Recent surgical innovations deliver

Continuing Medical Education activity supported by Allergan

By William W. Culbertson, M.D.

A variety of exciting corneal surgical procedures developed over the last 5 years are significantly changing the way we manage corneal disorders. These include new techniques in anterior and posterior lamellar keratoplasty, femtosecond laser corneal surgery and eye-bank cutting of donor tissue. These innovations can be credited to conceptual breakthroughs such as the Descemets� stripping endothelial keratoplasty procedure and technologic advancements such as the femtosecond laser. In this article, I will examine these contributions to creating new therapeutic options for patients with cornea-based vision problems.

Posterior Lamellar Keratoplasty
Perhaps the most significant, yet technologically simplest, breakthrough has been the evolution of posterior keratoplasty techniques designed to selectively replace the corneal endothelium. Previously, full-thickness penetrating keratoplasty (PKP) had been the only alternative for patients experiencing pain and poor vision from corneal edema caused by endothelial dysfunction. The typical postoperative course following PKP is characterized by slow visual recovery (6 to 24 months), frequent follow-up visits, unpredictable spherical and cylindrical refractive error and permanent vulnerability to trauma.

Early techniques to selectively transplant the posterior cornea lamella by myself (under a LASIK flap)¹ and Gerrit R. Melles, M.D. (into a posterior corneal pocket),² showed that the cornea could be rapidly deturgesced and cleared if healthy endothelium was transplanted. This latter procedure became known as �deep lamellar endothelial keratoplasty� or DLEK, and although a few surgeons obtained good results, the procedure was not universally adopted because of a steep learning curve and its technical complexity. Eventually, Dr. Melles simplified the procedure by demonstrating that similar corneal deturgescence could be obtained by using an air bubble to passively attach a thin lamella of posterior donor cornea to the back of the recipient cornea as an epigraft after stripping off the recipient cornea�s Descemets� membrane. Accordingly, this new procedure acquired the aptly descriptive yet awkward name of �Descemets� stripping endothelial keratoplasty� or DSEK.

DSEK Technique
In its present iteration, DSEK is performed by first fashioning a 100 �m to 200 �m lamella of donor corneal tissue using the Moria (Antony, France) ALTK artificial anterior chamber, which dovetails with the Carriazo-Barraquer microkeratome head (Moria). The cornea-scleral button is mounted on the chamber. Following pressurization of the chamber with balanced salt solution, tissue preservation medium, viscoelastic or simply air, the microkeratome head is translated across the cornea, leaving a residual posterior bed approximately 100 �m to 200 �m thick and 10 mm in diameter.

This posterior lamella is removed from the anterior chamber, placed stromal side down (endothelial side up) in a cutting block and then trephined from the endothelial side at a diameter of between 8 mm and 9 mm. The tissue is then placed in preservation medium, endothelial side up, in a container (e.g., petri dish) and maintained until transplantation. Although the cut tissue is usually immediately transplanted, it is possible to cut it 1 to 3 days prior to actual transplantation.

The recipient donor is prepared by making a 4-mm to 5-mm long scleral incision just outside the limbus and then beveling it into the anterior chamber. Paracentesis tracts are placed in the quadrants to provide access for positioning the graft. Vertical incisions are made in the paracentral cornea to permit drainage of fluid from the interface between the graft and the posterior recipient cornea.
A cystitome-like device is used to inscribe an 8-mm to 9-mm posterior descemetorhexis through the recipient endothelium and Descemets� membrane. A rake-like irrigating cannula is then used to peel off and remove Descemets� membrane over the area within the capsulorrhexis area, leaving behind bare stroma. The posterior stromal-endothelial lamellar graft is then folded and inserted into the anterior chamber (Figure 1). The incision is sutured closed and the graft is unfolded by expanding the anterior chamber with air so that the donor stromal side lies in apposition to the recipient posterior stroma. Fluid is aspirated from the donor-host interface through the paracentral corneal vents, which had been created at the beginning of the procedure. The patient lies face up for 15 to 60 minutes.

Next, approximately 50% of the air is vented off through the superior paracentesis. Over the next 24 hours, the grafted endothelium begins to deturgesce the entire cornea, providing remarkable improvement in vision overnight (Figure 2). The remainder of the air is rapidly absorbed. Over the next 4 to 6 weeks, maximum visual quality is attained with retention of close to the original refractive error of the eye. BCVA appears to be approximately one to two lines worse than the best potential acuity, probably because of loss of contrast at the level of the donor-host interface. However, the benefits of simple surgery in a closed-chamber environment, rapid visual recovery, minimal spherocylindical change and a relatively strong, secure globe all outweigh the slight shortfall in BCVA.
Shortcomings of DSEK

At present, the major drawback of DSEK is a high rate (10% to 30%) of non-attachment of the graft (Figure 3). The factors that affect graft attachment are currently unknown, but lower preservation times, thinner donor thickness and atraumatic graft insertion appear to be positively correlated. If the graft does not attach, it can usually be reattached by �rebubbling� or reinjection of air into the anterior chamber even a few days after the original surgery.

In cases of primary graft failure, the original graft can be easily removed and replaced. Surgery is commonly performed in combination with cataract-IOL surgery or after failed PKP. Because longstanding corneal edema is usually associated with permanent ground substance alterations, the cornea may not clear in spite of successful endothelial replacement and deturgesence.

Future improvements will come from more atraumatic preparation and insertion of the donor tissue, and from techniques that may decrease the percentage of cases with non-attachment of the graft. Eventually, the transplanted endothelium may come from ex-vivo expansion of autologous endothelial cells that are put into place using only stroma as a carrier. Alternatively, only Descemets� membrane might be transplanted without a carrier.

Figure 1. Folded DSEK button being inserted into anterior chamber through incision.

Femtosecond Laser-Enabled Keratoplasty
The femtosecond laser has proved to be a predictable, reliable technology in cutting the interface and side cut for LASIK flaps. More recently, it has been adapted to create incisions and lamellar interfaces to facilitate penetrating and lamellar keratoplasty with custom overlapping shaped edges.³ This remarkable innovation has been named �femtosecond laser-enabled keratoplasty� (FLEK) or �IntraLase-enabled keratoplasty� (IEK) (IntraLase Corp., Irvine, Calif.) if performed with the IntraLase femtosecond laser.

Figure 2. DSEK graft deturgesed 24 hours after surgery.

Corneal incisional procedures have traditionally been performed with metal blades and, in the case of penetrating keratoplasty, round metal trephines have been used since the first successful PKP performed by Dr. Edward Zirm more than 100 years ago. Although these trephines have been improved by adding suction and become sharper, the shape of the incision has been straight-edged and often beveled. As a result, the sutures must be placed tightly to close the incision and make it watertight. Unfortunately, these tight sutures create irregular tension and healing is prolonged and accompanied by unpredictable amounts of astigmatism. Alternatives to these straight-edged incision shapes were conceived by early cornea specialists (Jos� Barraquer, M.D., and Ram�n Castroviejo, M.D.), but their attempts to manually craft overlapping incisions were never embraced by ophthalmologists because of the difficulty in manually creating these incisions. As a result, shaped-edged PKP and anterior lamellar keratoplasty (ALK) have not become part of the regular repertoire of corneal surgeons.

With the recent adaptation of the femtosecond laser to custom-designed incisions, a variety of special-shaped, overlapping-edge PKPs have been designed and performed, including �top hat,� �mushroom� (Figure 4) and �zig-zag� shapes. The potential advantage of these overlapping shapes is better incision sealing with looser suture tension. Conceivably these incisions could heal faster, with less astigmatism and greater resistance to traumatic dehiscence of the wound.

Figure 3. Non-attached DSEK graft 1 day after surgery.

With the IntraLase FS laser, the incision shapes, thicknesses and diameter are all programmed through the incision design software and the planned incision is visualized on the computer screen. Both the donor cornea (mounted in an artificial anterior chamber) and the recipient cornea are cut under the laser with precise vertical and horizontal dimensions within 10 �m of the planned measurement. The recipient cornea is typically cut in the refractive surgery area where the femtosecond is used for LASIK surgery (usually housed in a different building from the operating suite in which the transplant will be performed). To avoid leaking incisions and decompression of the eye between when the laser incision is made and the surgery is performed, one of the recipient incisions is incomplete by design. When the surgery commences in the operating room, the incision is manually connected with a spatula, scissors or a blade. The donor and host fit together as a tongue-in-groove�like coadaptation and apposition so that the incision seals with minimal suture tension. With these wound configurations, the sealing component of the incision may become dynamically separated from the conformation of the anterior surface of the graft. Although these incisions theoretically offer considerable potential advantages over traditional straight-edged incisions, only time and large-scale studies will prove their efficacy.

Another procedure that may conceptually benefit from femtosecond laser technology is ALK. Traditional ALK, performed either with manual dissection or with a blade microkeratome, has been unpredictable because of donor-host size, shape and/or thickness differences. Postoperative VA results have often been disappointing, usually because of irregular astigmatism and donor-host interface haze.

Figure 4. �Mushroom� shaped femtosecond laser-enabled
penetrating keratoplasty 1 week postoperatively with
20/40 unaided vision.

The ability of the femtosecond laser to provide the exact match of donor-to-recipient dimensions in ALK may improve visual outcomes. As in femtosecond laser-enabled PKPs, the desired parameters for both donor and recipient are entered into the software. Either whole donor globes or corneo-scleral buttons mounted in an artificial anterior chamber are appropriate for use. The donor lamella is usually oversized by 0.1 mm, but the same thickness is used for both donor tissue and recipient bed. A vertical edge shape facilitates stability of the graft; suturing is usually unnecessary.

Currently, anterior grafts deeper than 200 �m do not have as smooth an interface as more superficial grafts, due to deep round folds caused by compression of the cornea during applanation by the laser cone. Postop refractive error or aberrations may be treated either on the surface or under the donor lamella as in a LASIK enhancement. Rehabilitation is rapid, and graft rejection does not occur in anterior lamellar grafts.

Eye-bank Cutting of Donor Tissue
The concept of precutting of donor tissue by eye banks is a novel advancement for the role of eye banks in the corneal transplant process. Previously, eye banks had the responsibility of obtaining the corneoscleral button from a cadaver, placing it in preservation medium, counting endothelial cells and then shipping it to the surgical location. The surgeon usually cut out the donor corneal button to the desired diameter with a trephine on a cutting block. The only decision that the surgeon made was in regard to the tissue diameter for transplantation.

During the beginning of the development of DSEK, the donor corneal lamella was personally fashioned by the operating surgeon. However, over the last 2 years this task is being performed with increasing frequency by technicians in eye banks.

In the case of DSEK, the eye bank donor tissue is screened, measured and selected for DSEK transplantation. Under a sterile hood, the corneo-scleral button is mounted in the Moria ALTK artificial anterior chamber. Following cutting, the residual donor bed is measured for diameter and thickness and the endothelium is photographed. The tissue is returned to the transport media and then shipped to the transplanting surgeon, who is able to proceed with the DSEK procedure without having to assemble a microkeratome and cut the tissue himself. This facilitates the procedure because operating room personnel usually do not know how to assemble and operate a microkeratome. In addition, the quality and appropriateness of the tissue that has been cut by the eye bank is already known before the patient is brought to the operating room, avoiding inadequate cuts and subsequent cancellations. The eye banks add an additional fee for cutting the tissue to cover their labor and equipment costs.

Similarly, tissue can be cut by a femtosecond laser based in an eye bank to match the dimensions designed by the operating surgeon. The tissue is then shipped to the surgeon who has designed the desired custom femtosecond laser cut shape. The matching shape is inscribed in the recipient cornea at the refractive laser site; the two edge shapes should match up well because of the precision of the cut even between two different lasers of the same manufacturer. Both recipient and donor corneas are then taken to the operating room and the transplant is performed. A processing fee is again charged by the eye bank to offset costs associated with this procedure. The advantage of having the eye bank cut the tissue rather than the surgeon is that the eye bank is licensed to process tissue. It is also able to routinely maintain the room where the tissue is cut in standardized condition.

Future Developments
Cutting of corneal tissue for transplantation, both in the case of DSEK and for FLEK, has become much more elaborate than the simple trephination of corneal tissue by the surgeon just prior to transplantation. As of yet, there are no special procedure codes that apply to the extra work and instrumentation involved in cutting of either donor and/or recipient tissue by the surgeon. This novel issue will eventually be addressed by the responsible agencies, although it is unclear at this point how it will be managed.

Ultimately, eye banks will assume even greater responsibilities including tissue culturing for ex-vivo expansion of autologous endothelial or limbal stem cell lines rather than simply harvesting tissue as they have in the past. The last 5 years have witnessed greater advances in cornea transplantation than had occurred cumulatively over the previous 50 years. Although we are all still in the development stage of these new procedures, it is certain that corneal transplantation has turned a significant conceptual and technological corner and will be quite different in the future. OM

References
1. Jones DT, Culbertson WW. Endothelial lamellar keratoplasty. ARVO abstract 342. Invest Ophthalmol Vis Sci.1998;39:S76.
2. Melles GR, Egglink FA, Lander F. A surgical technique for posterior lamellar keratoplasty. Cornea. 1998;17:618-626.
3. Ignacio TS, Nguyen TB, Chuck RS, Kurtz RM, Sarayba MA. Top hat wound configuration for penetrating keratoplasty using the femtosecond laser: a laboratory model. Cornea. 2006;25:336-340.