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Descemet Membrane Endothelial Keratoplasty: Safety and Outcomes

A Report by the American Academy of Ophthalmology
Published:September 16, 2017DOI:https://doi.org/10.1016/j.ophtha.2017.08.015

      Purpose

      To review the published literature on the safety and outcomes of Descemet membrane endothelial keratoplasty (DMEK) for the surgical treatment of corneal endothelial dysfunction.

      Methods

      Literature searches were last conducted in the PubMed and the Cochrane Library databases most recently in May 2017. The searches, which were limited to English-language abstracts, yielded 1085 articles. The panel reviewed the abstracts, and 47 were determined to be relevant to this assessment.

      Results

      After DMEK surgery, the mean best-corrected visual acuity (BCVA) ranged from 20/21 to 20/31, with follow-up ranging from 5.7 to 68 months. At 6 months, 37.6% to 85% of eyes achieved BCVA of 20/25 or better and 17% to 67% achieved BCVA of 20/20 or better. Mean endothelial cell (EC) loss was 33% (range, 25%–47%) at 6 months. Overall change in spherical equivalent was +0.43 diopters (D; range, –1.17 to +1.2 D), with minimal induced astigmatism of +0.03 D (range, –0.03 to +1.11 D). The most common complication was partial graft detachment requiring air injection (mean, 28.8%; range, 0.2%–76%). Intraocular pressure elevation was the second most common complication (range, 0%–22%) after DMEK, followed by primary graft failure (mean, 1.7%; range, 0%–12.5%), secondary graft failure (mean, 2.2%; range, 0%–6.3%), and immune rejection (mean, 1.9%; range, 0%–5.9%). Overall graft survival rates after DMEK ranged from 92% to 100% at last follow-up. Best-corrected visual acuity after Descemet’s stripping endothelial keratoplasty (DSEK) ranged from 20/34 to 20/66 at 9 months. The most common complications after DSEK were graft detachment (mean, 14%; range, 0%–82%), endothelial rejection (mean, 10%; range, 0%–45%), and primary graft failure (mean, 5%; range, 0%–29%). Mean EC loss after DSEK was 37% at 6 months.

      Conclusions

      The evidence reviewed supports DMEK as a safe and effective treatment for endothelial failure. With respect to visual recovery time, visual outcomes, and rejection rates, DMEK seems to be superior to DSEK and to induce less refractive error with similar surgical risks and EC loss compared with DSEK. The rate of air injection and repeat keratoplasty were similar in DMEK and DSEK after the learning curve for DMEK.

      Abbreviations and Acronyms:

      BCVA (best-corrected visual acuity), CME (cystoid macular edema), D (diopter), DM (Descemet membrane), DMEK (Descemet membrane endothelial keratoplasty), DSEK (Descemet’s stripping endothelial keratoplasty), EC (endothelial cell), IOP (intraocular pressure), PK (penetrating keratoplasty), SF6 (sulfur hexafluoride), VA (visual acuity)
      The American Academy of Ophthalmology prepares Ophthalmic Technology Assessments to evaluate new and existing procedures, drugs, and diagnostic and screening tests. The goal of an Ophthalmic Technology Assessment is to review systematically the available research for clinical efficacy, effectiveness, and safety. After appropriate review by all contributors, including legal counsel, assessments are submitted to the Academy's Board of Trustees for consideration as official Academy statements. The purpose of this assessment by the Ophthalmic Technology Assessment Committee Cornea and Anterior Segment Disorders Panel is to review the published literature on safety and outcomes of Descemet membrane endothelial keratoplasty (DMEK) to treat corneal endothelial dysfunction.

      Background

      Descemet membrane endothelial keratoplasty is a variation of endothelial keratoplasty for the treatment of corneal endothelial dysfunction. The concept of DMEK was introduced in 2002,
      • Melles G.R.
      • Lander F.
      • Rietveld F.J.
      Transplantation of Descemet’s membrane carrying viable endothelium through a small scleral incision.
      and the first case of DMEK use was published in 2006.
      • Melles G.R.
      • Ong T.S.
      • Ververs B.
      • van der Wees J.
      Descemet membrane endothelial keratoplasty (DMEK).
      According to the 2015 Eye Banking Statistical Report by the Eye Bank Association of America,
      Eye Bank Association of America
      2015 Eye banking statistical report.
      there has been an increase in DMEK procedures since 2012 in the United States. There was a 64% increase in the number of DMEK procedures performed in 2015 compared with 2014, resulting in a total of 4694 DMEK procedures in 2015. There has been a 4.1% decrease in Descemet’s stripping endothelial keratoplasty (DSEK) procedures since 2013, resulting in a total of 22 514 DSEK procedures in 2015. The increases in the number of DMEK procedures seems to coincide with the ability of the eye banks to offer prestripped DMEK tissues, a rapidly growing body of peer-reviewed literature, and extensive DMEK educational and skill transfer courses. Despite the difficult learning curve for the DMEK procedure, more corneal surgeons have started the transition from DSEK to DMEK since 2012 because of the purported advantages of DMEK over DSEK.
      Endothelial keratoplasty has evolved rapidly since the 1990s. It was first described in 1956 as posterior lamellar keratoplasty, whereby an anterior approach was used to replace the posterior corneal lamella using sutures.
      • Tillett C.W.
      Posterior lamellar keratoplasty.
      The technique was modified by Melles et al,
      • Melles G.R.
      • Lander F.
      • Beekhuis W.H.
      • et al.
      Posterior lamellar keratoplasty for a case of pseudophakic bullous keratopathy.
      and later by Terry and Ousley,
      • Terry M.A.
      • Ousley P.J.
      Deep lamellar endothelial keratoplasty in the first United States patients: early clinical results.
      to use a posterior approach and make a large scleral incision. The lamellar dissection of both the donor and recipient tissues was performed manually, and the donor lenticule was fixated onto the posterior stromal pocket using an air bubble instead of sutures. The manual dissection of the patient's posterior cornea proved to be too difficult to be adopted widely by corneal surgeons, and a variety of modifications were developed to improve the technique. Two modifications in particular since 2006 helped to improve and popularize the surgical procedure: (1) manual dissection of the posterior stroma was replaced with removal of the Descemet membrane (DM) from the recipient in a process described by Melles et al
      • Melles G.R.
      • Wijdh R.H.
      • Nieuwendaal C.P.
      A technique to excise the Descemet membrane from a recipient cornea (descemetorhexis).
      as descemetorhexis, and (2) manual dissection of donor tissue was replaced using the automated microkeratome starting in 2006.
      • Gorovoy M.S.
      Descemet-stripping automated endothelial keratoplasty.
      • Price Jr., F.W.
      • Price M.O.
      Descemet’s stripping with endothelial keratoplasty in 200 eyes: early challenges and techniques to enhance donor adherence.
      The procedure then was named Descemet's stripping automated endothelial keratoplasty and is generally referred to as DSEK, although the vast majority of donor tissues are now prepared by automated microkeratomes.
      An assessment on the safety and outcomes of DSEK by the American Academy of Ophthalmology in 2009
      • Lee W.B.
      • Jacobs D.S.
      • Musch D.C.
      • et al.
      Descemet’s stripping endothelial keratoplasty: safety and outcomes: a report by the American Academy of Ophthalmology.
      concluded that DSEK was superior to penetrating keratoplasty (PK) in terms of earlier visual recovery, refractive stability, refractive outcomes after surgery, wound- and suture-related complications, and suprachoroidal hemorrhage risk during and after surgery. Descemet’s stripping endothelial keratoplasty was found to be comparable with PK in terms of surgical risks, complication rates, graft survival (clarity), visual acuity (VA), and endothelial cell (EC) loss. Validation of the quality of precut tissues from eye banks further eliminated a major hurdle for most corneal surgeons who perform DSEK, and it became the surgical treatment of choice for corneal endothelial dysfunction. The number of DSEK procedures performed increased annually, and at the height of DSEK popularity (2013) the total number reached 23 465, accounting for 48.6% of all corneal transplantations performed in the United States.
      Eye Bank Association of America
      2015 Eye banking statistical report.
      Since the publication of the assessment by the American Academy of Ophthalmology in 2009, information on the long-term safety and outcomes of DSEK has become available. Although DSEK provides more rapid and predictable visual recovery than PK, the best-corrected VA (BCVA) after DSEK often is limited to 20/30 to 20/40. One study reported that only 20% of eyes with Fuchs' endothelial corneal dystrophy without other corneal pathologic features achieved 20/20 or better vision at year 5.
      • Wacker K.
      • Baratz K.H.
      • Maguire L.J.
      • et al.
      Descemet stripping endothelial keratoplasty for Fuchs’ endothelial corneal dystrophy: five-year results of a prospective study.
      A growing reason for DSEK regrafting was unsatisfactory BCVA relative to the visual potential.
      • Letko E.
      • Price D.A.
      • Lindoso E.M.
      • et al.
      Secondary graft failure and repeat endothelial keratoplasty after Descemet’s stripping automated endothelial keratoplasty.
      Interface opacity, irregularity of the posterior stroma, higher-order aberration of the posterior surface, and uneven cuts of the donor tissue contributed to the decreased optical quality.
      • Heinzelmann S.
      • Bohringer D.
      • Maier P.C.
      • Reinhard T.
      Correlation between visual acuity and interface reflectivity measured by Pentacam following DSAEK.
      • Rudolph M.
      • Laaser K.
      • Bachmann B.O.
      • et al.
      Corneal higher-order aberrations after Descemet’s membrane endothelial keratoplasty.
      The concept of transplanting only the DM (i.e., DMEK) was introduced in 2002 by Melles et al.
      • Melles G.R.
      • Lander F.
      • Rietveld F.J.
      Transplantation of Descemet’s membrane carrying viable endothelium through a small scleral incision.
      In DSEK, the endothelium, DM, and a thin layer of posterior stroma are transplanted as a single lamellar graft onto the surface of the host posterior stroma after descemetorhexis. In contrast, only the endothelium and DM are transplanted in DMEK. The thickness of the DM in adults (age range, 20–69 years) ranges from 6 to 15 μm, whereas the average graft thickness of tissues used in DSEK is 100 to 200 μm. Attachment of the DM graft to the posterior stromal surface may account for faster visual recovery, and it eliminates the issues of interface irregularity and haze as well as the refractive effect from the uneven stromal thickness of the microkeratome-cut DSEK graft. In the first small case series published in 2008,
      • Melles G.R.
      • Ong T.S.
      • Ververs B.
      • van der Wees J.
      Preliminary clinical results of Descemet membrane endothelial keratoplasty.
      3 of the 7 patients achieved a BCVA of 20/20 and 6 achieved a BCVA of 20/40 or better at 1 month after successful DMEK. The speed of visual recovery substantially was faster than that reported for DSEK, and this result was confirmed by subsequent larger series.
      • Ham L.
      • Dapena I.
      • van Luijk C.
      • et al.
      Descemet membrane endothelial keratoplasty (DMEK) for Fuchs endothelial dystrophy: review of the first 50 consecutive cases.
      • Price M.O.
      • Giebel A.W.
      • Fairchild K.M.
      • Price Jr., F.W.
      Descemet’s membrane endothelial keratoplasty: prospective multicenter study of visual and refractive outcomes and endothelial survival.
      Donor tissues for DMEK can be prepared in several ways. The initial technique to obtain DM grafts used a 9.0-mm trephine to obtain a cut in the DM. This 9.0-mm DM was peeled off from the posterior stroma using forceps.
      • Melles G.R.
      • Ong T.S.
      • Ververs B.
      • van der Wees J.
      Descemet membrane endothelial keratoplasty (DMEK).
      The submerged cornea using backgrounds away technique described in 2009
      • Price M.O.
      • Giebel A.W.
      • Fairchild K.M.
      • Price Jr., F.W.
      Descemet’s membrane endothelial keratoplasty: prospective multicenter study of visual and refractive outcomes and endothelial survival.
      consisted of the following steps. First, the peripheral DM just inside the trabecular meshwork was scored using forceps, a Sinskey hook, or a blade. A single nontooth forceps then was used to peel the DM from the stroma approximately halfway to the center for 360° while submerged in a viewing chamber to enhance the visualization of the DM.
      • Price M.O.
      • Giebel A.W.
      • Fairchild K.M.
      • Price Jr., F.W.
      Descemet’s membrane endothelial keratoplasty: prospective multicenter study of visual and refractive outcomes and endothelial survival.
      Finally, the DM was trephined to an appropriate size, and separation of the DM from the donor tissue was completed. Peeling the DM with 2 forceps reportedly reduced tension and thereby presumably reduced tears in the donor DM.
      • Laaser K.
      • Bachmann B.O.
      • Horn F.K.
      • et al.
      Donor tissue culture conditions and outcome after Descemet membrane endothelial keratoplasty.
      Other methods using hydrodissection, pneumodissection, and viscoelastics to separate the DM have been tested in the laboratory, but are not used commonly in actual tissue preparation for transplantation in the United States. The overall failure rate of DM donor preparation by the eye banks is approximately 5%
      • Vianna L.M.
      • Stoeger C.G.
      • Galloway J.D.
      • et al.
      Risk factors for eye bank preparation failure of Descemet membrane endothelial keratoplasty tissue.
      and is as low as 2% when the preparation is carried out by experienced surgeons.
      • Schlotzer-Schrehardt U.
      • Bachmann B.O.
      • Tourtas T.
      • et al.
      Reproducibility of graft preparations in Descemet’s membrane endothelial keratoplasty.
      A history of diabetes mellitus may increase the failure rate of donor preparation.
      • Greiner M.A.
      • Rixen J.J.
      • Wagoner M.D.
      • et al.
      Diabetes mellitus increases risk of unsuccessful graft preparation in Descemet membrane endothelial keratoplasty: a multicenter study.
      When completely separated from the stroma, the DM tissue curls into a scroll with the endothelium facing outside. Trypan blue is used to stain the DM for visualization just before loading it into the intraocular delivery device.
      After the central recipient DM is removed (descemetorhexis) under air, cohesive viscoelastic, or fluid, the DM graft is delivered into the anterior chamber using a glass tube, such as a glass pipet or modified Jones tube, or a plastic intraocular lens injector. There are several techniques for unfolding the DM scroll: a gentle tapping on the cornea (the no-touch technique),
      • Dapena I.
      • Moutsouris K.
      • Droutsas K.
      • et al.
      Standardized “no-touch” technique for Descemet membrane endothelial keratoplasty.
      a combination of small spurts of balanced salt solution and air under the endothelium,
      • Price M.O.
      • Giebel A.W.
      • Fairchild K.M.
      • Price Jr., F.W.
      Descemet’s membrane endothelial keratoplasty: prospective multicenter study of visual and refractive outcomes and endothelial survival.
      placement of a small air bubble between the graft and the host stroma,
      • Kruse F.E.
      • Laaser K.
      • Cursiefen C.
      • et al.
      A stepwise approach to donor preparation and insertion increases safety and outcome of Descemet membrane endothelial keratoplasty.
      a single cannula,
      • Deng S.X.
      • Sanchez P.J.
      • Chen L.
      Clinical outcomes of Descemet membrane endothelial keratoplasty using eye bank-prepared tissues.
      2 cannulas (the bimanual technique),
      • Guell J.L.
      • Morral M.
      • Gris O.
      • et al.
      Comparison of sulfur hexafluoride 20% versus air tamponade in Descemet membrane endothelial keratoplasty.
      or a gentle rolling on the corneal surface.
      • Dapena I.
      • Moutsouris K.
      • Droutsas K.
      • et al.
      Standardized “no-touch” technique for Descemet membrane endothelial keratoplasty.
      Various methods have been used to confirm the correct orientation of the DM graft. These include the use of orientation marks on the edge of the DM graft,
      • Kruse F.E.
      • Laaser K.
      • Cursiefen C.
      • et al.
      A stepwise approach to donor preparation and insertion increases safety and outcome of Descemet membrane endothelial keratoplasty.
      a blue cannula sign,
      • Dapena I.
      • Moutsouris K.
      • Droutsas K.
      • et al.
      Standardized “no-touch” technique for Descemet membrane endothelial keratoplasty.
      a hand-held slit beam,
      • Burkhart Z.N.
      • Feng M.T.
      • Price M.O.
      • Price F.W.
      Handheld slit beam techniques to facilitate DMEK and DALK.
      OCT during surgery,
      • Ehlers J.P.
      • Goshe J.
      • Dupps W.J.
      • et al.
      Determination of feasibility and utility of microscope-integrated optical coherence tomography during ophthalmic surgery: the DISCOVER study RESCAN results.
      and ink marks on the DM side of the graft.
      • Veldman P.B.
      • Dye P.K.
      • Holiman J.D.
      • et al.
      The S-stamp in Descemet membrane endothelial keratoplasty safely eliminates upside-down graft implantation.
      As soon as the donor tissue is unfolded in the correct orientation and centered, air is injected underneath the graft to attach it to the recipient cornea. Sulfur hexafluoride (SF6; 14% or 20%) gas can be used instead of 100% air to decrease the graft detachment rate because SF6 has a longer tamponade time than 100% air. The anterior chamber remains at full air or gas-filled for 10 minutes or up to 2 hours before some of the air or gas is removed to avoid pupillary block. Peripheral iridectomy is performed before or during the DMEK procedure by some surgeons to avoid pupillary block. The patient is instructed to stay in the supine position after surgery for 1 to 3 days to allow the maximal tamponade effect of the air or gas.

      Questions for Assessment

      The objective of this assessment is to address the following questions: (1) Is DMEK safe and effective as a treatment for corneal endothelial dysfunction? (2) Does DMEK offer any advantages over DSEK in terms of visual recovery, outcomes, and complications? The outcomes of different methods used to prepare DMEK donor tissue or to insert the donor tissue were not evaluated in this assessment.

      Description of Evidence

      Literature searches were conducted in the PubMed and Cochrane Library databases in October 2014, November 2015, November 2016, and May 2017 and were limited to peer-reviewed English-language abstracts. Key search terms were the MeSH headings Descemet membrane endothelial keratoplasty, Descemet's membrane endothelial keratoplasty, DMEK, posterior lamellar keratoplasty, and endothelial keratoplasty. Studies of nonhuman and deep anterior lamellar keratoplasty were excluded.
      The searches yielded 1085 citations, and after reviewing the abstracts of these articles, the panel selected 112 that potentially met the inclusion criteria. The panel reviewed the full text of the 112 articles to determine whether each met the criteria for inclusion in this assessment. Publications that included large case series (25 or more cases of DMEK); prospective, controlled clinical studies; and observational studies were selected for final review. Letters; editorials; reviews; abstracts of meeting presentations; small studies (fewer than 25 cases of DMEK); reports of histopathologic results, repeat DMEK, graft insertion devices or techniques, and storage mediums for donor tissues; and laboratory studies were excluded from this assessment. To avoid redundancy, in cases where multiple studies were performed by the same group, the initial smaller studies were excluded if the most recent larger studies were likely to include the same study population and if they investigated the same outcome measures. Only the clinical outcomes and complications from the larger studies were included for final review.
      A total of 47 articles met the inclusion criteria for the final review, and the panel methodologist (R.M.S.) assigned each study a rating according to the level of evidence. The rating scale was based on that developed by the Oxford Centre for Evidence-Based Medicine.
      A level I rating was assigned to well-designed and well-conducted randomized clinical trials; a level II rating was assigned to well-designed case-control and cohort studies and randomized clinical trials with substantial methodologic deficits; and a level III rating was assigned to case series, case reports, and poor-quality cohort and case-control studies. Of the 47 studies selected, 2 studies were rated level I, 15 studies were rated level II, and 30 studies were rated level III.

      Published Results

       Visual Outcomes

      The visual outcomes of DMEK are listed in Table 1. To allow for direct comparison, logarithm of the minimum angle of resolution measures of VA were converted to the Snellen VA equivalents. The mean length of follow-up ranged from 5.3 to 68 months. The mean BCVA ranged from 20/21 to 20/31 after DMEK during the follow-up period. Five studies
      • Tourtas T.
      • Laaser K.
      • Bachmann B.O.
      • et al.
      Descemet membrane endothelial keratoplasty versus Descemet stripping automated endothelial keratoplasty.
      • Guerra F.P.
      • Anshu A.
      • Price M.O.
      • et al.
      Descemet’s membrane endothelial keratoplasty: prospective study of 1-year visual outcomes, graft survival, and endothelial cell loss.
      • Laaser K.
      • Bachmann B.O.
      • Horn F.K.
      • et al.
      Descemet membrane endothelial keratoplasty combined with phacoemulsification and intraocular lens implantation: advanced triple procedure.
      • Rodriguez-Calvo-de-Mora M.
      • Quilendrino R.
      • Ham L.
      • et al.
      Clinical outcome of 500 consecutive cases undergoing Descemet’s membrane endothelial keratoplasty.
      • Schlögl A.
      • Tourtas T.
      • Kruse F.E.
      • Weller J.M.
      Long-term clinical outcome after Descemet membrane endothelial keratoplasty.
      reported that 33% to 67% of eyes achieved a BCVA of 20/25 or better and 3 studies
      • Guerra F.P.
      • Anshu A.
      • Price M.O.
      • et al.
      Descemet’s membrane endothelial keratoplasty: prospective study of 1-year visual outcomes, graft survival, and endothelial cell loss.
      • Gorovoy M.S.
      DMEK complications.
      • Rodriguez-Calvo-de-Mora M.
      • Quilendrino R.
      • Ham L.
      • et al.
      Clinical outcome of 500 consecutive cases undergoing Descemet’s membrane endothelial keratoplasty.
      reported that 29% to 32% achieved a BCVA of 20/20 or better at 3 months after surgery. Eleven studies
      • Tourtas T.
      • Laaser K.
      • Bachmann B.O.
      • et al.
      Descemet membrane endothelial keratoplasty versus Descemet stripping automated endothelial keratoplasty.
      • Hamzaoglu E.C.
      • Straiko M.D.
      • Mayko Z.M.
      • et al.
      The first 100 eyes of standardized Descemet stripping automated endothelial keratoplasty versus standardized Descemet membrane endothelial keratoplasty.
      • Guerra F.P.
      • Anshu A.
      • Price M.O.
      • et al.
      Descemet’s membrane endothelial keratoplasty: prospective study of 1-year visual outcomes, graft survival, and endothelial cell loss.
      • Laaser K.
      • Bachmann B.O.
      • Horn F.K.
      • et al.
      Descemet membrane endothelial keratoplasty combined with phacoemulsification and intraocular lens implantation: advanced triple procedure.
      • Parker J.
      • Dirisamer M.
      • Naveiras M.
      • et al.
      Outcomes of Descemet membrane endothelial keratoplasty in phakic eyes.
      • Monnereau C.
      • Quilendrino R.
      • Dapena I.
      • et al.
      Multicenter study of Descemet membrane endothelial keratoplasty: first case series of 18 surgeons.
      • Rodriguez-Calvo-de-Mora M.
      • Quilendrino R.
      • Ham L.
      • et al.
      Clinical outcome of 500 consecutive cases undergoing Descemet’s membrane endothelial keratoplasty.
      • Gundlach E.
      • Maier A.K.
      • Tsangaridou M.A.
      • et al.
      DMEK in phakic eyes: targeted therapy or highway to cataract surgery?.
      • Ham L.
      • Dapena I.
      • Liarakos V.S.
      • et al.
      Midterm results of Descemet membrane endothelial keratoplasty: 4 to 7 years clinical outcome.
      • Siggel R.
      • Adler W.
      • Stanzel T.P.
      • et al.
      Bilateral Descemet membrane endothelial keratoplasty: analysis of clinical outcome in first and fellow eye.
      • Debellemanière G.
      • Guilbert E.
      • Courtin R.
      • et al.
      Impact of surgical learning curve in Descemet membrane endothelial keratoplasty on visual acuity gain.
      reported that 32% to 85% achieved a BCVA of 20/25 or better, and 12 studies reported that 17% to 67% achieved a BCVA of 20/20 or better at 6 months after DMEK.
      Table 1Visual Outcomes and Complications of Descemet Membrane Endothelial Keratoplasty
      Author(s), YearCountryLevel of EvidenceTotal No. of EyesFollow-up (mos)Subgroups (No.)Mean Snellen Best-Corrected Visual Acuity after Descemet Membrane Endothelial KeratoplastyBest-Corrected Visual Acuity (6 mos)Endothelial Cell Loss (%)Air Injection Rate (%)Primary Graft Failure Rate (Secondary Graft Failure Rate; %)Immune Rejection Rate (%)Other Complications
      Price et al,
      • Price M.O.
      • Price Jr., F.W.
      • Kruse F.E.
      • et al.
      Randomized comparison of topical prednisolone acetate 1% versus fluorometholone 0.1% in the first year after Descemet membrane endothelial keratoplasty.
      2014
      United States and GermanyI29712PF (164)300CME, 0%; cataract, 1%; IOP elevation, 21.9%
      FML (161)311.4CME, 1.8%; IOP elevation, 6.1%; 5% of the eyes after DMEK/CE needed to change to PF
      Price et al,
      • Price M.O.
      • Feng M.T.
      • Scanameo A.
      • Price Jr., F.W.
      Loteprednol etabonate 0.5% gel vs. prednisolone acetate 1% solution after Descemet membrane endothelial keratoplasty: prospective randomized trial.
      2015
      United StatesI23312PF (167)290IOP elevation, 25%; corneal ulcer, 1%
      Loteprednol (167)320IOP elevation, 11%; allergic reaction, 3%
      Rudolph et al,
      • Rudolph M.
      • Laaser K.
      • Bachmann B.O.
      • et al.
      Corneal higher-order aberrations after Descemet’s membrane endothelial keratoplasty.
      2012
      GermanyII30DMEK (6.5); DSEK (22.6); PK (103)DMEK (30)20/29
      DSEK (20)20/37
      P < 0.05 comparing between groups or with the control.
      PK (20)20/48
      P < 0.05 comparing between groups or with the control.
      Tourtas et al,
      • Tourtas T.
      • Laaser K.
      • Bachmann B.O.
      • et al.
      Descemet membrane endothelial keratoplasty versus Descemet stripping automated endothelial keratoplasty.
      2012
      GermanyII386DMEK (38)20/30≥20/25 (50%)4182
      DSEK (35)20/46
      P < 0.05 comparing between groups or with the control.
      ≥20/25 (6%)
      P < 0.05 comparing between groups or with the control.
      3920
      P < 0.05 comparing between groups or with the control.
      Feng et al,
      • Feng M.T.
      • Burkhart Z.N.
      • Price Jr., F.W.
      • Price M.O.
      Effect of donor preparation-to-use times on Descemet membrane endothelial keratoplasty outcomes.
      2013
      United StatesII3613Donor prepared on day of surgery (130)28151.5 (—)
      Donor prepared 1 day before surgery (160)29131.9 (—)
      Donor prepared 2 days before surgery (71)29142.8 (—)
      Chaurasia et al,
      • Chaurasia S.
      • Price Jr., F.W.
      • Gunderson L.
      • Price M.O.
      Descemet’s membrane endothelial keratoplasty: clinical results of single versus triple procedures (combined with cataract surgery).
      2014
      United StatesII4926DMEK (292)20/25 (median)27303.1 (0)0CME, 1%
      DMEK/CE (200)20/20 (median)25293.5 (0)0CME, 1.5%
      Cabrerizo et al,
      • Cabrerizo J.
      • Livny E.
      • Musa F.U.
      • et al.
      Changes in color vision and contrast sensitivity after Descemet membrane endothelial keratoplasty for Fuchs endothelial dystrophy.
      2014
      The NetherlandsII297.3Phakic DMEK (12)20/22
      Pseudophakic DMEK (17)20/21
      Guell et al,
      • Guell J.L.
      • Morral M.
      • Gris O.
      • et al.
      Comparison of sulfur hexafluoride 20% versus air tamponade in Descemet membrane endothelial keratoplasty.
      2015
      SpainII8136SF6 (42)20/22 (86% ≥20/25)33 at 12 mos2.42.4 (0)0IOP elevation, 0%
      Air (39)20/25 (80% ≥20/25)34 at 12 mos12.8
      P < 0.05 comparing between groups or with the control.
      0 (0)0IOP elevation, 0%
      Hamzaoglu et al,
      • Hamzaoglu E.C.
      • Straiko M.D.
      • Mayko Z.M.
      • et al.
      The first 100 eyes of standardized Descemet stripping automated endothelial keratoplasty versus standardized Descemet membrane endothelial keratoplasty.
      2015
      United StatesII1006DMEK (100)20/26≥20/25 (67%); ≥20/20 (46%)2864 –03 upside-down grafts
      DSEK (100)20/32
      P < 0.05 comparing between groups or with the control.
      ≥20/25 (31%); ≥20/20 (13%)2620 –1
      Heinzelmann et al,
      • Heinzelmann S.
      • Maier P.
      • Bohringer D.
      • et al.
      Cystoid macular oedema following Descemet membrane endothelial keratoplasty.
      2015
      GermanyII1556DMEK (80)181.3 –CME, 12.5%
      DMEK/CE (75)234 –CME, 13.3%
      Veldman et al,
      • Veldman P.B.
      • Dye P.K.
      • Holiman J.D.
      • et al.
      The S-stamp in Descemet membrane endothelial keratoplasty safely eliminates upside-down graft implantation.
      2016
      United StatesII1656Unstamped (32)20/2629312.5 (0)3.1Upside-down graft, 9.4%
      S-stamped (133)20/2531130.8/00.8Upside-down graft, 0%
      Droutsas et al,
      • Droutsas K.
      • Lazaridis A.
      • Papaconstantinou D.
      • et al.
      Visual outcomes after Descemet membrane endothelial keratoplasty versus Descemet stripping automated endothelial keratoplasty-comparison of specific matched pairs.
      2016
      GreeceII2512DMEK (25)20/20 (median)44
      DSEK (25)20/40 (median)
      P < 0.05 comparing between groups or with the control.
      42
      Heinzelmann et al,
      • Heinzelmann S.
      • Bohringer D.
      • Eberwein P.
      • et al.
      Outcomes of Descemet membrane endothelial keratoplasty, Descemet stripping automated endothelial keratoplasty and penetrating keratoplasty from a single centre study.
      2016
      GermanyII45042DMEK (450)≥20/25 (53%)20— (7)7
      DSEK (89)≥20/25 (15%)— (20)21
      PKP (329)≥20/25 (10%)— (2)18
      Price et al,
      • Price M.O.
      • Scanameo A.
      • Feng M.T.
      • Price Jr., F.W.
      Descemet’s membrane endothelial keratoplasty: risk of immunologic rejection episodes after discontinuing topical corticosteroids.
      2016
      United StatesII40012Corticosteroid (123)–5.6/yr— (0)0IOP elevation, 1.6%
      No corticosteroid (277)–6.4/yr—(0.4)6
      P < 0.05 comparing between groups or with the control.
      IOP elevation, 0.04%
      Schaub et al,
      • Schaub F.
      • Enders P.
      • Snijders K.
      • et al.
      One-year outcome after Descemet membrane endothelial keratoplasty (DMEK) comparing sulfur hexafluoride (SF6) 20% versus 100% air for anterior chamber tamponade.
      2017
      GermanyII85412Air (749)20/29 (median)38540.1 –0.3Regraft rate, 2.3%; release of air to lower IOP, 4.9%
      SF6 (105)20/26 (median)36240 –0Regraft rate, 2.9%; release of gas to lower IOP, 7.6%
      Phillips et al,
      • Phillips P.M.
      • Phillips L.J.
      • Muthappan V.
      • et al.
      Experienced DSAEK surgeon’s transition to DMEK: outcomes comparing the last 100 DSAEK surgeries with the first 100 DMEK surgeries exclusively using previously published techniques.
      2017
      United StatesII1006DSEK (100)20/3220/20 (13%)19.9
      P < 0.05 comparing between groups or with the control.
      100Posterior synechia, 0%
      DMEK (100)20/2420/20 (55%)31.9500Posterior synechia, 15%
      Aravena et al,
      • Aravena C.
      • Yu F.
      • Deng S.X.
      Outcomes of Descemet membrane endothelial keratoplasty in patients with previous glaucoma surgery.
      2017
      United StatesII1089.7Control (60)20/25 (median)
      At 3-month follow-up.
      33231.71.7IOP elevation, 23%
      P < 0.05 comparing between groups or with the control.
      ; surgery to control IOP, 0%
      P < 0.05 comparing between groups or with the control.
      MT (14)20/30 (median)
      At 3-month follow-up.
      302400IOP elevation, 50%; surgery to control IOP, 14%
      ST (34)20/40 (median)
      At 3-month follow-up.
      45
      P < 0.05 comparing between groups or with the control.
      2100IOP elevation, 15%; surgery to control IOP, 9%
      P < 0.05 comparing between groups or with the control.
      Guerra et al,
      • Guerra F.P.
      • Anshu A.
      • Price M.O.
      • et al.
      Descemet’s membrane endothelial keratoplasty: prospective study of 1-year visual outcomes, graft survival, and endothelial cell loss.
      2011
      United StatesIII13612DMEK (136)20/24≥20/25 (72%); ≥20/20 (42%)36628.1 (0.7)5.1Complete detachment, 1; pupillary block, 0
      Laaser et al,
      • Laaser K.
      • Bachmann B.O.
      • Horn F.K.
      • et al.
      Descemet membrane endothelial keratoplasty combined with phacoemulsification and intraocular lens implantation: advanced triple procedure.
      2012
      GermanyIII616DMEK/CE20/31≥20/25 (38%)4074
      Parker et al,
      • Parker J.
      • Dirisamer M.
      • Naveiras M.
      • et al.
      Outcomes of Descemet membrane endothelial keratoplasty in phakic eyes.
      2012
      The NetherlandsIII526Phakic DMEK (52)35≥20/25 (85%); ≥20/20 (67%)3500 (0)0Angle closure, 11.5%; cataract, 10%
      Dirisamer et al,
      • Dirisamer M.
      • van Dijk K.
      • Dapena I.
      • et al.
      Prevention and management of graft detachment in Descemet membrane endothelial keratoplasty.
      2012
      The NetherlandsIII3824Partial detachment ≤1/3 (16)≥20/40 (88%)Edema spontaneously cleared in all eyes
      Partial detachment >1/3 (8)≥20/40 (50%)Progressive clearing observed in all eyes over 1 yr
      Upside down (4)≥20/40 (0%)Fibrosis in interface and reversed clearing pattern
      Free floating (8)≥20/40 (0%)Persistent corneal edema
      Anshu et al,
      • Anshu A.
      • Price M.O.
      • Price Jr., F.W.
      Risk of corneal transplant rejection significantly reduced with Descemet’s membrane endothelial keratoplasty.
      (Price) 2012
      United StatesIII14013DMEK (141)0.7
      DSEK (598)9
      PK (30)17
      Deng et al,
      • Deng S.X.
      • Sanchez P.J.
      • Chen L.
      Clinical outcomes of Descemet membrane endothelial keratoplasty using eye bank-prepared tissues.
      2014
      United StatesIII405.3DMEK (40)20/20 (median); ≥20/25 (77%); ≥20/20 (51%)31282.5 (0)0
      Gorovoy,
      • Gorovoy M.S.
      DMEK complications.
      2014
      United StatesIII753DMEKNA≥20/30 (85%)
      At 3-month follow-up.
      ; ≥20/20 (29%)
      At 3-month follow-up.
      2.7.2.7 –Pupillary block, 0
      Monnereau et al,
      • Monnereau C.
      • Quilendrino R.
      • Dapena I.
      • et al.
      Multicenter study of Descemet membrane endothelial keratoplasty: first case series of 18 surgeons.
      2014
      The NetherlandsIII4316DMEKNA≥20/25 (44%)47242.3 (6.3)3.7Regraft rate, 10%; failed to unfold, 1.2%; intraoperative hemorrhage, 0.5%; Descemet membrane wrinkle in center, 1.9%; IOP elevation, 2.8%; cataract, 0.2%
      Burkhart et al,
      • Burkhart Z.N.
      • Feng M.T.
      • Price Jr., F.W.
      • Price M.O.
      One-year outcomes in eyes remaining phakic after Descemet membrane endothelial keratoplasty.
      2014
      United StatesIII4912Phakic DMEK (49)20/20 (median); ≥20/25 (92%)25330 (0)Cataract progression, 76%; CE, 33%
      Tourtsas et al,
      • Tourtas T.
      • Schlomberg J.
      • Wessel J.M.
      • et al.
      Graft adhesion in Descemet membrane endothelial keratoplasty dependent on size of removal of host’s Descemet membrane.
      2014
      GermanyIII531Large descemetorhexis (30)6.7
      Small descemetorhexis (23)30.4
      P < 0.05 comparing between groups or with the control.
      Maier et al,
      • Maier A.K.
      • Wolf T.
      • Gundlach E.
      • et al.
      Intraocular pressure elevation and post-DMEK glaucoma following Descemet membrane endothelial keratoplasty.
      2014
      GermanyIII11712DMEK (117)20/33 at 6 mos2844.40 (0)0.9Pupillary block, 15.4%; I-K adhesion, 4.2%; IOP elevation, 10.4%
      Feng et al,
      • Feng M.T.
      • Price M.O.
      • Miller J.M.
      • Price Jr., F.W.
      Air reinjection and endothelial cell density in Descemet membrane endothelial keratoplasty: five-year follow-up.
      2014
      United StatesIII67360DMEK (673)39 (27 at 1 mo)301 air injection had no effect on EC loss
      Rodríguez-Calvo-de-Mora et al,
      • Rodriguez-Calvo-de-Mora M.
      • Quilendrino R.
      • Ham L.
      • et al.
      Clinical outcome of 500 consecutive cases undergoing Descemet’s membrane endothelial keratoplasty.
      2015
      The NetherlandsIII5006DMEK≥20/25 (75%); ≥20/20 (41%)3730.2 (0.2)0.2Regraft, 2.2%; complication during surgery, 16.8%; retinal detachment, 0.2%; cataract, 0.4%
      Gundlach et al,
      • Gundlach E.
      • Maier A.K.
      • Tsangaridou M.A.
      • et al.
      DMEK in phakic eyes: targeted therapy or highway to cataract surgery?.
      2015
      GermanyIII676Phakic DMEK (13)20/27≥20/25 (55%); ≥20/20 (36%)340Cataract, 15.4%; IOP elevation, 15.4%
      DMEK/CE (54)20/28≥20/25 (52%); ≥20/20 (17%)271.9IOP elevation, 7.4%
      Bhandari et al,
      • Bhandari V.
      • Reddy J.K.
      • Relekar K.
      • Prabhu V.
      Descemet’s stripping automated endothelial keratoplasty versus Descemet’s membrane endothelial keratoplasty in the fellow eye for Fuchs endothelial dystrophy: a retrospective study.
      2015
      IndiaIII3012DMEK (30)20/302410
      DSEK (30)20/44
      P < 0.05 comparing between groups or with the control.
      210
      Schoenberg et al,
      • Schoenberg E.D.
      • Price Jr., F.W.
      • Miller J.
      • et al.
      Refractive outcomes of Descemet membrane endothelial keratoplasty triple procedures (combined with cataract surgery).
      2015
      United StatesIII10811.9DMEK/CE20/20 (median); ≥20/25 (79%); ≥20/20 (51%)29
      Röck et al,
      • Röck T.
      • Bramkamp M.
      • Bartz-Schmidt K.U.
      • et al.
      Causes that influence the detachment rate after Descemet membrane endothelial keratoplasty.
      2015
      GermanyIII16013.9Centered (115)20/263215
      Decentered (45)20/39
      P < 0.05 comparing between groups or with the control.
      3544
      P < 0.05 comparing between groups or with the control.
      Maier et al,
      • Maier A.K.
      • Gundlach E.
      • Schroeter J.
      • et al.
      Influence of the difficulty of graft unfolding and attachment on the outcome in Descemet membrane endothelial keratoplasty.
      2015
      GermanyIII16917.7Straightforward (63)20/3221 at 6 mos370 (0)0.9CME, 3.8%
      Manipulation <5 mins (47)20/3124 at 6 mos450 (0)
      Manipulation >5 mins + repeat air exchange (32)20/3223 at 6 mos440 (0)
      Direct manipulation of graft (18)20/3742 at 6 mos500 (0)
      Gorovoy et al,
      • Gorovoy I.R.
      • Gorovoy M.S.
      Descemet membrane endothelial keratoplasty postoperative year 1 endothelial cell counts.
      2015
      United StatesIII12512DMEK (125)1953 –
      Ham et al,
      • Ham L.
      • Dapena I.
      • Liarakos V.S.
      • et al.
      Midterm results of Descemet membrane endothelial keratoplasty: 4 to 7 years clinical outcome.
      2016
      The NetherlandsIII25068DMEK (250)≥20/25 (83%); ≥20/20 (54%)≥20/25 (73%); ≥20/20 (44%)53 at 4 yrs1.6 (2.0)2.4Regraft rate, 16.8%
      Siggel et al,
      • Siggel R.
      • Adler W.
      • Stanzel T.P.
      • et al.
      Bilateral Descemet membrane endothelial keratoplasty: analysis of clinical outcome in first and fellow eye.
      2016
      GermanyIII12012DMEK (120)20/29≥20/25 (49%); ≥20/20 (20%)52760.8 (0.8)1.7IOP ≥30 mmHg, 6.7%; anterior chamber inflammation, 5.8%
      Hoerster et al,
      • Hoerster R.
      • Stanzel T.P.
      • Bachmann B.O.
      • et al.
      Intensified topical steroids as prophylaxis for macular edema after posterior lamellar keratoplasty combined with cataract surgery.
      • Hoerster R.
      • Stanzel T.P.
      • Bachmann B.O.
      • et al.
      Intensified early postoperative topical steroids do not influence endothelial cell density after Descemet membrane endothelial keratoplasty combined with cataract surgery (Triple-DMEK).
      2016
      GermanyIII1506Intense PF (75)20/303852Angle closure, 2.7%; elevated IOP from PF, 2.7%; CME, 0%
      Standard PF (75)20/303867Angle closure, 4.0%; no IOP elevation from PF; CME, 12%
      P < 0.05 comparing between groups or with the control.
      van Dijk et al,
      • van Dijk K.
      • Rodriguez-Calvo-de-Mora M.
      • van Esch H.
      • et al.
      Two-year refractive outcomes after Descemet membrane endothelial keratoplasty.
      2016
      The NetherlandsIII6724DMEK (67)20/24 at 12 mos
      Schlögl et al,
      • Schlögl A.
      • Tourtas T.
      • Kruse F.E.
      • Weller J.M.
      Long-term clinical outcome after Descemet membrane endothelial keratoplasty.
      2016
      GermanyIII9753DMEK (97)20/27≥20/25 (42%)
      At 3-month follow-up.
      44 at 5 yrs2 (1)1CME, 3%
      Hos et al,
      • Hos D.
      • Tuac O.
      • Schaub F.
      • et al.
      Incidence and clinical course of immune reactions after Descemet membrane endothelial keratoplasty: retrospective analysis of 1000 consecutive eyes.
      2017
      GermanyIII90518.5Rejection (12)1.3Probability of rejection at 1 yr, 0.9%; at 2 yrs, 2.3%; at 4 yrs, 2.3%
      Debellemanière, et al,
      • Debellemanière G.
      • Guilbert E.
      • Courtin R.
      • et al.
      Impact of surgical learning curve in Descemet membrane endothelial keratoplasty on visual acuity gain.
      2017
      FranceIII1096DMEK (109)>20/20 (18%); >20/25 (33%)38 at 6 mos183.7 (0)0.9Impossible unrolling, 2.8%; complete detachment, 1.8%; inverted graft, 1.8%; pupillary block, 7.3%; CME, 5.5%
      CE = cataract surgery with intraocular lens implantation; CME = cystoid macular edema; DMEK = Descemet membrane endothelial keratoplasty; DSEK = Descemet’s stripping endothelial keratoplasty; EC = endothelial cell; FED = Fuchs' endothelial dystrophy; FML = fluorometholone; IOP = intraocular pressure; MT = medically treated glaucoma group; - = not available; PF = prednisolone acetate; PK = penetrating keratoplasty; SF6 = sulfur hexafluoride 6; ST = surgically treated glaucoma group.
      P < 0.05 comparing between groups or with the control.
      At 3-month follow-up.
      Seven studies
      • Rudolph M.
      • Laaser K.
      • Bachmann B.O.
      • et al.
      Corneal higher-order aberrations after Descemet’s membrane endothelial keratoplasty.
      • Tourtas T.
      • Laaser K.
      • Bachmann B.O.
      • et al.
      Descemet membrane endothelial keratoplasty versus Descemet stripping automated endothelial keratoplasty.
      • Hamzaoglu E.C.
      • Straiko M.D.
      • Mayko Z.M.
      • et al.
      The first 100 eyes of standardized Descemet stripping automated endothelial keratoplasty versus standardized Descemet membrane endothelial keratoplasty.
      • Droutsas K.
      • Lazaridis A.
      • Papaconstantinou D.
      • et al.
      Visual outcomes after Descemet membrane endothelial keratoplasty versus Descemet stripping automated endothelial keratoplasty-comparison of specific matched pairs.
      • Heinzelmann S.
      • Bohringer D.
      • Eberwein P.
      • et al.
      Outcomes of Descemet membrane endothelial keratoplasty, Descemet stripping automated endothelial keratoplasty and penetrating keratoplasty from a single centre study.
      • Phillips P.M.
      • Phillips L.J.
      • Muthappan V.
      • et al.
      Experienced DSAEK surgeon’s transition to DMEK: outcomes comparing the last 100 DSAEK surgeries with the first 100 DMEK surgeries exclusively using previously published techniques.
      • Bhandari V.
      • Reddy J.K.
      • Relekar K.
      • Prabhu V.
      Descemet’s stripping automated endothelial keratoplasty versus Descemet’s membrane endothelial keratoplasty in the fellow eye for Fuchs endothelial dystrophy: a retrospective study.
      that directly compared the visual outcomes of DMEK and DSEK all showed a better visual recovery after DMEK than after DSEK (6 of these 7 studies were rated as level II evidence). Descemet membrane endothelial keratoplasty and DSEK cases were matched in 1 study, and the DMEK and DSEK groups in the other 6 studies were similar in terms of recipient age, recipient gender, and indications for surgery. In 6 studies, DMEK achieved a significantly better mean or median BCVA than DSEK did after surgery (20/30 vs. 20/46,
      • Tourtas T.
      • Laaser K.
      • Bachmann B.O.
      • et al.
      Descemet membrane endothelial keratoplasty versus Descemet stripping automated endothelial keratoplasty.
      20/26 vs. 20/32,
      • Hamzaoglu E.C.
      • Straiko M.D.
      • Mayko Z.M.
      • et al.
      The first 100 eyes of standardized Descemet stripping automated endothelial keratoplasty versus standardized Descemet membrane endothelial keratoplasty.
      20/29 vs. 20/37,
      • Rudolph M.
      • Laaser K.
      • Bachmann B.O.
      • et al.
      Corneal higher-order aberrations after Descemet’s membrane endothelial keratoplasty.
      20/20 vs. 20/40,
      • Droutsas K.
      • Lazaridis A.
      • Papaconstantinou D.
      • et al.
      Visual outcomes after Descemet membrane endothelial keratoplasty versus Descemet stripping automated endothelial keratoplasty-comparison of specific matched pairs.
      20/24 vs. 20/32,
      • Phillips P.M.
      • Phillips L.J.
      • Muthappan V.
      • et al.
      Experienced DSAEK surgeon’s transition to DMEK: outcomes comparing the last 100 DSAEK surgeries with the first 100 DMEK surgeries exclusively using previously published techniques.
      and 20/30 vs. 20/44
      • Bhandari V.
      • Reddy J.K.
      • Relekar K.
      • Prabhu V.
      Descemet’s stripping automated endothelial keratoplasty versus Descemet’s membrane endothelial keratoplasty in the fellow eye for Fuchs endothelial dystrophy: a retrospective study.
      ; all P < 0.05). When the VA levels of patients were compared, higher percentages of patients in the DMEK group than in the DSEK group achieved a BCVA of 20/25 or better (50% vs. 6%,
      • Tourtas T.
      • Laaser K.
      • Bachmann B.O.
      • et al.
      Descemet membrane endothelial keratoplasty versus Descemet stripping automated endothelial keratoplasty.
      67% vs. 31%,
      • Hamzaoglu E.C.
      • Straiko M.D.
      • Mayko Z.M.
      • et al.
      The first 100 eyes of standardized Descemet stripping automated endothelial keratoplasty versus standardized Descemet membrane endothelial keratoplasty.
      53% vs. 15%,
      • Heinzelmann S.
      • Bohringer D.
      • Eberwein P.
      • et al.
      Outcomes of Descemet membrane endothelial keratoplasty, Descemet stripping automated endothelial keratoplasty and penetrating keratoplasty from a single centre study.
      and 55% vs. 13%
      • Phillips P.M.
      • Phillips L.J.
      • Muthappan V.
      • et al.
      Experienced DSAEK surgeon’s transition to DMEK: outcomes comparing the last 100 DSAEK surgeries with the first 100 DMEK surgeries exclusively using previously published techniques.
      ) and a BCVA of 20/20 or better (46% vs. 13%).
      • Hamzaoglu E.C.
      • Straiko M.D.
      • Mayko Z.M.
      • et al.
      The first 100 eyes of standardized Descemet stripping automated endothelial keratoplasty versus standardized Descemet membrane endothelial keratoplasty.
      Two studies
      • Rudolph M.
      • Laaser K.
      • Bachmann B.O.
      • et al.
      Corneal higher-order aberrations after Descemet’s membrane endothelial keratoplasty.
      • Heinzelmann S.
      • Bohringer D.
      • Eberwein P.
      • et al.
      Outcomes of Descemet membrane endothelial keratoplasty, Descemet stripping automated endothelial keratoplasty and penetrating keratoplasty from a single centre study.
      compared the visual outcomes of DMEK, DSEK, and PK. Best-corrected VA or the percentage of eyes that achieved 20/25 or better VA after DMEK were significantly better than those after DSEK and PK (P < 0.05). The range of BCVA achieved after DMEK (20/21–20/31) was better than the ranges reported after DSEK by Lee et al
      • Lee W.B.
      • Jacobs D.S.
      • Musch D.C.
      • et al.
      Descemet’s stripping endothelial keratoplasty: safety and outcomes: a report by the American Academy of Ophthalmology.
      (20/34–20/66) during follow-up periods of similar lengths. The VA became stable by month 6 after DMEK and remained stable for more than 4 years (up to 7 years), as observed in 2 long-term studies.
      • Ham L.
      • Dapena I.
      • Liarakos V.S.
      • et al.
      Midterm results of Descemet membrane endothelial keratoplasty: 4 to 7 years clinical outcome.
      • Schlögl A.
      • Tourtas T.
      • Kruse F.E.
      • Weller J.M.
      Long-term clinical outcome after Descemet membrane endothelial keratoplasty.
      Descemet membrane endothelial keratoplasty can be performed concurrently with cataract surgery
      • Chaurasia S.
      • Price Jr., F.W.
      • Gunderson L.
      • Price M.O.
      Descemet’s membrane endothelial keratoplasty: clinical results of single versus triple procedures (combined with cataract surgery).
      • Laaser K.
      • Bachmann B.O.
      • Horn F.K.
      • et al.
      Descemet membrane endothelial keratoplasty combined with phacoemulsification and intraocular lens implantation: advanced triple procedure.
      • Gundlach E.
      • Maier A.K.
      • Tsangaridou M.A.
      • et al.
      DMEK in phakic eyes: targeted therapy or highway to cataract surgery?.
      • Schoenberg E.D.
      • Price Jr., F.W.
      • Miller J.
      • et al.
      Refractive outcomes of Descemet membrane endothelial keratoplasty triple procedures (combined with cataract surgery).
      or in phakic eyes
      • Cabrerizo J.
      • Livny E.
      • Musa F.U.
      • et al.
      Changes in color vision and contrast sensitivity after Descemet membrane endothelial keratoplasty for Fuchs endothelial dystrophy.
      • Parker J.
      • Dirisamer M.
      • Naveiras M.
      • et al.
      Outcomes of Descemet membrane endothelial keratoplasty in phakic eyes.
      • Burkhart Z.N.
      • Feng M.T.
      • Price Jr., F.W.
      • Price M.O.
      One-year outcomes in eyes remaining phakic after Descemet membrane endothelial keratoplasty.
      • Gundlach E.
      • Maier A.K.
      • Tsangaridou M.A.
      • et al.
      DMEK in phakic eyes: targeted therapy or highway to cataract surgery?.
      and in patients with previous trabeculectomy or glaucoma drainage devices.
      • Aravena C.
      • Yu F.
      • Deng S.X.
      Outcomes of Descemet membrane endothelial keratoplasty in patients with previous glaucoma surgery.
      A good visual outcome can be achieved without increasing complication rates. One study
      • Gundlach E.
      • Maier A.K.
      • Tsangaridou M.A.
      • et al.
      DMEK in phakic eyes: targeted therapy or highway to cataract surgery?.
      reported that a higher percentage of phakic patients achieved a BCVA of 20/20 or better at 6 months after DMEK alone if visually significant cataract did not develop than patients who underwent combined DMEK and cataract surgery.

       Complications

      Complications of DMEK include graft detachment, graft failure, intraocular pressure (IOP) elevation, immune rejection, cystoid macular edema (CME), and EC loss (Table 1). The most common complication of DMEK was partial graft detachment. However, the actual graft detachment rate was not reported by all studies because small peripheral detachments can reattach spontaneously without affecting the final visual outcome.
      • Dirisamer M.
      • van Dijk K.
      • Dapena I.
      • et al.
      Prevention and management of graft detachment in Descemet membrane endothelial keratoplasty.
      The mean air injection rate to reattach grafts was 28.8% (range, 2.4%–82%) after DMEK, which is higher than the 14% reported after DSEK (range, 0%–82%). In most cases, 1 air injection was sufficient to reattach the graft. There is evidence that the rate of air injection to treat detachment decreases substantially as the surgeon becomes more experienced in performing DMEK. One recent study
      • Rodriguez-Calvo-de-Mora M.
      • Quilendrino R.
      • Ham L.
      • et al.
      Clinical outcome of 500 consecutive cases undergoing Descemet’s membrane endothelial keratoplasty.
      that consisted of 500 DMEK cases reported an air injection rate of 3%. Two studies
      • Guell J.L.
      • Morral M.
      • Gris O.
      • et al.
      Comparison of sulfur hexafluoride 20% versus air tamponade in Descemet membrane endothelial keratoplasty.
      • Schaub F.
      • Enders P.
      • Snijders K.
      • et al.
      One-year outcome after Descemet membrane endothelial keratoplasty (DMEK) comparing sulfur hexafluoride (SF6) 20% versus 100% air for anterior chamber tamponade.
      showed that the use of 20% SF6 instead of 100% air also greatly decreased the air injection rate from 12.8% to 2.4 % and 54% to 24%, respectively. Small descemetorhexis and a decentered graft may increase the risk of partial graft detachment.
      • Tourtas T.
      • Schlomberg J.
      • Wessel J.M.
      • et al.
      Graft adhesion in Descemet membrane endothelial keratoplasty dependent on size of removal of host’s Descemet membrane.
      • Röck T.
      • Bramkamp M.
      • Bartz-Schmidt K.U.
      • et al.
      Causes that influence the detachment rate after Descemet membrane endothelial keratoplasty.
      Total graft detachment (i.e., a free-floating graft) and upside-down grafts were less common, accounting for less than 5% of DMEK procedures.
      • Dirisamer M.
      • van Dijk K.
      • Dapena I.
      • et al.
      Prevention and management of graft detachment in Descemet membrane endothelial keratoplasty.
      • Debellemanière G.
      • Guilbert E.
      • Courtin R.
      • et al.
      Impact of surgical learning curve in Descemet membrane endothelial keratoplasty on visual acuity gain.
      Marking of the graft was shown to decrease the rate of upside-down graft.
      • Veldman P.B.
      • Dye P.K.
      • Holiman J.D.
      • et al.
      The S-stamp in Descemet membrane endothelial keratoplasty safely eliminates upside-down graft implantation.
      In cases of large or complete detachment, a second keratoplasty (DMEK, DSEK, or PK) sometimes was required.
      • Monnereau C.
      • Quilendrino R.
      • Dapena I.
      • et al.
      Multicenter study of Descemet membrane endothelial keratoplasty: first case series of 18 surgeons.
      • Dapena I.
      • Ham L.
      • Droutsas K.
      • et al.
      Learning curve in Descemet’s membrane endothelial keratoplasty: first series of 135 consecutive cases.
      The incidence of a second keratoplasty ranged from 0% to 17.6%,
      • Monnereau C.
      • Quilendrino R.
      • Dapena I.
      • et al.
      Multicenter study of Descemet membrane endothelial keratoplasty: first case series of 18 surgeons.
      and these repeat grafts were not categorized as primary graft failure in 2 studies.
      • Monnereau C.
      • Quilendrino R.
      • Dapena I.
      • et al.
      Multicenter study of Descemet membrane endothelial keratoplasty: first case series of 18 surgeons.
      • Dapena I.
      • Ham L.
      • Droutsas K.
      • et al.
      Learning curve in Descemet’s membrane endothelial keratoplasty: first series of 135 consecutive cases.
      The average rate of primary DMEK graft failure was 1.9% (range, 0%–12.5%). In comparison, primary graft failure after DSEK ranged from 0% to 29%, with an average of 5%.
      • Lee W.B.
      • Jacobs D.S.
      • Musch D.C.
      • et al.
      Descemet’s stripping endothelial keratoplasty: safety and outcomes: a report by the American Academy of Ophthalmology.
      The rate of regrafting for primary graft failure after DMEK was reduced to 0.8% when standardized DMEK techniques were used.
      • Phillips P.M.
      • Phillips L.J.
      • Muthappan V.
      • et al.
      Experienced DSAEK surgeon’s transition to DMEK: outcomes comparing the last 100 DSAEK surgeries with the first 100 DMEK surgeries exclusively using previously published techniques.
      • Rodriguez-Calvo-de-Mora M.
      • Quilendrino R.
      • Ham L.
      • et al.
      Clinical outcome of 500 consecutive cases undergoing Descemet’s membrane endothelial keratoplasty.
      • Dapena I.
      • Ham L.
      • Droutsas K.
      • et al.
      Learning curve in Descemet’s membrane endothelial keratoplasty: first series of 135 consecutive cases.
      The second most common complication after DMEK surgery was IOP elevation (defined as >24 mmHg or a ≥10-mmHg increase from baseline IOP), which was reported to occur in 0% to 24% of patients during the follow-up period. Two randomized controlled clinical trials
      • Price M.O.
      • Price Jr., F.W.
      • Kruse F.E.
      • et al.
      Randomized comparison of topical prednisolone acetate 1% versus fluorometholone 0.1% in the first year after Descemet membrane endothelial keratoplasty.
      • Price M.O.
      • Feng M.T.
      • Scanameo A.
      • Price Jr., F.W.
      Loteprednol etabonate 0.5% gel vs. prednisolone acetate 1% solution after Descemet membrane endothelial keratoplasty: prospective randomized trial.
      showed that use of 0.1% fluorometholone or 0.5% loteprednol etabonate gel resulted in a significantly lower rate of IOP elevation than 1% prednisolone acetate (6.1% vs. 21.9% and 11% vs. 25%, respectively; P < 0.05) without an increase of rejection rate. Most of the IOP elevation after DMEK was corticosteroid induced, but angle closure or pupillary block were other mechanisms (range, 0%–15.4%) that led to IOP elevation during the period immediately after surgery.
      • Parker J.
      • Dirisamer M.
      • Naveiras M.
      • et al.
      Outcomes of Descemet membrane endothelial keratoplasty in phakic eyes.
      • Maier A.K.
      • Wolf T.
      • Gundlach E.
      • et al.
      Intraocular pressure elevation and post-DMEK glaucoma following Descemet membrane endothelial keratoplasty.
      Twenty-two studies evaluated the immune rejection rate after DMEK (Table 1). The mean rejection rate was 1.9% (range, 0%–5.9%) during follow-up periods ranging from 6 months to 8 years. The largest series, consisting of 905 cases, reported a rejection rate of 1.3% during the first year.
      • Hos D.
      • Tuac O.
      • Schaub F.
      • et al.
      Incidence and clinical course of immune reactions after Descemet membrane endothelial keratoplasty: retrospective analysis of 1000 consecutive eyes.
      This rate is lower than the mean rejection rate of 10% (range, 0%–45.5%) after DSEK.
      • Anshu A.
      • Price M.O.
      • Tan D.T.
      • Price Jr., F.W.
      Endothelial keratoplasty: a revolution in evolution.
      • Maier P.
      • Reinhard T.
      • Cursiefen C.
      Descemet stripping endothelial keratoplasty—rapid recovery of visual acuity.
      One study
      • Anshu A.
      • Price M.O.
      • Price Jr., F.W.
      Risk of corneal transplant rejection significantly reduced with Descemet’s membrane endothelial keratoplasty.
      in which the rejection rates of DMEK, DSEK, and PK were compared found that the rejection rate was lowest after DMEK (0.7%) and was higher after DSEK (9%) and PK (17%; P = 0.004). A 6% rejection rate was reported in patients who discontinued topical corticosteroids 1 year after DMEK, compared with 0% in patients who continued low-dose topical corticosteroids during the following year.
      • Price M.O.
      • Scanameo A.
      • Feng M.T.
      • Price Jr., F.W.
      Descemet’s membrane endothelial keratoplasty: risk of immunologic rejection episodes after discontinuing topical corticosteroids.
      Cystoid macular edema was another complication after DMEK. In most case series, the rate of CME developing was less than 7.4%, except in 1 series
      • Heinzelmann S.
      • Maier P.
      • Bohringer D.
      • et al.
      Cystoid macular oedema following Descemet membrane endothelial keratoplasty.
      in which a CME rate of 13.3% was detected after DMEK combined with cataract surgery and of 12.5% after DMEK alone using routine screening with OCT. One study showed that intense topical corticosteroid treatment during the first week after surgery decreased the rate of CME from 12% to 0% after combined DMEK and cataract surgery.
      • Hoerster R.
      • Stanzel T.P.
      • Bachmann B.O.
      • et al.
      Intensified topical steroids as prophylaxis for macular edema after posterior lamellar keratoplasty combined with cataract surgery.

       Graft Survival

      The average rate of secondary graft failure was 2.2% (range, 0%–6%) during follow-up periods of 6 months to 8 years (Table 1). Two studies
      • Ham L.
      • Dapena I.
      • Liarakos V.S.
      • et al.
      Midterm results of Descemet membrane endothelial keratoplasty: 4 to 7 years clinical outcome.
      • Schlögl A.
      • Tourtas T.
      • Kruse F.E.
      • Weller J.M.
      Long-term clinical outcome after Descemet membrane endothelial keratoplasty.
      reported a 0.95 and 0.96 probability of graft survival at 5 and 7 years, respectively. These probabilities are comparable with the 96% survival rate at 5 years after DSEK in eyes without glaucoma.
      • Anshu A.
      • Price M.O.
      • Price F.W.
      Descemet’s stripping endothelial keratoplasty: long-term graft survival and risk factors for failure in eyes with preexisting glaucoma.

       Endothelial Cell Loss

      Table 1 lists the mean EC losses after DMEK. A significant decrease in mean EC density (range, 27%–46%) at 3 months was reported, and the level of reduction tapered afterward. At 6 months, the mean EC loss was 33% (range, 25%–47%). Three studies
      • Feng M.T.
      • Price M.O.
      • Miller J.M.
      • Price Jr., F.W.
      Air reinjection and endothelial cell density in Descemet membrane endothelial keratoplasty: five-year follow-up.
      • Ham L.
      • Dapena I.
      • Liarakos V.S.
      • et al.
      Midterm results of Descemet membrane endothelial keratoplasty: 4 to 7 years clinical outcome.
      • Schlögl A.
      • Tourtas T.
      • Kruse F.E.
      • Weller J.M.
      Long-term clinical outcome after Descemet membrane endothelial keratoplasty.
      reported a 42% EC loss at 4 years, 39% at 5 years, and 65% at 7 years, respectively. Four of the 5 studies
      • Tourtas T.
      • Laaser K.
      • Bachmann B.O.
      • et al.
      Descemet membrane endothelial keratoplasty versus Descemet stripping automated endothelial keratoplasty.
      • Hamzaoglu E.C.
      • Straiko M.D.
      • Mayko Z.M.
      • et al.
      The first 100 eyes of standardized Descemet stripping automated endothelial keratoplasty versus standardized Descemet membrane endothelial keratoplasty.
      • Droutsas K.
      • Lazaridis A.
      • Papaconstantinou D.
      • et al.
      Visual outcomes after Descemet membrane endothelial keratoplasty versus Descemet stripping automated endothelial keratoplasty-comparison of specific matched pairs.
      • Bhandari V.
      • Reddy J.K.
      • Relekar K.
      • Prabhu V.
      Descemet’s stripping automated endothelial keratoplasty versus Descemet’s membrane endothelial keratoplasty in the fellow eye for Fuchs endothelial dystrophy: a retrospective study.
      compared the EC loss of DMEK with DSEK directly and failed to show a difference at 6 months. The fifth study showed a significantly higher EC loss after DMEK than after DSEK.
      • Phillips P.M.
      • Phillips L.J.
      • Muthappan V.
      • et al.
      Experienced DSAEK surgeon’s transition to DMEK: outcomes comparing the last 100 DSAEK surgeries with the first 100 DMEK surgeries exclusively using previously published techniques.
      One air injection,
      • Feng M.T.
      • Price M.O.
      • Miller J.M.
      • Price Jr., F.W.
      Air reinjection and endothelial cell density in Descemet membrane endothelial keratoplasty: five-year follow-up.
      the use of SF6,
      • Guell J.L.
      • Morral M.
      • Gris O.
      • et al.
      Comparison of sulfur hexafluoride 20% versus air tamponade in Descemet membrane endothelial keratoplasty.
      and marking of the graft
      • Veldman P.B.
      • Dye P.K.
      • Holiman J.D.
      • et al.
      The S-stamp in Descemet membrane endothelial keratoplasty safely eliminates upside-down graft implantation.
      were shown not to increase EC loss. Intense topical corticosteroid treatment during the first week after combined DMEK and cataract surgery did not have any effect on the EC loss at 6 months.
      • Hoerster R.
      • Stanzel T.P.
      • Bachmann B.O.
      • et al.
      Intensified early postoperative topical steroids do not influence endothelial cell density after Descemet membrane endothelial keratoplasty combined with cataract surgery (Triple-DMEK).
      Eyes with prior glaucoma trabeculectomy or shunt had a higher EC loss than those eyes without.
      • Aravena C.
      • Yu F.
      • Deng S.X.
      Outcomes of Descemet membrane endothelial keratoplasty in patients with previous glaucoma surgery.

       Refractive Outcomes

      Table 2 lists the refractive outcomes of DMEK. Twelve studies
      • Deng S.X.
      • Sanchez P.J.
      • Chen L.
      Clinical outcomes of Descemet membrane endothelial keratoplasty using eye bank-prepared tissues.
      • Guell J.L.
      • Morral M.
      • Gris O.
      • et al.
      Comparison of sulfur hexafluoride 20% versus air tamponade in Descemet membrane endothelial keratoplasty.
      • Droutsas K.
      • Lazaridis A.
      • Papaconstantinou D.
      • et al.
      Visual outcomes after Descemet membrane endothelial keratoplasty versus Descemet stripping automated endothelial keratoplasty-comparison of specific matched pairs.
      • Guerra F.P.
      • Anshu A.
      • Price M.O.
      • et al.
      Descemet’s membrane endothelial keratoplasty: prospective study of 1-year visual outcomes, graft survival, and endothelial cell loss.
      • Laaser K.
      • Bachmann B.O.
      • Horn F.K.
      • et al.
      Descemet membrane endothelial keratoplasty combined with phacoemulsification and intraocular lens implantation: advanced triple procedure.
      • Parker J.
      • Dirisamer M.
      • Naveiras M.
      • et al.
      Outcomes of Descemet membrane endothelial keratoplasty in phakic eyes.
      • Gundlach E.
      • Maier A.K.
      • Tsangaridou M.A.
      • et al.
      DMEK in phakic eyes: targeted therapy or highway to cataract surgery?.
      • Schoenberg E.D.
      • Price Jr., F.W.
      • Miller J.
      • et al.
      Refractive outcomes of Descemet membrane endothelial keratoplasty triple procedures (combined with cataract surgery).
      • van Dijk K.
      • Rodriguez-Calvo-de-Mora M.
      • van Esch H.
      • et al.
      Two-year refractive outcomes after Descemet membrane endothelial keratoplasty.
      • van Dijk K.
      • Ham L.
      • Tse W.H.
      • et al.
      Near complete visual recovery and refractive stability in modern corneal transplantation: Descemet membrane endothelial keratoplasty (DMEK).
      • Droutsas K.
      • Giallouros E.
      • Melles G.R.
      • et al.
      Descemet membrane endothelial keratoplasty: learning curve of a single surgeon.
      • Alnawaiseh M.
      • Rosentreter A.
      • Eter N.
      • Zumhagen L.
      Changes in corneal refractive power for patients with Fuchs endothelial dystrophy after DMEK.
      found a small hyperopic shift after DMEK (range, +0.03 to +1.2 D). Only 1 study
      • Maier A.K.
      • Gundlach E.
      • Gonnermann J.
      • et al.
      Superior versus temporal approach in Descemet membrane endothelial keratoplasty.
      found a myopic shift of –1.14 D.
      • Maier A.K.
      • Gundlach E.
      • Gonnermann J.
      • et al.
      Superior versus temporal approach in Descemet membrane endothelial keratoplasty.
      The overall mean change in the spherical equivalent of all 13 studies reviewed was +0.31 D, which was lower than the +1.1 D reported for DSEK.
      • Lee W.B.
      • Jacobs D.S.
      • Musch D.C.
      • et al.
      Descemet’s stripping endothelial keratoplasty: safety and outcomes: a report by the American Academy of Ophthalmology.
      The mean changes in astigmatism ranged from –0.6 to +1.11 D after DMEK, with an average of +0.03 D. Only 2 studies
      • Laaser K.
      • Bachmann B.O.
      • Horn F.K.
      • et al.
      Descemet membrane endothelial keratoplasty combined with phacoemulsification and intraocular lens implantation: advanced triple procedure.
      • van Dijk K.
      • Ham L.
      • Tse W.H.
      • et al.
      Near complete visual recovery and refractive stability in modern corneal transplantation: Descemet membrane endothelial keratoplasty (DMEK).
      found the changes to be statistically significant. Corneal curvature changes were reported in 7 studies
      • Laaser K.
      • Bachmann B.O.
      • Horn F.K.
      • et al.
      Descemet membrane endothelial keratoplasty combined with phacoemulsification and intraocular lens implantation: advanced triple procedure.
      • Parker J.
      • Dirisamer M.
      • Naveiras M.
      • et al.
      Outcomes of Descemet membrane endothelial keratoplasty in phakic eyes.
      • van Dijk K.
      • Ham L.
      • Tse W.H.
      • et al.
      Near complete visual recovery and refractive stability in modern corneal transplantation: Descemet membrane endothelial keratoplasty (DMEK).
      : 3 studies
      • Parker J.
      • Dirisamer M.
      • Naveiras M.
      • et al.
      Outcomes of Descemet membrane endothelial keratoplasty in phakic eyes.
      • van Dijk K.
      • Rodriguez-Calvo-de-Mora M.
      • van Esch H.
      • et al.
      Two-year refractive outcomes after Descemet membrane endothelial keratoplasty.
      • van Dijk K.
      • Ham L.
      • Tse W.H.
      • et al.
      Near complete visual recovery and refractive stability in modern corneal transplantation: Descemet membrane endothelial keratoplasty (DMEK).
      showed a significant shift after surgery in the anterior curvature (range, –0.4 to –0.7 D) and posterior curvature (range, –0.7 to 0.91 D), and 4 studies
      • Vianna L.M.
      • Stoeger C.G.
      • Galloway J.D.
      • et al.
      Risk factors for eye bank preparation failure of Descemet membrane endothelial keratoplasty tissue.
      • van Dijk K.
      • Rodriguez-Calvo-de-Mora M.
      • van Esch H.
      • et al.
      Two-year refractive outcomes after Descemet membrane endothelial keratoplasty.
      • Anshu A.
      • Price M.O.
      • Price F.W.
      Descemet’s stripping endothelial keratoplasty: long-term graft survival and risk factors for failure in eyes with preexisting glaucoma.
      • Price M.O.
      • Fairchild K.M.
      • Price D.A.
      • Price Jr., F.W.
      Descemet’s stripping endothelial keratoplasty five-year graft survival and endothelial cell loss.
      showed a higher shift in the posterior curvature than in the anterior curvature.
      Table 2Refractive Outcomes of Descemet Membrane Endothelial Keratoplasty
      Author(s), YearCountryLevel of EvidenceTotal No. of EyesFollow-up (mos)Mean Change in Spherical Equivalent (D)Mean Change in Refractive Astigmatism (D)Corneal Curvature Changes (D)
      Guell et al,
      • Guell J.L.
      • Morral M.
      • Gris O.
      • et al.
      Comparison of sulfur hexafluoride 20% versus air tamponade in Descemet membrane endothelial keratoplasty.
      2015
      SpainII8136SF6, +0.06; air, +0.74SF6, +0.43; air, –0.26
      Droutsas et al,
      • Droutsas K.
      • Lazaridis A.
      • Papaconstantinou D.
      • et al.
      Visual outcomes after Descemet membrane endothelial keratoplasty versus Descemet stripping automated endothelial keratoplasty-comparison of specific matched pairs.
      2016
      GreeceII2512DMEK, +0.5; DSEK, +0.6DMEK, +0.09; DSEK, +0.12
      Maier et al,
      • Maier A.K.
      • Gundlach E.
      • Gonnermann J.
      • et al.
      Superior versus temporal approach in Descemet membrane endothelial keratoplasty.
      2015
      GermanyII535.7All, –1.14 ± 1.70; superior incision, –1.61 ± 1.91; temporal incision, –0.19 ± 0.67All, +1.11 ± 0.85; superior incision, +1.42 ± 0.91; temporal incision, +0.81 ± 0.68
      Guerra et al,
      • Guerra F.P.
      • Anshu A.
      • Price M.O.
      • et al.
      Descemet’s membrane endothelial keratoplasty: prospective study of 1-year visual outcomes, graft survival, and endothelial cell loss.
      2011
      United StatesIII13612+0.24 ± 1.01+0.16 ± 0.87
      Laaser et al,
      • Laaser K.
      • Bachmann B.O.
      • Horn F.K.
      • et al.
      Descemet membrane endothelial keratoplasty combined with phacoemulsification and intraocular lens implantation: advanced triple procedure.
      2012
      GermanyIII616+1.2
      P < 0.05.
      –0.6
      P < 0.05.
      –0.4
      Parker et al,
      • Parker J.
      • Dirisamer M.
      • Naveiras M.
      • et al.
      Outcomes of Descemet membrane endothelial keratoplasty in phakic eyes.
      2012
      The NetherlandsIII526+0.74 ± 0.8
      P < 0.05.
      –0.03 ± 1.0Total, –1.78 ± 0.76
      P < 0.05.
      ; anterior, –0.74 ± 0.25
      P < 0.05.
      ; posterior, –0.91 ± 0.37
      P < 0.05.
      Van Dijk et al,
      • van Dijk K.
      • Ham L.
      • Tse W.H.
      • et al.
      Near complete visual recovery and refractive stability in modern corneal transplantation: Descemet membrane endothelial keratoplasty (DMEK).
      2012
      The NetherlandsIII3006All, +0.33 ± 1.08
      P < 0.05.
      ; phakic, +0.60 ± 0.86; pseudophakic, +0.25 ± 1.12
      P < 0.05.
      –0.36 D ± 1.07
      P < 0.05.
      Anterior, –0.4 ± 1.0
      P < 0.05.
      ; posterior, –0.7 ± 0.7
      P < 0.05.
      Droutsas et al,
      • Droutsas K.
      • Giallouros E.
      • Melles G.R.
      • et al.
      Descemet membrane endothelial keratoplasty: learning curve of a single surgeon.
      2013
      GermanyIII256+0.03+0.03NA
      Deng et al,
      • Deng S.X.
      • Sanchez P.J.
      • Chen L.
      Clinical outcomes of Descemet membrane endothelial keratoplasty using eye bank-prepared tissues.
      2014
      United StatesIII405.3+0.51NA
      Gundlach et al,
      • Gundlach E.
      • Maier A.K.
      • Tsangaridou M.A.
      • et al.
      DMEK in phakic eyes: targeted therapy or highway to cataract surgery?.
      2015
      GermanyIII676Phakic DMEK, +0.12; DMEK/CE, +0.39DMEK, –0.22; DMEK/CE, –0.09
      Schoenberg et al,
      • Schoenberg E.D.
      • Price Jr., F.W.
      • Miller J.
      • et al.
      Refractive outcomes of Descemet membrane endothelial keratoplasty triple procedures (combined with cataract surgery).
      2015
      United StatesIII10811.9+0.33 ± 1.26 from the targeted spherical equivalent0.1
      van Dijk et al,
      • van Dijk K.
      • Rodriguez-Calvo-de-Mora M.
      • van Esch H.
      • et al.
      Two-year refractive outcomes after Descemet membrane endothelial keratoplasty.
      2016
      The NetherlandsIII6724+0.19+0.26Anterior, –0.2
      P < 0.05.
      ; posterior, –0.8
      P < 0.05.
      Alnawaiseh et al,
      • Alnawaiseh M.
      • Rosentreter A.
      • Eter N.
      • Zumhagen L.
      Changes in corneal refractive power for patients with Fuchs endothelial dystrophy after DMEK.
      2016
      GermanyIII28Up to 9+0.33NA–0.88
      CE = cataract extraction; D = diopter; DMEK = Descemet membrane endothelial keratoplasty; DSEK = Descemet's stripping endothelial keratoplasty; NA = not available; SF6 = sulfur hexafluoride.
      P < 0.05.

      Discussion

      Over the last decade, DSEK has replaced PK as the procedure of choice for endothelial dysfunction.
      • Lee W.B.
      • Jacobs D.S.
      • Musch D.C.
      • et al.
      Descemet’s stripping endothelial keratoplasty: safety and outcomes: a report by the American Academy of Ophthalmology.
      Although a similar percentage of patients achieved a BCVA of 20/40 or better vision in DSEK and PK, a significantly lower number of patients achieved 20/20 vision after standard DSEK than after PK. With the introduction of DMEK in 2002 as a new endothelial keratoplasty procedure, interface irregularity could be reduced by eliminating corneal stromal tissue in the donor graft and visual outcome thereby could be improved. The purpose of this ophthalmic technology assessment was to evaluate the safety and outcomes of DMEK and to determine whether DMEK offers any advantages over DSEK in terms of visual recovery, outcomes, and complications.
      There seems to be sufficient evidence to support the conclusion that DMEK achieves a faster visual recovery and a better visual outcome than DSEK. All studies reviewed showed a rapid visual recovery after successful DMEK. In studies that compared DMEK and DSEK directly, all showed a significantly better VA achieved by DMEK than DSEK at 6 months. Only 6% of eyes after DSEK achieved VA 20/25 or better, whereas 50% of eyes after DMEK achieved the same level of VA in 1 study.
      • Tourtas T.
      • Laaser K.
      • Bachmann B.O.
      • et al.
      Descemet membrane endothelial keratoplasty versus Descemet stripping automated endothelial keratoplasty.
      Another study
      • Hamzaoglu E.C.
      • Straiko M.D.
      • Mayko Z.M.
      • et al.
      The first 100 eyes of standardized Descemet stripping automated endothelial keratoplasty versus standardized Descemet membrane endothelial keratoplasty.
      reported that 13% of eyes after DSEK and 46% of eyes after DMEK achieved 20/20 or better vision at 6 months. Long-term studies suggest that visual recovery is achieved by month 6 after DMEK and that the VA remains stable afterward. In contrast, visual recovery continues beyond 6 months after DSEK.
      Ultrathin DSEK, in which the thickness of the DSEK graft is less than 130 μm, has been shown to achieve a better BCVA than standard DSEK in a randomized controlled study.
      • Dickman M.M.
      • Kruit P.J.
      • Remeijer L.
      • et al.
      A randomized multicenter clinical trial of ultrathin Descemet stripping automated endothelial keratoplasty (DSAEK) versus DSAEK.
      The mean BCVA with ultrathin DSEK was within the range of BCVA achieved with DMEK, but this study did not report the percentage of eyes that achieved 20/20 or better vision and included only eyes with Fuchs' endothelial dystrophy, which have been shown to achieve a better visual outcome than eyes with pseudophakic bullous keratopathy. Only 1 additional published study reported the visual outcomes after ultrathin DSEK; 26% of patients achieved 20/20 vision at 6 months and 39% of patients achieved 20/20 vision at 1 year.
      • Busin M.
      • Madi S.
      • Santorum P.
      • et al.
      Ultrathin Descemet’s stripping automated endothelial keratoplasty with the microkeratome double-pass technique: two-year outcomes.
      One challenge of ultrathin DSEK is the difficulty of consistently obtaining grafts of the desired thickness; consequently, the procedure is performed by only a small number of experienced surgeons. Evidence from these 2 studies is insufficient to draw a conclusion about whether ultrathin DSEK achieves a visual outcome similar as DMEK does.
      The types of complications during and after DMEK are similar to those encountered with DSEK. They include graft detachment, primary and secondary graft failure, corticosteroid-induced IOP elevation, and angle closure resulting from pupillary block. The most common complication is graft detachment. The actual graft detachment rate is likely higher than reported because a small peripheral detachment may not be detected by slit-lamp examination as a result of corneal edema at the location of the detachment. In contrast, most graft detachments could be detected by slit-lamp examination in DSEK. The mean rate of air or gas injection for partial graft detachment after DMEK is higher than that after DSEK, although the ranges are similar in both procedures.
      • Lee W.B.
      • Jacobs D.S.
      • Musch D.C.
      • et al.
      Descemet’s stripping endothelial keratoplasty: safety and outcomes: a report by the American Academy of Ophthalmology.
      The rate of air injection decreased significantly when surgeons gained more experience performing DMEK. The use of SF6 instead of air also greatly decreased the rebubble rate to less than 3% after DMEK, which is within the range of that found after DSEK performed by experienced surgeons.
      • Gorovoy M.S.
      DMEK complications.
      • Rodriguez-Calvo-de-Mora M.
      • Quilendrino R.
      • Ham L.
      • et al.
      Clinical outcome of 500 consecutive cases undergoing Descemet’s membrane endothelial keratoplasty.
      Repeat air injections often were necessary in refractory cases in both DSEK and DMEK. One air injection was shown not to increase EC loss after DMEK.
      • Feng M.T.
      • Price M.O.
      • Miller J.M.
      • Price Jr., F.W.
      Air reinjection and endothelial cell density in Descemet membrane endothelial keratoplasty: five-year follow-up.
      In addition, a small peripheral detachment of graft (<1/3 graft area) later was shown to resolve spontaneously within 6 months after DMEK without air injection.
      • Dirisamer M.
      • van Dijk K.
      • Dapena I.
      • et al.
      Prevention and management of graft detachment in Descemet membrane endothelial keratoplasty.
      Therefore, air injection seems to be necessary only in cases of persistent corneal edema that results from large graft detachment in DMEK.
      Total graft detachment was managed differently in DMEK and DSEK because of the transparent nature of the DM: regrafting was used in DMEK and refloating was often used in DSEK. A higher level of visualization is needed to reattach the donor tissue in DMEK than in DSEK, in which a successful reattachment even with very edematous corneas can be achieved. When the regrafting rate for graft detachment and primary graft failure after DMEK were accounted for, the total rate of regrafting was between 0% and 16.8%, which was within the range of primary graft failure reported after DSEK (0%–29%). The rate of regrafting decreased to less than 1% after a standardized procedure was implemented.
      • Rodriguez-Calvo-de-Mora M.
      • Quilendrino R.
      • Ham L.
      • et al.
      Clinical outcome of 500 consecutive cases undergoing Descemet’s membrane endothelial keratoplasty.
      A similar range in the primary graft failure rate (0%–29%) was reported after DSEK.
      • Lee W.B.
      • Jacobs D.S.
      • Musch D.C.
      • et al.
      Descemet’s stripping endothelial keratoplasty: safety and outcomes: a report by the American Academy of Ophthalmology.
      One indication for regrafting after successful DSEK is to improve VA, which has not been reported after successful DMEK.
      The rates of IOP elevation from late-onset corticosteroid-induced or iatrogenic angle closure immediately after DMEK are similar to those reported for DSEK, despite the larger air bubble left in the eye after DMEK by many surgeons. These similar rates of IOP elevation resulting from angle closure possibly resulted from routine laser iridotomy or surgical iridectomy performed either before or during DMEK.
      A lower immune rejection rate was reported after DMEK than after DSEK. This difference was thought to be because less donor tissue was transplanted in DMEK. Two studies
      • Price M.O.
      • Price Jr., F.W.
      • Kruse F.E.
      • et al.
      Randomized comparison of topical prednisolone acetate 1% versus fluorometholone 0.1% in the first year after Descemet membrane endothelial keratoplasty.
      • Price M.O.
      • Feng M.T.
      • Scanameo A.
      • Price Jr., F.W.
      Loteprednol etabonate 0.5% gel vs. prednisolone acetate 1% solution after Descemet membrane endothelial keratoplasty: prospective randomized trial.
      showed that weaker corticosteroids, 0.1% fluorometholone and 0.5% loteprednol etabonate, could be used instead of the standard regimen after surgery of 1% prednisone acetate because the risk of immune rejection was seen to be lower with DMEK. The rate of immunologic rejection did not differ when either fluorometholone or loteprednol etabonate was used, whereas the rates of corticosteroid-induced IOP elevation decreased significantly. Therefore, DMEK may be preferred in patients with glaucoma.
      Reports have indicated a large EC loss in the early period after DMEK, a finding similar to what was observed after DSEK. This initial loss likely was the result of iatrogenic damage from graft manipulation. The rate of EC loss decreased after 3 months. Evidence indicates that the range of long-term EC loss is similar for DMEK and DSEK. Endothelial cell loss was 54% and 55% at 5 years after DSEK according to 2 studies,
      • Wacker K.
      • Baratz K.H.
      • Maguire L.J.
      • et al.
      Descemet stripping endothelial keratoplasty for Fuchs’ endothelial corneal dystrophy: five-year results of a prospective study.
      • Price M.O.
      • Fairchild K.M.
      • Price D.A.
      • Price Jr., F.W.
      Descemet’s stripping endothelial keratoplasty five-year graft survival and endothelial cell loss.
      whereas EC loss was reported to be 39% to 53% at 4 to 5 years after DMEK.
      • Feng M.T.
      • Burkhart Z.N.
      • Price Jr., F.W.
      • Price M.O.
      Effect of donor preparation-to-use times on Descemet membrane endothelial keratoplasty outcomes.
      • Ham L.
      • Dapena I.
      • Liarakos V.S.
      • et al.
      Midterm results of Descemet membrane endothelial keratoplasty: 4 to 7 years clinical outcome.
      • Schlögl A.
      • Tourtas T.
      • Kruse F.E.
      • Weller J.M.
      Long-term clinical outcome after Descemet membrane endothelial keratoplasty.
      Because a wide range (0.5%–9%) in the yearly EC decrease was reported among studies, additional long-term studies are needed to confirm the yearly rate of EC decline after DMEK. A greater EC loss was reported in eyes with prior glaucoma surgery after DMEK during a mean follow-up of 10 months. This is not the result of a higher cell loss during surgery, because the EC loss was similar in eyes with prior glaucoma surgery and those without at 3 months. A higher graft failure rate after DSEK in eyes with pre-existing glaucoma was reported,
      • Anshu A.
      • Price M.O.
      • Price F.W.
      Descemet’s stripping endothelial keratoplasty: long-term graft survival and risk factors for failure in eyes with preexisting glaucoma.
      and long-term studies are lacking to compare graft survival in such eyes after DMEK and DSEK.
      Secondary graft failure is usually caused by endothelial failure or allogenic rejection. Because many allogenic rejections could be reversed by restarting or increasing the dose of topical corticosteroids in DMEK and DSEK, the rate of secondary graft failure is relatively low after both procedures. There is evidence suggesting that 5-year graft survival rates were comparable for DMEK and DSEK. Although the rejection rate was lower after DMEK than after DSEK and long-term EC loss was similar in both procedures, it remains unknown whether long-term graft survival beyond 5 years is higher after DMEK than after DSEK.
      Like DSEK, DMEK is a refractive and astigmatically neutral procedure. The hyperopic shift after DSEK is thought to result from the lenticule-induced tissue effect. However, a small hyperopic shift was observed after DMEK, although the average shift was lower than that reported after DSEK (Table 2). The changes in the corneal curvature were likely a result of changes in the corneal hydration status; they persisted at 24 months after DMEK.
      • van Dijk K.
      • Rodriguez-Calvo-de-Mora M.
      • van Esch H.
      • et al.
      Two-year refractive outcomes after Descemet membrane endothelial keratoplasty.
      Because the hyperopic and astigmatic shift is so small, DMEK is considered a relatively refractive-neutral procedure.
      Currently, DMEK is performed mostly in eyes with Fuchs' endothelial dystrophy and uncomplicated pseudophakic bullous keratopathy. The complication rate will continue to decrease as the DMEK techniques mature and surgeon experience increases. Although DMEK has been shown to be performed successfully in eyes with prior vitrectomy and trabeculectomy or glaucoma drainage device placement,
      • Aravena C.
      • Yu F.
      • Deng S.X.
      Outcomes of Descemet membrane endothelial keratoplasty in patients with previous glaucoma surgery.
      the feasibility of performing DMEK in other complicated eyes, such as those with an anterior chamber intraocular lens, large iris defect, or absence of lens support, needs to be investigated further. In such eyes with abnormal anatomy, DSEK remains the preferred procedure to treat endothelial dysfunction.

      Conclusions

      There seems to be sufficient evidence to demonstrate that DMEK is superior to DSEK in achieving a faster visual recovery, a better visual outcome, and a lower immune rejection rate. Evidence also suggests that DMEK induces less refractive error than DSEK. The rate of EC loss, primary and secondary graft failure rate, and complications during and after DMEK are comparable with those during and after DSEK. However, DMEK is more technically challenging and could involve a higher rate of air injection than in DSEK during the early part of the learning curve.

      Future Directions and Research

      Future randomized controlled clinical trials are needed to confirm the above findings. Recent developments may introduce new treatment approaches for endothelial dysfunction, such as cell therapy using cultivated cornea ECs, a Rho kinase inhibitor, and descemetorhexis without endothelial keratoplasty in the treatment of Fuchs' endothelial dystrophy.

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