Corneal Transplants

Pioneers Discuss DSEK/DSAEK and other innovations.

BY JERRY HELZNER, SENIOR EDITOR

In the rapidly evolving, acronym-filled world of corneal transplantation, one fact is certain: partial corneal transplants are quickly becoming the procedure of choice in the numerous cases that involve endothelial cell failure. It is almost certain that the percentage of partial transplants performed for such conditions as Fuchs' Corneal Dystrophy and pseudophakic bullous keratopathy will continue to increase as more surgeons become comfortable doing these procedures.

After a half century of steady but slow progress in corneal transplantation, the new century has brought with it stunning new procedures and accompanying tools that have already improved the lives of tens of thousands of patients and given surgeons encouragement that even better outcomes lie ahead. It is estimated that a total of approximately 45,000 corneal transplants — including both full thickness and partial — were performed in the United States last year.

A number of leading transplant surgeons interviewed for this article all agree with their colleague William Culbertson, M.D., of Bascom Palmer Eye Institute, that there has been more progress made in corneal transplantation in the last several years than in the 50 years before.

At the center of that progress is a procedure called Descemet's Stripping Endothelial Keratoplasty (DSEK), which has emerged in the new century as a landmark advance in ophthalmic surgery. The basic DSEK procedure has led to the more advanced Descemet's Stripping Automated Endothelial Keratoplasty (DSAEK), which eliminates all manual dissections through the use of a microkeratome to cut tissue.

For the growing number of surgeons who have learned how to perform partial transplant procedures, the DSEK/DSAEK duo has rapidly supplanted penetrating keratoplasty (PKP) in cases in which there is endothelial cell involvement. PKPs are still indicated for corneal pathology interfering with vision and not related to endothelial cell dysfunction, such as scars, trauma, keratoconus and secondary changes to the stroma.

Cutting donor tissue for DSAEK with a Moria microkeratome.

Rick Palmon, M.D., of Fort Myers, Fla., definitely views the last five years as a revolutionary time in corneal transplantation.

"People with endothelial disease used to receive a full corneal transplant, even though the corneal surface was healthy," says Dr. Palmon. "Now, we have an excellent procedure to treat such endothelial diseases as Fuchs' Corneal Dystrophy, for which a partial transplant is the perfect treatment."

Recognizing the Pioneers

Steven Silverstein, M.D., of Kansas City, Mo., asserts that "the advances of the past 5 years are revolutionary — and are here to stay, but we have to remember that it took about 50 years to create the environment that allowed a procedure like DSEK to even exist."

Dr. Silverstein harks back to the work of corneal transplant pioneer Jose Barraquer, M.D., in the 1950s and 60s.

"I've seen some of Dr. Barraquer's transplants," says Dr. Silverstein. "Many of them were still functional decades after being implanted. His transplants were done under the most difficult conditions, without surgical microscopes and using primitive sutures."

A DSAEK procedure showing donor tissue centered in the anterior chamber.

Dr. Silverstein cites other major advances that created the foundation for the emergence of DSEK.

"Improvements in surgical equipment. Storage media that allowed us to keep donor tissue viable for a week instead of having to use it immediately. Eye banks such as Eye Banks of America and the Lions Eye Banks. Organizations such as Gift of Life that have been instrumental in encouraging all types of organ donations. All of these factors have come together to enable us to perform DSEK today," says Dr. Silverstein. "We should also remember that about 15 years of work went into developing the DSEK procedure itself."

Dr. Silverstein says that if there was a Mount Rushmore for DSEK, the four individuals who should surely be on it would be Gerrit Melles, M.D., of the Netherlands, and Francis Price, M.D., Mark Terry, M.D., and Mark Gorovoy, M.D., all of the United States.

"Those are the four names that come to my mind immediately," says Dr. Silverstein. "Though many others are contributing today to advancing the progress of corneal transplantation."

A fifth name for the corneal transplant Mount Rushmore is the aforementioned Dr. Culbertson, whose team pre-dated DSEK by proving in 1996 that the cornea could be cleared by replacing the damaged endothelium.

"At Bascom Palmer, we developed an anterior procedure called Endothelial Lamellar Keratoplasty (ELK) that required the cutting of a LASIK flap," says Dr. Culbertson. "It was in use for 3 or 4 years but it produced astigmatism and didn't have all the advantages that DSEK offers."

How DSEK Trumps PKP

The advent of DSEK about a decade ago offered surgeons the opportunity to learn and perform a procedure that provides numerous significant advantages to traditional PKP.

"DSEK maintains the preoperative shape of the cornea without inducing astigmatism," notes Michael Belin, M.D., of Albany, N.Y. This factor alone puts an end to what one surgeon calls "the wildly unpredictable" induced astigmatism of up to 12 D that often accompanies PKP procedures.

DSEK also allows functional vision to greatly improve in weeks to months, as opposed to a year or longer with PKP. DSEK avoids the so-called "open sky" nature of PKP, thereby greatly decreasing the risks of infection, inflammation, retinal detachment and supra-choroidal hemorrhage. In most cases, IOLs that have been previously implanted in patients can remain in the eye. Finally, because DSEK involves only partial layers of the cornea, it potentially has a lower percentage of rejection than PKP procedures that affect the full thickness of the cornea, though more studies will be required to confirm this theory.

In addition, surgeons say that DSEK is actually a simpler procedure to perform than PKP.

"You do need to develop a different skill set for DSEK," says Dr. Belin. "But PKP is actually more demanding. There is more suturing and you have to work more rapidly."

Dr. Belin notes that, even with all of its advantages, DSEK does not expand the candidate pool for corneal transplants.

"The candidates for transplant are still going to be the same group of patients," he says. "But we now have a better procedure to offer most of them."

Historical Perspective

Dr. Gorovoy, of Fort Myers, Fla., who innovated DSAEK by adding automated tissue-cutting to the DSEK procedure, puts the emergence of partial cornea transplant (also called selective layer transplantation) in historical perspective.

"If we list the five major advances in ophthalmic surgery in the last 50 years, that list should include phacoemulsification, YAG, vitrectomy, the advent of viscoelastics and DSEK/DSAEK. Everyone's practice is different but today I would estimate that 75% to 80% of corneal transplants are partial."

Dr. Gorovoy, who teaches a course that has helped train numerous surgeons in DSAEK, says performing selective layer transplantation is "a humbling procedure because there is a big learning curve."

However, he says that cooperation and communication among transplant surgeons has been a key to improving the procedure.

"The (graft) dislocation rate for these procedures has always been a problem, but surgeons keep coming up with little refinements in technique and that has brought the dislocation rate down dramatically. Experienced surgeons are now seeing dislocations in the 5% range, while less experienced surgeons are seeing about 10% dislocations. It's much better but still not zero."

Dr. Culbertson also attributes much of the recent progress in corneal transplant to improved communication among surgeons.

"First, we are talking about a truly compelling advance," he notes. "There still are surgeons who believe that full-thickness corneal transplant is a superior procedure, but their numbers are declining. Our ability to exchange information, especially electronically and at international meetings, has allowed new technology to be so readily adopted."

Comes the Revolution

The era of selective layer transplantation began about a decade ago when Dr. Melles pioneered a procedure in which the inside layers of the cornea were manually dissected and selectively replaced. This advance led to a procedure developed by Mark Terry, M.D., called Deep Lamellar Endothelial Keratoplasty (DLEK). Though a major improvement over PKP in terms of visual outcomes, wound integrity and reduced complications, DLEK was a tedious and exceedingly difficult procedure to perform and eventually proved to be a transitional step to DSEK and DSAEK.

Dr. Melles led the evolution of selective layer transplantation from DLEK to DSEK. Other DSEK pioneers, such Dr. Price of Indianapolis, have also made major contributions in advancing the procedure. Dr. Price is founder of the Cornea Research Foundation of America and has conducted a number of studies on various aspects of corneal transplantation.

The Pre-Cut Tissue Issue

While corneal transplant surgeons have been remarkably collegial in sharing knowledge and crediting colleagues for advances, the issue of the value of pre-cut tissue obtained from eye banks still remains an area of mild contention. Two studies conducted in 2006 and 2007 did show a higher rate of graft dislocations in selective layer transplantation procedures performed using pre-cut tissue from eye banks as opposed to a lower rate of dislocations with surgeon-cut tissue. The dislocation rate increased with the age of the tissue being used.

Dr. Gorovoy, whose daughter Stacey Gorovoy, M.D., conducted one of those studies, cuts all of his own tissue.

"I believe the quality of pre-cut tissue is improving, and may eventually approach the quality of surgeon-cut tissue, but pre-cut will never be as good as the surgeon cutting his own tissue," he asserts. "I try to have control over all aspects of the procedure."

Dr. Gorovoy does note that the substantial cost of eye bank tissue does provide high-volume surgeons with more of an incentive to purchase the equipment to cut their own tissue.

"We also now have a new Medicare code (+65757) that allows us to be paid for backbench tissue preparation, which is another factor in favor of surgeons cutting their own tissue," he says.

But Dr. Culbertson notes that the approximately $50,000 investment in equipment that enables a surgeon to have tissue cut in-house is not feasible for a surgeon who does about one partial transplant procedure a week.

"With one procedure a week, it's going to be costly to cut your own tissue," he asserts. "Also it's going to be hard to develop the skill to cut tissue doing that few procedures. The eye bank technician is likely to become more skilled in cutting tissue by doing it more often."

David Hardten, M.D., of Minneapolis, points out that "eye banks have a learning curve, too." He says that as eye banks have increasingly interacted with corneal transplant surgeons they have become more proficient in providing high-quality tissue.

"We conducted our own in-house study and found that eye bank tissue and surgeon-cut tissue produced similar results," says Dr. Hardten.

Dr. Silverstein agrees.

"I think the key is having a close relationship with the eye banks so that they understand the procedure and know the surgeon's needs," he says. "In Kansas City, we have this kind of relationship. In other parts of the country, that may not be the case as yet."

When Cornea Transplants Fail

BY JERRY HELZNER, SENIOR EDITOR After one or two failed corneal transplants using human tissue the odds of a successful tissue transplant grow longer. At that point, surgeons will consider implanting an artificial cornea (keratoprothesis). The two FDA-approved artificial corneas are the (Dohlman-Doane) Boston KPro, developed by Claes Dohlman, M.D., and initially approved in 1992, and the AlphaCor (Addition Technology), which was approved in 2002. Because of its high retention rate without complication, onestage implantation procedure (vs. two-stage for AlphaCor) and reports of superior visual outcomes, the Boston KPro has become the artificial cornea of choice for the large majority of U.S. corneal transplant surgeons. Surgeon preference for the KPro has been evidenced in the number of implantations of the two devices, journal articles and by a show of hands at the recent ASCRS meeting. However, there are some cases in which surgeons may choose to implant an AlphaCor. For example, Dr. Gorovoy anecdotally reports success in using the AlphaCor creatively in a less-invasive, single-stage procedure in which vision was improved for a young woman from counting fingers to approximately 20/200. James Chodosh, M.D., of Cambridge, Mass., has recently taken over much of the work for advancing the Boston KPro. "The Boston KPro is the most popular artificial cornea in the United States and in the world with more than 900 implanted worldwide in the past year," says Dr. Chodosh. "Its primary use is following corneal graft failure. Very few third attempts at transplant last. The KPro is also indicated for aniridia and corneal damage due to infection, injury or neovascularization. The KPro may not be the best choice if the patient has an autoimmune disease such as Stevens-Johnson Syndrome or severe dry eye." Dr. Chodosh says that almost all KPro recipients must wear a bandage-type soft contact lens as long as the implant is in the eye to avoid dehydration. "Glaucoma is an issue," says Dr. Chodosh. "Once the KPro is implanted, we can only test for glaucoma using finger tension. In addition, we cannot put the KPro into phakic patients. The implantation procedure must be accompanied by cataract surgery." Dr. Chodosh says the use of the antibiotic vancomycin has enabled KPro implantation with low infection risk. (Before) Slit-lamp photo of left eye of a 37-year-old man, following alkali injury and a failed corneal transplant. This eye had only hand-motion vision. The other eye had no light perception. (After) Appearance of same eye 6 months after Boston KPro implantation. The visual acuity was 20/25 uncorrected. An interesting sidelight to the KPro is that, in accordance with Dr. Dohlman's wishes, revenue from its sales accrue to the Massachusetts Eye and Ear Infirmary, which has poured this money back into KPro research. "There have been many improvements to the Boston KPro over the years that have led to its greater adoption by transplant surgeons, concludes Dr. Chodosh. "Dr. Dohlman has always viewed the KPro as a device that can continue to get better."

Is DMEK the Next Advance?

Not content with the advances in corneal transplantation that he achieved with DSEK, Dr. Melles has recently developed a new procedure called Descemet Membrane Endothelial Keratoplasty (DMEK) that uses only the thin Descemet's membrane to create a smooth interface that permits an even higher level of visual recovery than DSEK/DSAEK. Early studies of DMEK outcomes indicate that 20/20 and 20/25 vision has been achieved in some cases, as compared to an average of 20/30 to 20/40 average outcomes in DSEK/DSAEK.

"DMEK is the next step forward," says Dr. Palmon. "However, the procedure requires working with very thin and flimsy tissue that rolls into a scroll. The tissue is difficult to harvest and you often have to deal with tissue lost. DMEK is technically very difficult but it is a fantastic procedure when it works."

"The major positive with DMEK is that there are less interface irregularities," says Dr. Hardten. "At this point, it needs more work before it can be widely adopted."

"DMEK is a step in the continuum," notes Dr. Silverstein. "It offers better adherence and improved recovery time. The procedure is about where DSEK was 2 years ago."

Dr. Gorovoy, who has reservations about the future of DMEK, notes that "you can achieve better vision quicker, but only by a line or so. That may be a too-small improvement for a procedure with a higher detachment rate and loss of tissue. The interface is potentially better if you don't get folds."

The Future is Bright

DMEK is not the only emerging concept in corneal transplantation. Because spectacular advances have been achieved in a short space of time, the pioneers in the field are still active and working on new ideas. Also, a remarkable level of cooperation and idea-sharing exists in the cornea transplant community, enabling even the smallest advance to quickly become widely adopted by surgeons.

Among concepts whose potential has not yet been fully explored is the use of femtosecond lasers to custom-cut tissue, first for PKP and most recently for partial transplant procedures.

"I think we will see a growing use of femtosecond lasers in the cutting of donor tissue for partial transplants," says Dr. Culbertson. "Some of the eye banks have already invested in this equipment and are providing laser-cut tissue."

There is also growing use in the United States of Deep Anterior Lamellar Keratoplasty (DALK), which until now has been employed (primarily internationally) as an alternative to PKP as a treatment for severe keratoconus.

"DALK is a technically challenging procedure that carries less chance of rejection than a full thickness corneal transplant," says Dr. Hardten. "Keratoconus is basically the opposite of Fuchs' Dystrophy in that with keratoconus the stroma is unhealthy and endothelium is healthy, while with Fuchs' the stroma is healthy and the endothelium unhealthy."

Dr. Hardten performs DALK on appropriate patients but notes that the preference in the United States for early contact lens intolerance is to treat keratoconus with Intacs or corneal cross-linking in the hope of avoiding a transplant procedure.

Looking further out, surgeons see a future for the use of stem cells in corneal transplant or the possibility of growing the patient's own endothelial cells on a thin membrane in a lab and re-inserting them into the cornea with almost no chance of rejection.

"Conceptually, these ideas are 10 to 20 years away," says Dr. Silverstein. "But I expect to see them become a reality." OM