Ординатура / Офтальмология / Английские материалы / Corneal Endothelial Transplant (DSAEK, DMEK & DLEK)_John_2010

The Developmental Period 1900 to 1945

During this period, keratoplasty passed, progressively, from a stage of isolated trials to one of permanent practice especially due to advances in anesthesiology and antisepsis. Seven years after the first LKP (Table 14-1) Edward Zirm on December 7, 1905, performed the first penetrating keratoplasty (PKP) in Olmutz near Prague in Slovakia, previously called Czechoslovakia. The patient Alois Golgar had sustained lime injury and was blind in both eyes. Zirm used von Hippel’s 5.0 mm trephine for the surgery. According to Tomas A. Casey, the first autograft was performed by Plange in 1908 and this was a lamellar transplant. He replaced a patient’s scarred cornea with a lamellar graft taken from the patient’s other eye, which, although blind, had a normal cornea. The graft remained transparent for five years.1 In 1911, the idea of homografts being superior to heterografts was established by the French ophthalmologist A. Magitot.5

Between 1914 and 1930 many surgeons contributed to the improvements in surgical techniques and instruments

for keratoplasty. However, during this period their efforts were primarily directed towards PKP rather than to lamellar corneal surgery. Penetrating keratoplasty was considered to be an easier surgical technique that required less surgical time and yielded better postoperative visual results.

During the first thirty years of the last century many names were relevant in the development of lamellar transplants, such as, von Hippel and Lohlein in Germany; Magitot and Morax in France; Elschnig in Czechoslovakia (on January 1st, 1993 Czechoslovakia was split into the Czech Republic and Slovakia); Filatov in Russia; and Franceschetti in Switzerland. These authors further defined the indications and surgical techniques of lamellar corneal grafts. At that time PKP was not considered feasible.5

Between 1930 and the end of World War II, further surgical developments took place in PKP. In the mid 1930s, Ramon Castroviejo described rectangular PKP. Figure 14-2 displays a clear, square PKP. In contrast, the French school had consistently been emphasizing the value of lamellar corneal transplants throughout this same period.5

Figure 14-2: Clear, square, full-thickness penetrating keratoplasty (Courtesy Kenneth R Kenyon, MD).

The Period of Constant Improvement and Changes, from 1945 until the Mid-Nineties

Due to various limitations of LKP as compared to fullthickness PKP, lamellar surgical techniques were practically abandoned by most of the ophthalmic surgeons. However, in 1940 lamellar corneal surgery underwent resurgence, when the French surgeon from Lyon, Dr. Louis Paufique (1899–1981), improved the lamellar techniques and developed new surgical instruments for LKP.

In 1948, Louis Paufique, G. Philippe Sourdille, and Guy Offret published an excellent book on keratoplasty, namely,

Les Greffes de la Cornée. Paris; Masson & Cie,Editors. This was a rapport presented at the Société Française d’Ophtalmologie on May 23rd of that same year. It became a very important reference for LKP.5 Another French author of significant importance was Jacques Charleux of Lyon, who together with Paufique, Sourdille and Offret, played an important role in the development of the French School of Transplants that established the importance of LKP. They showed the usefulness of LKP not only as a tectonic or therapeutic procedure, but also as a surgical technique for improving vision.

The first reference in the ophthalmic literature on the subject of posterior lamellar keratoplasty (PLK) can be found in a paper written in 1950, by José Ignácio Barraquer (1916– 1988), from Bogota, Colombia (Figure 14-3), who stated, that it is “for cases of incipient endothelial dystrophies.”

Figure 14-3: Historic beginning of posterior lamellar keratoplasty (PLK).

Barraquer’s surgical technique consisted of a square anterior lamellar flap, with resection and replacement of the posterior corneal lamella, including the dissected Descemet’s membrane and endothelium. The flap was then put in place and sutured.6

In 1956, Charles W. Tillett from Charlotte, North Carolina, published an elegant paper (“Posterior Lamellar Keratoplasty”, AJO 1956) (Figure 14-3) proposing a new technique for LKP, for the treatment of endothelial dystrophies and opacities of the posterior layer. Tillett’s technique consisted of a sclerocorneal anterior chamber entrance at the 12 o’clock meridian, combined with a 10 mm corneal, posterior lamellar excision using right and left Katzin corneal scissors. The donor material, with a thickness of 300 µm, was sutured at the 2, 4, 8, and 10 o’clock meridians. Unfortunately, the patient developed severe postoperative glaucoma without any visual improvement. However, it is important to note, that the posterior lamellar graft remained in good position even after one year following the surgery, and the iris details could be visualized through the graft. This paper was presented in part at the 14th Clinical Meeting of the Wilmer Residents Association, at the Wilmer Ophthalmological Institute on March 31, 1955.7 Hence, Tillett´s technique should truly be considered as the pioneer idea of modern day techniques for PLK.

Also in 1955, yet another interesting historical paper was presented by Frederick Stocker, at a scientific section of the American Academy of Ophthalmology.8 The author presented in a motion picture a procedure, suggested by Louis Paufique, from Lyon, France, of scraping the endothelium off the posterior surface of the patient’s cornea, as a preliminary measure for the corneal grafts in patients with Fuchs’ endothelial dystrophy. This is the only

reference about this surgical technique in the literature. This surgical technique may be considered as the precursor for the newly established Descemet’s membrane stripping techniques in DSAEK surgery.

During the period between 1970 and 1990s several ophthalmic surgeons contributed to the continued onward progress of LKP.

The Modern Era

The year 1993 may be considered as the beginning of the modern era of PLK.9,10 In 1993, Ko et al,11 reported their animal study of PLK using a limbal approach. Five years later, in 1998, Gerrit Melles,12,13 from the Netherlands, pioneered the surgical principles for the modern day posterior endothelial keratoplasty with the first endothelial keratoplasty in humans where he used an air bubble in the anterior chamber to help in the adherence of the donor corneal disk to the patient’s cornea, eliminating the need for corneal suture attachment. The use of an air bubble to help attach the donor corneal disk to the patient’s cornea without the use of any corneal sutures may be considered a major milestone in the history of corneal transplantation. Melles et al called this technique PLK, the same term that Tillett7 used in 1956. In the United States, Mark A Terry worked in his laboratory in 1999 with PLK surgery testing the use of Healon viscoelastic (Bausch and Lomb Surgical, St. Louis, MO) rather than air to maintain the chamber, modifying the instrumentation, and adding an artificial anterior chamber for preparation of the donor tissue.14 In March 2000, Terry performed the first endothelial keratoplasty in the United States with this modified PLK technique that he renamed as deep lamellar endothelial keratoplasty (DLEK).15 Initially fluid was used to maintain the AC and air was used to unfold and attach the donor disk to the patient’s cornea. More recently, Terry M used Healon in the AC instead of fluid to maintain the AC in DSAEK.

In 2002, Melles et al16 modified his original PLK technique, to a smaller 5 mm incision technique by folding the donor corneal disk. Following Melles’ proposition of small incision and folded tissue insertion, Terry adopted this idea, moved the incision to the temporal side and advocated that the donor tissue be folded like a “taco,” in a 60/40 configuration to prevent “upside-down” unfolding.17 Terry went on to establish the legitimacy of DLEK surgery as an alternative to PKP with the largest prospective series in the world.17 John T first used indocyanine green (ICG) to stain the donor corneal stroma to facilitate better visualization of the donor corneal disk

through a cloudy cornea, to identify the stromal side from the endothelial side. For triple procedure of DLEK, phacoemulsification and PC IOL, John T. introduced a new technique which he called the upside-down phacoemulsification technique. Despite achieving good technical results with the DLEK surgery, irregularities in the surgical interface caused limitations in the Snellen visual acuity, and were deemed too difficult to perform by most surgeons.

In an attempt to improve the donor-recipient interface in PLK/DLEK surgery, Melles et al in 2004,18 stripped the recipient Descemet’s membrane and placed the donor corneal tissue directly onto the posterior surface of the cornea and again used an air bubble to help assist in the donor disk adherence to the patient’s cornea. Most importantly, manual dissection of the recipient cornea was eliminated, making the surgery much easier. These two factors were the major stimuli for the revised surgical technique to become popular and accelerated the interest in this type of surgery among most corneal surgeons. However, the increased ease of stripping Descemet’s membrane compared to manual lamellar dissection came at the price of increased postoperative complications of donor tissue dislocation and iatrogenic graft failure. This was especially true among corneal surgeons in the early part of their learning curve. Price et al confirmed the high rate of tissue dislocation to be above 50% especially in the initial series of cases.19 Price19 re-named the surgery Descemet’s stripping endothelial keratoplasty (DSEK) [See also Section 9, Descemet’s Stripping Automated Endothelial Keratoplasty (DSAEK)].

The artificial anterior chamber (AAC) was first introduced in 1976 by Ward and Nesburn.20 The AAC was developed for PKP to facilitate trephination from the epithelial side on both the donor and recipient corneas. It is a natural progression to use the AAC in DLEK surgery with manual dissection of the donor cornea. Jesus Vidauri working with Moria (Moria SA, Antony, France) first combined the use of a microkeratome with the Moria AAC

(personal communication, Moria SA). Subsequently, John T first used this combination of a Moria microkeratome and a Moria AAC for DLEK surgery (personal communication, Moria SA). DSEK, due to its relative simplicity over DLEK, soon became the dominant procedure for endothelial transplantation. Gorovoy21 used the microkeratome with the AAC in DSEK surgery and called it DSAEK, where the “A” represents automated. Presently, for the most part, donor corneal tissue for PLK procedures are prepared by the surgeon in the operating room or by a technician in the eye banks that distribute “pre-cut” tissues. The contribution of the AAC to the field of corneal transplantation further

Figure 14-4: LeftFirst modern day Textbook of Lamellar Keratoplasty [John T (Ed.)]; Right – Subsequent book on Step by Step Lamellar Keratoplasty.

Figure 14-5: John surgical instruments (ASICO Inc, Westmont, IL, USA) for posterior lamellar keratoplasty (Patent pending).

facilitated the advancement of modern day LKP. In 2006, Thomas John from Chicago, edited the first modern day textbook on lamellar keratoplasty (ALK & PLK) (Figure 14-4). He also designed various surgical instruments to facilitate DSAEK surgery (Figure 14-5). The unique curvature of the John Dexatome Spatula and the John DSAEK Scrubber (ASICO, Inc., Westmont, IL) (patent pending) allows easy access to all regions on the inner aspect of the patient’s corneal dome (Figure 14-5) (See also Chapter 11, New/Useful Surgical Instruments in DSAEK).”

DSAEK became the most popular procedure for endothelial keratoplasty (EK). The use of the microkeratome that was previously developed independently by Ramon Castroviejo and Jose I. Barraquer, improved the donorrecipient interface in both DLEK and DSAEK procedures.

Since 2006, the primary complications of donor dislocation and iatrogenic primary graft failure (IPGF)

following DSAEK surgery have been reported by multiple surgeons. In their most recent published series, surgeons using different DSAEK techniques reported different complication rates. Gorovoy has reported a dislocation rate of 25% and an IPGF rate of 6% in his initial series of 16 eyes.21 Koenig et al have reported a dislocation rate of 35% and an IPGF rate of 12% in their initial series of 26 eyes.22 Melles’ group has reported a dislocation rate of 14% and an IPGF rate of 14% in their series of 22 eyes.23 Looking at larger series, Price et al have reported a total dislocation rate of 11% and an IPGF rate of 3% in their initial retrospective series of 200 DSEK eyes24 and Terry et al have reported a dislocation rate of 1.5% and an IPGF rate of 0% in their initial prospective series of 200 DSAEK eyes.25 While it is tempting to say that a “learning curve” influenced the complication rates in all of these series, these disparate rates of complications likely reflect the variation in DSAEK surgical techniques rather than individual surgeon skill level, as the large Price series and the large Terry series included their initial DSAEK cases as well. In addition, the low complication rate of the Terry series (1.5% dislocations, 0% IPGF) included 4 surgeons (1 experienced and 3 novice) using the same DSAEK technique.25

Various surgical techniques have been advocated to reduce the DSAEK complication of dislocation including recommendations by Price and Price,24 namely, the removal of interface fluid with the use of recipient surface massage and full thickness, recipient cornea “venting” incisions (See also Chapter 27, Techniques to Facilitate Disk Adherence to Recipient Cornea in DSAEK). Terry and colleagues25,26 have recommended the use of peripheral recipient bed scraping to promote exposure of recipient stromal fibrils and peripheral donor edge adhesion. John T has described the wound architectural differences between DLEK and DSEK and compared the donor disk to a “pizza on the ceiling” and recommended the use of a large air bubble in the AC, especially during the intraoperative waiting period to enhance donor-recipient adhesion, much like holding a pizza on the ceiling with two hands. The air bubble size is subsequently decreased. Extended full chamber air bubble support postoperatively, followed by partial air release one hour later has been advocated by Gorovoy,21 but pupillary block glaucoma remains a risk with this technique and the rate of dislocation remains high at 25%, with an unknown toxic effect to the donor endothelium from prolonged air exposure. John T. utilizes a preoperative, inferior, peripheral laser iridotomy (recommended by Elizabeth Davis), combined with an intraoperative use of a large air bubble that fills 100% of the AC during the waiting time to facilitate donor disk attachment to the recipient corneal stroma. Inferior peripheral iridotomy is preferred since in the sitting

up position the air bubble moves to the superior region of the AC. Following this intra-operative waiting period the air bubble size is slightly reduced and replaced with BSS. John T combines this technique of large air bubble with roughening of the peripheral recipient corneal roughening (personal communication Terry, M) using the John DSAEK Scrubber (ASICO Inc., Westmont, IL).

Of greatest concern in DSAEK surgery is the acute and long term damage to the donor endothelium. The published 2 year prospective results reported by Terry et al27 on the endothelial survival in DLEK surgery on a large number of eyes (n=98) demonstrated that tissue inserted with folding through a 5 mm incision had much greater cell loss than tissue inserted through a 9.0 mm incision. In recent DSAEK surgery reports, surgeons are attempting to place donor tissue through an even smaller 3.0 mm clear corneal incision, using a variety of forceps, glides and “suture pull through” techniques.28-30 Mounting laboratory evidence indicates that tissue inserted through a 3.0 mm incision suffers extensively more overall acute damage to the donor endothelium than tissue inserted through a 5.0 mm incision, regardless of the method of insertion.31,32 Advances in technology with “tissue injectors” which avoid wound compression damage to donor tissue may allow safe use of 3 mm incisions DSAEK in the future.33,34 However, continued monitoring of the donor endothelium preand postoperatively will shed light as to the overall success of these techniques.

Long term donor endothelial cell death in DSAEK surgery is also of concern. Independently, Price35 and Terry36 have measured with central specular microscopy about a 35% loss of central endothelial cell density (ECD) 6 months after DSAEK surgery. While this cell loss may be stable from 6 to 12 months postoperatively,36 there appears to be a steady decline at 24 months and thereafter.35 In studies of EK, a plateau of this cell loss has not been documented (even out to 7 years) and the risk and rate of late endothelial graft failure in DSAEK surgery remains unknown.

In this journey of the history of corneal transplantation, the most recent “stop” is called “DMEK” or Descemet membrane endothelial keratoplasty. Melles et al, and Tappin et al [See also Chapter 36, True Endothelial Cell (TEnCell) Transplantation and Chapter 37, Descemet Membrane Endothelial Keratoplasty (DMEK)] have described the use of donor Descemet’s membrane with healthy endothelium and directly transplanting it to the patient’s cornea that is devoid of Descemet’s membrane and endothelium and attaching the donor tissue with an air bubble. This advanced surgical technique restores the patient’s cornea closer to the preoperative status with regard to the corneal thickness. Thus,

DLEK and DSAEK are additive procedures that result in an overall very thick cornea. In contrast, DMEK is a substitution procedure that restores the patient’s cornea back to its normal preoperative thickness. However, this surgical procedure is in its early developmental stage with various technical difficulties and hence it is not in the main stream of corneal transplant procedures. Busin recently simplified the technique of preparing the donor tissue [See also Chapter 37, Descemet Membrane Endothelial Keratoplasty (DMEK)] by using air injection to separate the donor Descemet’s membrane from the stroma, followed by trephination to obtain a donor disk of Descemet’s membrane and endothelium.

Recently, preparation of the donor tissue for DSAEK surgery has moved from the operating room to the distributing eye bank, with many eye banks offering “precut” tissue to the surgeon. While there was some concern initially that pre-cut tissue would swell en-route to the operating room and increase the complication rate,37 a recent publication by Chen and colleagues on their first consecutive 100 cases of DSAEK using pre-cut tissue demonstrated a dislocation rate of only 1% (1 case) and a primary graft failure rate of 0% (0 case).38 In extensive data analysis of donor characteristics, they also found that surgical technique is the overriding factor determining complications in DSAEK surgery, and that postoperative visual acuity, topography and refractive outcome were not correlated with any specific donor characteristic. However, it has to be kept in mind that in EK, the donor endothelial cells are the most important. When we use pre-cut donor corneal tissue we are transferring this important surgical step of donor disk preparation from the surgeon to eye bank technicians, and somewhat compromising the concept of “surgery by surgeons” (John T).

During this modern period of posterior lamellar keratoplasty transformation from DLEK to DMEK, it is of interest to mention that surgeons tried flap endokeratoplasty39,40 but it was short lived due to the limited clinical success of this surgical approach. Additionally, flap endokeratoplasty involved the creation of a surface corneal wound and surface corneal sutures.

A relatively new concept with the changing landscape of corneal transplant surgery is the use of a single donor cornea for three recipients.41 The anterior donor corneal cap for ALK surgery, the posterior disk for PLK surgery and the rim tissue for stem cell transplantation.41 Thus, one donor cornea can be used for three separate surgeries and in doing so, one has immediately tripled the donor corneal pool. Although, this approach of one donor cornea for multiple recipients is practiced in some parts of the world, it is currently not permitted in the United States

(personal communication with Illinois Eye Bank). Various surgical techniques are available for LKP42-44 and a review of these techniques would be beneficial for corneal surgeons who are interested in LKP.

As the readers can see, this journey from the “beginning of time” for corneal transplantation surgery to the present selective tissue corneal transplantation (STCT) surgery, is truly fascinating. It may continue to evolve where pure donor endothelial cells may one day be transplanted to the patient’s cornea or even more exciting may be the possibility of “exciting” and “rejuvenating” the patient’s endothelial cells to “re-energize” and reactivate and clear the patient’s cornea. Such dreams may one day become reality.

The various techniques in PLK have evolved due to the passion and hard work of corneal surgeons and the commitment of industry. Many other authors, who we did not have the opportunity to mention, were relevant in the development of our current knowledge on posterior lamellar techniques. To these colleagues and others, we extend our eternal gratefulness.

“In the end,

we will conserve only what we love, we will love only what we understand,

we will understand only what we are taught”

Baba Dioum

References

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27.Terry MA, Wall JM, Hoar KL, Ousley PJ. A prospective study of endothelial cell loss during the 2 years after deep lamellar endothelial keratoplasty. Ophthalmology 2007;114(4):631-9.

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33.Mehta JS, Thomas AS, Tan DT. Endothelial keratoplasty: Requirements of an insertion device. Ophthalmology 2008;115: 420.

34.Kuo AN, Harvey TM, Afshari NA. Novel delivery method to reduce endothelial injury in Descemet stripping automated endothelial keratoplasty. Am J Ophthalmol 2008;145:91-6.

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65.John T. Upside-down phaco with deep lamellar endothelial keratoplasty. Presented at the annual meeting of the American Society of Cataract and Refractive Surgery, San Francisco, CA, April 12-16, 2003.

66.Kaufman HE, Insler MS, Ibrahim-Elzembely HA, Kaufman SC. Human fibrin tissue adhesive for sutureless lamellar keratoplasty and scleral patch adhesion: A pilot study. Ophthalmology 2003;110:2168-72.

67.John T. New surgical technique: Use of indocyanine green and forced hydrodissection for total anterior lamellar keratoplasty. Presented at the Annual Meeting of the American Society of Cataract and Refractive Surgery (ASCRS), San Diego, CA, May 01-05, 2004.

68.John T. Use of fibrin glue in total anterior lamellar keratoplasty. Presented at the annual meeting of the American Academy of Ophthalmology, Chicago, Illinois, October 15–18, 2005.

69.John T. Use of indocyanine green (ICG) and forced hydrodissection in total anterior lamellar keratoplasty (TALK). Presented at the XXII Congress of the ESCRS, Paris, France, September 18-22, 2004.

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