Being the ‘boss’ of the graft

Caroline Richards, editor of Ophthalmology Times Europe®, interviews Dr Lamis Baydoun on how corneal transplantation has changed-and what has been learned-since the introduction of Descemet membrane endothelial keratoplasty (DMEK)

A high number of corneal diseases only affect the inner layers of the cornea, that is, the Descemet membrane (DM) and endothelium. Until a few years ago, full-thickness corneal transplants-or penetrating keratoplasty (PKP)-typically took place, irrespective of whether the disease affected one or all layers. However, surgeons can now replace just the diseased parts with corresponding layers from healthy donor tissue in posterior lamellar corneal transplantation procedures.

Dr Lamis Baydoun, former head of academy and corneal surgeon at the Netherlands Institute for Innovative Ocular Surgery (NIIOS) in Rotterdam, has been heavily involved in developments with posterior lamellar keratoplasty and the most recent type of corneal surgery to spring from this, Descemet membrane endothelial keratoplasty (DMEK). At NIIOS, she taught dozens of surgeons across the world how to perform DMEK surgery, and her research continues to push the field forward.WHO INVENTED DMEK?

Gerrit Melles is the founder of NIIOS and is regarded the ‘Pope’ of lamellar endothelial surgery. For 100 years, corneal surgeons performed only full-thickness penetrating keratoplasty-there was no other option to treat patients who have only one diseased layer. 

The results of Dr Melles’ experiments and his first surgeries opened up the field of endothelial keratoplasty. This started with deep lamellar endothelial keratoplasty (DLEK), then Descemet stripping (automated) endothelial keratoplasty (DSEK/DSAEK) and, finally, DMEK, the latest and most precise innovation, where you can practically restore the normal corneal anatomy.

HOW HAVE OPHTHALMOLOGISTS’ PERCEPTIONS OF DMEK CHANGED OVER TIME?

Many corneal surgeons were reluctant to adopt it at first. They were very uncomfortable with the technique and the graft itself, and perceived several obstacles.

Firstly, it was very difficult to recover the DMEK graft from a donor cornea. Secondly, the possibility of the graft unfolding during surgery incited fear in learning this technique because every time the delicate graft is touched, the corneal endothelial cells that are required to clear the cornea may be damaged.

The management of a new post-operative complication such as graft detachment (i.e., separation of the DMEK graft from the posterior stroma) was another concern. Patients faced complications that just did not occur with full-thickness penetrating keratoplasty (PKP) transplants, so surgeons felt they were far more comfortable remaining with the older technique.

However, over the longer term, the benefits of DMEK over all previous keratoplasty techniques were so overwhelming that the method could not be ignored any more-you could actually reach a level of visual outcomes that were comparable to those seen following lens or even refractive surgery! We had some very happy patients following the procedures. And when the patient is happy, of course, us doctors are also very happy.WHAT ARE THE CHALLENGES FOR OPHTHALMOLOGISTS WHO ARE NEW TO THE PROCEDURE?

It is worth mentioning that the technique is now becoming much easier to master. Dr Melles first performed the surgery in 2006, so we have 13 years of experience to draw on, and during this time period we developed a standardised procedure and learnt how to handle the graft and complications better.

However, it is, of course, a challenge for surgeons starting out with performing DMEK. This is why courses are offered in Rotterdam: to teach surgeons tips and tricks, and help them to get over common obstacles, thus enabling them to adapt to DMEK surgery more quickly.

The main issue beginner surgeons have is knowing which graft side is the right side up. This is a key step for a successful surgery, and certain intraoperative signs can help indicate the correct graft orientation.

An intraoperative OCT (iOCT) may be a useful tool during the DMEK learning curve to visualise graft orientation and positioning. Once the surgeons are familiar with the technique and the surgical set-up, they do not necessarily need to use it, although it may remain a helpful tool in eyes with very, very edematous corneas.

WHICH DISEASES ARE BEST TREATED WITH DMEK?

The answer to this is: all diseases that concern the corneal endothelium. So, the cornea normally consists of five layers. Going from the outside to inside, you have: the epithelium; the Bowman layer; the stroma; the Descemet membrane; and finally the endothelium-and these final two layers are replaced in endothelial diseases.

There is one disease-Fuchs endothelial corneal dystrophy-which is very common and effectively treated with DMEK, showing outstanding results. Then there is bullous keratopathy, which usually occurs when corneal endothelial cells are damaged during certain eye operations; for example, during surgery to treat glaucoma or remove cataracts. This is another disease that is well treated with DMEK.WHAT SHOULD PATIENTS EXPECT WHEN THEY ARE TOLD THEY NEED LAMELLAR CORNEAL SURGERY SUCH AS DMEK?

Patients can expect a minimally invasive treatment. Rather than excising the whole cornea and having the eye open during surgery, the surgeon will make only minimal, small incisions, entering  the eye with small instruments to remove the diseased layers before inserting a healthy donor graft.

Following this, the surgeon unfolds the graft before attaching it with an air bubble to the posterior stroma of the patient. This was actually how this surgery became so successful: previously, the graft was attached with sutures. These sutures can irritate the eye and induce inflammation, leading to possible transplant rejection.

Attaching the graft with an air bubble eliminates this problem, providing patients with a less traumatic surgery, and, after that, faster rehabilitation with better visual outcomes. From our experience at NIIOS, the graft can detach in about 10% of cases; however, not all cases may need a re-bubbling procedure. In my experience, graft detachment has become a controlled complication.

WHAT LESSONS HAVE YOU LEARNT SINCE THE FIRST PROCEDURE WAS PERFORMED?

What I have learnt is to no longer be afraid of the graft! This is something that at first is quite frightening. You are afraid of touching the graft and fearful because it behaves how it wants to behave. However, with experience, you realise that you can tell it what to do, and in most of the cases it will do what you want.

I have also learnt that not every surgery that is difficult necessarily ends up producing a bad result (it is often the other way around)-it can be surprisingly good even though it was a difficult surgery. These are mysteries that we still need to understand.WHAT ARE THE BENEFITS OF QUARTER-DMEK SURGERIES?

Quarter-DMEK surgery was invented at NIIOS and the first series was recently published. The surgery was offered to patients with central Fuchs dystrophy and not those with bullous keratopathy. The rationale for this is as follows.

Fuchs dystrophy is a disease that sometimes only causes central guttae with mild or localised corneal oedema, but still-functioning peripheral endothelial cells. So, in a similar way to how Dr Melles invented DMEK, to offer a selective treatment for the patient that only treats the diseased endothelium and DM, we took that thinking a step further. We asked: is standard DMEK, with its 9.0 mm descemetorhexis (i.e., removal of the DM and endothelium) and round 8.5–9.5 mm graft, really the most selective treatment for all forms of Fuchs dystrophy?

If you have a patient with Fuchs disease but only central guttae that cause visual disturbances such as stray lights during activities such as driving, it would seem sensible to remove just this small diseased central portion and provide the person with a small graft piece for quick visual rehabilitation while sustaining his/her own peripheral cells. This is the idea with quarter-DMEK; 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 endothelial cells react and how they migrate after DMEK surgery. It is not just simply a case of placing some graft tissue in the eye: much more than this takes place.WILL YOU BE ABLE TO USE PATIENTS’ OWN CELLS TO TREAT CERTAIN DISEASES IN THE FUTURE?

Potentially, yes. A lot is happening in this field at the moment. For example, in ‘Descemet stripping only’ or ‘Descemet stripping without endothelial keratoplasty’ for Fuchs disease, foreign tissue is not used, so there is no transplant. As a consequence, there is no risk of tissue rejection and so you avoid the problem of repeated transplants.

In this procedure, surgeons remove the DM and the endothelial layer in the centre of the cornea, which allows the cells from the periphery to migrate inwards to the centre and clear up the cornea. However, 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 currently feel that if we transplant a smaller quarter DMEK graft just in the centre of the optical axis and use it for these kinds of patients, then we 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.

In addition, a lot of research is being carried out on approaches with cell injections and cell carriers. I think we will still be doing some DMEKs for a couple of years, but it is likely such innovations will shake up the field again.

DR LAMIS BAYDOUN, MD
E: lamisbaydoun@hotmail.com
Dr Baydoun is a consultant ophthalmic surgeon at the ELZA Institute, Zurich/Dietikon, Switzerland and at the Department of Ophthalmology at the University Hospital Muenster, Germany.