Descemet's Membrane Endothelial Keratoplasty

Descemet’s Membrane Endothelial Keratoplasty Prospective Multicenter Study of Visual and Refractive Outcomes and Endothelial Survival Marianne O. Price, PhD,1 Arthur W. Giebel, MD,2 Kelly M. Fairchild,1 Francis W. Price, Jr, MD3 Purpose: To describe Descemet’s membrane endothelial keratoplasty (DMEK) techniques, perioperative challenges, management, and visual and refractive outcomes. Design: Prospective, multicenter, consecutive case series. Participants: Sixty eyes of 56 patients with Fuchs’ endothelial dystrophy, pseudophakic bullous keratopathy, or failed previous graft. Intervention: Descemet’s membrane (DM) and endothelium were stripped from donor corneas submerged in corneal storage solution in a corneal viewing chamber. Donor DM diameters were 8.5 or 9.0 mm. The central 7 mm of DM was stripped from the recipient cornea. After staining with trypan blue to improve visualization, donor DM was inserted through a 2.8-mm incision. Descemet’s membrane endothelial keratoplasty was performed alone (n ⫽ 48) or was combined with phacoemulsification and lens implantation (n ⫽ 11), pars plana vitrectomy (n ⫽ 2), or both. Main Outcome Measures: Best spectacle-corrected visual acuity (BSCVA), manifest refraction, and endothelial cell density. Results: Median BSCVA was 20/30 at 1 month (range, 20/20 –20/60), improving from 20/50 (range, 20/25– hand movements) before DMEK, excluding 4 eyes (7%) with preexisting ocular pathologic features that limited visual potential. At 3 months, 26% had 20/20 vision, 63% saw 20/25 or better, and 94% saw 20/40 or better. Refractive cylinder remained unchanged at 0.9 diopters (D; P ⫽ 0.93), and a hyperopic shift of 0.49⫾0.63 D (P ⫽ 0.0091) was noted in DMEK single procedures. Endothelial cell loss was 30%⫾20% at 3 months and 32%⫾20% in 38 eyes that reached the 6-month examination. Median pachymetry decreased from 660 ␮m before surgery to 530 ␮m. Descemet’s membrane stripped successfully from 60 of 72 donor corneas; 6 were converted successfully to Descemet’s stripping automated endothelial keratoplasty (DSAEK) and 6 (8%) were discarded. Only 1 graft detached completely, but air was reinjected in 38 eyes (63%), mainly for partial detachments. Five DMEK corneas (8%) failed to clear and were replaced successfully with DMEK or DSAEK. All remained clear at last follow-up. Conclusions: Compared with DSAEK, DMEK provided a significantly higher rate of 20/20 and 20/25 vision, with comparable endothelial cell loss. Descemet’s membrane endothelial keratoplasty restored physiologic pachymetry, but donor preparation and attachment currently are more challenging than with DSAEK. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2009;116:2361–2368 © 2009 by the American Academy of Ophthalmology. Descemet’s stripping automated endothelial keratoplasty (known as DSAEK or DSEK) has become the preferred treatment for endothelial dysfunction because it provides faster visual recovery and retains the strength and integrity of the eye better than standard penetrating keratoplasty (PK).1–3 In 2007, 85% of the donor corneas provided by the Eye Bank Association of America for patients with endothelial dysfunction were used in endothelial keratoplasty procedures (2007 Eye Banking Statistical Report, available from the Eye Bank Association of America at www.restoresight.org; accessed January 29, 2009). © 2009 by the American Academy of Ophthalmology Published by Elsevier Inc. In addition to providing faster visual recovery, DSAEK also provides more predictable refractive outcomes than PK,3– 8 and this has led to a paradigm shift in the timing of cataract surgery for patients with endothelial dysfunction. Whereas cataract surgery typically was postponed until after PK, so that it could be used to correct unpredictable refractive errors associated with the graft, cataract surgery usually is performed before DSAEK. However, variation in the thickness and contour of the DSAEK donor graft still causes some variability in the spherical equivalent refraction after DSAEK.9,10 In addition, the percentage of ISSN 0161-6420/09/$–see front matter doi:10.1016/j.ophtha.2009.07.010 2361 Ophthalmology Volume 116, Number 12, December 2009 patients who achieve 20/20 best spectacle-corrected visual acuity (BSCVA) generally is less than expected after DSAEK relative to visual potential.3– 8 Selective transplantation of only donor DM and endothelium, without any stroma, should restore normal corneal thickness and should improve refractive predictability by eliminating variations in donor stromal thickness and contour. Furthermore, eliminating donor stroma would preclude stromal irregularities or macrofolding or microfolding of donor stromal tissue that can lead to suboptimal vision after DSAEK. Melles et al11 reported in vitro studies that established proof of concept for DM transplantation in 1998 and 2002 (Melles GRJ, et al. Invest Ophthalmol Vis Sci 39 [Suppl]: ARVO Abstract 343, 1998). In 2006, they published a case report of a patient who achieved 20/20 vision within 1 week using a technique they called Descemet’s membrane endothelial keratoplasty (DMEK).12,13 They subsequently reported results of the first 50 DMEK cases for treatment of Fuchs’ dystrophy.14,15 The visual outcomes were impressive, with 75% of the eyes achieving 20/25 vision or better at 6 months, but the regraft rate was high (20%), and donor tissue loss while stripping DM was an additional concern.14 –17 This prospective, multicenter study was undertaken to evaluate whether DMEK provides better visual and refractive results than DSAEK and to assess the success rate for donor preparation and graft clearing. Patients and Methods Patients This was a prospective study of a consecutive series of 60 cases of DMEK performed by 2 surgeons at Price Vision Group (Indianapolis, Indiana) and Pacific Cataract and Laser Institute (Chehalis, Washington) between February and October 2009. The study included the first DMEK cases performed by 1 surgeon (FWP). The other surgeon (AWG) performed 2 cases before the prospective study began. An independent review board (IRB, Inc., Buena Park, CA) reviewed and approved the study, and all subjects read and signed an informed consent document for both the treatment and participation in the research. The study was registered on www. clinicaltrials.gov (accessed November 26, 2008) and was conducted in accord with Good Clinical Practices, the Declaration of Helsinki, and the Health Insurance Portability and Accountability Act. Inclusion criteria were endothelial keratoplasty candidates who consented to the procedure and were willing to return for study examinations. Exclusion criteria were glaucoma filters, large iris defects, or large fixed and dilated pupils, because of concern that the extremely thin and pliable donor DM could be lost in a glaucoma tube or in the posterior chamber in such eyes. During this series, DSAEK also was performed on EK candidates who met these criteria. Surgical Technique Donor Preparation. All steps of the surgical technique are shown in an online narrated video (video clips 1– 8, available at http:// aaojournal.org). At both sites, the donor graft was prepared using the submerged cornea using backgrounds away technique devel- 2362 oped by one of the authors (AWG),18 The donor corneal–scleral rim was lifted from the shipping container and was placed on a sterile flat surface. While stabilizing the rim with toothed forceps, the periphery was scored gently just inside the trabecular meshwork using blunt nontoothed forceps, a Y-hook, or a Connor wand to break through DM without tearing stromal fibers. The donor corneal–scleral rim usually was stained with trypan blue to highlight the scoring mark, and then it was placed in a corneal viewing chamber containing corneal storage solution (Optisol; Bausch & Lomb, Rochester, NY). The viewing chamber suspends the cornea below the fluid surface and away from the bottom of the container, significantly improving DM visualization when the microscope is focused on the donor cornea. The scoring mark was examined carefully for any jagged edges and irregular tags were torn off with blunt forceps to help make a smooth perimeter that would resist tearing as the membrane was stripped. While holding the donor rim with toothed forceps, the scored edge of DM was grasped with nontoothed forceps and slowly was stripped away from the stroma. It could be stripped this way completely, but in most cases, DM was stripped in a 3-step process: (1) DM was stripped approximately 20% to 40% of the way across and then it was laid back down on the stroma; (2) the donor cornea was placed on a punch block where the endothelial side was tapped lightly with a trephine, cutting through DM, but only partially through the stroma; and (3) the donor cornea was placed back in the viewing chamber and DM stripping was completed across the trephinated center (Fig 1). When using the 3-step technique, a mark often was placed on the periphery of the corneal rim to indicate where from the scored edge the initial stripping was performed. This made it easier to regrasp the loosened membrane in the same area to complete the stripping after the trephine cut. A partial stripping was carried out before the trephine cut because it is much easier to lift the edge away from an intact stromal bed. After it was stripped from the donor cornea, the donor DM typically curled up into a scroll with the endothelial side outward. It was stained with trypan blue to improve subsequent visualization while inserting and positioning it in the recipient eye. The 2 surgeons used slightly different staining procedures. One surgeon (FWP) removed the donor rim from the viewing chamber and placed it on a sterile surface, then gently placed the DM scroll in the center of the donor corneal rim and dripped trypan blue on it. The other surgeon (AWG) placed the stripped DM in a small plastic well filled with trypan blue. Recipient Preparation. The patients were prepped and draped and given topical anesthesia with monitored intravenous sedation or retrobulbar block without intravenous sedation. In 11 cases, cataract extraction and intraocular lens (IOL) implantation was performed before DMEK. In 2 cases, a pars plana vitrectomy was performed before DMEK. One surgeon (FWP) always made an inferior peripheral iridotomy so that the eye could be left filled with air at the end of the procedure without causing pupillary block. The other surgeon used a different air management strategy that did not require an iridotomy. In all primary graft cases, DM was stripped from the recipient cornea. The epithelium usually was lightly marked with the trephine used to cut the donor cornea and DM was stripped from an area that was 1 to 2 mm smaller in diameter so that the edge of the donor DM would overlap the recipient DM. The pupil was constricted to protect the graft from touching the lens. Graft Insertion and Positioning. The 2 surgeons used different techniques to insert the graft. One surgeon (AWG) placed the blue-stained donor DM in a modified IOL cartridge or semirigid nonstick tubing connected to a syringe filled with balanced salt solution (BSS). Short bursts of BSS then were used to irrigate the DM gently into the anterior chamber. The other surgeon (FWP) Price et al 䡠 Descemet’s Membrane Endothelial Keratoplasty Figure 1. Photograph showing the use of nontoothed forceps to strip Descemet’s membrane and endothelium from a donor cornea and scleral rim submerged in corneal storage solution in a corneal viewing chamber. Figure 3. Intraoperative photograph showing the trypan blue-stained donor Descemet’s membrane and endothelium being uncurled inside the recipient eye using short bursts of balanced salt solution injected through a cannula. used an implantable collamer lens inserter (Staar Surgical, Monrovia, CA) to insert the graft. He first filled the distal three fourths of the cartridge tip with 2% hydroxypropylmethylcellulose viscoelastic agent, Ocucoat (Bausch & Lomb). This is a water-soluble derivative of cellulose. The rest of the cartridge was filled with BSS to the area where the IOL usually is placed at the wings. The scrolled DM was dropped into the cartridge, past the wings, into the section with viscoelastic. The area of the wings was filled with the viscoelastic agent, it was loaded into the inserter with a foam-tipped plunger that had been soaked in BSS, and the DM was injected into the eye (Fig 2). Both of these techniques have been described in detail.18 The insertion incision was 2.8 or 3.0 mm wide. To prevent reflux of the donor DM, the eye was kept soft throughout the insertion procedure by venting a paracentesis or the main incision. After donor DM was in the eye, it was centered and oriented with the rolls of the scroll facing upward. A slit-lamp attachment on the operating microscope was found to be helpful for visualization of the scroll orientation. Short bursts of BSS from a 3-ml syringe were used as needed to orient and center the DM scroll correctly. The DM scroll was opened using additional short quick bursts of BSS (Fig 3). During this process, a shallow anterior chamber was helpful in keeping the edges of DM partially unwrapped. After the scroll was partially unwrapped, a small air bubble was injected to secure the orientation (Fig 4).19 The air was injected slowly and in controlled amounts from a 1-ml syringe with a 30-gauge cannula. An initial air bubble of approximately 0.02 ml helped to maintain membrane orientation, while still being small enough to allow the DM to continue to unfold and move as needed for proper centering. The recipient corneal surface was stroked or tapped with a cannula and fluid was injected into the interface, as needed, to help center and fully unwrap the donor DM. After it was positioned properly, the anterior chamber was filled with air and the patient was kept in a supine position for 30 to 60 minutes to allow the donor to adhere. Afterward, sufficient air was removed to prevent Figure 2. Photograph showing the injection of scrolled donor Descemet’s membrane and endothelium into a recipient eye through an intraocular lens inserter. Figure 4. Intraoperative photograph showing a small air bubble that was placed beneath the trypan blue-stained donor graft that resembles a partially unwrapped scroll. The air bubble helps to secure the graft orientation and to control further uncurling of the graft edges. 2363 Ophthalmology Volume 116, Number 12, December 2009 pupillary block, or, if the patient had an inferior iridotomy, the air was left in the eye. Air Reinjection. Patients were cautioned not to rub their eyes because that is known to dislodge DSAEK donor grafts. Patients usually were examined at the slit lamp 1 day, 2 days, and 1 week after surgery. Areas of graft detachment frequently were noted and air was reinjected as deemed necessary to promote graft attachment. In 2 patients, the postoperative slit-lamp view or optical coherence tomography images indicated that the DM scroll was oriented with the endothelial side upward. In those cases, the patient was taken back to the surgery center and the graft was flipped over and repositioned with air, as described previously. One of these patients demonstrated total detachment at the time of return to surgery, in the other, a residual air bubble prevented total detachment. Outcome Analysis. Central corneal thickness was measured before surgery and after surgery with ultrasonic pachymetry at one site and with a Pentacam (Oculus USA, Lynnwood, WA) at the other site. Donor endothelial cell density was measured by the provider eye banks using specular microscopy. Postoperative endothelial cell density was measured with specular or confocal microscopy (Noncon Robo, Konan Medical, Inc., Hyogo, Japan; ConfoScan 4, Nidek Technologies, Inc., Greensboro, NC), using the center’s method and manufacturer’s calibration and software. Manual counts were averaged from 3 separate images. Snellen BSCVAs were converted to logarithms of the minimum angle of resolution for statistical analysis. All outcome measures were tested for normality. Descriptive statistics for normally distributed variables are reported as mean⫾standard deviation. The median and range are reported for variables that were not normally distributed. Changes between preoperative and postoperative values were analyzed using the paired difference t test. Analysis of refractive change was restricted to eyes with 20/50 or better preoperative vision (n ⫽ 34), because it was difficult to obtain a reliable preoperative refraction in eyes with poorer visual acuity. Analysis of spherical equivalent change was restricted to eyes with 20/50 or better preoperative vision and a single DMEK procedure (n ⫽ 27) because combined cataract surgery can induce an intentional change in spherical equivalent refraction. Data were analyzed using SAS software version 9.0 (SAS Inc, Cary, NC). P values less than 0.05 were considered statistically significant. Results Demographics Sixty eyes in 56 patients were treated with DMEK. All 60 eyes were followed up through 1 month, and 57 (95%) completed the 3-month examination. The average patient age was 67 years (range, 48 – 84 years), and 57% were female. Patients with coexisting ocular pathologic features, such as primary open-angle glaucoma or macular degeneration, were included in this study. Indications for keratoplasty were Fuchs’ dystrophy, pseudophakic bullous keratopathy, failed PK, or failed endothelial keratoplasty (Table 1). The failed PK had significant corneal scarring and neovascularization, and the DMEK was performed for pain relief rather than to improve vision. Ten DMEK procedures were combined with phacoemulsification and IOL implantation as a triple procedure to treat coexisting cataract and Fuchs’ endothelial dystrophy (Table 1). One DMEK procedure was combined with pars plana vitrectomy, phacoemulsification, and IOL implantation as a quadruple procedure, and one was combined with pars plana vitrectomy. Forty-eight cases were stand-alone graft procedures. 2364 Table 1. Recipient Demographics and Surgical Procedures Mean age⫾standard deviation (yrs) Sex (female:male) Indications for DMEK (no. of eyes) Fuchs’ endothelial dystrophy Failed endothelial keratoplasty Failed penetrating keratoplasty Pseudophakic bullous keratopathy Surgical procedure DMEK DMEK/cataract extraction/IOL implantation DMEK/cataract extraction/IOL/pars plana vitrectomy DMEK/pars plana vitrectomy 68⫾9.9 (range, 48–85) 34:26 51 7 1 1 48 10 1 1 DMEK ⫽ Descemet’s membrane endothelial keratoplasty; IOL ⫽ intraocular lens. Visual Outcomes The median preoperative BSCVA was 20/50 (range, 20/25– hand movements), excluding 4 eyes (7%) that had significant ocular comorbidity: advanced macular degeneration (n ⫽ 2), previous retinal detachment and repair (n ⫽ 1), or extensive corneal scarring and neovascularization in a failed PK (n ⫽ 1). One month after DMEK, the mean and median BSCVA was 20/30 (range, 20/20 –20/60), 20% of the eyes recovered 20/20 vision, 31% were 20/25 or better, and 84% had 20/40 vision or better. Three months after DMEK, the mean and median BSCVA was 20/25 (range, 20/20 –20/50), 26% of the eyes had 20/20 vision, 63% had BSCVA of 20/25 or better, and 94% had BSCVA of 20/40 or better. Refractive Outcomes The mean preoperative refractive cylinder in eyes where a preoperative manifest refraction could be obtained reliably was 0.88⫾ 0.69 diopter (D; range, 0 –2.0 D). The mean postoperative refractive cylinder in those eyes was 0.85⫾0.70 D (range, 0 –2.5 D). This was not a statistically significant difference (P ⫽ 0.93). In the eyes that underwent a stand-alone DMEK procedure, the mean change in spherical equivalent refraction from before surgery to 1 month after surgery was ⫹0.49⫾0.63 D (range, –1.0 to ⫹1.5 D). This was a statistically significant hyperopic shift (P ⫽ 0.0091). Endothelial Cell Density and Pachymetry The mean donor endothelial cell density was 3010⫾200 cells/cm2 (range, 2520 –3430 cells/cm2). The mean cell loss at 3 months was 30%⫾20% (range, 2.7%–78%). The median preoperative central corneal thickness, assessed by ultrasonic pachymetry, was 656 ␮m (range, 506 –1030 ␮m). The median postoperative central corneal thickness was 528 ␮m (range, 424 – 678 ␮m). Perioperative Challenges and Management Stripping of 72 donor corneas was attempted. In 12, DM could not be stripped successfully because it had a tendency to tear. Six donor corneas were salvaged before the tear progressed into the central 8.5 to 9 mm by placing the partially stripped donor on an artificial anterior chamber and dissecting the cornea with a microkeratome for use with DSAEK. Six donor corneas (8%) could not be salvaged. Price et al 䡠 Descemet’s Membrane Endothelial Keratoplasty Air was reinjected at least once in 38 eyes (63%). Air reinjections were performed from 1 day to 3 months after surgery, but most were within the first 2 weeks. The 2 surgeons used different air management strategies. One surgeon (FWP) performed an inferior iridotomy and left the eye filled with air at the end of the case. Fifty-six of these cases were rebubbled (48% once and 8% twice). The other surgeon (AWG) left the eye completely filled with air for 30 to 60 minutes and then removed enough air to prevent pupillary block. In 85% of these cases (21% once, 50% twice, 7% thrice, and 7% 4 times), air was reinjected. Most air reinjections were carried out to treat partial graft detachment. The graft completely detached in only 1 eye. In 2 cases (1 partial detachment and 1 full detachment), the orientation of the curled DM indicated that the endothelial side was facing the recipient stroma instead of facing the anterior chamber, so the graft was flipped over and reattached with air. Five grafts (8%), including one that initially was oriented incorrectly, failed to clear and were regrafted successfully with DSAEK (n ⫽ 4) or DMEK (n ⫽ 1). The other flipped graft remained attached and had a 6-month endothelial cell count of 953 cells/mm2. In 2 eyes (3%), a rejection episode developed within the first 3 months. One eye was diagnosed with cystoid macular edema, per optical coherence tomography, at the 3-month examination. This eye had undergone cataract extraction 3 weeks before DMEK, and the cystoid macular edema was treated successfully with nonsteroidal anti-inflammatory eye drops. No pupillary block glaucoma or other complications occurred. Discussion This is the first prospective study on DMEK in the United States. The findings suggest that DMEK provides superior visual results and more predictable refractive outcomes, with comparable endothelial cell loss as DSAEK, which currently is the preferred method for treating endothelial dysfunction. However, donor preparation and attachment currently are more challenging with DMEK. At 1 month, 20% of the DMEK eyes had 20/20 vision, 31% were 20/25 or better, 84% were 20/40 or better, and by 3 months, 26% recovered 20/20 vision, 63% were 20/25 or better, and 94% were 20/40 or better, excluding 4 eyes with advanced ocular comorbidity. The 94% rate of 20/40 vision 3 months after DMEK compared favorably with the 80% to 97% rate at 6 months after DSAEK in eyes without comorbidity.5,7,8 The 3-month rates of 20/20 and 20/25 vision with DMEK exceeded the best rates that have been reported with DSAEK at 6 months and beyond.1– 8 They are significantly better (P⬍0.0001) than the published 6-month visual outcomes in an initial consecutive series of 100 DSAEK performed by one of the authors (FWP) using similar exclusion criteria for ocular comorbidity (Fig 5).8 The 3-month mean BSCVA of 20/25 was consistent with the 20/25 mean BSCVA in the initial DMEK series by Melles et al and was 1 to 2 lines better than the 6-month mean in DSAEK series with similar exclusion of ocular comorbidity.5,7,8,15 Descemet’s membrane endothelial keratoplasty is performed through a small 2.8- to 3.0-mm incision and, like DSAEK, causes no increase in mean refractive cylinder. Interestingly, a small 0.5-D mean hyperopic shift was observed after DMEK. This may have been associated with corneal deturgescence. Figure 5. Graph comparing the percentage of eyes that achieved different levels of best spectacle-corrected visual acuity in 2 consecutive series, the present Descemet’s membrane endothelial keratoplasty (DMEK) series and an earlier Descemet’s stripping automated endothelial keratoplasty (DSAEK) series performed by one of the same surgeons.8 Notably, the range of the spherical equivalent shift in this DMEK series (2.5 D) was substantially less than that typically reported after DSAEK (4 –5 D),4,6 suggesting that DMEK can provide more predictable refractive outcomes. This is not surprising, because Dupps et al9 showed that much of the variation in spherical equivalent refraction after DSAEK can be explained by variations in the central thickness and thickness gradient from center to periphery of the donor graft. Significant variation in donor graft thickness does not occur with DMEK, because the graft is a single cell layer with its basement membrane. Cataract extraction and IOL implantation typically are performed before DSAEK or DMEK, and the expected refractive change usually is factored into the IOL calculation. Improved refractive predictability could help more patients achieve emmetropia after DMEK. The mean endothelial cell loss was 30% in this DMEK series at 3 months. In a subset of the DMEK eyes that completed the 6-month examination (n ⫽ 38), the mean cell loss was 32%⫾20%. This was well within the 20% to 50% range reported within the first year in DSAEK series.3,6,15,20 –22 It has been shown with DSAEK that the bulk of the cell loss is realized at the first postoperative measurement point, typically 6 months, with minimal subsequent increase out to 1 year.20,21 The 6-month cell loss with DMEK was remarkably similar to the 28% cell loss in Melles’ initial DMEK series despite several technique differences.15 An IOL injector was used to insert the donor graft into the recipient eye, whereas Melles used a pipette. Furthermore, donor corneas stored in Optisol were used, and the donor endothelium and DM were transplanted immediately after stripping the DM. In contrast, Melles et al used corneas stored in organ culture medium, and the stripped donor endothelium and DM were returned to organ culture medium to recover for an extended period before use in transplantation. Descemet’s membrane endothelial keratoplasty restored central corneal thickness to within a normal range, whereas DSAEK increases corneal thickness by the addition of donor stromal tissue. Mean central corneal thickness was 530 ␮m in this DMEK series, whereas it exceeds 650 ␮m after DSAEK.2,4,7,8 2365 Ophthalmology Volume 116, Number 12, December 2009 Figure 6. Photograph showing peripheral detachment of Descemet’s membrane endothelial keratoplasty. When comparing perioperative complications and endothelial cell loss in DMEK and DSAEK series, it is important to keep in mind that DMEK is still a relatively new technique that is used by just a handful of surgeons who are all still early in their own learning curves, whereas DSAEK has benefited from several years of innovation and optimization by hundreds of surgeons worldwide.1,2,15,23 The complications encountered with DMEK were tearing of donor DM during the stripping procedure, graft detachment, and failure of the graft to clear. Eight percent of the donor tissue was lost in this series of 60 consecutive DMEK cases because DM tore during the stripping procedure. Partway through the DMEK series, it was realized that if partial tearing of DM occurred during the initial stripping step, the donor cornea could be converted to a DSAEK case. This can help to avoid tissue loss if a tear develops, but it is not within the central portion of the donor. The same 2 surgeons have not lost any donor tissue in their DSAEK series, which together exceed 1100 consecutive cases. However, one of the surgeons did convert a DSAEK case to DMEK after experiencing microkeratome difficulties, so being able to perform the case either way can help avoid loss of donor tissue with both procedures. Air was reinjected to promote donor adherence in more than half the eyes in this DMEK series, whereas the same 2 surgeons reinjected air in only 3% to 4% of their concurrent DSAEK cases. With DSAEK, air usually is reinjected only if the graft has totally detached, because it has been found that areas of partial detachment usually zipper down on their own over time. However, in this DMEK series, most air reinjections were used to treat partial detachments, which 2366 usually were in the graft periphery (Fig 6). Partial DMEK detachments do not seem to zipper down spontaneously over time as well as DSAEK detachments do, at least in part because the DMEK edge detachments had a tendency to curl under, maintaining the cleft. Therefore, the reinjections of air usually were used to uncurl and push the donor DM edges against the recipient cornea. Earlier in the series, the authors sometimes were slow to rebubble partial peripheral detachments, whereas later in the series, rebubbling usually was carried out within the first week. Only 1 eye was rebubbled after 1 month, and that was early in the series. It is the authors’ policy to strip DM from an area of the recipient cornea that is smaller than the planned graft diameter so that the donor endothelium overlaps somewhat onto recipient endothelium and no areas are left denuded of endothelial cells. Unfortunately, donor DM does not seem to adhere as well to residual recipient endothelium as it does to bare stroma. Despite the attachment challenges, the authors believe some overlap is important to help maximize endothelial cell density, which may be important for longterm graft survival.24 In this study, one of the surgeons used hydroxypropylmethylcellulose viscoelastic agent to protect the donor endothelium during graft insertion. This viscoelastic agent was chosen specifically for its water-soluble properties, which caused it to dissolve readily in the anterior chamber and not to collect in the graft interface. Typically, cohesive or dispersive hyaluronidase viscoelastic agents are used with DSAEK, and care must be taken to keep these out of the graft interface to promote graft adherence. Price et al 䡠 Descemet’s Membrane Endothelial Keratoplasty The primary graft failure rate was 8% in this DMEK series, whereas it is less than 1% in the same 2 surgeons’ concurrent DSAEK cases. Nevertheless, the regraft rate in this DMEK series was less than half that reported by Ham et al15 in his first 50 cases,15 and the graft failure rate is expected to continue to drop as additional corneal surgeons develop and share technique and as instrumentation improves. Two eyes experienced a graft rejection episode. This was comparable with the rate seen in a similar timeframe with DSAEK.25 Other complications that have been reported in some DSAEK series, such as pupillary block or epithelial downgrowth, were not seen in this series of 60 consecutive DMEK eyes. One potential advantage of DMEK over DSAEK is that DMEK requires no special instrumentation or startup costs, whereas DSAEK requires a microkeratome for donor dissection. This difference could be particularly important for surgeons in developing parts of the world. Although not required, the authors found that certain specialized equipment can greatly facilitate visualization of the extremely thin DMEK graft. In particular, anterior segment optical coherence tomography can be helpful for visualizing partial or complete donor detachment through a hazy cornea, when the slit lamp view is not clear. Also, a slit-beam attachment on the operating microscope is helpful for identifying the orientation of the curled DM after it is inserted in the anterior chamber. A second potential advantage of DMEK over DSAEK is that the only donor tissue requirements for DMEK are healthy DM and endothelium. Previous refractive surgery or stromal scars do not disqualify donor tissue for DMEK, whereas they may cause visual or refractive problems if the cornea were used for DSAEK. In addition, DM can be harvested while fully sparing the remaining tissue for deep anterior lamellar keratoplasty. So overall, DMEK seems to facilitate maximum use of available donor tissue, but further optimization of DM stripping techniques is needed to eliminate tissue loss during the stripping procedure. Eye bank technicians routinely dissect grafts for DSAEK, and it is anticipated that they also could strip DM and ship it for use in DMEK. This would be particularly helpful when dealing with occasional loss of donor tissue because the eye bank may be able to substitute another cornea or they at least can call the surgeon so the case can be rescheduled. However, a current impediment to having an eye bank technician prepare the tissue is that the DM scroll that results from use of the submerged cornea using backgrounds away technique is difficult to evaluate thoroughly with slit-lamp and specular microscopy after preparation, as is currently recommended by the Eye Bank Association of America (EBAA) standards for donor tissue prepared for DSAEK. Several surgeons have suggested other ways to isolate and implant donor DM. In 2007, Tappin26 reported clinical transplantation of a 7.5-mm diameter DM through an 8.0-mm scleral incision using a flat carrier device. He stripped the donor DM in air using forceps, and subsequently reported a high incidence of donor loss (personal communication, 2007). Studeny and Busin reported using a modified big-bubble approach to separate donor DM from stroma (Studeny P. Update on posterior lamellar keratoplasty/ Descemet membrane transplantation [DSEK/DSAEK/FSDSEK, and DMEK]. Course presented at: American Academy of Ophthalmology, Nov 11, 2008; Atlanta; Busin M. Video presentation. Presented at Cornea Day, American Society of Cataract and Refractive Surgery, April 4, 2008; Chicago). Also, Gardea et al27 published a deep hand dissection technique. Some of these alternate techniques would allow easier postpreparation evaluation by the eye banks. Overall, the small series that have been reported suggest that, compared with DSAEK, transplanting DM without stroma may provide better visual recovery, but isolation of donor DM and achieving graft attachment are more challenging with any of the DM methods.14 –16,26,27 This results in more donor tissue loss and primary graft failure than that seen with DSAEK, which is much further along in the development and optimization curve. Also, the higher rate of rebubbling entails additional surgical risks. This DMEK series did not include any eyes with glaucoma filters, large iris defects, or large fixed and dilated pupils. With current techniques, the authors were concerned that the donor DM was so pliable that it easily could be lost in a glaucoma tube or in the posterior chamber in such eyes. Descemet’s stripping automated endothelial keratoplasty may be preferable in those eyes, or some of the alternative DM transplantation methods mentioned previously may help address this concern. In eyes with a narrow anterior chamber, DMEK may be preferable to DSAEK because it does not add additional stromal tissue behind the recipient cornea. This study focused on 3-month outcomes. Longer follow-up and larger numbers of eyes will be needed to evaluate fully the relative merits of DMEK. In conclusion, the results of this prospective study of 60 consecutive DMEK cases provide further support for the concept that DMEK may provide even better visual and refractive outcomes than DSAEK. This study also helps to demonstrate which aspects of the DMEK technique require further optimization to minimize loss of precious donor tissue. References 1. Price MO, Price FW. Descemet’s stripping endothelial keratoplasty. Curr Opin Ophthalmol 2007;18:290 – 4. 2. Price MO. Comparison of endothelial keratoplasty and penetrating keratoplasty outcomes. In: Price FW, Price MO, eds. DSEK: All You Need to Know about Endothelial Keratoplasty. Thorofare, NJ: Slack, Inc.; 2008:37–52. 3. Bahar I, Kaiserman I, McAllum P, et al. Comparison of posterior lamellar keratoplasty techniques to penetrating keratoplasty. Ophthalmology 2008;115:1525–33. 4. Price MO, Baig KM, Brubaker JW, Price FW, Jr. Randomized, prospective comparison of precut vs surgeon-dissected grafts for Descemet’s stripping automated endothelial keratoplasty. Am J Ophthalmol 2008;146:36 – 41. 5. Gorovoy MS. Descemet’s-stripping automated endothelial keratoplasty. Cornea 2006;25:886 –9. 6. Koenig SB, Covert DJ, Dupps WJ Jr, Meisler DM. Visual acuity, refractive error, and endothelial cell density six months after Descemet’s stripping and automated endothelial keratoplasty (DSAEK). Cornea 2007;26:670 – 4. 2367 Ophthalmology Volume 116, Number 12, December 2009 7. Chen ES, Terry MA, Shamie N, et al. Descemet’s-stripping automated endothelial keratoplasty: six-month results in a prospective study of 100 eyes. Cornea 2008;27:514 –20. 8. Price MO, Price FW Jr. Descemet’s stripping with endothelial keratoplasty comparative outcomes with microkeratome-dissected and manually dissected donor tissue. Ophthalmology 2006; 113:1936 – 42. 9. Dupps WJ Jr, Qian Y, Meisler DM. Multivariate model of refractive shift in Descemet’s-stripping automated endothelial keratoplasty. J Cataract Refract Surg 2008;34:578 – 84. 10. Price MO, Price FW, Stoeger C, et al. Central thickness variation of precut DSAEK donor grafts. J Cataract Refract Surg 2008;34:1423– 4. 11. Melles GR, Lander F, Rietveld FJ. Transplantation of Descemet’s membrane carrying viable endothelium through a small scleral incision. Cornea 2002;21:415– 8. 12. Melles GR, Ong TS, Ververs B, van der Wees J. Descemet’s membrane endothelial keratoplasty (DMEK). Cornea 2006; 25:987–90. 13. Melles GR. Posterior lamellar keratoplasty: DLEK to DSEK to DMEK. Cornea 2006;25:879 – 81. 14. Melles GR, Ong TS, Ververs B, van der Wees J. Preliminary clinical results of Descemet’s membrane endothelial keratoplasty. Am J Ophthalmol 2008;145:222–7. 15. 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. Eye 2009; 23:1990 – 8. 16. Ham L, van der Wees J, Melles GR. Causes of primary donor failure in Descemet’s membrane endothelial keratoplasty. Am J Ophthalmol 2008;145:639 – 44. 17. Lie JT, Birbal R, Ham L, et al. Donor tissue preparation for Descemet’s membrane endothelial keratoplasty. J Cataract Refract Surg 2008;34:1578 – 83. 18. Giebel AW, Price FW. Descemet’s membrane endothelial keratoplasty (DMEK): the bare minimum. In: Price FW, Price MO, eds. DSEK: All You Need to Know about Endothelial Keratoplasty. Thorofare, NJ: Slack, Inc.; 2008:119 –146. 19. Giebel AW. Barosurgery, the surgical use of air, as a technique to promote adhesion between corneal layers in lamellar keratoplasty. Techniques in Ophthalmol 2008;6:35– 40. 20. Price MO, Price FW. Endothelial cell density after Descemet’s stripping endothelial keratoplasty: influencing factors and 2-year trend. Ophthalmology 2008;115:857– 65. 21. Terry MA, Chen ES, Shamie N, et al. Endothelial cell loss after Descemet’s stripping endothelial keratoplasty in a large prospective series. Ophthalmology 2008;115:488 –96. 22. Busin M, Bhatt PR, Scorcia V. A modified technique for Descemet’s membrane stripping automated endothelial keratoplasty to minimize endothelial cell loss. Arch Ophthalmol 2008;126:1133–37. 23. Price FW Jr, Price MO. Descemet’s stripping with endothelial keratoplasty in 200 eyes: early challenges and techniques to enhance donor adherence. J Cataract Refract Surg 2006;32: 411– 8. 24. Price FW, Price MO. Does endothelial cell survival differ between DSEK and standard PK? Ophthalmology 2009;116:367–8. 25. Price MO, Jordan CS, Moore G, Price FW. Graft rejection episodes after Descemet’s stripping with endothelial keratoplasty. Part two: the statistical analysis of probability and risk factors. Br J Ophthalmol 2009;93:391–5. 26. Tappin M. A method for true endothelial cell (Tencell) transplantation using a custom-made cannula for the treatment of endothelial cell failure. Eye 2007;21:775–9. 27. Gardea E, Adam P, Brasseur, Muraine M. Descemet’s membrane graft in a patient with Fuchs endothelial dystrophy. J Fr Ophthalmol 2007;30:658 –9. Footnotes and Financial Disclosures Originally received: February 12, 2009. Final revision: July 3, 2009. Accepted: July 6, 2009. Available online: October 23, 2009. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Manuscript no. 2009-198. 1 Cornea Research Foundation of America, Indianapolis, Indiana. 2 Pacific Cataract and Laser Institute, Chehalis, Washington. 3 Price Vision Group, Indianapolis, Indiana. Presented at: Fall Educational Symposium of the Cornea Society and Eye Bank Association of America, November 2008, Atlanta, Georgia. 2368 Supported by The Indiana Lions Eye and Tissue Transplant Bank, Indianapolis, Indiana, and SightLife, Seattle, Washington. Correspondence: Marianne O. Price, PhD, Cornea Research Foundation of America, 9002 North Meridian Street, Suite 212, Indianapolis, IN 46260. E-mail: [email protected].