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in Descemet Membrane Endothelial Keratoplasty...keratoplasty and Descemet stripping en-dothelial keratoplasty (DSEK) or Des-cemet stripping automated endothelial keratoplasty.1-4 Recently,

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  • ONLINE FIRST

    CLINICAL SCIENCES

    Prevention and Management of Graft Detachmentin Descemet Membrane Endothelial KeratoplastyMartin Dirisamer, MD; Korine van Dijk, BSc; Isabel Dapena, MD; Lisanne Ham, MSc;Oganesyan Oganes, MD; Laurence E. Frank, PhD; Gerrit R. J. Melles, MD, PhD

    Objective: To describe the prevention and manage-ment of various types of graft detachment after Des-cemet membrane endothelial keratoplasty.

    Methods: In 150 consecutive eyes that underwent Des-cemet membrane endothelial keratoplasty, the incidenceand type of graft detachment were studied at 1, 3, 6, 9,12, and 24 months after surgery in a nonrandomized, pro-spective clinical study at a tertiary referral center. Fourgroups of detachments were identified: a partial detach-ment of one-third or less of the graft surface area (n=16;group 1); a partial detachment of more than one-third ofthe graft surface area (n=8; group 2); a graft positionedupside down (n=4; group 3); and a free-floating Des-cemet roll in the host anterior chamber (n=8; group 4).

    Results: Partial or complete graft detachment was foundin 36 cases (24%), of which 18 (12%) were clinically sig-nificant. All 24 eyes with a partial detachment (groups 1and 2) showed spontaneous corneal clearance, and all but6 of these eyes (75%) reached visual acuity of 20/40 or bet-ter (�0.5). A reversed clearance pattern and interface spikeswere observed in eyes with the graft positioned upside down

    (group 3). Eyes with a free-floating graft (group 4) showedpersistent corneal edema. Detachments were associatedwith inward folds (12 eyes [33%]), insufficient air-bubble support (7 eyes [19%]), upside-down graft posi-tioning (4 eyes [11%]), use of plastic materials (2 eyes[6%]), irido-graft synechiae (1 eye [3%]), poor endothe-lial morphology (1 eye [3%]), and stromal irregularity un-der the main incision (1 eye [3%]); 14 (58%) of the par-tial detachments were localized inferiorly.

    Conclusions: Awaiting spontaneous clearance may beadvocated in eyes with a partial detachment. Minor ad-justments in surgical protocol as well as careful patientselection may further reduce the incidence of graft de-tachment after Descemet membrane endothelial kerato-plasty to 4% or less.

    Trial Registration: clinicaltrials.gov Identifier:NCT00521898

    Arch Ophthalmol. 2012;130(3):280-291.Published online November 14, 2011.doi:10.1001/archophthalmol.2011.343

    S INCE 1998, WE HAVE INTRO-duced various techniques forselective replacement of dis-eased corneal endothelium.These techniques have beenpopularized as deep lamellar endothelialkeratoplasty and Descemet stripping en-dothelial keratoplasty (DSEK) or Des-cemet stripping automated endothelialkeratoplasty.1-4 Recently, we further re-fined the concept of endothelial kerato-plasty by introducing selective transplan-tation of Descemet membrane (DM) andits donor endothelium, referred to as DMendothelial keratoplasty (DMEK).5-9

    From the introduction of deep lamel-lar endothelial keratoplasty, DSEK, andDescemet stripping automated endothe-lial keratoplasty, we learned that adapta-tion of a technique among peers may de-pend not only on the feasibility and clinicaloutcome but also on the incidence of com-

    plications and their possible manage-ment. With all endothelial keratoplastytechniques, graft detachment may be themost frequent complication. Because thin-ner graft thickness has been suggested asa risk factor for graft failure and/or de-tachment,10 isolated DM transplantationin DMEK may therefore be prone to higherdetachment rates.7

    The purposes of our study were to iden-tify potential causes of partial and com-plete graft detachments in DMEK and howthey can be avoided and to define pre-ferred treatment options through theanalysis of 150 consecutive DMEKs.

    METHODS

    A total of 150 eyes of 133 patients were en-rolled in our prospective study. All patientssigned an institutional review board–

    Author Affiliations:Department of Ophthalmology,Allgemeines Krankenhaus Linz,Linz, Austria (Dr Dirisamer);Netherlands Institute forInnovative Ocular Surgery andMelles CorneaClinic Rotterdam(Drs Dirisamer, Dapena, andMelles and Mss van Dijk andHam) and Amnitrans EyebankRotterdam (Dr Melles),Rotterdam, and Department ofMethodology and Statistics,Utrecht University, Utrecht(Dr Frank), the Netherlands;and Helmholtz MoscowResearch Institute of EyeDisease, Moscow, Russia(Dr Oganes).

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  • approved informed consent. The study was conducted accord-ing to the Declaration of Helsinki.

    All eyes underwent DMEK for isolated Fuchs endothelial dys-trophy as previously described.4-6 In short, from corneoscleralbuttons stored by organ culture at 31°C for 1 week, DM wasstripped off so that a 9.5-mm-diameter flap of posterior DM withits endothelial monolayer was obtained.11 Due to its elastic prop-erties, a Descemet roll formed spontaneously with the endothe-lium at the outer side. Each Descemet roll was then stored freefloating in organ culture medium until transplantation.

    In recipient eyes, a 9.0-mm-diameter descemetorhexis wascreated and the central portion of DM was removed from theeye. The donor Descemet roll was stained with a 0.06% trypanblue solution (VisionBlue; Dutch Ophthalmic Research Cen-ter International BV, Zuidland, the Netherlands) and suckedinto a custom-made injector (Dutch Ophthalmic Research Cen-ter International BV).4-6 Using the injector, the donor Des-cemet roll was inserted into the anterior chamber and the graftwas oriented with the endothelial side down (donor DM fac-ing recipient posterior stroma) onto the recipient posteriorstroma by careful, indirect manipulation of the tissue with airand fluid. The anterior chamber was completely filled with airfor 45 to 60 minutes, followed by an air-liquid exchange to pres-surize the eye. All operations were recorded on DVD.

    All eyes that underwent DMEK were examined before sur-gery and at 1, 3, 6, 9, 12, 18, and 24 months after surgery withPentacam imaging (Oculus Optikgeräte GmbH, Wetzlar, Ger-many), noncontact specular microscopy (SP3000; Topcon Medi-cal Europe, Capelle aan den IJssel, the Netherlands), anteriorsegment optical coherence tomography (Heidelberg Engineer-ing GmbH, Heidelberg, Germany), confocal microscopy (Con-foscan 4; Nidek Technologies, Padova, Italy), and slitlamp bio-microscopy (Topcon Medical Europe).

    Automated specular microscopy and confocal microscopywere used to document the presence of endothelial cells andthe endothelial cell density (ECD) under a detached Des-cemet graft (the exposed recipient posterior stroma under a freedonor Descemet flap hanging in the recipient anterior cham-ber). To determine the functionality of the endothelial cells,pachymetry measurements over the area with a detachment werecompared with adjacent corneal quadrants.

    Because the graft detachments varied in size from a loose pe-ripheral flange to a free-floating Descemet roll in the recipientanterior chamber, the clinical relevance was graded in 2 ways.First, the detachments were divided into 4 groups that showeddistinctive patterns of corneal clearance (group 1 indicated par-tial graft detachment of one-third or less of the graft surface areaand no or minimal interference with the final visual outcome;group 2, partial graft detachment of more than one-third of thegraft surface area and potentially interfering with the visual out-come; group 3, detachment with the graft positioned upside down;and group 4, complete graft detachment with severe interfer-ence with the visual outcome) (Table 1). Second, a clinicallysignificant graft detachment was defined as a detachment re-quiring secondary surgical intervention (graft rebubbling or asecondary DSEK or DMEK) or reducing visual outcome.

    For statistical analysis, 1-way analysis of variance was usedto compare the groups (groups 1-4) with the control group of114 eyes with a well-centered and completely attached Des-cemet graft, in terms of central ECD and central corneal pachym-etry measurements. Contrasts (simple effects) were used to cal-culate statistical difference from the control group. Forcomparison of central corneal pachymetry measurements, onlygroups 1 and 3 could be included in the comparisons becauseof violation of the homogeneity of variance assumption in groups2 and 4. Repeated-measures multivariate analysis of variancewas used to assess the difference between central ECD and pe-ripheral ECD adjacent to the Descemet graft between groups

    1, 2, and 3. Contrasts (simple effects) were used to examine inwhich group(s) central corneal ECD differed significantly fromperipheral ECD adjacent to the Descemet graft.

    All analyses were performed with SPSS version 18.0 statisti-cal software (SPSS Inc, Chicago, Illinois) using an � level of .05;P� .05 was considered statistically significant. All P values werecorrected with the Benjamini and Hochberg correction12 usingR version 2.12.1 statistical software (The R Foundation for Sta-tistical Computing, Vienna, Austria) because the use of mul-tiple tests increases the false-positive (significance) rate.

    RESULTS

    From a total of 150 eyes that underwent DMEK, 114 ob-tained complete attachment of the Descemet graft, andthe transplanted cornea showed a normal corneal clear-ance within 1 to 3 months. Of the remaining 36 eyes, 18(cases 17-19, 21-23, and 25-36; Table 1) showed a clini-cally significant detachment, ie, a detachment reducingthe final visual acuity and/or necessitating secondary sur-gical intervention. All remaining 18 eyes showed recov-ery of corneal transparency and normal pachymetry re-sults (Table 1).

    Overall, 4 categories of eyes with detachments couldbe identified (groups 1-4) (Figure 1 and Table 1).

    GROUPS

    Group 1: DMEK Graft Detached Over One-Thirdor Less of the Graft Surface Area

    Sixteen eyes (group 1, cases 1-16; Table 1) showed a par-tially (one-third or less) detached DMEK graft within thefirst weeks after surgery, sometimes with the formationof a (small) peripheral Descemet roll (Figure 1A andFigure 2A). Of these eyes, 2 (cases 5 and 16) showed aspontaneous adherence of the Descemet graft at the 3-to 6-month follow-up interval (Figure 3). In the re-maining 14 eyes, complete corneal clearance of the areaperipheral to the Descemet roll, ie, the area not coveredby the graft, was observed within the first year and mostoften in about 3 months (Figure 1A and Figure 2A). Slit-lamp examination showed that the denuded posterior stro-mal area, devoid of either a recipient or donor DM, hada tendency to clear from the corneal periphery towardthe center (Figure 1A and Figure 4). All but 2 eyes ob-tained best-corrected visual acuity of 20/40 (0.5) or bet-ter; 1 eye (case 1) had a poor visual acuity outcome of20/100 (0.2) attributed to a central wrinkle in the Des-cemet graft, and 1 highly myopic eye (case 6) had a maxi-mal visual acuity potential of about 20/50 (0.4).

    Group 2: DMEK Graft Detached OverMore Than One-Third of the Graft Surface Area

    An additional 8 eyes (group 2, cases 17-24; Table 1)showed a large detachment (more than one-third) of theDescemet graft. All eyes with follow-up longer than 1month (hence allowing re-endothelialization) showed pro-gressive corneal clearance starting at the first months af-ter DMEK, which was concurrent with endothelializa-tion of the recipient denuded posterior stroma (Figure 1A

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  • Table 1. Descemet Membrane Endothelial Keratoplasty Graft Detachment Patient Data

    Patient Detachment

    Postoperative Findings at 6-12 mo

    Case No.(Surgery No.)/

    Sex/Age, yOD/OS Localization

    SuspectedCause BCVA Status

    CentralCorneal ECD,

    Cells/mm2

    Peripheral ECDAdjacent toDescemet

    Graft,Cells/mm2

    CentralCorneal

    Pachymetry,µm

    Pachymetry OverDetachment

    Compared WithAdjacent

    Quadrant(s),µm (Change, %)

    Group 1a1 (15)/M/88 OD Inferior Inward fold 20/100 (0.2) Slowly clearing

    cornea despitepersistentdetachment;central wrinkle

    810 1150 650 1004−685=319(�46)

    2 (20)/F/58 OS Inferotemporal Traction byirido-Descemetadhesion

    20/25 (0.8) Clear cornea despitepersistentdetachment

    900 870 492 713−652=61(�9.4)

    3 (26)/M/74 OD Inferior Inward fold 20/30 (0.6) Clear cornea despitepersistentdetachment

    1820 1560 629 766−638=128(�20.1)

    4 (47)/F/65 OD Nasal Inward fold 20/23 (0.9) Clear cornea despitepersistentdetachment

    2350 1730 551 722−728=−6(−0.8)

    5 (67)/F/68 OS Inferior Unknown;spontaneousreattachment at 6mo

    20/25 (0.8) Clear cornea withminor detachmentat inferior edge

    1880 NA 466 736 − 748 = −12(−1.6)

    6 (71)/F/73 OS Nasal andtemporal

    Inward fold 20/50 (0.4) Clear cornea despitepersistentdetachment;subnormal BCVAattributed to highmyopia

    2480 1820 489 624−697=−73(−10.5)

    7 (80)/F/47 OD Nasal Inward fold 20/18 (1.2) Clear cornea despitepersistentdetachment

    1090 720 496 779−626=153(�24.4)

    8 (82)/M/56 OD Inferonasal Normal cell countbut poorendothelial cellmorphology at3-6 mo, withborderlinedecompensationat 30 mo

    20/20 (1.0) Clear cornea despitepersistentdetachment

    1730 600 602 944−762=182(�23.9)

    9 (93)/F/75 OD Inferior Inward fold 20/28 (0.7) Clear cornea despitepersistentdetachment

    1220 1140 523 814−800=14(�1.8)

    10 (103)/M/55 OD Superior Irregular incisionsite

    20/18 (1.2) Clear cornea withsmall detachmentsuperior

    1600 490 559 851−680=171(�25.2)

    11 (105)/M/51 OD Superior Inward fold 20/18 (1.2) Clear cornea despitepersistentdetachment

    1860 NA 540 795−712=83(�11.7)

    12 (106)/F/60 OD Inferior Inward fold 20/20 (1.0) Clear cornea despitepersistentdetachment

    1050 640 451 720−802=−82(−10.2)

    13 (109)/F/82 OS Inferior Unknown 20/30 (0.6) Clear cornea despitepersistentdetachment

    760 350 522 687−712=−25(−3.5)

    14 (110)/M/59 OD Inferior Inward fold 20/20 (1.0) Clear cornea despitepersistentdetachment

    1570 1380 522 647−723=−76(−10.5)

    15 (122)/F/70 OD Nasal Unknown 20/20 (1.0) Clear cornea despitepersistentdetachment

    1180 1010 572 821−649=172(�26.5)

    16 (123)/F/69 OS Inferior Unknown;spontaneousreattachment at6 mo

    20/23 (0.9) Clear cornea 1660 1060 525 706−843=−137(−16.3)

    (continued)

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  • Table 1. Descemet Membrane Endothelial Keratoplasty Graft Detachment Patient Data (continued)

    Patient Detachment

    Postoperative Findings at 6-12 mo

    Case No.(Surgery No.)/

    Sex/Age, yOD/OS Localization

    SuspectedCause BCVA Status

    CentralCorneal ECD,

    Cells/mm2

    Peripheral ECDAdjacent toDescemet

    Graft,Cells/mm2

    CentralCorneal

    Pachymetry,µm

    Pachymetry OverDetachment

    Compared WithAdjacent

    Quadrant(s),µm (Change, %)

    Group 2b17 (17)/F/70 OS Inferior

    quadrantsPossibly use of

    plastic materialsNA Secondary DSEK

    4 wk after DMEKNA NA NA NA

    18 (63)/F/82 OD Superiorquadrants

    Inadequateair-bubblesupport at endof surgery due tovitreouspressurec

    20/40 (0.5) Some cornealclearance orre-endothelializationover detachment at6 mo; secondaryDSEK 6 mo afterDMEK

    950 NA 949 NA

    19 (64)/M/61 OD Subtotaltemporal

    Inadequateair-bubblesupport at endof surgery due tovitreous pressure

    NA Corneal clearance ininferior quadrants;secondary DSEK4 mo after DMEK

    NA NA 833 NA

    20 (73)/F/75 OD Inferiorquadrants

    Unknown 20/150 (0.15) Clear cornea despitepersistentdetachment;BCVA notexplained bycornea

    1950 NA 558 845−746=99(�13.3)

    21 (74)/M/75 OS Subtotaltemporal

    Inadequateair-bubblesupport at endof surgery due tovitreous pressure

    CF (3/60) Corneal clearancedespite persistentdetachment, butwrinkled graft incorneal center;secondary DSEK7 mo after DMEK

    2270 NA 896 NA

    22 (79)/F/86 OD Inferiorquadrants

    Unknown 20/40 (0.5) Clear corneadespite persistentdetachment

    2070 NA 480 636−621=15(�2.4)

    23 (97)/F/74 OS Inferiorquadrants

    Inward foldd 20/30 (0.6) Clear corneadespite persistentdetachment

    1790 NA 780 NA

    24 (150)/M/55 OS Temporal Inward foldd 20/23 (0.9) Clear cornea despitepersistentdetachment;BCVA improvedto 20/23 (0.9)at 12 mo

    1800 1200 495 692−617=75(�12.2)

    Group 3e25 (19)/M/70 OD Complete

    (DM rollin AC)

    Graft positionedupside down;rebubblingunsuccessful

    NA No detectable cornealclearance orre-endothelializationat 5 wk; secondaryDSEK 5 wk afterDMEK

    NA NA NA NA

    26 (36)/F/70 OD Subtotal nasal Graft positionedupside down

    20/28 (0.7) Clear cornea despitepersistentdetachment

    340 560 627 725−1014=−289(−39.9)

    27 (38)/F/47 OS Subtotalinferior

    Graft positionedupside down

    20/20 (1.0) Clear cornea despitepersistentdetachment

    380 490 569 799−972=−173(−17.8)

    28 (96)/M/75 OD Inferiorquadrants

    Graft positionedupside down

    20/100 (0.2) Corneal clearance ininferior quadrantsat 3 mo; re-DMEK6 mo after primaryDMEK

    530 490 711 663−810=−147(−18.1)

    (continued)

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  • and Figure 4). Despite an extensive detachment, ie, with-out the graft covering the optical center, 4 eyes still reachedbest-corrected visual acuity of 20/40 (0.5) or better at 6months after surgery. Of the 4 remaining eyes, 2 (cases17 and 19) did not reach the 6-month follow-up. One

    eye (case 21) had best-corrected visual acuity of count-ing fingers attributed to extensive wrinkling and/or graftcontraction in the area over the pupil, and no explana-tion could be found for the reduced best-corrected vi-sual acuity in case 20.

    Table 1. Descemet Membrane Endothelial Keratoplasty Graft Detachment Patient Data (continued)

    Patient Detachment

    Postoperative Findings at 6-12 mo

    Case No.(Surgery No.)/

    Sex/Age, yOD/OS Localization

    SuspectedCause BCVA Status

    CentralCorneal ECD,

    Cells/mm2

    Peripheral ECDAdjacent toDescemet

    Graft,Cells/mm2

    CentralCorneal

    Pachymetry,µm

    Pachymetry OverDetachment

    Compared WithAdjacent

    Quadrant(s),µm (Change, %)

    Group 4f29 (2)/F/86 OD Complete (DM

    roll in AC)Unknown;

    insufficientair-bubble time atend of surgery

    NA Secondary DSEK 3wk after DMEK

    NA NR NA NR

    30 (8)/F/74 OD Complete (DMroll in AC)

    Large inward fold NA Secondary DSEK 4wk after DMEK

    NA NR NA NR

    31 (10)/M/70 OD Complete (DMroll in AC)

    Inadequateair-bubblesupport at end ofsurgery due tostatus afterposterior segmentsurgery

    NA Secondary DSEK 4wk after DMEK

    NA NR NA NR

    32 (16)/F/82 OS Complete (DMroll in AC)

    Possibly use ofplastic materials

    NA Secondary DSEK 3wk after DMEK

    NA NR NA NR

    33 (43)/F/68 OS Complete (DMroll in AC)

    Unknown;rebubblingunsuccessful

    NA No detectable cornealclearance orre-endothelializationat 4 mo; secondaryDSEK 4 mo afterDMEK

    NA NR NA NR

    34 (72)/M/80 OS Complete (DMroll in AC)

    Unknown NA No detectable cornealclearance orre-endothelializationat 4.5 mo;secondary DSEK4.5 mo after DMEK

    NA NR NA NR

    35 (95)/F/66 OS Complete (DMroll in AC)

    Inadequateair-bubblesupport at end ofsurgery due tovitreous pressure

    NR No detectable cornealclearance orre-endothelializationat 1 mo; secondaryDSEK 1 mo afterDMEK

    NA NR NA NR

    36 (75)/F/70 OD Complete (DMroll in AC)

    Unknown;rebubblingunsuccessfulc

    NR No detectable cornealclearance orre-endothelializationat 5 wk; secondaryDSEK 5 wk afterDMEK

    NA NR NA NR

    Abbreviations: AC, anterior chamber; BCVA, best-corrected visual acuity; CF, counting fingers; DM, Descemet membrane; DMEK, DM endothelial keratoplasty;DSEK, Descemet stripping endothelial keratoplasty; ECD, endothelial cell density; NA, not available; NR, not relevant.

    aGroup 1 indicates a Descemet graft detachment of one-third or less of the graft surface area. The mean (SD) central corneal ECD was 1500 (520) cells/mm2 (n=16;P=.13 compared with control group); the mean (SD) peripheral ECD adjacent to the Descemet graft was 1040 (460) cells/mm2 (n=14; P=.01 compared with cornealcenter); the mean (SD) central corneal pachymetry measurement was 537 (56) µm (n=16; P=.81 compared with control group); and the mean change in thepachymetry measurement from over the detachment compared with the adjacent quadrant(s) was �8.5% (n=16).

    bGroup 2 indicates a Descemet graft detachment of more than one-third of the graft surface area. The mean (SD) central corneal ECD was 1800 (460) cells/mm2(n=6; P=.81 compared with control group); the mean (SD) central corneal pachymetry measurement was 713 (198) µm (n=7; the variance was too high to comparewith control group).

    cThe left eye also had detachment but is not included in this series.dThe right eye underwent uncomplicated DMEK.eGroup 3 indicates detachment because the Descemet graft was positioned upside down. The mean (SD) central corneal ECD was 420 (100) cells/mm2 (n=3;

    P� .001 compared with control group); the mean (SD) peripheral ECD adjacent to the Descemet graft was 510 (40) cells/mm2 (n=3; P=.72 compared with cornealcenter); and the mean (SD) central corneal pachymetry measurement was 636 (71) µm (n=3; P=.01 compared with control group).

    fGroup 4 indicates a free-floating Descemet graft.

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  • Group 3: Reversed Corneal ClearanceWith a Partially or Completely Detached

    DMEK Graft Positioned Upside Down

    In 4 eyes with a total or subtotal detachment (cases 25-28; Table 1), a reversed corneal clearance pattern was seenwithin 1 to 3 months: the area overlying the detach-ment cleared, while persistent stromal edema up to 1 yearafter surgery was present in the area showing graft attach-ment (Figure 1B and Figure 5). In these cases, the ori-entation of the donor tissue was difficult to determine dur-ing surgery, and a review of the surgical videos indicatedthat the tissue had been positioned upside down. Apartfrom the reversed clearance pattern, a distinctive featurein these cases was the presence of spike-shaped fibrous scar-ring at the donor-host interface, ie, between the Des-cemet graft and the recipient posterior stroma (Figure 5);no interface scarring was observed in any other eye in theentire series of eyes that underwent DMEK with a well-oriented graft.

    Despite subtotal detachment, 2 of the 3 eyes with fol-low-up longer than 1 month achieved best-corrected vi-sual acuity of 20/28 (0.7) or better (cases 26 and 27); 1eye (case 28) had best-corrected visual acuity of 20/100(0.2), attributed to persistent central edema overlying anarea where the graft was attached (Figure 5).

    Group 4: Lack of Corneal ClearanceWith a Free-Floating Descemet Roll

    Eight eyes (cases 29-36; Table 1) had a complete graftdetachment with a free-floating Descemet roll, ie, ab-sence of physical contact between donor and host tis-sues, in the recipient anterior chamber (Figure 1C andFigure 2C). All of these eyes showed persistent cornealedema up to the time when a secondary DSEK was per-formed, up to 4.5 months after the initial DMEK. Fourof these eyes (cases 29-32; Table 1) had a secondary DSEKperformed within the first 3 or 4 weeks after the initialDMEK, so the postoperative interval was too short tomonitor a tendency toward spontaneous clearance of thetransplanted cornea.13-16

    INCIDENCE, LOCALIZATION, AND POTENTIALCAUSES OF DESCEMET GRAFT DETACHMENT

    A review of the surgical videos, sequential slitlamp pho-tography, and clinical observation revealed several poten-tial causes for Descemet graft detachment and its associ-ated localization (Table2). One-third of the detachmentswere attributed to the presence of an inward fold (a flangeof peripheral DM sandwiched between the larger part ofthe graft and the cornea) at the end of surgery. Slitlampobservation showed that these inward folds had a ten-dency to spring away from the recipient posterior stroma,causing a larger detachment than the size of the originalfold (Figure 4). A second main cause was insufficient air-bubble support of the donor tissue at the end of surgery,most frequently associated with vitreous pressure and pre-ceding vitreoretinal surgery (causing the air to escape tothe posterior segment), and/or other situations with an in-adequate air fill of the anterior chamber. Other causes iden-

    tified were stromal irregularity under the main incision,an irido–Descemet graft adhesion causing detachment bytraction (Figure 6), poor endothelial cell morphology(Figure7), the use of plastic materials contacting the do-nor tissue, and upside-down positioning of the graft. In 8cases (22%), no cause for the detachment could be iden-tified.

    Of the 24 eyes with a partial graft detachment, 14 (58%)showed a detachment in the inferior quadrant, which maybe explained by the air bubble being most effective in thesuperior quadrant with a 50% air fill of the anterior cham-ber at the end of surgery.

    The incidence of graft detachment decreased with sur-gical experience. The number of clinically significant de-tachments decreased from 20% in the first 75 cases (series1) to 4% in the next 75 cases (series 2) (Table 3). Inter-estingly, 2 eyes (cases 18 and 36) also had a graft detach-ment in the contralateral eye after DMEK. No rebubblingprocedure proved (completely) successful (Figure 8).

    No correlation could be found between graft detach-ment and recipient or donor age (P� .10).

    ECD AND PACHYMETRY MEASUREMENTS

    In the control group of 114 eyes with a completely at-tached and well-centered Descemet graft, the mean (SD)central ECD was 1750 (552) cells/mm2 and the mean (SD)pachymetry measurement was 532 (42) µm. Using thisgroup as a reference, the central ECD was not signifi-cantly lower in group 1 (graft detachment over one-thirdor less of the graft surface area; P=.13) (Figure 1A andTable 1). In groups 2 and 3, the central ECD represented

    A Edge descemetorhexis

    Partially detachedDMEK graft

    Groups 1 and 2 (cases 1-24)

    Clear

    B Edge descemetorhexis

    DMEK graftupside down

    Group 3 (cases 25-28)

    Clear Not clear

    Complete detachment andDescemet roll in anterior chamber

    C Edge descemetorhexis Group 4 (cases 29-36)

    Not clear

    Figure 1. Detachment patterns observed in our study. A, In the presence of apartially detached Descemet membrane endothelial keratoplasty (DMEK)graft, the central cornea covered by the graft as well as the host peripheralstroma not covered by the graft frequently showed either spontaneousreattachment of the graft or complete clearance within 1 to 6 months. B, Ifthe DMEK graft had been positioned upside down, a reversed clearancepattern was observed, ie, the area not covered by the graft showed completecorneal clearance within 1 to 6 months, whereas the area in which the graftwas attached showed persistent edema. C, No corneal clearance was seenwith a free-floating Descemet roll in the anterior chamber, ie, in the absenceof a touch between the graft and the recipient cornea.

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  • re-endothelialized recipient posterior stroma because theDescemet graft was largely detached (Figure 1B). The ECDin group 2 (graft detachment over more than one-third ofthe graft surface area) did not differ from that of the con-trol group (P=.81), whereas the ECD was significantlylower in group 3 (mean [SD], 420 [100] cells/mm2;P� .001) (Table 1). Accordingly, central pachymetry mea-surements did not differ between the control group andgroup 1 (Figure 2 and Table 1). In group 2, the variancewas too high for reliable statistical analysis. The centralpachymetry measurement was significantly higher in group3 (mean [SD], 636 [71] µm; P=.01) (Table 1). No ECDmeasurements could be obtained in group 4 owing to thepersistent corneal edema (Figure 1C and Table 1).

    The ECD under the detachment of one-third or less ofthe graft surface area (group 1) was lower than the centralECD (P=.01) (Table 1), and the cornea in these areas wasabout 8% thicker compared with the opposite or adjacentquadrants without a gap or detachment (Figure 2A andTable 1). In group 3, pachymetry measurements over thearea where the graft was detached were about 25% thin-

    ner than in the area showing graft attachment (Figure 2Band Table 1).

    COMPLICATIONS ASSOCIATED WITHDESCEMET GRAFT DETACHMENTS

    The only complication observed was a small corneal in-filtrate in the area with edema overlying a peripheral de-tachment in case 6 (Figure 9). All eyes that underwenta secondary DSEK had a postoperative course and best-corrected visual acuity similar to those after primaryDSEK.

    COMMENT

    Graft detachment may be the most frequently observedcomplication after endothelial keratoplasty. After DSEKor Descemet stripping automated endothelial kerato-plasty, graft detachments may occur in up to 82% ofcases (Table 4) and have been associated with lower

    A

    B

    C

    Groups 1 and 2

    Group 3

    Group 4

    OS

    T

    9 mm

    687

    672

    636 637524

    90°

    270°300

    °

    330°

    180°

    60°

    240°

    150° 30°

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    120°

    OS

    T

    9 mm

    867

    713

    788 709559

    90°

    270°300

    °

    330°

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    60°

    240°

    150° 30°

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    OS

    T

    9 mm

    1163

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    1091 1073

    90°

    270°300

    °

    330°

    180°

    60°

    240°

    150° 30°

    210°

    120°

    996

    Figure 2. Pachymetry and Scheimpflug images of 3 corneas 6 months after Descemet membrane endothelial keratoplasty. A, In groups 1 and 2, despite thepresence of a detachment of the donor Descemet graft (arrow), the entire cornea shows recovery of corneal clarity (asterisks) and normal pachymetry values. B,In group 3, in the presence of a graft positioned upside down (with the donor endothelium facing the recipient posterior stroma), a reversed clearance pattern isseen, ie, a clear cornea in the area of the detachment (white asterisks) but persistent corneal edema over the area where the donor tissue is attached (redasterisks). C, In group 4, complete graft detachment, ie, a free-floating Descemet roll in the anterior chamber (arrow), is associated with persistent corneal edema.

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  • ECDs. Similarly, an initial graft detachment rate of 20%to 60% has been reported after DMEK (Table 2), allow-ing further identification of its causes to define potentialprecautions as well as to determine its preferred clinicalmanagement.

    First, however, it may be important to better define agraft detachment because, especially in DMEK, small andtemporary detachments of a peripheral flange with littleclinical significance are frequently seen. If graft detach-ment is defined as a lack of adherence of the donor DM to

    the recipient posterior stroma, reducing visual outcomeand/or necessitating secondary intervention, the detach-ment rate in our study evaluating the first 150 consecu-tive DMEK eyes was 12% (18 of 150 eyes) (Table 1 andTable 3). When clinically insignificant detachments werealso included, the overall detachment rate was 24% (36of 150 eyes). Furthermore, with clinical experience, thedetachment rate decreased from 20% in the first series of75 eyes to 4% in the next series of 75 eyes (Table 3). Hence,

    A C

    B D

    Figure 3. Slitlamp photographs of an eye 1 month (A and B) and 6 months(C and D) after Descemet membrane endothelial keratoplasty. The initiallydetached Descemet graft (yellow arrows) spontaneously reattached to therecipient posterior stroma, with concurrent resolution of the stromal edema(green arrows).

    A B C

    Figure 4. Slitlamp photographs of a transplanted cornea 7 weeks (A), 3 months (B), and 10 months (C) after Descemet membrane endothelial keratoplasty. Theedema (white arrows) overlying the detached Descemet graft (yellow arrows) resolves with time, and stromal thinning with concomitant corneal clearanceprogresses from the periphery toward the corneal center (green arrows). Furthermore, note that the relatively small inward fold of the peripheral Descemet graftcauses a much larger detachment because the tissue springs away from the recipient posterior stroma. Inset of B, Inward fold at higher magnification.

    1 m

    o12

    mo

    A B C

    D E F

    Figure 5. Slitlamp photographs of a transplanted cornea 1 month (A-C) and12 months (D-F) after Descemet membrane endothelial keratoplasty. There isa reversed corneal clearance pattern with persistent stromal edema (bluearrows) overlying the area showing graft attachment as well as cornealclearance (green arrows) in the area where the Descemet graft (yellowarrows) is clearly detached. There is fibrous scarring at the donor-hostinterface (red arrows) that may be absent in uncomplicated eyes undergoingDescemet membrane endothelial keratoplasty. This reversed clearancepattern with interface fibrosis may be typical for eyes in which the Descemetgraft was positioned upside down.

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  • our study aimed to identify any factors that may aid in fur-ther reducing Descemet graft detachments as well as de-fining preferred treatment options.

    Intuitively, rebubbling appeared to be a first treatmentoption with all of these detachments to again position theDescemet graft against the recipient posterior stroma. Al-though initially pursued in a few cases, rebubbling provedless effective than expected. In fact, some eyes showed per-sistent detachment of the graft in the presence of an airbubble in the recipient anterior chamber (Figure 8). De-cision making on reintervention was further complicatedby an unexpected spontaneous clearance in several eyesthat underwent DMEK, despite the presence of a (nearly)complete graft detachment.13 While these eyes were sched-uled for a rebubbling procedure, re-endothelialization ofthe recipient posterior stroma was observed within the firstseveral months after surgery, with visual rehabilitation upto visual acuity of 20/20 (1.0). Given this observation, wechanged our decision tree for management of detach-ments after DMEK, using (1) the extent of the detach-ment and (2) interference with the visual acuity as pri-mary guidelines for reintervention (Figure 10).

    A first group of eyes showed a peripheral detach-ment of one-third or less of the graft surface area, appar-ently without affecting the visual acuity (Table 1). At 3to 6 months postoperatively, all of these eyes recoveredwith near-normal pachymetry measurements in the areaoverlying the detachment: either the graft reattached byitself or the recipient posterior stroma re-endothelial-ized (Figure 2A, Figure 3, and Figure 4). Only 1 of theseeyes required additional treatment. In this eye, a smallanterior corneal infiltrate developed within the still edema-tous area overlying the detachment (Figure 9); the cor-neal infiltrate quickly resolved with topical antibiotics.

    For these relatively benign peripheral detachments, 2main causes could be identified (Table 2). First, inwardfolds of the edge of the Descemet graft, ie, a fold sand-wiched between the larger body of the graft and recipientposterior stroma (with the endothelium touching thestroma in that area), that are left in situ at termination ofthe surgery may be associated with peripheral detach-ments because the tissue tends to spring away from thestroma within the first postoperative week (Figure 4). Oncerecognized, this complication can easily be avoided by so-called bubble bumping during surgery or by performingDroutsas taps (applying intermittent pressure to the outercorneal surface to move the air bubble over the tissue fold

    Figure 6. Slitlamp photograph of a transplanted cornea 2 months afterDescemet membrane endothelial keratoplasty. Gonioscopy showed anadhesion between the Descemet graft (arrows) and the peripheral iris,causing a local traction detachment because the detached part of a Descemetgraft tends to contract over time.

    Table 2. Suspected Cause of Graft Detachment

    Suspected Cause of Graft Detachment

    No. (%)

    Group 1a(n=16)

    Group 2a(n=8)

    Group 3a(n=4)

    Group 4a(n=8)

    Total(n=36)

    Inward fold 9 (57) 2 (25) 0 1 (12.5) 12 (33)Irregular incision site 1 (6) 0 0 0 1 (3)Irido–Descemet graft adhesion 1 (6) 0 0 0 1 (3)Poor endothelial cell morphology 1 (6) 0 0 0 1 (3)Use of plastic materials contacting donor tissue 0 1 (12.5) 0 1 (12.5) 2 (6)Inadequate air-bubble support due to vitreous

    pressure or preceding vitreoretinal surgery0 3 (37.5) 0 4 (50) 7 (19)

    Descemet graft upside down 0 0 4 (100) 0 4 (11)Unknown 4 (25) 2 (25) 0 2 (25) 8 (22)

    aGroup 1 indicates a Descemet graft detachment of one-third or less of the graft surface area; group 2, a Descemet graft detachment of more than one-third of thegraft surface area; group 3, detachment because the Descemet graft was positioned upside down; and group 4, a free-floating Descemet graft.

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  • inside the eye [see Figure 7 of the article by Dapena et al5])to completely unfold the donor DM.5 Second, a touch be-tween the outer flange of the Descemet graft and the re-

    cipient peripheral iris may result in a progressive detach-ment, due to contraction of the Descemet graft after surgerythat tends to stretch the detachment, making reattach-

    A B C D

    100

    µm100 µm

    Figure 7. Light microscopy (A), slitlamp (B and C), and specular microscopy (D) images of a Descemet graft before (A) and after (B-D) surgery. A, Although theendothelial cell layer appears normal during preoperative evaluation in the eyebank, Fuchs dystrophy–like changes are seen across the transplant after surgery,while the cell density is virtually normal. B, The arrows indicate the area in which the graft is detached; the overlying cornea cleared despite the detachment.

    A B

    Figure 8. Slitlamp photographs of an eye 1 week after Descemet membraneendothelial keratoplasty (A) and 1 day after rebubbling, 2 weeks after theinitial Descemet membrane endothelial keratoplasty (B). A, The Descemetgraft (arrows) is detached after surgery, and the detachment persists despitea secondary 60-minute air fill of the recipient anterior chamber followed by a50% air fill at the first postoperative day. The air bubble seems to provideinsufficient support because the detachment is visible directly over the airbubble.

    A B C

    Figure 9. Slitlamp photographs of an eye 5 months (A and B) and 12 months (C) after Descemet membrane endothelial keratoplasty. A and B, A small cornealinfiltrate (red arrows) is visible in an area of edema over a peripheral detachment of the Descemet graft (yellow arrows). C, After treatment with a topical antibiotic,the infiltrate resolved and the area over the detachment cleared (arrow) without sequelae.

    Table 3. Incidence of Graft Detachment

    Type

    No. (%)

    Series 1,Cases 1-75

    (n=75)

    Series 2,Cases 76-150

    (n=75)Total

    (N=150)

    Partial graft detachmentone-third or less

    6 (8) 10 (13) 16 (11)

    Partial graft detachmentmore than one-third

    5 (7) 3 (4) 8 (5)

    Graft upside down 3 (4) 1 (1) 4 (3)Complete graft detachment 7 (9) 1 (1) 8 (5)Total 21 (28) 15 (20) 36 (24)Clinically significant 15 (20) 3 (4) 18 (12)

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  • ment impossible. To avoid such graft-iris adhesions, it issuggested that the recipient anterior chamber is filled withair after graft positioning and the chamber angle is checkedto be sure it is open over 360°. Overall, with small detach-ments not affecting the visual acuity, awaiting spontane-ous clearing is suggested rather than performing a sec-ondary intervention (Figure 10).

    In eyes with a detachment of more than one-third ofthe graft surface area and thereby affecting the visual acu-ity, decision making proves more complex (Table 1).When a free-floating Descemet roll is observed inside therecipient anterior chamber, corneal edema may persistup to 6 to 9 months and patients may be advised to havea secondary DSEK, Descemet stripping automated en-dothelial keratoplasty, or re-DMEK performed withouttoo much delay.15 However, if the Descemet graft showspartial attachment, the transplanted cornea is found toclear much quicker and an acceptable visual outcome isobtained in about half of these cases (Table 1). A similarvisual outcome is reached when the graft is positionedupside down, although persistent corneal edema can beseen over the area in which the graft shows attachment(Figure 5 and Table 1). Hence, large partial detach-ments may be managed on an individual basis and ac-cording to the patient’s preferences (Figure 10). In ourstudy, the large or complete detachments appeared to beassociated with the presence of vitreous pressure dur-ing surgery and/or improper judgment of graft orienta-

    tion. Therefore, a soft eye should be obtained before com-mencing surgery (by performing ocular massage, applyinga Honan bal loon for 10 minutes, using anti-Trendelenburg positioning, and avoiding a tight eyelidspeculum) to minimize the risk of posterior pressure. Theorientation of the graft can be determined by the Mout-souris sign (see Figure 6 of the article by Dapena et al5)and/or marking the graft.5,31

    We previously described that the use of plastic and/orviscoelastic materials may be avoided in DMEK to mini-mize the risk of graft detachment. Performing the des-cemetorhexis under air may have the advantages that rem-nant host Descemet fragments are more easily identifiedand that the negative imbibition pressure facilitating graftadherence is better preserved (by avoiding stromal over-hydration with the use of balanced salt solution in com-bination with an anterior chamber maintainer). Also, suf-ficient air-bubble support for 45 to 60 minutes at thetermination of surgery may be a prerequisite for properDescemet graft adhesion.

    Hence, our study indicated that graft detachment maybe further reduced to 4% or less by minor surgical ad-justments and/or additional maneuvers (Figure 10 andTable 2).4,5,16 Furthermore, proper patient selection may

    Table 4. Detachment Rates in Endothelial Keratoplasty

    Source TechniqueEyes,No.

    Detachments,No. (%)

    DMEK, DMAEK,or DMEK-S

    Current study DMEK 150 18 (12)a/36 (24)b

    McCauley et al,17 2011 DMAEK 40 10 (25)Studeny et al,8 2010 DMEK-S 20 12 (60)Price et al,7 2009 DMEK 60 38 (63)

    DSEK or DSAEKBahar et al,18 2008 DSAEK 45 7 (16)Bahar et al,18 2008 DSEK 16 2 (13)Busin et al,19 2008 DSAEK 10 0Suh et al,20 2008 DSAEK 118 27 (23)Chen et al,21 2008 DSAEK 100 3 (3)O’Brien et al,22 2008 DSEK 89 23 (26)Basak,23 2008 DSEK 75 6 (8)Terry et al,24 2008 DSAEK 350 9 (3)Wylegała et al,25 2008 DSEK 11 3 (27)Koenig and Covert,26 2007 DSAEK 26 9 (35)Mearza et al,27 2007 DSEK 11 9 (82)Price and Price,28 2006 DSEK or

    DSAEK200 26 (13)

    DLEKFillmore et al,29 2010 DLEK 86 10 (12)Terry and Ousley,30 2005 DLEK 100 4 (4)Bahar et al,18 2008 DLEK 68 6 (9)

    Abbreviations: DLEK, deep lamellar endothelial keratoplasty; DMAEK,Descemet membrane automated endothelial keratoplasty; DMEK, Descemetmembrane endothelial keratoplasty; DMEK-S, Descemet membrane endothelialkeratoplasty with a stromal rim; DSAEK, Descemet stripping automatedendothelial keratoplasty; DSEK, Descemet stripping endothelial keratoplasty.

    aClinically significant detachments, ie, reducing visual outcome ornecessitating secondary intervention.

    bIncluding peripheral and temporary detachments.

    Check during surgery:Descemetorhexis under air; avoid stromal overhydrationAvoid use of viscoelastic and plastic materials contacting graftUpward orientation of Descemet graft (Moutsouris sign/tissue marking)Proper centration of Descemet graft; avoid PASComplete unfolding of Descemet graft; avoid inward folds50% Air fill in AC in pseudophakic eyes, 25% air fill in phakic eyes

    Stepladder approach in management of Descemet graft detachments

    After surgery: keep supine position for 24 h

    First postoperative week: if incomplete attachment

    No interference with BCVA Interference with BCVA

    Persistent corneal edema over detachment

    Partial detachment Free Descemetroll in AC

    First postoperative day: if incomplete attachment, continue supine position for 1-2 d

    Wait for 3 moExplain options to patients

    Await spontaneous clearanceReoperation

    Spontaneous clearanceSpontaneous reattachment

    ReoperationRebubble quickly or not at all

    Re-DMEKDSEK or DSAEK

    Figure 10. Diagram displaying recommendations to prevent detachments inDescemet membrane endothelial keratoplasty (DMEK) and a decision tree inthe event of a Descemet graft detachment. AC indicates anterior chamber;BCVA, best-corrected visual acuity; DSAEK, Descemet stripping automatedendothelial keratoplasty; DSEK, Descemet stripping endothelial keratoplasty;and PAS, peripheral anterior synechiae.

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  • be important: aphakic or postvitrectomy eyes or eyes witha large-sector iridectomy, glaucoma tube, extensive cor-neal decompensation, or tendency to have postopera-tive ocular hypotonia may be prone to Descemet graft de-tachment owing to a lack of air-bubble support and maybe managed with a modified surgical technique.32

    Submitted for Publication: June 20, 2011; final revi-sion received August 15, 2011; accepted August 23, 2011.Published Online: November 14, 2011. doi:10.1001/archophthalmol.2011.343Correspondence: Gerrit R. J. Melles, MD, PhD, Nether-lands Institute for Innovative Ocular Surgery, Laan opZuid 88, Rotterdam 3071 AA, the Netherlands (melles@niios.com).Author Contributions: Dr Melles had full access to all ofthe data in the study and takes responsibility for the in-tegrity of the data and the accuracy of the data analysis.Financial Disclosure: Dr Melles is a consultant for DutchOphthalmic Research Center International BV/DutchOphthalmic USA.

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    3. Price MO, Price FW. Descemet’s stripping endothelial keratoplasty. Curr OpinOphthalmol. 2007;18(4):290-294.

    4. Dapena I, Ham L, Melles GRJ. Endothelial keratoplasty: DSEK/DSAEK or DMEK:the thinner the better? Curr Opin Ophthalmol. 2009;20(4):299-307.

    5. Dapena I, Moutsouris K, Droutsas K, Ham L, van Dijk K, Melles GR. Standard-ized “no-touch” technique for Descemet membrane endothelial keratoplasty. ArchOphthalmol. 2011;129(1):88-94.

    6. Dirisamer M, Ham L, Dapena I, et al. Efficacy of Descemet membrane endothe-lial keratoplasty: clinical outcome of 200 consecutive cases after a learning curveof 25 cases [published online July 11, 2011]. Arch Ophthalmol. doi:10.1001/archophthalmol.2011.195.

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    11. Lie JT, Birbal R, Ham L, van der Wees J, Melles GR. Donor tissue preparationfor Descemet membrane endothelial keratoplasty. J Cataract Refract Surg. 2008;34(9):1578-1583.

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    14. Ham L, van der Wees J, Melles GRJ. Causes of primary donor failure in Des-cemet membrane endothelial keratoplasty. Am J Ophthalmol. 2008;145(4):639-644.

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    19. Busin M, Bhatt PR, Scorcia V. A modified technique for Descemet membranestripping automated endothelial keratoplasty to minimize endothelial cell loss.Arch Ophthalmol. 2008;126(8):1133-1137.

    20. Suh LH, Yoo SH, Deobhakta A, et al. Complications of Descemet’s stripping withautomated endothelial keratoplasty: survey of 118 eyes at one institute.Ophthalmology. 2008;115(9):1517-1524.

    21. Chen ES, Terry MA, Shamie N, Phillips PM, Friend DJ, McLeod SD. Descemet-stripping automated endothelial keratoplasty: insertion using a novel 40/60 un-derfold technique for preservation of donor endothelium. Cornea. 2008;27(8):941-943.

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    23. Basak SK. Descemet stripping and endothelial keratoplasty in endothelial dys-functions: three-month results in 75 eyes. Indian J Ophthalmol. 2008;56(4):291-296.

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    25. Wylegała E, Tarnawska D. Management of pseudophakic bullous keratopathy bycombined Descemet-stripping endothelial keratoplasty and intraocular lensexchange. J Cataract Refract Surg. 2008;34(10):1708-1714.

    26. Koenig SB, Covert DJ. Early results of small-incision Descemet’s stripping andautomated endothelial keratoplasty. Ophthalmology. 2007;114(2):221-226.

    27. Mearza AA, Qureshi MA, Rostron CK. Experience and 12-month results of Descemet-stripping endothelial keratoplasty (DSEK) with a small-incision technique. Cornea.2007;26(3):279-283.

    28. Price FW Jr, Price MO. Descemet’s stripping with endothelial keratoplasty in 200eyes: early challenges and techniques to enhance donor adherence. J CataractRefract Surg. 2006;32(3):411-418.

    29. Fillmore PD, Sutphin JE, Goins KM. Visual acuity, refractive error, and endothe-lial cell density 6 and 12 months after deep lamellar endothelial keratoplasty. Cornea.2010;29(6):601-606.

    30. Terry MA, Ousley PJ. Deep lamellar endothelial keratoplasty visual acuity, astig-matism, and endothelial survival in a large prospective series. Ophthalmology.2005;112(9):1541-1548.

    31. Bachmann BO, Laaser K, Cursiefen C, Kruse FE. A method to confirm correctorientation of Descemet membrane during Descemet membrane endothelialkeratoplasty. Am J Ophthalmol. 2010;149(6):922-925, e2.

    32. Dirisamer M, Ham L, Dapena I, van Dijk K, Melles GRJ. Descemet membraneendothelial transfer (DMET): ‘free floating’ donor Descemet implantation as a po-tential alternative to “keratoplasty.” Cornea. In press.

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