Bjoern O. Bachmann

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.

Corneal Higher-Order Aberrations after Descemet's Membrane Endothelial Keratoplasty

PURPOSE We compared corneal higher-order aberrations (HOAs) in eyes after Descemets membrane endothelial keratoplasty (DMEK), Descemets stripping automated endothelial keratoplasty (DSAEK), and penetrating keratoplasty (PK), and in a control group that had not undergone surgery. DESIGN Retrospective analysis of clinical data. PARTICIPANTS Thirty eyes of 30 patients who had undergone standard DMEK, 20 eyes of 20 patients after DSAEK, 20 eyes of 20 patients after PK, and 20 eyes of 20 controls were analyzed. METHODS In addition to standard postoperative examinations, each participant was analyzed with the Pentacam high-resolution rotating Scheimpflug imaging system (Pentacam HR, Oculus, Wetzlar, Germany). Data were compared between groups. MAIN OUTCOME MEASURES Visual acuity and HOAs. RESULTS The mean follow-up was 6.5 ± 1.2 months after DMEK, 22.6 ± 11.8 months after DSAEK, and 103.1 ± 74.2 months after PK. There were no statistically significant differences for the anterior 4.0-mm zones between the DMEK group and the controls or between the DMEK and DSAEK groups. The DMEK procedure compared with PK showed statistically significant differences in all terms for the 4.0-mm zones. All combined Zernike terms for mean posterior aberrations of the central 4.0-mm zones showed statistically significant higher aberrations for DMEK compared with controls. The DMEK procedure compared with DSAEK showed statistically significant lower mean values for all combined Zernike terms, except for coma and coma-like terms in the central 4.0-mm zones of the posterior corneal surface. Compared with PK, DMEK showed statistically significant lower mean values for all combined Zernike terms for the central 4.0-mm zones of the posterior corneal surface, except for spherical aberration (SA) and SA-like terms. Best spectacle-corrected visual acuity (BSCVA) after DMEK was statistically significantly better than after DSAEK (P=0.001) and PK (P=0.005). There was no statistically significant difference when BSCVA was compared with controls (P=0.998). CONCLUSIONS Both DSAEK and PK exhibit increased posterior corneal HOAs even years after surgery. Patients receiving DMEK display only slight changes in posterior corneal HOAs.

Promotion of Graft Survival by Vascular Endothelial Growth Factor A Neutralization After High-Risk Corneal Transplantation

OBJECTIVE To evaluate whether hemangiogenesis, lymphangiogenesis, and concomitant invasion of mononuclear phagocytes occurring after high-risk corneal transplantation in already vascularized high-risk recipient corneal beds increase the risk for subsequent immune rejection. METHODS Three intrastromal sutures were left in place for 6 weeks in the corneas of BALB/c mice, causing neovascularization. Three weeks after suture removal, keratoplasty was performed (donors C57BL/6 mice). The treatment group received a vascular endothelial growth factor A (VEGF-A)-neutralizing cytokine trap at 0, 4, 7, and 14 days postoperatively (Fc protein was used as the control treatment). Morphometry was performed in corneal flat mounts using lymphatic endothelial hyaluronan receptor-1 (a specific lymphatic endothelial marker), CD31 (a panendothelial marker), and F4/80 (a marker for mononuclear phagocytes). RESULTS After corneal transplantation, significant additional hemangiogenesis (mean area covered by vessels [SD], 68% [18%] postoperatively vs 40% [18%] preoperatively; P = .03) and lymphangiogenesis (12% [1.3%] postoperatively vs 9% [2.8%] preoperatively; P = .03) were observed. Postoperative neutralization of VEGF-A inhibited operation-induced hemangiogenesis (35% [8%]; P = .007) and lymphangiogenesis (6% [1.6%]; P = .03) and decreased the recruitment of mononuclear phagocytes into the graft (mean [SD], 501 cells/mm(2) [152] in treated mice vs 684 cells/mm(2) [35] in Fc controls; P = .03). After 8 weeks, 23% of the treated corneas were not rejected, whereas all control corneas were rejected after 21 days (P = .007). CONCLUSIONS Neutralization of VEGF-A after high-risk corneal transplantation effectively inhibits postoperative hemangiogenesis, lymphangiogenesis, and recruitment of antigen-presenting cells and improves corneal graft survival. CLINICAL RELEVANCE Blocking of VEGF-A after high-risk corneal transplantation may be a novel approach to improve graft survival.

Descemet Membrane Endothelial Keratoplasty Combined With Phacoemulsification and Intraocular Lens Implantation: Advanced Triple Procedure

PURPOSE To evaluate the functional and morphologic outcome of Descemet membrane endothelial keratoplasty (DMEK) combined with phacoemulsification and intraocular lens implantation in patients suffering from endothelial dysfunction and cataract. DESIGN Retrospective, single-center, consecutive case series. METHODS Triple-DMEK (DMEK with simultaneous cataract surgery) was performed in 61 consecutive eyes of 56 patients using corneal donor tissue pre-stored in either short-term culture (Optisol-GS) at 4 C or organ culture (Dulbeccos modified Eagles medium, CorneaMax medium) at 34 C. Main outcome measures included the number of air injections necessary for graft attachment as well as best-corrected visual acuity (BCVA [logMAR]), central corneal thickness (CCT), endothelial cell density (ECD), refractive spherical equivalent, refractive cylinder, and topographic cylinder at 1, 3, and 6 months postoperatively. RESULTS BCVA increased from 0.6 ± 0.23 logMAR preoperatively (n = 54) to 0.19 ± 0.22 logMAR at 6 months (n = 27) after surgery (P ≤ .05). ECD of donor corneas decreased from 2573 ± 235 cells/mm(2) (n = 61) to 1550 ± 326 cells/mm(2) (n = 29) after 6 months (P ≤ .05). CCT decreased from 651 ± 69 μm (n = 54) preoperatively to 521 ± 65 μm (n = 27) after 6 months (P ≤ .05). Refractive spherical equivalent was -0.3 ± 2.8 D (n = 27) preoperatively and 0.9 ± 1.5 D 6 months (n = 27) after surgery. A total of 54.5% of eyes were within 1 D of emmetropia (n = 12) and 77.3% were within 2 D of emmetropia (n = 17) 6 months (n = 22) after surgery. Refractive cylinder was -0.9 ± 1.0 D preoperatively (n = 49) and -1.5 ± 1.0 D 6 months (n = 23) after surgery. The change in refractive cylinder within the first month was statistically significant (P ≤ .05; Wilcoxon test). Topographic cylinder was 2.1 ± 1.7 D preoperatively (n = 58) and 1.7 ± 1.1 D 6 months (n = 28) after surgery. Between 3 and 6 months a significant change in topographic cylinder towards lower values was measured (P ≤ 0.05; Wilcoxon test). Optimized spherical results were achieved by selecting intraocular lenses based on a hyperopic shift of -0.75 D. CONCLUSION DMEK combined with cataract surgery (triple procedure) can routinely be performed in cases of endothelial dystrophy and cataract. The addition of cataract surgery to DMEK had no adverse effect on endothelial function or graft adhesion and did not increase the likelihood of postoperative complications.

A Method to Confirm Correct Orientation of Descemet Membrane During Descemet Membrane Endothelial Keratoplasty

PURPOSE Descemet membrane endothelial keratoplasty is a new technique for the replacement of diseased corneal endothelium with healthy donor endothelium. During this procedure, manipulation of the donor endothelium-Descemet membrane layer within the recipient anterior chamber can be associated with loss of the correct anterior-posterior orientation. Herein, we describe a simple method to keep the correct donor orientation during transplantation by marking the edge of the endothelium-Descemet membrane layer. DESIGN Interventional case series. METHODS Donor discs were created by stripping of the endothelium-Descemet membrane layer from corneoscleral buttons. Before completion of stripping, 3 circular marks were set in an identifiable order at the edge of the donor disc. After removal of the recipient Descemet membrane, the donor graft was inserted into the anterior chamber, unfolded, and attached to the posterior corneal stroma with an air bubble. Correct anterior-posterior orientation of the graft was identified by the clockwise order of the 3 marks. RESULTS The marks allowed identification of the anterior-posterior orientation of the endothelium-Descemet membrane layer after unfolding in the anterior chamber and attachment to the recipient stroma in all cases. In 4 of 25 patients, orientation was upside down after unfolding of the roll, requiring inversion of the refolded donor graft. CONCLUSIONS Marking the edges of the endothelium-Descemet membrane layer helps to keep the correct orientation without adverse effects on donor detachment or corneal clarity during and after Descemet membrane endothelial keratoplasty.

Donor Tissue Culture Conditions and Outcome after Descemet Membrane Endothelial Keratoplasty

PURPOSE To investigate the effect of culture conditions of donor tissue on functional outcome after Descemet membrane endothelial keratoplasty. DESIGN Retrospective, single-center, consecutive case series. METHODS Descemet membrane endothelial keratoplasty was performed routinely in 82 eyes of 82 consecutive patients using corneal donor tissue prestored in either short-term culture (Optisol-GS; Bausch & Lomb) at 4 C (group A; n = 37) or organ culture (Dulbecco Modified Eagle Medium [Biochrom]; CorneaMax Medium [Eurobio]) at 34 C (group B; n = 45) in a randomized fashion. Main outcome measures included the number of air injections necessary for graft attachment as well as best-corrected visual acuity (in logarithm of the minimal angle of resolution [logMAR] units), central corneal thickness, and endothelial cell density at 1, 3, and 6 months after surgery. RESULTS Best-corrected visual acuity increased from 0.69 ± 0.53 logMAR and 0.67 ± 0.31 logMAR before surgery to 0.33 ± 0.21 logMAR and 0.28 ± 0.18 logMAR after 1 month (P < .05), to 0.24 ± 0.16 logMAR and 0.18 ± 0.16 logMAR after 3 months (P < .05), and to 0.18 ± 0.12 logMAR and 0.15 ± 0.10 logMAR after 6 months (n.s.) in groups A and B, respectively. Endothelial cell density decreased from 2647 ± 236 cells/mm(2) and 2515 ± 249 cells/mm(2) before surgery to 1499 ± 277 cells/mm(2) and 1526 ± 205 cells/mm(2) after 1 month (P < .05), to 1441 ± 213 cells/mm(2) and 1443 ± 316 cells/mm(2) after 3 months (n.s.), and to 1587 ± 366 cells/mm(2) and 1457 ± 285 cells/mm(2) after 6 months (n.s.) in groups A and B, respectively. Central corneal thickness declined from 664 ± 89 and 662 ± 107 μm before surgery to 529 ± 92 μm and 517 ± 62 μm after 1 month (P < .05), to 511 ± 46 μm and 510 ± 46 μm after 3 months (P < .05), and to 529 ± 68 μm and 507 ± 50 μm after 6 months (n.s.) in groups A and B, respectively. Best-corrected visual acuity, endothelial cell density, and central corneal thickness values showed no significant differences between both groups at any time point after surgery. However, a significantly higher total number of air injections was necessary in group A (n = 34) compared with group B (n = 26) to obtain graft attachment (P < .05). CONCLUSIONS These findings suggest that donor tissue culture conditions have no significant effect on functional outcome, but may influence graft adhesion and rebubbling rate after Descemet membrane endothelial keratoplasty surgery.

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.

Transient postoperative vascular endothelial growth factor (VEGF)-neutralisation improves graft survival in corneas with partly regressed inflammatory neovascularisation

Background: High-risk keratoplasties are usually performed after an uninflamed and quiescent interval in corneas with partly regressed blood and lymphatic vessels. We analysed whether the inhibition of post-keratoplasty revascularisation in mice with partly regressed corneal vessels (“intermediate-risk”) improves graft survival. Methods: Three interrupted stromal sutures (11-0) in corneas of Balb/c mice (6–8 weeks old) were placed for 6 weeks. Six months after suture removal, penetrating keratoplasty was performed with C57BL/6 donors. The treatment group received a vascular endothelial growth factor-A specific cytokine trap (VEGF Trap) intraperitoneally at days 0, 4, 7 and 14 after keratoplasty (25 mg/kg per mouse; controls received equal amounts of Fc protein). Pathological haemangiogenesis and lymphangiogenesis prior to as well as 3 days or 8 weeks after keratoplasty and graft survival were analysed. Results: Three days after keratoplasty corneal revascularisation was sufficiently reduced by VEGF Trap (haem-vascularised areas 42.7% reduction; lymph-vascularised areas 54.7% reduction). Survival proportions 8 weeks after keratoplasty were 36% in the treatment group compared with 9% in the control group (n = 11; p<0.05). At that time no differences in haemangiogenesis or lymphangiogenesis were observed between the two groups. Conclusion: Early transient postoperative induction of haemangiogenesis and lymphangiogenesis and reformation of regressed corneal blood and lymphatic vessels are important for transplant rejections after “intermediate-risk” corneal transplantation.

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.

Pentacam-based big bubble deep anterior lamellar keratoplasty in patients with keratoconus.

Purpose: To describe the clinical results of Pentacam-based big bubble deep anterior lamellar keratoplasty (DALK) to achieve an intended 90% depth of initial lamellar trephination. Methods: Fifty consecutive eyes of 50 patients with keratoconus, keratoglobus, and anterior stromal scars were included. DALK was performed with the big bubble technique using a 90% intended depth for initial lamellar trephination based on preoperative pachymetry by Pentacam. Main outcome measures were success of surgery, best spectacle–corrected visual acuity, endothelial cell count, refractive astigmatism at 12-month follow-up, and rate of intra- and postoperative complications. Results: In 84% of the patients (n = 42), Pentacam-based big bubble DALK could be performed successfully. Successful big bubble formation could be achieved in 80% of the patients (n = 34). In case of macroperforation (n = 8), surgery was converted to standard penetrating keratoplasty representing a conversion rate of 16%. Intraoperative microperforation (n = 5) could be handled by an intracameral air injection at the end of operation with successful completion of the lamellar procedure. No allograft rejection was observed. Best spectacle–corrected visual acuity improved from 20/125 ± 20/160 preoperatively to 20/40 ± 20/80 at 12-month follow-up. Endothelial cell count was 2102 ± 318 cells per square millimeter preoperatively and 1735 ± 420 cells per square millimeter at 12-month follow-up. Refractive astigmatism was 7.09 ± 3.13 diopters preoperatively and decreased to 4.13 ± 2.41 diopters. Conclusion: Pentacam-based big bubble DALK using a 90% intended depth of initial lamellar trephination seems to be a safe and effective procedure for anterior corneal stromal disorders such as keratoconus. We suggest that Pentacam-based depth assessment allows for reliably deep initial preparation and may allow more successful bubble formation in DALK surgery.