Combined or sequential DMEK in cases of cataract and Fuchs endothelial corneal dystrophy-A systematic review and meta-analysis.

To compare the outcomes of Descemet membrane endothelial keratoplasty (DMEK) performed after phacoemulsification and intraocular lens (IOL) implantation (sequential DMEK) and DMEK combined with phacoemulsification and IOL implantation (combined DMEK) in patients with Fuchs endothelial corneal dystrophy (FECD) and cataract. Systematic literature review and meta-analysis performed according to the PRISMA guidelines and registered in PROSPERO. Literature searches were conducted in Medline and Scopus. Comparative studies reporting sequential DMEK and combined DMEK in FECD patients were included. The main outcome measure of the study was the corrected distance visual acuity (CDVA) improvement. Secondary outcomes were postoperative endothelial cell density (ECD), rebubbling rate and primary graft failure rate. Bias risk was assessed and a quality appraisal of the body of evidence was completed using the Cochrane Robin-I tool. A total of 667 eyes (5 studies) were included in this review, 292 eyes (43.77%) underwent a combined DMEK, while 375 (56.22%) eyes underwent a sequential DMEK surgery. We found no evidence of a difference between the two groups (mean difference, 95% CI) regarding: (1) CDVA improvement (-0.06; -0.14, 0.03 LogMAR; 3 studies, I2 : 0%; p = 0.86); (2) postoperative ECD (-62; -190, 67 cells/mm2 ; 4 studies, I2 : 67%; p = 0.35); (3) rebubbling (risks ratio: 1.04; 0.59, 1.85; 4 studies, I2 : 48%; p = 0.89); and primary graft failure rate (risks ratio: 0.91; 0.32, 2.57; 3 studies, I2 : 0%; p = 0.86). Of all the 5 non-randomized studies, all (100%) were graded as low quality. The overall quality of the analysed studies was low. Randomized controlled trials are needed to confirm no difference or superiority of one approach in terms of CDVA, endothelial cell count and postoperative complication rate between the two arms.

Impact of Early Intraocular Pressure Elevation on Postoperative Outcomes After Descemet Membrane Endothelial Keratoplasty in Non-glaucoma Patients.

PURPOSE: The purpose of this study was to investigate the impact of transient elevations in postoperative intraocular pressure (IOP) on the clinical outcome of Descemet membrane endothelial keratoplasty (DMEK) surgery in non-glaucoma patients. METHODS: Retrospective analysis from a prospective database of eyes without preexisting glaucoma that underwent DMEK with 90% anterior chamber and 20% sulfur hexafluoride endotamponade. Group A included eyes without postoperative IOP increase (IOP <30 mm Hg and a relative increase from preoperative value <10 mm Hg). Group B included eyes with IOP elevation (postoperative IOP ≥30 mm Hg or a relative increase from preoperative value ≥10 mm Hg) handled according to a standardized protocol. The impact of elevated IOP within 3 days after DMEK surgery was evaluated regarding best-corrected visual acuity (BCVA), central corneal thickness (CCT), and endothelial cell count (ECC) at 1, 3, and 6 months. RESULTS: One hundred seventy-six eyes from 164 patients were included. An IOP increase after DMEK occurred in 20 eyes (11.3%; 19 patients, group B), and the mean peak IOP was 48 ± 12 mm Hg (range 32-69 mm Hg). There were no significant postoperative differences in BCVA, CCT, and ECC on comparing both groups. The BCVA increased significantly (P < 0.001, respectively), whereas CCT (P < 0.001, respectively) and ECC (P < 0.001, respectively) decreased significantly from preoperative values. The rebubbling rate tended to be higher in group B without statistical significance (6.4% vs. 10%, P = 0.648). CONCLUSIONS: Temporary IOP elevation after DMEK may not affect functional and morphological outcomes in non-glaucoma patients. However, careful postoperative IOP monitoring and appropriate management are crucial to avoid irreversible ocular damage.

Epithelial downgrowth after Descemet membrane endothelial keratoplasty.

PURPOSE: To describe a patient with epithelial downgrowth after Descemet membrane endothelial keratoplasty. METHODS: Case report. RESULTS: A 73-year-old woman underwent triple Descemet stripping automated endothelial keratoplasty for cataract and corneal edema secondary to Fuchs endothelial dystrophy in the left eye elsewhere. Three years later, Descemet membrane endothelial keratoplasty was performed at our department due to graft failure. One month after the operation, her vision improved to 20/32 and maintained stable. At the 14-month visit, her visual acuity decreased, and a routine examination revealed epithelial downgrowth at the posterior surface of the cornea and partly beneath the graft, accompanied by presumed graft rejection. Therefore, repeat Descemet membrane endothelial keratoplasty with epithelial scraping and intracameral injection of 5-fluorouracil was indicated. She recovered 20/25 vision by 1 month after the surgery. However, small sheet-like epithelial downgrowth recurred 1 month later. The epithelial downgrowth was limited to the peripheral margin of the Descemet membrane endothelial keratoplasty graft and did not affect the visual axis. Epithelial downgrowth showed "islands" with connection between epithelial downgrowth and clear corneal incision on anterior segment optical coherence tomography images. Histopathologic evaluation of the removed Descemet membrane endothelial keratoplasty graft confirmed conjunctival epithelium as the source. Under close observation at the current 4-year follow-up, the epithelial downgrowth remained stable and localized and her vision increased to 20/20. CONCLUSION: Epithelial downgrowth can occur after Descemet membrane endothelial keratoplasty. The limited progression of epithelial downgrowth in this patient suggests that this condition after Descemet membrane endothelial keratoplasty even in the recurrence stage may cause less damage than expected and may only need to be observed closely if no progression occurs.

Immune reactions after modern lamellar (DALK, DSAEK, DMEK) versus conventional penetrating corneal transplantation.

In the past decade, novel lamellar keratoplasty techniques such as Deep Anterior Lamellar Keratoplasty (DALK) for anterior keratoplasty and Descemet stripping automated endothelial keratoplasty (DSAEK)/Descemet membrane endothelial keratoplasty (DMEK) for posterior keratoplasty have been developed. DALK eliminates the possibility of endothelial allograft rejection, which is the main reason for graft failure after penetrating keratoplasty (PK). Compared to PK, the risk of endothelial graft rejection is significantly reduced after DSAEK/DMEK. Thus, with modern lamellar techniques, the clinical problem of endothelial graft rejection seems to be nearly solved in the low-risk situation. However, even with lamellar grafts there are epithelial, subepithelial and stromal immune reactions in DALK and endothelial immune reactions in DSAEK/DMEK, and not all keratoplasties can be performed in a lamellar fashion. Therefore, endothelial graft rejection in PK is still highly relevant, especially in the "high-risk" setting, where the cornea's (lymph)angiogenic and immune privilege is lost due to severe inflammation and pathological neovascularization. For these eyes, currently available treatment options are still unsatisfactory. In this review, we will describe currently used keratoplasty techniques, namely PK, DALK, DSAEK, and DMEK. We will summarize their indications, provide surgical descriptions, and comment on their complications and outcomes. Furthermore, we will give an overview on corneal transplant immunology. A specific focus will be placed on endothelial graft rejection and we will report on its incidence, clinical presentation, and current/future treatment and prevention options. Finally, we will speculate how the field of keratoplasty and prevention of corneal allograft rejection will develop in the future.

Risk of Corneal Graft Rejection After High-risk Keratoplasty Following Fine-needle Vessel Coagulation of Corneal Neovascularization Combined With Bevacizumab: A Pilot Study.

BACKGROUND: Corneal neovascularization is considered an important risk factor for allograft rejection after corneal transplantation (keratoplasty). Therefore, the aim of this study was to determine whether preoperative reduction of corneal neovascularization by fine-needle thermal cauterization combined with bevacizumab reduces the incidence of allograft rejection after subsequent high-risk keratoplasty. METHODS: In this interventional uncontrolled clinical pilot study, 31 eyes of 31 patients with corneal neovascularization in at least one corneal quadrant were included. All eyes were treated by fine-needle thermal cauterization of corneal vessels and subconjunctival injection of bevacizumab. Both treatments were repeated in the cases of visible reperfusion of occluded vessels. Afterward, penetrating keratoplasty was performed. When corneal neovascularization was present on the day of keratoplasty, additional vessel cauterization and injection of bevacizumab was performed. Patients were then followed to determine the incidence of allograft rejection. RESULTS: In 18 eyes, vessel cauterization with bevacizumab injection was performed once before keratoplasty, whereas 13 eyes required retreatment before keratoplasty. No complications were observed. In 23 eyes, corneal neovascularization was present on the day of keratoplasty due to reperfusion of previously occluded vessels and simultaneous vessel cauterization with bevacizumab injection was performed. During follow-up (mean: 560 days; range: 59-1095 days), 4 graft rejection episodes in 4 eyes were observed. Estimated probabilities of corneal graft survival were 92.9% after 1 year (number at risk: 23), 78.4% after 2 years (number at risk: 9), and 78.4% after 3 years (number at risk: 3). CONCLUSIONS: Our initial results indicate that angioregressive treatment of pathological corneal vessels by fine-needle thermal cauterization combined with subconjunctival injection of bevacizumab before high-risk keratoplasty seems to result in graft survival rates comparable to survival rates seen in normal-risk keratoplasty. The findings of our pilot study warrant further controlled clinical trials with longer follow-up in a larger patient cohort.

Telemetric Intraocular Pressure Monitoring after Boston Keratoprosthesis Surgery Using the Eyemate-IO Sensor: Dynamics in the First Year.

PURPOSE: To analyze the dynamics of telemetrically measured intraocular pressure (IOP) during the first year after implantation of a Boston keratoprosthesis type I (BI-KPro) cornea and to compare agreement of telemetric IOP measurements with finger palpations. DESIGN: Prospective, open-label, multicenter, single-arm clinical trial. METHODS: In the ARGOS (NCT02945176) study, 12 individuals underwent implantation of an Eyemate-IO intraocular system. Follow-up after surgery took place 12 months later with 13 visits planned per patient. During BI-KPro surgery, an electromagnetic induction sensor ring enabling telemetric IOP data transfer to a hand-held reading device outside the eye was implanted into the ciliary sulcus with or without trans-scleral suture fixation. Comprehensive ophthalmic examinations and IOP assessments through the telemetric system were compared to IOP assessed by finger palpation by 2 experts. RESULTS: Preoperative IOP measured by Goldmann tonometry was 13.4 ± 6.2 mm Hg. Telemetric IOP peaked at 23.1 ± 16.5 mm Hg at the first postoperative day. On day 5, mean IOP was 16.0 ± 5.2 mm Hg and 20.95 ± 6.5 mm Hg after 6-12 months. IOP estimation by finger palpation was grouped in 4 categories: normal, A; soft/hypotonic, B; borderline, C; and hypertonic, D. Mean telemetric IOP was 18.2 ± 6.1 mm Hg in category A, 8.9 ± 2.8 mm Hg in B, 22.4 ± 4.9 mm Hg in C, and 34.3 ± 11.0 mm Hg in D. Differences in mean telemetric IOPs per category were statistically significant (P < .001). Daily IOP fluctuations and peaks could be identified. CONCLUSIONS: Telemetric IOP assessment seems to be able to identify postoperative IOP peaks and a longitudinal increase of IOP after BI-KPro surgery. IOP measurements using the telemetric Eyemate-IO sensor showed a satisfactory agreement with those of finger palpations by 2 experts.

Honeycomb-structured metasurfaces for the adaptive nesting of endothelial cells under hemodynamic loads.

The thrombogenicity of artificial materials comprising ventricular assist devices (VADs) limits their long-term integration in the human body. A living endothelium covering the luminal surface can provide a safe interface working compatibly with blood and circumventing this problem. However, the survival of endothelial cells is endangered by non-physiological hemodynamic conditions generated by VAD function, including high wall shear stress and deformation. Here, we introduce a surface topography comprising hexagonal honeycomb shelters in which cells remodel to generate coherently organized patterns of subcellular compartments. The resulting hexagonal array shows resistance to supraphysiological loads maintaining endothelium integrity and avoiding local discontinuities.

Intensified Early Postoperative Topical Steroids Do Not Influence Endothelial Cell Density After Descemet Membrane Endothelial Keratoplasty Combined With Cataract Surgery (Triple-DMEK).

PURPOSE: To investigate the effect of intensified postoperative topical steroid therapy after Descemet membrane endothelial keratoplasty combined with cataract surgery (Triple-DMEK) on postoperative endothelial cell density (ECD). METHODS: This comparative clinical study with historical controls was conducted at a tertiary hospital, specialized in corneal surgery. Patients undergoing DMEK or Triple-DMEK are included prospectively in the Cologne DMEK Database. Until April 2014, first week's postoperative standard therapy for lamellar keratoplasties was prednisolone acetate eye drops 1% applied 5× daily. After April 2014, first week's postoperative standard therapy changed to prednisolone acetate eye drops 1% applied hourly. We compared 75 consecutive eyes before (group 1) with 75 consecutive eyes after the change of therapy regimen (group 2). Patients received ECD analysis 3 and 6 months after surgery. RESULTS: ECD of grafts in group 1 before transplantation, and 3 months and 6 months after surgery was 2697 ± 218, 1765 ± 349, and 1703 ± 432 cells/mm, respectively. ECD of grafts in group 2 was 2696 ± 267, 1737 ± 450, and 1694 ± 482 cells/mm, respectively. Over 3 and 6 months, ECD in group 1 decreased by 35% ± 13% and 38% ± 18%, respectively. In group 2, ECD decreased by 36% ± 16% and 38% ± 16%, respectively. Neither absolute numbers nor decrease in ECD differed significantly between groups 1 and 2 at any time point (all P > 0.60). CONCLUSIONS: Intensified early postoperative topical steroid therapy during the first postoperative week does not stabilize ECD, nor does it have a toxic effect on endothelial cells during a follow-up of 6 months.

Immediate Postoperative Intraocular Pressure Changes After Anterior Chamber Air Fill in Descemet Membrane Endothelial Keratoplasty.

PURPOSE: To monitor the intraocular pressure (IOP) changes immediately after anterior chamber air tamponade in Descemet membrane endothelial keratoplasty (DMEK). METHODS: Twenty-four patients undergoing DMEK and 16 patients undergoing rebubbling after DMEK were enrolled (n = 40). All DMEK patients had inferior iridectomy and nearly full intracameral air tamponade with an aimed IOP of 25 mm Hg at the end of surgery. The IOP was measured at 1, 2, 3, 5, 12, 24 hours and 1 week postoperatively. RESULTS: After anterior chamber air fill in DMEK, the IOP increased from preoperative baseline, 12.1 ± 2.9 mm Hg, to 26.3 ± 4.7 mm Hg, P < 0.001. Mean IOP was significantly elevated in the first 2 hours, 19.4 ± 10.5 mm Hg and 17.0 ± 7.4 mm Hg, P = 0.007 and 0.006, respectively. Then, it lowered to the baseline level, 14.0 ± 4.7 mm Hg, P > 0.05, and remained stable during follow-ups. An asymptomatic IOP elevation above 30 mm Hg was detected in 3 patients (12.5%) within the first 2 hours. None had preexisting glaucoma. Most episodes could be controlled by antiglaucoma medications and upright positioning. The pattern of IOP changes after rebubbling was similar to that after DMEK but the IOP dropped sharply to the baseline level after 1 hour and had no incidence of IOP elevations beyond 30 mm Hg. CONCLUSIONS: Adequate inferior iridectomy greatly alleviates the risk and severity of acute IOP rises after nearly full anterior chamber air tamponade in DMEK. Standard IOP adjustment at the end of DMEK surgery with postoperative IOP monitoring especially in the first 2 postoperative hours is advisable when there is no postoperative default air release.

Intensified Topical Steroids as Prophylaxis for Macular Edema After Posterior Lamellar Keratoplasty Combined With Cataract Surgery.

PURPOSE: To analyze the effect of intensified topical steroid therapy after Descemet membrane endothelial keratoplasty combined with cataract surgery (triple-DMEK) on the incidence of postoperative cystoid macular edema (CME). DESIGN: Single-center comparative clinical study with historical controls. SETTING: Department of Ophthalmology, University of Cologne, Germany, tertiary hospital, performing 500 corneal transplant surgeries per year. PATIENTS: Total of 131 patients (150 eyes) undergoing triple-DMEK surgery. Inclusion Criterion: Triple-DMEK surgery. EXCLUSION CRITERIA: Prior retinal surgery, history of prior CME. INTERVENTIONS: Prednisolone acetate eye drops 1% 5 times daily for the first week after surgery. After an internal change of therapy regimen: Prednisolone acetate eye drops 1% hourly for the first postoperative week. We compared 75 consecutive eyes before with 75 consecutive eyes after the change of therapy regimen. Patients received macular spectral-domain optical coherence tomography (SD OCT) preoperatively, as well as 6 weeks and 3 and 6 months post surgery. MAIN OUTCOME MEASURE: Development of CME detected by macular SD OCT during 6 months postoperatively. RESULTS: Both groups were comparable regarding baseline age, sex, central corneal thickness, rebubbling rate, and visual acuity. With topical steroid therapy 5 times per day during the first postoperative week, we observed 9 cases of subsequent CME (12%). With hourly topical steroid therapy none of the patients developed CME subsequently (P = .003). Apart from the topical steroids during the first week, medical treatment was identical in both groups. CONCLUSIONS: Early intensified postoperative topical steroid therapy constitutes an effective prophylactic treatment to reduce incidence of CME after triple-DMEK surgery.

Larger Descemetorhexis to Improve Graft Adhesion in Descemet Membrane Endothelial Keratoplasty Does Not Cause Postoperative Peripheral Corneal Edema.

PURPOSE: To evaluate the incidence of peripheral corneal edema after Descemet membrane endothelial keratoplasty (DMEK) with respect to the size of the descemetorhexis. METHODS: A single-center retrospective review of data of 200 consecutive DMEK surgeries for Fuchs endothelial dystrophy was performed. Forty-eight eyes of 47 patients were enrolled in this study based on the presence of a peripheral zone of free denuded stroma between the margin of the graft and the host's Descemet membrane (DM) (group A) or a peripheral overlap between the graft and the host's DM (group B). In group A (n=26 eyes), the diameter of the descemetorhexis was approximately 10 mm, whereas in group B (n=22 eyes), the diameter was approximately 6 mm. Both groups received an 8-mm graft. Main outcome measures included peripheral corneal thickness (PCT) at 4 mm from the center, central corneal thickness (CCT), central-to-peripheral thickness ratio (CPTR), and endothelial cell density (ECD). RESULTS: Mean preoperative PCT±SD in group A was 728±52 µm and in group B was 708±49 µm (P=0.192). Four weeks after DMEK, mean PCT±SD was 703±43 µm in group A and 691±59 µm in group B (P=0.368). Mean preoperative CCT±SD was 642±53 µm and 627±58 µm in groups A and B, respectively (P=0.306). There was no significant difference in CCT between groups A and B 4 weeks after surgery (P=0.268). Mean preoperative CPTR±SD in group A was 0.88±0.05 and in group B was 0.89±0.05 (P=0.934). Four weeks after DMEK, CPTR was not significantly different between groups A and B (P=0.893). There was no significant difference in ECD between groups A and B, before and at 4 weeks after DMEK (P=0.093 and P=0.831, respectively). CONCLUSIONS: A larger descemetorhexis in DMEK resulting in a peripheral small zone of denuded stroma does not increase the incidence of peripheral corneal edema as compared with a small descemetorhexis with overlapping DMs.

Brittle Cornea Syndrome: Case Report with Novel Mutation in the PRDM5 Gene and Review of the Literature.

A 3-year-old boy presented with acute corneal hydrops on the left eye and spontaneous corneal rupture on the right eye. A diagnosis of brittle cornea syndrome was confirmed by molecular analysis. A novel mutation, the homozygous variant c.17T>G, p.V6G, was found in the gene for PR-domain-containing protein 5 (PRDM5) in exon 1. Brittle cornea syndrome is a rare connective tissue disease with typical ocular, auditory, musculoskeletal, and cutaneous disorders. Almost all patients suffer from declined vision due to corneal scarring, thinning, and rupture. The most common ophthalmologic findings include keratoconus, progressive central corneal thinning, high myopia, irregular astigmatism, retinal detachment, and high risk for spontaneous corneal or scleral rupture. In addition to describing the case with a novel mutation here we review the current literature on brittle cornea syndrome pathogenesis, clinical findings, and therapy.

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 Descemet's 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 Descemet's membrane, number of collagen lamellae between keratocytes and Descemet's 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 Descemet's 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 Descemet's 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-Descemet's 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 Descemet's membrane.

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.

Extracellular matrix alterations in late-onset Fuchs' corneal dystrophy.

PURPOSE: To characterize the alterations of extracellular matrix proteins in Descemet's membranes (DM) of patients with late-onset Fuchs' corneal dystrophy (FCD) and to differentiate them from nonspecific alterations in pseudophakic bullous keratopathy (PBK). METHODS: Human DM-endothelial cell complexes were obtained from patients with late-onset FCD (n = 40), PBK (n = 6), and control eyes (n = 5). Gene expression profiles of endothelial cells were compared using a commercial real-time PCR array and quantitative real-time PCR assays for confirmation of differentially expressed genes. A total of 24 extracellular matrix proteins were also localized in cryosections of corneal specimens from FCD (n = 10), PBK (n = 4), and control eyes (n = 5) by immunohistochemistry. RESULTS: Polymerase chain reaction array analysis revealed a significant upregulation of 27 out of 84 extracellular matrix-related genes including collagens, proteoglycans, glycoproteins, cell adhesion molecules, and matrix metalloproteinases in FCD specimens as compared to normal controls, which could be partly confirmed and quantified by real-time PCR. Comparative analysis of FCD and PBK specimens showed a significant and consistent FCD-specific upregulation of collagen types I, III, and XVI; fibronectin; agrin; clusterin; transforming growth factor beta-induced (TGFBI); and integrin α4 (3- to 18-fold, P < 0.05). Immunohistochemistry revealed an increased labeling of collagen (types III, VII, XV, XVI), agrin, fibulin-2, TGFBI, versican, and clusterin in the DM of FCD specimens compared to PBK specimens. CONCLUSIONS: The findings provide evidence for a specific upregulation, production, and deposition of collagen types III and XVI, agrin, TGFBI, and clusterin in late-onset FCD and thus point to the importance of matrix alterations in the pathophysiology of FCD.

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 host's 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 host's Descemet membrane. MAIN OUTCOMES AND MEASURES: Graft detachment rate, extent of graft detachment (in clock hours of graft's 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.

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.

Reproducibility of graft preparations in Descemet's membrane endothelial keratoplasty.

PURPOSE: To assess the reproducibility of manual graft preparation and evaluate the incidence rate and nature of structural anomalies of Descemet's membrane (DM) preventing successful graft preparation in DM endothelial keratoplasty (DMEK). DESIGN: Prospective, single-center, nonrandomized, consecutive case series. PARTICIPANTS: We analyzed 350 corneoscleral buttons from donors aged 18-95 years stored in Optisol-GS or Dulbecco's modified Eagle's medium and used for DMEK surgery in 343 consecutive patients with Fuchs' endothelial dystrophy or pseudophakic bullous keratopathy. METHODS: Residual endothelial cell-DM complexes obtained after successful DM stripping for DMEK and whole donor corneas obtained after unsuccessful DM stripping were examined by transmission electron microscopy and immunohistochemistry. MAIN OUTCOME MEASURES: Accuracy of the cleavage plane between DM and corneal stroma and structural abnormalities of the DM-stroma interface. RESULTS: Uneventful manual separation without any disruption of DM was achieved in 335 of 350 donor corneas (95.7%) by use of a previously established bimanual submerged preparation technique. Correspondingly, the peeled DM specimens revealed a regular and smooth cleavage plane exposing the amorphous interfacial matrix on their anterior surface. Although 8 of 350 donor corneas (2.3%) showed focal adhesions of DM to the corneal stroma and developed isolated tears during stripping, preparation of the graft could be successfully completed. However, 7 of the 350 donor corneas (2.0%) showed extremely strong adhesion and multiple tears of DM, preventing successful preparation of the graft. These specimens revealed either ultrastructural (peg-like interlockings) or biochemical abnormalities (increased staining intensities for adhesive glycoproteins) along the DM-stroma interface. CONCLUSIONS: Using an appropriate technique, manual preparation of grafts for DMEK with reproducible tissue qualities is possible in the vast majority (98%) of donor corneas. Although a relatively rare phenomenon, interindividual variations in DM structure and composition may be responsible for failure of graft preparation in about 2% of donor corneas. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any of the materials discussed in this article.