Bjoern O Bachmann

University of Cologne, Köln, North Rhine-Westphalia, Germany

Are you Bjoern O Bachmann?

Claim your profile

Publications (50)155.15 Total impact

  • F Schaub · D Hos · F Bucher · S Siebelmann · B O Bachmann · C Cursiefen
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Corneal transplantation in high-risk eyes remains a challenge. The Boston keratoprosthesis (B-KPro) is a final option for patients with end-stage corneal disease and a poor prognosis with conventional penetrating keratoplasty. In this article the results of the first 13 eyes that received a B-KPro type I at the Department of Ophthalmology, University of Cologne, Germany are reported and the usefulness of postoperative slit-lamp optical coherence tomography (SL-OCT) for control purposes is evaluated. Material and methods: All recipients of a B-KPro type I between September 2013 and May 2015 were included in the study. The feasibility of the operation, clinical outcomes, complications and revision surgery were investigated. The visualization of wound healing by SL-OCT was analyzed. Results: The age of the patients ranged from 26 to 92 years (mean 57.3 ± 20.9 years). In all 13 eyes from 12 patients (6 males and 6 females) dense corneal opacification with vascularization and sometimes also conjunctivalization was present. Preoperative visual acuity was reduced and ranged from mere light perception up to a maximum of 1/35 eye chart. All 13 eyes could be supplied with a B-KPro type I without any intraoperative complications, in 6 eyes no significant postoperative complications occurred, whereas in 7 eyes various additional surgical interventions were required and 1 B-KPro could not be preserved. Postoperative visual acuity ranged from light perception to 20/32 and was significantly improved in 85 % of the treated eyes. The use of SL-OCT reproducibly allowed the postoperative assessment of stromal thinning. Conclusion: The B-KPro provides the possibility of visual rehabilitation in high-risk eyes that could never be achieved without artificial cornea replacement. Despite higher complication rates this technique represents a significant progress in the surgical treatment of complex corneal pathologies. Regular and intensive postoperative controls are necessary to achieve good long-term results.
    No preview · Article · Jan 2016 · Der Ophthalmologe
  • [Show abstract] [Hide abstract]
    ABSTRACT: Boston keratoprosthesis (KPro) type I is a technique to treat patients with corneal diseases that are not amenable to conventional keratoplasty. Correct assembly and central implantation of the prosthesis are crucial for postoperative visual recovery. This study investigates the potential benefit of intraoperative optical coherence tomography (OCT) to monitor KPro surgery. Retrospective case series are presented for two patients who underwent Boston KPro type I implantation. The surgery in both patients was monitored intraoperatively using a commercially available intraoperative OCT (iOCT) device mounted on a surgical microscope. Microscope-integrated intraoperative OCT was able to evaluate the correct assembly and implantation of the KPro. All parts of the prosthesis were visible, and interfaces between the corneal graft and titanium backplate or anterior optics were clearly depictable. Moreover, iOCT visualized a gap between the backplate and graft in one case, and in the other case, a gap between the anterior optic and graft. Neither gap was visible with a conventional surgical microscope. The gap between the anterior optic and the graft could easily be corrected. Microscope-integrated iOCT delivers enhanced information, adding to the normal surgical microscope view during KPro surgery. Correct assembly can be controlled as well as the correct placement of the Boston KPro into the anterior chamber.
    No preview · Article · Jan 2016 · Journal of Biomedical Optics
  • Source
    D Hos · J Dörrie · N Schaft · F Bock · M Notara · F.E. Kruse · S Krautwald · C Cursiefen · B.O. Bachmann
    [Show abstract] [Hide abstract]
    ABSTRACT: The chemokine receptor CCR7 is essential for migration of mature dendritic cells (DCs) to the regional lymph nodes, and it has been shown that blocking of CCR7 improves graft survival after high-risk corneal transplantation in vascularized recipient corneas. However, it is so far unknown whether blocking of CCR7 reduces migration of DCs from the avascular cornea to the draining lymph nodes and whether this leads to improved graft survival also in the low-risk setting of corneal transplantation, which accounts for the majority of transplantations performed and which still has a graft rejection rate of 25 % within 6 years. Therefore, in this study, pellets containing Freund's adjuvants and bovine serum albumin (BSA) conjugated to Alexa488 fluorescent dye were implanted into the corneal stroma of BALB/c mice to analyze antigen uptake by corneal DCs and their migration to the regional lymph nodes. After pellet implantation, mice were either treated by local administration of a CCR7 blocking fusion protein that consisted of CCL19 fused to the Fc part of human IgG1 or a control-IgG. In vivo fluorescence microscopy showed uptake of Alexa488-conjugated BSA by corneal DCs within 8 hours. Furthermore, analysis of single cell suspensions of draining lymph nodes prepared after 48 hours revealed that 2.1 + 0.3 % of CD11c(+) cells were also Alexa488(+). Importantly, DC migration was significantly reduced after topical administration of CCL19-IgG (1.2 + 0.2 %; p<0.05). To test the effect of CCR7 blockade on graft rejection after allogeneic low-risk keratoplasty, corneal transplantations were performed using C57BL/6-mice as donors and BALB/c-mice as recipients. Treatment mice received two intraperitoneal loading doses of CCL19-IgG prior to transplantation, followed by local treatment with CCL19-IgG containing eye drops for the first two weeks after transplantation. Control mice received same amounts of control-IgG. Kaplan-Meier survival analysis showed that in the CCL19-IgG treated group, 76 % of the grafts survived through the end of the 8 week observation period, whereas 38 % of the grafts survived in the control group (p<0.05). Taken together, our study shows blockade of CCR7 reduces the migration of mature corneal DCs to the draining lymph nodes and leads to improved graft survival in low-risk corneal transplantation.
    Full-text · Article · Dec 2015 · Experimental Eye Research
  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose: To analyze the effect of intensified topical steroid therapy after Descemet's 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. Methods: Setting: Department of Ophthalmology, University of Cologne, Germany, tertiary hospital, performing 500 corneal transplant surgeries per year. Patients: 150 eyes of 131 patients 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, 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, gender, 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=0.003). Apart from the topical steroids during 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.
    No preview · Article · Dec 2015 · American Journal of Ophthalmology
  • [Show abstract] [Hide abstract]
    ABSTRACT: 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.
    No preview · Article · Nov 2015 · Cornea
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: 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.
    Full-text · Article · Jul 2015

  • No preview · Article · Jul 2015 · Ophthalmology
  • F Schaub · H G Simons · S Roters · L M Heindl · W Kugler · B O Bachmann · C Cursiefen
    [Show abstract] [Hide abstract]
    ABSTRACT: In posterior lamellar keratoplasties, such as Descemet membrane endothelial keratoplasty (DMEK) and Descemet's stripping automated endothelial keratoplasty (DSAEK) an air bubble is left inside the anterior chamber to promote graft attachment during the early postoperative period. In the case of insufficient graft adhesion a renewed intracameral air injection is often necessary. The use of sulfur hexafluoride diluted with air (SF6 20 %) as an alternative to pure air may further enhance graft attachment and reduce the rebubbling rate. The effect of SF6 20 % on corneal endothelium is currently unclear and was therefore examined in vitro. For this study 12 human corneoscleral discs were mounted in artificial anterior chambers, the systems were continuously filled with culture medium and the anterior chambers with air (n = 5) or SF6 20 % (n = 7) as tamponade. After 6 days of storage in the incubator endothelial cell density, toxicity on endothelial cells and corneal thickness were evaluated. There were no significant differences in endothelial cell loss (p = 1.000), endothelial cell count (p = 0.648), toxicity on endothelial cells (p = 0.048) and central corneal thickness (p = 0.905) between the two groups after 1 week. The level of significance was defined as p ≤ 0.05 and adjusted to p ≤ 0.0056 according to the Bonferroni correction for multiple testing. The use of SF6 20 % as tamponade in the anterior chamber for posterior lamellar keratoplasty can be proposed as a safe alternative to pure air filling related to endothelial cell loss. Increased toxic effects on the corneal endothelium by SF6 20 % were not detected in this study; however, further prospective clinical trials are needed to examine the long-term effects in humans.
    No preview · Article · May 2015 · Der Ophthalmologe
  • [Show abstract] [Hide abstract]
    ABSTRACT: The present study aimed to analyze the expression of epithelial-mesenchymal transition (EMT)-related cytokines in the aqueous humor of phakic and pseudophakic Fuchs' endothelial corneal dystrophy (FECD) eyes and their correlation to FECD severity. Aqueous humor samples from phakic FECD eyes (FECDph, n = 9), from pseudophakic FECD eyes more than 1 year after cataract surgery (FECDpsph, n = 13), and from cataract controls without FECD (Controlcat, n = 28) were obtained during Descemet membrane endothelial keratoplasty (DMEK) or cataract surgery. Expression of EMT-related cytokines (TGF-β1, TGF-β2, TGF-β3, MCP-1, BFGF, TNF-α, IL-1β) was measured using multiplex bead assay. Corneal central-to-peripheral thickness ratio at 3.5 mm from the center (CPTR3.5) was determined as an objective metric for FECD severity before surgery by slit-scanning pachymetry. Pseudophakic FECD eyes showed significantly elevated expression compared with Controlcat and FECDph eyes for TGF-β1 (P < 0.001, respectively), for TGF-β2 (P < 0.05, respectively), and MCP-1 (P < 0.001, respectively). Levels of TGF-β1 (r = 0.6116, P < 0.05) and MCP-1 (r = 0.5934, P < 0.05) were positively correlated with CPTR3.5. No differences in EMT-associated protein levels were detected comparing FECDph eyes and Controlcat eyes. Simultaneous elevation of TGF-β1, TGF-β2, and MCP-1 concentrations in FECDpsph eyes confirms that cataract surgery leads to long-term alterations of the intraocular microenvironment. Positive correlation of increased aqueous TGF-β1 and MCP-1 levels with CPTR3.5 in pseudophakic FECD eyes suggests that changed cytokine levels may be involved in corneal decompensation after cataract surgery. Unchanged aqueous humor levels of EMT-related proteins analyzed in phakic FECD patients indicate that there is no primary role of these aqueous cytokines in FECD pathogenesis.
    No preview · Article · Apr 2015 · Investigative ophthalmology & visual science
  • [Show abstract] [Hide abstract]
    ABSTRACT: To investigate the outcome of Descemet membrane endothelial keratoplasty (DMEK) in patients with graft failure after Descemet stripping automated endothelial keratoplasty (DSAEK). Retrospective cohort study METHODS: Setting: Institutional Study population: 15 eyes of 15 patients which underwent DMEK for graft failure with corneal decompensation following DSAEK were analyzed. 15 eyes with primary DMEK for Fuchs corneal dystrophy were included as control group. Best corrected visual acuity (BCVA), endothelial cell density (ECD), central corneal thickness (CCT), and rebubbling rate. DMEK surgery was successful in all cases of both groups. Mean BCVA (logMAR) before DMEK was 1.27 ± 0.34 in the DMEK after DSAEK group and 1.0 ± 0.40 in the Primary DMEK group. After DMEK, mean BCVA increased significantly to 0.23 ± 0.21 (p=0.012, DMEK after DSAEK group) and 0.29 ± 0.23 (p=0.042, Primary DMEK group) after three months. There were no significant differences in mean BCVA between both groups at each visit. The rebubbling rate was 13% in the DMEK after DSAEK group and 40% in the Primary DMEK group (p=0.1). Mean CCT decreased significantly in both groups one month after DMEK (p<0.05). Mean ECD and change of ECD did not differ significantly between both groups at each visit (p>0.05). The results after DMEK as a procedure to treat graft failure after DSAEK were as good as in patients that underwent DMEK as primary intervention to treat advanced Fuchs dystrophy. This indicates that the optical quality can be re-established by DMEK in patients with failed DSAEK. Copyright © 2015 Elsevier Inc. All rights reserved.
    No preview · Article · Mar 2015 · American Journal of Ophthalmology
  • [Show abstract] [Hide abstract]
    ABSTRACT: To evaluate the incidence of peripheral corneal edema after Descemet membrane endothelial keratoplasty (DMEK) with respect to the size of the descemetorhexis. 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). 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). 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.
    No preview · Article · Feb 2015 · Eye & Contact Lens Science & Clinical Practice
  • [Show abstract] [Hide abstract]
    ABSTRACT: 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. Observational consecutive 3-center case series. Fresh corneoscleral buttons from human donors (n = 19) and organ-cultured corneoscleral buttons (n = 10) obtained after Descemet's membrane endothelial keratoplasty. 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. 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. 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. 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. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
    No preview · Article · Nov 2014 · Ophthalmology

  • No preview · Article · Nov 2014 · Cornea
  • [Show abstract] [Hide abstract]
    ABSTRACT: 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.
    No preview · Article · May 2014 · Investigative ophthalmology & visual science
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Eye drops of aganirsen, an antisense oligonucleotide preventing insulin receptor substrate-1 expression, inhibited corneal neovascularization in a previous dose-finding phase II study. We aimed to confirm these results in a phase III study and investigated a potential clinical benefit on visual acuity (VA), quality of life (QoL), and need for transplantation. Multicenter, double-masked, randomized, placebo-controlled phase III study. Analysis of 69 patients with keratitis-related progressive corneal neovascularization randomized to aganirsen (34 patients) or placebo (35 patients). Patients applied aganirsen eye drops (86 μg/day/eye) or placebo twice daily for 90 days and were followed up to day 180. The primary end point was VA. Secondary end points included area of pathologic corneal neovascularization, need for transplantation, risk of graft rejection, and QoL. Although no significant differences in VA scores between groups were observed, aganirsen significantly reduced the relative corneal neovascularization area after 90 days by 26.20% (P = 0.014). This improvement persisted after 180 days (26.67%, P = 0.012). Aganirsen tended to lower the transplantation need in the intent-to-treat (ITT) population at day 180 (P = 0.087). In patients with viral keratitis and central neovascularization, a significant reduction in transplantation need was achieved (P = 0.048). No significant differences between groups were observed in the risk of graft rejection. However, aganirsen tended to decrease this risk in patients with traumatic/viral keratitis (P = 0.162) at day 90. The QoL analyses revealed a significant improvement with aganirsen in composite and near activity subscores (P = 0.039 and 0.026, respectively) at day 90 in the per protocol population. Ocular and treatment-related treatment-emergent adverse events (TEAEs) were reported in a lower percentage with aganirsen compared with placebo. Only 3 serious TEAEs (2 with aganirsen and 1 with placebo) were considered treatment-related. This first phase III study on a topical inhibitor of corneal angiogenesis showed that aganirsen eye drops significantly inhibited corneal neovascularization in patients with keratitis. The need for transplantation was significantly reduced in patients with viral keratitis and central neovascularization. Topical application of aganirsen was safe and well tolerated.
    Full-text · Article · May 2014 · Ophthalmology
  • [Show abstract] [Hide abstract]
    ABSTRACT: No standardized biomaterial exists for the surgical treatment of persistent corneal erosions and ulcerations. We analyzed the suitability and biocompatibility of defined non-crosslinked and UV/riboflavin crosslinked equine type I collagen membranes for the reconstruction of the corneal surface. Isolated human oral mucosa epithelial cells, a cell type in clinical use for the treatment of ocular surface diseases, were subcultivated on both types of membranes and examined concerning cell adhesion, proliferation and differentiation. Biocompatibility was evaluated following superficial and intrastromal corneal transplantation in New Zealand white rabbits. In cell cultures all collagen membranes supported adhesion of oral mucosa epithelial cells leading to the formation of multilayered epithelial cell sheets. After intrastromal corneal implantation clinical signs of degradation were seen in all variants of collagen membranes, which was fastest in non-crosslinked variants. On the histological and ultrastructural level invasion of keratocytes and production of new collagen fibers inside the collagen membranes could be detected in non-crosslinked variants. After superficial corneal implantation covering of the membranes by corneal epithelium over time was visible. Ultrastructural analysis showed a slower rate of degradation and less invading keratocytes in crosslinked variants compared to non-crosslinked collagen membranes. Crosslinked as well as non-crosslinked variants of the collagen membrane proofed to be suitable to serve as a carrier for epithelial stem cells in-vitro and showed a high biocompatibility in-vivo. These results indicate that the tested collagen membranes might be suitable for the reconstruction of the corneal surface in patients with non-healing ulcerations. Whether membranes with faster or slower degradation properties are preferable for the treatment of persistent corneal ulcerations might depend on the underlying corneal pathology and the degree of concomitant inflammation.
    No preview · Article · Mar 2014 · Tissue Engineering Part A
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective Eye drops of aganirsen, an antisense oligonucleotide preventing insulin receptor substrate-1 expression, inhibited corneal neovascularization in a previous dose-finding phase II study. We aimed to confirm these results in a phase III study and investigated a potential clinical benefit on visual acuity (VA), quality of life (QoL), and need for transplantation. Design Multicenter, double-masked, randomized, placebo-controlled phase III study. Participants Analysis of 69 patients with keratitis-related progressive corneal neovascularization randomized to aganirsen (34 patients) or placebo (35 patients). Patients applied aganirsen eye drops (86 μg/day/eye) or placebo twice daily for 90 days and were followed up to day 180. Main Outcome Measures The primary end point was VA. Secondary end points included area of pathologic corneal neovascularization, need for transplantation, risk of graft rejection, and QoL. Results Although no significant differences in VA scores between groups were observed, aganirsen significantly reduced the relative corneal neovascularization area after 90 days by 26.20% (P = 0.014). This improvement persisted after 180 days (26.67%, P = 0.012). Aganirsen tended to lower the transplantation need in the intent-to-treat (ITT) population at day 180 (P = 0.087). In patients with viral keratitis and central neovascularization, a significant reduction in transplantation need was achieved (P = 0.048). No significant differences between groups were observed in the risk of graft rejection. However, aganirsen tended to decrease this risk in patients with traumatic/viral keratitis (P = 0.162) at day 90. The QoL analyses revealed a significant improvement with aganirsen in composite and near activity subscores (P = 0.039 and 0.026, respectively) at day 90 in the per protocol population. Ocular and treatment-related treatment-emergent adverse events (TEAEs) were reported in a lower percentage with aganirsen compared with placebo. Only 3 serious TEAEs (2 with aganirsen and 1 with placebo) were considered treatment-related. Conclusions This first phase III study on a topical inhibitor of corneal angiogenesis showed that aganirsen eye drops significantly inhibited corneal neovascularization in patients with keratitis. The need for transplantation was significantly reduced in patients with viral keratitis and central neovascularization. Topical application of aganirsen was safe and well tolerated.
    Full-text · Article · Jan 2014 · Ophthalmology
  • [Show abstract] [Hide abstract]
    ABSTRACT: 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.
    No preview · Article · Dec 2013 · Jama Ophthalmology
  • [Show abstract] [Hide abstract]
    ABSTRACT: To describe the use of an accidentally torn Descemet membrane (DM) to successfully complete Descemet membrane endothelial keratoplasty (DMEK) surgery. 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. 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. 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.
    No preview · Article · Sep 2013 · Cornea
  • [Show abstract] [Hide abstract]
    ABSTRACT: 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). Prospective, single-center, nonrandomized, consecutive case series. 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. 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. Accuracy of the cleavage plane between DM and corneal stroma and structural abnormalities of the DM-stroma interface. 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. 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. The authors have no proprietary or commercial interest in any of the materials discussed in this article.
    No preview · Article · Jul 2013 · Ophthalmology

Publication Stats

1k Citations
155.15 Total Impact Points

Institutions

  • 2015-2016
    • University of Cologne
      • Department of Ophthalmology
      Köln, North Rhine-Westphalia, Germany
  • 2007-2015
    • Friedrich-Alexander Universität Erlangen-Nürnberg
      • • Department of Ophthalmology
      • • Department of Anatomy
      Erlangen, Bavaria, Germany
  • 2008-2014
    • Universitätsklinikum Erlangen
      • Department of Ophthalmology
      Erlangen, Bavaria, Germany
  • 2009
    • University of California, Berkeley
      Berkeley, California, United States