252 results on '"U, Pleyer"'
Search Results
2. Efficiency of Cytokine Gene Transfer in Corneal Endothelial Cells and Organ-Cultured Corneas Mediated by Liposomal Vehicles and Recombinant Adenovirus.
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E. Bertelmann, T. Ritter, K. Vogt, R. Reszka, C. Hartmann, and U. Pleyer
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- 2003
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3. Successful infliximab treatment of posterior scleritis in a 13-year-old child refractory to other immunosuppressive therapy.
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K. Weiss, R. Rieger, R. Keitzer, and U. Pleyer
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JUVENILE diseases ,EYE diseases ,INFLIXIMAB ,IMMUNOSUPPRESSIVE agents - Abstract
Abstract Background  Posterior scleritis is a potentially blinding inflammatory disorder rarely seen in children. Standard care consists of systemic administration of steroids and immunosuppressants such as methotrexate or ciclosporin A. We describe the case of a young girl suffering from therapy refractory posterior scleritis successfully treated with the tumor necrosis factor (TNF) inhibitor infliximab. Methods  This study was an interventional case report. The medical chart of a 13-year-old child treated with infliximab (5 mg/kg, 10 applications at a 4â8 week interval) was reviewed for changes of visual acuity, fundoscopy, optic choherence tomography, ultrasound imaging, and adverse events. Results  Infliximab therapy (5 mg/kg, 10 applications at a 4â8 week interval) led to a long-term remission of posterior scleritis after unsuccessful therapy with high dose prednisolone, methotrexate, and ciclosporin A. To date no side effects have been reported. Conclusions  Administration of infliximab may be considered under appropriate circumstances to treat children with posterior scleritis. [ABSTRACT FROM AUTHOR]
- Published
- 2007
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4. Ophthalmic Research Moves Online for Submission and Peer Review.
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U. Pleyer and N. Orlic
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- 2005
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5. S3 guideline: Diagnosis and treatment of epidermal necrolysis (Stevens-Johnson syndrome and toxic epidermal necrolysis) - Part 2: Supportive therapy of EN in the acute and post-acute stages.
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Paulmann M, Heuer R, Annecke T, Behr B, Boch K, Boos AM, Brockow K, French LE, Gille J, Gundlach V, Hartmann B, Höger P, Hofmann SC, Klein T, Lehnhardt M, Liß Y, Maier P, Mandel P, Marathovouniotis N, Marlok F, Mittelviefhaus H, Pleyer U, Pradeau M, Rall K, Rieg S, Rittner H, Sander F, Schnitzler S, Schut C, Stolle A, Vorobyev A, Wedi B, Weiss J, Zepp M, Ziemer M, Mockenhaupt M, and Nast A
- Abstract
Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are rare, predominantly drug-induced, acute life-threatening diseases of skin and mucosae. SJS and TEN are nowadays considered as variants of one disease entity with varying degrees of severity called epidermal necrolysis (EN). EN is associated with high morbidity and mortality and constitutes a major disease burden for affected patients. The guideline "Diagnosis and treatment of epidermal necrolysis (Stevens-Johnson syndrome and toxic epidermal necrolysis)" was developed under systematic consideration of existing scientific literature and in a formal consensus process according to regulations issued by the Association of Scientific Medical Societies in Germany (AWMF) to establish an evidence-based framework to support clinical decision-making. The interdisciplinary guideline commission consisted of representatives from various specialist societies and of patient representatives. The guideline is aimed at specialists in the fields of dermatology, ophthalmology, plastic surgery, intensive care, and pediatrics in hospitals and offices, as well as other medical specialties involved in the diagnosis and treatment of EN. The guideline is also aimed at patients, their relatives, insurance funds, and policymakers. The second part is concerned with the topics of supportive therapy in the acute phase of EN and outpatient follow-up treatment., (© 2024 The Author(s). Journal der Deutschen Dermatologischen Gesellschaft published by Wiley‐VCH GmbH on behalf of Deutsche Dermatologische Gesellschaft.)
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- 2024
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6. S3 guideline: Diagnosis and treatment of epidermal necrolysis (Stevens-Johnson syndrome and toxic epidermal necrolysis) - Part 1: Diagnosis, initial management, and immunomodulating systemic therapy.
- Author
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Heuer R, Paulmann M, Annecke T, Behr B, Boch K, Boos AM, Brockow K, French LE, Gille J, Gundlach V, Hartmann B, Höger P, Hofmann SC, Klein T, Lehnhardt M, Liß Y, Maier P, Mandel P, Marathovouniotis N, Marlok F, Mittelviefhaus H, Pleyer U, Pradeau M, Rall K, Rieg S, Rittner H, Sander F, Schnitzler S, Schut C, Stolle A, Vorobyev A, Wedi B, Weiss J, Zepp M, Ziemer M, Mockenhaupt M, and Nast A
- Subjects
- Humans, Germany, Immunomodulation, Immunologic Factors therapeutic use, Immunologic Factors adverse effects, Stevens-Johnson Syndrome diagnosis, Stevens-Johnson Syndrome therapy
- Abstract
Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are rare, predominantly drug-induced, acute, life-threatening diseases of skin and mucosae. SJS and TEN are nowadays considered variants of one disease entity with varying degrees of severity called epidermal necrolysis (EN). EN is associated with high morbidity and mortality and constitutes a major disease burden for affected patients. The guideline "Diagnosis and treatment of epidermal necrolysis (Stevens-Johnson syndrome and toxic epidermal necrolysis)" was developed under systematic consideration of existing scientific literature and in a formal consensus process according to regulations issued by the Association of Scientific Medical Societies in Germany (AWMF) to establish an evidence-based framework to support clinical decision-making. The interdisciplinary guideline commission consisted of representatives from various specialist societies and patient representatives. The guideline is aimed at specialists in the fields of dermatology, ophthalmology, plastic surgery, intensive care, and pediatrics in hospitals and offices, as well as other medical speciallved in the diagnosis and treatment of EN. The guideline is also aimed at patients, their relatives, insurance funds, and policymakers. This first part focuses on the diagnostic aspects, the initial management as well as the immunomodulating systemic therapy., (© 2024 The Author(s). Journal der Deutschen Dermatologischen Gesellschaft published by Wiley‐VCH GmbH on behalf of Deutsche Dermatologische Gesellschaft.)
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- 2024
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7. Treatment strategies for Spondyloarthritis: Implementation of precision medicine - Or "one size fits all" concept?
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Proft F, Duran TI, Ghoreschi K, Pleyer U, Siegmund B, and Poddubnyy D
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- Humans, Precision Medicine methods, Spondylarthritis diagnosis, Spondylarthritis drug therapy, Spondylarthritis therapy, Antirheumatic Agents therapeutic use
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Spondyloarthritis (SpA) is a term to describe a group of chronic inflammatory rheumatic diseases, which have common pathophysiological, genetic, and clinical features. Under the umbrella term SpA, two main groups are subsumed: axial SpA (radiographic axSpA and non-radiographic axSpA) and peripheral SpA (with the leading representative being psoriatic arthritis (PsA) but also arthritis associated with inflammatory bowel disease (IBD), reactive arthritis, and undifferentiated pSpA). The key clinical symptom in axSpA is chronic back pain, typically with inflammatory characteristics, which starts in early adulthood, while the leading clinical manifestations of peripheral SpA (pSpA) are arthritis, enthesitis, and/or dactylitis. Furthermore, extra-musculoskeletal manifestations (EMMs) (acute anterior uveitis, psoriasis, and IBD) can accompany axial or peripheral symptoms. All these factors need to be taken into account when making treatment decisions in SpA patients. Despite the major advances in the treatment landscape over the past two decades with the introduction of biological disease-modifying anti-rheumatic drugs (bDMARDs) and most recently targeted synthetic DMARDs (tsDMARDs), a relevant proportion of patients still does not achieve the desired state of remission (=absence of disease activity). With this implementation of new treatment modalities, clinicians now have more choices to make in the treatment algorithms. However, despite generalized treatment recommendations, all factors need to be carefully considered when deciding on the optimal treatment strategy for an individual patient in clinical practice, aiming at an important first step towards personalized treatment strategies in SpA. In this narrative review, we focus on the efficacy of approved and emerging treatment options in axSpA and PsA as the main representative of pSpA and discuss their selective effect on the different manifestations associated with SpA to provide guidance on drivers of treatment decisions in specific situations., Competing Interests: Declaration of competing interest TID: has nothing to disclose. FP: received grants and personal fees from Novartis, Eli Lilly, and UCB and personal fees from AbbVie, AMGEN, BMS, Celgene, Galapagos, Janssen, Hexal, Medscape, MSD, Pfizer and Roche outside the presented work. KG: received grants or contracts from Bristol Myers Squibb; received consulting fees from Abbvie, Lilly, Almirall, Janssen, Boehringer Ingelheim, Pfizer, Bristol Myers Squibb, and UCB; received payment /honoraria for lectures, presentations, speaker bureaus, manuscript writing or educational events from Abbvie Allergan Alimera Bayer Novartis Pfizer Roche Santen Thea; received support for attending meetings and/or travel from Abbvie, Almirall, BMS, and Lilly. UP: received grants or contracts from EU, BMBF; received consulting fees from Affibody, Alcon, Allergan, Janssen, Novartis, Panoptes, Pfizer, Roche, Thea, Lilly, Pfizer, Santen. Holds patents EP 19732357.9, PCT/EP2019/066419, PCT/J/2020–570,837.BS: received grants or contracts from Pfizer; received consulting fees from Abbvie, Abivax, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Endpoint Health, Falk Pharma, Galapagos, Gilead, Janssen, Landos, Lilly, Pfizer, and Takeda; received payment /honoraria for lectures, presentations, speaker bureaus, manuscript writing or educational events from Abbvie, BMS, CED Service GmbH, Eli Lilly, Falk Pharma, Ferring, Galapagos, Janssen, Lilly, Pfizer, and Takeda.DP: received consulting fees from AbbVie, Biocad, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, MSD, Moonlake, Novartis, Pfizer, Samsung Bioepis and UCB; received payment /honoraria for lectures, presentations, speaker bureaus, manuscript writing or educational events from AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, MSD, Medscape, Novartis, Peervoice, Pfizer and UCB., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
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- 2024
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8. Complement Component C5a and Fungal Pathogen Induce Diverse Responses through Crosstalk between Transient Receptor Potential Channel (TRPs) Subtypes in Human Conjunctival Epithelial Cells.
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Rech L, Dietrich-Ntoukas T, Reinach PS, Brockmann T, Pleyer U, and Mergler S
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- Humans, Transient Receptor Potential Channels metabolism, Calcium Signaling, TRPV Cation Channels metabolism, Epithelial Cells metabolism, Epithelial Cells microbiology, Conjunctiva metabolism, Conjunctiva microbiology, Calcium metabolism, Complement C5a metabolism
- Abstract
The conjunctiva has immune-responsive properties to protect the eye from infections. Its innate immune system reacts against external pathogens, such as fungi. The complement factor C5a is an important contributor to the initial immune response. It is known that activation of transient-receptor-potential-vanilloid 1 (TRPV1) and TRP-melastatin 8 (TRPM8) channels is involved in different immune reactions and inflammation in the human body. The aim of this study was to determine if C5a and mucor racemosus e voluminae cellulae (MR) modulate Ca
2+ -signaling through changes in TRPs activity in human conjunctival epithelial cells (HCjECs). Furthermore, crosstalk was examined between C5a and MR in mediating calcium regulation. Intracellular Ca2+ -concentration ([Ca2+ ]i ) was measured by fluorescence calcium imaging, and whole-cell currents were recorded using the planar-patch-clamp technique. MR was used as a purified extract. Application of C5a (0.05-50 ng/mL) increased both [Ca2+ ]i and whole-cell currents, which were suppressed by either the TRPV1-blocker AMG 9810 or the TRPM8-blocker AMTB (both 20 µM). The N-terminal peptide C5L2p (20-50 ng/mL) blocked rises in [Ca2+ ]i induced by C5a. Moreover, the MR-induced rise in Ca2+ -influx was suppressed by AMG 9810 and AMTB, as well as 0.05 ng/mL C5a. In conclusion, crosstalk between C5a and MR controls human conjunctival cell function through modulating interactions between TRPV1 and TRPM8 channel activity.- Published
- 2024
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9. Monomorphic papules in tattooed skin areas with associated bilateral uveitis.
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Lu A, Nguyen K, Moritz R, Pleyer U, and Korsing S
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- Humans, Uveitis etiology, Uveitis pathology, Male, Diagnosis, Differential, Adult, Skin pathology, Female, Tattooing adverse effects
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- 2024
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10. Treatment exit options for non-infectious uveitis registry: participant characteristics at 3 years.
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Fink DJ, Dell J, Heinz C, Wintergerst MWM, Höller T, Berger M, Schmid M, Boden KT, Pleyer U, Reitsamer H, Deuter CME, Lohmann TK, and Finger RP
- Abstract
Purpose: The Treatment exit Options For non-infectious Uveitis (TOFU) registry documents disease courses for non-anterior non-infectious uveitis entities with and without treatment to generate more evidence for clinical management recommendations including treatment exit strategies. In this article, we present the participants' baseline characteristics after the first 3 years., Methods: TOFU is an observational, prospective registry and recruits patients ≥18 years of age with non-anterior non-infectious uveitis with or without a history of previous disease-modifying antirheumatic drugs (DMARDs) treatment. The data are collected in the electronic data capture software REDCap and include ophthalmological and general medical history as well as clinical findings., Results: Between 24.10.2019 and 27.12.2022, 628 patients were enrolled at 25 clinical sites in Germany and Austria. Patients with intermediate uveitis were most frequently included (n=252; 40.1%) followed by posterior uveitis (181; 28.8%), panuveitis (n=154; 24.5%) and retinal vasculitis (n=41, 6.5%). At baseline, 39.6% were treated with systemic corticosteroids, 22.3% with conventional synthetic (cs) DMARDs, 20.5% with biological (b) DMARDs and 3.6% with other systemic treatments. Average best corrected visual acuity (BCVA) was 0.69 decimal. Patients with panuveitis had the worst BCVA with 0.63 decimal. Overall, only 8 patients (1.3%) suffered from severe visual impairment., Conclusions: Less than half of participants required DMARD treatment at baseline, with csDMARDs used more frequently than bDMARDs. The presence of severe visual impairment was low, mostly affecting patients with panuveitis. These findings are in line with comparable monocentric cross-sectional studies of tertiary uveitis centres in Germany and will allow us to generate generalisable evidence in TOFU., Competing Interests: Competing interests: CH is a consultant for Alimera Sciences (Aldershot, Hampshire, UK) and received Honoria from AbbVie and Novartis. MWMW is a consultant for Heine Optotechnik GmbH and glaucare GmbH, has received honoraria from ASKIN & CO GmbH, Bayer AG, Berlin-Chemie AG, Heidelberg Engineering, Novartis Pharma GmbH, Pro Generika e.V., Eyepress Fachmedien GmbH, and Science Consulting in Diabetes GmbH, and research funding from CenterVue SpA, Carl Zeiss Meditec, and Novartis Pharma GmbH. RPF is a consultant for Alimera, Apellis, Biogen, Böhringer-Ingelheim, Bayer, Caterna, Novartis, ODOS, ProGenerika, Roche/Genentech, has received honoraria from Roche and research funding from Biogen. He is member of the advisory board of Stada Pharm, Roche and Opthea. CMED is a member of the advisory board of Alimera and he has received honoraria from AbbVie, Novartis, Santen and Thea. His institution received funding for clinical trials from Tarsier and Roche. UP received study support from Abbvie and honoraria from Abbvie, Alimera and Novartis. None of the following authors have any proprietary interests or conflicts of interest related to this submission: DJF, JD, TH, MB, MS, HR, KTB and TKL., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2024
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11. Fluocinolone acetonide 0.2 µg/day intravitreal implant in non-infectious uveitis affecting the posterior segment: EU expert user panel consensus-based clinical recommendations.
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Pleyer U, Pavesio C, Miserocchi E, Heinz C, Devonport H, Llorenç V, Burke T, Nogueira V, Kodjikian L, and Bodaghi B
- Abstract
Background: Non-infectious uveitis affecting the posterior segment of the eye (NIU-PS) is an inflammatory disease, which can significantly impair visual acuity if not adequately treated. Fluocinolone-acetonide sustained-release-0.2 µg/day intravitreal (FAc) implants are indicated for prevention of relapse in recurrent NIU-PS. The aim here was to provide treating clinicians with some consensus-based-recommendations for the clinical management of patients with NIU-PS with 0.2 µg/day FAc implants., Methods: A European-clinical-expert-group agreed to develop a consensus report on different issues related to the use of FAc implants in patients with NIU-PS., Results: The Clinical-expert-panel provided specific recommendations focusing on clinical presentation (unilateral/bilateral) of the NIU-PS; systemic involvement of NIU-PS and the lens status. Treatment algorithms were developed; one that refers to the management of patients with NIU-PS in clinical practice and another that establishes the best clinical scenarios for the use of FAc implants, both as monotherapy and as adjuvant therapy. Additionally, the Clinical-expert-panel has provided recommendations about the use of the FAc implants in a clinical-setting. The Clinical-expert-panel also considered the safety profile of FAc implants and their possible implications in the daily practice., Conclusions: As more clinical experience has been gained using FAc implants, it was necessary to update the clinical recommendations that guide patient management in the clinic. The current consensus document addresses relevant issues related to the use of FAc implants on different types of patients with various etiologies of NIU-PS, and was conducted to standardize approaches to help specialists obtain better clinical outcomes., (© 2024. The Author(s).)
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- 2024
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12. Outcomes after reversed corneal graft rejection: a report from the European VISICORT project.
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Iselin KC, Hjortdal J, Armitage WJ, Tole D, Pleyer U, Vabres B, Griffin MD, and Murphy CC
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- Humans, Male, Female, Middle Aged, Aged, Graft Survival, Europe epidemiology, Keratoplasty, Penetrating, Prospective Studies, Adult, Intraocular Pressure physiology, Endothelium, Corneal pathology, Descemet Stripping Endothelial Keratoplasty methods, Treatment Outcome, Corneal Diseases surgery, Immunosuppressive Agents therapeutic use, Risk Factors, Graft Rejection immunology, Graft Rejection prevention & control, Visual Acuity
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Objective: This study aims to describe the outcome of corneal grafts, both low risk and high risk, after successfully reversed immunological rejection., Methods: Datasets on reversed rejection episodes in penetrating and endothelial keratoplasties between 2014 and 2019 (n=876) were extracted from the Adverse Immune Signatures and their Prevention in Corneal Transplantation database, which contains the prospectively and consecutively collected corneal transplants from five European centres. Stratified by the preoperatively determined risk status for immunological rejection, the outcome parameters analysed included visual acuity, intraocular pressure, endothelial cell density and central corneal thickness before and after reversed rejection episodes., Results: Fourty-seven (52%) out of a total of 91 identified rejection episodes were successfully reversed and were available for analysis (23 penetrating and 24 endothelial keratoplasties). No statistically significant change was found for any of the parameters studied between the values before and the values 3 months after the rejection episode, irrespective of the preoperative risk status., Conclusion: The outcome of corneal grafts that survive immunological rejection may be clinically indistinguishable from the state before immunological rejection, irrespective of graft type and risk status. These findings support clinicians by providing information on prognosis after reversed rejection episodes and by giving patients realistic expectations regarding the outcome., Competing Interests: Competing interests: One of the co-authors is an editor., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2024
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13. Fluocinolone Acetonide Implant for Uveitis: Dissecting Responder and Non-Responder Outcomes at a Tertiary Center.
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Abu Arif J, Knecht VA, Rübsam A, Lussac V, Jami Z, Pohlmann D, Müller B, and Pleyer U
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Macular edema (ME) remains a primary cause of visual deterioration in uveitis. Visual acuity (VA) can often be maintained using corticosteroid depot systems. This study evaluated the efficacy of a fluocinolone acetonide (FAc) intravitreal implant (ILUVIEN
® ) in treating non-infectious uveitis using real-world data. This retrospective analysis included 135 eyes subdivided into responders and non-responders. Central retinal thickness (CRT), VA, and intraocular pressure (IOP) were followed over time. A significant decrease in CRT and an increase in VA were observed in all eyes throughout the follow-up period ( p < 0.01). An IOP increase ( p = 0.028) necessitated treatment in 43% of eyes by Month 6. Non-responders were older ( p = 0.004) and had been treated with more dexamethasone (DEX) implants ( p = 0.04); 89.3% had a defect in the external limiting membrane (ELM) and inner/outer segment (IS/OS) zone ( p < 0.001). Immunomodulatory therapy had no impact on treatment response. Pars plana vitrectomy (PPV) patients had a mean CRT reduction of 47.55 µm and a reduced effect by Month 24 ( p = 0.046) versus non-PPV patients. We conclude that the FAc implant achieves long-term control of CRT and improves VA. Increases in IOP were manageable. Eyes with a previous PPV showed milder results. Data showed a correlation between older age, a damaged ELM and IS/OS zone, frequent DEX inserts, and poorer outcome measures.- Published
- 2024
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14. Fundus Autofluorescence in Posterior and Panuveitis-An Under-Estimated Imaging Technique: A Review and Case Series.
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Mauschitz MM, Zeller M, Sagar P, Biswal S, Guzman G, Terheyden JH, Meyer CH, Holz FG, Heinz C, Pleyer U, Finger RP, and Wintergerst MWM
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- Humans, Fluorescein Angiography methods, Panuveitis diagnostic imaging, Panuveitis diagnosis, Fundus Oculi, Optical Imaging methods
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Fundus autofluorescence (FAF) is a prompt and non-invasive imaging modality helpful in detecting pathological abnormalities within the retina and the choroid. This narrative review and case series provides an overview on the current application of FAF in posterior and panuveitis. The literature was reviewed for articles on lesion characteristics on FAF of specific posterior and panuveitis entities as well as benefits and limitations of FAF for diagnosing and monitoring disease. FAF characteristics are described for non-infectious and infectious uveitis forms as well as masquerade syndromes. Dependent on the uveitis entity, FAF is of diagnostic value in detecting disease and following the clinical course. Currently available FAF modalities which differ in excitation wavelengths can provide different pathological insights depending on disease entity and activity. Further studies on the comparison of FAF modalities and their individual value for uveitis diagnosis and monitoring are warranted.
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- 2024
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15. Viral Anterior Uveitis: Differences in Retinal Vessel Area Density between the Affected and Non-Affected Eye Using Optical Coherence Tomography Angiography.
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Maier AB, Mandrossa D, Reitemeyer E, Winterhalter S, Rübsam A, and Pleyer U
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Purpose: To investigate differences in the retinal vessel area density (VAD) on optical coherence tomography angiography (OCTA) between eyes with unilateral herpetic viral anterior uveitis (VAU) (herpes-simplex virus (HSV) and varicella-zoster virus (VZV)) and the non-affected fellow eye., Methods: In this monocentric, observational, prospective case series we analyzed the VAD of the macula, optic disc, and peripapillary region in affected and non-affected eyes of 22 patients with HSV-positive and 22 patients with VZV-positive VAU using OCTA. We analyzed also the visual field mean deviation (MD), the retinal nerve fiber layer (RNFL) thickness, Bruch's Membrane Opening-Minimum Rim Width (BMO-MRW), and ganglion cell layer (GCL) thickness on OCT and correlated the results with the different VADs., Results: The macular VAD in the superficial vascular plexus (SVC) was significant lower in the affected compared to the non-affected eye for both viruses (HSV: 33.0% ± 3.3% vs. 34.7% ± 2.6%, p = 0.011; adjusted p = 0.040; VZV: 33.1% ± 3.2% vs. 34.3% ± 2.8%, p = 0.012; adjusted p = 0.050). Additionally, the VAD of the peripapillary SVC differed between the affected and non-affected eye for VZV-positive VAU (47.1% ± 6.2% vs. 50.5% ± 6.3%, p = 0.048, adjusted p = 0.100). For both HSV-positive and VZV-positive VAU, there were correlations between macular or peripapillary SVC VAD and BMO-MRW, GCL thickness, RNFL thickness or MD of the affected eye., Conclusion: We observed vascular dysfunction characterized by decreased macular and peripapillary VAD in the superficial plexus on OCTA in eyes with HSV- and VZV-positive VAU compared to non-affected fellow eyes. These changes might be an early sign of glaucomatous damage or may be a direct consequence of the herpes viruses themselves.
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- 2024
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16. The role of age in ocular toxoplasmosis: clinical signs of immunosenescence and inflammaging.
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Eraghi AT, Garweg JG, and Pleyer U
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Purpose: This study aimed to investigate the association between age, immune response, and clinical presentation of ocular toxoplasmosis (OT)., Design: This was a monocentric, retrospective, observational cohort study., Methods: A review of the medical records of patients with active OT at the Uveitis Center, Charité Universitätsmedizin, was conducted. Baseline parameters included age at presentation, visual acuity, intraocular pressure (IOP), size and location of active lesions, inflammatory activity, antibody index (AI), and complications of intraocular inflammation. The data were presented as the mean ± standard deviation (SD). The level of significance was set at a p -value of <0.05., Results: Between 1998 and 2019, 290 patients with active OT were diagnosed at our tertiary reference center. The mean age of the participants was 37.7 ± 17.1 years, 53.8% of them were female individuals, and 195 patients (70.9%) showed recurrent disease. Older age was associated with lower baseline visual acuity ( p = 0.043), poor visual outcome ( p = 0.019), increased inflammatory activity ( p < 0.005), and larger retinal lesions ( p < 0.005). Older patients presented a lower AI (<35 years: 45.1 ± 82.7, median: 12.1; ≥35 years: 18.6 ± 50.5, median: 5.8; p = 0.046), confirmed by a decrease in AI with increasing age ( R
2 = 0.045; p = 0.024). Finally, AI was correlated with lesion size (multiple linear regression analysis: p = 0.043). Macular involvement (24.3% of patients) was positively correlated with complications (macular/peripapillary edema and retinal detachment, p < 0.005) and poor visual outcome ( p < 0.005) and was negatively correlated with inflammatory activity ( p < 0.005)., Conclusion: We found a strong and clinically relevant impact of age on the clinical presentation and course of OT. While an unspecific inflammatory response increased with age, the specific, local humoral immune response declined. These findings are well in line with the concept of immunosenescence and inflammaging in uveitis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Eraghi, Garweg and Pleyer.)- Published
- 2024
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17. Knowledge and Current Practices in Monogenic Uveitis: An International Survey by IUSG and AIDA Network.
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Gaggiano C, Gupta V, Agrawal R, De Smet MD, Frediani B, Tosi GM, Paroli MP, Sridharan S, Pavesio CE, Pleyer U, Denisova EV, Babu K, de-la-Torre A, Yang P, Davis JL, Cunningham ET, Carreño E, Goldstein D, Fonollosa A, Cantarini L, Sobrin L, and Fabiani C
- Abstract
Introduction: This study aims to explore awareness, knowledge, and diagnostic/therapeutic practices in monogenic uveitis (mU) among uveitis experts., Methods: This is an explorative, cross-sectional survey study. An anonymous, semi-structured, electronic survey was delivered to uveitis experts from the Autoinflammatory Diseases Alliance (AIDA) Network and International Uveitis Study Group (IUSG). We included respondents answering ≥ 50% of the survey., Results: Seventy-seven participants rated their knowledge of mU as proficient (3.9%), adequate (15.6%), sufficient (16.9%), or poor (63.6%). When asked about the first mU gene they thought of, 60.4% mentioned NOD2, 3.9% mentioned NLRP3 or MEFV, and 49.4% provided incorrect or no answers. Success rates in clinical scenarios varied from 15.6% to 55.8% and were higher for ophthalmologists working in multidisciplinary teams (p < 0.01). Genetic testing was ordered for suspected mU by 41.6% of physicians. The availability of molecular techniques did not significantly differ based on geography (p > 0.05). The public healthcare system ensured a higher percentage of tests prescribed were obtained by patients compared to private insurances (p < 0.00). In terms of disease-modifying anti-rheumatic drugs (DMARDs), tumor necrosis factor-α inhibitors were the most familiar to uveitis experts. The difficulties with off-label therapy procedures were the primary barrier to DMARDs prescription for patients with mU and correlated inversely with the obtained/prescribed drug ratio for interleukin-1 (p < 0.01) and interleukin-6 (p < 0.01) inhibitors., Conclusions: This survey identifies proficiency areas, gaps, and opportunities for targeted improvements in patients care. The comprehensive outputs may inform evidence-based guidelines, empowering clinicians with standardized approaches, and drive an AIDA Network-IUSG unified effort to advance scientific knowledge and clinical practice., (© 2023. The Author(s).)
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- 2024
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18. Shared and Distinct Gut Microbiota in Spondyloarthritis, Acute Anterior Uveitis, and Crohn's Disease.
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Essex M, Rios Rodriguez V, Rademacher J, Proft F, Löber U, Markó L, Pleyer U, Strowig T, Marchand J, Kirwan JA, Siegmund B, Forslund SK, and Poddubnyy D
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- Humans, Clostridiales metabolism, HLA-B27 Antigen genetics, Acute Disease, Crohn Disease drug therapy, Crohn Disease complications, Gastrointestinal Microbiome genetics, Spondylarthritis drug therapy, Spondylarthritis complications, Uveitis, Anterior drug therapy, Antirheumatic Agents
- Abstract
Objective: Spondyloarthritis (SpA) is a group of immune-mediated diseases highly concomitant with nonmusculoskeletal inflammatory disorders, such as acute anterior uveitis (AAU) and Crohn's disease (CD). The gut microbiome represents a promising avenue to elucidate shared and distinct underlying pathophysiology., Methods: We performed 16S ribosomal RNA sequencing on stool samples of 277 patients (72 CD, 103 AAU, and 102 SpA) included in the German Spondyloarthritis Inception Cohort and 62 back pain controls without any inflammatory disorder. Discriminatory statistical methods were used to disentangle microbial disease signals from one another and a wide range of potential confounders. Patients were naive to or had not received treatment with biological disease-modifying antirheumatic drugs (DMARDs) for >3 months before enrollment, providing a better approximation of a true baseline disease signal., Results: We identified a shared, immune-mediated disease signal represented by low abundances of Lachnospiraceae taxa relative to controls, most notably Fusicatenibacter, which was most abundant in controls receiving nonsteroidal antiinflammatory drug monotherapy and implied to partially mediate higher serum C-reactive protein. Patients with SpA showed an enrichment of Collinsella, whereas human leukocyte antigen (HLA)-B27+ individuals displayed enriched Faecalibacterium. CD patients had higher abundances of a Ruminococcus taxon, and previous conventional/synthetic DMARD therapy was associated with increased Akkermansia., Conclusion: Our work supports the existence of a common gut dysbiosis in SpA and related inflammatory pathologies. We reveal shared and disease-specific microbial associations and suggest potential mediators of disease activity. Validation studies are needed to clarify the role of Fusicatenibacter in gut-joint inflammation, and metagenomic resolution is needed to understand the relationship between Faecalibacterium commensals and HLA-B27., (© 2023 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)
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- 2024
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19. HLA-B27-positive anterior uveitis : Clinical aspects, diagnostics, interdisciplinary management, and treatment.
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Werkl P, Rademacher J, and Pleyer U
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- Young Adult, Humans, Adult, HLA-B27 Antigen genetics, Inflammation, Acute Disease, Chronic Disease, Uveitis, Anterior diagnosis, Uveitis, Spondylarthritis
- Abstract
Acute anterior uveitis (AAU) associated with human leukocyte antigen (HLA) B27 is the most common form of noninfectious intraocular inflammation and is considered to be a separate clinical entity. Young adults between the ages of 20 and 40 years are predominantly affected. The HLA-B27 positive AAU typically presents as a unilateral, fulminant disruption of the blood-aqueous humor barrier, which is accompanied by pronounced cellular infiltration and fibrinous exudation. Other characteristics are reduced intraocular pressure and a high tendency to relapse, which can also involve the partner eye. Patients with HLA-B27 positive AAU share a high risk for other genetically associated diseases, especially spondylarthritis, chronic inflammatory bowel diseases and psoriasis. As up to 40% of those affected have a systemic disease that has not yet been diagnosed, the ophthalmologist is of major importance for early detection., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)
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- 2024
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20. Impact of adalimumab in patients with active non-infectious intermediate, posterior, and panuveitis in real-life clinical practice: HOPE study.
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Pleyer U, Al-Mutairi S, Murphy CC, Hamam R, Hammad S, Nagy O, Szepessy Z, Guex-Crosier Y, Julian K, Habot-Wilner Z, and Androudi S
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- Adult, Humans, Adalimumab therapeutic use, Quality of Life, Prospective Studies, Treatment Outcome, Panuveitis drug therapy, Uveitis
- Abstract
Background/aim: This study evaluated real-life adalimumab impact in patients with active non-infectious intermediate, posterior, or panuveitis (NIIPPU)., Methods: Adults with active NIIPPU received adalimumab in this prospective, observational study (06/2017-04/2020). Patients were evaluated at baseline (V0) and four follow-up visits over 12 months (V1-V4)., Primary Endpoint: proportion of patients achieving quiescence (anterior chamber (AC) cells grade and vitreous haze (VH) grade≤0.5+ in both eyes, no new active chorioretinal lesions) at any follow-up visit. Secondary endpoints: proportion of patients achieving quiescence at each visit; proportion of patients maintaining response; and proportion of patients with flares. Workability, visual function, healthcare resource utilisation, and safety were evaluated., Results: Full analysis set included 149 patients. Quiescence at any follow-up visit was achieved by 129/141 (91%) patients. Quiescence at individual visits was achieved by 99/145 (68%), 110/142 (77%), 102/131 (78%), and 99/128 (77%) patients at V1-V4, respectively. Number of patients in corticosteroid-free quiescence increased from 51/147 (35%; V1) to 67/128 (52%; V4; p<0.05). Proportion of patients with maintained response increased from 89/141 (63%; V2) to 92/121 (76%; V4; p<0.05) and proportion of patients with flare decreased from 25/145 (17%; V1) to 13/128 (10%; V4; p=0.092). Workability and visual function improved throughout the study. Proportion of patients with medical visits for uveitis decreased from 132/149 (89%; V0) to 27/127 (21%; V4). No new safety signals were observed., Conclusion: These results demonstrated adalimumab effectiveness in improving quality of life while reducing economic burden of active NIIPPU., Competing Interests: Competing interests: UP has served as a principal investigator or consultant for AbbVie, Alcon, Allergan, Dompé, Novartis, Santen, Shire, and Thea. CM received research grant funding, speaker fees and honoraria, and conference sponsorship from AbbVie. RH received research grant funding from AbbVie, speaker fees from AbbVie and Amgen, and served as a consultant for Novartis. KJ has served as a principal investigator and consultant for AbbVie. YG-C has served as a principal investigator for AbbVie. SH is an employee of AbbVie and may hold AbbVie stock or options. ON was an employee of AbbVie at the time of the study and is a current contractor of AbbVie and may hold AbbVie stock or options. ZH-W served as a consultant and received speaker fees from AbbVie. SA received research support from AbbVie, Alcon, Allergan, Bayer, Novartis, Roche, Servier, and Xoma., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2023
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21. Cytomegalovirus-positive Posner-Schlossman syndrome: to compare differences in retinal vessel area density between the affected and non-affected eye using optical coherence tomography angiography.
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Hülse P, Reitemeyer E, Rübsam A, Pleyer U, and Maier AB
- Abstract
Purpose: To analyse differences in the retinal microvasculature in eyes with cytomegalovirus (CMV)-positive Posner-Schlossman syndrome (PSS) compared to the non-affected eyes using optical coherence tomography angiography (OCTA)., Methods: In this monocentric, observational prospective case series, 25 patients with unilateral CMV-positive PSS were included. We compared the vessel area densities (VAD) in the macula, optic disc, and peripapillary region in PSS-affected and non-affected eyes using OCTA. We compared the visual fields (VF) of the affected and healthy eyes of each patient. The mean deviation (MD) of the VF was analysed together with the retinal nerve fibre layer (RNFL) thickness to evaluate the strength of correlation with the VAD parameters., Results: The VAD of the peripapillary superficial vascular complex (SVC) is significantly reduced in CMV-positive PSS-affected eyes (46.1 ± 9.3% versus 50.1 ± 6.3%, p = 0.008, adjusted p = 0.048). The VAD of the deeper macular, papillary, and peripapillary layers showed no differences between the affected and non-affected eyes. The mean deviation and the retinal nerve fibre layer thickness had correlations with the VAD of the macula (r = 0.451, p = 0.001, r = 0.553, p < 0.001), the peripapillary SCV (r = 0.430, p = 0.002, r = 0.723, p < 0.001), and the papillary region (r = 0.512, p < 0.001, r = 0.292, p = 0.039). Patients receiving systemic antiviral therapy (SAT) showed better VAD of the peripapillary choriocapillary layer (p = 0.001, no therapy: 31.4 ± 1.9%, SAT: 35.0 ± 1.6%), and choroidal layer (p = 0.009, no therapy: 34.2 ± 0.3%, SAT: 36.3 ± 1.8%) compared to those with no SAT., Conclusion: A lower peripapillary VAD in the SVC might indicate vascular dysfunction as a sign of glaucomatous damage. SAT might have positive effects on the microcirculation in the deep retinal and choroidal layers., Trial Registration: TRN: DRKS00028266, https://www.drks.de/drks_web/ ., (© 2023. The Author(s).)
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- 2023
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22. On the Current Care Situation and Treatment of Ocular Mucous Membrane Pemphigoid in Germany.
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Yaïci R, Roth M, Juergens L, Nawaiseh SA, Burkhard D, Besgen V, Fuest M, Girbardt C, Hampel U, Heichel J, Heiligenhaus A, Herwig-Carl MC, Kakkassery V, Kontopoulou K, Löffler KU, Maier PC, Nölle B, Pach J, Paul S, Pleyer U, Pöllmann M, Saeger M, Schmidt E, Siebelmann S, Sokolenko E, Strudel L, Stübiger N, Tarhan M, Theuersbacher J, van Oterendorp C, Walker M, Wiecha C, Wykrota AA, and Geerling G
- Subjects
- Humans, Immunosuppressive Agents therapeutic use, Azathioprine therapeutic use, Mucous Membrane, Pemphigoid, Bullous chemically induced, Pemphigoid, Bullous drug therapy, Pemphigoid, Benign Mucous Membrane diagnosis, Pemphigoid, Benign Mucous Membrane drug therapy, Pemphigoid, Benign Mucous Membrane epidemiology
- Abstract
Background: Ocular involvement in mucous membrane pemphigoid (MMP) is relatively rare, with a prevalence of 25 cases per million population, equating to approx. 2,100 patients throughout Germany. Diagnosis can be difficult - especially in cases of isolated ocular involvement - and treatment can be complex and lengthy. Immunosuppressants or immunomodulatory drugs are often used. Due to the complexity of diagnosis and treatment, MMP patients are usually referred to specialized centers. The aim of this project was to evaluate the current care situation of patients with ocular MMP in Germany., Methods: A paper-based survey was designed and sent to all university eye clinics and other specialized centers in Germany in April 2020. The survey asked about the existence of a specialized outpatient service, the total annual number of patients with MMP, the annual number of newly diagnosed patients, any interdisciplinary collaboration for diagnostic or therapeutic purposes, as well as the local and systemic therapy used., Results: Of a total of 44 clinics, 28 (64%) responded, reporting a total average of 27 ± 42 (0 - 200) patients and 3.6 ± 2.2 (0 - 10) new cases per year. This corresponds to a total of 741 patients. Only nine (32%) of the responding clinics offer specialized MMP clinics. 93% of the centers collaborate with the local dermatology department. 79% perform serological and histological diagnostics in-house. About half of the centers (n = 16) apply a standardized treatment regime. Systemic glucocorticoids (66.7%) are most commonly used, followed by mycophenolate mofetil and dapsone (57.1%), rituximab (33.3%), azathioprine and cyclophosphamide (28.6%), as well as methotrexate (19.0%). The least frequently used treatment is intravenous immunoglobulin (14.3%)., Conclusion: This survey of German ophthalmology departments obtained data from about one third of the estimated total cohort of all patients with MMP in Germany. These are presumed to be exclusively patients with at least one ocular involvement. The complex care of these patients is usually provided in collaboration with a dermatologist and with the use of systemic anti-inflammatory medication. Currently, an ophthalmological MMP register is being established to better record the epidemiology and care situation of this rare disease in Germany and to improve it in the long term., Competing Interests: Martina Herwig-Carl: Forschungsförderung: EPIC-XS (Projektnr. 823839, gefördert durch das Horizon 2020 Programm der EU), Deutsche Forschungsgemeinschaft (HE5775/5-1); Beratung und Vortragstätigkeit: GlaxoSmithKline. Ich erkläre, dass die anderen Autoren während der letzten 3 Jahre keine wirtschaftlichen oder persönlichen Verbindungen im oben genannten Sinne angeben./ Martina Herwig-Carl: Research grant: EPIC-XS (project no. 823839, funded by the Horizon 2020 programme of the EU), German Research Foundation (HE5775/5-1); lectures and consultancy work: GlaxoSmithKline. I declare that the other authors have not declared any economic or personal connections as defined above in the past 3 years., (Thieme. All rights reserved.)
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- 2023
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23. L-Carnitine Suppresses Transient Receptor Potential Vanilloid Type 1 Activation in Human Corneal Epithelial Cells.
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Lucius A, Chhatwal S, Valtink M, Reinach PS, Li A, Pleyer U, and Mergler S
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- Humans, Capsaicin pharmacology, Capsaicin metabolism, Calcium metabolism, Epithelial Cells metabolism, TRPV Cation Channels metabolism, Carnitine pharmacology, Carnitine metabolism, Antineoplastic Agents metabolism
- Abstract
Tear film hyperosmolarity induces dry eye syndrome (DES) through transient receptor potential vanilloid type 1 (TRPV1) activation. L-carnitine is a viable therapeutic agent since it protects against this hypertonicity-induced response. Here, we investigated whether L-carnitine inhibits TRPV1 activation by blocking heat- or capsaicin-induced increases in Ca
2+ influx or hyperosmotic stress-induced cell volume shrinkage in a human corneal epithelial cell line (HCE-T). Single-cell fluorescence imaging of calcein/AM-loaded cells or fura-2/AM-labeled cells was used to evaluate cell volume changes and intracellular calcium levels, respectively. Planar patch-clamp technique was used to measure whole-cell currents. TRPV1 activation via either capsaicin (20 µmol/L), hyperosmolarity (≈450 mosmol/L) or an increase in ambient bath temperature to 43 °C induced intracellular calcium transients and augmented whole-cell currents, whereas hypertonicity induced cell volume shrinkage. In contrast, either capsazepine (10 µmol/L) or L-carnitine (1-3 mmol/L) reduced all these responses. Taken together, L-carnitine and capsazepine suppress hypertonicity-induced TRPV1 activation by blocking cell volume shrinkage.- Published
- 2023
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24. Vernal keratoconjunctivitis: Current immunological and clinical evidence and the potential role of omalizumab.
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Doan S, Papadopoulos NG, Lee JK, Leonardi S, Manti S, Lau S, Rondon C, Sharma V, Pleyer U, Jaumont X, and Lazarewicz SB
- Abstract
Vernal keratoconjunctivitis (VKC) is a severe ocular allergic disease characterized by chronic inflammation of the cornea and conjunctiva that may lead to loss of visual acuity and blindness. The disease occurs primarily in children and is more common in geographical regions characterized by warm temperatures and high humidity. The clinical manifestations of VKC, when inadequately treated, may lead to severe complications and corneal damage. The prevalence of allergen sensitization, specific serum immunoglobulin E (IgE), and specific tear IgE was reported in approximately 55%-60% of patients with VKC, confirming the involvement of IgE-mediated and non-IgE-mediated mechanisms in the pathophysiology of the condition. This article explores current knowledge on the immunological pathways of VKC and the role of the monoclonal anti-IgE antibody, omalizumab, in its management. The review evaluated the effects of omalizumab beyond the direct IgE-mediated reactions and discusses its potential as a therapeutic target for VKC. Multiple retrospective analyses, case series, and case reports have reported the effectiveness of omalizumab in the management of VKC. A summary of the clinical data from these studies revealed that in children with VKC omalizumab treatment was well tolerated with improvement or resolution of ocular symptoms, reduction in steroid use, and enhancement of quality of life. Omalizumab may serve as a promising treatment option for VKC due to its ability to target both IgE-mediated and non-IgE-mediated pathophysiological pathways. Larger, controlled clinical trials are needed to support these findings., (© 2023 The Authors.)
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- 2023
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25. Effect of Anti-TNF Treatment on Mooren's Ulcer: A Case Series and Review of the Literature.
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Xia A, Dietrich-Ntoukas T, and Pleyer U
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- Humans, Tumor Necrosis Factor Inhibitors therapeutic use, Retrospective Studies, Ulcer, Corneal Ulcer diagnosis, Corneal Ulcer drug therapy, Corneal Ulcer surgery, Corneal Transplantation methods
- Abstract
Purpose: To report the efficacy of systemic anti-TNF agents in Mooren's ulcer., Design: Retrospective, consecutive case series., Methods: We report on clinical characteristics and outcome of five patients with Mooren's ulcer with anti-TNF treatment., Results: During a mean follow-up of 30 months, relief of symptoms and arrest of corneal melting were observed in all eyes. Systemic corticosteroid treatment could be discontinued or reduced to threshold levels. No patient experienced adverse effects on bDMARDs., Conclusions: Our results suggest that bDMARDs are effective in Mooren's ulcer unresponsive to conventional treatment. This is in line with accumulating evidence in the current literature. Therefore, more targeted immunomodulatory approaches might be an effective first-line therapy in the future.
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- 2023
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26. Keep an Eye on the Back: Spondyloarthritis in Patients With Acute Anterior Uveitis.
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Rademacher J, Müllner H, Diekhoff T, Haibel H, Igel S, Pohlmann D, Proft F, Protopopov M, Rios Rodriguez V, Torgutalp M, Pleyer U, and Poddubnyy D
- Subjects
- Humans, Male, Acute Disease, HLA-B27 Antigen, Spondylarthritis complications, Uveitis, Anterior epidemiology, Uveitis complications, Psoriasis complications, Arthritis, Rheumatoid complications
- Abstract
Objectives: This study was undertaken to analyze the prevalence of spondyloarthritis (SpA) in patients with acute anterior uveitis (AAU), to identify parameters associated with the presence of SpA, and to evaluate the performance of referral algorithms for identifying patients with a high probability of having SpA., Methods: Prospectively recruited consecutive patients with noninfectious AAU underwent structured rheumatologic assessment including magnetic resonance imaging of the sacroiliac joints, allowing a definitive diagnosis/exclusion of concomitant SpA. Fisher's exact test and Mann-Whitney U test were used to compare AAU patients with SpA and AAU patients without SpA. Furthermore, logistic regression analyses were performed. The predictive performance of SpA referral strategies was analyzed by calculating the sensitivity, specificity, positive predictive value, and positive and negative likelihood ratios., Results: Among the 189 AAU patients evaluated, 106 (56%) were diagnosed as having SpA. The majority of SpA patients (93%) had predominantly axial SpA and 7 patients had peripheral SpA. In 74 patients (70%), the SpA diagnosis was established for the first time. In multivariable logistic regression analysis, psoriasis (odds ratio [OR] 12.5 [95% confidence interval (95% CI) 1.3-120.2]), HLA-B27 positivity (OR 6.3 [95% CI 2.4-16.4]), elevated C-reactive protein level (OR 4.8 [95% CI 1.9-12.4]), and male sex (OR 2.1 [95% CI 1.1-4.2]) were associated with the presence of SpA. None of the ophthalmologic parameters were found to be predictive of SpA. The Dublin Uveitis Evaluation Tool (DUET) showed higher specificity for SpA recognition than the Assessment of SpondyloArthritis international Society (ASAS) tool for the early referral of patients with a suspected diagnosis of axial SpA (specificity for SpA 42% versus 28%), whereas the sensitivity of the ASAS tool was slightly higher than the DUET tool (sensitivity for SpA 80% versus 78%). However, more than 20% of the AAU patients in this study who were diagnosed as having SpA would have been missed by both referral strategies., Conclusion: Our study revealed a high prevalence of SpA in AAU patients overall, as well as a high prevalence of previously undiagnosed SpA in AAU patients. Therefore, we propose rheumatologic evaluation for all AAU patients with musculoskeletal symptoms., (© 2022 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)
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- 2023
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27. S2k Guideline for the diagnosis and treatment of mucous membrane pemphigoid.
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Hofmann SC, Günther C, Böckle BC, Didona D, Ehrchen J, Gaskins M, Geerling G, Gläser R, Hadaschik E, Hampl M, Haßkamp P, Jackowski J, Kiritsi D, Nast A, Pleyer U, Reichel C, Roth M, Schumann M, Sticherling M, Worm M, Zillikens D, Goebeler M, and Schmidt E
- Subjects
- Humans, Mucous Membrane pathology, Fluorescent Antibody Technique, Direct, Biopsy, Pemphigoid, Bullous pathology, Pemphigoid, Benign Mucous Membrane diagnosis, Pemphigoid, Benign Mucous Membrane therapy
- Abstract
Mucous membrane pemphigoid (MMP) is a pemphigoid disease with predominant mucous membrane involvement. It mainly affects the mucous membranes of the mouth, eyes, nose and pharynx, but also the larynx, trachea, esophagus, genital and perianal regions. The manifestation of the disease covers a wide spectrum from gingival erythema and single oral lesions to severe tracheal strictures that obstruct breathing and conjunctival scarring with marked visual impairment and, not infrequently, blindness. In addition to a clinical picture of predominant mucosal involvement, diagnosis is based on direct immunofluorescence of a peri-lesional biopsy and serology. The main target antigen is BP180 (collagen XVII), and reactivity with laminin 332 is associated with malignancy in approximately 25 % of MMP patients. The treatment of MMP is challenging. On the one hand, due to the involvement of different mucous membranes, good interdisciplinary cooperation is required; on the other hand, due to the rarity of the disease, no randomized controlled clinical trials are available. The aim of this guideline is to present the clinical picture, including severity and scoring systems, and to give guidance for diagnosing and treating this complex disease. In MMP, interdisciplinary cooperation plays an essential role as well as the prompt diagnosis and initiation of adequate therapy in order to avoid irreversible damage to the mucous membranes with serious complications., (© 2022 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)
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- 2022
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28. S2k-Leitlinie zur Diagnostik und Therapie des Schleimhautpemphigoids.
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Hofmann SC, Günther C, Böckle BC, Didona D, Ehrchen J, Gaskins M, Geerling G, Gläser R, Hadaschik E, Hampl M, Haßkamp P, Jackowski J, Kiritsi D, Nast A, Pleyer U, Reichel C, Roth M, Schumann M, Sticherling M, Worm M, Zillikens D, Goebeler M, and Schmidt E
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- 2022
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29. A new small molecule DHODH-inhibitor [KIO-100 (PP-001)] targeting activated T cells for intraocular treatment of uveitis - A phase I clinical trial.
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Thurau S, Deuter CME, Heiligenhaus A, Pleyer U, Van Calster J, Barisani-Asenbauer T, Obermayr F, Sperl S, Seda-Zehetner R, and Wildner G
- Abstract
Uveitis is a T cell-mediated, intraocular inflammatory disease and one of the main causes of blindness in industrialized countries. There is a high unmet need for new immunomodulatory, steroid-sparing therapies, since only ciclosporin A and a single TNF-α-blocker are approved for non-infectious uveitis. A new small molecule inhibitor of dihydroorotate dehydrogenase (DHODH), an enzyme pivotal for de novo synthesis of pyrimidines, has a high potency for suppressing T and B cells and has already proven highly effective for treating uveitis in experimental rat models. Systemic and intraocular application of KIO-100 (PP-001) (previously called PP-001, now KIO-100) could efficiently suppress rat uveitis in a preventive as well as therapeutic mode. Here we describe the outcome of the first clinical phase 1 trial comparing three different doses of a single intraocular injection of KIO-100 (PP-001) in patients with non-infectious posterior segment uveitis. No toxic side effects on intraocular tissues or other adverse events were observed, while intraocular inflammation decreased, and visual acuity significantly improved. Macular edema, a sight-threatening complication in uveitis, showed regression 2 weeks after intraocular KIO-100 (PP-001) injection in some patients, indicating that this novel small molecule has a high potential as a new intraocular therapy for uveitis., Clinical Trial Registration: [https://www.clinicaltrials.gov/ct2/show/NCT03634475], identifier [NCT03634475]., Competing Interests: Authors FO, SS, and RS-Z were employed by Kiora Pharmaceuticals Inc. (previously Panoptes Pharma GmbH). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Thurau, Deuter, Heiligenhaus, Pleyer, Van Calster, Barisani-Asenbauer, Obermayr, Sperl, Seda-Zehetner and Wildner.)
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- 2022
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30. Anti-CD20 therapy for multiple sclerosis-associated uveitis: A case series.
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Stascheit F, Rübsam A, Otto C, Meisel A, Ruprecht K, and Pleyer U
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- Humans, Neoplasm Recurrence, Local, Retrospective Studies, Tomography, Optical Coherence methods, Treatment Outcome, Multiple Sclerosis complications, Multiple Sclerosis diagnostic imaging, Multiple Sclerosis drug therapy, Retinal Vasculitis complications, Uveitis drug therapy, Uveitis etiology
- Abstract
Background and Purpose: Approximately 1% of patients with multiple sclerosis (MS) have uveitis, but data on the effects of immunotherapies for MS on MS-associated uveitis are scarce. The aim of this study was to investigate the ophthalmological outcomes in patients with MS-associated uveitis treated with anti-CD20 therapy., Methods: A retrospective study of 12 eyes of six patients with MS-associated uveitis, refractory to previous immunotherapies, was conducted. Uveitis activity was assessed before initiation of anti-CD20 therapy and at regular follow-up visits. Primary outcome measures were: vitreous haze score; retinal vasculitis score, determined on fluorescein angiography images; macular edema, as quantified by central retinal thickness (CRT) on optical coherence tomography; and visual acuity (VA). Secondary outcomes included number of annualized uveitis or MS relapses, disease activity on cerebral magnetic resonance imaging (cMRI) and Expanded Disability Status Scale (EDSS) score., Results: After a median (interquartile range [IQR]) treatment time of 28.5 (8-43) months, anti-CD20 therapy was associated with an improvement of vitreous haze score (p = 0.002), retinal vasculitis score (p = 0.001), CRT (p = 0.002), and VA (p = 0.007). The median (IQR) annualized uveitis relapse rate declined from 0.59 (0.56-0.94) before to 0 (0-0.49) after the start of anti-CD20 therapy. The median (IQR) annualized MS relapse rate declined from 0.62 (0.26-2.84) before to 0 (0-0) after the start of anti-CD20 therapy. After initiation of anti-CD20 therapy, there was no disease activity on cMRI, and EDSS score improved (n = 2) or remained stable (n = 4). No severe adverse events were observed., Conclusion: These findings suggest that anti-CD20 therapy may be a valuable treatment option for MS-associated uveitis., (© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)
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- 2022
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31. Peripheral blood immune cell profiling of acute corneal transplant rejection.
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Hjortdal J, Griffin MD, Cadoux M, Armitage WJ, Bylesjo M, Gabhann PM, Murphy CC, Pleyer U, Tole D, Vabres B, Walkinshaw MD, Gourraud PA, Karakachoff M, Brouard S, and Degauque N
- Subjects
- Adult, Cross-Sectional Studies, Graft Rejection diagnosis, Graft Rejection etiology, Graft Survival, Humans, Corneal Transplantation, Leukocytes, Mononuclear
- Abstract
Acute rejection (AR) of corneal transplants (CT) has a profound effect on subsequent graft survival but detailed immunological studies in human CT recipients are lacking. In this multi-site, cross-sectional study, clinical details and blood samples were collected from adults with clinically diagnosed AR of full-thickness (FT)-CT (n = 35) and posterior lamellar (PL)-CT (n = 21) along with Stable CT recipients (n = 177) and adults with non-transplanted corneal disease (n = 40). For those with AR, additional samples were collected 3 months later. Immune cell analysis was performed by whole-genome microarrays (whole blood) and high-dimensional multi-color flow cytometry (peripheral blood mononuclear cells). For both, no activation signature was identified within the B cell and T cell repertoire at the time of AR diagnosis. Nonetheless, in FT- but not PL-CT recipients, AR was associated with differences in B cell maturity and regulatory CD4
+ T cell frequency compared to stable allografts. These data suggest that circulating B cell and T cell subpopulations may provide insights into the regulation of anti-donor immune response in human CT recipients with differing AR risk. Our results suggest that, in contrast to solid organ transplants, genetic or cellular assays of peripheral blood are unlikely to be clinically exploitable for prediction or diagnosis of AR., (© 2022 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)- Published
- 2022
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32. Longitudinal Comparison of Constant Artifacts in Optical Coherence Tomography Angiography in Patients with Posterior Uveitis Compared to Healthy Subjects.
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Pohlmann D, Berlin M, Reidl F, Künzel SE, Pleyer U, Joussen AM, and Winterhalter S
- Abstract
Background: Knowledge about artifacts in optical coherence tomography angiography (OCTA) is important to avoid misinterpretations. An overview of possible artifacts in posterior uveitis provides important information for interpretations. Methods: In this monocentric prospective study, OCTA images from a total of 102 eyes of 54 patients with posterior uveitis, and an age-matched control group including 34 healthy subjects (67 eyes), were evaluated (day 0, month 3, month 6). We assigned different artifacts to distinct layers. Various types of artifacts were examined in different retinal layers. The χ2 test for the comparison between the control and uveitis group and Cochran’s Q test for the longitudinal comparison within the uveitis group were used. Results: A total of 2238 images were evaluated; 1836 from uveitis patients and 402 from healthy subjects. A total of 2193 artifacts were revealed. Projection (812 [36.3%]), segmentation (579 [25.9%]), shadowing (404 [18.1%]), and blink artifacts (297 [13.3%]) were the most common artifact types. The uveitis group displayed significantly more segmentation artifacts and projection artifacts (p < 0.001). No segmentation artifacts were documented in healthy subjects. The consecutive examinations within the uveitis group revealed the same artifact types without significance (p > 0.1). Conclusions: The uveitis patients showed more segmentation and projection artifacts than the control group. Within the uveitis group, artifacts remained longitudinally constant in terms of artifact type and pattern. The artifacts therefore appear to be reproducible on an individual level.
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- 2022
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33. S2k-Leitlinie: Rosazea.
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Clanner-Engelshofen BM, Bernhard D, Dargatz S, Flaig MJ, Gieler U, Kinberger M, Klövekorn W, Kuna AC, Läuchli S, Lehmann P, Nast A, Pleyer U, Schaller M, Schöfer H, Steinhoff M, Schwennesen T, Werner RN, Zierhut M, and Reinholz M
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- 2022
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34. S2k guideline: Rosacea.
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Clanner-Engelshofen BM, Bernhard D, Dargatz S, Flaig MJ, Gieler U, Kinberger M, Klövekorn W, Kuna AC, Läuchli S, Lehmann P, Nast A, Pleyer U, Schaller M, Schöfer H, Steinhoff M, Schwennesen T, Werner RN, Zierhut M, and Reinholz M
- Subjects
- Brimonidine Tartrate, Erythema drug therapy, Humans, Ivermectin therapeutic use, Metronidazole therapeutic use, Dermatologic Agents therapeutic use, Rosacea diagnosis, Rosacea drug therapy
- Abstract
This updated and upgraded S2k guideline deals with the diagnosis and treatment of rosacea, which is a common, chronic inflammatory skin disease mostly affecting the face. Initially, rosacea is characterized by recurrent erythema, telangiectasia and flushing. Later, the inflammatory component predominates, with persistent erythema with follicular papules, papulopustules and pustules. The development of phyma, which usually occurs on the acral localizations, is the most severe manifestation. For the treatment of rosacea, the interdisciplinary guideline committee, with representatives of the German Dermatological Society (DDG), the Professional Association of German Dermatologists (BVDD), the German Opthalmological Society (DOG), the Society for Dermopharmacy (GD), the Swiss Society for Dermatology and Venereology (SGDV) and the German Rosacea Aid e. V., recommends the avoidance of trigger factors and topical applications of metronidazole, azelaic acid or ivermectin. For symptomatic treatment of persistent centrofacial erythema, the topical vasoconstrictors brimonidine or oxymetazoline can also be used. Systemic therapy is recommended for therapy-resistant and severe forms of rosacea papulopustulosa. The drug of choice is low-dose doxycycline. Alternatively, low-dose isotretinoin can be recommended. Ocular rosacea should be treated with lid margin hygiene. For topical treatment, ciclosporin eye drops, azithromycin, ivermectin or metronidazole are suggested., (© 2022 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)
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- 2022
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35. Rubella Virus- and Cytomegalovirus-Associated Anterior Uveitis: Clinical Findings and How They Relate to the Current Fuchs Uveitis Syndrome Classification.
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Yermalitski A, Rübsam A, Pohlmann D, Metzner S, and Pleyer U
- Abstract
Rubella virus (RV) and cytomegalovirus (CMV) have both been implicated in anterior uveitis (AU). Clinical phenotypes can vary widely among both etiologies, including Fuchs uveitis syndrome (FUS) as a very distinct phenotype that has been associated with both RV and CMV. The Standardization of Uveitis Nomenclature (SUN) Working Group recently updated the classification criteria for FUS as unilateral AU, including either heterochromia or diffuse iris atrophy combined with stellate keratic precipitates as key findings. The aim of this study was to determine whether our patients adhere to the classification criteria of FUS as previously reported and whether RV- or CMV-associated uveitis can be differentiated by clinical findings. Therefore, this study investigated the clinical characteristics of patients with AU and intraocular presence of either RV or CMV determined by the Goldmann-Witmer coefficient (GWC). Our study included 100 patients (107 eyes) with AU and positive GWC for RV (86) and CMV (21). Clinical findings of RV-positive eyes were as follows: keratic precipitates (91.9%) with a predominantly diffuse distribution (81.4%), unilateral cataract (80.2%), pseudophakia (73.5%), and vitreous cells (59.7%), whereas heterochromia was present in only 39.5% of eyes and iris atrophy in 12.9% of eyes. In CMV-positive eyes, conversely, a higher incidence of ocular hypertension with markedly increased intraocular pressures above 30 mmHg (66.7%), keratic precipitates (81.0%), which were most commonly distributed in the center of the cornea (63.6%), an unaffected lens (55.0%), absent iris atrophy (100%), and absent posterior synechiae (90.5%) could be detected. This indicates a clinical presentation that was mainly compatible with Posner-Schlossman syndrome. In our cohort of RV-positive FUS patients, we saw a different cluster of clinical findings compared to the classification criteria suggested by the SUN Working Group. The main criteria, such as unilaterality, were mostly fulfilled. When applying all classification criteria, only 8.4% of 107 eyes and 10.5% of all 86 RV-positive eyes would qualify for the diagnosis of FUS. In addition, in our cohort of predominantly Caucasian patients, the clinical findings in patients with proven CMV infection differed from the clinical presentation typically associated with FUS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yermalitski, Rübsam, Pohlmann, Metzner and Pleyer.)
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- 2022
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36. Cytomegalovirus-Positive Posner-Schlossman Syndrome: Impact on Corneal Endothelial Cell Loss and Retinal Nerve Fiber Layer Thinning.
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Lenglinger M, Schick T, Pohlmann D, and Pleyer U
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- Corneal Endothelial Cell Loss, Cytomegalovirus, Humans, Intraocular Pressure, Nerve Fibers, Retrospective Studies, Tomography, Optical Coherence, Cytomegalovirus Infections diagnosis, Cytomegalovirus Infections drug therapy, Glaucoma, Open-Angle
- Abstract
Purpose: To report objective morphologic changes in cytomegalovirus (CMV)-positive Posner-Schlossman syndrome (PSS)., Design: Retrospective, consecutive case series., Methods: We reviewed the charts of patients with unilateral PSS tested positive for CMV by Goldmann-Witmer coefficients between 2007 and 2018 at our tertiary eye clinic. We report data on corneal endothelial cell (CEC) count, peripapillary retinal nerve fiber layer (RNFL), choroidal thickness (CT) using optical coherence tomography (OCT) as well as clinical findings and management. The unaffected eye served as control., Results: Fifty-two eyes of 52 patients were included and followed for 32.8 ± 28.3 months. The peak intraocular pressure was 45 ± 11 mm Hg. The CEC (2241.7 ± 381.1 cells/mm
2 vs 2529.4 ± 351.9 cells/mm2 , P = .0004) and the global RNFL thickness (80.81 ± 21.01 µm vs 97.38 ± 9.75 µm, P = .0001) were significantly reduced, whereas CT was nonsignificantly higher (295.69 ± 45.46 µm vs 274.00 ± 67.85 µm, P = .156) in the affected eyes compared to the fellow eye. Forty (76.9%) patients were treated with oral valganciclovir (VGC), 2 (3.8%) with topical ganciclovir alone, and 10 (19.2%) received no antiviral therapy. Eight eyes (15.4%) underwent trabeculectomy with mitomycin C. After cessation of oral VGC, 23 patients (57.5%) had recurrences., Conclusions: In our cohort, CMV-positive PSS was often associated with RNFL thinning and CEC loss. Highly elevated intraocular pressures usually present the most relevant challenge. In conjunction with aqueous humor sampling, monitoring by OCT scans and endothelial microscopy may help to guide therapy decisions., (Copyright © 2022 Elsevier Inc. All rights reserved.)- Published
- 2022
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37. Viral Anterior Uveitis.
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Baquet-Walscheid K, Pohlmann D, and Pleyer U
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- Antiviral Agents therapeutic use, Aqueous Humor, Humans, Eye Infections, Viral diagnosis, Eye Infections, Viral drug therapy, Glaucoma drug therapy, Uveitis drug therapy, Uveitis, Anterior diagnosis, Uveitis, Anterior drug therapy
- Abstract
Differential diagnosis of viral anterior uveitis (AU) based on the typical clinical findings (anterior chamber inflammation, morphology of the keratic precipitates, severity of IOP increase in relapse) is often straightforward. When differential diagnosis is difficult clinically, analysis of aqueous humour by PCR and/or antibody testing (Goldmann-Witmer coefficient) may be helpful. While both modalities are highly specific, they lack absolute sensitivity. Patients with HSV, VZV and CMV associated uveitis require both antiviral as well as antiinflammatory medication and often additional antiglaucomatous therapy, depending on IOP. In contrast, specific antiviral treatment is not possible in rubella associated AU and steroids should be administered with extreme caution due to their adverse effects. With all subtypes of virus associated AU, recurrent episodes put the patients at risk of developing secondary glaucoma, which often requires surgical treatment., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht./The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)
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- 2022
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38. A Comprehensive Update on Retinal Vasculitis: Etiologies, Manifestations and Treatments.
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Agarwal A, Rübsam A, Zur Bonsen L, Pichi F, Neri P, and Pleyer U
- Abstract
Retinal vasculitis is characterized by inflammatory involvement of retinal arterioles, venules and/or capillaries and can be associated with a myriad of systemic and ophthalmic diseases. In this review, we have comprehensively discussed the etiologies, clinical manifestations, and presentations of retinal vasculitis. We have also included newer advances in imaging in retinal vasculitis such as OCTA and widefield imaging.
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- 2022
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39. Findings and Graduation of Sarcoidosis-Related Uveitis: A Single-Center Study.
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Zur Bonsen LS, Pohlmann D, Rübsam A, and Pleyer U
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- Adolescent, Adult, Aged, Aged, 80 and over, Child, Eye pathology, Female, Humans, Male, Middle Aged, Uveitis classification, Young Adult, Sarcoidosis complications, Uveitis complications
- Abstract
Ocular involvement is present in up to 79% of sarcoid patients. Uveitis is the main ocular manifestation and presents as a chronic intraocular inflammatory condition with potentially detrimental effects on visual acuity and quality of life. This retrospective study was conducted to explore the incidence and characteristics of ocular sarcoidosis in a single tertiary ophthalmology center. Medical records of 84 patients presenting between June 2007 and March 2021 were analyzed. Based on the "International Workshop on Ocular Sarcoidosis" (IWOS) criteria, ocular sarcoidosis was determined as: definite ( n = 24; 28.6%), presumed ( n = 33; 39.3%), probable ( n = 10; 11.9%), and indefinite ( n = 17; 20.2%) in our study population. In 43.9% of the definite and presumed cases, the eye was primarily affected. In addition to specific ocular findings, the diagnosis was supported by biopsy (28.6%) and chest x-ray or computer tomography (66.7%). Moreover, an increased soluble interleukin-2 receptor (sIL-2R) expression (76.2%), elevated angiotensin-converting enzyme (ACE) levels (34.8%), and lymphocytopenia (35.1%) were valuable laboratory findings. Co-affected organs were lungs (60.7%), skin (15.5%), and central nervous system (8.3%). Our findings support the prominent role of the eye in the early detection of sarcoidosis. In addition to the IWOS criteria, sIL-2R, in particular, was shown to be relevant in establishing the diagnosis.
- Published
- 2021
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40. Acute macular neuroretinopathy (AMN) following COVID-19 vaccination.
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Drüke D, Pleyer U, Hoerauf H, Feltgen N, and Bemme S
- Abstract
Purpose: To describe a case of acute macular neuroretinopathy (AMN) in a 23-year-old Caucasian female after a COVID-19 vaccination (Vaxzevira)., Observations: Our patient perceived visual symptoms in both eyes one day after COVID-19 vaccination. Hyporeflective petalloid shaped perifoveal lesions appeared in infrared reflectance (IR) imaging, and Spectral domain-optical coherence tomography (SD-OCT) revealed structural alterations of outer retinal layers that resulted in persistent disruption of the ellipsoid zone (EZ) and the interdigitation zone (IZ)., Conclusions and Importance: We report a novel association between AMN and COVID-19 vaccination. In addition to a febrile infection and oral contraception, previous vaccination should also be considered a potential risk factor for AMN., Competing Interests: The authors declare that there is no conflict of interest., (© 2021 The Authors.)
- Published
- 2021
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41. Estimates of Toxoplasmosis Incidence Based on Healthcare Claims Data, Germany, 2011-2016.
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Krings A, Jacob J, Seeber F, Pleyer U, Walker J, Stark K, and Wilking H
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- Antibodies, Protozoan, Delivery of Health Care, Female, Germany epidemiology, Humans, Incidence, Pregnancy, Risk Factors, Seroepidemiologic Studies, Toxoplasma, Toxoplasmosis epidemiology
- Abstract
Toxoplasmosis is a zoonotic infection contracted through Toxoplasma gondii-contaminated food, soil, or water. Seroprevalence in Germany is high, but estimates of disease incidence are scarce. We investigated incidences for various toxoplasmosis manifestations using anonymized healthcare claims data from Germany for 2011-2016. Patients with a toxoplasmosis diagnosis during the annual observational period were considered incident. The estimated incidence was adjusted to the general population age/sex distribution. We estimated an annual average of 8,047 toxoplasmosis patients in Germany. The average incidence of non-pregnancy-associated toxoplasmosis patients was 9.6/100,000 population. The incidence was highest in 2011, at 10.6 (95% CI 9.4-12.6)/100,000 population, and lowest in 2016, at 8.0 (95% CI 7.0-9.4)/100,000 population. The average incidence of toxoplasmosis during pregnancy was 40.3/100,000 pregnancies. We demonstrate a substantial toxoplasmosis disease burden in Germany. Public health and food safety authorities should implement toxoplasmosis-specific prevention programs.
- Published
- 2021
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42. New pharmacotherapy options for noninfectious posterior uveitis.
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Pleyer U, Neri P, and Deuter C
- Subjects
- Adolescent, Adrenal Cortex Hormones therapeutic use, Anti-Inflammatory Agents therapeutic use, Humans, Antirheumatic Agents therapeutic use, Uveitis drug therapy, Uveitis, Intermediate, Uveitis, Posterior diagnosis, Uveitis, Posterior drug therapy
- Abstract
Introduction: Noninfectious inflammation of the posterior eye segment represents an important cause of visual impairment. It often affects relatively young people and causes a significant personal and social impact. Although steroids and nonbiologic- Disease-Modifying Antirheumatic Drugs (nbDMARDs) are effective both in acute and long- lasting diseases, however they are increasingly being replaced by biologic (DMARDs). bDMARD. This article therefore aims to identify recent advances in the therapy of noninfectious posterior segment uveitis., Methods: A Medline-search was conducted using the terms: nbDMARD, bDMARD, posterior uveitis, intermediate uveitis, treatment, corticosteroid. In addition, clinical studies were included as registered at ClinicalTrials.gov., Results: Currently two major lines of treatments can be identified: (1) the intraocular application of anti-inflammatory agents and (2) the introduction of new agents, e.g., (bDMARDs) and small-molecule-inhibitors. Whereas intravitreal treatments have the advantage to avoid systemic side effects, new systemic agents are progressively earning credit on the basis of their therapeutic effects., Conclusion: Even when current treatment strategies are still hampered by the limited number of randomized controlled trials, promising progress and continuous efforts are seen.
- Published
- 2021
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43. L-carnitine suppresses transient receptor potential vanilloid type 1 activity and myofibroblast transdifferentiation in human corneal keratocytes.
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Turan E, Valtink M, Reinach PS, Skupin A, Luo H, Brockmann T, Ba Salem MHO, Pleyer U, and Mergler S
- Subjects
- Carnitine pharmacology, Cells, Cultured, Corneal Stroma cytology, Drug Evaluation, Preclinical, Humans, Myofibroblasts, TRPV Cation Channels drug effects, Carnitine therapeutic use, Cell Transdifferentiation drug effects, Corneal Keratocytes drug effects, Corneal Stroma drug effects, TRPV Cation Channels metabolism
- Abstract
Corneal stromal wound healing is a well-balanced process promoted by overlapping phases including keratocyte proliferation, inflammatory-related events, and tissue remodeling. L-carnitine as a natural antioxidant has shown potential to reduce stromal fibrosis, yet the underlying pathway is still unknown. Since transient receptor potential vanilloid 1 (TRPV1) is a potential drug target for improving the outcome of inflammatory/fibrogenic wound healing, we investigated if L-carnitine can mediate inhibition of the fibrotic response through suppression of TRPV1 activation in human corneal keratocytes (HCK). We determined TRPV1-induced intracellular calcium transients using fluorescence calcium imaging, channel currents by planar patch-clamping, and cell migration by scratch assay for wound healing. The potential L-carnitine effect on TRPV1-induced myofibroblast transdifferentiation was evaluated by immunocytochemical detection of alpha smooth muscle actin. RT-PCR analysis confirmed TRPV1 mRNA expression in HCK. L-carnitine (1 mmol/l) inhibited either capsaicin (CAP) (10 µmol/l), hypertonic stress (450 mOsmol/l), or thermal increase (>43 °C) induced Ca
2+ transients and corresponding increases in TRPV1-induced inward and outward whole-cell currents. This was accompanied by suppression of injury-induced increases in myofibroblast transdifferentiation and cell migration. In conclusion, L-carnitine contributes to inhibit stromal scarring through suppressing an injury-induced intrinsic TRPV1 activity that is linked with induction of myofibroblast transdifferentiation in HCK cells.- Published
- 2021
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44. Screening for common eye diseases in the elderly with Optos ultra-wide-field scanning laser ophthalmoscopy: a pilot study with focus on ocular toxoplasmosis.
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Logroño Wiese PE, Seeber F, Endres AS, Brockmann C, and Pleyer U
- Subjects
- Aged, Cross-Sectional Studies, Female, Humans, Lasers, Male, Ophthalmoscopy, Pilot Projects, Toxoplasmosis, Ocular diagnosis, Toxoplasmosis, Ocular epidemiology
- Abstract
Purpose: Studies on the occurrence of ocular toxoplasmosis (OT) in a general population are rare. Therefore, we conducted this pilot study to assess whether a nonmydriatic ultra-wide-field (UWF) scanning laser ophthalmoscope (SLO) is suitable for a simple, rapid screening procedure., Methods: The population of this cross-sectional study was randomly recruited from a cohort of hospital-based patients in an urban geriatric hospital. Ophthalmologic evaluation was performed on 201 eyes from 101 participants through nonmydriatic UWF-SLO (Optos Daytona) and assessed for suspicious lesions and other relevant ocular findings. All images were evaluated by two independent examiners. Individuals who presented lesions with a morphological appearance suggestive of OT underwent fundoscopy and serological analysis of Toxoplasma gondii-specific antibodies., Results: The mean age of the study group was 76 years, and 63 (62%) were female. Despite many health restrictions, the SLO examination was carried out easily in this geriatric population. Three participants presented findings by SLO suspicious for T. gondii-related injury. Further clinical examination and serological investigation confirmed the diagnosis, with funduscopic evaluation and positive T. gondii ELISA testing. In addition, a high rate of arterial hypertension and dyslipidemias within the cohort led to a high incidence of vascular changes and age-related fundus findings., Conclusion: In our study, we confirm that UWF-SLO technology is helpful in the rapid detection of peripheral retinal injuries in elderly patients such as OT and may be used as a routine screening tool.
- Published
- 2021
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45. Analysis of peripheral inflammatory T cell subsets and their effector function in patients with Birdshot Retinochoroiditis.
- Author
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Trombke J, Loyal L, Braun J, Pleyer U, Thiel A, and Pohlmann D
- Subjects
- Adult, Aged, CD4-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes immunology, Female, Humans, Immunologic Memory immunology, Lymphocyte Activation immunology, Male, Middle Aged, Pilot Projects, Birdshot Chorioretinopathy immunology, T-Lymphocyte Subsets immunology
- Abstract
Birdshot Retinochoroiditis (BSRC) is a progressive non-infectious intraocular inflammation that affects choroid and retina. Inflammatory processes have adverse effects on vision by affecting photoreceptor-bearing cells that do not regenerate. This study aimed at characterizing inflammatory CD4
+ and CD8+ T cell subsets in the peripheral blood of active and inactive BSRCs. Furthermore, we correlated phenotypical and functional immunological analyses with clinical data. We observed a slight increase of terminally differentiated effector memory CD8+ T cells expressing CD45RA (TEMRA ) in blood of inactive, compared to active BSRCs. Moreover, we identified a trend for a decreased population of TH 2 cells and increased TH 1 frequencies in active BSRCs, a typical sign of ongoing autoimmune processes. Functional assays demonstrated severe and overall impairment of effector function of both, CD4+ and CD8+ inflammatory T cells, which might reflect T cell exhaustion. Although the eye is the main site of inflammation in BSRC, we observed altered T cell subset compositions in the peripheral blood, dependent on the disease status. Our results indicate that T cells may play a major role in BSRC pathology, although our cohort size is too limited for definitve conclusions. Future studies with larger BSRCs have to be performed.- Published
- 2021
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46. Treatment Strategy in Human Ocular Toxoplasmosis: Why Antibiotics Have Failed.
- Author
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Garweg JG and Pleyer U
- Abstract
Background: There is currently no clear evidence of the effectiveness of antibiotic therapy in acute ocular toxoplasmosis (OT), but its effect as a secondary prophylaxis is undisputed. The majority of uveitis specialists advocate treatment. This meta-analytic review aims to critically analyze determinants of treatment success and to update current treatment strategies for OT in order to explain this discrepancy., Methods: A systematic literature search was performed in NCBI/PubMed, Clinical Trials, Google Scholar and ScienceDirect to retrieve pro- and retrospective studies using the key terms "ocular toxoplasmosis" or "retinochoroiditis" and "immunocompetent" and "treatment" or "therapy" and "human." Of these, larger case series and prospective clinical studies and cross references identified from meta-analyses were selected by a manual search, and primary and secondary outcome parameters were extracted., Results: Ten case series and clinical trials reported success parameters for treatment outcomes, and four additional for recurrence prophylaxis. Five treatment studies were randomized clinical trials, three comparative and two noncomparative case series. Though several outcome parameters were reported, five of them defined time to healing, four visual gain and one lesion size as primary and secondary outcome parameters, recurrence rate as a secondary outcome parameter was reported once. No conclusive evidence was found for an antibiotic treatment effect. Four prophylaxis studies addressed the prevention of recurrences after treatment. The primary outcome in all studies was the effect of treatment and prophylaxis on recurrences, and all four found a significant effect on the risk of and time to recurrences., Conclusions: Antibiotic treatment of OT aims at controlling parasite proliferation. The absence of an effect on visual acuity and time to healing is thus not surprising. The fact that time to and number of recurrences respond to recurrence of prophylaxis proves the antibiotic effect on parasite activity.
- Published
- 2021
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47. Structural Endpoints and Outcome Measures in Uveitis.
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Wintergerst MWM, Liu X, Terheyden JH, Pohlmann D, Li JQ, Montesano G, Ometto G, Holz FG, Crabb DP, Pleyer U, Heinz C, Denniston AK, and Finger RP
- Subjects
- Diagnostic Techniques, Ophthalmological, Fluorescein Angiography, Humans, Outcome Assessment, Health Care, Tomography, Optical Coherence, Uveitis diagnosis
- Abstract
Most uveitis entities are rare diseases but, taken together, are responsible for 5-10% of worldwide visual impairment which largely affects persons of working age. As with many rare diseases, there is a lack of high-level evidence regarding its clinical management, partly due to a dearth of reliable and objective quantitative endpoints for clinical trials. This review provides an overview of available structural outcome measures for uveitis disease activity and damage in an anatomical order from the anterior to the posterior segment of the eye. While there is a multitude of available structural outcome measures, not all might qualify as endpoints for clinical uveitis trials, and thorough testing of applicability is warranted. Furthermore, a consensus on endpoint definition, standardization, and "core outcomes" is required. As stipulated by regulatory agencies, endpoints should be precisely defined, clinically important, internally consistent, reliable, responsive to treatment, and relevant for the respective subtype of uveitis. Out of all modalities used for assessment of the reviewed structural outcome measures, optical coherence tomography, color fundus photography, fundus autofluorescence, and fluorescein/indocyanine green angiography represent current "core modalities" for reliable and objective quantification of uveitis outcome measures, based on their practical availability and the evidence provided so far., (© 2021 S. Karger AG, Basel.)
- Published
- 2021
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48. The impact of extra-musculoskeletal manifestations on disease activity, functional status, and treatment patterns in patients with axial spondyloarthritis: results from a nationwide population-based study.
- Author
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Redeker I, Siegmund B, Ghoreschi K, Pleyer U, Callhoff J, Hoffmann F, Marschall U, Haibel H, Sieper J, Zink A, and Poddubnyy D
- Abstract
Objective: The aim of this study was to investigate the association of extra-musculoskeletal manifestations (EMMs) with disease activity, functional status, and treatment patterns in a large population-based cohort of patients with axial spondyloarthritis (axSpA)., Methods: A stratified random sample of patients with axSpA, drawn from health insurance data, received a survey on disease-related characteristics including history (ever presence) of the following EMMs: inflammatory bowel disease (IBD), psoriasis (PSO), and anterior uveitis (AU). Survey data were linked to health insurance data, gathering additional information on current occurrence (within one year) of EMMs and drug prescriptions. Separate multivariable linear regression models were calculated to determine the association of EMMs with disease activity (Bath Ankylosing Spondylitis Disease Activity Index), and functional status (Bath Ankylosing Spondylitis Functional Index) after adjustment for relevant parameters, including treatment., Results: A total of 1729 patients with axSpA were included in the analyses (response: 47%; mean age: 56 years; 46% female) of whom 6% (9%) had current (ever) IBD, 10% (15%) had current (ever) PSO, and 9% (27%) had current (ever) AU. Ever presence of IBD and history of PSO were significantly associated with higher level of disease activity. Ever presence of PSO was also associated with higher level of functional impairment, whereas current AU was significantly associated with lower disease activity. Patients with current IBD or PSO received more frequently biological and conventional synthetic disease-modifying anti-rheumatic drugs as well as systemic steroids. AU was associated with a higher use of conventional synthetic disease-modifying anti-rheumatic drugs only., Conclusion: Disease activity is higher in patients with axSpA with history of IBD or history of PSO. Functional impairment is also higher in patients with axSpA with history of PSO. The presence of different EMMs was associated with different treatment patterns in axSpA., Competing Interests: Conflict of interest statement: I. Redeker, J. Callhoff, F. Hoffmann, A. Zink declare no conflicts of interest. U. Marschall is an employee of BARMER. H. Haibel reports consulting fees or members of speakers’ bureau from AbbVie, Janssen, MSD, Novartis, Pfizer, and Roche. B. Siegmund, has served as a consultant for AbbVie, Boehringer, Celgene, Falk, Janssen, Lilly, Pfizer, Prometheus, Takeda and received speaker’s fees from AbbVie, CED Service GmbH, Falk, Ferring, Janssen, Novartis, Takeda (BS served as representative of the Charité). J. Sieper reports consulting fees or members of speakers’ bureau from AbbVie, Janssen, Lilly, MSD, Novartis, and Pfizer and grants from AbbVie, MSD, and Pfizer. D. Poddubnyy reports consulting fees or members of speaker’s bureau from AbbVie, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, and UCB and grants from AbbVie, MSD, Novartis and Pfizer., (© The Author(s), 2020.)
- Published
- 2020
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49. The impact of impending / onset of vision loss on depression, anxiety, and vision-related quality of life in Birdshot-Retinochoroiditis and Serpiginous Choroiditis.
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Pohlmann D, Barth A, Macedo S, Pleyer U, Winterhalter S, and Albayrak Ö
- Subjects
- Adult, Aged, Aged, 80 and over, Anxiety Disorders diagnosis, Birdshot Chorioretinopathy complications, Case-Control Studies, Cross-Sectional Studies, Depression diagnosis, Female, Humans, Linear Models, Male, Middle Aged, Severity of Illness Index, Sickness Impact Profile, Statistics, Nonparametric, Vision Disorders etiology, Visual Acuity, White Dot Syndromes complications, Anxiety Disorders etiology, Birdshot Chorioretinopathy pathology, Depression etiology, Quality of Life, Vision Disorders psychology, White Dot Syndromes pathology
- Abstract
To evaluate the impact of Birdshot-Retinochoroidopathy (BSRC) and Serpiginous Choroiditis (SC) on depression, anxiety, and vision-related quality of life. 72 individuals (BSRC: n = 28, SC: n = 8; healthy control group (HC): n = 36) completed the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and the Visual Function Questionnaire (VFQ-25). Multivariate linear regression models were used to analyze different subscales of the PHQ-9, the GAD-7 and the VFQ-25. The results showed that the mean of PHQ-9 was significantly higher while the mean of the VFQ-25 and its´ subscales were consistently lower in the disease group compared to HC. The mean of GAD-7 was not significantly lower in the disease group compared to HC. Stratification for different disease severity stages and duration of disease did not reveal any differences in sum scores of PHQ-9, GAD-7, and VFQ-25, whereas there were significant differences in some subscales of the VFQ-25. We conclude that BSRC and SC patients show higher levels of depression and a reduced visual quality of life due to imminent loss of vision. Because depression and quality of life are adversely affected by lack of social contacts and functioning, psychological treatment should enable patients to maintain their independence and ability to social interaction. Psychosomatic care should be taken in account for the treatment of BSRC and SC., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2020
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50. Uveitis in spondyloarthritis.
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Rademacher J, Poddubnyy D, and Pleyer U
- Abstract
Uveitis is the most frequent extra-articular manifestation of axial spondyloarthritis (SpA), occurring in up to one-third of the patients. In the majority of patients, uveitis is acute, anterior and unilateral and presents with photosensitivity, sudden onset of pain and blurred vision. Topical steroids are an effective treatment; however, recurrent or refractory cases may need conventional disease-modifying antirheumatic drugs or biological treatment with monoclonal tumor necrosis factor (TNF) inhibitors, thus also influencing treatment strategy of the underlying SpA. Though the exact pathogenesis of SpA and uveitis remains unknown, both seem to result from the interaction of a specific, mostly shared genetical background (among other HLA-B27 positivity), external influences such as microbiome, bacterial infection or mechanical stress and activation of the immune system resulting in inflammation. Up to 40% of patients presenting with acute anterior uveitis (AAU) have an undiagnosed SpA. Therefore, an effective referral strategy for AAU patients is needed to shorten the diagnostic delay of SpA and enable an early effective treatment. Further, the risk for ophthalmological manifestations increases with the disease duration in SpA; and patients presenting with ocular symptoms should be referred to an ophthalmologist. Thus, a close collaboration between patient, rheumatologist and ophthalmologist is needed to optimally manage ocular inflammation in SpA., Competing Interests: Conflict of interest statement: JR: grant/research support from AbbVie, consultancy for Novartis. DP research grants from: AbbVie, Lilly, MSD, Novartis, Pfizer. Consultancy/speaker fees from: AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, UCB. UP served as principal investigator or consultant for: Abbvie, Alcon, Allergan, Alimera, Bayer, Dompé, Lilly, Novartis, Santen, Shire, Thea and Winzer., (© The Author(s), 2020.)
- Published
- 2020
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