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Being the Boss of the Graft

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 development of a completely new type of corneal surgery called “posterior lamellar keratoplasty” – something 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 were typically complete corneal transplants (a procedure called “penetrating keratoplasty”, or PKP) irrespective of whether the disease affected one or all of the layers. But a number of corneal diseases only affect the deep layers of the cornea, and lamellar corneal transplantation procedures have now been developed that allow surgeons to replace only the diseased layers with corresponding layers from donor tissues.

This approach has the advantage of leaving the rest of the person’s cornea intact, which results in better 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 lamellar corneal surgery is called DMEK – Descemet’s membrane endothelial where the host Descemet membrane (DM) layer and endothelial cell layer are replaced by donor DM and endothelium. However, DMEK surgery is particularly challenging for surgeons to learn.

Dr. Baydoun spent seven years at the Netherlands Institute for Innovative Ocular Surgery (NIIOS) in Rotterdam, working closely with the inventor of DMEK, Gerrit Melles, and she has taught dozens of surgeons across the world how to perform this surgery in her previous role as Director of the NIIOS Academy, and her research today continues to push the field forward even more. Here’s what she has to say. 

What corneal surgeries do you perform?

Before my time at NIIOS, I started as 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.

The Pope?

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 that opened up the field of endothelial keratoplasty (which is surgery on the innermost layer of the cornea). That started with DLEK, then with DSEK, and then DMEK, and DMEK is the latest and most precise innovation, where you can really restore a normal corneal anatomy of the eye.

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 graft itself; it was very difficult to harvest the graft. The graft has to be folded like a taco to be inserted through a small incision into the receiving patient’s eye. and then the unfolding was a problem for people to learn (every time you touch the donor cornea, you kill corneal endothelial cells, which is a concern). Then you might have to  deal with post-operative complications like graft detachments, so these were all obstacles and reasons why corneal surgeons did not adopt it in the first place. People could up with 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, they saw that the results of DMEK were so overwhelming – you could actually have visual outcomes that were excellent, and really comparable to lens surgery! And of course, we had some very happy patients afterwards. 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 has five layers, so the epithelium, the stroma, between the epithelium and the stroma, you have Bowman’s layer, then comes the stroma than the Descemet’s membrane, and then the endothelium – and those last two layers, those are diseased in endothelial diseases, and there is one common disease that’s called Fuchs’ dystrophy, that’s very common, especially in Europeans. So this kind of disease is very effectively treated with this DMEK procedure. You can also have 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 this DMEK.

So DMEK is a difficult to technique to master?

It was. Of course, now it’s getting easier. The surgery was first performed in 2006, so we now have 13 years of experience and with these 13 years, we’ve learned how to handle the graft better. But in the first place, it is, of course a challenge for a new surgeon to do this procedure. That’s why we offered courses in Rotterdam, and I was the Head of Academy the academy there for many years, where we taught surgeons how to get over these obstacles and to better adapt to DMEK surgery.

You taught most surgeons in Europe how to perform DMEK?

Well, we actually had corneal surgeons from all over the world wanting to adopt this surgery, over the last six and a half years I practically attended and taught in every course.

What does it mean for a patient when they get told you lamellar, surgery you need DMEK? What should they expect?

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 the instruments, then you insert a graft after removing the diseased layer. After that, you attach the graft with an air bubble. This was actually the phenomenon why this surgery got so successful, because before we used to treat with sutures, and sutures can tend to irritate the eye, they make the transplant reject. But the bubble eliminates this, so patients can expect to have a less invasive and less traumatic surgery, and then after that, faster rehabilitation and a better visual outcome. Sometimes the graph can detach so in 10 percent of cases but in my experience, I don’t have to perform many re-bubblings.

What lessons have been learned over the 13 years since the first DMEK was performed?

What I’ve learned in the last few years is not to be afraid of the grafts 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 realise that no, I’ll tell you what to do, and 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.

We had some cases where we actually removed the graft and then checked it under the microscope and you could see there were no cells, but I asked myself sometimes if we had attached it would it really be that it doesn’t have any cells? I’m not really convinced.

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. I actually did all of those surgeries in Rotterdam – the quarter DMEK surgeries. This is actually a surgery that we don’t offer for patients with Bullous Keratopathy, only for patients with Fuchs’ Dystrophy that we expect to have just central guttae. Let me explain.

Fuchs’ dystrophy is a disease where you have a thickening of the Descemet’s membrane and you have mushroom-shaped ‘boutons’, so in a similar way to how Gerrit Melles invented DMEK, to offer a selective treatment for the patient that only treats the diseased layers, we have taken that thinking a step further. We asked: is standard DMEK, with its round 8.5 mm graft, really the most selective treatment for all endothelial diseases? Is it that if you have a patient like with early Fuchs’ disease or a patient that has just central guttae but is disturbed by stray lights from these guttae during driving the car etc., wouldn’t it be enough to give that person just a small piece? That’s the idea with quarter-DMEK, and that’s why we are approaching these kinds of new treatments.

Endothelial keratoplasty brought to a point where further innovations that are possible because of how the cells react, how they migrate after DMEK surgery. It’s not simply placing some graft tissue in the eye: much more 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’s stripping without endothelial keratoplasty. That means surgeons remove the endothelial layer in the centre of the cornea, which let the cells from the periphery migrate inwards to the centre 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 than a few months. 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, and still give the patient fast visual rehabilitation.

What’s next?

Now we have to be very alert for what’s coming, because there is a lot happening in this field at the moment. Descemet’s stripping without endothelial keratoplasty means that you’re not putting in foreign tissue, so there’s no transplant occurring, so there’s no chance of tissue rejection, and you avoid the problem of repeated transplants. But we don’t know which patients will do fine because if cells migrate, are they these as good as cells that are on the transplant?

So, there are cell injections, 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 I’m sure 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 side is the right side up, and iOCT shows this. But once you’re familiar with the technique and the surgical set-up, you don’t need this – you will just be able to look down the surgical microscope, check your marks and you know which side is which. The one time I did use an iOCT, I didn’t find that it helped me. But still, never say never – there may be a few cases in which it might be needed, like very oedematous corneas, but even in the few cases I’ve performed like that, I’ve not needed it. But there can be worse cases, so as I say, never say never.

What are you presenting at ESCRS/EuCornea?

Like every year, we will have an instructional course at EuCornea. and I will still attend the NIIOS DMEK instructional course, but what I will present is my research on allograft rejection. I am doing a PhD 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 – even if the surgery was straightforward and went well. After DMEK, there is still a small possibility for a graft failure from corneal decompensation, so our aim is to identify those eyes as early as possible to 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, but it’s in the hundreds. 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, but at the moment since I’ve made this transition, I do less research at the moment and more clinical work these days. I have to finish up my PhD so this is the main call on my spare time at the moment, so I cannot take more projects!

So how are you finding Zurich? 

Well as you know, I started my ophthalmology career here in Zurich in the year 2000. I wanted to become a neurologist, but a good friend of my parents who was an ophthalmologist and he told me in 2000 he said, “Come on, why do you do neurology, it cannot save people? Just do neuro-ophthalmology.” And I’m like, “That’s just the eye; I’ve studied medicine!” And then he said, “Just do this last.” In Germany, they have the last year of medical school where you do three medical specialty rotations – we have like three new you enter three specialties, surgery, internal medicine and a chosen one. I wanted to do neurology, so he said, “Do ophthalmology, 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.

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 he put the light on just before I went along a completely different path. Zurich is a place I left 8 years ago, but I really enjoyed it, so it didn’t surprise me that I came back!

I feel bad for doctors that choose a specialty that isn’t ophthalmologists, but I also feel sorry for the retina people. I (jokingly) tell medical students if you chose a specialty that isn’t ophthalmology, I feel really sad for you, but I also say if they choose anything that isn’t cornea, that’s also very sad!

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.

 

 

 

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