CORNEAL TRANSPLANTS

Advances in Corneal Transplant Surgery

New techniques and procedures are improving outcomes and minimizing complications.

By Carrie Lembach, DO, & Greg DeNaeyer, OD, FAAO

Corneal transplant surgery has been helping individuals regain vision for more than a century. According to the Eye Bank Association of America, more than one million corneal transplants have been performed since the 1960s. Penetrating keratoplasty (PK) or full-thickness corneal transplants have been the primary surgery for most of this time period. However, in the past decade partial-thickness transplant techniques have developed that offer patients new options for addressing corneal disease that is refractory to contact lens or medical intervention.

Penetrating Keratoplasty (PK)

The first documented corneal transplant, which was a PK, was performed in 1905 by Dr. Eduard Zirm (Armitage et al, 2006). A PK (Figure 1) is a full-thickness replacement of corneal tissue by a donor graft that has a global success rate of approximately 90 percent (Troutman and Lawless, 1987). The categories for a PK include optical, therapeutic, tectonic, and cosmetic. Optically, PKs replace scarred and/or irregular corneas. Tectonic transplantations are performed to re-establish structural integrity of the eye. Therapeutic corneal transplantations are performed on corneas that are painful, but have no vision potential. Finally, cosmetic transplants improve the appearance of the eye, but not visual function. The most common indications for a PK are keratoconus, Fuchs' endothelial dystrophy, and pseudophakic bullous keratopathy (Table 1). Less common indications include corneal dystrophies, corneal scarring, and chemical injury.

Figure 1. A penetrating keratoplasty.

For a PK, the corneal surgeon uses a trephine to cut a full-thickness section from the recipient's cornea and then replaces it with donor tissue from a cadaver eye that has been screened for pathology and has a healthy endothelial cell count. Occasionally, smaller grafts are used as a patch in the case of corneal perforation (Figure 2). The graft is secured with a series of interrupted or running sutures. The patient is immediately put on short-term antibiotic drops to prevent infection and is put on long-term topical steroid drops to prevent rejection. Oral antivirals are given pre- and post-operatively if the patient has a history of herpes simplex to avoid reactivation of the virus. Visual recovery is slow and may take between six and 12 months. The sutures are often left in place indefinitely unless removed secondary to becoming loose or in an attempt to help correct for postoperative astigmatism. PK may be combined with cataract surgery if the patient has visually significant crystalline lens opacities. Unfortunately, in a combined procedure, postoperative refractive outcomes are difficult to predict secondary to the possibility of induced astigmatism from the PK procedure.

Figure 2. Smaller grafts are sometimes used to act as a patch in the case of corneal perforation.

The most common reason for a corneal graft to fail is an immune-mediated corneal graft rejection. The estimated corneal graft rejection rate is between 9 percent and 12 percent (Sangwan et al, 2005; Triqui et al, 2005). This relatively low rate, as compared to other organ allograft transplants, is because the eye has immune privilege secondary to a blood brain barrier and lack of lymphatic drainage (Taylor, 2005; Streilein, 2003). Graft rejections are treated with high dose topical steroids and sometimes with oral steroids. Long-term failure may result secondary to recurrence of disease, as can occur in keratoconus or in some corneal dystrophies. Finally, a graft may fail as a result of late-onset endothelial dysfunction.

The greatest visual complication from PKs that can challenge both practitioners and patients is postoperative regular and/or irregular astigmatism. It is important to inform patients pre-operatively that their best-corrected vision after a successful surgery may require them to wear glasses or contact lenses. In some cases, specialty GP lenses are required to mask front-surface irregularity so that patients can achieve their vision potential (Figure 3). If the graft surface is regular, then soft contact lenses can be considered for the following cases: if the patient desires glasses-free vision; to manage anisometropia; or to correct for aphakia.

Figure 3. Specialty GP lenses are sometimes required to mask front-surface irregularity.

There is debate about when a patient is able to safely wear a contact lens after a PK. The answer depends on many factors for each patient, but generally speaking, most patients are able to be fit with a contact lens between six and 12 months after their surgery as long as they are without complications, their refractive error is stable, and the surgeon gives consent. Patients with corneal grafts who wear contact lenses need to be monitored carefully for secondary lens complications. Of primary concern is the development of lens-induced neovascularization, particularly stromal, which increases the risk of corneal graft rejection (Kaufman et al, 1998). Using high-Dk lens materials will reduce this hypoxic complication, but a lens that irritates a suture site (Figure 4) may also evoke unwanted vessel formation.

Figure 4. A lens that irritates a suture site may evoke unwanted vessel formation.

Postoperative regular astigmatism may be addressed surgically with options including wedge resections, astigmatic keratotomy (AK), and laser refractive procedures, such as laser-assisted in situ keratomileusis (LASIK) or photorefractive keratectomy (PRK).

Endothelial Keratoplasty (EK)

Several lamellar (partial thickness) corneal surgeries have been developed to address corneal pathology while attempting to avoid some of the complications that are associated with a PK. Endothelial keratoplasty (EK) is a lamellar surgery that specifically addresses a dysfunctional endothelial layer.

Common indications for this type of surgery include Fuchs' endothelial dystrophy, pseudophakic bullous keratopathy, and failed PK (Table 2). Although there are several different versions of EK, currently Descemet's stripping automated endothelial keratoplasty (DSAEK) is most commonly performed.

Descemet's Stripping Automated Endothelial Keratoplasty (DSAEK) The first step of a DSAEK procedure involves stripping the diseased endothelial surface and removing it, all of which is performed through a corneal limbal incision or scleral tunnel. In many instances, the surgeon is able to widen an incision that was used for a previous cataract surgery. A posterior donor button procured from a local eye bank is then readied and cut down to its final size as determined by the surgeon in the operating room. This button of tissue includes endothelium, Descemet's membrane, and stroma, with a resulting thickness of 100 microns. Interestingly, as the donor button includes only the posterior stroma of the cornea, this may expand the donor pool for this surgery by making available tissue that was excluded for PK because of anterior stromal scars, pterygia, and previous corneal refractive procedures (Phillips et al, 2009).

The donor tissue is folded to enter the wound and is then positioned to match up with the recipient's eye. An air bubble is then positioned to temporarily secure the interface attachment. The pumping action of the endothelial cells helps the donor tissue permanently stick into place and position (Shamie, 2010). Conditions that increase the difficulty of a DSEAK procedure include patients who are phakic, who have anterior chamber IOLs, and those who have undergone trabeculectomy.

DSAEK has numerous advantages over PK for endothelial dysfunction. First, it is a less invasive surgery so the postoperative eye heals more rapidly and is structurally more stable, diminishing the likelihood for wound rupture. The visual recovery for DSEAK, which averages three months, is much quicker as compared to PK, and there is little to no postoperative induced astigmatism. This, of course, makes fitting a contact lens easier if one is needed or desired after surgical recovery.

A 2009 study by Bahar et al of 12 patients who had PK in one eye and DSAEK in the other eye concluded that patients who had DSAEK had better uncorrected visual acuity, bestcorrected visual acuity, and contrast acuity as compared to PK. Another study by Yamaguchi et al in 2010 showed that postoperative irregularity was greater after PK than after DSAEK. These improvements over PK have caused a paradigm shift that allows for earlier surgical intervention. This is important with regard to endothelial dysfunction as long-standing corneal edema can cause permanent changes in the epithelial basement membrane and anterior stroma that can limit the patient's final visual outcome.

DSAEK has revolutionized corneal transplant surgery for patients who have endothelial disorders, but it's not without its limitations. First, there is a steep learning curve for surgeons, and the placement of the donor tissue can be difficult. Handling the tissue gently is imperative because excessive manipulation can result in loss of endothelial cells, leading ultimately to loss of graft clarity, which is the principal cause of failed DSAEK (Zhang et al, 2010). Another potential difficulty with this procedure is the positioning of the air bubble. Patients are instructed to lay face up on the night of the procedure to keep the bubble in place. If the patient is noncompliant or has physical difficulty with this, then this could result in an unsuccessful donor-to-host attachment. In some cases, repositioning and rebubbling or using new donor tissue may be necessary to achieve success. Too much air left in the anterior chamber can induce pupillary block, resulting in acute angle closure glaucoma.

Another limitation of DSAEK is that the patient's best vision potential ranges between 20/25 and 20/30 secondary to increased postoperative stromal thickness and interface issues. Educating patients about this is critical because a 20/30 result may disappoint those who anticipate a 20/20 or better outcome.

The other potential optical issue with DSAEK is that patients may have a postoperative hyperopic shift in their refractive error. A thickness differential between the center and the peripheral back surface may induce posterior curvature changes that result in this hyperopic shift (Scorcia et al, 2009). This has the potential to disappoint pseudophakic patients who were satisfied with their refractive status before the DSAEK procedure.

Endothelial rejection can occur and should be treated promptly with high dose steroids. Finally, just like in a PK, late-term endothelial dysfunction can eventually cause the graft to fail.

Descemet's Membrane Endothelial Keratoplasty (DMEK) Although DSAEK is currently the most widely used endothelial keratoplasty, other procedures are being pioneered that have the potential to improve EK results. One of these surgeries is termed DMEK. This endothelial keratoplasty is similar to DSAEK except that with DMEK the donor tissue is comprised of Descemet's/endothelial complex and does not have any attached central stromal tissue. The result of a thinner donor profile is that it improves the patient's visual potential and decreases the trend towards hyperopia as compared to DSAEK.

A 2009 study by Price et al concluded that DMEK, as compared to DSAEK, provided a significantly higher rate of 20/20 and 20/25 vision (Price et al, 2009). However, ultimately the relatively thin donor tissue increases the difficulty of the procedure. In fact, the donor tissue is so ultrathin that it can be difficult to unfold and orientate properly onto the donor bed. Interestingly, a hybrid technique of DSAEK and DMEK has been developed that addresses some of the negatives of each procedure. Essentially, the donor is prepared so that the graft has a bare Descemet's/endothelial complex while the peripheral rim includes stroma (McCauley et al, 2009). Thus, the center optic zone is left thin to improve vision potential and the thicker periphery allows the tissue to unfold and handle more easily.

Deep Anterior Lamellar Keratoplasty (DALK)

DALK is a relatively new lamellar corneal transplant surgery that is indicated for corneal pathology located anterior to Descemet's membrane. Indications include keratoconus, stromal scars, and stromal dystrophies (Table 3).

In this procedure, the host stroma is separated from the Descemet's/endothelial complex by injection of a bubble deep into the cornea. This allows the surgeon to remove and transplant the host stroma and epithelial layers. DALK has a number of advantages compared to PK, one of which is that the eye maintains its structural and immunologic integrity. Secondly, the grafted eye after DALK is not at risk for an endothelial rejection and has less risk of endothelial cell loss as compared to PK. Several recent studies have demonstrated that visual acuity outcomes of DALK are comparable to those of PK for keratoconus. However, DALK cases have had fewer postoperative complications (Han et al, 2009; Sarnicola et al, 2010; Javadi et al, 2010).

The learning curve for performing a DALK procedure is steep and may be a limiting factor for some surgeons. Breaching the Descemet's/endothelial complex during the surgery is a major complication that would require the patient to need a PK. In some cases, interface scarring could limit a patient's vision potential.

Keratoprosthesis

The patients who may be candidates for keratoprostheses include patients who have severe corneal scarring or pathology and have multiple failures with corneal transplants, or patients for whom a corneal transplant will most likely fail.

The AlphaCor keratoprosthesis (Addition Technology) is a biocompatible, one-piece artificial cornea that has optics for either phakic or aphakic patients. It requires a two-step surgical procedure. The first step involves implanting the device into a lamellar corneal pocket (University of Iowa Ophthalmology, 2010). The corneal surface is then covered with a conjunctival flap or bandage soft contact lens. Two to three months later, the scar tissue that covers the device is then removed. According to company data, the outer skirt is a PHEMA sponge that will biointegrate with the host tissue.

The Boston keratoprosthesis (Figure 5) was developed by Dr. Claes Dohlman in the 1960s. The device consists of two plastic rings that clamp to a corneal graft that is sutured into the host cornea. For protection postoperatively, it is highly recommended that patients wear a soft bandage contact lens over the prosthesis on a continuous-wear basis (University of Illinois at Chicago).

Figure 5. The Boston keratoprosthesis.

There is some research that supports the future applications of using biosynthetic corneas. A recent paper by Bentley et al (2010) demonstrated a biosynthetic corneal implant with a polymer hybrid complex that was well-tolerated in dogs and may have human applications.

Conclusion

The evolution of corneal surgery continues to advance the ways in which practitioners are able to help patients who have corneal irregularity, dysfunction, or scarring. New techniques and procedures are improving outcomes and minimizing complications. Ultimately, these changes will continue to improve the quality of life for patients who have corneal pathology. CLS

For references, please visit www.clspectrum.com/references.asp and click on document #183.

	Dr. Lembach practices in Columbus, Ohio at Arena Eye Surgeons. Her specialty is cornea, cataract, and external disease. She is a consultant or advisor to Allergan.
	Dr. DeNaeyer is the clinical director for Arena Eye Surgeons in Columbus, Ohio. His primary interests include specialty contact lenses. He is a consultant or advisor to Visionary Optics and an advisory panel member of Inspire Pharmaceuticals. Contact him at gdenaeyer@arenaeyesurgeons.com.