While full-thickness corneal transplant techniques have not changed much over the past century, lamellar corneal transplant techniques have evolved rapidly. To novices, the numerous acronyms that accompany the various corneal transplant techniques can easily become a disorienting alphabet soup. This article aims to introduce readers to the keratoplasty techniques that are most commonly used today (Figure 1).

A Brief History of Keratoplasty

When Eduard Konrad Zirm performed the first successful full thickness penetrating keratoplasty in a human in 1905, he became the first person to perform a solid organ transplant. Ironically, he performed the surgery for one of the most challenging indications in ophthalmology – bilateral alkali burns (1-3). His donor was an 11-year-old boy whose eye was enucleated due to foreign body penetration and scleral injury. Emulating Zirm's technique, surgeons began to perform corneal grafting over the subsequent 30 years using enucleated eyes of living donors (4). Vladomir Petrovich Filatov, a Russian ophthalmologist, became known for his work on eye banking in the early 1900s. He suggested using cadaver corneas as donor tissue and developed a method to do so (4).

Over the past century, keratoplasty techniques have evolved considerably. There were early efforts to devise selective tissue replacement techniques that might preserve healthy corneal tissue and avoid risks associated with full-thickness grafting. Anton Elschnig performed the first anterior lamellar keratoplasty in 1914, for a case of interstitial keratitis. Charles Tillet performed the first successful endothelial keratoplasty (EK) case in 1956 for corneal edema. However, the introduction of lamellar techniques actually propelled penetrating keratoplasty (PK) to the forefront of popularity after 1950 (1). Initially, anterior lamellar techniques were fraught with the problems of interface haze, scarring, and epithelial ingrowth. Tillet's EK technique, although successful, was not repeated and no additional clinical cases were reported for decades.

It was not until the late 1990s that EK was reinvestigated, revised, and reintroduced into clinical practice, launching the modern era of lamellar keratoplasty. Gerrit Melles experimented with eye bank cadaver eyes and then with animal eyes to bring EK into the modern era. Melles described an approach called posterior lamellar keratoplasty (PLK), in which the posterior cornea was dissected out and replaced with posterior stroma and endothelium from donor corneal tissue (1, 5-7) . Melles contributed the foundational concept of self-adherent graft tissue that required no sutures and could be supported initially by an air bubble. In 1999, Mark Terry introduced modifications to simplify Melles' PLK technique, developed new instrumentation, and coined the technique deep lamellar endothelial keratoplasty (DLEK) (1, 8) . However, these techniques were technically difficult to perform, required extensive manual lamellar dissection, and were not adopted widely. Patients healed rapidly compared to full-thickness transplants, but the presence of a deep stroma-to-stroma interface limited postoperative visual acuity typically to the 20/40-20/50 range.

In 2004, Melles made additional technical modifications, and introduced the idea of stripping and removing the patient's Descemet membrane and endothelium with his Descemetorhexis technique. This new technique was renamed Descemet stripping endothelial keratoplasty (DSEK). After Mark Gorovoy introduced the microkeratome for automated preparation of donor cornea, manual lamellar dissection could be eliminated entirely, and the procedure was again renamed as Descemet stripping automated endothelial keratoplasty (DSAEK). Francis Price proposed additional technical modifications, and again, Terry introduced simplifications and new instrumentation. DSAEK allowed patients to achieve improved postoperative visual acuity results, to the 20/25-20/30 range, because its graft-host interface is more smooth (1, 9) . With the advent of eye bank prepared donor tissue in 2006, financial and technical obstacles were removed, and DSAEK surgery became the most commonly performed method of endothelial keratoplasty and procedure of choice for the treatment of corneal edema.

In 2006, Melles went on to describe a technique known as Descemet membrane endothelial keratoplasty (DMEK) that allowed for transplantation of a pure Descemet membrane and endothelium graft, and exact anatomical replacement of diseased tissue in cases of endothelial dysfunction. Compared to DSAEK, DMEK allows even faster visual recovery, better postoperative visual acuity results, and greater overall patient satisfaction due to elimination of the stroma-to-stroma graft-host interface (10). However, the initial donor preparation failure rate and surgical learning curve prevented widespread application after introduction of this technique (1). Mirroring the evolution of DSAEK, as surgical techniques have become standardized and eye banks have begun to prepare DMEK graft tissue, DMEK is rapidly becoming the procedure of choice for endothelial keratoplasty for the treatment of Fuchs endothelial dystrophy and pseudophakic bullous keratopathy.

Additionally, anterior lamellar keratoplasty (ALK) techniques have been refined over the past 40 years. In the late 1970's Malbran and Gasset were performing deep anterior lamellar keratoplasty (DALK) to excise and replace the corneal tissue anterior to the deepest stromal lamellae with impressive results including 80% of keratoconus patients achieving 20/40 or better visual acuity (1, 11) . However, obstacles remained that limited the popularity of this approach, including achievement of a reproducible separation plane between posterior stroma and, ideally, Descemet membrane. In 2002, Anwar and Teichmann introduced their "big bubble" pneumodissection technique in which a bubble of air is injected deep into the corneal stroma to establish separation of the posterior stroma from Descemet membrane (12). Their technique has allowed surgeons to achieve more consistent results than previous methods, but in some cases, intraoperative conversion to a full-thickness PK is still required. For patients with keratoconus or scarring that does not involve Descemet membrane or endothelium, DALK is considered by most to be the surgical treatment of choice (1), although extended operating times due to the need for careful lamellar dissection have limited its popularity.

Keratoprosthesis, the transplantation of an artificial cornea, was first performed in Italy by Benedetto Strampelli the 1960s (1). Patients requiring repeat corneal transplantation highlighted the need for an alternative to corneal allograft treatment, as graft survival rates drop with each additional procedure. Historical options have included the osteo-odonto-keratoprosthesis (OOKP) and AlphaCor artificial cornea. These have since been largely replaced by the Boston Type I Keratoprosthesis (KPro), which became approved for use by the U.S. Food and Drug Administration in 1992 (1, 13). The device consists of a clear plastic optic and a prosthetic plate that are sandwiched around a donor allograft or the patient's own corneal tissue. The device is then sutured onto the recipient eye to replace a failed graft or the native cornea. Keratoprosthesis surgery is a procedure of last-resort, reserved for patients who are not candidates for other types of keratoplasty.

Deep Anterior Lamellar Keratoplasty (DALK)

DALK is a partial-thickness cornea transplant procedure that involves selective transplantation of the corneal stroma, leaving the native Descemet membrane and endothelium in place. A trephine of an appropriate diameter is used to make a partial-thickness incision into the patient's cornea, followed by pneumodissection or manual dissection of the anterior stroma. This is followed by placement of a graft prepared from a full-thickness punch in which the donor endothelium-Descemet membrane complex has been removed. The intention is to preserve the patient's Descemet membrane and endothelium. Similar to PK, the graft is secured with interrupted and/or running sutures (Figure 5) and these are then selectively removed post-operatively (Figure 6).

DALK is useful for processes involving the corneal stroma in the presence of healthy endothelium. Examples include corneal ectasia (such as keratoconus in the absence of hydrops), corneal scars that are not full-thickness, and corneal stromal dystrophies (1, 15, 16).

Because it is not a full-thickness procedure, the resultant wound is stronger than that of a PK. Leaving the host endothelium intact significantly decreases the risk of endothelial rejection.

The surgery is more complex and difficult to perform than PK. If the Descemet membrane is perforated intraoperatively, the surgeon must convert to a PK. The "big bubble" technique makes dissection more consistent and is the preferred technique at our institution (12).

Video 2: Big bubble DALK technique. Video contributed by Matt Ward, MD and Mark Greiner, MD -- If video fails to load, use this link

1. Mark the center of the host cornea with a Sinskey hook, and use a calipers to plan the host trephination.
2. Trephinate the host cornea to a depth of 90%.
3. Insert a 27-gauge needle, or a Fogla dissector followed by a Fogla 25-gauge cannula, into the posterior stroma.
4. Inject air to dissect Descemet membrane posteriorly with a large bubble.
5. Remove approximately 70% of the anterior stroma using a crescent blade or Devers dissector.
6. Create a paracentesis incision to release aqueous.
7. After marking the stroma and placing Healon over the mark, make an incision through the mark.
8. Inject Healon into the space between the posterior stroma and Descemet membrane. Complete the separation between these two layers using a cyclodialysis spatula.
9. Resect the remaining stroma using curved corneal scissors.

Additional Resources:

• DALK for post-LASIK Keratoconus

• Surgical Management of Keratoconus
• Deep Anterior Lamellar Keratoplasty

Descemet Membrane Endothelial Keratoplasty (DMEK)

DMEK is a partial-thickness cornea transplant procedure that involves selective removal of the patient's Descemet membrane and endothelium, followed by transplantation of donor corneal endothelium and Descemet membrane without additional stromal tissue from the donor. The graft tissue is merely 10-15 microns thick. Similar to DSAEK, direct contact with the DMEK graft tissue should be avoided to prevent endothelial cell damage and graft failure. A clear corneal incision is created, the recipient endothelium and Descemet membrane are removed, and the graft is loaded into an inserter. After injecting the tissue into the anterior chamber, the surgeon orients and unscrolls the graft, and a bubble of 20% sulfur hexafluoride (SF6) is placed in the anterior chamber to support graft adherence (Figure 10). A variation known as Descemet membrane automated endothelial keratoplasty (DMAEK) utilized an automated preparation of the donor tissue that left a rim of donor stroma peripherally for easier tissue handling (Figure 11), but the procedure is no longer performed due to advances in DMEK that have allowed for easier insertion and manipulation of the graft tissue.

The indications for DMEK are similar to those for DSAEK, including endothelial dystrophies (such as Fuchs corneal dystrophy and posterior polymorphous corneal dystrophy), pseudophakic bullous keratopathy, ICE syndrome, and other causes of corneal endothelial dysfunction (1, 10, 17).

DMEK offers the most rapid visual rehabilitation of any keratoplasty technique to date (Figure 12). Final visual acuity can be outstanding due to minimal optical interface effects. Because less tissue is transplanted, there is a lower risk of allograft rejection and less long-term reliance on topical steroids compared with other types of keratoplasty. Discontinuation of topical steroids can be considered at or before 1 year after the procedure, especially for patients with elevated intraocular pressure.

Because of thinness, fragility, and its characteristic scrolling properties (with the endothelium facing outward), the donor tissue can be difficult to handle and contribute to technical difficulties with the procedure. There is a higher risk of graft edge lifts (Figure 13) compared with DSAEK, sometimes requiring a re-bubble procedure.

Video 4: Phakic DMEK, If video fails to load or resize, use this link

Basic procedure steps (Video 4):

1. Create two to four paracentesis sites.
2. Fill the anterior chamber with Healon.
3. Create an inferior peripheral iridotomy using a bent 30-gauge needle and Sinskey hook to prevent post-operative pupillary block.
4. Mark the recipient's corneal epithelium with a circular ring slightly larger than the planned graft diameter to create a template for resection of the host tissue.
5. Score Descemet membrane peripherally using a reverse Terry-Sinskey hook, then peel Descemet membrane from the overlying stroma.
6. Create an incision temporally using a keratome, then remove the free Descemet membrane using forceps.
7. Remove the Healon using the irrigation/aspiration handpiece.
8. Inject Miochol to constrict the pupil and BSS to normalize the pressure.
9. Carefully lift the donor tissue by grasping the outermost edge with tying forceps and submerge it in trypan blue solution for 60 seconds to stain the tissue and make it more visible.
10. Place the tissue in a BSS-filled petri dish and it will scroll spontaneously.  Aspirate it into a modified glass Jones tube.
11. Insert the tip of the glass tube into the clear corneal incision and inject the donor tissue into the anterior chamber.
12. Release fluid from a paracentesis to flatten the anterior chamber.
13. Gently tap and swipe on the anterior corneal surface until the graft is appropriately positioned and unscrolled.
14. Inject 20% SF6 into the anterior chamber to secure the graft and wait 10-15 minutes for adhesion.
15. Close the main incision with a 10-0 nylon suture.
16. Perform an air-fluid exchange to ensure there is no gas trapped behind the iris and assess for graft adhesion.
17. Injection another bubble of 20% SF6 to cover the graft, about 80-90% of the anterior chamber.

Keratoprosthesis

Keratoprosthesis implantation is a procedure that involves full-thickness removal of the cornea and replacement by an artificial cornea. The Boston Type I Keratoprosthesis is currently the most commonly used keratoprosthesis device in the US. It consists of a clear plastic polymethylmethacrylate (PMMA) optic and back plate sandwiched around a corneal graft and secured with a titanium locking ring (Figure 15). After the device is assembled, a partial-thickness trephination is performed on the host cornea. Full-thickness resection of the patient's cornea is then completed using curved corneal scissors. The keratoprosthesis is then secured to host tissue using interrupted or running sutures. Generally, patients who have a history of multiple failed PKs are candidates for a keratoprosthesis transplant. Other indications include severe keratitis or ocular surface disease resulting from limbal stem cell failure, such as Stevens-Johnson syndrome (Figure 16), ocular cicatricial pemphigoid, aniridia (Figure 17) and chemical injury (1, 13). The Boston Type II Keratoprosthesis is a similar device with a longer optic designed to extend through an opening made in the upper eyelid (Figure 19). It is indicated for the most severe cicatrizing ocular surface diseases.

KPro placement offers relatively fast visual rehabilitation. The devices are amenable for use in many situations in which other types of keratoplasty are not an option.

There is significant long-term risk of complications for those with a keratoprosthesis. Because the KPro is a foreign body, there is risk of infection or extrusion of the device. Post-operative glaucoma is common and intraocular pressure is difficult to evaluate as the hard optic makes traditional tonometry impossible. For this reason, glaucoma tube shunts are typically placed at the time of the corneal transplant at the University of Iowa. The Diaton is currently the preferred way to measure intraocular pressure in these patients in our institution. Patients can form retroprosthetic membranes requiring treatment with a Nd:YAG laser or surgical membranectomy (21).

Basic procedure steps (Video 5):

1. Mark the center of the host cornea using a Sinskey hook and measure the cornea to determine the appropriate transplant size.
2. Trephine the donor cornea.
3. Assemble the keratoprosthesis by sandwiching the corneal graft between the front and back plates of the KPro device.
4. Trephinate the host cornea to approximately 90% depth.
5. Create a paracentesis, in the trephination groove or the corneal periphery, and inject Healon into the anterior chamber to preserve anterior chamber depth and stability.
6. After using a blade to enter the eye through the trephination groove, resect the host cornea tissue using curved corneal scissors.
7. Secure the donor tissue of the assembled KPro to the host corneal tissue using interrupted and/or running 9-0 nylon sutures.
8. Rotate the sutures to bury the knots.