133 results on '"Steven, Philipp"'
Search Results
102. Fluorescence Lifetime Imaging Unravels C. trachomatis Metabolism and Its Crosstalk with the Host Cell
- Author
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Szaszák, Márta, primary, Steven, Philipp, additional, Shima, Kensuke, additional, Orzekowsky-Schröder, Regina, additional, Hüttmann, Gereon, additional, König, Inke R., additional, Solbach, Werner, additional, and Rupp, Jan, additional
- Published
- 2011
- Full Text
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103. Conjunctiva-Associated Lymphoid Tissue – Current Knowledge, Animal Models and Experimental Prospects
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Steven, Philipp, primary and Gebert, Andreas, additional
- Published
- 2009
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104. Comparison of Cornea Module and DermaInspect for noninvasive imaging of ocular surface pathologies
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Steven, Philipp, primary, Müller, Maya, additional, Koop, Norbert, additional, Rose, Christian, additional, and Hüttmann, Gereon, additional
- Published
- 2009
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105. MASSIVE COATS DISEASE–LIKE TUMOR AFTER RETINAL DETACHMENT
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Schrader, Stefan, primary, Kusserow, Christine, additional, Steven, Philipp, additional, Müller, Maya, additional, Hoerauf, Hans, additional, and Laqua, Horst, additional
- Published
- 2009
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106. Intestinal Trefoil Factor/TFF3 Promotes Re-epithelialization of Corneal Wounds
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Paulsen, Friedrich P., primary, Woon, Chee-Wai, additional, Varoga, Deike, additional, Jansen, Anne, additional, Garreis, Fabian, additional, Jäger, Kristin, additional, Amm, Marita, additional, Podolsky, Daniel K., additional, Steven, Philipp, additional, Barker, Nicholas P., additional, and Sel, Saadettin, additional
- Published
- 2008
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107. Experimental Induction and Three-Dimensional Two-Photon Imaging of Conjunctiva-Associated Lymphoid Tissue
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Steven, Philipp, primary, Rupp, Jan, additional, Hu¨ttmann, Gereon, additional, Koop, Norbert, additional, Lensing, Carmen, additional, Laqua, Horst, additional, and Gebert, Andreas, additional
- Published
- 2008
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108. Non-Invasive Multi-Dimensional Two-Photon Microscopy enables optical fingerprinting (TPOF) of immune cells.
- Author
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Gehlsen, Uta, Szaszák, Marta, Gebert, Andreas, Koop, Norbert, Hüttmann, Gereon, and Steven, Philipp
- Abstract
Mucosal surfaces are constantly exposed to pathogens and show high immunological activity. In a broad variety of ocular surface disorders inflammation is common, but underlying mechanisms are often not fully understood. However, the main clinical problem is that inflammatory processes are difficult to characterize and quantify due to the impossibility of repeated tissue probing of the delicate ocular surface. Therefore non-invasive optical methods are thought to have the potential for intravital investigation of ocular surface inflammation. This study demonstrates the general potential of two-photon microscopy to non-invasively detect and discriminate key players of inflammation in the ocular surface by using intrinsic fluorescence-based features without the necessity of tissue probing or the use of dyes. The use of wavelength dependent measurements of fluorescence lifetime, in addition to autofluorescence intensity enables a functional differentiation of isolated immune cells in vitro at excitation wavelengths between 710 to 830 nm. Mixed cell cultures and first in vivo results indicate the use of excitation wavelength of 710 to 750 nm for further experiments and future use in patients. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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109. Anatomical Definition of the Subglottic Region
- Author
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Kutta, Hannes, primary, Steven, Philipp, additional, and Paulsen, Friedrich, additional
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- 2006
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110. VEGF expression in adult permanent thyroid cartilage: implications for lack of cartilage ossification
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Pufe, Thomas, primary, Mentlein, Rolf, additional, Tsokos, Michael, additional, Steven, Philipp, additional, Varoga, Deike, additional, Goldring, Mary B, additional, Tillmann, Bernhard N, additional, and Paulsen, Friedrich P, additional
- Published
- 2004
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111. Aberrant Lens Fiber Differentiation in Anterior Subcapsular Cataract Formation: A Process Dependent on Reduced Levels of Pax6
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Lovicu, Frank J., primary, Steven, Philipp, additional, Saika, Shizuya, additional, and McAvoy, John W., additional
- Published
- 2004
- Full Text
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112. Topische antiinflammatorische Therapieoptionen
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Siebelmann, Sebastian, Bucher, Franziska, Grajewski, Rafael S., and Steven, Philipp
- Published
- 2016
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- View/download PDF
113. Orcein-Picroindigocarmine. A New Multiple Stain.
- Author
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STEVEN, Philipp, primary, PAULSEN, Friedrich, additional, and TILLMANN, Bernhard, additional
- Published
- 2000
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114. Activated CD4+ T cells enter the splenic T-cell zone and induce autoantibody-producing germinal centers through bystander activation.
- Author
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Banczyk, David, Kalies, Kathrin, Nachbar, Lars, Bergmann, Lars, Schmidt, Philipp, Bode, Ulrike, Teegen, Bianca, Steven, Philipp, Lange, Tanja, Textor, Johannes, Ludwig, Ralf J., Stöcker, Winfried, König, Peter, Bell, Eric, and Westermann, Jürgen
- Abstract
CD4
+ T (helper) cells migrate in huge numbers through lymphoid organs. However, little is known about traffic routes and kinetics of CD4+ T-cell subsets within different organ compartments. Such information is important because there are indications that CD4+ T cells may influence the function of microenvironments depending on their developmental stage. Therefore, we investigated the migration of resting (naïve), activated, and recently activated (memory) CD4+ T cells through the different compartments of the spleen. Resting and recently activated CD4+ T cells were separated from thoracic duct lymph and activated CD4+ T cells were generated in vitro by cross-linking the T-cell receptor and CD28. The present study shows that all three CD4+ T-cell subsets selectively accumulate in the T-cell zone of the spleen. However, only activated T cells induce the formation of germinal centers (GCs) and autoantibodies in rats and mice. Our results suggest that in a two-step process they first activate B cells independent of the T-cell receptor repertoire and CD40 ligand (CD154) expression. The activated B cells then form GCs whereby CD154-dependend T-cell help is needed. Thus, activated T cells may contribute to the development of autoimmune diseases by activating autoreactive B cells in an Ag-independent manner. [ABSTRACT FROM AUTHOR]- Published
- 2014
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115. Could cannabis have potential in treating neuropathic dry eye? Topically-delivered cannabinoids reached target tissues without adverse effects.
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Steven, Philipp
- Subjects
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MEDICAL marijuana , *DRUG side effects ,TREATMENT of dry eye syndromes - Published
- 2017
116. Positive Effects of Oral Antibiotic Administration in Murine Chronic Graft-Versus-Host Disease.
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Sato, Shinri, Shimizu, Eisuke, He, Jingliang, Ogawa, Mamoru, Asai, Kazuki, Yazu, Hiroyuki, Rusch, Robert, Yamane, Mio, Yang, Fan, Fukuda, Shinji, Kawakami, Yutaka, Tsubota, Kazuo, Ogawa, Yoko, and Steven, Philipp
- Subjects
GRAFT versus host disease ,HEMATOPOIETIC stem cell transplantation ,BONE marrow transplantation ,SUPPRESSOR cells ,T helper cells - Abstract
Chronic graft-versus-host disease (cGVHD) is one of the most frequent complications experienced after allogeneic hematopoietic stem cell transplantation. Reportedly, dysbiosis and severe damage to the microbiome are also closely associated with GVHD. Herein, we aimed to elucidate the positive and negative effects of the administration of various antibiotics in a murine model of cGVHD. For allogeneic bone marrow transplantation (allo-BMT), bone marrow from B10.D2 mice were transplanted in BALB/c mice to induce cGVHD. The cGVHD mice were orally administered ampicillin, gentamicin (GM), fradiomycin, vancomycin, or the solvent vehicle (control group). Among the antibiotic-treated mice, the systemic cGVHD phenotypes and ocular cGVHD manifestations were suppressed significantly in GM-treated mice compared to that in control mice. Inflammatory cell infiltration and fibrosis in cGVHD-targeted organs were significantly attenuated in GM-treated mice. Although regulatory T cells were retained at greater levels in GM-treated mice, there were significantly fewer Th17 cells and interleukin (IL)-6-producing macrophages in cGVHD-targeted organs in these mice. Collectively, our results revealed that orally administered GM may exert positive effects in a cGVHD mouse model. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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117. Outcomes and complications of cataract surgery in patients with chronic ocular graft-versus-host-disease—a multicenter, retrospective analysis.
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Gehlsen, Uta, Faust, Christiane, Blecha, Christiane, Dietrich-Ntoukas, Tina, Eberwein, Philipp, Issleib, Susanne, Meyer-ter-Vehn, Tobias, Braun, Regine, Westekemper, Henrike, and Steven, Philipp
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PHACOEMULSIFICATION , *CATARACT surgery , *SURGICAL complications , *HEMATOPOIETIC stem cell transplantation , *VISUAL acuity , *CORNEA injuries - Abstract
Purpose : To evaluate the outcome of phacoemulsification in patients with chronic ocular Graft-versus-host disease (oGVHD) after allogeneic hematopoietic stem cell transplantation (aHSCT). Methods: Retrospective, observational multicenter study from 1507 oGVHD patients. From the patient files, data were collected including best-corrected visual acuity (BCVA), intraocular pressure (IOP), Schirmer's test I, tear film break-up time (TFBUT), corneal fluorescein staining score, postoperative complications, and pre- and post-operative topical therapy. Results: Seventy-three patients underwent cataract surgery in 104 eyes. In n = 84 eyes, the oGVHD NIH grade was documented; 12% (n = 12) of analyzed eyes were staged oGVHD NIH grade 1, 31% (n = 32) NIH 2 and 39% (n = 41) NIH 3. The mean BCVA improved in 82% of the eyes (n = 86 eyes). BCVA significantly increased from 0.7 ± 0.5 to 0.4 ± 0.4 LogMAR after surgery independent from oGVHD severity. The mean IOP decreased from 14 ± 4 to 13 ± 4 mmHg after surgery. Visual acuity was moderately correlated to the pre-operative degree of corneal staining (Pearson p = 0.26, p = 0.002, Cohen's effect size f = 0.29). The visual acuity decreased by 0.078 LogMar units (95% CI = 0.027–0.141) with each increase of corneal staining by one grade (p = 0.05). After surgery, corneal epitheliopathy increased significantly in 42% (n = 44) of the eyes. Postoperative complications included corneal perforation (n = 6, 6%), cystoid macular edema (n = 4, 4%), and endophthalmitis (n = 1, 1%). Conclusion: Phacoemulsification in patients with chronic oGVHD significantly improves visual acuity, but is associated with an increased risk of complications in particular corneal epitheliopathy and corneal perforations. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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118. Novel lubricant drops stabilize, relieve evaporative dry eye symptoms.
- Author
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Charters, Lynda and Steven, Philipp
- Subjects
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OPHTHALMIC drugs , *DRY eye syndromes , *LUBRICATION & lubricants , *TREATMENT effectiveness , *EVALUATION , *THERAPEUTICS - Abstract
The article discusses a study led by Philipp Steven and his team at the University of Cologne which examined the efficacy of perfluorohexyloctane (F6H8) in treating hyperevaporative dry eye disease. Topics covered include the decrease in tear osmolarity in the right eyes, the improvement in the patients meibum quality and the positive responses to the use of the drug and symptom relief.
- Published
- 2016
119. Innovative cyclosporine solution shows excellent safety, tolerability in study.
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Guttman Krader, Cheryl and Steven, Philipp
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CYCLOSPORINE , *DRUG tolerance , *IMMUNOLOGICAL adjuvants , *OPHTHALMIC drugs , *PATIENT safety - Abstract
The article discusses a study on semi-fluorinated alkanes (SFA) technology to show its safety, local tolerability and systemic exposure. A double-blind, randomized, crossover design was used where 18 subjects without dry eye were treated with the cyclosporine 0.05% solution or placebo which was then crossed over to the alternate agent. While the studies suggest a potential advantage of SFA-based products, it remains to be seen if the advantage translates into improved clinical outcomes.
- Published
- 2014
120. Deep learning-based automatic meibomian gland segmentation and morphology assessment in infrared meibography.
- Author
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Setu, Md Asif Khan, Horstmann, Jens, Schmidt, Stefan, Stern, Michael E., and Steven, Philipp
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DEEP learning , *MEIBOMIAN glands , *MORPHOLOGY , *EYE diseases , *MORPHOMETRICS - Abstract
Meibomian glands (MG) are large sebaceous glands located below the tarsal conjunctiva and the abnormalities of these glands cause Meibomian gland dysfunction (MGD) which is responsible for evaporative dry eye disease (DED). Accurate MG segmentation is a key prerequisite for automated imaging based MGD related DED diagnosis. However, Automatic MG segmentation in infrared meibography is a challenging task due to image artifacts. A deep learning-based MG segmentation has been proposed which directly learns MG features from the training image dataset without any image pre-processing. The model is trained and evaluated using 728 anonymized clinical meibography images. Additionally, automatic MG morphometric parameters, gland number, length, width, and tortuosity assessment were proposed. The average precision, recall, and F1 score were achieved 83%, 81%, and 84% respectively on the testing dataset with AUC value of 0.96 based on ROC curve and dice coefficient of 84%. Single image segmentation and morphometric parameter evaluation took on average 1.33 s. To the best of our knowledge, this is the first time that a validated deep learning-based approach is applied in MG segmentation and evaluation for both upper and lower eyelids. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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121. Detection of systemic immunosuppressants in autologous serum eye drops (ASED) in patients with severe chronic ocular graft versus host disease.
- Author
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Tahmaz, Volkan, Wiesen, Martin H. J., Gehlsen, Uta, Sauerbier, Laura, Stern, Michael E., Holtick, Udo, Gathof, Birgit, Scheid, Christof, Müller, Carsten, and Steven, Philipp
- Subjects
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GRAFT versus host disease , *EYE drops , *IMMUNOSUPPRESSIVE agents , *TANDEM mass spectrometry , *CYCLOSPORINE - Abstract
Purpose: Chronic graft versus host disease is a major consequence after allogeneic stem cell transplantation (allo-SCT) and has great impact on patients' morbidity and mortality. Besides the skin, liver, and intestines, the eyes are most commonly affected, manifesting as severe ocular surface disease. Treatment protocols include topical steroids, cyclosporine, tacrolimus, and ASED. Since these patients often receive systemic immunosuppressant therapy from their oncologists, a topical re-administration of these drugs via ASED with potentially beneficial or harmful effects is possible. The purpose of the study was to determine whether and to which extent systemic immunosuppressants are detectable in ASED. Methods: A total of 34 samples of ASED from 16 patients with hemato-oncological malignancies after allo-SCT were collected during the manufacturing process and screened for levels of cyclosporine, mycophenolic acid, everolimus, and tacrolimus via liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The study followed the tenets of the Declaration of Helsinki and informed consent was obtained from the subjects after explanation of the nature and possible consequences of the study. Results: Cyclosporine was found in 18 ASED samples in concentrations ranging from 6.5–105.0 ng/ml (32.0 ± 22.8 ng/ml, mean ± SD). The concentration range of mycophenolic acid in 19 samples was 0.04–25.0 mg/l (4.0 ± 5.4 mg/l, mean ± SD). Everolimus and tacrolimus concentrations were well below the respective limits of quantification (< 0.6 and < 0.5 ng/ml) of the established LC-MS/MS method in all samples. Conclusions: Our study suggests that orally administered cyclosporine and mycophenolic acid for the treatment of systemic GvHD, but not everolimus and tacrolimus, are distinctly detectable in ASED in relevant concentrations. It is highly likely that these agents affect topical therapy of ocular GvHD. However, the extent of this effect needs to be evaluated in further studies. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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122. The novel role of lymphatic vessels in the pathogenesis of ocular diseases.
- Author
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Clahsen, Thomas, Hadrian, Karina, Notara, Maria, Schlereth, Simona L., Howaldt, Antonia, Prokosch, Verena, Volatier, Thomas, Hos, Deniz, Schroedl, Falk, Kaser-Eichberger, Alexandra, Heindl, Ludwig M., Steven, Philipp, Bosch, Jacobus J., Steinkasserer, Alexander, Rokohl, Alexander C., Liu, Hanhan, Mestanoglu, Mert, Kashkar, Hamid, Schumacher, Björn, and Kiefer, Friedemann
- Subjects
- *
LYMPHATIC metastasis , *GRAFT versus host disease , *LIMBAL stem cells , *DRY eye syndromes , *OCULAR tumors , *GRAFT rejection - Abstract
Historically, the eye has been considered as an organ free of lymphatic vessels. In recent years, however, it became evident, that lymphatic vessels or lymphatic-like vessels contribute to several ocular pathologies at various peri- and intraocular locations. The aim of this review is to outline the pathogenetic role of ocular lymphatics, the respective molecular mechanisms and to discuss current and future therapeutic options based thereon. We will give an overview on the vascular anatomy of the healthy ocular surface and the molecular mechanisms contributing to corneal (lymph)angiogenic privilege. In addition, we present (i) current insights into the cellular and molecular mechanisms occurring during pathological neovascularization of the cornea triggered e.g. by inflammation or trauma, (ii) the role of lymphatic vessels in different ocular surface pathologies such as dry eye disease, corneal graft rejection, ocular graft versus host disease, allergy, and pterygium, (iii) the involvement of lymphatic vessels in ocular tumors and metastasis, and (iv) the novel role of the lymphatic-like structure of Schlemm's canal in glaucoma. Identification of the underlying molecular mechanisms and of novel modulators of lymphangiogenesis will contribute to the development of new therapeutic targets for the treatment of ocular diseases associated with pathological lymphangiogenesis in the future. The preclinical data presented here outline novel therapeutic concepts for promoting transplant survival, inhibiting metastasis of ocular tumors, reducing inflammation of the ocular surface, and treating glaucoma. Initial data from clinical trials suggest first success of novel treatment strategies to promote transplant survival based on pretransplant corneal lymphangioregression. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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123. [Correction: Objective analysis of corneal nerves and dendritic cells].
- Author
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Steven P and Setu A
- Abstract
Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht.
- Published
- 2024
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124. Objective Analysis of Corneal Nerves and Dendritic Cells.
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Steven P and Setu A
- Subjects
- Humans, Ophthalmic Nerve, Deep Learning, Corneal Diseases diagnosis, Corneal Diseases pathology, Pattern Recognition, Automated methods, Image Processing, Computer-Assisted methods, Intravital Microscopy methods, Algorithms, Cornea innervation, Dendritic Cells, Microscopy, Confocal methods
- Abstract
Corneal nerves and dendritic cells are increasingly being visualised to serve as clinical parameters in the diagnosis of ocular surface diseases using intravital confocal microscopy. In this review, different methods of image analysis are presented. The use of deep learning algorithms, which enable automated pattern recognition, is explained in detail using our own developments and compared with other established methods., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht./The authors declare that there is no conflict of interest., (Thieme. All rights reserved.)
- Published
- 2024
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125. Immunologic basis for development of keratoconjunctivitis sicca in systemic autoimmune diseases: Role of innate immune sensors.
- Author
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Stern ME, Theofilopoulos AN, Steven P, Niederkorn JY, Fox R, Calonge M, Scheid C, and Pflugfelder SC
- Subjects
- Humans, Conjunctiva immunology, Conjunctiva pathology, Tears immunology, Tears metabolism, Keratoconjunctivitis Sicca immunology, Immunity, Innate, Autoimmune Diseases immunology
- Abstract
The literature is filled with citations reporting an increased incidence of chronic dry eye disease, also known as keratoconjunctivitis sicca, in patients with systemic autoimmune diseases such as rheumatoid arthritis, Sjögren's Syndrome, systemic sclerosis and lupus. As the most environmentally exposed mucosal surface of the body, the conjunctiva constantly responds to environmental challenges which are typically self limited, but when persistent and unresolved may provoke pathogenic innate and adaptive immune reactions. Our understanding of the pathophysiological mechanisms by which systemic autoimmune diseases cause dry eye inducing ocular surface inflammation continues to evolve. Conjunctival immune tone responds to self or foreign danger signals (including desiccating stress) on the ocular surface with an initial non-specific innate inflammatory response. If unchecked, this can lead to activation of dendritic cells that present antigen and prime T and B cells resulting in an adaptive immune reaction. These reactions generally resolve, but dysfunctional, hyper-responsive immune cells found in systemic autoimmune diseases that are recruited to the ocular surface can amplify inflammatory stress responses in the ocular surface and glandular tissues and result in autoimmune reactions that disrupt tear stability and lead to chronic dry eye disease. We here propose that unique features of the ocular surface immune system and the impact of systemic immune dysregulation in autoimmune diseases, can predispose to development of dry eye disease, and exacerbate severity of existing dry eye., Competing Interests: Declaration of competing interest M. Stern – Consultantships - Kala. A. Theofilopoulos - None. P. Steven- Bausch & Lomb, URSA-PHARM, Marinomed, Bitop J. Niederkorn - None. R. Fox - None. M. Calonge - None. C. Scheid - None. S. Pflugfelder - None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
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126. Murine models of graft versus host disease (GVHD): Focus on ocular GVHD.
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Steven P, Perez VL, and Sharma A
- Subjects
- Animals, Mice, Disease Models, Animal, Dry Eye Syndromes etiology, Hematopoietic Stem Cell Transplantation adverse effects, Graft vs Host Disease metabolism, Lacrimal Apparatus metabolism
- Abstract
Graft versus host disease (GVHD) remains a major and serious complication of allogeneic hematopoietic stem cell transplantation. Based on the time of onset, clinical phenotypes, progression kinetics, and pathophysiology, GVHD is stratified into acute, chronic, and overlapping types. The eyes are among the most commonly affected organs in GVHD. Mouse models have played an important role in understanding the several key elements of GVHD pathobiology. The current review discusses the immunology, pathology, and key phenotypic features of mouse models of systemic GVHD. Furthermore, a critical appraisal of mouse models of ocular GVHD (oGVHD) is provided. The disease mechanisms underlying the ocular surface, meibomian gland, and lacrimal gland injury in these models are reviewed, and the relevance of oGVHD murine models to clinical oGVHD is also included., Competing Interests: Declaration of competing interest Authors do not have any financial conflict of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2023
- Full Text
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127. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: IV. The 2020 Highly morbid forms report.
- Author
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Wolff D, Radojcic V, Lafyatis R, Cinar R, Rosenstein RK, Cowen EW, Cheng GS, Sheshadri A, Bergeron A, Williams KM, Todd JL, Teshima T, Cuvelier GDE, Holler E, McCurdy SR, Jenq RR, Hanash AM, Jacobsohn D, Santomasso BD, Jain S, Ogawa Y, Steven P, Luo ZK, Dietrich-Ntoukas T, Saban D, Bilic E, Penack O, Griffith LM, Cowden M, Martin PJ, Greinix HT, Sarantopoulos S, Socie G, Blazar BR, Pidala J, Kitko CL, Couriel DR, Cutler C, Schultz KR, Pavletic SZ, Lee SJ, and Paczesny S
- Subjects
- Chronic Disease, Consensus, Humans, Incidence, National Institutes of Health (U.S.), Quality of Life, United States, Graft vs Host Disease
- Abstract
Chronic graft-versus-host disease (GVHD) can be associated with significant morbidity, in part because of nonreversible fibrosis, which impacts physical functioning (eye, skin, lung manifestations) and mortality (lung, gastrointestinal manifestations). Progress in preventing severe morbidity and mortality associated with chronic GVHD is limited by a complex and incompletely understood disease biology and a lack of prognostic biomarkers. Likewise, treatment advances for highly morbid manifestations remain hindered by the absence of effective organ-specific approaches targeting "irreversible" fibrotic sequelae and difficulties in conducting clinical trials in a heterogeneous disease with small patient numbers. The purpose of this document is to identify current gaps, to outline a roadmap of research goals for highly morbid forms of chronic GVHD including advanced skin sclerosis, fasciitis, lung, ocular and gastrointestinal involvement, and to propose strategies for effective trial design. The working group made the following recommendations: (1) Phenotype chronic GVHD clinically and biologically in future cohorts, to describe the incidence, prognostic factors, mechanisms of organ damage, and clinical evolution of highly morbid conditions including long-term effects in children; (2) Conduct longitudinal multicenter studies with common definitions and research sample collections; (3) Develop new approaches for early identification and treatment of highly morbid forms of chronic GVHD, especially biologically targeted treatments, with a special focus on fibrotic changes; and (4) Establish primary endpoints for clinical trials addressing each highly morbid manifestation in relationship to the time point of intervention (early versus late). Alternative endpoints, such as lack of progression and improvement in physical functioning or quality of life, may be suitable for clinical trials in patients with highly morbid manifestations. Finally, new approaches for objective response assessment and exploration of novel trial designs for small populations are required., (Copyright © 2021 The American Society for Transplantation and Cellular Therapy. All rights reserved.)
- Published
- 2021
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128. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: IIa. The 2020 Clinical Implementation and Early Diagnosis Working Group Report.
- Author
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Kitko CL, Pidala J, Schoemans HM, Lawitschka A, Flowers ME, Cowen EW, Tkaczyk E, Farhadfar N, Jain S, Steven P, Luo ZK, Ogawa Y, Stern M, Yanik GA, Cuvelier GDE, Cheng GS, Holtan SG, Schultz KR, Martin PJ, Lee SJ, Pavletic SZ, Wolff D, Paczesny S, Blazar BR, Sarantopoulos S, Socie G, Greinix H, and Cutler C
- Subjects
- Chronic Disease, Consensus, Early Diagnosis, Humans, National Institutes of Health (U.S.), United States, Graft vs Host Disease diagnosis
- Abstract
Recognition of the earliest signs and symptoms of chronic graft-versus-host disease (GVHD) that lead to severe manifestations remains a challenge. The standardization provided by the National Institutes of Health (NIH) 2005 and 2014 consensus projects has helped improve diagnostic accuracy and severity scoring for clinical trials, but utilization of these tools in routine clinical practice is variable. Additionally, when patients meet the NIH diagnostic criteria, many already have significant morbidity and possibly irreversible organ damage. The goals of this early diagnosis project are 2-fold. First, we provide consensus recommendations regarding implementation of the current NIH diagnostic guidelines into routine transplant care, outside of clinical trials, aiming to enhance early clinical recognition of chronic GVHD. Second, we propose directions for future research efforts to enable discovery of new, early laboratory as well as clinical indicators of chronic GVHD, both globally and for highly morbid organ-specific manifestations. Identification of early features of chronic GVHD that have high positive predictive value for progression to more severe manifestations of the disease could potentially allow for future pre-emptive clinical trials., (Copyright © 2021 The American Society for Transplantation and Cellular Therapy. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
129. [Second Survey on Patient-centred Care of Ocular Graft-versus-Host Disease in Germany].
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Faust C, Dietrich-Ntoukas T, and Steven P
- Subjects
- Child, Germany, Humans, Quality of Life, Surveys and Questionnaires, Graft vs Host Disease diagnosis, Graft vs Host Disease therapy, Hematopoietic Stem Cell Transplantation adverse effects
- Abstract
Background: graft-versus-host disease (GvHD) is a common complication after allogeneic haematopoietic stem cell transplantation (allo-SCT) and causes immunological rejection of host tissues, which can occur both acute or chronically. Approximately 40 - 80% of patients with the diagnosis of chronic GvHD (cGvHD) also develop ocular GvHD. For these patients, immediate and uncomplicated access to interdisciplinary patient-centred care is important. We performed this survey to improve understanding of the structure of patient-centred care in Germany., Methods: The GvHD working party of the Cornea Section of the German Society of Ophthalmology sent the "Survey of ocular GvHD 2016" to all university and specialised hospitals in Germany. We evaluated the data and compared the information with survey results from 2014, in order to draw conclusions about the structure and process of patient-centred care in ocular GvHD. Besides the questions from 2014 on the numbers of allo-SCT, frequency of examinations, etc. there were additional questions on the prescription of ciclosporin and autologous serum eye drops. The question on frequency examination was further expanded to include examinations of paediatric patients., Results: Of 30 participating hospitals, 22 had already taken part in the first survey. According to the information they provided, approx. 1860 allo-SCTs were performed in the transplantation units of the participating eye hospitals in 2016. This was more than half of the transplantations performed in Germany. Ophthalmologists examined between 2 and 250 Patients per year per centre. Eight clinics provide a specialised outpatient clinic for ocular GvHD. Nearly all the participating clinics prescribe ciclosporin eye drops. About ⅔ provide autologous serum eye drops, seven obtain them from external sources. Overall approx. 125 - 140 children were examined in 2016., Conclusions: Due to the potential severity of ocular GvHD with immobilisation of the patients and the imminent loss of sight, further improvements in eye care are required. For example, offers such as special consultations, with expertise located close to any transplantation unit are recommended. This requires in particular ophthalmologists to participate in the patient care to enhance quality of life after allo-SCT. In summary, we conclude that the present structures are not sufficient to treat all patients suffering from ocular GvHD in Germany, but the situation has evidently improved., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)
- Published
- 2020
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- View/download PDF
130. [Influence of Aging on Severity and Anti-Inflammatory Treatment of Experimental Dry Eye Disease].
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Steven P, Braun T, Krösser S, and Gehlsen U
- Subjects
- Administration, Ophthalmic, Administration, Topical, Animals, Dry Eye Syndromes pathology, Female, Mice, Mice, Inbred BALB C, Treatment Outcome, Aging immunology, Anti-Inflammatory Agents administration & dosage, Disease Models, Animal, Dry Eye Syndromes drug therapy, Dry Eye Syndromes immunology
- Abstract
Purpose Aging is an important factor in dry-eye disease that has not been studied in the context of therapeutic measures. Aging-associated modifications of the ocular immune system implicate that anti-inflammatory therapies may act differently among younger individuals in terms of onset and effect of different substances. The goal of this study was to determine differences in clinical phenotype and topical anti-inflammatory therapy using a desiccating stress mouse model. Methods An experimental dry-eye disease (desiccating stress model) was induced in 12-week and 12-month-old female BALB/c mice. Topical therapy included 0.05% cyclosporine/F4H5 (Novaliq), F4H5, 0.05% cyclosporine (Restasis
® , Allergan) and dexamethasone (Monodex® , Thea Pharma) for 3 consecutive weeks. A control group received no therapy whatsoever. Readout parameters included tear secretion, corneal fluorescein staining at 5 timepoints and histological analysis of goblet cell count at the end of the experiments. Results The older mice demonstrated a significantly stronger dry eye phenotype than the younger mice. Following therapy, the older mice responded to topical anti-inflammatory therapy significantly later than the younger individuals. Regarding the different substances used, cyclosporine/F4H5 showed a significantly faster decrease in corneal fluoresceine staining after only 1 week of therapy in comparison to all other groups. This substance was also superior regarding tear secretion and goblet cell count in age matched groups and in comparison to younger mice. Conclusions These experimental data support the implication that aging should be considered as an important factor in daily clinical practice. Furthermore, the differences found between substance classes, such as calcineurin antagonists and steroids, as well as different drug formulations, should be considered in future pre-clinical and clinical trials., (Georg Thieme Verlag KG Stuttgart · New York.)- Published
- 2017
- Full Text
- View/download PDF
131. [New Therapeutic Approaches in Inflammatory Diseases of the Eye - Targeting Lymphangiogenesis and Cellular Immunity: Research Unit FOR 2240 Presents Itself].
- Author
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Cursiefen C, Bock F, Clahsen T, Regenfuss B, Reis A, Steven P, Heindl LM, Bosch JJ, Hos D, Eming S, Grajewski R, Heiligenhaus A, Fauser S, Austin J, and Langmann T
- Subjects
- Animals, Disease Models, Animal, Immunity, Cellular immunology, Immunotherapy methods, Treatment Outcome, Angiogenesis Inhibitors administration & dosage, Endophthalmitis drug therapy, Endophthalmitis immunology, Immunity, Cellular drug effects, Lymphangiogenesis drug effects, Lymphangiogenesis immunology, Translational Research, Biomedical trends
- Abstract
Background Ophthalmology, principally, is a very successful subdiscipline in medicine. Nonetheless, there are still unmet medical needs which necessitate translational research. Methods The funding instrument of a Research Unit (RU) of the German Research Foundation (DFG) is presented as exemplified by the RU 2240 at the Department of Ophthalmology at the University of Cologne. Results The Research Unit integrates different research groups working on pathologic ocular inflammation, macrophages/microglia and (lymph)angiogenesis to collaborate in a synergistic way. Rotation positions allow young clinicians to rotate into research labs for a defined period of time. A Research Unit is also a powerful strategic tool to strengthen clinical and experimental ophthalmology at individual medical faculties. Conclusions The funding instrument of a Research Unit is highly suitable for fostering translational research in a medical subdiscipline such as ophthalmology, supporting the next generation of (clinician) scientists in ophthalmology and finding new cures for our patients., (Georg Thieme Verlag KG Stuttgart · New York.)
- Published
- 2017
- Full Text
- View/download PDF
132. [Topical Anti-Inflammatory Therapy Options].
- Author
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Siebelmann S, Bucher F, Grajewski RS, and Steven P
- Subjects
- Administration, Topical, Anti-Inflammatory Agents, Non-Steroidal administration & dosage, Humans, Anti-Inflammatory Agents administration & dosage, Dermatologic Agents administration & dosage
- Abstract
Competing Interests: Interessenkonflikt: Die Autoren bestätigen, dass kein Interessenkonflikt vorliegt.
- Published
- 2016
- Full Text
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133. Activated CD4+ T cells enter the splenic T-cell zone and induce autoantibody-producing germinal centers through bystander activation.
- Author
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Banczyk D, Kalies K, Nachbar L, Bergmann L, Schmidt P, Bode U, Teegen B, Steven P, Lange T, Textor J, Ludwig RJ, Stöcker W, König P, Bell E, and Westermann J
- Subjects
- Adoptive Transfer, Animals, Bystander Effect, CD40 Ligand genetics, Cells, Cultured, Immunologic Memory, Lymphocyte Activation, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Rats, Rats, Inbred Lew, Autoantibodies metabolism, CD4-Positive T-Lymphocytes immunology, Germinal Center immunology, Spleen immunology, T-Lymphocyte Subsets immunology
- Abstract
CD4(+) T (helper) cells migrate in huge numbers through lymphoid organs. However, little is known about traffic routes and kinetics of CD4(+) T-cell subsets within different organ compartments. Such information is important because there are indications that CD4(+) T cells may influence the function of microenvironments depending on their developmental stage. Therefore, we investigated the migration of resting (naïve), activated, and recently activated (memory) CD4(+) T cells through the different compartments of the spleen. Resting and recently activated CD4(+) T cells were separated from thoracic duct lymph and activated CD4(+) T cells were generated in vitro by cross-linking the T-cell receptor and CD28. The present study shows that all three CD4(+) T-cell subsets selectively accumulate in the T-cell zone of the spleen. However, only activated T cells induce the formation of germinal centers (GCs) and autoantibodies in rats and mice. Our results suggest that in a two-step process they first activate B cells independent of the T-cell receptor repertoire and CD40 ligand (CD154) expression. The activated B cells then form GCs whereby CD154-dependent T-cell help is needed. Thus, activated T cells may contribute to the development of autoimmune diseases by activating autoreactive B cells in an Ag-independent manner., (© 2013 The Authors. European Journal of Immunology published by Wiley-VCH Verlag GmbH & Co. KGaA Weinheim.)
- Published
- 2014
- Full Text
- View/download PDF
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