|Ahead of print publication
Descemet membrane endothelial keratoplasty in eyes with glaucoma
Bryan Le1, Clemence Bonnet2, Madeline Yung3, Sophie X Deng3
1 Stein Eye Institute, Department of Ophthalmology, David Geffen School of Medicine, University of California, Los Angeles, CA; College of Medicine, Drexel University, Philadelphia, Pennsylvania, USA
2 Stein Eye Institute, Department of Ophthalmology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA; Cornea Department, Cochin Hospital, Paris Cité Université, Paris, France
3 Stein Eye Institute, Department of Ophthalmology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
|Date of Submission||19-Feb-2022|
|Date of Acceptance||17-Jul-2022|
|Date of Web Publication||16-Nov-2022|
Sophie X Deng,
Stein Eye Institute, University of California, Los Angeles, 200 Stein Plaza, Los Angeles, CA 90095
Source of Support: None, Conflict of Interest: None
Endothelial keratoplasty has become the standard for the treatment of endothelial dysfunction. In Descemet membrane endothelial keratoplasty (DMEK), only the endothelium and Descemet membrane are transplanted, providing superior outcomes compared to Descemet stripping endothelial keratoplasty (DSEK). A substantial subset of patients who require DMEK have comorbid glaucoma. Even in eyes with complex anterior segment such as eyes with previous trabeculectomy or tube shunts, DMEK can restore meaningful vision and outperforms DSEK in terms of visual recovery, decreased rejection rate, and the need for high dose of topical steroids. However, accelerated endothelial cell loss and secondary graft failure have been described in eyes with previous glaucoma surgery, namely trabeculectomy and drainage device. During DMEK and DSEK procedures, raised intraocular pressure is required to attach the graft, which could worsen preexisting glaucoma or cause de novo glaucoma. Mechanisms of postoperative ocular hypertension include delayed air clearance, pupillary block, steroid response, and damage to angle structures. Medically treated glaucoma has increased risk for postoperative ocular hypertension. By understanding these additional complications and making appropriate modifications in surgical techniques and postoperative management, DMEK can be performed successfully and achieve very good visual outcome in eyes with glaucoma. Such modifications include precisely controlled unfolding technique, iridectomies that can help avoid pupillary block, tube shunts that can be trimmed to facilitate graft unfolding, air fill tension that can be adjusted, and postoperative steroid regimens that can be modified to decrease the risk for steroid response. Long-term survival of the DMEK graft, however, is shorter in eyes with previous glaucoma surgery than those without, as observed after other types of keratoplasty.
Keywords: Corneal edema, endothelial keratoplasty, glaucoma, glaucoma drainage device, graft survival, trabeculectomy
| Introduction|| |
Endothelial keratoplasty is now the standard of care for visually significant corneal endothelial failure., Descemet membrane endothelial keratoplasty (DMEK) transplants only the corneal endothelium and Descemet membrane, resulting in faster visual recovery, a lower rate of rejection, and a reduced requirement for postoperative steroids., For these reasons, DMEK has gained in popularity, even in complex cases such as failed penetrating keratoplasty (PK), iridocorneal endothelial syndrome, and history of glaucoma surgery.,,,,,
Glaucoma is a blinding disorder that affects four million people in the United States., Glaucoma drainage surgery, laser iridotomy, laser trabeculoplasty, and even elevated intraocular pressure (IOP) from glaucoma itself can accelerate corneal endothelial cell loss, leading to corneal decompensation. Glaucoma not only predisposes to corneal transplantation, but can damage graft endothelium, as seen in PK.,, Conversely, keratoplasty itself may engender or exacerbate glaucoma.
DMEK and glaucoma exist in a complex relationship of cause and effect, of which clinical data are still emerging and optimal management strategies are unclear. This review summarizes the current literature on outcomes, surgical techniques, postoperative management, and special considerations for performing DMEK and postoperative management in the setting of comorbid glaucoma.
| Methods of Literature Review|| |
A review of the literature was conducted in the PubMed database of studies in the English language published from January 1, 2006 (first report of human DMEK transplant) to December 1, 2021, using the search terms “Descemet membrane endothelial keratoplasty” AND “glaucoma” OR “trabeculectomy” OR “Ahmed” OR “tube shunt” OR “Baerveldt” OR “ocular hypertension” OR “intraocular pressure” OR “steroid response”. Clinical trials, cohort studies, observational studies, case reports, and case series with significant findings on DMEK and glaucoma were included. Reviews, editorials, comments, and articles that did not have a substantial focus or clinical information on DMEK and glaucoma were excluded. One hundred and twenty-one articles were identified, and 27 on DMEK and glaucoma were included. Main outcomes reviewed were visual acuity, graft detachment, primary and secondary graft failure (SGF) rates, endothelial rejection rate, and IOP changes. Details on the surgical techniques and postoperative steroid regimens were also provided.
| Results|| |
Effect of Descemet membrane endothelial keratoplasty on glaucoma
IOP elevation is the second most common complication of DMEK. Early ocular hypertension may arise from air/gas overfill, pupillary block, or retained viscoelastic, while late episodes are classified as steroid-dependent or steroid-independent responses [Table 1].,,, Steroid-independent hypertension can be further divided into exacerbation of preexisting glaucoma or new onset of glaucoma. Most studies define clinically significant ocular hypertension as increase in absolute IOP above 24 mmHg or an increase of 8–10 mmHg or more above the preoperative baseline [Table 2].,,,,,,
|Table 1: Causes of elevated intraocular pressure after Descemet membrane endothelial keratoplasty and strategies for management|
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|Table 2: Published studies on Descemet membrane endothelial keratoplasty in eyes with previous glaucoma surgery|
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Perioperative IOP elevation in DMEK is related to the injection of air into the anterior chamber. Adequate air fill is crucial for successful DMEK, given that graft detachment is its most common complication, with rebubbling rates ranging from 2.7% to 76%., IOP increases immediately after air fill, often surpasses 40 mmHg, and can remain asymptomatic above 30 mmHg. Patients require close monitoring in the immediate postoperative period, with possible air release or medications to lower IOP., If appropriately managed, perioperative IOP fluctuations do not seem to affect early endothelial cell loss at 1 month.
In addition, errant air bubbles may increase IOP through classic pupillary block by occluding the pupil with an iris bombe configuration, reverse pupillary block with full air fill and a concave iris, or migration of air behind the iris, with reported rates ranging from 0% to 15%,, and with higher rates in phakic patients. Pupillary block is generally managed with peripheral iridectomy, cautious air release, mydriasis, supine positioning, and/or aqueous suppressants.
Late IOP elevations can result from steroid-dependent and steroid-independent responses. Steroid response tends to occur as early as 2 weeks postoperatively., Meanwhile, exacerbation of preexisting glaucoma or new-onset glaucoma can result from clogging of the trabecular meshwork with inflammatory debris, formation of peripheral anterior synechiae, and damage to the angle.,
The rates of late-onset ocular hypertension range from 2% to 34% in patients without glaucoma and similarly 9% to 30% in patients with a history of glaucoma surgery [Table 2].,, Some studies find that preexisting medical glaucoma increases the risk for IOP elevation, with rates ranging from 25% to 77%, while others find no significant association.,,,,, In addition, patients of Asian or African ethnicity may be at a greater risk for IOP elevation due to the high frequency of shallow chamber and steroid response, respectively. Fortunately, development of ocular hypertension was not found to impact visual acuity or endothelial cell loss if managed promptly.
Descemet membrane endothelial keratoplasty outcomes in eyes with glaucoma
Previous studies have shown that DMEK is feasible in eyes with glaucoma and even in eyes with previous glaucoma surgery.,,,,, With appropriate surgical techniques and postoperative management, DMEK can provide functionally significant and worthwhile outcomes.
Whereas routine DMEK is most commonly performed for Fuchs endothelial corneal dystrophy, the most frequent indications for DMEK in eyes with previous glaucoma surgery are pseudophakic bullous keratopathy (52-72%), viral endotheliitis (20%), and failed previous corneal transplant (22%–39%).,,
Patients with medically or surgically treated glaucoma on average start with worse preoperative vision and corneal edema than those without glaucoma, but gain more lines of vision compared to nonglaucomatous patients.,, Postoperative visual acuity does not differ between the control nonglaucomatous group and medically treated glaucoma group, with 88%–93% reaching 20/40 or better. DMEK in the setting of previous glaucoma surgery achieved 3.3 more lines of visual improvement, though on average lower final visual acuity. Bonnet et al. found that 40% of eyes with glaucoma surgery reached 20/40 or better, maintained up to 4 years postoperatively after primary DMEK, while Birbal et al. reported that 73% of eyes with glaucoma surgery gained two or more lines of vision at 1 year after DMEK. Over half of glaucoma patients who underwent DMEK have additional comorbidities that may further limit vision including limbal stem cell deficiency, age-related macular degeneration, epiretinal membrane, and macular edema., DMEK in these patients has also demonstrated significant visual improvement, with several studies reporting visual improvement at 12 months, ranging from 0.49 to 0.55 logMAR in patients, comparable to the 12-month improvement range of 0.66 to 0.71 logMAR in their cohort without visual comorbidities., Although advanced glaucoma or other comorbidities may limit visual potential and DMEK outcomes, DMEK does provide meaningful visual restoration that improves patient independence and quality of life.
Descemet membrane endothelial keratoplasty versus Descemet stripping endothelial keratoplasty
Descemet stripping endothelial keratoplasty (DSEK) is another surgical treatment for corneal endothelial cell failure that is often compared with DMEK when managing endothelial dysfunction in the setting of previous glaucoma surgery, primarily for less complex graft preparation and handling. In DSEK performed on individuals with previous glaucoma surgery, graft survival at 3 to 5 years has been reported between 25% to 69%, marking the need to conduct studies aimed at directly assessing outcomes for both DMEK and DSEK in this patient population. DMEK presents several advantages over DSEK for patients with previous glaucoma surgery; the thinner graft results in faster visual recovery and better visual outcomes. Lin et al. found that in patients with previous glaucoma surgery, DMEK patients recovered more quickly at as early as 1 month postoperatively, with 47% of patients who underwent DMEK achieving a best corrected visual acuity of 20/40 or better, compared to 15% of patients who received DSEK in 1 year. Alshaker et al. conveyed similar findings up to 24 months, noting significantly better postoperative BCVA in the DMEK group in patients with previous glaucoma surgery than in the corresponding DSEK group. DMEK patients also had lower risk of SGF compared to DSEK, although long-term studies are required to confirm this finding. In addition, reduced risk for graft rejection with DMEK allows milder postoperative steroid regimens and in turn lower rates of steroid induced IOP elevation, an advantage especially important in eyes with comorbid glaucoma.,, In our experience, remaining indications for DSEK include the presence of anterior chamber intraocular lens and unstable intraocular lens that requires intraocular lens exchange at the time of endothelial keratoplasty. We routinely perform DMEK on eyes with extensive anterior synechia because the adhesion can be lysed and the anterior chamber is often reformed afterward. Eyes with large iris defect up to 60% could still be candidates for DMEK as long as the depth of anterior chamber could be controlled. However, the decision as to which type of endothelial keratoplasty mainly depends on the experience and preference of the surgeons.
While outcomes from standard DMEK and DSEK techniques are often compared against one another, the emergence of other endothelial keratoplasty variations necessitates further investigation into their efficacy, such as ultra-thin DSEK in these patients.
Several studies have examined the postoperative complication rates of DMEK in eyes with previous glaucoma surgery. There is no significant difference in the rate of postoperative air injection (7%–57% vs. 2.7%–76%), endothelial rejection (0%–16% vs. 0%–21%), cystoid macular edema (0%–16% vs. 0%–12%), or primary graft failure (0%–11.1% vs. 0%–12.5%) in eyes with previous glaucoma surgery compared with eyes without previous glaucoma surgery.,,,,,
All DMEK grafts show an initial decline within the first 1–3 months in endothelial cell density, attributed to the surgical trauma.,,, However, the presence of either a trabeculectomy and/or a tube shunt has been shown to accelerate endothelial cell loss in the absence of clinical anterior chamber inflammation and immune rejection. Endothelial cell loss in eyes with prior glaucoma surgery continues past the early postoperative period. The percentage of endothelial cell loss has been reported between 41% and 68%,,, at 1 year, 68%–74%, at 4 years, and is overall 12%–22% higher than in eyes without previous glaucoma surgery [Table 2]. Correspondingly, eyes with previous glaucoma surgery demonstrate a continuous increased rate of SGF, reported between 58% and 83% at 4 years. Whereas, the rate of SGF in eyes without glaucoma remains stable between 2.4% and 12% over 10 years follow-up.,, The mechanisms of chronic endothelial toxicity remain to be further investigated; hypotheses include direct mechanical damage from tube endothelial contact and introduction of inflammatory or toxic mediators through the breakdown of the blood aqueous barrier.
Considerations for performing Descemet membrane endothelial keratoplasty in eyes with previous glaucoma surgery
Eyes with previous glaucoma surgery often have other anterior segment abnormalities such as peripheral iridocorneal adhesions, large iris defects, fibrotic membranes on the posterior cornea, angle and iris, and unstable capsular support that may increase the technical difficulty of DMEK. Before DMEK, the IOP should be well controlled with room to add additional glaucoma medications if needed postoperatively. In addition, achieving sufficient air fill to attach the graft without inducing severe pressure spikes is challenging and should be reserved to experienced surgeons. Nevertheless, with appropriate surgical and postoperative modifications, DMEK in these complex eyes could be successful treatment for patients with endothelial failure and is now our preferred therapeutic option.
Preoperative planning for DMEK should account for any altered anatomy from previous glaucoma surgery. The main incision should avoid filtering blebs, tubes, or other previous surgical incisions, and ideally spare the superior conjunctiva in the event of future glaucoma surgery. Over two thirds of patients with previous glaucoma surgery will require additional procedures such as lysis of iridocorneal adhesion and tube trimming to create sufficient space in the anterior chamber previous to graft insertion.,, Once the iridocorneal adhesion has been lysed, the anterior chamber is often reformed.
Intraoperative surgical iridotomies is preferred to prevent pupillary block-related complications as preoperative laser iridotomy is not successful in eyes with severe corneal edema.,, In eyes with chronic severe corneal edema, removal of edematous corneal epithelium usually improves the visualization to an adequate level for DMEK. If needed, side lighting using a vitrectomy light pipe could further enhance the visualization of the anterior chamber.
Adjustments of donor graft size might be needed based on the white to white and the location of the shunt. A larger graft is desired as it will transplant more endothelial cells. Large grafts can also be planned for buphthalmic eyes with congenital glaucoma for the same reason.
Graft delivery techniques should minimize intraocular manipulation, especially in the presence of a glaucoma tube shunt. The touch-no touch technique entails staining the donor tissue with trypan blue, then inducing a double scroll by gently shaking the graft in saline. Once loaded, the injector is rotated until the double scroll faces upward before intraocular delivery. A 30-gauge cannula is then used to unfold the Descemet surface of the graft in small outward circular motions in the interface, all without touching the endothelium. The Moutsouris sign, where the tip of the cannula appears blue as it slides into the scroll, can be used to confirm correct orientation of the graft during unfolding. A pull-through technique described by Busin could be an alternative approach to deliver the graft., Oganesyan et al. employ a modified three-quarter DMEK technique for patients with tube shunts which follows the standard touch-no touch technique using a larger diameter graft (11–12 mm), with the missing quarter portion of the donor graft directly overlying the tube shunt area, to avoid contact between donor endothelial cells and the silicone tube. However, in our opinion, given the accelerated endothelial cell loss presented in eyes with previous glaucoma surgery, it is more desirable to maximize the graft size by trimming the shunt to make room instead of reducing the size of the graft. The shunt could be easily trimmed using intraocular anterior segment scissors.
Close control of intraoperative and postoperative IOP is essential to maximizing visual outcomes. Adequate air fill is important for graft attachment, while avoiding excessive pressure is essential to protect the optic nerve in glaucomatous eyes. For this reason, we do not recommend the use of SF6 as a primary tamponade agent. The appropriate IOP required to successfully attach the graft without damaging the optic nerve is unknown. Pilger et al. found that air tamponade over 2 h conducted at a physiologic IOP was associated with a lower rate of graft detachment compared with lower or higher IOP. We recommend that the IOP should not exceed 30-35 mmHg during a ten-minute full air fill and should be adjusted to mid-10 mmHg or less 1–2 h after the surgery, with a low threshold for additional glaucoma medications during the immediate postoperative period.
Adequate air fill can be more difficult to maintain in eyes with previous glaucoma surgery due to escape into the subconjunctival space, but with additional air injection, a full air filled is often achieved in eyes with Ahmed shunt. However, in eyes with Baerveldt shunt, the shunt might need to be tied at the of DMEK surgery and the suture is then lysed a couple weeks later once the graft is fully attached., SF6 should be used with caution in patients with advanced glaucoma as the outflow system is abnormal. Severe IOP spike could occur a few hours after the surgery.,,
Postoperative intraocular pressure management
Air or gas clearance is often delayed in eyes with glaucoma. It is imperative to check IOP 1–2 h after DMEK before discharging patient home. Releasing air from the paracentesis is an effective way of lowering IOP. This could be easily performed at the bedside using a portable slit lamp.
The different mechanisms of IOP elevation after DMEK must be recognized and managed appropriately [Table 1]. In the immediate postoperative period, IOP, extent of air fill, patency of any peripheral iridectomy, and anterior chamber anatomy should be closely monitored, especially in phakic patients. Total air fill, nonpatent iridotomies, or altered iris configurations leading to ocular hypertension can be managed with pupillary dilation, supine positioning, air release to as low as 30% fill, and glaucoma medications. Any preexisting glaucoma medication regimens should be restarted on the day after surgery. With regards to IOP measurement after DMEK, due to high intermodality variation noted, pneumotonometry and dynamic contour tend to overestimate Goldmann IOP readings, while the iCare overestimates low IOP and underestimates high IOP. IOP measurement using a Tonopen or pneumotonometer are preferred in cases with frank corneal edema. Additional glaucoma surgery might be necessary for adequate IOP control during the long term postoperative period.,,,
In routine cases, DMEK's low rejection rate allows shorter and lower potency steroid regimens, which decrease the risk for steroid response. However, patients with glaucoma surgery often require multiple concomitant procedures such as lysis of iridocorneal adhesions or tube trimming, and the subsequent inflammation may require more frequent or potent steroids during the immediate postoperative period. We often start taper topical steroids starting at 3 months. The rejection is not higher in eyes with previous glaucoma surgery than those without history of glaucoma. However, one study noted that from 37.5% to 70% of the rejection episodes occurred shortly after steroid taper. This highlights the need for future studies to determine whether a slower steroid taper or use of steroid sparing agents may decrease rejection rates in this population.
| Conclusions|| |
DMEK allows a rapid visual improvement, decreased rate of rejection, and excellent visual acuity. Previous glaucoma surgery increases the technical difficulty of the surgery, the risk for SGF, and the risk for possible repeat keratoplasty. Nevertheless, using modified surgical technique and postoperative management, DMEK can achieve very good outcomes in these complex eyes.
Financial support and sponsorship
Conflicts of interest
The authors declare that there are no conflicts of interests of this paper.
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[Table 1], [Table 2]