s kind. The research, published in Science Translational Medicine today, is a 24 month follow-up of the phase one clinical study led by Per Fagerholm, Professor of Ophthalmology at Linköping University. The cornea is a vital component of the eye acting as the outermost lens, controlling and focusing light as it enters the eye as well as shielding it from germs and infection. However, millions of people worldwide suffer from corneal disease and damage, which can lead to blindness. Currently, the best way to correct corneal damage is through transplanting a human donor cornea. But there is a huge worldwide shortage of human donor corneas, and eye and tissue banking is not carried out in many countries because of concerns with donor-derived infection.
The new findings by Fagerholm and his colleagues could make the long waiting lists for replacement corneas a thing of the past. “Produced from human collagen the artificial biological cornea mimics the corneal structure and is aimed at promoting regeneration.” explains Fagerholm, also a corneal surgeon who carried out the implant operations. However, ten years ago when studies into the biosynthetic collagen cornea were starting to progress, most researchers were sceptical. “A decade ago most researchers were concentrating on synthetic [plastic] cornea research,” says May Griffith, Professor of Regenerative Medicine at Linköping University, Sweden and co-author of the study. "But in 1999 we showed it was possible could reconstruct the cornea. " she says referring to her research published in Science which was the basis for getting the biosynthetic approach into clinical trials.
In 2007, after five years of pre-clinical testing and regulatory hurdles, ten patients were chosen for the phase one clinical study. “The study was designed to test the safety of the novel biosynthetic corneas.” says Griffiths. Patients were chosen with corneal damage and disease focusing on those suffering from advanced keratoconus or a central scar.
Two years and nine months into the study the results are encouraging. “After two years six out of the ten patients saw their vision improve and the eyesight of all ten improved with contact lenses with one patient restoring 20-20 vision,” she says. And as the researchers monitored the patients recovery, other results were surprising. “Normally when human donor corneas are implanted, drugs including steroid immunosuppressions are given for between six months and one year as a preventative measure to ward off infection.” says Griffith. “However using biosynthesized corneas we phased the steroids out after about seven weeks because the patients showed no signs of needing them after the post-operation inflammation had gone down,” says Griffith.
Not only this, but the human nerve regeneration was unprecedented. In nine out of ten patients nerves regenerated and the cornea was sensitive to mechanical stimulation. “In human donor corneas the nerves don’t always grow back.” says Griffith. “So we were very happy to see nerve densities increasing in the two years after implantation of biosynthetic corneas. We had seen nerves growing back in tests with healthy animals, but we were unsure what to expect”.
Earlier studies, including the European ‘Artificial Cornea Project’ which finished in 2008, paved the way for the development of synthetic corneas. Using a new version of a polymer plastic designed specifically for eye tissue the synthetic cornea has pioneered cornea implants in patients with extreme corneal damage and disease.
“For some patients, the cornea is so badly damaged there is only connective tissues left and a synthetic cornea is the only implant that can work,” explains Wolfgang G.K. Müller-Lierheim, director of the company Coronis who market the synthetic cornea. “But unfortuntaely, synthetic cornea’s are not the answer for most patients. The plastic is a foreign object and can only work in eyes that have excessive scarring so the plastic cornea is held in place,” he says. “The synthetic cornea has a small and specific market.”
In contrast, the biosynethetic cornea can fully interact with the eye tissue. This leads to regeneration of the cells and nerves that hold the implanted cornea in place, which means the biosynthetic cornea’s could have much wider application as a substitute for human donor corneas. “The biosynthetic corneas look very promising as a way to solve the current worldwide shortage of donor corneas,” says Müller-Lierheim.
So what’s next for biosynthetic cornea research? “Today, creating the biosynthetic cornea’s is manual work and the collagen is expensive,” says Fagerholm. “We will continue the clinical studies and there are things we want to improve. However we hope in the next five years we will have completed phases two and three of the clinical studies,” he continues. So it looks like within the next decade the widepsread use of biosynthetic coreas to correct cornea damage and disease could become a reality. “We have now shown that biosynthetic corneas can work in humans and could be a real alternative to human donor corneas,” says Griffith.
Image: Implanted biosynthetic cornea of one of the ten patients one day after implantation and 24 months after implantation of the biosynthetic cornea / Per Fagerholm and Neil Lagali