Corneal edema is a major cause of reversible vision loss. The past 20 years have seen huge advances in corneal transplantation since the first procedure done in 1905 by Eduard Zirm.¹ Gerrit R. J. Melles, MD, PhD, one of the pioneers of the recent advances, developed a novel technique for replacing dysfunctional corneal endothelium called Descemet’s membrane endothelial keratoplasty (DMEK). Outcomes include better clarity and quality of vision, quicker visual recovery, lower endothelial rejection rates and lower refractive error changes compared with conventional Descemet’s stripping endothelial keratoplasty (DSEK) and penetrating keratoplasty (PKP).²

As DMEK gained in popularity, variations of the technique emerged. One of the primary issues comparing DMEK to DSEK is the learning curve, which may be slightly longer, and the skill set, which is different with DMEK. Our aim in this article is to to distill the peer-reviewed medical literature to help educate both experienced and novice DMEK surgeons on some of the basic techniques that may improve DMEK outcomes.

PREOPERATIVE STEPS

Some critical steps for successful DMEK can be performed preoperatively. This includes a laser iridotomy placed inferiorly to prevent possible pupil block. Another step is obtaining pre-stripped, pre-stamped and — if possible — pre-loaded DMEK donor tissue.

Patient cooperation in any procedure is extremely helpful. So, to enable both pain management and akinesia, a retrobulbar block is commonly used.

A low IOP facilitates the keratoplasty. It prevents the graft from inadvertent ejection through the main incision. A shallow, but not flat, anterior chamber allows the graft to unscroll without recoiling or “swimming” uncontrollably. Methods to soften the eye include reverse Trendelenburg positioning, intravenous mannitol, acetazolamide or the Honan balloon. In extremely shallow chambers, decompression with core vitrectomy can be considered, although rarely needed.

Inducing miosis maximizes the area of iris, which serves as a platform to unscroll the DMEK graft as well as maintain the air tamponade at the conclusion of the case. This reduction in pupil diameter can be achieved with preoperative pilocarpine drops and/or intracameral acetylcholine.

INTRAOPERATIVE STEPS

Marking the cornea to outline the descemetorhexis can be helpful. It serves to:

1. Avoid graft overlap with a paracentesis so they can be utilized for graft manipulation, and
2. Guide centration of the graft. A typical diameter ranges from 8 to 9 mm.

Typically, two or three paracenteses and a short main corneal (or corneoscleral) incision of 2.4 to 3.2 mm in width are constructed (Figure 1, page 29). An appropriate match between the corneal wound size and graft insertion device is important to avoid graft ejection.

The anterior chamber can be maintained with cohesive ophthalmic viscosurgical devices (OVDs) (eg, sodium hyaluronate), air or constant irrigation during construction of the descemetorhexis. Descemetorhexis with a reverse Sinsky hook or descemetorhexis forceps is performed with caution to avoid stromal fibers or tags that can potentially obstruct graft manipulation and attachment.

A 10-0 nylon pre-placed suture at the main incision can help prevent graft extrusion in later steps (Figure 2).

If OVD was placed, it is thoroughly aspirated and exchanged for balanced salt solution (BSS) to avoid interfering with graft apposition.

GRAFT PREPARATION

Prior to insertion, inspection of the graft ideally shows a well-stained graft with a bold orientation stamp on the stromal side of the graft. However, if this is not the case, consider reapplication of Trypan blue for two minutes followed by a gentle rinse in BSS.

When it comes time to cut the DMEK graft with the graft flush against the donor stroma (which is fixated by suction), cut it to 0.5 to 1 mm smaller than that of the descemetorhexis with a guarded or gentle punch. Undersizing the graft avoids overlap with the host Descemet’s, which has been reported to be a cause of DMEK graft detachment.³ The area of mismatch is typically not visually significant since gaps between graft and host endothelium eventually repopulate and the intervening corneal edema resolves.⁴

Extracting the rim of the DMEK graft with non-toothed forceps confirms a complete punch. If adhesions are present, the same punch can be reapplied. Consider restaining the graft with Trypan blue to maintain visibility of the graft during prolonged cases. At this point, the graft can be loaded into an inserter.

INSERTION

To use glass inserters, the graft is rinsed with BSS so that it configures naturally into a scroll — if possible, a double scroll, as this makes for easier positioning and unfolding. The elasticity of the DM causes the graft to roll with the endothelium outwards, and the DM inward,⁵ so care must be taken to avoid direct contact. The graft, which is in a bath of BSS, is aspirated into a submerged Straiko-Jones glass tube (2.75- to 3.5-mm diameter), Geuter DMEK inserter (2.4-mm diameter) or the Melles injector (3.0-mm diameter, DORC International) with care to avoid drawing air.

Commercially available IOL injectors have the advantage of requiring smaller corneal wound incision sizes, but loading the graft may be more complex and traumatic to the endothelium. When the surgeon chooses an IOL injector, the DMEK graft is layered with BSS and forceps fold the endothelium inward, in a trifold manner. The graft is then pulled or placed with forceps into a BSS bath within the IOL inserter.

GRAFT POSITIONING

A shallowed anterior chamber enables uptake of the fluid bolus that carries the DMEK graft. Graft delivery involves monitoring the double scroll closely and rotating the inserter to maintain the upward facing scrolls. Once the graft is in the anterior chamber and freed from the inserter, the corneal wound is guarded during extraction of the inserter then closed with a 10-0 nylon suture(s).

The surgeon can use a variety of methods to confirm proper graft orientation. The Moutsouris sign entails inserting the tip of the cannula into the burrito or double scroll. If the graft is properly oriented, the silver sheen of the proximal cannula is anterior to the periphery of the well-stained graft, while the distal cannula appears blue as the cannula is inserted into the scroll. Other techniques include recognizing the orientation “S” stamp and use of a hand-held slit lamp or the vitrectomy endoilluminator to identify upward facing scrolls. To correct an upside down graft, consider flipping the graft by directing small fluid pulses under the graft scroll(s).

The surgeon can achieve centration by various maneuvers:

1. Tapping peripheral to the graft directs AC fluid centrally,
2. Small fluid jets through a paracenteses push the fluid centrally, and
3. Egress of fluid from a paracentesis or the main incision cause the graft to follow peripherally.

The last resort for a very stubborn graft is a technique described by Melles. Drag the Descemet’s side of the graft into position using a Sinsky hook or 30-G bent needle. Exercise caution, though, as this contact will cause endothelial loss.

Unscrolling is best accomplished when the graft does not exhibit folds or points — in these cases, the anterior chamber can be deepened to release the crease and then unscrolled further. The arduous process of graft unfolding depends on its orientation.

ADDITIONAL TECHNIQUES

• Double scroll: The “no touch” technique utilizes a central AC enlargening air bubble to flatten the graft against the iris. The air is then evacuated and reinjected to tamponade the graft to the corneal stroma.⁶
• The Yoeruck technique: Applies taps on the cornea centrally. The compressed fluid flows laterally, sweeping the leaflets apart. The anterior chamber is also shallowed to entrap the graft between the cornea and the iris, which prevents the graft from recoiling.
• Tight single scroll: The Dirisamer maneuver is also known as the double cannula technique. Fluid injected from a cannula creates a current that liberates an edge of the graft. One cannula pins the free edge of the graft between the host cornea and iris, while the other cannula taps to unroll the scroll.
• The Dapena maneuver: An air bubble is placed in the lumen to loosen the scroll. Graft unfolding is then completed using the “no touch” technique.
• Loose graft: This subtype is at high risk for placement upside down because there is little to no curvature in the scroll to verify which side is endothelial.⁷ It emphasizes the necessity of orientation markers. These grafts tend to flatten or form a taco fold. A single cannula sweep can readily set the graft position.
• Trifold: The DMEK graft is either injected or pulled into the anterior chamber. Compression on the corneal surface is used to move fluid laterally and open the leaflets of the trifold.

GRAFT ATTACHMENT

The surgeon fixates the DMEK graft to the recipient stroma by tamponade with air or 20% sulfur hexafluoride (SF6). The bubble is delivered centrally to maintain graft centration and to express fluid out of the interface using a long 27- to 30-G cannula on a 1- to 3-mL syringe.

The advantage of 20% SF6 is prolonged tamponade with retention of up to six days with SF6 vs. one to two days with air. A meta-analysis of retrospective studies comparing 20% SF6 to 100% air shows 58% risk reduction in rebubble rates.⁸ Concerns regarding higher risk of pupillary block and endothelial toxicity were not evident in this comparison.

Given the graft’s tendency to fold inward, the graft periphery may need additional tapping to express residual fluid and release peripheral folds that could predispose the graft to detach. This method is best performed before complete air/gas fill.

Full air or gas fill should be maintained over a range of 10 to 120 minutes. Leakage through corneal wounds can be avoided with 10-0 nylon suture closure. The bubble is then reduced with the objective of unobstructing the inferior iridotomy. Larger bubbles in the anterior chamber (75-80%) have lower rebubbling rates.^9,10 A retrospective study suggests that graft tamponade from a full bubble to a reduced-size bubble is equally effective with physiologic IOP (Figure 3, page 32).¹¹ Postoperative supine positioning is maintained for one to two hours in the recovery area, followed by supine positioning as much as tolerated for the duration of the bubble (24 to 96 hours) with 20 minutes breaks as needed for meals and restroom use.

OUTCOMES

No prospective clinical trials comparing the various techniques are yet underway. A gestalt is the best that can be determined from each study due to the multifactorial nature of the various techniques that we have described. For example, differences exist in the donor storage methods, graft preparation, graft insertion, technique with centration and positioning, tamponade times and material (air or SF6) intraoperatively and postoperatively, and there is a range of postoperative medication regimens. So, at this time, DMEK surgeons are still learning and contributing to the refinement of the technique.

CONCLUSION

Corneal edema is a major cause of worldwide vision loss. Thankfully, after a century of minimal changes to our corneal transplantation techniques, the past several decades have seen rapid advances. DMEK is the latest and most sophisticated surgical technique to reverse corneal edema. Although the learning curve might be slower and require new skills, corneal surgeons can make the transition to this current state-of-the-art procedure with some basic concepts under their belts. OM

REFERENCES

1. Moffatt SL, Cartwright VA, Stumpf TH. Centennial review of corneal transplantation. Clin Experiment Ophthalmol. 2005;33:642-657.
2. Deng SX, et al. DMEK: Safety and Outcomes. A Report by the AAO. Ophthalmology 2018;125:295-310.
3. Kruse FE, Schlötzer-Schrehardt U, Tourtas T. Optimizing outcomes with Descemet’s membrane endothelial keratoplasty. Curr Opin Ophthalmol. 2014;25:325-334.
4. Tong CM, Gerber-Hollbach N, Nieves JP, Liarakos V, et al. “No-touch” DMEK surgical technique. Vis. Pan-Am. 2015;14:72-76.
5. Moshirfar M, Jarstad A, Khalifa YM. Descemet membrane endothelial keratoplasty: Why does the donor tissue roll? Cornea. 2013 Apr;32:e52-53
6. Liarakos VS, Dapena I, Ham L, van Dijk K, Melles GR. Intraocular graft unfolding techniques in descemet membrane endothelialkeratoplasty. JAMA Ophthalmol. 2013 Jan;131:29-35.
7. Veldman PB, Mayko ZM, Straiko MD, et al. Intraoperative S-Stamp Enable Rescue of 3 inverted DMEK grafts. Cornea 2017;36:661-664.
8. Esteves Marques, R., Guerra PS, Sousa DC, et al. SF6 20% versus Air 100% for Anterior Chamber Tamponade in DMEK: A Meta-Analysis. Cornea. 2018;37:691-697.
9. Leon PE, Parekh M, Nahum Y, et al. Factors associated with early graft detachment in primary DMEK. Am J Ophthalmology. 2018;187:117-124.
10. Cirkovic A, Beck C, Weller JM, et al. Anterior chamber air bubble to achieve graft attachment after DMEK: Is bigger always better? Cornea. 2016;35:482-485.
11. Schmeckenbacher N, Frings A, Kruse FE, et al. Role of Initial IOP in graft adhesion after DMEK. Cornea. 2017;36:7-10.

About the Authors

Francis S. Mah, MD, is director of Cornea Service at Scripps Clinic in La Jolla, Calif.

Elizabeth Viriya, MD is clinical assistant professor of Cornea, External Disease and Refractive Surgery at New York University School of Medicine, New York, N.Y.
Disclosure: The authors do not report any relevant financial relationships.