Endothelial keratoplasty challenges the primacy of full-thickness transplantation

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 Gerrit R.J. Melles, MD, PhD, pioneered endothelial keratoplasty in the late 1990s. More recently, femtosecond laser technology has enhanced wound architecture and wound healing in PK.

Endothelial keratoplasty 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).

Francis W. Price Jr., MD, said that the reliability of cornea donor preparation needs to improve before DMEK and DMAK procedures are more widely performed. Image: Price FW

Deep anterior lamellar keratoplasty (DALK) is indicated for anterior irregularities such as keratoconus and corneal scarring.

Indications for transplantation are based on the presence of endothelial or stromal pathology, or both, Edwin S. Chen, MD, said.

“The main procedures right now are DSAEK for endothelial dysfunction, DALK for anterior stromal problems and PK if they are combined,” Dr. Chen said.

Endothelial and refined anterior lamellar techniques have moved to the forefront of practice in recent years, OSN Cornea/External Disease Board Member Francis W. Price Jr., MD, said.

“The two biggest changes that have happened in what we offer for transplants are the advent of endothelial keratoplasty and more reliable ways of anterior lamellar grafts,” Dr. Price said. “Now, in endothelial keratoplasty, that’s probably the biggest change that we’ve seen in transplant. It’s been a phenomenal change.”

Currently, endothelial keratoplasties comprise more than one-third of all corneal transplants performed in the United States, Dr. Price said.

Michael W. Belin

“We looked at our practice and we did a little over 320 transplants last year, and of those 320 transplants, there were only 50 penetrating keratoplasties and there were about 45 DALKs. The rest of them were endothelial keratoplasties, DSAEK,” Mark A. Terry, MD, said.

However, long-term outcomes of endothelial keratoplasty are unknown and will remain so for several years, Michael W. Belin, MD, said.

“I think the big controversy right now, which is really an unknown, is what the long-term endothelial survival is of endothelial keratoplasty vs. full-thickness transplants,” Dr. Belin said. “It will probably be a number of years before that question is really answered.”

PK vs. endothelial keratoplasty

An ophthalmic technology assessment conducted by the American Academy of Ophthalmology and published in Ophthalmology showed DSEK to be a safe and effective treatment for corneal endothelial disease. The conclusion was based on peer-reviewed literature on DSEK safety and outcomes.

Results also showed that DSEK and PK had similar visual outcomes and graft survival. However, DSEK appeared to offer more rapid visual recovery and more wound stability.

The authors noted that long-term data on endothelial cell survival and rejection are not available. Still, the likelihood of graft failure from DSEK is minimal in low-risk cases, Dr. Belin said.

DSAEK maintains normal corneal topography, whereas PK involves surface incisions that change the topography, Dr. Terry said.

“It’s literally impossible for penetrating keratoplasty to consistently give you the normal topography that we get routinely with DSAEK,” he said. “At this point, I think that a penetrating keratoplasty should not be used on any patient who has endothelial dysfunction as their primary pathology.”

In a series of 700 to 800 DSAEK procedures, Dr. Terry and colleagues saw a graft dislocation rate of 2% or less and a primary graft failure rate of less than one in 700. Also, at 6 months after surgery, 16% of patients had visual acuity of 20/20 or better, 35% with 20/25, and 98% of patients had visual acuity of 20/40 or better.

“With that type of high benefit and low risk, DSAEK surgery is the procedure of choice for endothelial dysfunction,” Dr. Terry said.

DMEK offers mixed results

DMEK and DMAEK have yielded positive visual outcomes, Dr. Price said.

“DMAEK is a hybrid between DMEK and DSEK where we leave an outer rim of stroma just like with the DSEK graft, but in the center all you have is endothelium and Descemet’s membrane,” he said. “The outer rim of stroma makes it easier to handle and the center area of Descemet’s gives you very good vision.”

The downside: DMEK and DMAEK have shown tissue loss rates of more than 10%, Dr. Price said.

“We’re working on trying to improve the predictability and minimize the loss of donors,” he said.

Dr. Terry said that conclusive data are not yet available on the safety and efficacy of DMEK and that the procedure offers only marginal improvement in visual outcomes over DSAEK. For example, 16% of patients saw 20/20 or better with DSAEK and 26% saw 20/20 or better with DMEK.

Mark A. Terry

“The re-bubble rate with our DSAEK technique is only 2%, and the published re-bubble rate with DMEK is 60%. Primary graft failure is less than 1% in DSAEK and greater than 8% in DMEK,” Dr. Terry said.

“It’s not that big an improvement in vision compared to the complication rate,” he said. “If you look at the data that are currently available … what you find is that the visual results are quite good with DMEK and maybe superior to what we have with DSAEK. However, the complication rate is abominable. And we have a long way to go with the DMEK procedure.”

DMEK will likely become safer as surgeons gain experience with the technique, Dr. Chen said.

“DMEK is in its infancy right now, and it’s very promising,” he said.

According to Dr. Price, publications by Dr. Melles’ group and now confirmed in a multicenter study show approximately a one- to two-line improvement in best corrected visual acuity for DMEK eyes compared with DSEK or DSAEK at the respective centers. He noted that it is important to compare visual results of DMAEK and DMEK to initial DSAEK and DSEK series at the same centers, not different centers that may use different criteria or testing methods for visual acuity results.

“The problems with donor preparations are indeed a challenge, but we have multiple eye banks and multiple surgeons in the U.S. and worldwide preparing DMEK and DMAEK grafts,” Dr. Price said. “The reliability of donor preparation needs to be improved before we can have widespread adoption of these surgeries, and we are making progress with this.”

Previous refractive surgery

Some surgeons support using corneal donor tissue that has undergone previous laser refractive surgery. However, Dr. Belin said there are concerns about refractive outcomes resulting from the use of such tissue.

“In the days of full-thickness transplantation, we never used corneas from patients with prior refractive surgery because basically you would be transplanting a cornea that has been physically altered and you would not know the refractive result,” Dr. Belin said. “Say someone had a –6 D PRK or LASIK and you transplant that onto an individual — you would have a huge refractive surprise.”

Corneas that have undergone previous refractive surgery may be used in DMEK because only the Descemet’s membrane and attached endothelium are stripped off. However, DMEK has shown a high rate of tissue loss during graft preparation, Dr. Belin said.

“While you would think that’s a nice indication because you would be able to save tissue by doing DMEK, the percentage of lost donors trying to prepare that tissue is fairly high, so it’s probably not a net gain,” he said. “In the U.S. at the moment, we have a surplus of tissue, and I’m not comfortable using patients with prior refractive surgery.”

Dr. Price said he also has reservations about using corneal tissue that has undergone laser refractive surgery.

“The problem is that we will not usually have the preoperative history for how much laser refractive surgery was done,” he said. “The reason that’s an issue is that the visual axis, when we do a laser, is not centered on the center of the cornea. It’s decentered because the pupil is decentered. When we punch a cornea for a transplant, we punch it based on the center of the cornea. That means that your punching is going to be decentered relative to the previous treatment, resulting in variable amounts of irregular astigmatism in the DSAEK graft.”

Still, some ablated corneas may be viable candidates for endothelial keratoplasty with proper donor screening, Dr. Price said.

“I actually think that if we can identify people that have had previous laser refractive surgery, those are the ones that we should be using for the endothelial keratoplasties where we just transplant the Descemet’s centrally,” Dr. Price said. “Then, changes in the stroma from laser refractive surgery don’t matter.”

In a study published in Cornea, Dr. Terry and colleagues reported that tissue excluded from use in PK because of stromal flaws or previous refractive surgery was suitable for DSAEK.

“We found that there is absolutely no reason not to use tissue for DSAEK that has had refractive surgery,” Dr. Terry said. “It’s very healthy. It’s already been approved by the Eye Bank Association of America. Our published data has shown that using donors with prior RK, PRK or LASIK is not an issue. Surgeons should never worry about that. They should simply ask their eye bank to pre-cut the tissue for them.”

Femtosecond-enabled PK

PK performed with the IntraLase femtosecond laser (Abbott Medical Optics) has resulted in positive visual outcomes. Some surgeons have reported that PK with femtosecond zigzag and top-hat incisions offer faster visual recovery and less induced astigmatism than conventional PK.

“I think the zigzag pattern is tremendous, not only for penetrating grafts but also the deep anterior lamellar grafts. That’s been a great advance,” Dr. Price said.

IntraLase-enabled keratoplasty (IEK) enables contoured incisions that are stronger than other incisions, he said.

“It’s like in carpentry. You know from carpentry that if you just put straight (vertical) edges together, it’s hard to keep them in place and get good alignment,” Dr. Price said. “But if you do a tongue-in-groove, then you can get more perfect alignment and you have a stronger joint. It seals better and stronger. You have more surface area for the wound, and it doesn’t slide apart as easily. That’s what we’re able to do with the femtosecond laser.”

Dr. Terry said there are advantages of an angled incision in IEK vs. a vertical incision in conventional PK.

“Clinically, it’s been described as a stronger wound than a standard full-thickness vertical incision,” he said. “That’s quite logical because with the physical shape of the incision, it’s going to be more self-sealing than a vertical incision.”

However, Dr. Chen said that IEK is more complex, time-consuming and expensive than conventional techniques.

Edwin S. Chen

“The problem with IEK is that it requires a femtosecond laser on site, which is very expensive and is challenging to get unless you do a very high volume or have a very high-volume refractive practice,” Dr. Chen said. “Femtosecond refractive procedures are commonly done in a refractive suite. Corneal transplantation is typically done at a surgery center or at a hospital. Then, that requires either transport of the patient with a partially cut cornea or a whole host of other logistical problems.”

Dr. Terry also described the clinical and economic downsides of IEK.

“The disadvantages of the procedure are that with sutures out, it has not been shown to have less astigmatism than a standard penetrating keratoplasty,” he said. “The other disadvantage is that there is at least one paper that showed a higher cell loss with a femtosecond laser keratoplasty than with the penetrating keratoplasty. The final disadvantage, and this is the biggest one, is that IEK takes more time, is more difficult and is more expensive than standard PK.”

Surgeons should refrain from purchasing femtosecond lasers exclusively for IEK, Dr. Terry said.

“I don’t think this procedure is ever going to allow surgeons to buy a femtosecond laser for the purpose of doing PK. They need to have a femtosecond laser already on board for refractive procedures,” he said. – by Matt Hasson

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

References:

• Eye Bank Association of America announces eye banking statistics for 2008 [news release]. Washington, DC: Eye Bank Association of America; April 24, 2009. http://www.restoresight.org/files/2008pressrelease_statreport.pdf. Accessed Jan. 12, 2010.
• 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. Ophthalmology. 2009;116(9):1818-1830.
• 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 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):2361-2368.

• Michael W. Belin, MD, can be reached at University of Arizona, 655 N. Alvernon Way, No. 108, Tucson, AZ 85711; 518-527-1933; e-mail: mwbelin@aol.com.
• Edwin S. Chen, MD, can be reached at Wills Eye Cornea Service, 840 Walnut St., Philadelphia, PA 19107; 866-337-7167; fax: 215-928-3854; e-mail: eschen37@hotmail.com.
• Francis W. Price Jr., MD, can be reached at Price Vision Group, 9002 N. Meridian St., Suite 100, Indianapolis, IN 46260; 317-844-5530; fax: 317-844-5590; e-mail: fprice@pricevisiongroup.net.
• Mark A. Terry, MD, can be reached at Devers Eye Institute, 1040 NW 22nd Ave., Suite 200, Portland, OR 97210; 503-413-8202; fax: 503-413-6937; e-mail: mterry@deverseye.org.