Lamis Baydoun on how corneal transplantation has changed – and what’s been learned – since the introduction of DMEK
Dr. Lamis Baydoun has been a key character in the recent developments and modifications of a new type of corneal surgery called “posterior lamellar keratoplasty” – a procedure that has completely transformed the world of corneal transplant surgery since its introduction. The cornea is composed of five layers (Figure 1), but until a few years ago, corneal transplantations typically were full-thickness corneal transplants (called “penetrating keratoplasty”, or PKP) irrespective of whether the disease affected one or all of the layers. But a high number of corneal diseases only affect the inner layers of the cornea (i.e. Descemet membrane and endothelium). Those layers are treated in posterior lamellar corneal transplantation procedures that have been developed and revolutionized by Dr. Gerrit Melles, founder of the Netherlands Institute for Innovative Ocular Surgery (Rotterdam, The Netherlands). These procedures now allow corneal surgeons to replace only the diseased layers with corresponding layers from donor tissues.
This approach has the advantage of leaving the healthy anterior parts of the person’s cornea intact, which results in faster visual rehabilitation and outstanding visual outcomes. It’s also a less invasive technique, as rather than completely removing the cornea and replacing it, lamellar corneal surgery requires only a few small incisions for it to be performed, so recovery times are faster too. Lastly, the risk of rejection is reduced dramatically. The most recent and currently the best performing posterior lamellar corneal surgery is called DMEK – Descemet membrane endothelial keratoplasty where the host Descemet membrane (DM) and endothelial cell layer are replaced by healthy donor DM and endothelium. However, DMEK surgery is particularly challenging for surgeons to learn.
Dr. Baydoun spent more than six years at the Netherlands Institute for Innovative Ocular Surgery (NIIOS) in Rotterdam, working closely with the inventor of DMEK, Gerrit Melles. As Head of the NIIOS Academy, she has taught dozens of surgeons across the world how to perform this surgery and her research today continues to push the field forward. Here’s what she has to say.
What corneal surgeries do you perform?
Before my time at NIIOS, I was an anterior segment surgeon and Director of a cataract department, so I was doing a lot of lens surgeries, and yet I was a cornea consultant. I wanted to subspecialize, so that’s why I went to The Netherlands, but somehow, I ended staying there for seven years instead of the six months I intended.
What was it about NIIOS then? Was it Gerrit?
Yeah, it was Gerrit Melles, the Pope of lamellar surgery and inventor of DMEK.
Yes, he’s really a “Pope” of this surgical field. It’s amazing because, for 100 years, corneal surgeons performed only the full-thickness penetrating keratoplasty – there was no other option to treat patients that have only one diseased layer. It was 100 years later when Gerrit showed the results of his experiments and his first surgeries that opened up the field of endothelial keratoplasty (which is surgery on the innermost layer of the cornea). That started with DLEK (Deep lamellar endothelial keratoplasty, then with DSEK/DSAEK (Descemet stripping (automated) endothelial keratoplasty, and then DMEK. DMEK is the latest and most precise innovation, where you can restore the normal corneal anatomy.
I understand there was a lot of trepidation; people were not happy to adopt DMEK in the first place.
That’s true, a lot of people were very uncomfortable with the technique and the graft itself; Many steps were perceived as obstacles. First, it was very difficult to recover the DMEK graft from a donor cornea. Second, graft unfolding during surgery was a main fear to learn this technique because every time you touch this delicate graft you may damage corneal endothelial cells that are required to clear the cornea. And third, the management of a new post-operative complication, i.e. graft detachment, was another main concern, which is why many corneal surgeons were reluctant to adopt it in the first place. People faced complications that just didn’t occur with full-thickness PKP transplants, so these surgeons felt they were far more comfortable with remaining with the older techniques. But over the longer term, the benefits of DMEK over all previous keratoplasty techniques were so overwhelming that DMEK could not be ignored anymore – you could actually reach a level of visual outcomes that were so excellent and comparable to that after lens or even refractive surgery! And of course, we had some very happy patients afterward. And when the patient is happy, of course, we doctors are also very happy.
What diseases are best treated with DMEK?
All diseases that concern the corneal endothelium. So, the cornea normally consists of five layers. From outside to inside: the epithelium, the stroma, between the epithelium and the stroma, you have Bowman layer, then comes the Descemet membrane, and then the endothelium – and those last two layers are replaced in endothelial diseases. There is one disease called Fuchs endothelial dystrophy, that’s very common and very effectively treated with DMEK. Then there is also Bullous Keratopathy, which usually occurs when corneal endothelial cells are damaged during certain eye operations, like surgery to treat glaucoma or remove cataracts. These are cases that are also well treated with DMEK.
So DMEK is a difficult to technique to master?
It was. Of course, now it’s getting much easier. The surgery was first performed in 2006 by Gerrit Melles, so we have now 13 years of experience and with these 13 years, we now have a standardized procedure and have learned how to handle the graft better. But in the first place, it is, of course, a challenge for a surgeon to perform this procedure. That’s why we offer courses in Rotterdam, where we teach surgeons tips and tricks and how to get over these obstacles to adapt to DMEK surgery more quickly.
You taught most surgeons in Europe how to perform DMEK?
Well, we actually had corneal surgeons from all over the world wanting to learn this surgery and during my NIIOS time of six and a half years, I practically taught and performed live surgeries in every course.
What should patients expect when they’re told they need lamellar corneal surgery like DMEK?
Well, what you expect is that it’s a less invasive treatment, so instead of excising the whole cornea and having the eye open during surgery, you have only minimal, small incisions where you enter the eye with small instruments, then you insert a graft after removing the diseased layers. After that, you unfold the graft before attaching it with an air bubble to the posterior stroma of the patient. This was actually the phenomenon why this surgery got so successful because before we used to attach the graft with sutures, and sutures can irritate the eye, can induce inflammation, that can lead to transplant rejection. Attaching the graft with an air bubble eliminates this, so patients can expect a less invasive and less traumatic surgery, and after that, faster rehabilitation with better visual outcomes. Sometimes the graft can detach in about 5–10 percent of cases, still not all cases need a re-bubbling procedure, in my experience graft detachment has become a controlled complication.
What lessons have been learned over the 13 years since the first DMEK was performed?
What I’ve learned in the last years is not to be afraid of the graft anymore! This is something that just at the beginning is quite frightening. You’re afraid of touching it, you’re afraid of the graft itself, because it behaves how it wants to behave, but with experience, you realize that no, I’ll tell you what to do, and in most of the cases it will do what you want.
What I’ve also learned is not every surgery that is difficult necessarily ends up in a bad result (it’s the other way around actually) – it can be surprisingly good even though it was a difficult surgery. These are mysteries we still need to understand.
That brings us to the research where people are doing almost like sham DMEK, or are putting in small grafts…
Yes, that’s also an invention we did at NIIOS. I performed the first series in Rotterdam – the quarter DMEK surgeries. This is actually a surgery that we don’t offer to patients with Bullous Keratopathy, but only to patients with central Fuchs Dystrophy. Let me explain.
Fuchs Dystrophy is a disease where you sometimes only have central guttae with mild or localized corneal edema, but still functioning peripheral endothelial cells. So, in a similar way to how Gerrit Melles invented DMEK, to offer a selective treatment for the patient that only treats the diseased endothelium, we have taken that thinking a step further. We asked: is standard DMEK, with its 9.0 mm descemetorhexis and round 8.5–9.5 mm graft, really the most selective treatment for all forms of Fuchs Dystrophy? Is it that if you have a patient with Fuchs disease but with only central guttae that cause visual disturbances by stray lights from these guttae during driving the car etc., wouldn’t it be enough to remove just this small diseased central portion and give that person just a small graft piece for quick visual rehabilitation while sustaining his/her own peripheral cells? That’s the idea with quarter-DMEK, besides the fact that you can use endothelial donor tissue more efficiently, hence instead of one standard graft, you can recover four quarter DMEK grafts from one donor cornea.
Endothelial keratoplasty brought us new understandings in cell biology and physiology. Further innovations are possible because of how the cells react, how they migrate after DMEK surgery. It’s not just simply placing some graft tissue in the eye: much more happens than this.
Is that the case where you’re replacing the membrane above the diseased endothelium and removing the diseased cells, and the patient’s own endothelial cells migrate in to fill the gap?
Yes, so you may have heard of the Fuchs disease-treating concept called Descemet stripping without endothelial keratoplasty. That means surgeons remove the Descemet membrane and the endothelial layer in the center of the cornea, which allows the cells from the periphery to migrate inwards to the center and clear up the cornea. It may take a couple of months until the cornea clears, and of course, you want to offer a patient a treatment that shows faster visual rehabilitation. We still don’t know which cases should be treated without a transplant (and still profit from this treatment with fast visual recovery), so we thought if we transplant a smaller graft just in the center of the optical axis and use it for these kinds of patients, then you will have combined the benefits of the migration approach, use less graft tissue with the chance of further reduction of rejection, and still give the patient fast visual rehabilitation.
Now we have to be very alert for what’s coming, because a lot is happening in this field at the moment. Descemet stripping without endothelial keratoplasty means that you’re not putting in foreign tissue, so there’s no transplant, and consequently no risk of tissue rejection anymore, and you avoid the problem of repeated transplants. But we don’t know which patients will do fine because if cells migrate, are these as good as cells that are on the transplant?
Also, there are approaches with cell injections and cell carriers, there’s a lot of research being done on that…
You can culture your own cells presumably and try that?
Exactly so. I think we are fortunate that we will still be doing some DMEKs for a couple of years longer, but probably something like that will come along next to “replace” it.
What do you think of intraoperative OCT?
I think intraoperative OCT (iOCT) is a good tool to help you learn how to do DMEK, as the main issue beginner surgeons have is knowing which graft side is the right side up, and iOCT shows you this during surgery. But once you’re familiar with the technique and the surgical set-up, you don’t necessarily need it anymore. But still, it may be a helpful tool in eyes with very, very edematous corneas.
What are you presenting at ESCRS/EuCornea?
Like every year, we will have a wet lab and a NIIOS instructional course at the ESCRS and I will present research on allograft rejection. I am doing a Ph.D. on allograft rejection and DMEK and endothelial cell failure/survival rates, so what I was researching over the last years is how to identify eyes that are prone to reject the DMEK graft before the actual rejection starts.
So my most recent research has just been accepted as a free paper in the EuCornea meeting, and I will present how we saw changes on Scheimpflug imaging and specular microscopy in patients that later developed rejection, whereas we didn’t see all those signs in eyes that have not developed rejections. We assume that if you perform these standard diagnostic techniques on these patients, you might be able to identify patients at risk of rejecting their DMEK graft after surgery. After DMEK, there is still a risk for graft failure from allograft rejection, so we aim to identify those eyes as early as possible to start treatment earlier and hereby save them from failure.
Using the tools that ophthalmologists already have in their offices rather than having to do biomarker assessments of tear films, and so on?
This would also be something interesting to do, but yes, this is using two diagnostic instruments you already have in a cornea specialist practice. I don’t think everyone does both of them, but if you can do them it could be helpful to identify these eyes. We still have to see how it works in a clinical setting.
So how many corneal surgeries do you think you’ve done across your career?
So far? Oh, don’t ask me this! I have not counted them. I mean, I don’t do corneal surgery as often as cataract surgery, but I can look it up for you!
How much time do you spend doing research as opposed to surgery?
At NIIOS, it was a very big part of my work, so I would say I’d have it half-half. I am still finishing some projects at the NIIOS, but now mainly working at the University in Munster, Germany, in general, I do less research and more clinical work these days. I have to finish up my Ph.D. so this is the main call on my spare time at the moment, so I cannot take many more projects!
So how are you finding Zurich?
Well, as you know, I started my ophthalmology career here in Zurich in the year 2000.
During my studies I was fascinated by neuroanatomy and neurology, therefore I wanted to become a neurologist. A good friend of my parents who was an ophthalmologist told me back then, “Come on, why do you do neurology, it cannot save people? Just do ophthalmology, and you could specialize in neuro-ophthalmology.” And I’m like, “That’s just the eye; I’ve studied medicine!”
In Germany, we have the last year of medical school where you do three medical specialty rotations – that is surgery, internal medicine and a third specialty individually chosen by each student. That ophthalmologist then suggested: “Do ophthalmology as your chosen rotation, and if you don’t like it just keep neurology after that.” I said okay, that’s a deal. So, I did it here in Zurich and it was wonderful. Zurich is a place I left 19 years ago with great memories, so it didn’t surprise me that I now came back!
But the cornea is at the wrong end of the eye for brain tissue, right?
Of course, but still, ophthalmologists are one of the happiest specialists in medicine, so I’m happy that this ophthalmologist put the light on just before I went along a completely different path. I feel bad for doctors that choose a specialty other than ophthalmology, but I (jokingly) also feel sorry for those ophthalmologists that specialize in anything other than the cornea.
Lamis Baydoun, MD, is a Consultant Ophthalmic Surgeon at the ELZA Institute, Zurich and at the UKM Uniklinikum Muenster, and is Head of the NIIOS Academy in Rotterdam.