Endothelial keratoplasty challenges the primacy of full-thickness transplantation

During a DMEK surgery, Gerrit R.J. Melles, MD, PhD, loads the donor Descemet-roll that was pre-dissected in Amnitrans Eyebank into an inserter to prepare it for injection into the recipient anterior chamber. Image: Melles GRJ

Corneal transplantation has long been the preferred treatment for pathologies that respond poorly to topical medications or implants. Prevailing techniques include full-thickness penetrating keratoplasty, endothelial keratoplasty and anterior lamellar keratoplasty.

Variants of these basic techniques are indicated for specific clinical circumstances. Each technique presents benefits and risks, requiring clinicians to meticulously diagnose corneal disorders and design an appropriate treatment plan.

PK, indicated for full-thickness corneal disease combined with endothelial irregularities, dominated corneal transplantation until deep lamellar techniques, both anterior and posterior, were developed. More recently, femtosecond laser technology has enhanced wound architecture and wound healing in PK.

Deep anterior lamellar keratoplasty (DALK) is indicated for anterior corneal irregularities in pathologies that do not involve the endothelium, such as keratoconus and corneal scarring. Various surgical methods to separate the Descemet’s membrane have been proposed, the most popular of which is the Anwar big-bubble technique.

Endothelial keratoplasty was introduced by Gerrit R.J. Melles, MD, PhD, in the late 1990s and is indicated for endothelial dysfunction. Variants of endothelial keratoplasty include Descemet’s stripping endothelial keratoplasty (DSEK), Descemet’s stripping automated endothelial keratoplasty (DSAEK), Descemet’s membrane endothelial keratoplasty (DMEK) and Descemet’s membrane automated endothelial keratoplasty (DMAEK).

From DLEK to DMEK

Endothelial and refined anterior lamellar techniques have moved to the forefront of practice in recent years, Dr. Melles said.

“Compared to conventional penetrating keratoplasty, they provide safer, ‘closed system’ surgeries with less morbidity and better clinical outcomes,” he said. “In the population eligible for lamellar surgery, they have major advantages for both the surgeon and the patient, such as longer graft survival, less aftercare and less dependency on the health care system.”

Posterior corneal disorders, or endotheliopathies, are the indication for surgery in about 50% of all corneal transplants. In most cases, only the diseased endothelial layer needs to be replaced, not the entire cornea. Endothelial keratoplasty is therefore gaining widespread popularity as an alternative to PK.

Dr. Melles was the first to develop the concept of posterior lamellar grafting.

“Basically, it started as a hobby project in 1993. We first evaluated an endothelial transplant underneath a microkeratome flap. Then we started experimenting with replacing a posterior corneal button through a scleral incision,” he explained.

The main advantage was that no corneal surface incisions or sutures were necessary. This technique was later popularized as deep lamellar endothelial keratoplasty (DLEK).

“To simplify the technique, the descemetorhexis was developed, and in 2001 we performed the first procedure that now is known as DSEK/DSAEK. An unsutured posterior corneal button was placed against the recipient posterior stroma,” he said.

In 1998, Dr. Melles and colleagues also evaluated isolated Descemet’s membrane transplantation, and in 2004, after setting up their own eye bank, they started performing this type of transplant in a clinical setting. This technique is now referred to as DMEK.

Meanwhile, Pavel Studeny, MD, developed a technique that is in between DSEK/DSAEK and DMEK, and is now referred to as DMAEK, in which Descemet’s membrane is transplanted with a peripheral stromal rim.

DMEK is currently the technique that Dr. Melles prefers, and it has produced better results.

“As with any technique, personal preference may play a role in the choice. Purely from a visual acuity point of view, DMEK and DMAEK may provide the best outcome, and the endothelial cell count seems slightly better than after DSEK/DSAEK. This may be explained by the fact that DMEK usually can be performed as a completely ‘no-touch’ technique,” he explained.

The main drawback with all endothelial keratoplasty techniques may still be the donor detachment rate.

“We are improving our techniques of tissue harvesting, dissection and preservation. In our DMEK series, donor detachment rate has gone down from 10% to 20%, to 2% to 5%. Still too much, but we are slowly getting there,” Dr. Melles said.

DSAEK the current gold standard

Despite the potentially better visual outcomes of DMEK, DSAEK is currently the gold standard of endothelial techniques in Europe and elsewhere.

Massimo Busin

“I performed DMEK in a wide number of cases. I also introduced my own variation with a sickle-shaped stromal support that made implantation easier and didn’t have the same detachment rate of the ring-shaped support. However, I still wonder if it is worth using a technique that is so much more difficult than DSAEK,” Massimo Busin, MD, said.

DSAEK with microkeratome dissection is a fairly easy, reproducible and safe technique, he noted.

“Easier than manual, better than femtosecond, microkeratome DSAEK is a technique that every experienced surgeon can do and every hospital can afford. Eye bank precut donor grafts are also available,” he said.

Less than 1% of the DSAEK procedures worldwide are currently performed with a microkeratome, and cost is not the main reason.

“If you want your patients to see well, the microkeratome is, at present, the best choice,” Dr. Busin noted.

Recently, he has been implanting ultra-thin grafts that are less than 100 µm thick. He said studies are showing that they lead to optimal visual quality, “as if the stroma was not there.”

A first corneal debulking with a 300-µm head removes two-thirds of the stroma, leaving a 150- to 200-µm thick lamella. This is followed by a second cut, using dedicated 50-µm or 90-µm heads.

“We obtain very thin lamellae, with all the advantages of DSAEK: They can be manipulated, dyed and marked, and behave in the eye like a normal DSAEK graft. Contrary to what many people think, the presence of even a thin stromal layer facilitates adherence to the cornea, while the bare Descemet’s membrane has a tendency to detach,” Dr. Busin said.

As a surgical procedure, DSAEK is not difficult and is forgiving, he noted. Even when the recipient endothelium is not thoroughly removed, the graft adheres well. Ophthalmic viscosurgical devices should not be used, he recommended, and all incisions should be tightly closed to prevent any air loss during bubble inflation. Peripheral iridectomy should be performed to prevent pupillary block.

Advantages over PK

Around the world, the number of lamellar endothelial procedures is increasing.

Rudy Nuijts

“At the end of 2000, they were less than 3% of the total volume of corneal transplantation, and by now they are 50%,” Rudy Nuijts, MD, PhD, said. “In my practice, I have almost entirely converted to lamellar, with the exception of the few cases where both the endothelium and stroma are affected.”

“In the past year, we performed only two PKs, both in complicated eyes. I guess that our proportion of PK is now around 1%,” Dr. Melles said.

An increasing number of studies and data sets show that lamellar techniques offer faster visual recovery, more wound stability and better visual outcomes than PK.

“Lamellar techniques produce minimal corneal curvature changes. Since you only make a cut of 4.5 mm to insert the graft, postoperative astigmatism is more or less the same as preoperatively. It’s literally impossible for penetrating keratoplasty to consistently give you the normal topography that we get routinely with DSAEK. The interface of DSAEK is also extremely smooth. On average, my patients get a postoperative vision around 20/32. Some patients achieve 20/20,” Dr. Nuijts said.

“More than 30% of my patients achieve 20/20 or better within 3 months from surgery and 80% achieve 20/40 or better within 1 month,” Dr. Busin noted.

“In our DMEK series, 75% of eyes currently achieve a visual acuity of 20/25 or better at 6 months. Not uncommonly, such result is achieved at 1 week after surgery. This group includes also elderly patients, who may have sometimes a lower visual potential. About 50% of the patients achieve 20/20 at 1 month,” Dr. Melles said.

Contrary to what was believed at first, recent data show that lamellar procedures have a lower rate of endothelial cell loss than PK and are likely to lead to a longer graft survival.

“If surgery is performed correctly, endothelial cell loss at 1 year is comparable to PK, around 20% to 30%. However, the curve of cell loss tends to stabilize after DSAEK between year 2 and 3, while it continues to grow following PK. This might be due to the fact that a larger portion of diseased endothelium, around 8.5 mm to 9 mm in diameter, is replaced with DSAEK. The PK graft is normally around 8 mm, and this leaves a larger reservoir of diseased cells in the periphery,” Dr. Busin explained.

Femtosecond lasers and PK

The use of femtosecond lasers may reinvigorate the use of PK. According to Dr. Nuijts and other surgeons, the femto-architecture of the wound offers a great advantage in comparison to regular PK.

“The better wound construction, the smoother surfaces and the better adherence between donor and recipient results in better healing, less sensitivity to trauma and, possibly, better visual outcomes,” Dr. Nuijts said.

Could the femtosecond laser help PK regain competitive advantages over lamellar techniques?

“It is quite unlikely that PK will regain its primitive position,” Dr. Nuijts said. “If only the surface is affected, there is no reason why we should not try to keep the host endothelium intact, and for endothelial diseases there is no reason why we should replace the whole cornea. Lamellar is marvelous, and only for those who have opacities throughout the cornea, the use of penetrating techniques, predominantly femtosecond, is feasible. I have performed about 40 femtosecond-assisted PK procedures up to now, and the volume is not growing significantly.”

New ways of combining femtosecond laser and deep anterior and posterior lamellar techniques will be developed in the future, and femtosecond PK may eventually replace conventional PK, Dr. Nuijts said. However, modifications and improvements are needed.

“There are corneas where the opacities are so intense that you can’t go through them with the femtosecond laser energy. We also need to improve the donor-recipient matching in corneas where there is a mismatch of tissue thickness, like in some cases of keratoconus where the rim of the recipient is very thin while the donor graft is much thicker,” he said.

Cost is also a significant problem with femtosecond lasers.

“In Europe, the national authorities that look at our data require solid evidence of the safety and efficacy of a procedure before they agree to higher reimbursements,” Dr. Nuijts said. “We need cost-effectiveness studies.” – by Michela Cimberle and Matt Hasson

What are the long-term benefits and risks of PK vs. DSEK?

References:

• Bahar I, Kaiserman I, McAllum P, Slomovic A, Rootman D. Comparison of posterior lamellar keratoplasty techniques to penetrating keratoplasty. Ophthalmol. 2008;115(9):1525-1533.
• Busin M, Bhatt PR, Scorcia V. A modified technique for descemet membrane stripping automated endothelial keratoplasty to minimize endothelial cell loss. Arch Ophthalmol. 2008;126(8):1133-1137.
• Chen ES, Terry MA, Shamie N, Hoar KL, Friend DJ. Descemet-stripping automated endothelial keratoplasty: six-month results in a prospective study of 100 eyes. Cornea. 2008;27(5):514-520.
• Cheng YY, Hendrikse F, Pels E, et al. Preliminary results of femtosecond laser-assisted descemet stripping endothelial keratoplasty. Arch Ophthalmol. 2008;126(10):1351-1356.
• Dapena I, Ham L, Melles GR. Endothelial keratoplasty: DSEK/DSAEK or DMEK—the thinner the better? Curr Opin Ophthalmol. 2009;20(4):299-307.
• Ham L, van Luijk C, Dapena I, et al. Endothelial cell density after descemet membrane endothelial keratoplasty: 1- to 2-year follow-up. Am J Ophthalmol. 2009;148(4):521-527.
• Lee WB, Jacobs DS, Musch DC, Kaufman SC, Reinhard WJ, Shtein RM. Descemet’s stripping endothelial keratoplasty: safety and outcomes: a report by the American Academy of Ophthalmology. Ophthalmol. 2009;116(9):1818-1830.
• Melles GR. Posterior lamellar keratoplasty: DLEK to DSEK to DMEK. Cornea. 2006;25(8):879-881.
• Melles GR, Eggink FA, Lander F, et al. A surgical technique for posterior lamellar keratoplasty. Cornea. 1998;17(6):618-626.
• Melles GR, Ong TS, Ververs B, van der Wees J. Descemet membrane endothelial keratoplasty (DMEK). Cornea. 2006; 25(8):987-990.
• Phillips PM, Terry MA, Shamie N, et al. Descemet’s stripping automated endothelial keratoplasty (DSAEK) using corneal donor tissue not acceptable for use in penetrating keratoplasty as a result of anterior stromal scars, pterygia, and previous corneal refractive surgical procedures. Cornea. 2009;28(8):871-876.
• Price FW Jr, Price MO. Femtosecond laser shaped penetrating keratoplasty: one-year results utilizing a top-hat configuration. Am J Ophthalmol. 2008;145(2):210-214.
• 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. Ophthalmol. 2009;116(12):2361-2368.
• Terry MA, Chen ES, Shamie N, Hoar KL, Friend DJ. Endothelial cell loss after Descemet’s stripping endothelial keratoplasty in a large prospective series. Ophthalmol. 2008;115(3):488-496.

• Gerrit R.J. Melles, MD, PhD, can be reached at Netherlands Institute for Innovative Ocular Surgery, Laan Op Zuid 88, 3071 AA Rotterdam, Netherlands; +31-10-297-4444; fax: +31-10-297-4440; e-mail: melles@niios.nl.
• Rudy Nuijts, MD, PhD, can be reached at University Hospital of Maastricht, Department of Ophthalmology, P.O. Box 5800, 6202 AZ Maastricht, Netherlands; +31-43-3877344; fax: +31-43-3875343; e-mail: rnu@soog.azm.nl.
• Massimo Busin, MD, can be reached at Via Del Camaldolino 8, 47100 Forlì, Italy; e-mail: mbusin@yahoo.com.