Claus Cursiefen

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

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Publications (284)641.58 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Fuchs endothelial corneal dystrophy (FECD) is a genetically heterogeneous disease. Hypothesizing that cellular senescence may be relevant in FECD pathogenesis, genetically undifferentiated late-onset FECD endothelial samples were analyzed to identify common changes of specific senescence-related transcripts. Total RNA was extracted from 21 FECD endothelial samples retrieved from patients undergoing lamellar keratoplasty due to clinically diagnosed end-stage FECD and from 12 endothelial samples retrieved from normal autopsy eyes. Taqman low density array (TLDA) cards were used to analyze differential expression of 89 cellular senescence-related transcripts. Result validation was performed using individual real-time PCR assays. TLDA-analysis demonstrated differential expression of 31 transcripts (fold-change >1.5; p<0.05). Thereof, 27 showed significant up-regulation and 4 significant down-regulation. Markedly elevated mRNA-levels of the constitutively active and reactive oxygen species-generating enzyme NOX4 were found in all evaluable FECD samples. In addition, increased expression of CDKN2A and its transcriptional activators ETS1 and ARHGAP18 (SENEX) along with decreased expression of CDKN2A inhibitor ID1 were detected in FECD samples. Consistent over-expression of NOX4 in FECD endothelial samples suggests a role as pathogenic factor and as a potential new treatment target in FECD. Transcriptional up-regulation of the CDKN2A-pathway provides further evidence for increased cellular senescence in FECD endothelium.
    Experimental Eye Research 10/2014; · 3.03 Impact Factor
  • C Cursiefen
    Der Ophthalmologe : Zeitschrift der Deutschen Ophthalmologischen Gesellschaft. 10/2014;
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    ABSTRACT: To evaluate the potential of lowering intraocular pressure in pseudoexfoliation glaucoma with combined phacoemulsification, Trabectome, and trabecular aspiration (triple procedure) compared to phacoemulsification and trabecular aspiration alone.
    Albrecht von Graæes Archiv für Ophthalmologie 09/2014; · 1.93 Impact Factor
  • Der Ophthalmologe : Zeitschrift der Deutschen Ophthalmologischen Gesellschaft. 09/2014;
  • Cornea 07/2014; · 1.75 Impact Factor
  • Deniz Hos, Claus Cursiefen
    The Journal of pediatrics. 07/2014;
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    ABSTRACT: The adult sclera is free of lymphatic vessels, but contains a net of blood vessels. Whether and when this selectively lymphangiogenic privilege is achieved during embryologic development is not known yet. Therefore, we investigated the developing human sclera for blood- and lymphatic vessels in 34 abortions/stillborns (12-38 weeks of gestation). The probes were subdivided into three groups (group 1: 12-18 weeks of gestation, n=10; group 2: 19-23 weeks of gestation, n=13; group 3: 24-38 weeks of gestation, n=11), and prepared for paraffin sections followed by immunohistochemistry against CD31 to detect blood vessels, and against lymphatic vessel endothelial hyaluronan receptor-1 (LYVE1)/podoplanin to detect lymphatic vessels. We could show, that in the human episclera distinct CD31+ blood vessels are present as early as week of gestation 13. Their amount increased during pregnancy, whereas stromal CD31+ blood vessels were elevated in early pregnancy and regressed with ongoing pregnancy. In the lamina fusca CD31+ blood vessels were absent at any time point investigated. Single LYVE1+ cells were identified primarily in the episclera; their amount decreased significantly with increasing gestational ages (group 1 compared to group 3: p<0.01). However, LYVE1+/podoplanin+ lymphatic vessels were not detectable in the sclera at any gestational ages analyzed. In contrast to the conjunctiva where LYVE1+ /podoplanin+ lymphatic vessels were detectable as early as week 17, the amount of LYVE1+ cells in the sclera was highest in early pregnancy (group 1), with a significant decrease during continuing pregnancy (p<0.001). These findings are the first evidence for a fetal lymphangiogenic privilege of the sclera and show, that the fetal human sclera contains CD31+ blood vessels, but is primarily alymphatic. Our findings suggest a strong expression of selectively antilymphangiogenic factors, making the developing sclera a potential model to discern antilymphangiogenic mechanisms.
    Experimental Eye Research 06/2014; · 3.03 Impact Factor
  • C Ammermann, C Cursiefen, M Hermann
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    ABSTRACT: Background: Corneal cross-linking (CXL) with riboflavin is being used more frequently for the treatment of therapy-resistant microbial keratitis, since increasing drug resistance and specific pathogens, e.g. contact lens-associated Acanthamoeba, make this therapy appear as an attractive option to avoid a keratoplasty à chaud. Patients and Methods: This retrospective case series of 11 consecutive patients (4 women, 7 men, aged 24-82 years) who received standardised antimicrobial CXL for therapy-resistant keratitis to avoid a keratoplasty à chaud, included 4 cases with detection of bacterial pathogens, one case with proven fungal infection and 6 cases without pathogen detection. Analysed data comprised ophthalmic medical history, general risk factors for microbial keratitis, treatment before and after CXL. The characterisation of the corneal ulcer included photometric measurements of the infiltrates with a median of 16.2 mm² and four unmeasurable cases due to extended, not circumscribed lesions. Results: Within the follow-up period (mean 134 ± standard deviation 82 days), a penetrating keratoplasty was successfully avoided in 6 patients (55 %). After CXL 9 patients (82 %) received additionally amniotic membrane transplantation. After CXL treatment, topical antibiotic therapy was continued for a mean 27 ± 13 days postoperatively. Steroids were applied in 91 % of the patients. The cornea cleared at least to some extent in 9 patients (82 %). Patients with neurotrophic keratopathy or potentially compromised immune system showed no increased failure rate. Conclusion: These results suggest that antimicrobial CXL might be a useful option in patients with therapy-resistant corneal ulcer in order to avoid a perforating keratoplasty à chaud. For a comprehensive scientific assessment of this therapy, however, further, ideally prospective randomised interventional studies with large sample sizes are needed.
    Klinische Monatsblatter fur Augenheilkunde. 06/2014; 231(6):619-625.
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    ABSTRACT: To analyze potential alterations in corneal nerve morphology and function in different stages of Fuchs' endothelial corneal dystrophy (FECD).
    05/2014;
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    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.
    Ophthalmology 05/2014; · 5.56 Impact Factor
  • U Gehlsen, C Cursiefen, P Steven
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    ABSTRACT: Background: Ocular allergy belongs to the most common ocular diseases globally. Following clinical phenotype and immunopathogenesis different forms of allergy are distinguished, which require different forms of therapeutic approach. This manuscript reviews the basic immunological processes involved in the development of ocular allergies and current and future therapeutic approaches. Methods: Results of a literature search in PubMed and our own clinical and experimental experience are presented. Results: In the immunopathogenesis of ocular allergy different immune cells such as dendritic cells, B-cells, T-cells, mast cells, eosinophils and regulatory T-cells are involved. Therapeutic approaches focus on either relief of symptoms using antihistamins or mast cell stabilisers or combinations of both. In severe cases steroids or calcineurin inhibitors are used. Discussion: Despite great progress in the investigation of ocular allergy in the past decade several open questions remain, such as the relation of ocular allergy with dry eye disease. Future therapeutic approaches will likely be based on recently identified new aspects such as lymphangiogenesis and will allow better and potentially causal treatment of ocular allergy.
    Klinische Monatsblätter für Augenheilkunde 05/2014; 231(5):490-5. · 0.70 Impact Factor
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    ABSTRACT: The VEGF-A family plays a crucial role in the induction of pathological corneal neovascularization. The role of the different VEGF-A isoforms during lymphangiogenesis is only little-known. Current anti-angiogenic therapies in the eye and other organs inhibit all VEGF-A isoforms, and have effects on both blood and lymphatic vessels. Here we investigate whether selective targeting of the isoform VEGF 165 is able to inhibit corneal lymphangiogenesis under inflammatory conditions. The mouse model of suture-induced corneal neovascularization was used to assess the antihem- and antilymphangiogenic effect of topically applied pegaptanib. Corneal blood and lymph vascularized areas were analyzed morphometrically. Furthermore, we analyzed the proliferative effects of VEGF A 121, 165, and 189 on blood and lymphatic endothelial cells (BEC/LEC) via a cell-proliferation assay. Pegaptanib significantly inhibited inflammatory corneal hemangiogenesis (p < 0.01), but not lymphangiogenesis in vivo (p > 0.05), both topically as well as systemically, in the inflamed cornea. In vitro, BECs were more susceptible to pegaptanib than LECs. Targeting VEGF-A 165 significantly inhibits hem- but not lymphangiogenesis, suggesting VEGF-A 165 to be critical for hem-, but dispensable for lymphangiogenesis, at least in the inflamed cornea.
    Albrecht von Graæes Archiv für Ophthalmologie 04/2014; · 1.93 Impact Factor
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    ABSTRACT: Purpose: Tumor-derived vascular endothelial growth factor A (VEGF-A), apart from expediting sufficient vascularization, subsequent tumor growth and metastatic spread, can act on malignant cells themselves provided that VEGF receptors 1 or 2 (VEGF-R1, -R2) are co-expressed. The study goal was to investigate whether such autocrine VEGF-A signaling exists in uveal melanoma (UM). Methods: Primary (MEL-270, OM-431) and metastatic (OMM-2.3, OMM-2.5) UM cells were analyzed for VEGF-A, VEGF-R1, and VEGF-R2 expression by RT-PCR, ELISA (VEGF-A protein) and immuno¬cytochemistry (VEGF receptors). Proliferation of UM cells incubated with neutralizing anti-VEGF-A antibody bevacizumab (≤ 2.5 mg/ml), or VEGF-A (≤ 100 ng/ml) was assessed by BrdU ELISA. It was measured by real-time PCR, whether VEGF-A (100 ng/ml) modulated the expression ratio of VEGF-A itself and its antiangiogenic antagonist pigment epithelium-derived factor (PEDF). Results: All UM cells expressed VEGF-A, VEGF-R1, VEGF-R2 mRNA and protein. In each cell line, the proliferation was stimulated by VEGF-A or inhibited by blocking VEGF-A, or both: Bevacizumab significantly decreased the proliferation in MEL-270 (p=0.005), OMM-2.3 (p=0.001), and OMM-2.5 (p=0.011). Increased VEGF-A signaling significantly raised the proliferation in MEL-270, OM-431 (p<0.001, respectively), and OMM-2.3 (p=0.043) in a dose-dependent manner, but did not significantly change the VEGF-A/PEDF mRNA expression ratio. Conclusions: Autocrine VEGF-A signaling seems to be present in UM sustaining the proliferation of both primary and metastatic UM cells. Apparently, VEGF-A signaling in UM cells does neither retroact on VEGF-A expression in the sense of a feedback loop, nor contribute to an proangiogenic shift of the VEGF-A/PEDF ratio.
    Investigative ophthalmology & visual science 03/2014; · 3.43 Impact Factor
  • Der Ophthalmologe 03/2014; · 0.53 Impact Factor
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    ABSTRACT: To describe the use of intraoperative online optical coherence tomography (iOCT) for improving deep anterior lamellar keratoplasty (DALK) surgery. Retrospective case series of 6 eyes of 6 male patients with keratokonus, corneal dystrophy or herpetic stromal scars undergoing DALK were investigated using intraoperative optical coherence tomography and postsurgical image/video analysis. Main outcome measures were: visibility of surgical steps, especially, assessment of placement depth of injection needle, preparation of bare Descemet's membrane and drainage of interface fluid. iOCT enables real-time visualisation of all surgical steps of DALK procedure in all patients. Placement of air injection needle above Descemet's membrane was reliably monitored as was presence of bare Descemet's membrane and potential interface fluid. iOCT assists with visualisation of injection needle placement and with assessment of bare Descemet's membrane as well as interface fluid during the DALK procedure. Overall iOCT may be a helpful device that supports surgeons in all steps of DALK procedure.
    The British journal of ophthalmology 03/2014; · 2.92 Impact Factor
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    ABSTRACT: Abstract Thrombospondins are a family of large multi-domain glycoproteins described as matricelluar proteins based on their ability to interact with a broad range of receptors, matrix molecules, growth factors or proteases, and to modulate array of cellular functions including intracellular signaling, proliferation and migration. Two members of the thrombospondin family, thrombospondin 1 (TSP-1) and thrombospondin 2 (TSP-2) are studied extensively to determine their structure and function. While expressed at low levels in normal adult tissues, their increased expression is seen predominantly in response to cellular perturbations. Despite structural similarities, a notable functional difference between TSP-1 and TSP-2 includes the ability of former to activate of latent TGF-β and its competitive inhibition by the latter. Both these thrombospondins are reported to play important roles in TGF-β rich ocular environment with most reports related to TSP-1. They are expressed by many ocular cell types and detectable in the aqueous and vitreous humor. TSP-1 and TSP-2 influence many cellular interactions in the eye such as angiogenesis, cell migration, wound healing, TGF-β activation and regulation of inflammatory immune responses. Together, these processes are known to contribute to the immune privilege status of the eye. Emerging roles of TSP-1 and TSP-2 in ocular functions and pathology are reviewed here.
    Current eye research 02/2014; · 1.51 Impact Factor
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    ABSTRACT: The migratory capacity of donor corneal endothelial cells after Descemet membrane endothelial keratoplasty (DMEK) is not fully understood. We report 2 patients who developed immune reactions after DMEK with endothelial precipitates detectable not only on the grafts but also on host corneal areas stripped off the host Descemet membrane during surgery and initially not covered by the donor Descemet membrane and endothelium ("naked stroma"), strongly suggesting that migration of donor-derived endothelial cells had occurred. Observational case series of 2 patients. A 71-year-old man (case 1) and an 84-year-old man (case 2) with Fuchs endothelial dystrophy underwent successful DMEK surgery. Postoperatively, the peripheral corneal stroma showed a denuded area that was not covered by the DMEK graft or by the patients' residual Descemet membrane (because of large descemetorhexis and slight graft decentration). After 18 (case 1) and 6 (case 2) months, a diffuse endothelial immune reaction with precipitates on the graft and, surprisingly, also on peripheral corneal areas that were initially denuded of the host Descemet membrane and not covered by the donor Descemet membrane was observed. The outermost corneal parts covered by the patients' own residual Descemet membrane showed no precipitates. Under treatment with topical corticosteroids, the precipitates rapidly disappeared. Visual acuity, central corneal thickness, and endothelial cell counts were not significantly affected. The immune reaction episodes in our patients with endothelial precipitates detectable on adjacent host areas initially stripped off and not covered by donor Descemet membrane provide direct in vivo evidence of donor corneal endothelial cell migration after DMEK, filling areas of "naked stroma."
    Cornea 01/2014; · 1.75 Impact Factor
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    ABSTRACT: To analyze the incidence and spectrum of ocular disease in patients with metastatic cutaneous melanoma. One hundred and eight consecutive patients with metastatic cutaneous melanoma were screened for ocular diseases using standardized eye examination, including measurement of visual acuity and intraocular pressure, slit-lamp examination, funduscopy in mydriasis, and spectral-domain optical coherence tomography (SDOCT) of the retina. Selected cases with atypical findings underwent electrophysiological studies. One patient was examined for hypercortisolism by a dexamethasone suppression test. Ocular diseases were found in 65 out of 108 patients (60 %) with metastatic cutaneous melanoma, significantly more often in older patients (p = 0.004). Cataract was present in 27 patients (25 %), pseudophakia in 22 patients (20 %), macular disease in 29 patients (28 %), diabetic retinopathy in ten patients (9 %), hypertensive retinal disease in 14 patients (13 %), retinal venous and arterial occlusive disease in three patients (3 %), optic neuropathy in four patients (4 %), and uveitis in one patient (1 %). Eight patients (8 %) had choroidal or iridal nevi, one patient (1 %) choroidal hemangioma, and one patient (1 %) choroidal metastasis. No patient had periocular neoplastic lesions. Paraneoplastic retinopathy manifesting as acute exudative polymorphous vitelliform maculopathy (AEPVM)-like disease was diagnosed in two patients (2 %) with multifocal central serous chorioretinopathy and development of vitelliform or fibrin-like subretinal deposits in one patient. Patients with metastatic cutaneous melanoma reveal ocular diseases with a spectrum similar to the normal population of this age range. Very rarely, uveal metastasis as well as paraneoplastic retinopathy can occur.
    Albrecht von Graæes Archiv für Ophthalmologie 01/2014; · 1.93 Impact Factor
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    ABSTRACT: Purpose: To investigate whether the normal adult human sclera contains lymphatic vessels and to study their relation to immune cells and blood vessel anatomy. Methods: Scleral tissue probes from 35 adult human donor bulbi were analyzed by immunohistochemistry and confocal microscopy for blood vessels (CD31+), lymphatic vessels (LYVE1+, podoplanin+), and macrophages (CD68+) at twelve locations (anterior, equatorial and posterior at 3, 6, 9 and 12 o'clock position of the eye) in all three scleral layers (episclera, stroma and lamina fusca). Approval for scientific examination was obtained. Results: CD31+ blood vessels were detectable in the human sclera, where the percentage area covered by CD31+ blood vessels is highest in the anterior episclera, followed by equatorial and posterior episclera and is lowest in the scleral stroma(regardless of location). LYVE1+ podoplanin+ lymphatic vessels were not detectable in any location investigated, although there was a high number of LYVE1+ CD68+ macrophages. These macrophages were concentrated around blood vessels. Whereas in the episclera the amount of detected LYVE1+ CD68+ macrophages is comparable in all locations, within the stroma their number increases towards the posterior part of the eye. Conclusions: The adult sclera contains blood vessels, but lacks, as revealed by immunohistochemistry and confocal microscopy true lymphatic vessels. LYVE1+ CD68+ macrophages are located adjacent to the longitudinal axis of blood vessels. The function of these cells needs further investigation, but could be a next step in a better understanding of pathological disorders, such as inflammation, tumor, trauma or glaucoma.
    Investigative ophthalmology & visual science 01/2014; · 3.43 Impact Factor
  • F Bucher, Y Bi, U Gehlsen, D Hos, C Cursiefen, F Bock
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    ABSTRACT: Corneal (lymph) angiogenesis is a predominant risk-factor for immune rejection after transplantation. Techniques to regress pre-existing pathological corneal lymphatic vessels prior to transplantation are missing so far. Therefore we analysed the possibility to regress corneal lymphatic vessels by photodynamic therapy (PDT), after intrastromal verteporfin injection. Combined hemangiogenesis and lymphangiogenesis was induced in female BALB/c mice using the murine model of suture-induced inflammatory neovascularisation. Thereafter, the treatment group received an intrastromal injection of verteporfin (controls: phosphate buffered saline (PBS)) followed by PDT. Corneas were excised at different time points (1 day, 5 days and 10 days) after PDT and corneal whole mounts were stained with CD31 and LYVE-1 to quantify hemangiogenesis and lymphangiogenesis. Whereas blood vessels showed no significant reduction after PDT, lymphatic vessels could significantly be reduced with PDT after intrastromal verteporfin injection: 1 day after PDT, lymphatic vessels were reduced by 62% (p=0.20). After 5 days and 10 days, lymphatic vessels were reduced by 51% and 48% (p<0.001), respectively. This study for the first time shows that PDT after corneal intrastromal verteporfin injection can selectively regress lymphatic vessels. This may become a new 'preconditioning strategy' to reduce pre-existing corneal lymphatic vessels prior to transplantation and thereby reduce allograft rejection in high-risk patients.
    The British journal of ophthalmology 01/2014; · 2.92 Impact Factor

Publication Stats

4k Citations
641.58 Total Impact Points

Institutions

  • 2011–2014
    • University of Cologne
      • Department of Ophthalmology
      Köln, North Rhine-Westphalia, Germany
  • 2013
    • University of Freiburg
      Freiburg, Baden-Württemberg, Germany
  • 2012–2013
    • Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
      Shanghai, Shanghai Shi, China
  • 1970–2013
    • Friedrich-Alexander Universität Erlangen-Nürnberg
      • Department of Ophthalmology
      Erlangen, Bavaria, Germany
  • 2007–2012
    • Universitätsklinikum Erlangen
      • Department of Ophthalmology
      Erlangen, Bavaria, Germany
  • 2003–2011
    • Universität zu Lübeck
      • Department of Ophthalmology
      Lübeck, Schleswig-Holstein, Germany
    • University of Sydney
      Sydney, New South Wales, Australia
  • 2010
    • Philipps-Universität Marburg
      • Klinik für Augenheilkunde (Marburg)
      Marburg an der Lahn, Hesse, Germany
    • Netherlands Institute for Innovative Ocular Surgery
      Rotterdam, South Holland, Netherlands
    • Aristotle University of Thessaloniki
      • Faculty of Medicine
      Thessaloníki, Kentriki Makedonia, Greece
  • 2008
    • University of Tuebingen
      Tübingen, Baden-Württemberg, Germany
  • 2006
    • Semmelweis University
      • Department of Ophthalmology
      Budapest, Budapest fovaros, Hungary
  • 2004–2006
    • Schepens Eye Research Institute
      Boston, Massachusetts, United States
    • Harvard Medical School
      Boston, Massachusetts, United States
  • 2003–2006
    • Massachusetts Eye and Ear Infirmary
      • • Schepens Eye Research Institute
      • • Department of Ophthalmology
      Boston, MA, United States
  • 2001
    • Justus-Liebig-Universität Gießen
      Gieben, Hesse, Germany
  • 1999
    • Universitätsklinikum Tübingen
      Tübingen, Baden-Württemberg, Germany