Cutting-edge research into corneal transplants
Something as simple as cleaning an oven can have life-changing consequences if things go wrong. One accidental splash of caustic cleaner into an eye can leave people with loss of vision and pain from ulceration. And up until now, no effective treatment existed.
“While severe chemical burns to the eye are most common in industrial accidents, they can also happen at home with routine jobs like cleaning the oven or water pipes with caustic cleaners that get into the eye,” says corneal surgeon Associate Professor Mark Daniell.
As the director of surgical research at the Centre for Eye Research Australia (CERA) in Melbourne, Daniell heads an ongoing trial involving 15 patients who, on compassionate grounds, have undergone experimental eye resurfacing and rejuvenation of the outer layer of the cornea – the epithelium – with good results.
The cornea is the clear protective layer over the front of the eye that has three microscopic layers that each play an important role in focusing vision.
About 2000 corneal transplants are performed in Australia each year to restore vision for a range of diseases and injuries but they have proved ineffective in treating surface scarring caused by burns and some types of corneal disease.
“When surgeons in the past tried doing a full thickness corneal transplant [from donated cadaver cells] on burns victims, it always failed,” says Daniell.
It has to do with the fact that this layer of the eye facing the air is like skin in that it has adult stem cells that constantly rejuvenate the surface.
Donated tissue contains none of these natural healing cells and patients end up with blood vessels and scarring growing straight back over the transplant.
“And when a corneal transplant doesn’t heal, it’s a disaster,” says Daniell. “Patients get infections and melting of the cornea and end up losing their eye, so we don’t do them anymore.”
The trial has been running for a decade with the team carefully monitoring patients’ progress to refine the technique.
Patients’ injuries include thermal and chemical burns, such as that of a young man who received alkali burns from wet cement slurry at high pressure on a worksite.
“We remove the scar tissue and blood vessels off the surface of the eye and then take cultured stem cells from either a donor or the patient if possible and sew those on to the surface with microscopic stitches,” says Daniell.
One of the early participants, Peter Uther, 61, an Anglican minister from Coolangatta, knows all about eye surface damage thanks to the complications of the congenital condition aniridia, which is the absence of an iris.
Because of his condition, the cells that protect the epithelium are sparse and unhealthy. This has left him with a rough eye surface that distorts light, similar to a burns victim. Another complication is an underdeveloped optic nerve that restricts his vision to 5 per cent.
“I’ve never been able to drive but I got by with an education in a school for the vision impaired and an office job,” Uther says.
“But in 1999 after I became an ordained minister and had my own parish, I was starting to lose that small amount of vision due to the deteriorating state of my eye surface.
“I always knew there was nothing doctors could do, but I was so desperate I went to my ophthalmologist in Brisbane who told me the only thing that would save my sight would be a stem cell transplant, and he rightly predicted that was years away.”
It was in 2007, after a relative saw Daniell on television talking about corneal surface rejuvenation, that Uther went to Melbourne and was accepted into the trial.
He has had three operations – the first two with transplanted donor cells and the latest this year with his own cells from the inside of his mouth.
Dr Karl Brown, who is part of the CERA team and is responsible for the cell harvesting and culturing, describes the process:
“We currently take a small amount of tissue preferably from the patient, just a few millimetres across. If the patient has one bad eye, we can take a tiny bit of cornea from the good eye. If not, we get the tissue from the inside of the mouth. These locations have adult stem cells of the kind we need to replace in the damaged eye.
“It takes about two weeks in the laboratory to grow this initial tiny quantity of tissue into a sheet of cells ready to transfer to the patient’s eye.”
Uther says the fact he got four years out of the first operation and six years out of the second seemed like a miracle because it saved his job and restored his independence, which, he says, “you don’t appreciate until you’ve lost it”.
“I’ll never have more than 5 per cent of sight because of my dysfunctional optic nerve, but I got down to about 1 per cent before the last procedure and for the first time in my life I had to learn how to use a cane,” he says.
Uther is as keen as the researchers to see if this third operation with his own cells lengthens the time between operations.
“The other great thing with this last operation is I don’t have to take anti-rejection medication. They caused my blood pressure to rise, which meant then I had to take more medication to bring it down,” he says. “I guess you could say my prospects before this technology were pretty dim.”
Mark Daniell says improvements in vision and comfort were recorded in 14 of the 15 patients but the results are still being analysed.
“The main improvement is in their comfort,” he says. “They often get a lot of sensitivity in the eyes as well as ulceration pain. So making the cornea smoother again gives them huge relief.”
The trial, which now has funding for another 10 patients, could translate to standard treatment within three years depending on funding availability.
It is the first of its type in Australia and similar trials are under way in other countries including India, which has a high rate of caustic burns.
Australia has a strong history in corneal advancements that date back to the first corneal transplant performed in 1940 in Brisbane.
In 1985 the Australian Corneal Graft Registry at Flinders University in Adelaide was established and so far has tracked more than 30,000 corneal transplants to identify risk factors for improving patient outcomes. Its vast store of information has helped guide surgeons and researchers worldwide.
Using layers of the cornea rather than full thickness corneal transplants is now the preferred technique, not only for better patient outcomes but also for economy of tissue from donated corneas.
But with emerging bioengineering technology worldwide, researchers such as Daniell and Brown predict donors may soon become a thing of the past.
Their corneal resurfacing work is one of two major highly collaborative bioengineering projects under way at CERA and exciting results in both have persuaded them this is the way of the future.
“The rejection rate with donor tissue, according to the Australian Corneal Graft Registry, is 30 per cent over five years,” says Daniell.
“By using a patient’s own stem cells you can bring that down to zero, and the bonus is that it also eliminates the need for anti-rejection drugs.”
This article was first published in the print edition of The Saturday Paper on May 27, 2017 as "Saved by the cells". Subscribe here.