Descemet’s membrane endothelial keratoplasty (DMEK) offers patients visual recovery within 2 to 4 weeks, improved visual outcomes, and reduced rejection rates (primary graft failure rates are 0% to 9%) compared to PKP.¹ Additionally, prestripped, prestained, prepunched, and preloaded DMEK tissue often can be placed as quickly as routine cataract surgery and can be performed in conjunction with cataract surgery in cases in which the patient has a visually significant cataract, in addition to corneal endothelial decompensation.

Because DMEK can also be challenging, with incidences of graft detachment and incomplete corneal clearing, knowledge of the associated surgical techniques, possible complications and management, and the ideal patient candidates are imperative for success.

Associated Surgical Techniques

• Anesthesia. Anesthesia for DMEK cases can include topical, peribulbar, subtenon’s, or retrobulbar anesthesia. For beginning DMEK surgeons, I highly recommend a peribulbar or subtenon’s block. This will allow for best patient akinesia and anesthesia, permitting the surgeon to have maximum control of the globe and perform an efficient operation without worrying about going too quickly. There is also a benefit of slight increase in posterior pressure, which will allow for a shallower anterior chamber and easier DMEK graft unfolding. For more experienced surgeons, topical anesthesia with topical lidocaine gel and intraocular lidocaine can work well, as the surgeon will be much faster at performing DMEK.

• Laser peripheral iridotomy (LPI). Performing an inferior LPI in DMEK cases is crucial to preclude post-operative pupillary block. An LPI can be created using a YAG laser, days to a few weeks prior to the scheduled DMEK; intraoperatively; creating an inferior stab incision, removing a portion of the iris tissue out of this paracentesis using forceps, and snipping a small portion of the tissue with Vanas scissors; using a bent 30-gauge needle, placing it under the inferior iris, and scratching the tip with a Sinskey hook to create a small iris opening, or using an anterior vitrector on the irrigation-cut setting. All methods are effective, so choice is based on surgeon convenience.

Personally, I opt for intraoperative LPIs using an anterior vitrector on the aspiration-cut setting and reducing the cut rate to 1 cut per minute to allow for a controlled creation of a PI. I feel this precludes the need for the patient to come in for a preoperative LPI procedure, and is a more controlled method in my hands versus using Vanas scissors or a 30-gauge needle.

Prior to LPI creation and DMEK graft insertion, preoperative pilocarpine drops or intraoperative acetylcholine chloride or carbachol intraocular solution should be administered to ensure good pupillary miosis. Pupillary miosis is important to protect the graft from contact with the IOL or crystalline lens, as well as to prevent the thin DMEK graft from descending posteriorly past the iris opening and zonules.

In cases in which a combined cataract surgery and DMEK is performed, consider dilation of the pupil using weaker mydriatics, such that pupillary miosis can be easily achieved after the cataract removal is complete. Agents that I use for pupillary dilation in combination cataract and DMEK cases include intraocular epinephrine only, or 1 drop of topical phenylephrine 2.5% and tropicamide 0.5%.

• Graft sizing and Descemet’s membrane stripping. Measuring the patient’s corneal white-to-white diameter and assessing the graft size, especially if precut tissue will be ordered, is important. This helps the surgeon think ahead to what size graft would work best for the patient’s eye. I have found that a 7.75 mm or 8 mm graft works well in most eyes, but a 7.5 mm graft may be more suitable in eyes that have a smaller white-to-white diameter.

Descemet’s membrane (DM) should be stripped about 0.5 mm larger than the graft size to allow for better peripheral graft adherence. The reason: Peripheral DM tags that overlap with the DMEK graft can increase graft detachment risk. Lastly, stripping DM should be done under air or viscoelastic. I use a cohesive viscoelastic to allow for easy removal of all viscoelastic prior to graft insertion. Any residual viscoelastic in the anterior chamber prevents the DMEK graft from unfolding.

• Methods of insertion. DMEK grafts can be inserted via stripping, staining, and loading the surgeon’s designated DMEK tissue. Many eye banks provide prestripped, pre-stained, prestamped, preloaded DMEK tissue, and have been instrumental in simplifying the learning curve for this procedure. I use preloaded DMEK tissue in a tube. Four devices are available: a Geuder Pre-Loaded Glass Cannula (CorneaGen) can be inserted through a 2.2 mm to 2.4 mm incision. A Jones Tube (Eversight) or a Modified Jones Tube (Eversight) are typically inserted through a 3.0 mm to 3.5 mm incision. The EndoGlide (Eversight) is used to perform a pull-through DMEK technique.² The surgeon and eye bank both determine the insertion device choice.

Pro tips: When choosing DMEK tissue donors, older donors (age >55) are preferred, as younger donor grafts tend to curl tightly and are hard to unfold and position easily. Additionally, a graft stamp (e.g., “S,” “F,” or the 1 and 2 dash method) is needed to ensure proper graft orientation (Figure 1).

• Tapping maneuvers and anterior chamber maintenance. It is often advised to place a suture in the main wound to protect egress of the graft out of the anterior chamber and to help maintain chamber stability. Timing of suture placement can vary based on surgeon preference.

I typically place a 10-0 nylon suture after insertion of the DMEK tissue and tie and rotate the knot prior to tissue manipulation to ensure the anterior chamber remains formed at all times. Other surgeons may opt to place the suture after tissue manipulation and gas injection once all steps are completed. Creating directional fluid waves with gentle taps on the corneal surface, using 30-gauge or 27-gauge cannulas while maintaining a shallow anterior chamber, is the key to unfolding a DMEK graft. Many educational tools are available on the various tapping maneuvers. I recommend a surgical video series by Dr. Michael Straiko (https://nwcorneainstitute.com/category/videos/dmek-videos/ ) and by Dr. Peter Veldman (https://patientready.org/ ) (Figure 2).

• Methods of tamponade. Tamponade of the DMEK graft can be achieved with an iso-expansile gas or air injection. I utilize 20% sulfur hexafluoride (SF6) gas, as it typically lasts 5 to 7 days in the anterior chamber and permits adequate graft tamponade to prevent graft detachment. This is why patients who have glaucoma drainage implants or who have undergone prior vitrectomies may benefit from gas. I leave a full gas bubble in the eye for 5 minutes in the OR and then perform a gas-balanced salt solution exchange to allow for an 80% gas bubble to remain to clear the inferior PI. Additionally, I advise patients to remain supine for 3 to 5 days until the gas bubble is barely visible to them or their family members. I teach family members how to recognize the meniscus of the gas bubble, so they can assist in gauging bubble resolution.

The time spent supine may be less with air, as air resolves more quickly than gas. These patients likely will need to remain supine closer to 3 days. In addition, a larger anterior chamber fill may be required to compensate for the fast air evacuation.

It is important to always ensure the air or gas bubble left intraoperatively clears the inferior PI. Also, ensuring that the gas concentration is diluted properly is crucial, as incorrect dilutions can cause gas to expand postoperatively and cause pupillary block.

Complications and Management

• Graft extrusion. This can occur out of the injector, out of the main wound, or into the posterior chamber. If the graft comes out of the injector or main wound, it can easily be re-loaded into the tube after re-staining the graft in trypan blue dye and placing the graft into a Petri dish with balanced salt solution. If the graft dislocates posteriorly, a retina surgeon may need to assist in retrieving the graft, and new tissue may be needed.
• Iris heme formation. Intraoperative PI creation can be susceptible to iris bleeding, especially in light-colored irides. The quick inflation of the eye with viscoelastic increases IOP for several minutes to tamponade the area of bleeding. Typically, after roughly 5 minutes, the bleeding stops, and the anterior chamber can be irrigated. This is important, as the evacuation of all hemorrhage prevents fibrin formation, which can cause the DMEK graft to become sticky and difficult to unfold.
• Fibrin formation/anterior chamber vitreous. Fibrin causes the DMEK graft to adhere to itself. This prevents it from unfolding easily, and can increase the chances of graft detachment or graft failure.² It can occur from aggressive or prolonged tapping to unfold the graft, especially if the patient has an open posterior capsule or areas of unknown zonulopathy. In cases of a known open capsule, I recommend achieving excellent pupillary miosis and gentle/minimal tapping to prevent vitreous from migrating forward. If fibrin is encountered in the anterior chamber, the anterior chamber can be gently irrigated to remove all fibrin. Some studies show use of intracameral tissue plasminogen activator mitigates anterior chamber fibrin formation in DMEK cases.³If anterior chamber vitreous is encountered, an anterior vitrector must be carefully used to amputate and remove all vitreous strands, as using irrigation/aspiration or manual amputation may cause unwanted vitreous traction. Sometimes, the DMEK graft must be removed from the anterior chamber prior to removal of fibrin or vitreous.
• Pupillary block. Persistent pupillary block can lead to Urrets-Zavalia syndrome in DMEK patients, which can cause permanent iris and vision changes in patients. Gas or air can be removed from a limbal paracentesis to make the bubble smaller to ensure clearance of the inferior PI. The iris can also be dilated with a cycloplegic agent to accomplish this.
• Graft detachments. I have found that this typically occurs 7 to 10 days after DMEK surgery, or once the gas or air bubble has resolved. I usually see DMEK patients 10 to 14 days postoperatively to better detect early graft detachments. If the graft detachments are small and peripheral, they typically can be observed, as they will often resolve spontaneously. If the detachments encompass a large area (~1/3 of the cornea) and edema is present in the central visual axis, earlier graft re-bubbling is advised to secure the graft. If detachment persists, a graft may need to be re-bubbled 2 or 3 times to achieve full graft adhesion. Re-bubbling can be performed at the slit lamp or in a minor procedure room; rarely is the OR required. If the detachment does not improve, a repeat DMEK procedure may be required.
• Graft rejection. Although rare, this can occur due to patient non-compliance to drops or a viral disease (e.g., herpes simplex or cytomegalovirus). Initiating antiviral therapy, in addition to increasing topical, oral, intravenous, or subtenon’s steroids, can help preserve these grafts. Repeat grafting can be done if needed.

Ideal Candidates

Pseudophakic patients who have an intact posterior capsule with Fuchs’ endothelial dystrophy or bullous keratopathy make ideal candidates for DMEK. I recommend starting with the former patients, as DM stripping is often easier than in pseudophakic bullous keratopathy cases, and anterior chamber maintenance is also more predictable for graft unfolding (see “Complex Cases”.). Requesting back-up Descemet’s stripping automated endothelial keratoplasty (DSAEK) tissue makes sense for the first few cases in the event DMEK surgery proves unsuccessful.

Sometimes, if patients have Fuchs’ endothelial dystrophy with guttae concentrated only in the central 4 mm of the cornea with robust peripheral endothelial cells (>1000 cells/mm²), they may be candidates for a Descemet’s stripping only (DSO) procedure.

In this procedure, a central, circular 4 mm descemetorhexis is performed using a reverse Sinskey hook, along with forceps under viscoelastic or air. No gas or air needs to be injected, as no transplant tissue is placed afterward. The peripheral endothelial cells are thought to migrate and regenerate to fill the central area from which the diseased endothelial cells are removed. This is a good option for patients who are interested in a non-transplant surgical option, who may have contraindications for using long-term corticosteroids, or who are unable to maintain a supine position for air or gas tamponade in the initial postoperative period.

Patients without good peripheral endothelial cells or who have diffuse corneal edema or scarring secondary to other conditions, such as bullous keratopathy, are not DSO candidates. Patients need to be counseled that if the central cornea does not clear after 3 or 4 months, there is a high chance for an endothelial keratoplasty (either DMEK or DSAEK). Some surgeons utilize Rho-associated protein kinase inhibitors after DSO to help the endothelial cells repopulate successfully. DSO can also be performed concurrently with cataract surgery.

A Rewarding Procedure

DMEK cases can be rewarding, as long as there is full knowledge of the associated surgical techniques, possible complications and management, and the optimal patient candidates. CP

References:

1. Beşek NK, Yalçınkaya G, Kırgız A, et al. Graft survival and clinical outcomes of Descemet membrane endothelial keratoplasty: long-term results. Int Ophthalmol. 2022;42(1): 269-279.
2. Benage M, Korchak M, Boyce M, et al. Intraoperative fibrin formation during Descemet membrane endothelial keratoplasty. Am J Ophthalmol Case Rep. 2020;18: 100686.
3. Ferguson TJ, Traboulsi EI, Goshe JM. Successful pediatric DMEK facilitated by intracameral tissue plasminogen activator to mitigate anterior chamber fibrin reaction. Am J Ophthalmol Case Rep. 2020;19: 100812.
4. Bhullar PK, Venkateswaran N, Kim T. Case Series of Urrets-Zavalia Syndrome After Descemet Membrane Endothelial Keratoplasty. Cornea. 2021;40(5):652-655.
5. Din N, Cohen E, Popovic M, et al. Surgical Management of Fuchs Endothelial Corneal Dystrophy: A Treatment Algorithm and Individual Patient Meta-Analysis of Descemet Stripping Only. Cornea. 2022;41(9):1188-1195.

 

DR. VENKATESWARAN practices at Massachusetts Eye and Ear Harvard Medical School Department of Ophthalmology, where she is also an instructor. Her specialties: complex and premium cataract surgery, cornea and external diseases, corneal cross-linking, and refractive surgery. She consults for CorneaGen.