Descemet’s Stripping Automated Endothelial Keratoplasty

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Review

www.expert-reviews.com ISSN 1746-9899© 2010 Expert Reviews Ltd10.1586/EOP.10.18

Federico Luengo Gimeno1,2, Michael Lang1, Jodhbir S Mehta†1,2,3 and Donald T Tan1,2,4

1Singapore Eye Research Institute, Singapore2Singapore National Eye Center, Singapore3Duke Medical School of Medicine, National University of Singapore, Singapore4Yong Loo Lin School of Medicine, National University of Singapore, Singapore†Author for correspondence:Tel.: +65 6227 7255 Fax: +65 6227 7290 [email protected]

Descemet’s stripping automated endothelial keratoplasty (DSAEK) is the gold standard for the surgical treatment of corneal endothelial diseases. Following its introduction over the last decade, DSAEK has evolved, showing excellent results in a variety of pathologies; for example, Fuchs’ endothelial dystrophy, pseudophakic bullous keratopathy, endothelial failure after penetrating keratoplasty or iridocorneal endothelial syndrome. Since it involves the use of a small incision that replaces only the affected part of the cornea, one of the advantages of this procedure is the rapid visual recovery compared with penetrating keratoplasty. DSAEK also poses major technical challenges to corneal surgeons and novel improvements are under the scope of researchers, such as the use of cultivated human corneal endothelial cells and the development of specific inserter devices to insert the endothelial graft. Owing to this innovation in endothelial keratoplasty surgery, a new chapter in the long history and evolution of corneal transplantation is upon us.

Keywords: corneal transplant • descemetorrhexis • Descemet’s stripping automated endothelial keratoplasty • endothelial cell culture • insertion devices • posterior corneal graft

Descemet’s stripping automated endothelial keratoplasty: past, present and futureExpert Rev. Ophthalmol. 5(3), 303–311 (2010)

endothelium. The current preferred technique of EK is called Descemet’s stripping automated endothelial keratoplasty (DSAEK), in which a posterior stromal donor lenticule is obtained by microkeratome dissection and is attached to the recipient posterior stromal surface after stripping removal of recipient Descemet’s mem-brane and endothelium [5–8]. DSAEK is rapidly gaining popularity as the treatment of choice over PK in the surgical management of corneal endothelial diseases such as Fuchs endothelial dystrophy, pseudophakic bullous keratopathy, endothelial failure after PK and iridocorneal endothelial syndrome [9]. Its advantages include the lack of sutures (hence no suture-related complications), faster visual rehabilitation, less surgically induced astigmatism and ametropia, less long-term risk of wound dehiscence and a reduced risk of intraoperative expulsive hemor-rhage [10]. With PK, patients’ corneal denerva-tion causes a neurotrophic status leading to epi-thelial complications, which is rarely seen in EK surgery [11].

Corneal transplantation has undergone a rapid advance in the last decade with the develop-ment of new procedures in the field of lamellar surgery, particularly posterior lamellar graft or endothelial keratoplasty (EK) for endo-thelial dysfunction. The paradigm shift in the increased use of these partial posterior corneal transplants is the beginning of a new era in corneal transplant surgery.

The principle behind partial thickness trans-plantation is to only replace the necessary affected tissue instead of the entire cornea. Currently, this takes several forms, such as using lamellar grafts of a donor cornea for total stromal replacement; EK, in which the endothelium is replaced by a lamellar donor graft; and using ex vivo expanded epithelial cellular sheets, cultivated from limbal stem cells [1,2] or oral mucosal epithelium [3,4], to replace the corneal epithelium.

In contrast to penetrating keratoplasty (PK), EK replaces only the diseased endo-thelium with a graft consisting of a thin layer of posterior stroma, Descemet’s membrane and

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Expert Rev. Ophthalmol. 5(3), (2010)304

Review Luengo Gimeno, Lang, Mehta & Tan

PastPenetrating keratoplasty has been the gold standard for visual rehabilitation following corneal diseases. Von Hippel performed the first transplant of a lamellar graft in 1886 [12]. However, it was Zirm who performed the first successful full-thickness human corneal transplant surgery in 1905 [13]. His technique spread and Castroviejo published his series of square penetrating grafts in the 1950s [14]. Since the original description of this surgery there have been some improvements in the technique, namely the change to a circular graft shape from a square and the incorporation of additional procedures, such as cataract extraction [15].

Penetrating keratoplasty offers the patient the benefit of optical rehabilitation but it also carries some risks, such as suture-related complications, anisometropia, long duration of visual rehabilita-tion, risk of intraoperative expulsive hemorrhage, and the long-term risk of corneal allograft rejection or wound rupture with minor trauma.

Tillett was the first surgeon to perform a successful EK in a human eye in 1956. This was performed by removing the recipi-ent posterior part of the cornea after making a partial thickness keratectomy of half of the cornea and then reflecting this inferi-orly. The recipient posterior cornea is then dissected manually. A partial thickness donor tissue is placed in the anterior chamber and sutured to the recipient anterior cornea [16]. Following this initial description, two approaches were taken to try to perfect the procedure. Some preferred replacing the endothelium from an anterior approach (similar to Tillett), while others pursued a technically more challenging posterior approach.

The former, termed endothelial lamellar keratoplasty or endo-keratoplasty, was first described by Polack, who performed a technique where he first fashioned an anterior corneal flap that was retracted to trephine the recipient posterior stroma, and then positioned a posterior lamellar donor corneal button. The original anterior flap was repositioned and sutured into place [17,18]. Jones et al. further improved the technique with the description of using a microkeratome, and the surgery was named microkeratome-assisted posterior keratoplasty [19,20]. However, the procedure was not without complications, and Busin et al. described a series of seven patients for whom flap complications such as epithelial ingrowth and corneal melting occurred at a rate of 14% [21]. Since the surgery involved a large incision, patients with this operation still suffered from suture-related complications, such as irregular astigmatism, ametropia and interface haze between the donor and host lamellae.

The second approach, the posterior one, was first described in a rabbit model by Ko et al. They used a scleral incision to access the endothelium and following removal they replaced it with a donor tissue [22]. Melles et al. named this approach posterior lamellar keratoplasty [23,24]. In Melles’ original description he per-formed a 9-mm limbal incision and made an air-guided dissec-tion of a stromal lamellar pocket. An intralamellar trephine and microscissors were placed in the pocket and the posterior stro-mal disc with the Descemet’s membrane and endothelium were removed. A same-diameter donor disc of posterior stroma and endothelium harvested from whole donor eye was then positioned

into the anterior chamber using a viscoelastic-covered spoon-shaped glide (Dutch Ophthalmic Research Center, Zuidland, The Netherlands). A large air bubble was subsequently injected into the anterior chamber to support the donor and tamponade it to the recipient stroma, and the limbal incision was sutured. Melles was the first to come up with a technique that did not require sutures to hold the donor graft in place. In a published series the transplanted lamellar disc remained attached for up to 12 months even following mild trauma. At 6–12 months follow-up the average postoperative astigmatism was 1.45 D and the average endothelial cell loss was 18% [25,26]. Terry and Ousley modified the technique described by Melles, developing a different line of instruments, specifically those used to prepare the donor tissue; they introduced the use of an artificial anterior chamber for donor harvesting. They also renamed this procedure deep lamellar endothelial keratoplasty [27,28].

Posterior lamellar keratoplasty was an innovative technique and changed the outlook of corneal transplantation for endothelial disease. However, there were still some issues such as the inter-face haze from donor–recipient lamellae, which lead to glare and opacity, the surgery was still relatively traumatic for the recipient and there was still relatively high surgery-induced astigmatism owing to the 9-mm incision. For these reasons, new attempts were made to refine posterior lamellar keratoplasty (deep lamel-lar endothelial keratoplasty) by replacing less recipient tissue and using a smaller incision.

PresentEndothelial surgery has now shifted to use smaller incisions and automated techniques. The aim of the modifications made was to improve the reproducibility of obtaining donor tissue and obtain a faster visual rehabilitation (Figure 1).

In 2002, in order to reduce the amount of surgically induced astigmatism, the limbal incision was reduced to 5 mm and curved scissors were used instead of the intrastromal trephine [29,30]. In turn, to use a smaller incision it was suggested that the donor disc could be folded and placed into the anterior chamber. There was an improvement in clinical results with respect to intraoperative safety, postoperative astigmatism, stability of refraction and visual acuity. The visual acuity results in particular were superior or at least equivalent to those obtained with PK [31,32]. However, there were concerns about increased endothelial cell loss from excessive donor manipulation in the anterior chamber.

The recipient dissection was still time consuming and the donor stromal bed was rough, so Melles et al. described a technique of providing a smoother donor interface – descemetorrhexis (Figure 2) [33]. In this technique, only the Descemet’s membrane is removed through a small limbal incision. Price and Price published the first clinical results with this technique and they renamed this modified EK as Descemet’s stripping endothelial keratoplasty (DSEK) [34]. This was a remarkable innovation since only the Descemet’s membrane is stripped from the recipient with less trauma to the recipient and it was theorized that a better opti-cal interface would result in improved visual outcomes due to less interface haze. Since the middle-anterior recipient corneal

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ReviewDescemet’s stripping automated endothelial keratoplasty: past, present & future

structure was not modified, secondary refractive surgery proce-dures could always be performed at a later date. However, Terry et al. published a large series study of 2 years of follow-up that the mean donor cell loss after DSEK was as high as 34% and appeared to remain stable for up to 1 year [35].

In 2006, endothelial surgeons started to use an automated motorized microkeratome to split the posterior lamella out from the donor cornea. The surgery was subsequently renamed DSAEK. This brought many improvements such as a smoother donor interface, a reduced surgical operative time and also a more predictable donor thickness, compared with manual dissection. It is believed that DSAEK could have lower rates of allograft rejection in corneal transplants for endothelial failure [36]. With the advent of femtosecond lasers, Mehta et al. and Cheng et al. have described the possibility of further improving the donor quality by using a femtosecond laser to cut the tissue (Figure 3).

They have both shown better accuracy of donor thickness com-pared with microkeratome-cut tissue but nomograms are still being developed to improve the quality of the donor stromal bed [37]. Other authors suggested that use of the femtosecond laser resulted in poorer visual acuity and that it is a more expen-sive approach [38,39]. Since the preparation of donor tissue is one of the most important parts of the procedure of DSAEK and it requires a vast amount of experience to obtain it, there are some eye banks that can send the donor tissue precut. They obtain this tissue by either femtosecond laser or microkeratome with minimal cell loss at 2 days, but there are still no large randomized studies to demonstrate its usefulness [40,41].

The main concern regarding the use of DSAEK remains the rate of postoperative endothelial cell loss [42]. There have been several publications showing endothelial cell loss to be in the range of 24–50% at 12–24 months. At 1 year post DSAEK, Bahar et al. published 36% cell loss [43], Busin et al. reported

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24% cell loss [44], Covert and Koening published 57% [45,46] and Gorovoy et al. 40% [47]. At 2 years, the rate of endothelial cell loss is between 41 (Price and Price [48]) and 36% (Terry et al. [49,50]). The greatest endothelial cell loss seems to occur during donor insertion, hence several surgeons have described different tech-niques to circumvent this [42]. Some authors have persevered in the use of a folding technique but with the use of noncrushing forceps [51]. These forceps have been designed so that they do not oppose along their entire length to minimize contact with the tissue and so minimize donor endothelium loss. However, this does not obviate the problem of further manipulation of unfolding the donor in the anterior chamber. Other authors have approached this problem using novel insertion techniques.

Harvey described insertion of the poste-rior lamellar button using a nylon suture loop pulled by a hook through a Monarch II B Cartridge (Alcon Laboratories, TX, USA) [52]. Vajpayee et al. used a stitch loop to help unfold the DSAEK lenticule, already inserted with forceps [53]. Macsai et al. [54] and Kaiserman et al. [55] used a stitch to introduce the lenticule without the use of forceps [54,55]. Mehta et al. described a modified sheet glide to introduce the unfolded graft (Figure 4) [56]. Recently, Bahar et al. incorporated the use of a Busin glide (Moria Inc., Antony, France) and a trac-tion suture without forceps to insert the donor [57]. Balachandran et al. published a simple technique using a plastic guide

and a 30-gauge needle to insert the donor posterior lamellar disk into the anterior chamber and also to unfold it [58]. Many tech-niques have been described but few have long-term endothelial cell-loss data; nevertheless, the short-term results seem to show an improvement in unfolded lenticules compared with conventional donor folding [59].

Recently, several novel DSAEK donor insertion devices have been described, and at least eight different devices are currently undergoing clinical trials, mainly in the USA. Most of these devices utilize a ‘donor push’ concept in which donor tissue is rolled into a circular inserter device, similar in nature to intraocular lens inserters or injectors, and are pushed or propelled into the anterior chamber by a plunger or irrigation mechanisms akin to a phacoemulsification

handpiece. Such devices at various stages of clinical trials include the Shiuey Endoshield (Keramed, CA, USA), the Neusidl Corneal Insertion Spatula (Fisher Surgical, MO, USA), the Harvey Steinert Injector (Rhein Medical, FL, USA), the Kaneka Ide Injector (Kaneka Corporation, Osaka, Japan), the Al-Ghoul Injector (Ension, PA, USA), and the EndoSaver Injector device (Network Medical Products, NC, USA). Other devices advocate an alternative ‘donor pull-through’ approach. This includes the currently available Busin Glide (Moria Inc.), a metal shovel-shaped instrument that facilitates donor coiling and is used as a donor carrier to be placed outside the wound, with the donor being pulled through the wound into the eye using intraocular forceps, introduced from the nasal limbus out through the temporal wound, to grasp and pull in the donor. The Tan EndoGlide (Network Medical Products) is another pull-through device currently approved for clinical use, which uses a disposable transparent plastic coiling

Figure 3. A posterior donor disc obtained by femtosecond laser. With the femtosecond laser it is possible to obtain a 150-µm posterior lenticule after making vertical and lamellar trephination. (A) A smooth stromal surface can be observed. (B) Lamellar edges showing the vertical trephination.

Figure 4. The unfolded donor lenticule on a bed of viscoelastic is introduced into the anterior chamber. A modified sheet glide is used as a donor carrier through a 5-mm wound and an intraocular forceps is used to pull in the donor.



chamber in which the donor is coiled in a unique double-coil configuration reducing endothelial-to-endothelial touch. The EndoGlide is inserted through a 4.5-mm temporal wound with the help of an anterior glide, and the donor is pulled in by forceps introduced from the nasal limbus (Figure 5). Early unpublished clinical results suggest a significant reduction of endothelial cell loss below 20% at 6 months, compared with Busin glide and folding studies that report endothelial cell loss rates between 25 and 35% [Tan D, Pers. Comm.].

The problem with DSAEK is that we are exchanging the recipient Descemet’s membrane and endothelial cells with donor stroma, Descemet’s membrane and endothelial cells. In order to obtain a more anatomical transplantation, Melles et al. described a new technique called Descemet’s membrane endothelial kerato-plasty (DMEK) [60]. In the DMEK procedure, a 9.0-mm diam-eter flap of Descemet’s membrane with its endothelial monolayer is stripped from the posterior stroma following storage in culture medium [61]. During surgery, the Descemet’s roll is transferred to the anterior chamber by a 3-mm tunnel incision (already used for the recipient 9.0-mm diameter descemetorrhexis). The graft is placed over the iris and is manipulated by air to unroll it and posi-tion it onto the recipient posterior stroma. Many advantages are proposed for DMEK since a large graft may be utilized composed only of Descemet’s and endothelial cells, and this is transplanted using a small incision. Melles et al. [62] and Price et al. [63] recently reported 2-year results showing faster visual rehabilitation and higher rates of 20/20 and 20/25 vision (≥20/30 at 1 month in 43% and at 2 years in 86%) compared with PK, with a near-perfect anatomical restoration of the recipient cornea. There is also no need for specialized equipment, such as microkeratome or femtosecond laser, to obtain the donor [64]. However, compli-cation rates are still high with this new procedure, with a 20% detachment rate, and long-term graft survival may be affected by an equivalent endothelial cell loss compared with DSAEK (35% cell loss at 2 years) [64]. Recently, Studene et al. described a new technique to obtain the donor tissue in 20–30 min, without using either microkeratome or femtosecond laser. They obtain an endothelium and Descemet’s membrane with a stromal support-ing rim using a modified big bubble technique. This technique, called DMEK-S, involves mounting the donor corneoscleral discs endothelial side up in a Barron artificial anterior chamber (Katena, NJ, USA). The separation of Descemet’s membrane and stroma is performed by the big bubble technique, placing a 1-cc insulin syringe (B Braun, Melsungen, Germany) in the far periphery of the donor disc. The corneoscleral disc is then turned up and 80% of the upper thickness of the donor cornea is cut off using a crescent knife (Huco, St. Blaise, Switzerland), followed by the perforation of the 6-mm central stroma with a cornea diamond knife (Huco) to reach the big bubble. Finally, a cyclospatula (Jezek, Jistebnice, Czech Republic), as an alter-native to a grooved spatula, is used to incise the stromal body and the donor disc is trephined by a Barron disposable punch (Katena). With this procedure, the authors obtained a best cor-rected visual acuity of 1.0 or better in ten out of 18 eyes, and 17 reached 0.5 or better at 1 year. Primary graft failure occurred Fi

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in two eyes. The average endothelial cell count at 1 year was 1608 ± 503 cells/mm2, a mean cell loss from preoperative values of 44% [65]. At this time, DSEK/DSAEK offers a more refractive neutral procedure, the possibility of a quicker visual rehabilitation and a lower risk of intraoperative complications compared with conventional PK [66].

FutureNew innovations in technology and pharmaceuticals are continu-ally improving surgical outcomes and they offer the potential for expanding the field of human corneal transplantation to the next level.

Although human corneal endothelium is believed to have minimal regenerative capacity in vivo [67], recent studies confirm that human corneal endothelial cells (HCECs) do retain the capacity to proliferate [68–70] and different techniques for grow-ing HCECs in vitro have been reported [71]. Preclinical studies in rabbits implanted with HCECs have shown variable results, as even though the HCECs demonstrated physiological function, the innate proliferative capacity of rabbit endo thelium may have influenced the results [72,73]. However, primates offer a similar model to HCECs and, like humans, they have a limited pro-liferative activity, thus several monkey endothelial dysfunction models have been described. The use of cultured HCEC grafts in the treatment of primate endothelial disease has been suc-cessfully employed as proof of principle [74]. In summary, some advances have been achieved with this innovative regenerative treatment and they offer the possibility of using an autologous tissue on this new and promising therapy [75,76], even though more primate and in vitro studies are still required to estab-lish a treatment of proven efficacy. Once this is established, a clinical study in patients with endothelial dysfunction could be started. In the future, precursor endothelial cells from embry-onic or other multipotent stem cells could also be used to replace the endothelium.

As HCEC culture techniques advance, new ideas emerge. In the last 2 years many researchers have developed drug delivery devices. Most of them are made of gelatin and can be used as endothelial cell carriers that at the same time are able to release diverse pharmaceutical compounds (Figure 6) [77,78].

Although the main concern currently surrounding DSAEK remains the rate of postoperative endothelial cell loss [79], it is likely that this issue will be solved soon with the advancement of novel donor insertion techniques. There are many reports describ-ing the use of genetically modified endothelial cells that have been shown to have reduced cell injury after transplantation and gene therapy has been used successfully to prolong experimental corneal allograft survival by decreasing corneal endothelial cell damage following surgery implantation [80–82].

Endothelial keratoplasty, with its inherent major advantages over conventional PK, now poses major technical challenges to corneal surgeons and novel scientific improvements are continu-ously published. Due to the innovation of EK surgery, a new chap-ter in the long history and evolution of corneal transplantation is upon us.

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ReferencesPapers of special note have been highlighted as:• of interest•• of considerable interest

1 Shortt A, Secker G, Notara M. Transplantation of ex vivo cultured limbal epithelial stem cells: a review of techniques and clinical results. Surv. Ophthalmol. 52, 483–502 (2007).

2 Pellegrini G, Traverso CE, Franzi AT. Long-term restoration of damaged corneal surfaces with autologous cultivated corneal epithelium. Lancet 349, 990–993 (1997).

3 Nakamura T, Endo K, Cooper LJ et al. The successful culture and autologous transplantation of rabbit oral mucosal epithelial cells on amniotic membrane. Invest. Ophthalmol. Vis. Sci. 44, 106–116 (2003).

4 Higa K, Shimazaki J. Recent advances in cultivated epithelial transplantation. Cornea 27, S41–S47 (2008).

5 Melles GR, Wijdh RH, Nieuwendaal CP. A technique to excise the Descemet membrane from a recipient cornea (descemetorhexis). Cornea 23, 286–288 (2004).

6 Price FW Jr, Price MO. Descemet’s stripping with endothelial keratoplasty in 200 eyes: early challenges and

techniques to enhance donor adherence. J. Cataract Refract. Surg. 32, 411–418 (2006).

7 Price MO, Price FW Jr. Descemet’s stripping with endothelial keratoplasty: comparative outcomes with microkeratome-dissected and manually dissected donor tissue. Ophthalmology 113, 1936–1942 (2006).

8 Gorovoy MS. Descemet-stripping automated endothelial keratoplasty. Cornea 25, 886–889 (2006).

9 Mau K. What DSAEK is going on? An alternative to penetrating keratoplasty for endothelial dysfunction. Optometry 80, 513–523 (2009).

10 Price FW, Price MO. Descemet’s stripping with endothelial keratoplasty in 50 eyes: a refractive neutral corneal transplant. J. Refract. Surg. 21, 339–345 (2005).

11 Martin XY, Safran AB. Corneal hypoesthesia. Surv. Ophthalmol. 33, 28–40 (1988).

12 Von Hippel A. Über transplantationen der kornea. Ber. Ophthalmol. Ges. Heidelberg 18–54 (1886).

13 Zirm E. Eine erfolgreiche totale keratoplastik. Arch. Ophthalmol. 64, 580–593 (1906).

14 Castroviejo R. Keratoplasy for the treatment of keratoconus. Trans. Am. Ophthalmol. Soc. 46, 127–153 (1948).

15 Malbran ES, Malbran E, Buonsanti J, Adrogué E. Closed-system phaco-emulsification and posterior chamber implant combined with penetrating keratoplasty. Ophthalmic Surg. 24, 403–406 (1993).

16 Tillet CW. Posterior lamellar keratoplasty. Am. J. Ophthalmol. 41, 530–533 (1956).

17 Polack FM. Queratoplastia lamellar posterior. Revista Peruana Oftalmologia 2, 62–64 (1965).

18 Polack FM, Smelser GK, Rose J. Long-term survival of isotopically labeled stromal and endothelial cells in corneal homografts. Am. J. Ophthalmol. 57, 67–78 (1964).

19 Jones DT, Culbertson WW. Endothelial lamellar keratoplasty (ELK). Invest. Ophthalmol. Vis. Sci. 39, S76 (1998) (Abstract 342).

20 Azar DT, Jain S, Sambursky R. A new surgical technique of microkeratome-assisted deep lamellar keratoplasty with a hinged flap. Arch. Ophthalmol. 118, 1112–1115 (2000).

Key issues

• On a worldwide basis, penetrating keratoplasty (PK) remains the gold standard treatment for endothelial dysfunction, but Descemet’s stripping automated endothelial keratoplasty is rapidly growing in use, and is likely to supersede PK in the future surgical management of corneal endothelial diseases owing to faster visual rehabilitation, less surgically induced astigmatism and stronger globe integrity.

• Improvements in the surgical technique are still occurring, such as the use of femtosecond laser to cut the donor or the use of insertion devices to avoid excessive manipulation of the implant.

• Endothelial cell culture endothelial keratoplasty technology offers an exciting future for transplantation surgery.

Expert commentaryDescemet’s stripping automated endothelial keratoplasty is a small-incision surgery that replaces only the affected part of the cornea. One of the advantages of this procedure is the rapid visual recovery and a reduced incidence of graft rejection compared with PK. Following its introduction over the last decade, DSAEK has become embraced worldwide as the preferred method for treating endothelial dysfunction. Indications include Fuchs’ endothelial dystrophy, pseudophakic bullous keratopathy, endothelial failure after PK and iridocorneal endothelial syndrome. DSAEK provides quicker rehabilitation and an improved safety profile compared with standard PK.

Smaller incisions, donor insertion devices, femtosecond laser donor cutting, more anatomical transplants and bioengineered endothelial cell implants are continually improving surgical outcomes and they offer the potential for expanding the field of human corneal transplantation in the next millennium.

Five-year viewCorneal endothelial transplantation has undergone dramatic improvements in the last decade and is becoming widely embraced as the preferred surgical therapeutic treatment for many corneal endothelial diseases. It is our impression that EK surgery has caused a technical revolution in transplantation surgery. Over the next 5 years DSAEK will become the gold standard for endothelial replacement worldwide.

Financial & competing interests disclosureJodhbir S Mehta and Donald T Tan have financial interest in the Tan EndoGlide (Network Medical Products, Ripon, North Yorkshire, UK). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.



21 Busin M, Arffa RC, Sebastiani A. Endokeratoplasty as an alternative to penetrating keratoplasty for the surgical treatment of diseased endothelium: initial results. Ophthalmology 107, 2077–2082 (2000).

22 Ko W, Freuh B, Shield C, Costello M, Feldman S. Experimental posterior lamellar transplantation of the rabbit cornea. Invest. Ophthalmol. Vis. Sci. 34, 1102 (1993).

• Firstauthorperformingaposteriorcorneallamellartransplantinanimals.

23 Melles GR, Eggink FA, Lander F et al. A surgical technique for posterior lamellar keratoplasty. Cornea 17, 618–626 (1998).

•• FirstauthordescribingtheposteriorlamellarkeratoplastysurgeryfromwhichDescemet’sstrippingautomatedendothelialkeratoplasty(DSAEK)wouldbeborn.

24 Melles GR, Lander F, van Dooren BT, Pels E, Beekhuis WH. Preliminary clinical results of posterior lamellar keratoplasty through a sclerocorneal pocket incision. Ophthalmology 107, 1850–1856 (2000).

25 Terry M, Ousley P. Deep lamellar endothelial keratoplasty causes minimal surface topography changes. Presented at: 25th Annual Session of the Castroviejo Corneal Society. Orlando, FL, USA, 23 October 1999.

26 van Dooren B, Melles G, Lander F, Beekhuis W, Binder P. Preliminary clinical results of posterior lamellar keratoplasty. Invest. Ophthalmol. Vis. Sci. 40, S632 (1999).

27 Terry MA, Ousley PJ. Deep lamellar endothelial keratoplasty in the first United States patients: early clinical results. Cornea 20, 239–243 (2001).

• Improvedthesurgicalinstrumentation,specificallythoseusedinthepreparationofthedonortissue.Introducedtheuseofanartificialanteriorchamberfordonorharvesting.

28 Terry MA, Ousley PJ. Replacing the endothelium without corneal surface incisions or sutures: the first United States clinical series using the deep lamellar endothelial keratoplasty procedure. Ophthalmology 110, 755–764 (2003).

29 Melles GR, Lander F, Nieuwendaal C. Sutureless, posterior lamellar keratoplasty: a case report of a modified technique. Cornea 21, 325–327 (2002).

30 Terry MA, Ousley PJ. Small-incision deep lamellar endothelial keratoplasty (DLEK): six-month results in the first prospective clinical study. Cornea 24, 59–65 (2005).

31 Terry MA, Ousley PJ. In pursuit of emmetropia: spherical equivalent refraction results with deep lamellar endothelial keratoplasty (DLEK). Cornea 27, 619–626 (2003).

32 Terry MA, Ousley PJ. Rapid visual rehabilitation after endothelial transplants with deep lamellar endothelial keratoplasty (DLEK). Cornea 23, 143–153 (2004).

33 Melles GR, Wijdh RH, Nieuwendaal CP. A technique to excise the Descemet membrane from a recipient cornea (descemetorrhexis). Cornea 23, 286–288 (2004).

•• Descemetorrhexisisintroduced.

34 Price FW Jr, Price MO. Descemet’s stripping with endothelial keratoplasty in 50 eyes: a refractive neutral corneal transplant. J. Refract. Surg. 21, 339–345 (2005).

•• FirstDescemet’sstrippingendothelialkeratoplasty(DSEK)clinicalresultsarepublished.

35 Terry MA, Chen ES, Shamie N, Hoar KL, Friend DJ. Endothelial cell loss after Descemet’s stripping endothelial keratoplasty in a large prospective series. Ophthalmology 115, 488–496 (2008).

36 Prakash G, Jhanji V, Titiyal JS. Will Descemet’s stripping with automated endothelial keratoplasty (DSAEK) lower the rates of allograft rejection in corneal transplants for endothelial failure? Med. Hypotheses 69, 1117–1119 (2007).

37 Mehta JS, Shilbayeh R, Por YM, Cajucom-Uy H, Beuerman RW, Tan DT. Femtosecond laser creation of donor cornea buttons for Descemet-stripping endothelial keratoplasty. J. Cataract Refract. Surg. 34, 1970–1975 (2008).

• Thefemtosecondlaserisintroducedtoobtainthedonortissue.

38 Cheng YY, Hendrikse F, Pels E et al. Preliminary results of femtosecond laser-assisted Descemet stripping endothelial keratoplasty. Arch. Ophthalmol. 126, 1351–1356 (2008).

39 Cheng YY, Pels E, Nuijts RM. Femtosecond-laser-assisted Descemet’s stripping endothelial keratoplasty. J. Cataract Refract. Surg. 33, 152–155 (2007).

40 Suwan-Apichon O, Reyes JM, Griffin NB, Barker J, Gore P, Chuck RS. Microkeratome versus femtosecond laser predissection of corneal grafts for anterior and posterior lamellar keratoplasty. Cornea 25, 966–968 (2006).

41 Rose L, Briceño CA, Stark WJ, Gloria DG, Jun AS. Assessment of eye bank-prepared posterior lamellar corneal tissue for endothelial keratoplasty. Ophthalmology 115, 279–286 (2008).

42 Terry MA, Saad HA, Shamie N et al. Endothelial keratoplasty: the influence of insertion techniques and incision size on donor endothelial survival. Cornea 28, 24–31 (2009).

43 Bahar I, Kaiserman I, McAllum P et al. Comparison of posterior lamellar keratoplasty techniques to penetrating keratoplasty. Ophthalmology 115, 1525–1533 (2008).

44 Busin M, Bhatt PR, Scorcia V. A modified technique for Descemet membrane stripping automated endothelial keratoplasty to minimize endothelial cell loss. Arch. Ophthalmol. 126, 1133–1137 (2008).

45 Covert DJ, Koenig SB. Descemet stripping and automated endothelial keratoplasty (DSAEK) in eyes with failed penetrating keratoplasty. Cornea 26, 692–696 (2007).

46 Koenig SB, Covert DJ, Dupps WJ Jr, Meisler DM. Visual acuity, refractive error, and endothelial cell density six months after Descemet stripping and automated endothelial keratoplasty (DSAEK). Cornea 26, 670–674 (2007).

47 Gorovoy MS. Descemet-stripping automated endothelial keratoplasty. Cornea 25, 886–889 (2006).

48 Price MO, Price FW. Endothelial cell density after Descemet’s stripping endothelial keratoplasty: influencing factors and two-year trend. Ophthalmology 115, 857–865 (2008).

49 Terry MA, Shamie N, Chen ES et al. Endothelial keratoplasty: the influence of preoperative donor endothelial cell densities on dislocation, primary graft failure, and 1-year cell counts. Cornea 27, 1131–1137 (2008).

50 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 114, 631–639 (2007).

51 Ide T, Yoo SH, Goldman JM, Perez V, O’Brien TP. Descemet-stripping automated endothelial keratoplasty: effect of inserting forceps on DSAEK donor tissue viability by using an in vitro delivery model and vital dye assay. Cornea 26, 1079–1081 (2007).

52 Harvey TM. Small incision insertion of posterior lamellar button. J. Refract. Surg. 22, 429 (2006).



53 Jhanji V, Greenrod E, Sharma N, Vajpayee RB. Modifications in the surgical technique of DSAEK. Br. J. Ophthalmol. 92, 1311 (2008).

54 Macsai MS, Kara-Jose AC. Suture technique for Descemet stripping and endothelial keratoplasty. Cornea 26, 1123–1126 (2007).

55 Kaiserman I, Bahar I, McAllum P, Slomovic AR, Rootman DS. Suture-assisted vs forceps-assisted insertion of the donor lenticula during Descemet stripping automated endothelial keratoplasty. Am. J. Ophthalmol. 145, 986–990 (2008).

56 Mehta JS, Por YM, Beuerman RW, Tan DT. Glide insertion technique for donor cornea lenticule during Descemet’s stripping automated endothelial keratoplasty. J. Cataract Refract. Surg. 33, 1846–1850 (2007).

57 Bahar I, Kaiserman I, Sansanayudh W, Levinger E, Rootman DS. Busin guide vs forceps for the insertion of the donor lenticule in Descemet stripping automated endothelial keratoplasty. Am. J. Ophthalmol. 147, 220–226 (2009).

58 Balachandran C, Ham L, Birbal RS, Wong TH, van der Wees J, Melles GR. Simple technique for graft insertion in Descemet-stripping (automated) endothelial keratoplasty using a 30-gauge needle. J. Cataract Refract. Surg. 35, 625–628 (2009).

59 Dapena I, Ham L, Melles GR. Endothelial keratoplasty: DSEK/DSAEK or DMEK: the thinner the better? Curr. Opin. Ophthalmol. 20, 299–307 (2009).

60 Melles GR. Posterior lamellar keratoplasty: DLEK to DSEK to DMEK. Cornea 25, 879–881 (2006).

• Descemet’smembraneendothelialkeratoplastyisdescribedforthefirsttime,whichconsistsofamoreanatomicaltransplant.MellescompareshisresultsfromdeeplamellarendothelialkeratoplastyandDSEK/DSAEKresults.

61 Melles GR, Ong TS, Ververs B, van der Wees J. Descemet membrane endothelial keratoplasty (DMEK). Cornea 25, 987–990 (2006).

62 Dapena I, Ham L, Lie J, Van-Der-Wees J, Melles GR. Descemet membrane endothelial keratoplasty (DMEK): two-year results. Arch. Soc. Esp. Oftalmol. 84, 237–243 (2009).

63 Price MO, Giebel AW, Fairchild KM, Price FW. Descemet membrane endothelial keratoplasty: prospective multicenter study of visual and refractive outcomes and endothelial survival. Ophthalmology 116, 2361–2368 (2009).

64 Ham L, van Luijk C, Dapena I et al. Endothelial cell density after Descemet membrane endothelial keratoplasty: 1- to 2-year follow-up. Am. J. Ophthalmol. 148, 521–527 (2009).

65 Studeny P, Farkas A, Vokrojova M, Liskova P, Jirsova K. Descemet’s membrane endothelial keratoplasty with a stromal rim (DMEK-S). Br. J. Ophthalmol. DOI: 10.1136/bjo.2009.165134 (2009) (Epub ahead of print).

66 Shih CY, Ritterband DC, Palmiero PM et al. The use of postoperative slit-lamp optical coherence tomography to predict primary failure in Descemet stripping automated endothelial keratoplasty. Am. J. Ophthalmol. 147, 796–800 (2009).

67 Kaufman HE, Capella JA, Robbins JE. The human corneal endothelium. Am. J. Ophthalmol. 61, 835–841 (1966).

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70 Zhu C, Rawe I, Joyce NC. Differential protein expression in human corneal endothelial cells cultured from young and older donors. Mol. Vis. 14, 1805–1814 (2008).

71 Engelmann K, Bednarz J, Valtink M. Prospects for endothelial transplantation. Exp. Eye Res. 78, 573–578 (2004).

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73 Hitani K, Yokoo S, Honda N, Usui T, Yamagami S, Amano S. Transplantation of a sheet of human corneal endothelial cell in a rabbit model. Mol. Vis. 14, 1–9 (2008).

74 Koizumi N, Sakamoto Y, Okumura N et al. Cultivated corneal endothelial transplantation in a primate: possible future clinical application in corneal endothelial regenerative medicine. Cornea 27, S48–S55 (2008).

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•• Preliminaryresultsshowsthattransplantationofcultivatedhumancornealendothelialcellscouldbeatherapeuticoptioninthefuture.

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78 Natu MV, Sardinha JP, Correia IJ, Gil MH. Controlled release gelatin hydrogels and lyophilisates with potential application as ocular inserts. Biomed. Mater. 2, 241–249 (2007).

79 Terry MA, Saad HA, Shamie N et al. Endothelial keratoplasty: the influence of insertion techniques and incision size on donor endothelial survival. Cornea 28, 24–31 (2009).

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81 Parker DG, Brereton HM, Coster DJ, Williams KA. The potential of viral vector-mediated gene transfer to prolong corneal allograft survival. Curr. Gene Ther. 9, 33–44 (2009).

82 Koh SW, Chandrasekara K, Abbondandolo CJ, Coll TJ, Rutzen AR. VIP and VIP gene silencing modulation of differentiation marker N-cadherin and cell shape of corneal endothelium in human corneas ex vivo. Invest. Ophthalmol. Vis. Sci. 49, 3491–3498 (2008).

Descemet’s Stripping Automated Endothelial Keratoplasty

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