Thomas Reinhard

University of Freiburg, Freiburg, Baden-Württemberg, Germany

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Publications (396)554.49 Total impact

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    ABSTRACT: Purpose: Astigmatism is a significant problem in penetrating keratoplasty. Lower astigmatism and better visual outcomes had been expected from laser-assisted penetrating keratoplasty, that is, from the top-hat, mushroom, or zig-zag cutting profiles. We report the long-term outcomes of 141 femtosecond laser-assisted penetrating keratoplasties retrospectively. We compare these outcomes with those of penetrating keratoplasty using the guided trephine system (GTS). Methods: In all, 141 femtosecond laser-assisted penetrating keratoplasties had been performed in 119 patients. The results were compared with those of conventional keratoplasty (n = 1254; visual and refractive outcomes, graft rejections, and graft failure). Results: Follow-up averaged 33 months. In eyes with keratoconus, the time to achieve a visual acuity of 10/20 (Snellen) was shorter in the mushroom than in the GTS group. However, there was no relevant long-term difference. Graft astigmatism was higher in the laser groups [keratometric astigmatism at the end of follow-up: -4.5 ± 4 (GTS), -5.8 ± 3.3 (top-hat), -5.9 ± 3.2 D (mushroom); P < 0.01]. In eyes with keratoconus, rates of graft rejection were highest in the mushroom group (55%). In the other groups, top-hat keratoplasty resulted in lower rates of rejection than GTS keratoplasty (31%). Conclusions: There is no significant difference in the refractive and visual outcomes after femtosecond laser-assisted penetrating keratoplasty compared with GTS keratoplasty. The benefits from the use of the femtosecond laser may be limited and should be weighed against an increased risk of immune reactions, higher surgical complexity, and higher costs.
    No preview · Article · Jan 2016 · Cornea

  • No preview · Article · Jan 2016 · Ophthalmology
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    ABSTRACT: Purpose: According to some pioneer surgeons, lamellar endothelial keratoplasty techniques (EK), including Descemet membrane endothelial keratoplasty (DMEK) and Descemet stripping automated endothelial keratoplasty (DSAEK), yield excellent clinical results. However, there is a lack of studies with high levels of evidence and results of large national keratoplasty registers are contradictory. Therefore, two large cohorts of DMEK and DSAEK procedures are compared to a cohort of penetrating keratoplasty (PK). Methods: The study reports 868 keratoplasty procedures at a single centre (694 eyes with Fuchs endothelial dystrophy (FED) and 174 with bullous keratopathy (BK)). Patients underwent DMEK (450 eyes), DSAEK (89 eyes), or PK (329 eyes). Postoperative visual acuity, endothelial cell density (ECD), rate of regrafting, and rejections were recorded. Results: Visual acuity recovers faster and to a greater extent in EK compared to PK. DMEK performs better than DSAEK. ECD drops faster initially for EK compared to PK. In EK the rate of regrafting is higher than in PK (7 % in DMEK, 20 % in DSAEK and 2 % in PK in FED). The rejection rate is lowest following DMEK (7 % after DMEK, 21 % after DSAEK and 18 % after PK in FED). Conclusions: In contrast to recent reports from national keratoplasty registers, the overall clinical outcome of EK in FED and BK is superior to PK. Including ocular comorbidities and learning curves, these data reflect a realistic setting for comparing the different keratoplasty techniques. Corneal surgeons may be encouraged to preferentially use DMEK in FED and BK.
    No preview · Article · Jan 2016 · Albrecht von Graæes Archiv für Ophthalmologie
  • P Maier · S Heinzelmann · D Böhringer · T Reinhard
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    ABSTRACT: PurposeThe number of antigen-presenting cells decreases during organ culture of corneoscleral discs. This might result in a decrease of immune reactions with increasing duration of organ culture. To investigate this hypothesis, we performed a retrospective analysis of all penetrating keratoplasties that were consecutively performed over the last 5 years.Patients and methodsAll cases of penetrating keratoplasties (n=1006) were divided into two groups, with the division made at the median of the storage time (21 days). These two groups were compared by a Cox proportional hazards survival model regarding the incidence of endothelial immune reactions, clear graft survival, and chronic endothelial cell loss following penetrating keratoplasty considering patient's age, donor's age, and risk situation as co-variates.ResultsWe observed statistically significantly fewer endothelial immune reactions (20.1% (95% confidence interval 15.5-24.5%) after 2 years) in the group with a storage time of more than 21 days compared with the group with a storage time of <21 days (26.5% (95% confidence interval 21.6-31.2%) after 2 years). However, the duration of organ culture did not have a statistically significant effect on clear graft survival or chronic endothelial cell loss.Conclusion Our results demonstrate that an increased duration of organ culture leads to a lower incidence of endothelial immune reactions following penetrating keratoplasty. However, we do not recommend increased storage times in general as overall graft survival did not improve. The reason for this apparent paradox may be that the endothelial cell count decreases during storage time.Eye advance online publication, 23 October 2015; doi:10.1038/eye.2015.207.
    No preview · Article · Oct 2015 · Eye (London, England)
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    ABSTRACT: Purpose: The number of outpatient operations in Germany is not registered in a centralised manner. To estimate the development of the outpatient intraocular surgery especially since the implementation of the intravitreal injections, surveys among ophthalmic surgeons were analysed. Methods: Between 2006 and 2013 surveys were done among ophthalmic surgeons in Germany using questionnaires. An average of 318 completed questionnaires were sent back. The mean participation ratio was 37 %. Results: Between 2006 and 2013 an extrapolated mean of 347 564 cataract operations and 139 946 intravitreal injections were reported. Whereas the number of cataract operations was constant in the observation period, the number of injections increased considerably from 35 135 in 2006 to 274 714 in 2013. Conclusion: A saturation in the development of the numbers of the intravitreal injections could not yet be observed. Other outpatient operations, especially cataract procedures were not replaced by the increase of the injections in the recent years. Georg Thieme Verlag KG Stuttgart · New York.
    No preview · Article · Aug 2015 · Klinische Monatsblätter für Augenheilkunde
  • P C Maier · S Heinzelmann · D Böhringer · T Reinhard
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    ABSTRACT: The opacification of an artificial intraocular lens is a rare but serious complication following cataract surgery as an exchange of the intraocular lens can become necessary. At our eye center we observed single cases of IOL opacifications following complicated posterior lamellar keratoplasty (Descemet stripping automated endothelial keratoplasty = DSAEK or Descemet membrane endothelial keratoplasty = DMEK). Therefore, we performed a retrospective analysis of all our digital charts regarding the incidence of this serious complication with respect to posterior lamellar keratoplasty, penetrating keratoplasty or sole cataract extraction. We searched our digital patient database from 2003 to 2015 using the following headings: intraocular lens, artificial lens or IOL and opacification or calcification and selected only those patients who had undergone either DSAEK, DMEK, penetrating keratoplasty or sole cataract surgery (n = 19,565). In total we found five IOL opacifications out of 153 DSAEK and two out of 450 DMEK cases, respectively. Five of these seven cases had a complicated clinical course with repeated rebubbling or additional intraocular surgery (i.e., repeat DSAEK or DMEK or secondary penetrating keratoplasty). There were no documented IOL opacifications following penetrating keratoplasty or sole cataract extraction. In two cases intraocular lens exchange became necessary. All opacifications showed similar clinical appearance in form of small granular deposits on the surface of the intraocular lens. Almost all implanted lenses were made from hydrophilic acrylate. In total we found seven cases of intraocular lens opacification that have only been observed following DSAEK or DMEK. According to reports from the literature these opacifications are superficial calicifications of the hydrophilic lenses. As five of the seven cases had a complicated clinical course, the repeated air contact of the lens could be one major factor in inducing the calcification. Besides the air contact a breakdown of the blood-aqueous barrier could also play a role in the induction of calcium phosphate crystallisation on the intraocular lens. The risk of this serious complication in mainly hydrophilic intraocular lenses with respect to posterior lamellar keratoplasty should be kept in mind for the selection of the type of intraocular lens in patients with endothelial diseases or in patients undergoing combined cataract extraction and DSAEK/DMEK. Georg Thieme Verlag KG Stuttgart · New York.
    No preview · Article · Aug 2015 · Klinische Monatsblätter für Augenheilkunde
  • Laura Gasser · Julia Biermann · Thomas Reinhard
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    ABSTRACT: PURPOSE: To present the 3-year results regarding the safety and efficacy of the Epi.Lens N, a new posterior chamber phakic intraocular lens (PC pIOL). SETTING: Eye Center, University Hospital Freiburg, Freiburg, Germany. DESIGN: Prospective clinical study. METHODS: A PC pIOL was implanted in highly myopic eyes of consecutive patients. Standardized follow-up examinations including uncorrected (UDVA) and corrected (CDVA) distance visual acuities and refractions were performed 1, 3, and 6 months and 1, 2, and 3 years postoperatively. RESULTS: The patient cohort consisted of 30 eyes of 16 patients. The study eyes had a mean manifest refraction spherical equivalent of -10.1 diopters (D) +/- 3.4 (SD), which decreased to -0.3 +/- 0.8 D postoperatively. After 3 years, all eyes achieved (47%) or exceeded (53%) their preoperative CDVA, thus improving the mean CDVA from 20/21 (0.94) preoperatively to 20/18 (1.14) postoperatively. The mean postoperative UDVA (20/20 [0.98]) resembled the preoperative CDVA (20/21 [0.94]). When analyzing all eyes with good visual potential (preoperative CDVA 20/20 or better; n = 18), 94% achieved a postoperative UDVA of 20/20 or better. One small-diameter PC pIOL contacted the crystalline lens, which led to slight anterior subcapsular lens opacification. Despite this, the patient achieved a CDVA of 20/20. CONCLUSION: The 3-year results of this pilot study of a new PC pIOL showed good efficacy and safety. (C) 2015 ASCRS and ESCRS
    No preview · Article · Aug 2015 · Journal of Cataract and Refractive Surgery
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    ABSTRACT: Corneal cross-linking is widely used to treat keratoconus. However, to date, only limited data from randomized trials support its efficacy. The efficacy and safety of corneal cross-linking for halting progression of keratoconus were investigated in a prospective, randomized, blinded, placebo controlled, multicentre trial. Twenty-nine keratoconus patients were randomized in three trial centres. The mean age at inclusion was 28 years. Longitudinal changes in corneal refraction were assessed by linear regression. The best corrected visual acuity, surface defects and corneal inflammation were also assessed. These data were analysed with a multifactorial linear regression model. A total of 15 eyes were randomized to the treatment and 14 to the control group. Follow-up averaged 1098 days. Corneal refractive power decreased on average (+/−standard deviation) by 0.35 +/− 0.58 dioptres/year in the treatment group. The controls showed an increase of 0.11 +/− 0.61 dioptres/year. This difference was statistically significant (p = 0.02). Our data suggest that corneal cross-linking is an effective treatment for some patients to halt the progression of keratoconus. However, some of the treated patients still progressed, whereas some untreated controls improved. Therefore, further investigations are necessary to decide which patients require treatment and which do not. Trial registration NCT00626717, Date of registration: February 20, 2008.
    Preview · Article · Jul 2015 · BMC Ophthalmology
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    Laura Gasser · Thomas Reinhard · Daniel Böhringer
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    ABSTRACT: Measurement of corneal endothelial cell density is important both for clinical diagnosis as well as clinical studies. Since endothelial cell loss is considered irreversible in humans, even small changes in endothelial cell density are relevant. Therefore it is important to know whether different instruments for endothelial cell density measurements give the same results and can thus be used interchangeably. In this study we compare corneal endothelial cell density and morphometry measurements from two widely used non-contact specular microscopes, the Topcon SP3000P and Konan Noncon Robo SP8000. Endothelial cell measurements were performed with both the Topcon SP3000P and Konan Noncon Robo SP8000 on 34 eyes of 18 consecutive patients of our cornea clinics with poor image quality being the only exclusion criterion. Images were obtained using the auto-focussing method and manual cell selection. Endothelial cell density (ECD), hexagonal cell ratio (HEX) and coefficient of value (CV) of the endothelial cell layer were calculated by the instruments' built-in software. ECD values calculated by the Konan were systematically higher than Topcon values: in 94 % of eyes Konan gave a higher value than Topcon, leading to a mean difference in ECD between the instruments of 187 cells/mm(2) (P < 0.001 in paired Wilcoxon test). HEX showed a broad range of values and differed greatly with only weak correlation between the two instruments. CV values for Konan mostly exceeded Topcon values, and only showed a weak correlation between the two instruments as well. Values for ECD between the Konan and the Topcon do correlate well, but the ECDs calculated by the Konan are systematically higher than Topcon values. Both HEX and CV vary greatly and do not correlate sufficiently. Thus we recommend not to use the Konan and the Topcon instrument interchangeably.
    Preview · Article · Jul 2015 · BMC Ophthalmology
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    ABSTRACT: Within the concept of integrin growth factor receptor (GFR) cross-talk, little is known about the effects of GFRs on focal adhesions (FAs). Therefore, we tested the hypothesis whether EGF can modulate constituents of FAs and subsequent down-stream events. To this end, EGF-treated keratinocytes were subjected to combined fluorescence imaging and western blotting, to quantify expression and/or activation of molecules, involved in integrin GFR cross-talk, and receptor proximal and distal signaling events. Generally, EGF response revealed an amplified redistribution or activation of molecules under study, which will be explained in detail from the plasma membrane to the cell interior. In addition to significant activation of EGF receptor (EGFR) at tyrosine Tyr845, a remarkable redistribution was detectable for the focal adhesion constituents, integrin ß1 and ß3, and zyxin. Increased activation also applied to focal adhesion kinase (FAK) by phosphorylation at Tyr397, Tyr576, and Src at Tyr418, while total FAK remained unchanged. Risen activity was seen as well for the analyzed distal down-stream events, p190RhoGAP and MAP kinases p42/44. Intriguingly, Src-specific inhibitor Herbimycin A abrogated the entire EGF response except FAK Tyr397 phosphorylation, independent of EGF presence. Mechanistically, our results show that EGF modulates adhesion in a dual fashion, by firstly redistributing focal adhesion constituents to adhesion sites, but also by amplifying levels of activated RhoA antagonist p190RhoGAP, important for cell motility. Further, the findings suggest that the observed EGF response underlies an EGFR integrin cross-talk under recruitment of receptor proximal FAK and Src, and MAP kinase and p190RhoGAP as receptor distal events. Copyright © 2015. Published by Elsevier B.V.
    Full-text · Article · Jun 2015 · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
  • N J Gross · D Böhringer · P Maier · T Reinhard
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    ABSTRACT: This study compared the postoperative results and patient satisfaction between penetrating keratoplasty (PK) and Descemet stripping automated endothelial keratoplasty (DSAEK) in patients who underwent PK in one eye and DSAEK in the other eye. A total of 15 patients were identified from the corneal database register and the medical charts were analyzed for best corrected visual acuity (BCVA), keratometric astigmatism, endothelial cell density and postoperative complications. Patient satisfaction was evaluated by a standardized interview. Median follow-up time for PK was 55 months and 18 months for DSAEK (p < 0.01). Median BCVA in PK was 0.8 and 0.5 in DSAEK (p = 0.01) at the end of follow-up. Median keratometric astigmatism was 3.1 diopters after PK and 1.9 diopters after DSAEK (p = 0.2). Median endothelial cell density was 831 cells/mm(2) after PK and 860 cells/mm(2) after DSAEK (p = 0.63). For the interventions 57 % of the patients preferred PK, 36 % preferred DSAEK and 7 % were undecided. Patients assigned the better performing eye to the PK side in 64 % and in 29 % to the DSAEK side and 7 % perceived equal visual performance in both eyes. The results leave doubt about the superiority of DSAEK compared to PK; however, exceptionally good refractive results of the 15 PK eyes analyzed and significantly longer follow-up times after PK could be the reason for the unexpectedly high patient preference for PK.
    No preview · Article · May 2015 · Der Ophthalmologe
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    ABSTRACT: To present 2 cases with long-term relapse-free intervals only after limbo-keratoplasty but not after conventional penetrating keratoplasty in granular dystrophy. Retrospective review of the patient charts and photographs taken during long-term follow-up of 2 cases with granular dystrophy, in which 1 eye received penetrating keratoplasty and the fellow eye received penetrating limbo-keratoplasty. In the first patient, 1 eye showed extensive recurrence of granular deposits 17 years after penetrating keratoplasty was performed while in the second eye two-thirds of the corneal transplant adjacent to the transplanted limbal area remained clear 12 years after the limbo-corneal transplant. In the second patient, 1 eye showed no signs of recurrence 5 years after limbo-keratoplasty, whereas a recurrence of granular corneal deposits occurred 18 months after surgery in the fellow eye. These cases show that the simultaneous transplantation of healthy donor limbus when performing penetrating keratoplasty may prolong recurrence in granular corneal dystrophy. Although we were unable to prove it on the molecular level, these clinical courses may support the hypothesis that a limbal transplant helps prevent a recurrence.
    Preview · Article · May 2015 · Medicine
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    ABSTRACT: In September 2011 the cornea section of the German Ophthalmological Society (DOG) established the first German Acanthamoeba keratitis registry. The data of this multicenter survey are being collected, compiled and evaluated at the Department of Ophthalmology at the Saarland University. The aim of this article is to present an intermediate report. Data from 172 eyes with Acanthamoeba keratitis were collected during the last 10 years. For this interim report we actually evaluated 121 eyes (60.2 % female patients, average age 41.3 years) and collected the following data: date of onset of symptoms, date and method of diagnosis, initial diagnosis, anamnestic data, clinical symptoms and signs at diagnosis and during follow-up, conservative and surgical therapy. Criteria for inclusion in the Acanthamoeba registry was the established diagnosis of an Acanthamoeba keratitis with at least one of the methods described in this article. Acanthamoeba keratitis could be histologically proven in 55.3 % of the cases, via PCR in 25.6 %, with confocal microscopy in 20.4 % and using in vitro cultivation in 15.5 %. Clinical symptoms and signs in Acanthamoeba keratitis were pain in 67.0 %, ring infiltrates in 53.4 %, pseudodendritiform epitheliopathy in 11.7 % and keratoneuritis in 5.8 %. In 47.6 % of the cases the initial diagnosis was herpes simplex virus keratitis followed by bacterial keratitis in 25.2 % and fungal keratitis in 3.9 %. Acanthamoeba keratitis was the correct initial diagnosis in only 23.2 % of cases. The average time period between first symptoms and diagnosis was 2.8 ± 4.0 months (range 0-23 months). A triple therapy with Brolene® Lavasept® and antibiotic eye drops at least 5 ×/day was used in 54.5 % of eyes (n = 66). Penetrating keratoplasty was performed in 40.4 %, in 18 cases in combination with cryotherapy of the cornea. The mean graft diameter was 7.9 ± 1.1 mm (range 3.5-11.0 mm). The final visual acuity (Snellen visual acuity chart at 5 m) was comparable in the two groups of eyes with (5/40 ± 5/25) and without (5/32 ± 5/25) keratoplasty. Acanthamoeba keratitis is a rare and often very late diagnosed disease and two thirds of the cases were initially misdiagnosed. The early recognition of the typical symptoms is crucial for the prognosis of the disease. All ophthalmological departments in Germany are invited to submit further data of all confirmed cases (berthold.seitz@uks.eu), whether retrospectively or prospectively in order to generate an adequate standardized diagnostic and therapeutic approach for this potentially devastating disease.
    Full-text · Article · Apr 2015 · Der Ophthalmologe

  • No preview · Article · Mar 2015 · Acta ophthalmologica
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    ABSTRACT: Chordin-Like 1 (CHRDL1) mutations cause non-syndromic X-linked megalocornea (XMC) characterized by enlarged anterior eye segments. Mosaic corneal degeneration, presenile cataract and secondary glaucoma are associated with XMC. Besides that CHRDL1 encodes Ventroptin, a secreted Bone Morphogenetic Protein (BMP) antagonist, the molecular mechanism of XMC is not well understood yet. In a family with broad phenotypic variability of XMC we identified the novel CHRDL1 frameshift mutation c.807_808delTC [p.H270Wfs*22] presumably causing CHRDL1 loss-of-function. Using Xenopus laevis as model organism we demonstrate that chrdl1 is specifically expressed in the ocular tissue at late developmental stages. The chrdl1 knockdown directly resembles the human XMC phenotype and confirms CHRDL1 deficiency to cause XMC. Interestingly, secondary to this bmp4 is down regulated in the Xenopus eyes. Moreover, phospho-SMAD1/5 is altered and BMP receptor 1A is reduced in a XMC patient. Together, we classify these observations as negative-feedback regulation due to the deficient BMP antagonism in XMC. As CHRDL1 is preferentially expressed in the limbal stem cell niche of adult human cornea, we assume that CHRDL1 plays a key role in cornea homeostasis. In conclusion, we provide novel insights into the molecular mechanism of XMC as well as into the specific role of CHRDL1 during cornea organogenesis, amongst others by establishment of the first XMC in vivo model. We show that unravelling monogenic cornea disorders like XMC - with presumably disturbed cornea growth and differentiation - contributes to the identification of potential limbal stem cell niche factors that are promising targets for regenerative therapies of corneal injuries.
    No preview · Article · Feb 2015 · Human Molecular Genetics
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    ABSTRACT: The cornea is a central component of the camera eye of vertebrates and even slight corneal disturbances severely affect vision. The transcription factor PAX6 is required for normal eye development, namely the proper separation of the lens from the developing cornea and the formation of the iris and anterior chamber. Human PAX6 mutations are associated with severe ocular disorders such as aniridia, Peters anomaly and chronic limbal stem cell insuffi-ciency. To develop the zebrafish as a model for corneal disease, we first performed transcriptome and in situ expression analysis to identify marker genes to characterise the cornea in normal and pathological conditions. We show that, at 7 days post fertilisation (dpf), the zebrafish cornea expresses the majority of marker genes (67/84 tested genes) found also expressed in the cornea of juvenile and adult stages. We also characterised homozygous pax6b mutants. Mutant embryos have a thick cornea, iris hypoplasia, a shallow anterior chamber and a small lens. Ultrastructure analysis revealed a disrupted corneal endothelium. pax6b mutants show loss of corneal epithelial gene expression including regulatory genes (sox3, tfap2a, foxc1a and pitx2). In contrast, several genes (pitx2, ctnnb2, dcn and fabp7a) were ectopically expressed in the malformed corneal endothelium. Lack of pax6b function leads to severe disturbance of the corneal gene regulatory programme.
    Full-text · Article · Feb 2015 · PLoS ONE
  • H. Reinshagen · D. Boehringer · B. Seitz · T. Reinhard
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    ABSTRACT: In der Sektion Gewebetransplantation und Biotechnologie der Deutschen Ophthalmologischen Gesellschaft waren im Jahr 2013 25 Hornhautbanken organisiert (Tab. 1). Im Laufe des Jahres 2013 wurden die Hornhautbanken Wiesbaden und Würselen geschlossen; ihre Leistungszahlen wurden bis zur Schließung aufgenommen.Die Hornhautbanken werden seit 2009 jährlich im Auftrag der Deutschen Ophthalmologischen Gesellschaft gebeten, ihre Daten zu Hornhautbeschaffung, -konservierung, -verteilung sowie zur Gewinnung von Amnionmembranen zu melden.Die Leistungszahlen der Jahre 2009, 2010 und kumuliert 2011/2012 wurden publiziert [1, 2, 3]. Dies ist somit der 4. Leistungsbericht seit Bestehen der DOG-Sektion Gewebetransplantation und Biotechnologie. Im Jahr 2013 haben 24 Hornhautbanken ihre Daten zur Verfügung gestellt.HornhauttransplantateIm Jahr 2013 wurden 7920 Hornhäute in Kultur genommen (Tab. 2). Das entspricht einem Rückgang von 1,2 % (im Vorjahr 8024 Hornhäute); 645 Hornhäute wurden aus dem Ausland im ...
    No preview · Article · Jan 2015 · Der Ophthalmologe
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    ABSTRACT: Purpose: Corneal transplantation is the most frequent and successful form of tissue transplantation in adults (<10% rejection). In young children, any corneal opacity should be corrected as early as possible to prevent lifelong visual impairment. However, the corneal graft rejection rate is dramatically increased in infants younger than 12 months of age (up to 85% rejection), and immunosuppressive therapy is particularly challenging in this age group. Regulatory T cells (Tregs) are a well-characterized T cell subpopulation with the potential to prevent autoimmune disorders or transplant rejection. Antigen-specific Tregs were shown to inhibit graft rejection in adult stem cell transplantation. Less is known about the role of naïve Tregs.The purpose of the present study was to elucidate the relevance of naïve Tregs in juvenile corneal transplantation in a baby rat keratoplasty model that reproduces the accelerated rejection in young patients. Methods: Counts and inhibitory potential of Tregs were studied in spleens of 3- and 10-week-old rats. Unprimed Tregs (CD4+CD25+) were isolated from the spleens of 10-week-old Lewis rats and systemically or subconjunctivally administered in vivo in allogenic keratoplasty in 3- and 10-week-old Lewis recipient rats. In subconjunctival tissue, transcription was analyzed for induction of transforming-growth-factor beta (TGF-β). Results: In 3-week-old rats, CD4 T cell counts, but not FoxP3 T cell counts were lower than in 10-week-old rats. The Tregs of both age groups had the potential to inhibit T cell activation in vitro. No significant delay in rejection was observed when Tregs were applied systemically before keratoplasty. However, subconjunctival application of Tregs abrogated rejection in 66.7% and 33.3% of the 3- and 10-week-old recipients, respectively. Analysis of the conjunctival tissue revealed a transplantation-induced increase in TGF-β transcription in the 3-week-old rats. Conclusions: Our data suggest that local application of unprimed regulatory T cells may be a therapeutic strategy for preventing corneal graft rejection in young recipients.
    Full-text · Article · Dec 2014 · Molecular vision
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    ABSTRACT: Background: Penetrating keratoplasty can commonly restore vision in corneal blindness. However, immunological graft reactions may induce irreversible graft failure in a substantial percentage. Repeat keratoplasties in turn are associated with increased risk of graft failure and possibly irreversible blindness. Topical as well as systemic immunosuppressants are administered for prophylaxis. However, severe adverse effects limit long-term usage. By contrast, matching for transplantation antigens might be effective for a long time. Methods: FANCY is a prospective, controlled, randomised, double-blind, multi-centre clinical trial with two parallel arms. The primary objective is to evaluate superiority of the proposed HLA matching strategy in comparison to random graft assignment with respect to the primary endpoint 'time to first endothelial graft rejection'. Relevant inclusion criteria are age over 18 years and waiting for penetrating or endothelial lamellar keratoplasty. The most important exclusion criteria are abuse of medication and/or drugs and an anticipated waiting time for an HLA match longer than 6 months. After randomisation, patients either receive a HLA-matched graft (experimental intervention) or a random graft (control intervention). The calculated sample size is 620 patients. The trial started in 2009 with a recruitment period of 24 months. A total of 654 patients were included during this time. Discussion: The primary goal of FANCY is to assess whether histocompatibility matching is feasible and effective in the broad clinical routine. However, during the course of the trial, the landscape of keratoplasty changed due to the rise of Descemet Membrane Endothelial Keratoplasty (DMEK). Nowadays, immune reactions are confined mostly to the 'high-risk' subgroups. If we would design FANCY in 2014, we would narrow down the inclusion criteria to include only the high risk patients and accept longer waiting times for a matching donor here.
    Full-text · Article · Dec 2014 · BMC Ophthalmology

  • No preview · Article · Dec 2014 · Der Ophthalmologe

Publication Stats

4k Citations
554.49 Total Impact Points

Institutions

  • 2003-2016
    • University of Freiburg
      Freiburg, Baden-Württemberg, Germany
  • 2004-2015
    • Universitätsklinikum Freiburg
      • • Department of Ophthalmology
      • • Department of Oral Biotechnology
      • • Department of Neuroradiology
      Freiburg an der Elbe, Lower Saxony, Germany
    • Universität Mannheim
      Mannheim, Baden-Württemberg, Germany
  • 2014
    • Evangelische Hochschule Freiburg, Germany
      Freiburg, Baden-Württemberg, Germany
  • 2012
    • University College London
      • Division of Infection and Immunity
      London, ENG, United Kingdom
  • 2011
    • The Bracton Centre, Oxleas NHS Trust
      Дартфорде, England, United Kingdom
  • 2010
    • University of Duisburg-Essen
      Essen, North Rhine-Westphalia, Germany
  • 2009
    • Charité Universitätsmedizin Berlin
      Berlín, Berlin, 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
  • 1989
    • RWTH Aachen University
      • Department of Ophthalmology
      Aachen, North Rhine-Westphalia, Germany