On September 15th 2022, the António Champalimaud Vision Award was attributed to two physician-scientists, both of them ophthalmologists, for their pioneering work in the understanding and treatment of corneal disease. Gerrit Melles from the Netherlands Institute for Innovative Ocular Surgery, and Claes Dohlman, from Mass Eye & Ear and Harvard University, shared the prestigious one million euro award – the former for his innovative surgical methods of corneal transplant, the latter for his advancement of cornea research and the development of an artificial cornea, the “Boston K-Pro”.
The cornea deserves the well-known metaphor “window of the eye”: it’s the transparency, smoothness and curvature of this millimeter-thin, delicate, virtually invisible ocular front layer that are the basis of most of the eye's focusing power, allowing us to perceive the outside world in an unclouded, undistorted fashion, akin to a high-quality glass pane set in a window.
As the eye’s outer layer, most physical injuries to the eye affect the cornea, and when diseases and disorders – such as Fuchs dystrophy or keratoconus – cloud this structure, make it bumpy or alter its shape, vision impairment and even blindness ensue. Today, new surgical techniques and even prosthetics are managing to make corneal repair much safer and more effective than it was a few decades ago.
The conventional way to treat corneal opacities is by corneal transplant, which has existed for more than a century. Its technical name is “penetrating keratoplasty” (simply put, full-thickness corneal surgery). To perform it, ophthalmological surgeons cut a hole in the central part of the cornea of the patient’s eye and replace it with a whole cornea “button” from a donor.
The cornea essentially has five layers, so these are transplanted together in the conventional procedure. This can cause well-known complications, such as astigmatism due to the presence of sutures and donor graft rejection by the transplant recipient. Often, the corticosteroids used to treat inflammation resulting from these classic transplants can lead to glaucoma, a potentially serious eye condition.
But Melles’ more recent techniques only remove the affected part – the affected layer – of the patient’s cornea. “What we do is to selectively transplant one layer of the cornea, the one that is really damaged, and we do not touch the others”, he told us during an interview in Lisbon.
A layered approach
How did he start looking into this? “During my training as a cornea surgeon, I saw a lot of patients who had had corneal transplants, and a lot of them had problems after surgery: astigmatism was one of them, because the new cornea was not perfectly spherical due to the sutures”, Melles said.
Martine Jager, dutch ophthalmologist and cornea surgeon from Leiden University who this year nominated Melles for the António Champalimaud Vision Award, was present at the Foundation for the Award Ceremony. She told us: “Melles thought to himself, ‘that’s weird, you don’t take out the whole leg if you only have a bone problem! So why not just replace the one layer of the cornea that is ill?’ And that’s what he did”.
So more than two decades ago, like many others, Melles started thinking that maybe the procedure itself was downright conceptually wrong and needed to be radically improved. “If you are going to replace certain layers that are not really ill, you will get the complications from removing them, but no benefits”, he reasoned. “But if, for instance, only the endothelium [the innermost layer] is damaged, and you just take it out and put a new one in, the rest of the layers are not going to give rise to complications.”
“I happened to see the third patient that Gerrit treated himself”, says Jager. “But I couldn’t find any sutures… This was six months after the patient’s surgery, and the patient had 80% vision. We had never seen anything like that! Then I figured out that Melles must have used the new technique that he was talking about. And he had. And it was brilliant!”
Today, “lamellar keratoplasty” techniques (which go by acronyms such as DMEK, DSEK, DSAEK, DALK, depending on the technique and the layer of the cornea that is transplanted) are used around the world. In countries like the United States or Germany, the number of lamellar keratoplasties has surpassed the number of penetrating keratoplasties.
In spite of the success and the increasing simplicity of his techniques and equipment, Melles is cautious about the possibility of making lamellar corneal transplant as ubiquitous as cataract surgery, which involves replacing the lens of the eye by a synthetic lens and needs much less further care.
“The problem with donor tissue”, he says, “is that most of the time people need access to medical care in the long term – because of the risk of rejection, for example. But what about people who go back to where they live and never have medical care again? Would it help someone who has 10% vision if they had the surgery, suffered this kind of problems, and ended up with less than 10% vision? And there are also huge numbers of patients who do not have access to healthcare at all.”
Melles stood his ground when criticised for his novel techniques. “When they made his life difficult where he worked, he set up his own clinic. When they made his life difficult with the biobank [the facility where human donor tissue is received, stored and prepared for transplant], he developed his own biobank”, says Jager. “And then he started teaching the world how to perform the surgeries. And now all these doctors only replace one layer. For influencing the lives of so many people, I think he is absolutely the best person to get the Champalimaud Vision Award.”
Artificial window
Claes Dohlman, often recognized as the father of modern corneal science, also shared the 2022 António Champalimaud Vision Award. The Swedish-born cornea specialist celebrated his 100th birthday four days before receiving the award in Lisbon. Incredibly, he is still actively contributing to the writing of scientific papers and participating in his lab’s work, a lab he founded more than 60 years ago.
Dohlman is proud, among a large body of work, of being recognised for inventing a prosthetic cornea known as the Boston K-Pro. “An artificial window – an obvious solution if you have [to substitute] an opaque cornea”, he says. “But it’s not as simple as that, because the procedure has to be safe, affordable, effective and easy for the surgeon. The problem is that it is still too expensive.”
In developing his corneal prostheses, Dohlman succeeded where many others failed. What was the “trick” that did it? “Just continuing the previous effort to create an artificial cornea”, he told us. “A number of people have tried, very bright people, surgeons, but they didn’t have the patience. They didn’t carry on decade after decade after decade. They gave up too early.”
In fact, the Boston K-Pro comes in when corneal transplant does not work – that is, for people whose eyes are too damaged. “[Claes] Dohlman’s long-term quest for an artificial cornea, especially for patients whose eyes are too damaged to benefit from traditional donor transplantation, led to his development of the Boston KPro, which is now in global use”, said the Champalimaud Foundation in a statement. It has become the most widely used artificial cornea, restoring sight to more than 15,000 patients in the United States and in 52 other countries.
What does “damaged” mean? “It’s the degree of inflammation that counts”, said Dolhman. “If there is very little inflammation, then one can go straight to tissue transplant, such as a full-thickness keratoplasty or Gerrit Melles’ layer-by-layer approach. But if there is an obvious inflammatory situation – the eye is red, painful and so on – then it is unlikely that a transplant will do.”
In the Western world, half of the corneal opacities are not derived from corneal disease, but from edema – which means there’s very little inflammation. “So, probably, the Western world will follow Gerrit Melles’ path and continue replacing the cornea with donor tissue, layer by layer”, Dohlman said. But in the developing world, “where 90% of the cornea-blind live, and try to make a living”, the degree of corneal inflammation, caused by eye infections and other injuries to the eyes, is much higher. “If there’s a lot of inflammation, this will tip the scale toward an artificial cornea like the Boston K-Pro”, he added.
One of the main complications of the K-Pro, however, is the so-called secondary glaucoma in patients with severe corneal disease fitted with the prosthesis. “The details of this complication were not known to us nor to anybody. But we learned about glaucoma, and that’s the most important. And we are beating it”, Dolhman said.
What they found is that when the eye suffers a chemical burn, for instance, certain cells in the cornea secrete specific inflammatory proteins (cytokines), collectively called tumour necrosis factors alpha or TNF-alpha, which diffuse out to the rest of the eye very quickly by infiltration. And this process affects cells that are associated with glaucoma.
“We now [also] know that antibodies against TNF-alpha are phenomenally effective to inhibit the bad effects of TNF-alpha.” We have submitted a paper [about our results] to the journal Ophthalmology Science”, he points out. This could mean, according to Dohlman, that secondary glaucoma associated to the Boston K-Pro could be prevented by a “cocktail” of TNF-alpha inhibitors, among other compounds. “It will work, I know it will. In another ten years or so.”
As the laureates left Lisbon after the award ceremony, celebrations continued back in Rotterdam and Boston. In Rotterdam, Melles, who also happens to be a classical music composer and founder of the Melles Classical Music Foundation, celebrated the event with a concert. Dohlman gathered more than 60 former and current colleagues at the Harvard Faculty Club, and also reunited with almost 40 children, grandchildren and great-grandchildren to celebrate the award as well as his 100th birthday.
By Ana Gerschenfeld, Health&Science writer of the Champalimaud Foundation.
