The number of Descemet’s membrane endothelial keratoplasty procedures performed in the United States per year soared past 10,000 for the first time in 2018, representing a 41-percent increase.1 DMEK (including a modified version called DMAEK) now accounts for 35 percent of all endothelial keratoplasty surgeries. A far cry from the 344 DMEK procedures that were completed in 2011.2
“We are at the flash point in the evolution of DMEK,” says Portland, Oregon, surgeon Mark A. Terry, one of a few surgeons whose pioneering work has developed and refined this form of endothelial keratoplasty since it was introduced in 2006. “DSAEK (Descemet’s stripping automated keratoplasty) has been the runaway preferred procedure and is still the leading form of endothelial keratoplasty. But DMEK started to take off in 2014, the same way DSAEK did in 2005. Now DMEK is exploding in usage.3 The surgery will account for at least 45 percent or more of all endokeratoplasty procedures by the end of 2019. And it will just keep going up.”
With numbers like these, you may be thinking of offering DMEK soon or you may be caring for patients who have undergone the procedure. Or you may be a seasoned DMEK veteran. No matter which category you’re in, this article is for you. Please read along as leading DMEK surgeons review important techniques and explain how you can use them to achieve success.
Dawning of DMEK
DMEK emerged in 2009. Indications for the procedure are similar to those established for DSAEK, including endothelial dystrophies (such as Fuchs’ corneal dystrophy and posterior polymorphous corneal dystrophy), pseudophakic bullous keratopathy, iridocorneal endothelial syndrome and other causes of corneal endothelial dysfunction.
“The vast majority of cases for these transplants are for Fuchs’ corneal dystrophy,” says Yuri McKee, MD, MS, a corneal and refractive surgeon at East Valley Ophthalmology in Mesa, Arizona. “I would strongly recommend DMEK for these patients, even if it requires referral to another surgeon.” Patients who wouldn’t be appropriate for most DMEK surgeries include those who have undergone complex surgeries and those who have aniridia or implanted IOLs, he notes. “You don’t want any situation in which the DMEK transplant gets lost in the posterior vitreous,” he adds.
DMEK involves the transplantation of only Descemet’s membrane and endothelium, just 10 µm thick without any stromal tissue, leading to significantly better visual acuity and slightly less endothelial cell loss than DSAEK, surgeons say.
Compared to DSAEK, DMEK provides a significantly higher rate of 20/20 and 20/25 vision with comparable endothelial cell loss.4 (Dr. McKee notes that a free digital guide to performing this procedure, “The Digital Manual of Ophthalmic Surgery and Theory of DMEK,” authored by himself, Francis W. Price Jr., MD, and others, is available for free through Apple Books.)
Dr. Terry, director of Corneal Services at Legacy Devers Eye Institute in Portland, says DMEK represents the latest improvement in endokeratoplasty, resulting in improved vision, comfort and visual recovery. “The big advantage of DMEK surgery is that you’re not taking out Descemet’s membrane and replacing it with a thicker membrane attached to stromal tissue, as is the case in DSAEK. No matter how well DSEK and DSAEK perform, you still have the stromal interface under the DSEK and DSAEK donor tissue creating less-than-perfect surfaces.”
Encouraging More Surgeons
DMEK surgeons notice that more of their colleagues are trying DMEK for the first time. The procedure, while still a challenge to learn, is easier to master than it has been in years past. Why?
Because more than 50 eye banks now offer specially processed tissue that has been pre-marked, pre-stained, pre-trephinated and pre-loaded for DMEK procedures, making the procedure faster and easier, says Dr. Terry. “This has also taken the risk out of the operating room. Now we have pre-cut, pre-stained, pre-marked and pre-loaded tissue, which is available across the United States. The process now minimizes the risk of inadvertently destroying tissue while preparing it for insertion. As a result, surgeons can feel more secure in introducing DMEK to their practices, without losing thousands of dollars in out-of-pocket costs.”
Although the DMEK learning curve remains steep, innovations like these simplify the procedure, while larger innovations loom on the horizon. (See “DSO: Clearing Vision Without a Transplant,” at right.)
A number of studies show that modern DMEK is safer and more effective than in the past. For example, in a study of 80 consecutive Fuchs’ cases, Dr. Terry and his colleagues used tissue prestripped by an eye bank technician, standardized DMEK techniques, a glass injector and a 20% concentration of sulfur hexafluoride (SF6) gas for prolonged tissue support.5
Twenty-five donors were premarked with an “S” stamp for intraoperative orientation. Surgery was performed by two experienced DMEK surgeons and two inexperienced cornea fellows. Complications were recorded, and the percent of endothelial cell loss was calculated at six months postoperatively. The results showed that five patients received an air bubble injection postoperatively (6 percent rebubble rate). Six grafts immediately failed, two of them because of excessive surgical trauma and four because of upside-down graft placement, documented by OCT.
Significantly, none of the 25 cases with an S stamp failed. Corneas cleared quickly with no clinical evidence of toxicity from the (SF6) gas bubble in the remaining corneas. The grafts experienced a mean endothelial cell loss of 27 percent at six months. As a result, Dr. Terry and his fellow researchers concluded that you can safely rely on (SF6) gas for prolonged tissue support and reduce the rebubble rate when performing DMEK. Predictably, only unrecognized upside-down grafts were the primary cause of graft failure in this series. This finding reinforced experts’ advice that you can eliminate upside-down grafts by using donor tissue that has been premarked by the eye bank with an S orientation stamp.
You’re Not Alone
If you’re just getting started on DMEK, you won’t be operating in a vacuum, like the early DMEK surgeons.
“The take-home point is that the learning curve is not nearly as difficult or fraught with hazards as it was 10 years ago,” Dr. Terry says. “Back then, we were trying to determine the best way to do the surgery. Now, we have standardized the techniques in the literature being taught at multiple courses across the country. There are YouTube videos. There is so much now that, if you follow the technique and don’t try to do your own thing, you can get a very rapid rise in success and minimize your risks and complications.”
Gerrit Melles, MD, PhD, founder of the Netherlands Institute for Innovative Ocular Surgery, and his colleagues offer these tips for beginners:
• Overcome the learning curve and succeed as soon as possible.
• Ensure that you’ve selected
• Choose the right diameter graft and, if possible, the right degree of graft tightness, depending on the depth of the anterior chamber.
• Flush the graft a few times outside of the eye to eliminate all the organ cultures.
• Make sure you achieve a double roll of the graft before inserting it.
• Pressurize the eye properly after surgery and leave the air-bubble in the eye long enough for the graft to attach.
Among the biggest challenges facing DMEK surgeons today are graft failure, the threat of infection and complications, such as the emergent need for re-bubbling, primary graft failure, rejection and late endothelial failure. “Late failure of DMEK grafts typically occurs for two reasons,” says Dr. Melles. “The first is due to endothelial cell attrition and the second is rejection, though this is thankfully very uncommon.”
“We routinely monitor patients with both specular microscopy and Scheimpflug imaging,” notes Isabel Dapena, MD, PhD, medical director and corneal surgeon at the Netherlands Institute for Innovative Ocular Surgery in Rotterdam. “Published studies have found that changes seen in these images can potentially precede a rejection. This allows you to detect a rejection and treat the patient before the rejection takes a foothold.”6,7
Doctors say patients affected by the beginning of rejection frequently respond promptly to topical steroid therapy. “A re-operation is not required in most cases,” says Dr. Sorcha Ni Dhubhghaill, MB, PhD MRCSI (Ophth), FEBO, an anterior segment ophthalmic surgeon at University Hospital Antwerp in Belgium.
“However, if there is a secondary graft failure and inflammation, then a re-DMEK may be the best option,” adds Dr. Melles.
Dr. McKee says he’s had only one primary graft failure since 2015. “When I was a fellow, we ran a rejection clinic on the side of our normal clinic,” he recalls. “We’d have a DSAEK rejection walk in every day.”
He notes that the first sign of a complication is typically corneal -edema. “You have to ask yourself: Is this graft attached but not pumping fluid or is it detached and, therefore, it’s obviously not going to pump fluid out of the cornea? You can use a slit lamp exam or anterior OCT to determine the graft’s configuration—such as upside down, right-side up, detached or attached.”8
Your institution may have a treatment algorithm to follow if you suspect areas of graft separation. “The decision to rebubble for areas of graft separation still remains fairly subjective,” says Dr. Terry. “Some surgeons would rebubble any separated edge and have rebubble rates of 70 percent or higher. Using Melles’ guideline of rebubbling only grafts that have 30 percent or more of separation yields a rebubble rate of about 10 percent or less, and the grafts that aren’t rebubbled will attach up to 30 percent of the separation on their own. It’s uncommon to have a primary graft failure unless the tissue is upside-down, and this is prevented by having a distinct ‘S’ or ‘F’ mark on the tissue to determine orientation.
“If the corneal edema doesn’t clear within six weeks after surgery, it’s a primary graft failure,” continues Dr. Terry. “If the graft sticks and clears the cornea and later gets edematous, then it’s a secondary graft failure. If that occurs, a rejection or some other issue should be suspected. But that’s very rare with DMEK. Once it clears and attaches well and looks good by three weeks or less, you’re almost always home free.”
Another challenge is unfolding the graft in the eye and discovering that it’s upside down.
“DMEK is like a jellyfish in water,” says Dr. McKee. “It can change its configuration very quickly, turning upside down or right-side up. The grafts always curl when you unscroll. The endothelium is always on the outside of the scroll. So, when you’re preparing the DMEK tissue, as some of us still do, you need to be very careful. I never begin to unfold the graft until I know it’s in the correct orientation. I’ve had a 100-percent success rate with this, using a hand-held slit beam that shows me if the curls are coming up toward me or away from me.”
When done right, the best part of DMEK is that it’s almost like the graft isn’t there at all. “The best way to think of DMEK is that it provides perfect anatomic replacement,” says Dr. Terry. “When you have perfect anatomic replacement, visual results are comparable to that of a normal eye. There’s no better service that you can provide your patients.” REVIEW
Dr. Terry claims no financial interests in DMEK surgical devices, but he receives royalties from Bausch + Lomb for the design of a surgical instrument used in DSAEK. Dr. Price is a consultant for Alcon, Allergan, Eyepoint, Haag-Streit, Kedrion, STAAR and Sun Ophthalmics; he’s an equity owner of Interactive Medical Publishing, RxSight and Strathspey Crown. He receives grant support from Aerie. Dr. Melles is a consultant for DORC International/ Dutch Ophthalmic USA and SurgiCube International. Drs. McKee, Dapena and Dhubhghaill have no financial interest in any of the products discussed.
1. 2018 Eye Banking Statistical Report, Eye Bank Association of America, Washington, D.C.
2. 2012 Eye Banking Statistical Report, Eye Bank Association of America, Washington, D.C.
3. 2017 Eye Banking Statistical Report, Eye Bank Association of America, Washington, D.C.
4. Price MO, Giebel AW, Fairchild KM, Price FW, Jr. Descemet’s membrane endothelial keratoplasty: Prospective multicenter study of visual and refractive outcomes and endothelial survival. Ophthalmology 2009;116:12:2361-8.
5. Terry MA, Straiko MD, Veldman PV, et al. A standardized DMEK technique: Reducing complications using pre-stripped tissue, novel glass injector, and sulfur hexafluoride (SF6) gas. Cornea 2015;34:8:845-52.
6. Monnereau C, Bruinsma M, Ham L, et al. Endothelial cell changes as an indicator for upcoming allograft rejection following descemet membrane endothelial keratoplasty. Am J Ophthalmol 2014;158:3:485-95.
7. Baydoun L, Bruinsma M, Santander-García D, et al. Combined specular microscopy and Scheimpflug imaging to improve detection of an upcoming allograft rejection after DMEK. Acta Ophthalmol 2019 Sep 4.
8. Patel AS, Goshe JM, Srivastava SK, Ehlers JP. Intraoperative optical coherence tomography-assisted Descemet membrane endothelial keratoplasty in the DISCOVER Study: First 100 Cases.