Corneal transplantation, corneal grafting or keratoplasty is a surgical procedure in which a damaged or diseased cornea is replaced by a healthy corneal tissue from a recently deceased donor. Indications for a corneal transplantation include optical, tectonic, therapeutic or cosmetic indications. Optical reasons are the most frequent, and usually aim to improve the visual acuity, which has been compromised by bullous keratopathy, corneal dystrophies like Fuchs endothelial dystrophy, keratoconus, corneal degeneration, as well as scarring due to keratitis and trauma.
Corneal transplantation techniques developed mainly in the first part of the 20th century, with penetrating keratoplasty (PK) or full thickness keratoplasty as the golden standard surgery performed in most corneal diseases.1-4 However, in the last 30 years, innovative surgical techniques for corneal transplantation, that is, advanced lamellar keratoplasty techniques, were introduced, allowing the seldom replacement of the affected layers of the cornea;7 i.e. the anterior or the posterior portion of the cornea separately.5-10
Early efforts in corneal transplantation
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The idea of corneal transplantation was first thought of in the late 1700s,11 but the first attempts were not performed until the late 1800s. In 1813 and 1824, Himley and Reisinger introduced the term 'keratoplasty' into the world of ophthalmology. Attempts of corneal transplantation were performed using corneas of different animal species (heterografts). Most of these keratoplasty try-outs were not successful and ceased in the first half of the 19th century. In 1872, Henry Power reported his first experimental work on animals and humans,12 and in 1905 the first successful human penetrating keratoplasty was performed by Dr. Eduard Zirm in Slovakia.13 He performed two partial penetrating corneal transplants on Alois Glogar, who had been bilaterally blinded by a lime injury 15 months before.13 Another pioneer was Ramon Castroviejo from Spain, who did his first transplantation in 1936 in an advanced case of keratoconus, achieving significant improvement in patient's vision. He also devised numerous instruments, which were of great importance in the improvement of corneal surgery.14 A Russian eye surgeon, Vladimir Filatov, started with his first attempt in 1912 and continued until 1931 in which he successfully grafted a patient using corneal tissue from a deceased human donor. He is also considered to be the father of eye banking, and is credited with popularizing the use of cadaveric corneas for corneal transplantation.15,16
Corneal transplantation evolved dramatically in the 1940s, because of the availability of antibiotics and the introduction of steroids in corneal surgery. The last decades of the 20th century proved important for a better understanding of corneal anatomy and physiology, especially with regard to the corneal endothelium. Also the introduction of microsurgical techniques, advances in corneal preservation, clarification of corneal immunology, and the development of anti-inflammatory and immunosuppressive agents, resulted in a higher success rate of corneal grafting.5
In 1959, Townley Paton was the first to set up an eye bank in New York and in 1961 the Eye Bank Association of America (EBAA) was established.17 This organization developed the standards for obtaining, preserving, storing and using donor tissue, which significantly influenced the outcome of corneal transplant surgery. The specular microscope developed by Maurice, and the start of the eye bank made it possible to evaluate the endothelium and check the donor cornea's viability prior to surgery.18 The development of corneal preservation with the introduction of MK medium by McCarey and Kaufman in 1974 made it possible to plan surgeries.19 All this was of great importance in order to achieve a successful graft transplantation.
Techniques in corneal transplantation
Penetrating keratoplasty (PK) has been the preferred treatment method in corneal transplantation throughout the last century. Although technically often succesful, PK came with several disadvantages. First, it often presented with high astigmatism, a long term unstable refraction,20 as well as suture-related problems and ineffective wound healing. Secondly, the presence of an avascular graft-to-host wound reduced globe stability and beared the risk of wound dehiscence, even years after surgery. Furthermore, the visual rehabilitation was slow and the final outcome often dissapointing.1-4,20-22
Just to about 15 years ago, surgical treatment for posterior corneal diseases like pseudophakic bullous keratopathy and Fuchs dystrophy, was limited to PK.16 However, with the introduction of Posterior lamellar keratoplasty (LK), it was made possible to substitute only the diseased layers of the cornea. Charles Tillet was the first to carry out lamellar replacement of the endothelium underneath a stromal flap, in 1956,.23 Other early attempts were pioneerd in the 1960s by Barraquer et al., who used a similar approach.24 However these early efforts in PLK were relatively unsuccesful, and presented more technical difficulties when compared with PK, while PK provided a better quality of vision.25
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It was not until 1998, that an endothelial keratoplasty (EK) concept was described that proved clinically succesful, with the introduction of a new technique called posterior lamellar keratoplasty (PLK) by Melles et al,26-28 later popularized as deep lamellar endothelial keratoplasty (DLEK) in the United Stated in 2001 by Terry et al.29 Through a 9-mm sclerocorneal incision, a posterior lamella build of posterior stroma, Descemet membrane, and endothelium was dissected from the recipient´s cornea. A donor button build of the same tissue layers was then inserted in the recipient anterior chamber, and held in position by an air bubble, while the patient was laid down in a supine position.28 In 2000, this technique was modified by Melles et al., now using a 5-mm instead of 9-mm incision, and by folding the donor tissue like a taco to enable insertion.28 Terry et al. adopted the 5-mm DLEK, now called small incision DLEK.29-32 Promising results after DLEK were tempered by the technical difficulty of the procedure, which necessitated the manual lamellar dissection of both donor and host tissues.
To facilitate the EK-concept, and in particular to avoid the challenge of manually dissecting the host cornea, a new approach for removing the host diseased corneal endothelial by a 'descemetorhexis' was introduced by Melles et al. at the AAO 2003.33 After the descemetorhexis, ie scraping the host Descemet membrane with a reversed Sinkey hook from the posterior cornea, a donor posterior lamella similar to that used in DLEK was positioned onto the host denuded posterior stroma. This technique was later popularized by Price et al. as Descemet stripping endothelial keratoplasty (DSEK).33 This method for removing the host Descemet membrane is being still persued for removing the host diseased tissue in all currently used endothelial keratoplasty techniques.34
Meanwhile corneal tissue preparation techniques were further pioneered by Gorovoy et al., to enable the dissection of a donor lamella from a corneo-scleral button (in the absence of whole globes as available in The Netherlands). Instead of manually dissecting the donor tissue, a microkeratome assisted preparation technique was introduced, changing the nomenclature to Descemet stripping automated endothelial keratoplasty (DSAEK),35-38 and when the femtosecond laser became available, the Femto-second laser assisted Descemet stripping endothelial keratoplasty (FS-DSEK).39 With the development of these eyebank techniques, pre-cut donor tissue became available, permitting a decrease of surgical time and allowing full evaluation of the cornea prior to surgery, which better ensured the quality of the tissue.
The new EK techniques significantly improved clinical outcomes and also reduced the complication rate, when compared with conventional PK. Few or no sutures were used, which induced less suture related problems and minimal astigmatism. The absence of sutures at the junction between graft and host tissues limited the incidence of vascular ingrowth and reduced the incidence of graft rejections. The absence of a large full-thickness penetrating wound also lowered the risk of graft dehiscence. However, major drawbacks of the current DSEK/DSAEK techniques may be the suboptimal visual acuity, probably related to the presence of posterior stroma in the donor lenticule, as well as the need of expensive equipment to perform the surgery.
With further refinement of the endothelial keratoplasty concept in 2002, a selective transplantation of only Descemet with its endothelial cells was introduced by Melles et al., tentatively named Descemet membrane endothelial keratoplasty (DMEK) (Figure 1).40-43 Meanwhile, Studeny et al. refined DSEK to DMEK-S, a technique in which a manually dissected graft composed of an isolated Descemet membrane in the optical center with a stromal ring in the periphery, was transplanted.44 Later on, Da Reitz Pereira et al. and McCauley et al. described a modification of DMEK-S, in which the donor graft was partially dissected by a microkeratome, a technique popularized as Descemet membrane automated endothelial keratoplasty (DMAEK).45-47 Although DMEK-S/DMAEK surgery provided better visual outcomes compared to DS(A)EK and was suggested to be technically easier than DMEK, it faced a relatively high incidence of graft detachments, often requiring secondary air re-bubblings to achieve graft adherence.44,47 In the same time frame, DMEK was standardized as a 'no-touch' transplantation procedure, facilitating its feasibility and minimizing the risk of complications. The advantage of DMEK may be that it provides a near anatomical restoration of the host cornea, with a fast and nearly complete visual recovery and quick rehabilitation .As such, DMEK may have potential to become the preferred treatment for endothelial disorders within the next decade.
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Figure 1. Schematic figure of different techniques in corneal transplantation (LH: Cite ARTICLE here).
In short the current Posterior Lamellar Keratoplasty (PLK)/ Endothelial keratoplasty (EK) techniques
Deep lamellar endothelial keratoplasty (DLEK): Host posterior stromal dissection and removal thereof with its Descemet membrane and endothelium. The graft is build from the same tissue layers and inserted through a 9- or 5- mm incision .
Descemet stripping endothelial keratoplasty (DSEK): Stripping of host Descemet membrane and endothelium (descemetorhexis) and replaced by a manually dissected donor posterior transplant containing posterior stroma, Descemet membrane and endothelium.
Descemet stripping automated endothelial keratoplasty (DSAEK): same as DSEK but with this technique the donor posterior transplant is dissected with a microkeratome prior to surgery.
Femto-second laser assisted Descemet stripping endothelial keratoplasty FS-DSEK: same as DSEK but the donor is dissected by a femto-second laser prior to surgery.
Descemet membrane endothelial keratoplasty with a stromal rim (DMEK-S): the same as DS(A)EK, but the donor lamella is characterized by a denuded Descemet membrane in the optical center, carrying a stromal ring in the periphery.
Descemet membrane automated endothelial keratoplasty (DMAEK): the same as DMEK-S, but the donor is partially dissected with a microkeratome.
Descemet membrane endothelial keratoplasty (DMEK): the same as DSEK/DMEK-S/DMAEK, but the donor consists of only an isolated Descemet membrane and its endothelium.
What started in the 1700s and 1800s with an attempt in animals, took until the beginning of the 1900s, when the first human corneal transplantation was performed. Thus, for over 100 years, corneal transplantation was performed by PK. In the past decade, the field of corneal transplantation may have changed dramatically with the introduction of EK, in all of its current forms practiced today: DLEK, DS(A)EK, FS-DSEK, DMEK-S, DMAEK and DMEK. This latter technique, DMEK is the focus of this thesis, that aims to discuss most of the relevant issues regarding this new corneal transplantation technique.