Theofilos Tourtas

Descemet Membrane Endothelial Keratoplasty Versus Descemet Stripping Automated Endothelial Keratoplasty

PURPOSE To evaluate visual outcome and endothelial cell survival after Descemet membrane endothelial keratoplasty (DMEK) in comparison with Descemet stripping automated endothelial keratoplasty (DSAEK). DESIGN Single-center, retrospective, consecutive case series. METHODS Thirty-eight eyes of 38 consecutive patients undergoing DMEK, who completed a 6-month follow-up, were compared with 35 eyes of 35 consecutive patients undergoing DSAEK for Fuchs endothelial dystrophy or pseudophakic bullous keratopathy. Main outcome measures included best-corrected visual acuity (in logarithm of the minimal angle of resolution [logMAR] units) and endothelial cell density within a 6-month follow-up. RESULTS Best-corrected visual acuity increased from 0.70 ± 0.48 logMAR and 0.75 ± 0.32 logMAR before surgery to 0.21 ± 0.14 logMAR and 0.48 ± 0.19 logMAR 3 months after DMEK and DSAEK (P < .001), respectively, and to 0.17 ± 0.12 logMAR and 0.36 ± 0.15 logMAR 6 months after DMEK and DSAEK (P < .001), respectively. Endothelial cell density decreased from 2575 ± 260 cells/mm(2) and 2502 ± 220 cells/mm(2) before surgery to 1498 ± 244 cells/mm(2) and 1778 ± 420 cells/mm(2) 3 months after DMEK and DSAEK (P < .001), respectively, and to 1520 ± 299 cells/mm(2) and 1532 ± 495 cells/mm(2) 6 months after DMEK and DSAEK (P = .483), respectively. Central corneal thickness decreased from 652 ± 92 μm before surgery to 517 ± 45 μm 6 months after DMEK, and from 698 ± 137 μm before surgery to 618 ± 66 μm 6 months after DSAEK. CONCLUSIONS DMEK provided faster and more complete visual rehabilitation when compared with DSAEK. However, there were no significant differences concerning endothelial cell survival within a 6-month follow-up.

Graft Adhesion in Descemet Membrane Endothelial Keratoplasty Dependent on Size of Removal of Host's Descemet Membrane

IMPORTANCE It is essential to devise strategies that improve graft adhesion after Descemet membrane endothelial keratoplasty (DMEK) to reduce the rebubbling rate. OBJECTIVE To evaluate the influence of the extent of descemetorhexis on graft adhesion properties after DMEK. DESIGN, SETTING, AND PARTICIPANTS Single-surgeon, retrospective, observational case series conducted in the Department of Ophthalmology, University of Erlangen-Nuremberg, Germany, that reviewed the medical records of 200 consecutive patients undergoing DMEK. Fifty-three eyes of 51 patients undergoing DMEK for Fuchs endothelial dystrophy fulfilling the inclusion criteria were enrolled in this study. Based on intraoperative drawings, postoperative slitlamp examination, and photographs, eyes were divided into 2 groups. The diameter of the descemetorhexis was approximately 10 mm in group A (30 eyes), resulting in a peripheral 1-mm zone of denuded stroma between the graft and the hosts Descemet membrane, and approximately 6 mm in group B (23 eyes), resulting in a peripheral 1-mm zone of overlapping between the graft and the hosts Descemet membrane. MAIN OUTCOMES AND MEASURES Graft detachment rate, extent of graft detachment (in clock hours of grafts circumference), and rebubbling rate. RESULTS Four days after DMEK, the graft detachment rate was 33.3% (10 of 30) in group A and 78.3% (18 of 23) in group B (P = .002). The mean (SD) extent of graft detachment was 0.6 (0.9) and 2.8 (2.5) clock hours in groups A and B, respectively (P < .001), 4 days after surgery. The rebubbling rate was 6.7% (2 of 30) and 30.4% (7 of 23) for groups A and B, respectively (P = .03). CONCLUSIONS AND RELEVANCE A larger descemetorhexis in DMEK is correlated with better graft adhesion and lower rebubbling rates. Therefore, patients with a larger descemetorhexis require less intensive follow-up.

Randomized comparison of topical prednisolone acetate 1% versus fluorometholone 0.1% in the first year after descemet membrane endothelial keratoplasty.

Purpose: The aim of this study was to compare the efficacy and side effects of prednisolone acetate 1% versus fluorometholone 0.1% after Descemet membrane endothelial keratoplasty (DMEK). Methods: DMEK recipients used prednisolone acetate 1% for 1 month, and they were randomized to either prednisolone or fluorometholone for months 2 through 12. Dosing was 4 times daily in months 1 to 3, thrice daily in month 4, twice daily in month 5, and once daily in months 6 to 12. The main outcomes were immunologic rejection episodes and intraocular pressure (IOP) elevation (defined as ≥24 mm Hg or ≥10 mm Hg increase over the preoperative baseline level), assessed by the Kaplan–Meier survival analysis. Results: The study included 325 eyes (99% were white, 96% had Fuchs dystrophy, and 9% had a previous glaucoma diagnosis). No eyes (0%) assigned to prednisolone versus 2 eyes (1.4%) assigned to fluorometholone experienced a possible (n = 1) or probable (n = 1) rejection episode (P = 0.17). Both rejection episodes resolved successfully with increased topical steroids. In the prednisolone arm, a significantly higher proportion exceeded the defined IOP elevation threshold (22% vs. 6%, P = 0.0005), and glaucoma medications were initiated or increased more often (17% vs. 5%, P = 0.0003). The most frequent reasons for discontinuing the assigned intervention were IOP management (n = 13 eyes assigned to prednisolone) or inflammation management (n = 3 eyes assigned to fluorometholone). One-year endothelial cell loss was comparable in both arms (30% vs. 31%, P = 0.50). Conclusions: DMEK has a remarkably low rejection episode rate (<1% through 1 year), as confirmed in this prospective randomized study. This provides a unique opportunity to reduce postoperative topical corticosteroid strength and thereby reduce the risk of steroid-associated complications.

Optimizing outcomes with Descemet's membrane endothelial keratoplasty.

Purpose of review To review recent advances in posterior lamellar keratoplasty and to describe strategies that enhance the outcome of Descemets membrane endothelial keratoplasty (DMEK) and should lead to a more widespread use of this technique. Recent findings DMEK offers significant advantages over Descemets stripping automated endothelial keratoplasty (DSAEK) such as less immune reaction and better visual acuity because of less higher order aberrations. Donor selection should exclude donors under 50 years because of tissue elasticity; several advanced techniques now allow donor preparation from both cold and organ-cultured tissue in about 99% minimizing the risk of graft loss. Oversizing the area of Descemets stripping in relationship to graft size enhances graft attachment and use of a standardized approach for graft delivery. Air bubble-driven nontouch unfolding techniques and, possibly, gas tamponade in the anterior chamber further enhance graft attachment and reduce surgery-induced endothelial cell loss. Graft orientation is made earlier by marking, slit beam and optical coherence tomography. Novel understanding of the functional anatomy of Descemets membrane as well as migration of endothelial cells will allow to further refine DMEK and improve its outcome. Summary Although the superiority of DMEK over Descemets stripping automated endothelial keratoplasty in terms of safety and functionality had been further elucidated, remarkable progress has been made in the recent past regarding tissue preparation, insertion and intraoperative manipulation that will foster the more widespread use of DMEK among corneal surgeons.

Ultrastructure of the Posterior Corneal Stroma

PURPOSE To reinvestigate the ultrastructure of the posterior stroma of the human cornea and to correlate the findings with the stromal behavior after big-bubble creation. DESIGN Observational consecutive 3-center case series. SPECIMENS Fresh corneoscleral buttons from human donors (n = 19) and organ-cultured corneoscleral buttons (n = 10) obtained after Descemets membrane endothelial keratoplasty. METHODS Corneal specimens were divided into central (3 mm), mid peripheral (8 mm), and peripheral parts by trephination and processed for transmission electron microscopic and immunohistochemical analyses. A big bubble was created by air injection into the stroma of organ-cultured corneas before fixation. MAIN OUTCOME MEASURES The distance of keratocytes to Descemets membrane, number of collagen lamellae between keratocytes and Descemets membrane, diameter and arrangement of collagen fibrils, thickness of stromal lamella created by air injection, and immunopositivity for collagen types III, IV, and VI. RESULTS Stromal keratocytes were observed at variable distances from Descemets membrane, increasing from 1.5 to 12 μm (mean, 4.97±2.19 μm) in the central, 3.5 to 14 μm (mean, 8.03±2.47 μm) in the midperipheral, and 4.5 to 18 μm (mean, 9.77±2.90 μm) in the peripheral regions. The differences in mean distances were significant (P < 0.0001). The number of collagen lamellae between Descemets membrane and most posterior keratocytes varied from 2 to 10 and the diameter of collagen fibrils averaged 23.5±1.8 nm and corresponded with that of the remaining stroma. A thin layer (0.5-1.0 μm thick) of randomly arranged, unaligned collagen fibers, which was positive for collagen types III and VI, was observed at the Descemet-stroma interface. The residual stromal sheet separated by air injection in 8 of 10 donor corneas varied in thickness from 4.5 to 27.5 μm, even within individual corneas (≤3-fold), and was composed of 5 to 11 collagen lamellae that revealed keratocytes on their anterior surface and in between. CONCLUSIONS Barring an anchoring zone of interwoven collagen fibers at the Descemet-stroma interface, the findings did not provide any evidence for the existence of a distinctive acellular pre-Descemets stromal layer in the human cornea. The intrastromal cleavage plane after pneumodissection seems to be nonreproducibly determined by the intraindividually and interindividually variable distances of keratocytes to Descemets membrane.

Involvement of ZEB1 and Snail1 in excessive production of extracellular matrix in Fuchs endothelial corneal dystrophy

Fuchs endothelial corneal dystrophy (FECD) due to corneal endothelial cell degeneration is a major cause of corneal transplantation. It is characterized by abnormal deposition of extracellular matrix (ECM), such as corneal guttae, accompanied by a loss of endothelial cells. Although recent studies have revealed several genomic factors, the molecular pathophysiology of FECD has not yet been revealed. In this study, we establish a cellular in vitro model by using immortalized corneal endothelial cells obtained from late-onset FECD and control patients and examined the involvement of epithelial mesenchymal transition (EMT) on excessive ECM production. We demonstrate that the EMT-inducing genes ZEB1 and SNAI1 were highly expressed in corneal endothelial cells in FECD and were involved in excessive production of ECM proteins, such as type I collagen and fibronectin through the transforming growth factor (TGF)-β signaling pathway. Furthermore, we found that SB431542, a specific inhibitor of TGF-β type I ALK receptors, suppressed the expression of ZEB1 and Snail1 followed by reduced production of ECM. These findings suggest that increased expression levels of ZEB1 and Snail1 in FECD cells were responsible for an increased responsiveness to TGF-β present in the aqueous humor and excessive production of ECM. In addition, these results suggest that the regulation of EMT-related genes by blocking the TGF-β signaling pathway may be a feasible therapeutic strategy for FECD.

Clinical and ultrastructural characteristics of graft failure in DMEK: 1-year results after repeat DMEK.

Purpose: To evaluate the role of preexisting corneal pathology on the outcome of Descemet membrane endothelial keratoplasty (DMEK), and also to evaluate the long-term outcome of repeat DMEK for graft failure after primary DMEK. Methods: Eighteen patients undergoing repeat DMEK after failed DMEK were enrolled; 9 of 18 patients had successful primary DMEK on the fellow eye. Evaluations included preoperative anterior chamber depth, intraoperative degree of difficulty, transmission electron microscopy images (n = 14), best-corrected visual acuity (BCVA), endothelial cell density, central corneal thickness, corneal volume, and patient satisfaction. Results: Surgeries that led to graft failure had a higher intraoperative degree of difficulty compared with successful surgeries (P = 0.002). Eight of 14 failed grafts showed ultrastructural abnormalities, that is, inclusions or deposits of abnormal fibrillar material in Descemet membrane, indicating endothelial dysfunction before transplantation. BCVA on day 10 after surgery was worse in eyes with graft failure compared with successful DMEK (P = 0.008). Median BCVA (logarithm of the minimum angle of resolution) improved from 0.5 before DMEK and 1.9 before repeat DMEK to 0.3 at 1-year follow-up (P = 0.011). One year after repeat DMEK, endothelial cell density (cells/mm2) of donor corneas decreased from 2501 ± 264 to 1373 ± 270 (P < 0.001), central corneal thickness (µm) decreased from 807 ± 160 to 576 ± 178 (P = 0.002), and corneal volume (mm3) decreased from 84.1 ± 13.0 to 64.4 ± 12.5 (P = 0.002). Patient satisfaction showed no difference between primary and repeat DMEK. Conclusions: A preexisting subclinical corneal endothelial dysfunction may contribute to primary DMEK failure. Repeat DMEK can be performed safely with good long-term outcome.

Use of accidentally torn descemet membrane to successfully complete descemet membrane endothelial keratoplasty.

Purpose: To describe the use of an accidentally torn Descemet membrane (DM) to successfully complete Descemet membrane endothelial keratoplasty (DMEK) surgery. Methods: Retrospective, observational case series of 3 eyes of 3 patients undergoing DMEK with a DM accidentally torn into 2 pieces during graft preparation. The mean outcome measures included best-corrected visual acuity, endothelial cell density, and central corneal thickness, before and at 1, 3, and 6 months after the DMEK surgery was performed. Results: During graft preparation, immediately before transplantation, a large tear within the 8.0-mm marking line of the DM occurred, resulting in a DM torn into 2 pieces. In all the eyes, both pieces were successfully implanted into the anterior chamber, unfolded and attached to the posterior corneal stroma, one after the other. Six months after the surgery was performed, the best-corrected visual acuity ranged between 20/30 and 20/25. Endothelial cell loss was about 30% (range 28%–32%) 6 months after the surgery. Pachymetry findings showed normal corneal thickness 6 months after the surgery. All corneas remained clear without any signs of graft failure within 6 months of follow-up. Conclusions: DMEK surgery can be successfully completed despite the accidental tearing of donor DMs during the preparation of DMEK grafts by the sequential implantation of both DM pieces.

Feasibility and Outcome of Descemet Membrane Endothelial Keratoplasty in Complex Anterior Segment and Vitreous Disease.

Purpose: Descemet membrane endothelial keratoplasty (DMEK) is becoming the method of choice for treating Fuchs endothelial dystrophy and pseudophakic bullous keratopathy. We investigated whether DMEK can serve as a routine procedure in endothelial decompensation even in complex preoperative situations. Methods: Of a total of 1184 DMEK surgeries, 24 consecutive eyes with endothelial decompensation and complex preoperative situations were retrospectively analyzed and divided into 5 groups: group 1: irido-corneo-endothelial syndrome (n = 3), group 2: aphakia, subluxated posterior chamber intraocular lens or anterior chamber intraocular lens (n = 6), group 3: DMEK after trabeculectomy (n = 4), group 4: DMEK with simultaneous intravitreal injection (n = 6), and group 5: DMEK after vitrectomy (n = 5). Main outcome parameters were best-corrected visual acuity, central corneal thickness, endothelial cell density, rebubbling rate, and graft failure rate. Results: Best-corrected visual acuity (logMAR) increased from 0.98 to 0.53 (P = 0.002), 0.53 (P = 0.091), and 0.57 (P = 0.203) after 1, 3, and 6 months, respectively. Central corneal thickness decreased from 731 ± 170 to 546 ± 152 &mgr;m (P = 0.001), 514 ± 66 &mgr;m (P = 0.932), and 554 ± 98 &mgr;m (P = 0.004) after 1, 3, and 6 months, respectively. Donor endothelial cell density decreased from 2478 ± 185 to 1454 ± 193/mm2 (P < 0.001), 1301 ± 298/mm2 (P = 0.241), and 1374 ± 261/mm2 (P = 0.213), after 1, 3, and 6 months, respectively. The rebubbling rate was 46% (11/24). Four patients (17%) had secondary graft failure. Conclusions: Our data provide evidence that DMEK is feasible for the treatment of endothelial decompensation in complex preoperative situations.

Anterior Chamber Air Bubble to Achieve Graft Attachment After DMEK: Is Bigger Always Better?

Purpose: To analyze the influence of the size of the air bubble subsequent to Descemet membrane endothelial keratoplasty (DMEK) surgery on the rate of graft detachment and need for rebubbling, the incidence of pupillary block, and the observed endothelial cell loss. Methods: This is a single-center, retrospective, consecutive case series of 74 cases undergoing DMEK and fulfilling the inclusion criteria concerning the size of the air bubble at the end of surgery. Based on the medical records, patients were divided into 2 groups (n = 37, respectively). The first group had an air bubble with a volume of approximately 50% and the second group of approximately 80% of the anterior chamber (AC) volume, respectively. Patients who did not comply with instructions to remain in the supine position until complete resorption of AC air or cases in which difficulties in graft preparation (eg, radial breaks) occurred were excluded from data analysis. The central corneal thickness and endothelial cell density were measured 6 months after surgery. Results: Ten of 37 patients (27.0%) in the 50% air bubble group and 3 of 37 patients (8.1%) in the 80% air bubble group needed 1 rebubbling procedure (P = 0.032). There was no difference between the groups after 6 months regarding endothelial cell density and central corneal thickness. No pupillary block was observed. Conclusions: Larger air bubbles of 80% anterior chamber volume decrease the risk of graft detachment after DMEK with no detrimental effect on the outcome and risk for pupillary block.