CLINICAL SCIENCES. Clinical Outcome of 200 Consecutive Cases After a Learning Curve of 25 Cases

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1 ONLINE FIRST CLINICAL SCIENCES Efficacy of Descemet Membrane Endothelial Keratoplasty Clinical Outcome of 2 Consecutive Cases After a Learning Curve of 25 Cases Martin Dirisamer, MD; Lisanne Ham, MSc; Isabel Dapena, MD; Kyros Moutsouris, MD; Konstantinos Droutsas, PhD; Korine van Dijk, BSc; Laurence E. Frank, PhD; Silke Oellerich, PhD; Gerrit R. J. Melles, MD, PhD Objective: To evaluate Descemet membrane endothelial keratoplasty for management of corneal endothelial disorders. Methods: Descemet membrane endothelial keratoplasty was performed in 2 patients with Fuchs endothelial dystrophy or bullous keratopathy. Best-corrected visual acuity, subjective and objective refractive outcome and stability, and endothelial cell density were evaluated at 1, 3, and 6 months postoperatively, and intraoperative and postoperative complications were documented. Results: At 6 months, 9% reached a best-corrected visual acuity of 2/ or better (.5); 77%, 2/25 or better (.); 7%, 2/2 or better ( 1.), and 16%, 2/17 or better ( 1.2) (n=159). The preoperative to 6 months postoperative spherical equivalent showed a mean (SD).3 (1.2) diopter hyperopic shift (P=.1) that correlated with a decrease in central corneal thickness (n=13) (P=.7). Two-thirds of eyes showed refractive stability at 3 months. Donor endothelial cell density showed a decrease from mean (SD ) 256 (16) cells/ mm 2 preoperatively to 169 (52) cells/mm 2 at 6 months after surgery (n=173) (P.1). Graft detachment was the main complication and occurred in 1 eyes (9%). Recipient Descemet membrane remnants were present in eyes (6%). Secondary glaucoma was seen in eyes (%), of which showed air-bubble dislocation behind the iris. In 2 of 33 phakic eyes (6%), a secondary cataract developed requiring phacoemulsification. Conclusions: Descemet membrane endothelial keratoplasty may offer complete visual rehabilitation within 1 to 6 months after surgery in a majority of eyes. Similar to earlier keratoplasty techniques, Descemet membrane endothelial keratoplasty may be associated with a one-third decrease in donor endothelial cell density in the early postoperative phase. Incidence of (partial) graft detachment stabilized at about 5% but could be further reduced by patient selection and/or technique modification. Trial Registration: clinicaltrials.gov Identifier: NCT5219. Arch Ophthalmol. 211;9(11): Published online July 11, 211. doi:1.11/archophthalmol Author Affiliations: Netherlands Institute for Innovative Ocular Surgery (Drs Dirisamer, Dapena, Moutsouris, Droutsas, Oellerich, and Melles and Mss Ham and van Dijk), Melles Cornea Clinic Rotterdam (Drs Dirisamer, Dapena, Moutsouris, Droutsas, Oellerich, and Melles and Mss Ham and van Dijk), and Amnitrans Eyebank Rotterdam (Dr Melles and Ms Ham), Rotterdam, and Department of Methodology and Statistics, Utrecht University, Utrecht (Dr Frank), the Netherlands; and Ophthalmology Department, AKh Linz, Linz, Austria (Dr Dirisamer). SINCE 199, WE HAVE INTROduced various techniques for treatment of corneal endothelial disorders, popularized as deep lamellar endothelial keratoplasty and Descemet stripping (automated) endothelial keratoplasty (DSEK/DSAEK). 1-5 Recently, we described a technique for selective transplant of the Descemet membrane (DM), referred to as Descemet membrane endothelial keratoplasty (DMEK). 1,2 Our initial results showed that if successful, DMEK may enable significantly better visual outcomes than deep lamellar endothelial keratoplasty and DSEK/DSAEK 6 and faster visual rehabilitation. 7 These results have been confirmed by others,,9 who also reported a best-corrected visual acuity (BCVA) of 2/ or better (.5) in about 95% of patients and 2/25 or better (.) in about 6% at 6 months postoperatively. All of these reports included the first DMEK cases performed by these surgeons, so the overall outcome may have been negatively biased by a learningcurve effect. In our initial cases, DMEK was relatively frequently complicated by graft detachment. 1,11 Hence, extensive in vitro studies were performed to minimize the risk of detachment and to further standardize the technique to allow its efficacy. Hence, our study aimed to evaluate the surgical protocol for standardized no-touch DMEK by documenting the clinical outcome of 2 consecutive DMEK cases performed after a first series of 25 learning-curve cases. ARCH OPHTHALMOL / VOL 9 (NO. 11), NOV American Medical Association. All rights reserved. Downloaded From: on //217

2 METHODS Our prospective study included 2 consecutive eyes of 166 patients with Fuchs endothelial dystrophy or bullous keratopathy who underwent DMEK (Table 1). The 2 cases evaluated were cases 26 to 225 from the first 225 consecutive DMEK surgeries performed by our group, after an initial learning curve of 25 DMEK eyes. The 2 surgeries were (partially) performed by 5 surgeons (M.D., I.D., K.M., K.D., and G.R.J.M.), and in 51 cases, the entire surgery was conducted by the fellow alone. After institutional review board review of the study protocol, all patients signed an institutional review board approved informed consent; the study was conducted according to the Declaration of Helsinki and registered at (NCT5219). DONOR TISSUE PROTOCOL A procedure for harvesting of the DM graft has been previously described. 13 In short, from donor globes obtained 36 hours or less post mortem, corneoscleral buttons were excised and stored by organ culture at 31 C. After 1 week of culture, endothelial cell morphology and viability were evaluated and the corneoscleral buttons were mounted endothelial side up on a custom-made holder. Being submerged in saline, a 9.5-mmdiameter DM sheet with its endothelium was stripped from the posterior stroma. Because of the elastic tissue properties, a Descemet roll formed spontaneously, with the endothelium at the outer side. Each Descemet roll was then stored for 5 to 1 days in organ culture medium until the time of transplant. 13 Table 1. Demographics for Patients Who Underwent DMEK No. (%) (N=2 Eyes) Patients 166 Age, mean (SD), y [range] 66 () [31-93] Men 96 () Women 1 (52) Phakic eyes 33 (17) Abbreviation: DMEK, Descemet membrane endothelial keratoplasty. SURGICAL PROTOCOL All eyes were operated on under local anesthesia ( ml of ropivacaine hydrochloride, 1%, with 15 IE of Hyason), followed by ocular massage and application of a Honan balloon for 1 minutes, and the patient was positioned in an anti- Trendelenburg position. Surgeries were performed as previously described. A 3.-mm tunnel incision was made at the limbus, the anterior chamber was filled with air, and a circular portion of DM was scored with an inversed Sinskey hook (DORC International, Zuidland, the Netherlands) and stripped from the posterior stroma so that a 9.-mm-diameter descemetorhexis was created. 1 The donor Descemet roll was stained with a trypan blue solution,.6% (VisionBlue; DORC International), and sucked into a custom-made injector (DMEK inserter; DORC International) to inject the Descemet roll into the recipient anterior chamber and the graft was oriented endothelial side down (donor DM facing recipient posterior stroma) by indirect manipulation with air and balanced salt solution. The graft was then gently spread out over the iris, and an air bubble was injected underneath the graft to position it onto the recipient posterior stroma. The anterior chamber was left completely filled with Patients, % BCVA Postoperative Time After DMEK, mo Figure 1. Graph displaying the best-corrected visual acuity (BCVA) before () and at 1, 3, and 6 months after Descemet membrane endothelial keratoplasty (DMEK) surgery. Table 2. Analysis of Clinical Outcome of DMEK in 2 Eyes Exclusion Criteria BCVA No. of Eyes Subjective Refractive Data BCVA CF BCVA 2/6 Pentacam a Data Endothelial Cell Density 1 Follow-up measurements not available Low visual potential 23 Secondary DSEK Secondary DMEK b (5) (5) (5) (5) (5) Spontaneous corneal clearance despite graft detachment Total excluded Total evaluated Abbreviations: BCVA, best-corrected visual acuity; CF, counting fingers; DMEK, Descemet membrane endothelial keratoplasty; DSEK, Descemet stripping endothelial keratoplasty;, preoperative. a Oculus, Wetzlar, Germany. b All secondary DMEK performed after the 6-month study evaluation interval. These values are in parentheses because they are not part of the total sum of eyes excluded. ARCH OPHTHALMOL / VOL 9 (NO. 11), NOV American Medical Association. All rights reserved. Downloaded From: on //217

3 Table 3. Visual Outcome After DMEK No. of Eyes (%) (n=159) BCVA erative 1 mo 3 mo 6 mo 2/ (.5) 57 (36) 135 (5) 16 (92) 15 (9) 2/25 (.) 9 (6) 5 (53) 13 (65) 3 (77) 2/2 ( 1.) 35 (22) 57 (36) 7 (7) 2/17 ( 1.2) 5 (3) 9 (6) 25 (16) Abbreviations: BCVA, best-corrected visual acuity; DMEK, Descemet membrane endothelial keratoplasty. air for 3 to 6 minutes followed by an air-liquid exchange to pressurize the eye. Each surgical procedure was recorded on DVD (DVR-RT61H-S; Pioneer, Tokyo, Japan). In all eyes, a YAG laser peripheral iridotomy was made at the -o clock position 1 to 2 weeks before the surgery to reduce the potential risk of pupillary block glaucoma after surgery due to the 3% to 5% air bubble in the anterior chamber. Because patients were requested to lie in a supine position after surgery (with the Bell phenomenon rotating the eye upward on eye closure), the iridotomy was made at the - o clock position. MEASUREMENTS AND STATISTICS Donor endothelial cell density (ECD) was evaluated in vitro (Axiovert inverted light microscope; Zeiss, Göttingen, Germany) and photographed (PixeLINK PL-A662; Zeiss). 13 In patient eyes, ECD was evaluated in vivo using a Topcon SP3p noncontact autofocus specular microscope (Topcon Medical Europe BV, Capelle a/d IJssel, the Netherlands). Images of the central corneal window were manually corrected and 3 measurements were averaged. All recipient eyes were examined before and after DMEK at 1, 3, and 6 months with biomicroscopy, Pentacam imaging (Oculus, Wetzlar, Germany), noncontact specular microscopy, and slitlamp photography (Topcon Medical Europe BV). Bestcorrected visual acuity, ECD, and intraoperative and postoperative complications were recorded in a database. For all comparisons, 2-sided paired-sample t tests were performed (SPSS version 1.; IBM SPSS, Chicago, Illinois). P values for the Pentacam and refractive data were corrected with the Benjamini and Hochberg correction (multiple tests increase false positives). 15 After correction, all P values.5 represented statistical significance. The relation between the change in spherical equivalent (SE) and central corneal thickness (induced hyperopic shift) was estimated with the Pearson correlation. RESULTS DEMOGRAPHICS The first 2 consecutive DMEK cases were evaluated. Hence, surgical cases 26 to 225 were evaluated at 1, 3, and 6 months after surgery, 33 (17%) of them with phakic eyes (Table 1). In patients with phakic eyes referred to us for combined cataract extraction and DMEK, phacoemulsification was performed 1 to 2 months prior to the transplant. Postphacoemulsification measurements were used as preoperative DMEK refractive data to avoid bias related to the margin of error in the refractive effect after intraocular lens implantation. BEST-CORRECTED VISUAL ACUITY From a total of 2 eyes, 1 were excluded from visual acuity analysis: 23 had low visual potential, had secondary DSEK performed after DMEK failure, showed spontaneous corneal clearance despite graft detachment, 16 and 2 had incomplete measurements (Table 2). At 6 months, all but 9 eyes (9%) reached a BCVA of 2/ or better (.5); 77%, 2/25 or better (.); 7%, 2/2 or better ( 1.); and 16%, 2/17 or better ( 1.2) (n=159) (Figure 1)(Table 3). At 1 month, these percentages were 5%, 53%, 22%, and 3%, respectively, and at 3 months, 92%, 65%, 36%, and 6% (Figure 1) (Table 3). In 23 patients under the 2/25 (.) level, the BCVA changed 2 or more lines from the 3 to the 6 months examination: 21 eyes (91%) improved and 2 (9%) deteriorated. The latter 2 had a decrease from 2/2 (.7) to 2/5 (.) and 2/2 (1.) to 2/2 (.7) without an apparent cause. SE OF SUBJECTIVE REFRACTION From 13 patients with a preoperative BCVA of at least counting fingers, refractive data were available at all follow-up intervals (Table ). Because the reliability of refraction may be compromised by low visual acuity, we performed the same analysis for the 115 eyes with a preoperative BCVA of 2/6 or better (.3), but similar correlations were found (Table 5). For the whole group (n=13), the mean (SD) preoperative to postoperative change in SE (hyperopic and myopic shifts in corneal power averaged) was.9 (1.2) diopter (D) (P.1) at 3 months and.3 (1.2) D (P=.1) at 6 months (Table ). The mean (SD) preoperative to postoperative absolute change in SE (absolute change in corneal power) was.96 (.) D at 3 months and.9 (.) D at 6 months (Table ). For the group of 115 eyes with a preoperative BCVA of 2/6 or better (.3), the data are presented in Table 5. CYLINDRICAL ERROR OF SUBJECTIVE REFRACTION For the whole group (n=13), the mean (SD) preoperative to postoperative change in refractive cylinder (hyperopic and myopic shifts in cylindrical power averaged) was.36 (1.2 ) D (P=.2) at 3 months and.29 (1.1) D (P=.6) at 6 months (Table ). The mean (SD) preop- ARCH OPHTHALMOL / VOL 9 (NO. 11), NOV American Medical Association. All rights reserved. Downloaded From: on //217

4 Table. Subjective Refractive Outcome of DMEK in 13 Eyes With a erative BCVA of at Least CF ( 1/6) Mean (SD), D P Value SE.19 (1.) Sphere.31 (1.) Cyl 1.1 (.9) 3-mo Postop SE.29 (1.5) Sphere.9 (1.6) Cyl 1.37 (1.) 6-mo Postop SE.1 (1.6) Sphere.3 (1.6) Cyl 1.3 (1.) SE 3 mo vs.9 (1.2).1 a SE 3 mo vs absolute.96 (.) SE 6 mo vs.3 (1.2).1 a SE 6 mo vs absolute.9 (.) SE 6 mo vs 3 mo.11 (.7).9 Cyl 3 mo vs.36 (1.2).2 a Cyl 3 mo vs absolute.93 (.) Cyl 6 mo vs.29 (1.1).6 a Cyl 6 mo vs absolute.91 (.7) Cyl 6 mo vs 3 mo.7 (.9).35 Abbreviations: BCVA, best-corrected visual acuity; CF, counting fingers; Cyl, cylindrical error; D, diopter; DMEK, Descemet membrane endothelial keratoplasty; Postop, postoperative;, preoperative; SE, spherical equivalent. a Significant. Table 5. Subjective Refractive Outcome of DMEK in 115 Eyes With a erative BCVA of 2/6 or Better (.3) Mean (SD), D P Value SE.1 (1.3) Sphere.32 (1.) Cyl 1. (.) 3-mo Postop SE.3 (1.2) Sphere.9 (1.2) Cyl 1.36 (1.) 6-mo Postop SE.17 (1.3) Sphere.2 (13) Cyl 1.32 (1.) SE 3 mo vs. (1.1).1 a SE 3 mo vs absolute.93 (.7) SE 6 mo vs.3 (1.1).5 a SE 6 mo vs absolute. (.) SE 6 mo vs 3 mo.13 (.7).1 Cyl 3 mo vs.36 (1.1). a Cyl 3 mo vs absolute.7 (.) Cyl 6 mo vs.31 (1.).5 a Cyl 6 mo vs absolute.6 (.7) Cyl 6 mo vs 3 mo.5 (.).53 Abbreviations: BCVA, best-corrected visual acuity; CF, counting fingers; Cyl, cylindrical error; D, diopter; DMEK, Descemet membrane endothelial keratoplasty; Postop, postoperative;, preoperative; SE, spherical equivalent. a Significant. erative to postoperative absolute change in refractive cylinder (absolute change in cylindrical power) was.93 (.) D at 3 months and.91 (.7) D at 6 months (Table ). For the group of 115 eyes with a preoperative BCVA of 2/6 or better (.3), the data are presented in Table 5. STABILITY OF REFRACTION Refractive stability was analyzed by comparing preoperative with postoperative refraction, as well as 3-month with 6-month postoperative refractions (n=13). The change in SE before and at 3 months after surgery was.5 D or less in 3% and 1. D or less in 62% of eyes and at 6 months,.5 D or less in 3% and 1. D or less in 69% (Table 6). The change in cylindrical error before and at 3 months after surgery was 1. D or less in 66% and 2. D or less in 9% of eyes and at 6 months, 1. D or less in 6% and 2. D or less in 95% (Table 6). From 3 to 6 months, no significant change in SE (P=.9) or cylindrical error (P=.35) was found (Table ). Patients were fitted with glasses if desired at 3 months or continued wearing their preoperative glasses. All patients obtained full binocular vision, except for 1 case (monoculus). OBJECTIVE CORNEAL POWER MEASUREMENTS Using topographic maps (n=15), the change in true net power mean (SD) keratometric values before surgery and at 3 months was 1. (.7) D and at 6 months, 1.2 (.7) D(P.1) (Table 7). The change in anterior corneal curvature before surgery and at 3 months was.5 (.) D and at six months,.3 (.) D (both P.1) (Figure 2) (Table 7), and the change in posterior corneal curvature before surgery and at 3 months was. (.) D and at 6 months,.7 (.) D (P.1) (Figure 2) (Table 7). Although there was a change from before surgery to 3 months postoperatively, no significant difference in topographic astigmatism was found at the 6-month interval (P=.) (Table 7). PACHYMETRY Central corneal thickness decreased from mean (SD) 675 (9) µm before surgery to 526 (6) µm at 3 months and 527 (5) µm at 6 months (n=15), ie, a decrease of 19 () µm and 1 () µm, respectively (P.1) (Figure 2) (Table ). A significant negative correlation was found between the preoperative and 6-month central corneal thickness and SE values (n=6) (r 2 =.32; P=.7), which represents a small effect (Figure 3). ENDOTHELIAL CELL DENSITY Of the DMEK eyes with an attached Descemet graft, preoperative and postoperative ECD measurements were available in 173 eyes. Mean (SD) donor ECD was 256 (16) cells/mm 2 preoperatively and 169 (52) cells/ mm 2 at 6 months after surgery (P.1) (Table 9). In all eyes in which graft attachment was obtained, the transplanted cornea cleared within 1 to weeks (Figure A and B). No clearance was seen in the pres- ARCH OPHTHALMOL / VOL 9 (NO. 11), NOV American Medical Association. All rights reserved. Downloaded From: on //217

5 Table 6. Stability of Refraction After DMEK in 13 Eyes SE3movs.5 D SE3movs 1. D Cyl3movs 1. D Cyl3movs 2. D No. (%) SE6movs.5 D SE6movs 1. D Cyl6movs 1. D Cyl6movs 2. D 55 (3) (62) 9 (66) 13 (9) 5 (3) 9 (69) 91 (6) 136 (95) Abbreviations: Cyl, cylindrical error; D, diopter; DMEK, Descemet membrane endothelial keratoplasty;, preoperative; SE, spherical equivalent. Table 7. Objective Refractive Outcome (Pentacam a Measurements) After DMEK in 15 Eyes Mean (SD), D 3-mo Postop 6-mo Postop K TA K TA K TA K3mo vs TA3mo vs K6mo vs TA6mo vs True net power 2.3 (2.2) 1.9 (1.6).9 (1.5) 2. (1.7) 1.1 (1.5) 2.1 (1.5) 1. (.7).5 (.1) 1.2 (.7).2 (.1) P value.1 b. b.1 b. Anterior corneal curvature 2.9 (1.9) 1.6 (1.5) 2. (1.5) 1.9 (1.) 2.6 (1.5) 1.7 (1.3).5 (.).3 (.1).3 (.).1 (.2) P value.1 b.3 b.1 b. Posterior corneal curvature 5.6 (.).5 (.) 6. (.).5 (.5) 6.3 (.).5 (.6). (.). (.1).7 (.). (.2) P value.1 b..1 b.1 Abbreviations: D, diopter; DMEK, Descemet membrane endothelial keratoplasty; K, keratometric value; Postop, postoperative;, preoperative; TA, topographic astigmatism. a Oculus, Wetzlar, Germany. b Significant. ence of a complete graft detachment, eg, a Descemet roll in the recipient anterior chamber (Figure C and D), although spontaneous clearance despite graft detachment was seen in eyes (Figure E and F) (Table 2). INTRAOPERATIVE COMPLICATIONS Failure to unfold the Descemet graft in the anterior chamber occurred in 1 case (.5%) and vitreous pressure was present in 15 cases (7.5%) (Table 1). In patients with pseudophakic eyes (2%), an intraoperative hemorrhage, originating from the iris root, was caused by traction on the peripupillary iris while positioning an air cannula underneath the unfolded Descemet graft prior to lifting the graft toward the recipient posterior cornea (Table 1). POSTOPERATIVE COMPLICATIONS None of the transplanted corneas failed to clear in the presence of an attached Descemet graft; in other words, a failure of the transplanted cornea to clear was only seen in the presence of graft detachment. One eye showed a secondary graft failure at 1 months after surgery (Table 1). Graft detachment was defined as a lack of adherence between the Descemet graft and the recipient posterior stroma (frequently seen as a free-floating Descemet roll in the recipient anterior chamber within the first postoperative week) or a partial lack of adherence requiring secondary surgical intervention (rebubbling or regraft). Overall, 9% (1 of 2) of eyes showed a graft detachment, % ( of 2) a complete and 5% (1 of 2) a partial detachment (Figure C and D) (Table 1). Small peripheral detachments occurred in 7% (1 of 2). Twelve eyes (6%) had recipient DM remnants at the donor-to-host interface after surgery (Figure 5). 17 Three eyes (1.5%) of 3 patients developed an allograft rejection. One patient noticed discomfort and a reduced visual acuity, but no subjective complaints were experienced by the other patients, who both had discontinued their steroid medication prematurely (Table 1). At 3 months after DMEK, 1 eye (.5%) presented with a small peripheral infiltrate in an area with remnant peripheral corneal edema that resolved with topical antibiotics (Table 1). Because a 5% air fill of the anterior chamber was maintained at the end of the surgery, the operated-on DMEK eyes were considered at risk to develop pupillary block glaucoma. Hence, a YAG laser iridotomy was made at the -o clock position prior to surgery. Although no true pupillary block glaucoma was observed, secondary glaucoma due to air-bubble dislocation behind the iris and/or mechanical forward displacement of the iris diaphragm occurred in 2% ( of 2) of eyes (Table 1). An additional eyes developed another type of secondary glaucoma after DMEK surgery (2% [ of 2]) (Table 1). One patient with bilateral DMEK developed a steroid-induced glaucoma in both eyes within the first postoperative month. One case with preexisting openangle glaucoma developed mm Hg spikes after surgery that required additional topical antiglaucoma medication. One eye developed peripheral anterior synechiae resulting in recurrent intraocular pressure elevations, eventually necessitating glaucoma surgery. One eye that had undergone phacoemulsification, penetrating keratoplasty (PK), and vitrectomies showed hypotonia for several weeks after the DMEK (Table 1). ARCH OPHTHALMOL / VOL 9 (NO. 11), NOV American Medical Association. All rights reserved. Downloaded From: on //217

6 A B 6 mo Postop C Sagittal curvature (front) Sagittal curvature (front) 9 6 OS 9 6 OS Difference map Sagittal curvature (front) T D Sagittal curvature (back) E Sagittal curvature (back) F OS T OS 2 27 Sagital curvature (back) T 2 27 T 2 27 G H I Corneal thickness Corneal thickness 9 6 OS 9 6 OS Corneal thickness Figure 2. Topographic corneal power maps of the anterior corneal curvature (A-C), posterior corneal curvature (D-F), and central corneal thickness (G-I) before Descemet membrane endothelial keratoplasty () (A, D, and G) and 6 months after Descemet membrane endothelial keratoplasty (Postop) (B, E, and H) and the corresponding difference maps (C, F, and I). The anterior corneal curvature is stable, but the posterior curvature does show a change of approximately 1. diopter. Compare with Table 7. In phakic eyes, mild anterior crystalline lens opacities were sometimes observed after DMEK and usually faded within months. However, in 2 of 33 phakic eyes (6%), the induced lens opacities required phacoemulsification (Table 1). 1 Cystoid macular edema developed in 1 patient (.5% [1 of 2]) after creating a YAG laser iridotomy prior to DMEK (Table 1). One high-myopic eye (.5% [1 of 2]) presented with a retinal detachment at 2 months after surgery requiring vitrectomy (Table 1). One eye developed a macular hole (.5% [1 of 2]) and 2 eyes, a macular pucker (1% [2 of 2]) within the first months after surgery (Table 1). SECONDARY CORNEAL PROCEDURES A rebubbling procedure was performed in 7 eyes (3.5%), eyes (6%) underwent a second DSEK, and 5 eyes (2.5%) ARCH OPHTHALMOL / VOL 9 (NO. 11), NOV American Medical Association. All rights reserved. Downloaded From: on //217

7 Table. Central Corneal Thickness (Pentacam a Measurements) After DMEK in 15 Eyes 3-mo Postop 6-mo Postop CT 3 mo vs CT 6 mo vs CCT, µm, mean (SD) 675 (9) 526 (6) 527 (5) 19 () 1 () P value.1 b.1 b Abbreviations: CCT, central corneal thickness; DMEK, Descemet membrane endothelial keratoplasty; Postop, postoperative;, preoperative. a Oculus, Wetzlar, Germany. b Significant. Δ Spherical Equivalent, D r 2 = Δ Corneal Thickness, µm A C B D Figure 3. Scatterplot displaying the difference in preoperative to 6 months postoperative central corneal thickness and spherical equivalent, which revealed a significant correlation. D indicates diopters. E F Table 9. Donor Endothelial Cell Density Before and After DMEK in 173 Eyes erative 6 mo Density, cells/mm 2, mean (SD) 256 (16) 169 (52) Decrease in density, % 33.9 P value.1 a Abbreviation: DMEK, Descemet membrane endothelial keratoplasty. a Significant. underwent a second DMEK (Figure 6) (Table 1). All of the secondary DSEK and DMEK procedures were successful, and visual outcomes were similar to primary DSEK or DMEK procedures. 19 COMMENT To our knowledge, this is the first prospective study on the efficacy of DMEK, ie, an analysis of its outcomes in a large patient series, unbiased by a learning-curve effect. In past years, the donor preparation protocol was validated, 13 and the surgical technique could be standardized as a completely no-touch technique. Hence, the present data may allow a new baseline for clinical outcome in keratoplasty surgery. VISUAL OUTCOME AND REHABILITATION RATE Figure. Slitlamp and Scheimpflug images of an eye 1 month after successful Descemet membrane endothelial keratoplasty (DMEK) surgery (A and B), and another eye 1 and 6 months after DMEK surgery complicated by graft detachment (C-F). Note the near normal corneal anatomy after successful DMEK surgery, while the other eye initially showed corneal decompensation (C and D) (arrows) followed by spontaneous clearance of the transplanted cornea despite persistent graft detachment (E and F) (arrows). About % of cases reached a BCVA of 2/25 or better (.) at 6 months after DMEK, with about 5% reaching 2/2 or better ( 1.). These visual outcomes may compare favorably with any earlier keratoplasty technique. Historic studies on PK for Fuchs endothelial dystrophy reported a visual outcome of 2/ or better (.5) at 1 year in % to 5% of patients. 2 Descemet stripping endothelial keratoplasty/dsaek may surpass PK, with visual acuities up to 2/ (.5) in most cases but with only small percentages reaching 2/25 or better (.). 1-5,21 Clinical observation suggests that (cultured) donor posterior stroma in DSEK/DSAEK grafts degrades the optical quality of a transplanted cornea. 2,22,23 Furthermore, the rate of visual rehabilitation may also be faster after DMEK, with most patients reaching their maximal visual potential in 1 to 3 months, 7 compared with 6 to months following DSEK/DSAEK and PK. 3-5,2,2,25 REFRACTIVE CHANGE AND STABILITY After DMEK, both the SE and the cylindrical error were within 1. D from the preoperative refractive error. Pachymetry and refractive data suggested that the transplanted cornea stabilizes approximately 3 months after DMEK, so new glasses could commonly be prescribed at this point, until which most patients were able to continue wearing their own glasses. ARCH OPHTHALMOL / VOL 9 (NO. 11), NOV American Medical Association. All rights reserved. Downloaded From: on //217

8 Table 1. Complications After DMEK Complications, No. (%) (n=2) Intraoperative Failed to unfold/position DMEK 1 (.5) graft Vitreous pressure during surgery 15 (7.5) Iris root hemorrhage (2.) Postoperative Graft related Secondary graft failure 1 (.5) Graft detachment Complete (); first 1 cases: 5 (5); second 1 cases: 3 (3) Partial 1 (5); first 1 cases: (); second 1 cases: 2 (2) Total 1 (9); first 1 cases: 13 (13); second 1 cases: 5 (5) Recipient related Remnant recipient Descemet (6) membrane at interface Allograft rejection 3 (1.5) Corneal infiltrate 1 (.5) Intraocular pressure Pupillary block glaucoma Air bubble induced (2) angle-closure glaucoma Hypotonic eye 1 (.5) Secondary glaucoma (2) Crystalline lens Iatrogenic-induced cataract 2 (6) (Of 33 phakic eyes) Posterior segment Cystoid macular edema 1 (.5) Macular hole 1 (.5) Macular pucker 2 (1) Retinal detachment 1 (.5) Reoperations Rebubbling 7 (3.5) Second DSEK (6) Second DMEK 5 (2.5) Abbreviations: DMEK, Descemet membrane endothelial keratoplasty; DSEK, Descemet stripping endothelial keratoplasty. A B 1 Eyes reoperated on Second DMEK 5 7 Rebubbling 1 Second DSEK Figure 6. Diagram displaying the number and sequence of secondary interventions after the 2 Descemet membrane endothelial keratoplasty (DMEK) surgeries performed in this study. DSEK indicates Descemet stripping endothelial keratoplasty. carried by the endothelial transplant (being thinner centrally than at its peripheral flange). Since only an isolated donor DM is transplanted in DMEK, the hyperopic shift in DMEK cannot be explained by the same mechanism. The correlation found between the SE and the decrease in central corneal thickness (Figure 3) may indicate that the refractive shift in DMEK results from the preoperative to postoperative difference in recipient corneal hydration and the associated posterior corneal curvature change.,26 The change in anterior corneal power is only about.3 D and falls within the margin of error in intraocular lens power calculation, so established nomograms may be used to calculate the intraocular lens power for cataract surgery at any time prior to DMEK. 26 ENDOTHELIAL CELL DENSITY In the first 6 months after DMEK surgery, the donor ECD decreased about 3% compared with the preoperative counts, similar to the 31% to 3% decrease in ECD after DSEK/DSAEK Longer-term follow-up may reveal how the decline in ECD after DMEK compares with PK and DSEK/DSAEK. Since DMEK graft diameters (9.-1. mm) exceed those in PK (7.-. mm) and DSEK/DSAEK (.- 9. mm), more endothelium is transplanted, potentially providing longer graft survival in DMEK. 3 3 Clear COMPLICATIONS AND THEIR MANAGEMENT Figure 5. Slitlamp photographs of an eye 1 month after Descemet membrane endothelial keratoplasty. Note the recipient Descemet membrane remnant (arrows) in the paracentral cornea (A), potentially interfering with the visual acuity (B). HYPEROPIC SHIFT IN DMEK AND LENS POWER CALCULATION FOR CATARACT SURGERY Unexpectedly, our study revealed about a.-d hyperopic shift after DMEK. In DSEK/DSAEK, a 1.5-D shift may result from the negative-lenticle effect of the stroma (Partial) graft detachment, the most frequent complication in endothelial keratoplasty, 2-,11,3 occurred in 1 eyes (9%): 13 in the first 1 cases and 5 in the second 1 cases (Table 1) (Figure 6), despite general precautions, such as a 6-minute air fill of the anterior chamber at the end of the surgery to support the graft and avoiding the use of plastic and/or viscoelastic materials. 1 Three additional risk factors were identified: intraoperative vitreous pressure, improper graft positioning, and postoperative ocular hypotonia. Hence, it may be advocated to obtain a soft eye before surgery. Inward folds (causing partial detachments by the graft springing away from the recipient stroma) may be managed by bubble bumping, ie, applying intermittent pressure on the corneal surface to completely unfold the graft. Upside-down po- ARCH OPHTHALMOL / VOL 9 (NO. 11), NOV American Medical Association. All rights reserved. Downloaded From: on //217

9 sitioning may be avoided by inserting the Descemet graft as a double roll and checking its upward orientation. Eyes at risk of developing postoperative hypotonia (eyes with aphakia, sector iridectomy, shallow anterior chamber, glaucoma shunt tube, or preceding posterior segment surgery) may be managed with a modified surgical technique.,3 Secondary glaucoma due to air bubble misdirection may be avoided by leaving a 2% to 3% (instead of 5%) air bubble in phakic eyes. 3 Performing the descemetorhexis under air may avoid the risk of remnant recipient DM fragments at the donor-to-host interface, potentially interfering with the optical performance of the transplanted cornea. 17 All other complications may have been coincidental. In conclusion, standardized no-touch DMEK may provide complete visual rehabilitation in a far majority of eyes, with a decrease in donor ECD similar to earlier keratoplasty techniques and with 5% to 9% (partial) graft detachment as the most frequent complication. Submitted for Publication: February 22, 211; final revision received April 15, 211; accepted April 1, 211. Published Online: July 11, 211. doi:1.11 /archophthalmol Correspondence: Gerrit R. J. Melles, MD, PhD, Netherlands Institute for Innovative Ocular Surgery, Rotterdam, the Netherlands (melles@niioc.nl). Financial Disclosure: Dr Melles is a consultant for DORC International/Dutch Ophthalmic USA. Additional Information: A video of the surgical technique is available at REFERENCES 1. Melles GRJ. Posterior lamellar keratoplasty: DLEK to DSEK to DMEK. Cornea. 26;25(): Dapena I, Ham L, Melles GRJ. Endothelial keratoplasty: DSEK/DSAEK or DMEK the thinner the better? Curr Opin Ophthalmol. 29;2(): Price MO, Price FW. 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