Descemet membrane endothelial keratoplasty (DMEK) has been increasing in popularity as the treatment of choice for endothelial disease and corneal edema over the past several years—from 344 cases (0.7% of all keratoplasty procedures) performed in the United States in 2011 to 2,865 cases (6.2% of all keratoplasty procedures) performed in 2014.¹ This trend is likely due to the potential benefits of DMEK compared with penetrating keratoplasty and Descemet stripping endothelial keratoplasty (DSEK), including faster visual recovery and better quality vision with minimal refractive change.^2-6

DMEK is not without its compromises, however, which include difficult graft creation, higher primary graft failure and rebubbling rates, and a steeper learning curve compared with Descemet stripping automated endothelial keratoplasty (DSAEK).^7,8 To deal with these potential problems, great attention has been paid by DMEK pioneers to improve donor graft preparation and surgical techniques. With these advances, good outcomes can be achieved for patients by their aspiring DMEK surgeons.

GRAFT PREPARATION

Perhaps one of the most critical steps of DMEK is the preparation of the donor graft, which is extremely fragile and can easily be torn or damaged. They can be prepared reliably, however, with minimal tissue wastage and acceptable levels of endothelial cell loss.

Graft preparation has evolved from Melles’ original description in 2006 to its most utilized current form, which involves widely scoring and peeling Descemet membrane followed by trephination. This eliminates the direct handling of the graft until right before it is loaded into the injector.^9,10 The success rate of preparing tissue in this manner by a single high-volume surgeon in the OR has been reported to approach 99%.¹¹ This result, however, might not reflect the same experiences as that of a lower-volume DMEK surgeon, who only occasionally prepares tissue. For this reason, an increasing number of eye banks in the United States have started to prepare prestripped DMEK donor tissue, offering surgeons reliable access to quality tissue in the same light that helped propagate the popularity of DSAEK. The results of using prestripped tissue have been promising.^12,13

Additional techniques performed at the time of graft preparation have been described to help the surgeon in the OR, specifically to aid in the determination of correct orientation of the graft inside the eye. For example, punching three asymmetrically placed notches at the edge of the graft can help verify orientation after unfolding in the anterior chamber.¹⁴ Also, the stamping of a gentian violet ‘S’ on the stromal side of Descemet membrane at the time of graft preparation can easily provide confidence in the graft orientation by direct visualization. The ‘S’ stamp has not been associated with significant endothelial cell loss and shows promise of preventing iatrogenic primary graft failure due to upside-down grafts.¹⁵

SURGICAL TECHNIQUE

One of the most significant barriers that many corneal surgeons perceive as a deterrent to performing DMEK is its technical difficulty and steep learning curve.¹⁶ Are the potential benefits of a more anatomic end result worth the risk to the more fragile graft? Studies suggest that DMEK outcomes rival those of DSEK, without a significant increase in complications or endothelial cell loss.^8,17

In one series of 450 consecutive cases that were performed after an initial learning curve of 25 cases, postoperative visual results, reduction of endothelial cell counts, and complication rates were examined. The 450 cases were divided into three groups: (1) an extended learning curve group (cases 1–125), (2) a transition to technique standardization group (cases 126–250), and (3) a standardized technique group (cases 251–450). There was no statistically significant difference among the three groups in visual acuity outcomes or percentage of endothelial cell reduction. Graft detachment rates did trend lower with more experience but did not reach statistical significance (P=.06), suggesting that improved patient outcomes might be appreciated early in the learning process despite the initial rates of rebubbling.¹⁸ Several groups have recently reported successful results with their standardized techniques.^19-22 Further prospective studies are necessary to confer an advantage of one variation over another.

Various devices are available in the United States for inserting a DMEK scroll, including IOL injectors and cartridges (ICL cartridge, STAAR Surgical; Softec, Lenstec.; AT.Smart, Carl Zeiss Meditec; or Viscoject, Medicel) and a modified glass Straiko-Jones tube.¹³ There are two other commonly used glass injectors available outside the United States: the Melles long pipette glass injector (DORC International) and the Geuder glass injector (Geuder). However, neither of these injectors is approved by the FDA for use in the United States.^13,23,24 The IOL injectors and glass Straiko-Jones tube are approved by the FDA for human use, and modifications allow for off-label use of these devices for use as DMEK tissue inserters.

Unfolding the graft in the anterior chamber is perhaps the most challenging step of the surgical procedure. Several techniques have been described that involve either short bursts of fluid and a small air bubble used to unfold the graft or variations of taps to the cornea and limbus that generate fluid waves to move the tissue.^{13,19-21,23,24} Older donor-age grafts with high endothelial cell densities unfold significantly faster than younger ones.²⁶

Confidently maintaining correct graft orientation is of utmost importance to prevent iatrogenic primary graft failure and can be extremely difficult without the aid of some visual clues or external devices. Placing a cannula over a graft and being able to maneuver the tip under an upward-curling (correct orientation) roll is called Moutsouris sign.²⁰ The use of handheld slit lamps, endoilluminators, and optical coherence tomography to verify intraoperative graft orientation has also been described.^26-28 As previously mentioned, asymmetrically placed graft-edge notches or a stamped ‘S’ can help verify orientation after unfolding. After starting the use of the stamped ‘S,’ iatrogenic primary graft failure was eliminated in one series.⁸

Sulfur hexafluoride (SF6) 20% gas has evolved as a tamponading tool to improve outcomes in DMEK.¹³ SF6 is an inert gas that, because of its density and slow absorption, can remain in the anterior chamber significantly longer than air, promoting graft adhesion. Güell et al²⁹ compared their 3-year results with air versus SF6 and found that endothelial cell loss was similar in both groups. There was a significant difference in rebubbling rates, however. In the group that used 20% SF6, 2.38% of patients required rebubbling. In the group that used 100% air, 12.8% of patients required rebubbling (P<.01). No cases of IOP spikes or pupillary block glaucoma were observed.

CONCLUSION

DMEK is commonly deemed a demanding procedure in terms of both donor graft preparation and surgical technique. Its pioneers, however, have developed strategies to reliably minimize tissue wastage and endothelial cell loss, reduce complication rates, and improve patients’ visual outcomes to rival that of other endothelial transplant techniques. Implementing these standardized strategies is within reach of both eye banks and corneal surgeons and might help soften the learning curve for DMEK surgeons. For these reasons, DMEK is gaining in popularity as the treatment of choice for conditions like Fuchs endothelial dystrophy and pseudophakic bullous keratopathy.

1. Park CY, Lee JK, Gore PK, Lim CY, Chuck RS. Keratoplasty in the United States: a 10-year review from 2005 through 2014. Ophthalmology. In press.

2. Tourtas T, Laaser K, Bachmann BO, Cursiefen C, Kruse FE. Descemet membrane endothelial keratoplasty versus Descemet stripping automated endothelial keratoplasty. Am J Ophthalmol. 2012;153:1082-1090.

3. Ham L, Balachandran C, Verschoor CA, van der Wees J, Melles GR. Visual rehabilitation rate after isolated Descemet membrane transplantation: Descemet membrane endothelial keratoplasty. Arch Ophthalmol. 2009;127:252-255.

4. Price MO, Giebel AW, Fairchild KM, Price FW Jr. Descemet’s membrane endothelial keratoplasty: prospective multicenter study of visual and refractive outcomes and endothelial survival. Ophthalmology. 2009;116:2361-2368.

5. Guerra FP, Anshu A, Price MO, Price FW. Endothelial keratoplasty: fellow eyes comparison of Descemet stripping automated endothelial keratoplasty and Descemet membrane endothelial keratoplasty. Cornea. 2011;30:1382-1386.

6. Guerra FP, Anshu, Price MO, Giebel AW, Price FW. Descemet’s membrane endothelial keratoplasty: prospective study of 1-year visual outcomes, graft survival, and endothelial cell loss. Ophthalmology. 2011;118:2368-2373.

7. Gorovoy MS. DMEK complications. Cornea. 2014;33(1):101-104.

8. Hamzaoglu EC, Straiko MD, Mayko ZM, et al. The first 100 eyes of standardized Descemet stripping automated endothelial keratoplasty versus standardized Descemet membrane endothelial keratoplasty at one institution. Ophthalmology. 2015;122(11):2193-2199.

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

10. Lie JT, Birbal R, Ham L, van der Wees J, Melles GR. Donor tissue preparation for Descemet membrane endothelial keratoplasty. J Cataract Refract Surg. 2008;34:1578-1583.

11. Tenkman LR, Price FW, Price MO. Descemet membrane endothelial keratoplasty donor preparation: navigating challenges and improving efficiency. Cornea. 2014;33:319-325.

12. Deng SX, Sanchez PJ, Chen L. Clinical outcomes of Descemet membrane endothelial keratoplasty using eye bank-prepared tissues. Am J Ophthalmol. 2015;159:590-596.

13. Terry MA, Straiko MD, Veldman PB, et al. Standardized DMEK technique: reducing complications using prestripped tissue, novel glass injector, and sulfur hexafluoride (SF6) gas. Cornea. 2015;34:845-852.

14. Bachmann BO, Laaser K, Cursiefen C, Kruse FE. A method to confirm correct orientation of Descemet membrane during Descemet membrane endothelial keratoplasty. Am J Ophthalmol. 2010;149(6):922-925.

15. Veldman PB, Dye PK, Holiman JD, et al. Stamping an S on DMEK donor tissue to prevent upside-down grafts: laboratory validation and detailed preparation technique description. Cornea. 2015;34:1175-1178.

16. Terry MA. Endothelial keratoplasty: why aren’t we all doing Descemet membrane endothelial keratoplasty? Cornea. 2012;31:469-471.

17. Gorovoy IR, Gorovoy MS. Descemet membrane endothelial keratoplasty postoperative year 1 endothelial cell counts. Am J Ophthalmol. 2015;159:597-600.

18. Satué M, Rodríguez-Calvo-de-Mora M, Naveiras M, Cabrerizo J, Dapena I, Melles GR. Standardization of the Descemet membrane endothelial keratoplasty technique: outcomes of the first 450 consecutive cases. Arch Soc Esp Oftalmol. 2015;90(8):356-364.

19. Price MO, Giebel AW, Fairchild KM, Price FW Jr. Descemet’s membrane endothelial keratoplasty prospective multicenter study of visual and refractive outcomes and endothelial survival. Ophthalmology. 2009;116:2361-2368.

20. Dapena I, Moutsouris K, Droutsas K, Ham L, van Dijk K, Melles GR. Standardized “no-touch” technique for descemet membrane endothelial keratoplasty. Arch Ophthalmol. 2011;129(1):88-94.

21. Kruse FE, Laaser K, Cursiefen C, et al. A stepwise approach to donor preparation and insertion increases safety and outcome of Descemet membrane endothelial keratoplasty. Cornea. 2011;30:580-587.

22. Feng MT, Price MO, Miller JM, Price FW Jr. Air reinjection and endothelial cell density in Descemet membrane endothelial keratoplasty: five-year follow-up. J Cataract Refract Surg. 2014;40:1116-1121

23. Yoeruek E, Bayyoud T, Hofmann J, Bartz-Schmidt KJ. Novel maneuver facilitating Descemet membrane unfolding in the anterior chamber. Cornea. 2013;32:370-373.

24. Liarakos VS, Dapena I, Ham L, van Dijk K, Melles GR. Intraocular graft unfolding techniques in Descemet membrane endothelial keratoplasty. JAMA Ophthalmol. 2013;131:29-35.

25. Heinzelmann S, Hüther S, Böhringer D, Eberwein P, Reinhard T, Maier P. Influence of donor characteristics on Descemet membrane endothelial keratoplasty. Cornea. 2014;33(6):644-648.

26. Burkhart ZN, Feng MT, Price MO, Price FW. Handheld slit beam techniques to facilitate DMEK and DALK. Cornea. 2013;32(5):722-724.

27. Jacob S, Agarwal A, Agarwal A, Narasimhan S, Kumar DA, Sivagnanam S. Endoilluminator-assisted transcorneal illumination for Descemet membrane endothelial keratoplasty: enhanced intraoperative visualization of the graft in corneal decompensation secondary to pseudophakic bullous keratopathy. J Cataract Refract Surg. 2014;40(8):1332-1336.

28. Droutsas K, Bertelmann T, Schroeder FM, Papaconstantinou D, Sekundo W. A simple rescue maneuver for unfolding and centering a tightly rolled graft in Descemet membrane endothelial keratoplasty. Clin Ophthalmol. 2014;8:2161-2163.

29. Güell JL, Morral M, Gris O, Elies D, Manero F. Comparison of sulfur hexafluoride 20% versus air tamponade in Descemet membrane endothelial keratoplasty. Ophthalmology. 2015;122:1757-1764.