T Reinhard

Evangelische Hochschule Freiburg, Germany, Freiburg, Baden-Württemberg, Germany

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Publications (355)466.84 Total impact

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    ABSTRACT: To determine the incidence and potential risk factors of cystoid macular oedema (CMO) following Descemet membrane endothelial keratoplasty (DMEK) with or without simultaneous cataract surgery.
    The British journal of ophthalmology. 08/2014;
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    ABSTRACT: Background: ReLEx®flex is a corneal refractive procedure performed by removing corneal lenticules with a femtosecond (fs) laser system. Using electron microscopy, tissue parameters of extracted lenticules were analysed for potential correlations to the refractive results. Furthermore, the effect of previous contact lens (CL) wear on refractive stability (regression) was tested. Patients and Methods: 19 lenticules from 11 patients (age 24–56 years, 8 f, 3 m) were prepared for EM. The central areas of the samples were photographed and the distance between the collagen fibres and their diameters were digitally measured. ANOVA analysis was used to correlate postoperative refractional stability with time of preoperative CL use, fibre diameter and the coefficient of variation (CV) of fibre distance. Results: 14 of 19 lenticules were from patients who had worn CL preoperatively. The cumulative duration of CL wear averaged around 31.2 ± 35.5 thousand hours. Preoperative CL use significantly influenced the postoperative regression: the longer time patients had worn CL, the greater was the regression towards myopia (p = 0.01). Additionally, the morphological parameters collagen fibre diameter (p = 0.09) and CV of fibre distance (p = 0.07) had an impact on regression. Conclusions: Prolonged CL use and alterations in ultrastructural patterns affected the refractive stability after ReLExflex. Although the pathophysiological relationships between CL use, corneal morphological parameters, and refractive stability are still poorly understood, these findings could potentially be used as prognostic markers for postoperative refraction after ReLExflex.
    Klinische Monatsblätter für Augenheilkunde 07/2014; · 0.70 Impact Factor
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    ABSTRACT: Background: It has been observed that formerly rejected opaque corneal transplants can regain clarity in the rat. We hypothesized that graft endothelium is regenerated by the host. Therefore, we used green fluorescent protein (GFP) transgenic rats to assess the origin of cells following keratoplasty. Methods: Allogeneic corneal transplantations were carried out between Fischer strain rats as graft donors and GFP-transgenic Lewis rats as recipients. In a second group, syngeneic transplantations were performed between GFP-negative Lewis donors and GFP-positive Lewis recipients, where endothelial-cell-free grafts after mechanical endothelial debridement were used. All grafts were followed up clinically for signs of opacity and rejection. After 6 weeks, corneal flatmounts counterstained with DAPI were analyzed by confocal microscopy. Results: Syngeneic transplantation of endothelial-cell-free grafts led to medium opacity levels without rejection and to subsequent clearing. All grafts showed a population of GFP-positive, host-derived endothelial cells on the graft after 6 weeks. In the allogeneic transplantation group, all grafts but one were rejected after a median of 17 days. While the graft that was not rejected maintained the GFP-negative transplant endothelium, all formerly rejected grafts showed GFP-positive endothelium on the transplant after 6 weeks, accompanied by clinical clearing of the graft. Conclusion: GPF positivity shows that in both a syngeneic and an allogeneic setting, the host-derived corneal endothelium can compensate for the endothelial cell loss of the graft. Following rejection, the grafts are repopulated by host-derived endothelial cells in the rat. This finding demonstrates a high regenerative capacity of the peripheral corneal endothelium in the rat, which should be considered whenever interpreting rat keratoplasty results. © 2014 S. Karger AG, Basel.
    Ophthalmic research. 07/2014; 52(2):60-64.
  • S J Lang, C Auw-Hädrich, T Reinhard
    Klinische Monatsblatter fur Augenheilkunde. 06/2014;
  • Klinische Monatsblatter fur Augenheilkunde. 06/2014;
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    ABSTRACT: In this review we summarise the new insights into corneal dystrophies following publication of the IC3D classification in 2008. Topics covered are new mutations, new clinical/histological phenotypes, first descriptions of known mutations in previously not mentioned ethnic groups, new dystrophic entities after modern corneal surgery and potentially new types of conservative therapy.
    Klinische Monatsblatter fur Augenheilkunde. 06/2014; 231(6):611-618.
  • S J Lang, D Böhringer, T Reinhard
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    ABSTRACT: PurposeWe retrospectively studied the efficacy and safety of different surgical approaches to treating pediatric limbal dermoids with regard to intra and postoperative complications.Methods The data of 12 consecutive patients (14 eyes), who underwent monocentric surgery of a limbal demoid in the past 9 years, were retrospectively analyzed for intra and postoperative complications. Group one consists of eleven eyes: seven eyes with a bare-sclera deep lamellar excision of the dermoid and four eyes with an additional amniotic membrane transplantation subsequent to excision. Group two consists of three eyes: two eyes treated with Mitomycin C 0.02% over 2 min following the excision, and one eye treated with Mitomycin C and amniotic membrane transplantation after removal of the dermoid. Follow-up ranged from 2 to 53 months (median 17 months).ResultsIntraoperative complications did not occur in any of the patients. Postoperatively, all patients showed corneal reepithelialization within a week. Limbal stem cell deficiency with a pseudopterygium developed in four eyes, one treated with bare-sclera excision and the others with amniotic membrane transplantation. One pseudopterygium had to be removed surgically because of visual acuity deterioration. Not a single eye treated with Mitomycin C developed a pseudopterygium.Conclusions The transplantation of amniotic membrane following removal of a limbal dermoid cannot prevent the occurrence of a pseudopterygium. However, the use of Mitomycin C seems to have a protective effect.Eye advance online publication, 23 May 2014; doi:10.1038/eye.2014.112.
    Eye (London, England) 05/2014; · 1.97 Impact Factor
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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
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    ABSTRACT: Penetrating keratoplasty is being replaced by posterior lamellar techniques like Descemet stripping automated endothelial keratoplasty or Descemet membrane endothelial keratoplasty (DMEK) for the surgical treatment of patients with endothelial insufficiency. Although DMEK leads to the best visual results, Descemet stripping automated endothelial keratoplasty is still the standard procedure for many surgeons because it is technically more standardized. Here, we investigated how donor characteristics may influence DMEK surgery. After in vitro preparation of DMEK grafts (n = 28), we measured the width of the graft roll, which we correlated to various donor characteristics. In 31 DMEK cases, we measured the intraoperative time from implantation to attachment of the graft, which we correlated to the respective donor characteristics and endothelial cell loss. We used Pearson's method and a multifactorial linear model for the statistical assessments. We found a statistically significant correlation between donor age (P < 0.001) and endothelial cell density (P < 0.05), and the width of the DMEK rolls. That is, older donors and grafts with higher endothelial cell densities formed broader graft rolls. Donor age also showed a trend to directly influence the unfolding time that took longer using younger grafts. Furthermore, the relative endothelial cell loss increased with longer unfolding times. We found that donor age and endothelial cell density influence the properties of DMEK grafts, and thereby the duration of the surgical procedure. Increased unfolding times result in higher endothelial cell loss. Therefore, it seems reasonable to accept preferably older donors with high endothelial cell densities for DMEK, which may be particularly true for inexperienced surgeons or complex clinical situations.
    Cornea 03/2014; · 1.75 Impact Factor
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    ABSTRACT: In order to prevent rejection of an allogeneic corneal transplant after perforating (high risk) keratoplasty, active agents from different classes of pharmacological substances are used, as with solid organ transplantation. In addition to glucocorticoids, antiproliferative agents, small molecule inhibitors and antibodies, those belonging to the group of macrolides with their many derivatives represent an interesting class of substances in this context. As a supplement to cyclosporin A (CSA) the most successful macrolide in transplantation medicine, animal experiments are currently being carried out to test newer macrolide derivatives, such as sanglifehrin A (SFA). This overview describes the classes of drugs and modes of action of currently administered standard medications in the clinical routine and new developments are presented.
    Der Ophthalmologe 03/2014; 111(3):270-82. · 0.53 Impact Factor
  • Klinische Monatsblätter für Augenheilkunde 03/2014; 231(3):262-5. · 0.70 Impact Factor
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    ABSTRACT: Background: The matching of favorable human leukocyte antigen (HLA) combinations is rarely performed in penetrating keratoplasty procedures for primary prophylaxis of immune reactions. However, clinical studies suggest that the incidence of graft rejection decreases substantially when patients receive favorably matched grafts. Objective: The aim of this study was to assess the cost-effectiveness of HLA matching for patients undergoing penetrating keratoplasty in everyday clinical practice. Methods: In the absence of a randomized controlled clinical trial, we used administrative data from the Freiburg University Eye Hospital in Germany. Our study population consisted of all patients who underwent their first keratoplasty between 11/2003 and 01/2010 and for whom information on HLA histocompatibility was available. We used propensity score matching to estimate a causal effect of favorable HLA matching, parametric survival regression techniques to predict graft survival and expert opinion to model incremental cost for HLA matching. Because the availability of favorable HLA histocompatibility ultimately depends on the patients' HLA phenotype, we modeled the incremental cost-effectiveness ratio (ICER) as a function of the probability that a patient will receive a favorably matched HLA, and used expert opinion to set a point estimate. Results: We predicted that corneal grafts with favorable HLA matching were associated with improved rejection-free graft survival time (more than 1,000 days). We estimated the incremental cost of HLA matching at EUR 1,200 and the ICER at EUR 4.62 per additional day of graft survival. Conclusions: The ICER of HLA matching is acceptable, given the high cost of alternative treatment and the shortage of corneal donors in Germany.
    International Journal of Technology Assessment in Health Care 02/2014; · 1.55 Impact Factor
  • Ophthalmology 01/2014; · 5.56 Impact Factor
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    ABSTRACT: As the desire for spectacle independence following cataract surgery grows, so does interest in the implantation of multifocal intraocular lenses. However, glare phenomena, reduced intermediate vision and loss of image quality are known problems associated with this new generation of lenses. We compared the functional results achieved by the implantation of the diffractive-refractive Acri.LISA 366D lenses to those achieved from implanting monofocal Acri.Smart 46LC lenses. In a retrospective data analysis we followed ten patients who received bifocal intraocular lenses (Acri.LISA 366D) and ten patients who received monofocal intraocular lenses (Acri.Smart 46LC). Lenses were always implanted in both eyes. In each group we assessed visual acuity and contrast sensitivity with the Freiburg Vison Test (FrACT) at multiple distances ranging from 0.5 to 5 m. Additionally, we assessed near vision with the Birkhaeuser charts. We also evaluated photopic phenomena and patient satisfaction using a standardised questionnaire. One patient in the Acri.LISA group and six patients in the control group missed the recommended follow-up visits. We found good uncorrected distance and near visual acuity. Only three of nine patients wore glasses occasionally. Although their contrast sensitivity decreased by a factor of two compared to the control group, patients did not complain about visual disturbances. Patient satisfaction was predominantly high following Acri.LISA 366D implantation. With the Acri.LISA 366D, patients demonstrate excellent near and distance vision, albeit with reduced contrast sensitivity. Acri Lisa is a viable option in patients that do not want to depend on spectacles.
    Albrecht von Graæes Archiv für Ophthalmologie 01/2014; · 1.93 Impact Factor
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    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.
    Ophthalmology 01/2014; · 5.56 Impact Factor
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    ABSTRACT: Little is known about the behavior of the endothelial cell (EC) layer following keratoplasty. In vitro experiments suggested that the peripheral endothelium might have a higher regenerative capacity than the central endothelium, and some authors hypothesized that endothelial progenitor cells are present in the limbal area. Thus, we analyzed the corneal endothelial regenerative capacity in vivo in a rat model of bullous keratopathy using either bullous central grafts or bullous peripheral recipient corneas to analyze differences in EC regeneration depending on central versus peripheral cell origin.
    Molecular vision 01/2014; 20:683-90. · 1.99 Impact Factor
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    ABSTRACT: When comparing follow-up endothelial cell (EC) density measurements it is only possible to demonstrate cell loss in large cohorts or in pronounced cases due to the standard deviation of measurements. However, especially in clinical studies or refractive surgery patients, EC stability is an important factor. Thus we developed a computer program to achieve cell-by-cell alignment of conventional specular non-contact EC photographs. This is a pilot study to evaluate whether this new diagnostic technique is applicable in postoperative patients. Digitized endothelial cell photos of 30 eyes following implantation of a phakic posterior chamber intraocular lens for correction of high myopia were analyzed. All EC centroids were dotted on each image, and early and late follow-up pictures were automatically aligned on the basis of these centroids. The tracking results were confirmed via alternating image presentation of the corresponding image areas, and were reviewed for loss of individual cells. In addition, conventional EC density measurements were performed. Mean time interval between first and second postoperative EC image was 1.4 years (range 3 months - 2.2 years), with early images taken at a median of 5.5 months after IOL implantation (lower/upper quartile 1.2-12.3 months). Extrapolated central EC density was 2812±500/mm2 at the first time point, and 2797±524/mm2 at the second time point. In 26 out of 30 image pairs, the EC mosaic was successfully retraced; cell loss in this area was excluded via photo flickering. Only in 4 image pairs, the EC mosaic could not be matched. We demonstrate that the corneal EC mosaic of clinical routine non-contact microscope pictures can be superimposed and compared on single cell level over time with our new computer based program. This new method is valuable to judge on EC stability even in small cohorts since it does not require mean values and standard deviations.
    PLoS ONE 01/2014; 9(3):e88603. · 3.73 Impact Factor
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    ABSTRACT: Purpose To test whether subconjunctival cyclosporine A (CsA) implants affect the incidence and the degree of corneal neovascularization occurring after penetrating keratoplasty. Design Prospective, randomized, multicenter, controlled phase 2/3 clinical trial. The study comprised 43 trial sites in Germany, India, and the United States. Participants Enrolled patients (n = 97) were randomized to 1 of 3 groups: treatment group A (n = 36), treatment group B (n = 40), and the control group (n = 21). Methods Patients from each group received either of 2 doses of subconjunctival CsA (group A, low-dose CsA; group B, high-dose CsA) or placebo (carrier only) implants at the time of high-risk penetrating keratoplasty. Main Outcome Measures The incidence and degree of corneal neovascularization occurring after penetrating keratoplasty were evaluated in a substudy (LX201-01 study: NCT00447187). A web-based image upload system was developed. Standardized digital slit-lamp pictures were quantitatively and objectively evaluated using CellˆF morphometry software. Results No statistically significant difference in incidence and degree of corneal neovascularization developing after penetrating keratoplasty was found between treatment groups and placebo group. Mean corneal neovascularization area at week 52 (visit 12) was 2.32±1.79% in treatment group A versus placebo (2.79±2.11%; P = 0.45) and 2.74±2.22% in treatment group B versus placebo (2.79±2.11%; P = 0.94). Conclusions High-dose subconjunctival CsA implants do not significantly affect corneal neovascularization after high-risk penetrating keratoplasty. This suggests that local CsA has negligible antiangiogenic effects in the human cornea, at least in the transplant setting.
    Ophthalmology 01/2014; · 5.56 Impact Factor
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    ABSTRACT: Zur Unterbindung einer allogenen Hornhauttransplantatabstoßung nach perforierenden (Hochrisiko-)Keratoplastiken kommen – wie auch bei transplantierten soliden Organen – Wirkstoffe verschiedenster pharmakologischer Substanzklassen zum Einsatz. Neben Glukokortikoiden, antiproliferativen Agenzien, Small-molecule-Inhibitoren und Antikörpern stellt vor allem die Gruppe der Makrolide mit ihren zahlreichen Derivaten eine interessante Wirkstoffklasse in diesem Kontext dar. Ergänzend zu Ciclosporin A, dem erfolgreichsten Makrolid in der Transplantationsmedizin, erfolgen derzeit tierexperimentelle Studien, um die Wirksamkeit neuerer Makrolidderivate, wie z. B. Sanglifehrin A, zu testen. In dieser Übersicht werden die Wirkstoffklassen und Wirkungsweisen der derzeit im klinischen Alltag verwendeten Standardmedikamente beschrieben und neue Entwicklungen dargestellt.
    Der Ophthalmologe 01/2014; 111(3). · 0.53 Impact Factor
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    ABSTRACT: Since it has been observed that melanocytic lesions can alter their appearance during pregnancy, we analyzed whether hormone receptors are expressed in conjunctival nevi as well as conjunctival melanoma. We further analyzed whether the number of estrogen (ER) or progesterone receptors (PR) might be associated with the disease course in conjunctival melanoma. Twenty-seven paraffin-embedded samples of conjunctival nevi and 27 conjunctival melanoma specimens were examined using immunohistological analysis with antibodies against PR and ER. The percentage of stained cells were analyzed, taking into account patient gender and age. Out of the melanoma group, all patients with complete data for tumor thickness, tumor localization, age at diagnosis, gender, and follow-up including recurrence, metastasis and tumor-related death were included in the second part of the study (n = 15), where hormone receptor rates were associated with tumor outcome, regarding recurrences, metastasis or death. Written consent was received from all included patients. Both nevi and melanomas showed high rates of PR- and ER-positive cells. In Nevi, 64 ± 25 % of cells stained positive for PR and 35 ± 34 % for ER. In melanoma specimens, 68 ± 30 % showed PR and 44 ± 34 % ER expression. Differences between men and women in expression rates were not statistically significant. Out of 15 melanoma patients (nine female, six male), 53 % (five women and three men) experienced 1-4 recurrences, and four patients developed metastases. The median estimated survival time was 12.2 years. A multivariate survival model taking into account known risk factors for prognosis in conjunctival melanoma confirmed tumor location to be an important predictive factor for outcome (p = 0.05). The rate of PR or ER did not show a statistically significant correlation with the disease course in our cohort. We observed that conjunctival melanocytic lesions express hormone receptors, which could explain why these tumors can alter their appearance under hormonal changes. Regarding the prognosis of conjunctival melanoma, no statistically significant correlation between hormone receptor expression and event-free survival was found in this analysis.
    Albrecht von Graæes Archiv für Ophthalmologie 11/2013; · 1.93 Impact Factor

Publication Stats

2k Citations
466.84 Total Impact Points

Institutions

  • 2014
    • Evangelische Hochschule Freiburg, Germany
      Freiburg, Baden-Württemberg, Germany
  • 2004–2014
    • Universitätsklinikum Freiburg
      • Department of Ophthalmology
      Freiburg an der Elbe, Lower Saxony, Germany
    • Universität Mannheim
      Mannheim, Baden-Württemberg, Germany
  • 2003–2014
    • University of Freiburg
      • Department of Microsystems Engineering (IMTEK)
      Freiburg, Baden-Württemberg, Germany
  • 2010–2013
    • University College London
      • Division of Infection and Immunity
      London, ENG, United Kingdom
    • University of Duisburg-Essen
      Essen, North Rhine-Westphalia, Germany
  • 2012
    • Johannes Gutenberg-Universität Mainz
      Mayence, Rheinland-Pfalz, Germany
    • Ludwig-Maximilian-University of Munich
      München, Bavaria, Germany
  • 2011
    • Nottinghamshire Healthcare NHS Trust
      Nottigham, England, United Kingdom
    • University of Louisville
      Louisville, Kentucky, United States
  • 2009
    • Charité Universitätsmedizin Berlin
      Berlín, Berlin, Germany
  • 2008
    • Martin Luther University of Halle-Wittenberg
      • Poliklinik für Augenheilkunde
      Halle, Saxony-Anhalt, Germany
  • 1992–2005
    • Heinrich-Heine-Universität Düsseldorf
      • Augenklinik
      Düsseldorf, North Rhine-Westphalia, Germany
  • 2001
    • Universität Heidelberg
      Heidelburg, Baden-Württemberg, Germany
  • 1994
    • Universitätsklinikum Düsseldorf
      Düsseldorf, North Rhine-Westphalia, Germany