To evaluate 4-year outcomes of Descemet membrane endothelial keratoplasty (DMEK) in eyes with previous glaucoma surgery.
Retrospective, comparative case series.
Patients with previous trabeculectomy or glaucoma drainage device (GDD) implantation who later underwent DMEK (study group) were matched for follow-up duration with Fuchs dystrophy DMEK patients (control group). The minimum follow-up was 18 months. Primary outcomes included graft survival and rejection rates, and secondary outcomes included rates of detachment/rebubble, endothelial cell loss, best spectacle-corrected visual acuity, intraocular pressure, and glaucoma medications/surgeries. Subgroup analysis compared eyes with and without a GDD.
Ninety-four eyes of 91 patients were included. There were 51 eyes of 49 patients in the study group (GDD = 32 eyes, no GDD = 19 eyes) and 43 eyes of 42 patients in the control group. The mean follow-up was 37.9 ± 15.2 and 33.8 ± 13.5 months, respectively ( P = .322). Graft survival probability of the study group at 12, 24, 36, and 48 months was 75%, 60%, 43%, and 27%, respectively, compared with a consistent 88% in the control group ( P < .001). Survival curves of study subgroups (GDD and no GDD) were significantly lower than the control group ( P < .001). Rejection rates in the study and control groups were 19.6% and 2.3%, respectively ( P = .010). Endothelial cell loss in the study group was 12%-22% higher than the control group at 12, 24, 36, and 48 months ( P = .049, P = .027, P = .200, and P = .004).
In eyes with previous glaucoma surgery, DMEK has good early outcomes, but longer-term rejection and failure rates are high. Physicians and patients should be cognizant of the high likelihood of graft failure in this setting.
Endothelial keratoplasty has become the treatment of choice for corneal endothelial cell failure and continues to evolve as more data on surgical outcomes become available. Nevertheless, performing endothelial keratoplasty in some scenarios continues to be challenging. In eyes with a history of trabeculectomy or implantation of a glaucoma drainage device (GDD), adequate gas tamponade may be more difficult to achieve due to either active filtration of gas through the surgical glaucoma drain or posterior dislocation of gas through a large peripheral iridectomy. In addition, graft positioning and manipulation can be harder to perform due to either direct spatial interference created by a GDD or extensive synechiae.
Published data show good short-term outcomes of Descemet membrane endothelial keratoplasty (DMEK) in the setting of previous glaucoma surgery, albeit not as good as surgical outcomes in less complex eyes, such as those with Fuchs dystrophy. , In addition to lower visual outcomes of DMEK in eyes with previous glaucoma surgery, a possible trend toward increased rejection and secondary failure rates has been previously described. Secondary failure in the setting of previous glaucoma surgery may be linked to either increased rejection rates or to direct endothelial cell loss caused by the presence of a GDD. The risk of graft rejection and secondary failure is cumulative, and therefore longer-term follow-up is required to better understand survival of DMEK grafts in the setting of previous glaucoma surgery.
A recent study evaluating long-term outcomes of Descemet stripping endothelial keratoplasty (DSEK) in eyes with a GDD found that while DSEK was effective, graft survivability was only 50% at 3 years. To the best of our knowledge, published data on survival of DMEK grafts in the same setting are only available up to the second postoperative year. The purpose of this study was to evaluate 4-year outcomes of DMEK in eyes with previous glaucoma surgery, with an emphasis on 4-year graft survivability and rejection rates.
A retrospective chart review was performed, including all eyes with a history of trabeculectomy or GDD implantation who later underwent DMEK between 2013 and 2017 at Toronto Western Hospital and the Kensington Eye Institute (Toronto, Ontario, Canada) and had ≥18 months of follow-up. Overall, 51 eyes of 49 patients with previous glaucoma surgery were included. Four-year survival as well as rejection, detachment, rebubble, and endothelial cell loss rates were compared with a control group consisting of eyes with Fuchs dystrophy that underwent simultaneous DMEK and cataract extraction by the same corneal surgeon (D.S.R.). This retrospective interventional case series received Research Ethics Board approval by the University Health Network (Toronto Western Hospital, Toronto, Ontario, Canada) and adhered to the tenets of the Declaration of Helsinki.
Sample size calculation was performed to determine the required control group size. Two-year survival probability of DMEK in eyes with previous glaucoma surgery (the longest available DMEK survival data in this setting) has been reported to be 67% by Birbal and associates. Two-year DMEK survival rates of 91% have been previously reported by our group in patients with Fuchs dystrophy. Assuming a statistical power of 80% and a significance level of P = .05, a control group size of 43 subjects was required, given the previously reported survival rates of 67% for the study group and 91% for the control group. , Pairwise matching using propensity score matching (caliper size = 0.25 standard deviations) was performed to match 43 eyes of 42 patients with Fuchs dystrophy who underwent DMEK (out of 95 available eyes). Matching was performed for follow-up time, given the importance of follow-up time for survival parameters.
All donor tissue used was stored in corneal storage solution (Optisol; Bausch & Lomb, Rochester, New York, USA) and received from the Eye Bank of Canada, Ontario division. The mean donor age was 66.8 ± 4.8 years. All procedures were performed by a single experienced corneal surgeon (D.S.R.) and were not among the first 50 DMEK surgeries performed by him. DMEK grafts were prepared as previously described. Graft preparation was done according to the modified Melles technique using an “F” marking through a scleral window.
Our DMEK technique has been described previously. Briefly, descemetorhexis size was marked on the cornea, and 2 limbal paracenteses were performed at 2 and 10 o’clock. A temporal 2.4-mm clear corneal incision was performed. An anterior chamber maintainer was inserted inferotemporally into the anterior chamber. In previously vitrectomized eyes, a pars plana infusion was used to better control anterior chamber depth. A descemetorhexis was created using a reverse Sinskey hook under balanced salt solution (BSS) infusion followed by removal of the recipient Descemet membrane. Vision Blue (D.O.R.C., Zuidland, Netherlands) was injected into the anterior chamber to ensure complete removal of Descemet membrane remnants. The 7 mm-9 mm donor Descemet membrane (size was chosen according to recipient white-to-white measurements) was loaded into either a glass pipet (Geuder AG, Heidelberg, Germany) or an intraocular lens injector (Monarch D, Alcon Labs Inc, Fort Worth, Texas, USA), and injected into the anterior chamber through the clear corneal incision. The anterior chamber infusion was turned on and off as needed to keep the anterior chamber shallow but was removed after injection of the donor tissue into the anterior chamber. The tapping technique was used to unfold and position the graft, and the anterior chamber was then filled with air. BSS was injected into the anterior chamber, between the air bubble and the iris, to reduce the air bubble size up to a diameter slightly larger than that of the graft. No peripheral iridectomy was performed. Cyclopentolate hydrochloride 1% (MINIMS Cyc 1.0; Chauvin Pharmaceuticals Ltd, UK) and phenylephrine hydrochloride 2.5% (MINIMS PHNL 2.5; Chauvin Pharmaceuticals Ltd) were instilled to prevent pupillary block.
All patients remained supine for 2 hours and were then instructed to remain so as much as possible at home until the next morning. All patients were examined 2 hours and 1 day after surgery. Four patients required air release due to either elevated intraocular pressure (IOP) or a total anterior chamber air fill. All eyes underwent pressure patching overnight. The following day, 0.1% dexamethasone sodium phosphate and 0.3% tobramycin antibiotic (Tobradex; Alcon, Mississauga, Ontario, Canada) eye drops were administered 4 times daily for 1 week. Then, the antibiotic steroid drops were discontinued and 0.1% dexamethasone sodium phosphate (Maxidex; Alcon Labs Inc) eye drops were tapered down from 4 times daily to once daily over a 3-month period and continued once daily thereafter for a prolonged period of time. Hypotensive drops were maintained as preoperatively and changed according to clinical indication. Patients were examined at 1 week, 1 month, quarterly for the first postoperative year, semiannually for the second postoperative year, and annually thereafter.
Graft detachment was defined as any total or partial separation of the graft from the host cornea. Rebubbling was performed within 24 hours in eyes with Descemet membrane detachment of more than one-third of the DMEK graft area if no air bubble was left in the anterior chamber. Rebubbling was also performed 7-45 days postoperatively if there was unresolved Descemet membrane detachment that was causing persistent corneal edema either limiting rapid visual recovery or causing significant ocular surface discomfort. In cases of uncertainty, anterior segment optical coherence tomography (Optovue, Fremont, California, USA) was performed to determine whether there was graft detachment. Primary graft failure was defined as persistent, nonclearing corneal edema 2 months after DMEK. Secondary graft failure was defined as corneal decompensation after an initially functional DMEK graft. Endothelial graft rejection was defined as the presence of inflammation as evidenced by anterior chamber cells, keratic precipitates or endothelial rejection line, or the presence of corneal edema with conjunctival injection and symptoms of pain or light sensitivity.
Primary outcomes included graft survival and graft rejection rates. Secondary outcomes included rates of detachment/rebubble, visual acuity, endothelial cell loss, IOP, and glaucoma medications/surgeries.
Data Collection and Statistical Analysis
The data collected in this study included patient demographics, best spectacle-corrected visual acuity (BSCVA), associated operative procedures (including details on timing and indication for glaucoma surgeries), IOP, number of hypotensive ocular medications, intraoperative and postoperative complications, corneal donor characteristics, and endothelial cell density using a noncontact specular microscope (Robo, KSS 300; Konan Medical, Hyogo, Japan). In eyes where graft failure occurred, follow-up data were included up to the point of graft failure. Data after graft failure was not included in endothelial cell loss and BSCVA analyses. Data were also recorded on the management of failed grafts. In addition to comparison of the study group with a control group of patients with Fuchs dystrophy, a subgroup analysis within the study group compared survival, detachment, and rebubble rates between eyes that had a GDD (n = 32) and those that did not have a GDD (n = 19).
Data were recorded in Microsoft Excel 2016 (Microsoft Corp, Redmond, Washington, USA) and analyzed using the XLSTAT add-in (v 2019.1.2; Addinsoft, New York, New York, USA). Continuous paired variables were compared using the Wilcoxon nonparametric test. Continuous nonpaired variables were compared with the Mann-Whitney U test. Repeated measures analysis of variance and mixed effect models were used where appropriate. Categorical variables were analyzed using the Fisher exact test. Graft survival was analyzed using Kaplan-Meier survival analysis and was compared between groups using the log-rank test. All tests were 2-tailed, and the threshold for statistical significance was defined as a P < .05.
Fifty-one eyes of 49 patients (20 men and 29 women) aged 68.0 ±16.1 years (range 26-94 years) were included in the study group. The mean follow-up time was 37.9 ± 15.2 months (range 18-66 months) in eyes with no failure and 24.1 ± 14.9 months (range 2-62 months) in eyes with failure. Forty-four eyes were pseudophakic, 3 eyes were phakic, and 4 eyes were aphakic. Thirty-two eyes had previous GDD implantation and 19 eyes had glaucoma surgery other than GDD implantation. Details on previous glaucoma procedures are shown in Table 1 .
|Type of Glaucoma Surgery||Eyes, n|
|GDD combined with trabeculectomy||7|
|GDD and a microshunt a||1|
|Trabeculectomy and a microshunt b||1|
a Hydrus Microstent (Ivantis, Inc, Irvine, California, USA).
Indications for DMEK in the study group were pseudophakic bullous keratopathy (25 eyes), failed Descemet stripping endothelial keratoplasty (DSAEK; 12 eyes), failed penetrating keratoplasty (10 eyes), Fuchs endothelial dystrophy (3 eyes), and iridocorneal endothelial syndrome (1 eye). Details on additional surgical procedures that were combined with DMEK are shown in Table 2 .
|Implantation of a scleral-fixated IOL (in aphakia)||2|
|IOL fixation (of a subluxed IOL)||2|