Special Report
The Changing Landscape of Corneal Transplant Surgery
By Thomas John, MD
Worldwide, more than 10 million people have corneal blindness that can be corrected to varying extent with corneal transplantation. The landscape of such corneal transplant surgery has changed rapidly in the immediate past, and continues to change for the betterment of our patients, with improved quality of vision, no induced corneal astigmatism (depending on the procedure type), and faster visual recovery, all of which will fit into the modern lifestyle of our present day active patients.1-8 In the past several decades, corneal transplant meant full-thickness replacement surgery regardless of where the corneal pathology was located within the human cornea. This meant in addition to replacing the diseased portion of the cornea, the healthy part of the patient's cornea was also discarded. This may be less than optimal in a young patient with keratoconus who has healthy corneal endothelial cells and a long life span ahead. The present shift in the corneal transplantation formula is to replace the diseased parts with similar donor tissue and retain the healthy parts of the recipient cornea. This means retaining the healthy endothelium in a young keratoconus patient. Such a transplant approach is called selective-tissue corneal transplant (STCT) surgery.9
STCT Surgery
There are two types of STCT surgery. When the front part of the cornea is replaced, it is called anterior lamellar ker-atoplasty (ALK), and when the reverse approach is used, it is called posterior lamellar keratoplasty (PLK). In ALK the patient's corneal endothelium is retained (Figure 1), while in PLK the patient's corneal stroma and epithelium are retained (Figure 2). Retention of a patient's healthy parts of his cornea may contribute to a more biomechanically stable cornea. ALK may be performed for corneal scars, corneal dystrophies and keratoconus, while PLK is performed for any condition that has endothelial decompensation and corneal edema with compromised vision. However, we are not discarding full-thickness penetrating keratoplasty (PKP), only replacing it for the most part with STCT. The John-Malbran classification further subdivides the ALK procedure into superficial-ALK (SALK <160 µm), mid-ALK (MALK 160-400 µm), deep-ALK (DALK 400-490 µm) and total-ALK (TALK >490 µm, almost 100% stroma).1 In order to separate the collagen lamellae within the corneal stroma various surgical techniques have been utilized including air injection, big-bubble technique, vis-coelastic and fluid injection.1 The corneal stroma may be removed as a single disc of varying thickness, or alternatively, a divide-and-conquer technique may be used. Also, staining techniques such as the use of indocyanine green or trypan blue can increase the visibility of the stromal layers and facilitate the dissection. An intraoperative slit lamp can help in the assessment of the depth of dissection in ALK surgery. Alternatively, air in the anterior chamber has been used and the thickness of the stromal bed is assessed against the air bubble. With deeper corneal stromal dissection, the risk of accidentally tearing the recipient Descemet's membrane increases. However, when there is a full-thickness scar that is located centrally in the visual axis, a PKP may be the procedure of choice. Another difference between ALK and PLK is that in PLK there are no corneal sutures or a few sutures, and no corneal 360-degree circular wound. In contrast, except for SALK, the other lamellar procedures have corneal sutures much like a PKP and all ALK procedures have a circular corneal wound that will induce surgical corneal astigmatism. However, with the corneal endothelium being retained in these ALK techniques, patients will not experience an endothelial graft rejection throughout the life of the STCT procedure. This is a paradigm shift in corneal transplantation where endothelial graft rejection has been eliminated from the surgical equation.
Figure 1. Total anterior lamellar keratoplasty, 5 months following surgery, in a patient with advanced keratoconus and paracentral corneal stromal scarring. Left: Slit-lamp photograph shows a clear corneal graft comprising of a donor cornea that is devoid of Descemet's membrane and donor endothelium; Right: Corneal OCT image showing uniform, regular attachment of the patient's Descemet's membrane with endothelium to the inner concave surface of the donor corneal graft.
Figure 2. Descemet membrane endothelial keratoplasty (DMEK). Left: Slit-lamp view of DMEK day 1 following surgery, residual air bubble is seen in the anterior chamber; Right: DMEK, same eye, 10 days following DMEK showing a clear cornea and uncorrected vision of 20/30.
There has been continued momentum in refining and improving PLK procedures as well. The PLK procedure was born with deep lamellar endothelial keratoplasty (DLEK) in the 1950s (although it was not called DLEK at that time), first performed by Jose I. Barraquer, and subsequently by Charles Tillett. But this new PLK procedure was never popularized until decades later, when the advantage of using an anterior chamber air-bubble was more fully understood.4 However, DLEK was a much more demanding procedure that required a high level of skills to perform the procedure on a repeated basis.1-4 The surgeon had to split the corneal stroma limbus-to-limbus without perforating the patient's cornea anteriorly onto the corneal surface or posteriorly into the anterior chamber. This single factor dampened the popularity of the procedure and hence, never threatened the PKP procedure in any major way. Surgeons continued to stay on the sidelines and practice PKP procedures.
Embracing DSEK and DASEK
All of this changed when Descemet stripping endothelial keratoplasty (DSEK) and Descemet's stripping automated endothelial keratoplasty (DASEK) evolved into a much simpler surgical procedure without the advanced surgical skill needed in performing the older procedures. With the selective stripping of the Descemet's membrane from the patient's cornea,10 there was no longer any need to split the corneal stroma. It was simpler and the total corneal transplant landscape had changed permanently! This was a turning point in the history of corneal transplantation.
Corneal surgeons globally embraced this procedure for all forms of endothelial decompensations. Visual recovery was much faster than with a PKP and no induced corneal astigmatism made it a welcome procedure. However, DSEK and DSAEK are tissue-addition procedures where the patient's corneal anatomy is somewhat altered with increased final corneal thickness. It is much like the old epikeratoplasty procedure in a reverse fashion, where the corneal disk is attached to the posterior corneal surface with the end result being the same, namely a final thicker cornea. Questions relating to lateral tissue expansion of the donor corneal stroma onto the inner recipient corneal surface and beyond are yet to be fully understood and longer follow-up time may be required. However, for the most part, DSAEK has established itself as a relatively simple, safe and reproducible procedure and has finally replaced PKP for corneal endothelial decompensation.
DMEK Enters the Picture
Reproducibility and simplicity are the two driving forces for any surgical procedure to move to the center stage in the surgical arena. DSAEK certainly possesses these two factors. In contrast, Descemet membrane endothelial keratoplasty (DMEK) appears to be a much better procedure than DSAEK. DMEK a tissue-neutral, anatomically near normal procedure, but lacks two vital components. DMEK is neither simple (risk of donor tissue loss secondary to Descemet membrane damage), nor is it easily reproducible (steeper learning curve as compared to DSAEK). Hence it remains on the side-stage waiting to replace DSAEK when it matures into a surgically simple and reproducible procedure. In an effort to simplify the DMEK procedure, various surgical instruments are being developed for DMEK (including the John DMEK set, ASICO, Inc.). Certainly, the corneal transplant landscape has changed from PKP to DALK, TALK, DSAEK and DMEK.
Corneal transplantation currently goes beyond the landscape of eye-bank dependent, donor tissue transplantation (described above) to eye-bank independent artificial corneal transplantation. In the past, artificial cornea or keratopros-thesis had several limitations and postoperative complications. Two significant players in this arena include AlphaCor artificial cornea and Boston keratoprosthesis. Continued research efforts and deligence, along with persistence of Harvard corneal surgeon and “father of cornea” in the United States, Dr. Claes Dohlman, has led to the present day version of the Boston keratoprosthesis (K-Pro)(Figure 3) and has gained significant popularity globally. It has been used for high risk multi-graft failure cases. However, it does use a donor cornea in the final attachment and anchorage to the recipient cornea. In certain select cases, a Boston K-Pro may be used as the primary transplant procedure rather than a PKP. Additionally, Dr. Aquavella's group has introduced the Boston K-Pro into the pediatric transplant arena where graft failure is a significant problem when donor corneas are used in a PKP procedure. Continued work focuses on the issue of glaucoma management with such artificial corneal devices.
Figure 3. An artificial cornea. Slit lamp and OCT views of the Boston keratoprosthesis.
Corneal transplantation does not stop with artificial cornea. The landscape continues to remodel and change and it is moving into new, yet largely unexplored territory of bio-engineered corneas. This may be the answer to a shortage of human donor tissue worldwide along with the potential for graft rejection in donor corneas. Bioengineered corneas are substitutes for human donor corneal tissue that are designed to replace part of the damaged or diseased corneas of the patient. Until recently, this was a concept or hypothetical possibility. However, it has now become a reality with initial surgical procedures having been performed in Sweden on 10 patients with a 2-year follow-up. Biosynthetic mimics of corneal extracellular matrix were implanted to replace the pathologic anterior corneas in these patients with significant vision loss by Dr. Per Flagerholm. Postoperative findings included nerve regeneration, sensitivity was restored, and stro-mal cells recruited into these implants. Vision improved in 6 of these patients. However, presently, the outcomes are not entirely comparable to human donor corneas and it is not suitable for endothelial transplantation. Although this technique has potential, it is not ready for widespread clinical use.
Continued follow-up and research both laboratory and clinical, may make such bioengineered corneas as the transplant of choice in appropriate cases, but we are not there yet! The final step in this journey of corneal transplantation may be pure endothelial cell replacement in otherwise healthy corneas with diseased endothelium.
The landscape of corneal transplantation has certainly changed and continues to change for the betterment of human vision restoration for our patients all over the world. Synthetic and bioengineered replacement surgery will unlock the donor-dependent procedure to donor-independent corneal surgery that can be extended to larger population of those who have corneal blindness. Better surgery for improved vision and a promising new landscape in corneal transplantation lies ahead.
References:
1. John T (Ed): Surgical Techniques in Anterior and Posterior Lamellar Keratoplasty. Jaypee Brothers Medical Publishers (P) Ltd., Pages 1-687, Chapters 1-63, 2006.
2. John T (Ed): Step by Step Anterior and Posterior Lamellar Keratoplasty. Jaypee Brothers Medical Publishers (P) Ltd., Pages 1-297, Chapters 1-15, 2006.
3. John T (Ed): Lamellar Corneal Surgery. McGraw-Hill Companies, New York, NY, Pages 1-687, Chapters 1-63, 2008.
4. John T (Ed): Endothelial Transplant, DSAEK, DMEK, & DLEK. Jaypee-Highlights Medical Publishers Inc., Pages 1-428, Chapters 1-39, 2010.
5. John T (Ed): The Chicago Eye and Emergency Manual. Jaypee-Highlights Medical Publishers Inc., Pages 1-387, 2011.
6. Darlington JK, Adrean SD, Schwab IR: Trends of penetrating keratoplasty in the United States from 1980 to 2004. Ophthalmology. 2006;113:2171-2175.
7. Straiko MD, Shamie N, Terry MA: Endothelial keratoplasty: past, present, and future directions. Int Ophthalmol Clin. 2010; 50:123-135.
8. Price MO, Price FW Jr.; Endothelial keratoplasty - a review. Clin Experiment Ophthalmol. 2010; 38:128-140.
9. John T: (Editorial) Selective tissue corneal transplantation: A great step forward in global vision restoration. Journal–Expert Rev Ophthalmol 1: 5-7, 2006.
10. Melles GR, Eggink FA, Lander F, Pels E, Rietveld FJR, Houdijn-Beekhuis W, Binder PS: A surgical technique for posterior lamellar keratoplasty. Cornea 1998; 17:618-626.
Thomas John, MD, is clinical associate professor at Loyola University and in private practice at the Thomas John Vision Institute in Chicago (Oak Brook, Tinley Park, and Oak Lawn). He is one of the world leaders in lamellar corneal surgery. He is the Editor-in-Chief of the journal Techniques in Ophthalmology. He may be reached at tjcornea@gmail.com. |