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Zusammenfassung Hintergrund Die okuläre Toxoplasmose (OT) ist die häufigste infektiöse Ursache einer posterioren Uveitis. Diese Erhebung soll das derzeitige diagnostische und therapeutische Vorgehen bei OT in Deutschland evaluieren. Material und Methoden Ein detaillierter Fragebogen mit spezifischen Patientenbeispielen wurde im Juli 2021 an die Mitglieder der Sektion Uveitis der Deutschen Ophthalmologischen Gesellschaft (DOG) und der Retinologischen Gesellschaft (RG) versandt. Ergebnisse Der Fragebogen wurde von 53 (29 RG und 24 DOG) Ophthalmologen beantwortet. Sechzehn (30 %) Befragte arbeiten in einer Praxis, 18 (34 %) in einer Klinik und 19 (36 %) in einer Universitätsklinik. Neun (17 %) Augenärzte (AÄ) betreuen weniger als 50, 28 (53 %) 50 bis 200 und 16 (30 %) mehr als 200 Uveitispatienten pro Jahr. Der klinische Befund gilt weiterhin als Goldstandard (87 %) für die Diagnose der OT und wird bei Erstmanifestation in 60 % durch spezifische serologische Antikörperuntersuchungen unterstützt. Eine Diagnose allein anhand des klinischen Befundes stellen 10 von 53 (19 %) AÄ, 25 (47 %) Befragte stützen sich auf einen Ig(Immunglobulin)M-Test, 6 (11 %) erwarteten einen IgG-Titer-Anstieg und einer (2 %) den Nachweis spezifischer IgA-Antikörper. Die Mehrheit (n = 28 [53 %]) der AÄ würde die Diagnose im Zweifelsfall durch eine Vorderkammerpunktion sichern; dabei präferieren 20 (38 %) die Polymerasekettenreaktion (PCR), 3 (6 %) die Bestimmung des Goldmann-Witmer-Koeffizienten und 5 (9 %) eine Kombination beider Verfahren. Zur Therapie wurde am häufigsten Clindamycin eingesetzt (n = 21 [40 %]), gefolgt von Pyrimethamin/Sulfadiazin (n = 17 [32 %]) und Trimethoprim + Sulfamethoxazol (TMP/SMX) (n = 10 [19 %]); Letzteres wird auch (n = 40 [75 %]) zur Sekundärprophylaxe eingesetzt. Schlussfolgerungen Die Ergebnisse lassen neben dem klinischen Befund als „Goldstandard“ zur Diagnosestellung kein einheitliches Vorgehen zu Diagnose und Therapie der OT erkennen. Die hohe Nachfrage nach Serum-IgM-Antikörpern weist auf eine weitverbreitete Unsicherheit über die Bedeutung serologischer Befunde hin. Dies ist angesichts der weiterhin hohen Seroprävalenz in Deutschland kritisch zu werten.

Background Uveitis in juvenile idiopathic arthritis (JIAU) is frequently associated with the development of complications and visual loss. Topical corticosteroids are the first line therapy, and disease modifying anti-rheumatic drugs (DMARDs) are commonly used. However, treatment has not been standardized. Methods Interdisciplinary guideline were developed with representatives from the German Ophthalmological Society, Society for Paediatric Rheumatology, Professional Association of Ophthalmologists, German Society for Rheumatology, parents’ group, moderated by the Association of the Scientific Medical Societies in Germany. A systematic literature analysis in MEDLINE was performed, evidence and recommendations were graded, an algorithm for anti-inflammatory treatment and final statements were discussed in a consensus meeting (Nominal Group Technique), a preliminary draft was fine-tuned and discussed thereafter by all participants (Delphi procedure). Results Consensus was reached on recommendations, including a standardized treatment strategy according to uveitis severity in the individual patient. Thus, methotrexate shall be introduced for uveitis not responding to low-dose (≤ 2 applications/day) topical corticosteroids, and a TNFalpha antibody (preferably adalimumab) used, if uveitis inactivity is not achieved. In very severe active uveitis with uveitis-related deterioration of vision, systemic corticosteroids should be considered for bridging until DMARDs take effect. If TNFalpha antibodies fail to take effect or lose effect, another biological should be selected (tocilizumab, abatacept or rituximab). De-escalation of DMARDs should be preceded by a period of ≥ 2 years of uveitis inactivity. Conclusions An interdisciplinary, evidence-based treatment guideline for JIAU is presented.

BackgroundPatients with acute anterior uveitis (AAU) have an increased risk for concomitant spondyloarthritis (SpA). Different referral strategies have been proposed to identify AAU patients with high probability of SpA, among them an Assessment of SpondyloArthritis international Society(ASAS)-based referral strategy focusing on patients with chronic back pain starting before the age of 45 years and the Dublin Uveitis Evaluation Tool (DUET) also including psoriasis, HLA-B27 and arthralgia (Poddubnyy et al., Haroon et al., both ARD 2015).ObjectivesTo analyse the prevalence of SpA in patients with AAU, to identify parameters associated with SpA presence, and to evaluate referral algorithms.MethodsPatients with non-infectious AAU underwent structured rheumatologic assessment including magnetic resonance imaging of 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 and without SpA. Furthermore, logistic regression analyses were performed. Sensitivity, specificity, positive predictive value, positive and negative likelihood ratios were analysed for referral strategies.ResultsThe 189 AAU patients with complete rheumatologic assessment and SIJ imaging were 40.8 years old, and 55% were males. SpA was diagnosed in 106 AAU patients (56%). The majority (93%) had predominantly axial SpA, 7 patients peripheral SpA. In 74 patients (70%), the SpA diagnosis was established for the first time. Pelvic X-rays were available for 88 (89%) of the axSpA patients, 66% of whom were classified as having radiographic axSpA.SpA was equally frequent in patients experiencing the first episode of AAU and in patients with recurrent disease. In our cohort, AAU patients with and without underlying SpA showed no differences in their ophthalmologic examination. In multivariable logistic regression analysis, psoriasis (OR 12.5 [95%CI 1.3-120.2]), HLA-B27 positivity (OR 6.3 [95%CI 2.4-16.4]), elevated CRP (OR 4.8 [95%CI 1.9-12.4]) and male sex (OR 2.1 [95%CI 1.1-4.2]) were associated with SpA presence.Table 1.Parameters associated with the presence of spondyloarthritis in patients with acute anterior uveitis.univariablemultivariableOR95%CIOR95%CIPsoriasis (ever)14.6(1.9; 112.4)12.5(1.3; 120.2)HLA-B27 positivity6.2(2.7; 14.6)6.3(2.4; 16.4)Elevated CRP (≥ 5 mg/l)4.1(1.8; 9.0)4.8(1.9; 12.4)Male sex2.2(1.2; 4.0)2.1(1.1; 4.2)Inflammatory back pain (ASAS definition)2.1(1.2; 3.9)1.9(0.9; 4.0)Any peripheral manifestation (ever)1.9(1.1; 3.5)1.9(0.9; 3.8)Age in years1.0(1.0; 1.0)1.0(1.0; 1.0)Univariable and multivariable logistic regression analyses. ASAS Assessment of SpondyloArthritis international Society; CRP C-reactive protein; OR odds ratio; CI confidence interval.The Dublin Uveitis Evaluation Tool showed higher specificity for SpA recognition than the ASAS referral tool (42% vs. 28%), which had slightly higher sensitivity (78% vs. 80%). However, both referral strategies would have missed more than 20% of SpA patients.ConclusionWe revealed a high prevalence of overall and previously undiagnosed SpA in AAU patients. Therefore, we propose rheumatologic evaluation for all AAU patients with musculoskeletal symptoms. Rheumatologists should consider that SpA in AAU patients might present “atypically” with back pain starting after 45 years and lasting shorter than 3 months.Figure 1.Performance of Referral Strategies in Patients with Acute Anterior Uveitis. Dublin Uveitis Evaluation Tool (DUET) and an ASAS-based referral tool (ASAS). + respective tool fulfilled, - not fulfilled. ASAS Assessment of SpondyloArthritis international Society; AxSpA axial spondyloarthritis, pSpA peripheral spondyloarthritis.AcknowledgementsThe authors would like to thank the rheumatologists S. Lüders, B. Muche and A.-K. Weber for participating in the clinical data acquisition; and A. Langdon and L. Meinke for their support monitoring and coordinating this study. Furthermore, we are grateful to all participating ophthalmologists who included their patients in this study and to all patients. The study was supported by an unrestricted research grant from AbbVie. AbbVie had no role in the study design or in the collection, analysis, or interpretation of the data, the writing of the manuscript, or the decision to submit the manuscript for publication. Dr. Judith Rademacher and Dr. Dominika Pohlmann are participants in the BIH-Charité Clinician Scientist Program funded by the Charité –Universitätsmedizin Berlin and the Berlin Institute of Health.Disclosure of InterestsJudith Rademacher: None declared, Hanna Müllner: None declared, Torsten Diekhoff Speakers bureau: AbbVie, MSD, Novartis, Canon MS, Consultant of: Lilly, Hildrun Haibel Speakers bureau: AbbVie, MSD, Janssen, Roche, Pfizer, Sobi, Consultant of: Janssen, Sobi, Novartis, Sabrina Igel: None declared, Dominika Pohlmann Speakers bureau: Bayer, Consultant of: AbbVie, Celgene, Janssen, Novartis, UCB, Grant/research support from: Bayer, Allergan, Fabian Proft Speakers bureau: AMGEN, AbbVie, BMS, Celgene, Janssen, MSD, Novartis, Pfizer, Roche, UCB, Consultant of: AbbVie, Celgene, Janssen, Novartis, UCB, Grant/research support from: UCB, Novartis, Lilly, Mikhail Protopopov Consultant of: Novartis, Valeria Rios Rodriguez Consultant of: AbbVie, Falk e.V., Murat Torgutalp: None declared, Uwe Pleyer Shareholder of: stock or stock options from Novartis, BionTec, Speakers bureau: AbbVie, Alimera, Novartis, Grant/research support from: AbbVie, Denis Poddubnyy Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer and UCB, Consultant of: AbbVie, Biorad, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, MSD, Novartis, Pfizer, Samsung Bioepis and UCB, Grant/research support from: AbbVie, Eli Lilly, MSD, Novartis, Pfizer

This article reports on the sixth scientific workshop of the European Crohn's and Colitis Organisation [ECCO] on the pathogenesis of extraintestinal manifestations [EIMs] in inflammatory bowel disease [IBD]. This paper has been drafted by 15 ECCO members and 6 external experts [in rheumatology, dermatology, ophthalmology, and immunology] from 10 European countries and the USA. Within the workshop, contributors formed subgroups to address specific areas. Following a comprehensive literature search, the supporting text was finalized under the leadership of the heads of the working groups before being integrated by the group consensus leaders.

Die durch Adenoviren ausgeloste Keratoconjunctivitis (epidemica, KCE; ICD-10 B30.0+) ist haufig, kann schwer verlaufen und verursacht eine erhebliche Morbiditat. In der Fruhphase ist es oft schwierig, allein aufgrund des klinischen Befundes die KCE von anderen Ursachen eines anderen „roten Auges“ zu unterscheiden. Aufgrund hoher Kontagiositat kann sich die Erkrankung rasch zu einem epidemischen Geschehen auswachsen. Daher bleibt eine rasche Virusidentifikation und Vermeidung weiterer Ausbreitung der Infektion eine wesentliche Herausforderung. Da es schwierig ist, kurzfristig den labortechnischen Erregernachweis zu fuhren, wird der Anfangsverdacht zunachst rein klinisch geausert. Neuentwicklungen wie Screeningtests sind von praktischer Bedeutung und konnen die Fruhdiagnose unterstutzen. Adenoviren sind klinisch problematisch, da sie eine hohe Resistenz gegenuber Umweltfaktoren aufweisen und hoch entwickelte „Escape-Mechanismen“ eine Persistenz des Virus auch uber lange Zeit an der Augenoberflache ermoglichen. Bestandteile der Virusproteine verbleiben haufig in der Hornhaut, vor allem in der Bowman-Schicht. Hier fuhren sie zu immunologischen Reaktionen und den typischen subepithelialen Infiltraten („Nummuli“). Die Behandlung der KCE beschrankt sich zurzeit auf symptomatische Oberflachenpflege. Das Hauptproblem, die Persistenz subepithelialer Infiltrate, ist schwierig anzugehen. Eine risikoarme Option ist die Anwendung von Ciclosporin-A-Augentropfen. Die Behandlung mit topischen Steroiden ist eher problematisch, kann jedoch in allen Krankheitsstadien diskutiert werden. Da die Verbreitung von Adenoviren oft nosokomial erfolgt, bleibt die Pravention der Infektion eine zentrale Verantwortung der Ophthalmologen.

Purpose To evaluate the long-term safety of DEX in patients treated for RVO-related macular edema (ME) or NIPSU in clinical practice. Methods Multicenter (102 sites in France, Germany, Spain, United Kingdom), prospective, observational, post-authorization safety study in adult patients treated with DEX. Treatment and follow-up were at physicians’ discretion. Data collected up to 2 years after enrollment included serious adverse events (SAEs) and adverse events of special interest (AESIs; adverse drug reactions with DEX as listed in the Summary of Product Characteristics). Results Overall, 753 patients (610 RVO, 143 NIPSU) received on-study DEX treatment and 73.0% completed 24 months follow-up; 74.0% had not used DEX previously. Median number of on-study injections per treated eye was 2 (range, 1–7) with median re-injection interval of 27 weeks; 36.4% of patients received >2 injections. Non-ocular SAEs affected 8.9% of patients; none were considered related to DEX. Ocular SAEs (most common: cataract progression) were reported in 3.4% of treated eyes. Non-ocular and ocular SAEs were similar in eyes stratified by previous DEX use and number of on-study DEX injections (≤2 or >2), regardless of indication (RVO or NIPSU). The most common AESIs reported were increased intraocular pressure (IOP) in 19.3% of treated eyes, cataract progression and cataract formation in 19.5% and 19.3% of treated phakic eyes (n=528), and vitreous hemorrhage in 3.2% of treated eyes. Cataract progression and vitreous hemorrhage were more frequent in eyes that received >2 DEX injections. Among eyes with RVO, cataract progression was more frequent in eyes previously treated with DEX. Conclusions The long-term safety profile of DEX was acceptable. The 2-year incidence of cataract and increased IOP was lower than previously reported (LOUVRE study). No new safety concerns were identified.

ZusammenfassungIntraokulare Entzündungen sind im Kindesalter eine der häufigsten Ursachen gesetzlicher Blindheit in Europa. Daher kommt der Diagnostik und Behandlung der Uveitis im Kindesalter besondere Bedeutung zu. Der oft asymptomatische Beginn der Entzündung und die dadurch verzögerte Diagnose führen nicht selten zu einer funktionell schlechteren Prognose gegenüber Erkrankungen im späteren Lebensalter. Bei etwa 20–30 % betroffener Augen verbleiben irreversible Schäden. Ziel dieses Beitrages ist es, auf die diagnostischen und therapeutischen Besonderheiten einzugehen, um Risiken und Komplikationen auf ein Minimum zu reduzieren.

Currently, the identification of apoptotic or damaged human corneal endothelial (HCE) cells is limited to a morphological assessment and vital staining. Specific electrophysiological investigations may prospectively help to identify damaged HCE cells at an earlier stage. Besides calcium imaging, the so-called patch-clamp technique is an important test method enabling one to assay the effect of various substances on ion channels and receptors of the cell membrane. First electrophysiological pilot experiments with cultivated and freshly isolated HCE cells have revealed promising results. In this way, the expression of certain transient receptor potential channels (TRPs) could be demonstrated. However, the function of these channels is still not fully elucidated. In humans, TRPs play a crucial role in the sense of taste, pheromones, temperature and pain and are involved in osmolarity. This review summarises the current literature on the electrophysiology of the human corneal endothelium and deduces potential approaches to a sensitive vitality and function test under utilisation of the electrophysiological properties of HCE cells.

An involvement of the visual system can be found in many neurologic diseases. Especially demyelinating processes of the central nervous system (CNS) and multiple sclerosis (MS) in particular present with a variety of ophthalmological abnormalities. While optic neuritis (ON) is known to be a positive predictor for the development of MS and can be considered a symptom of the disease, the high frequency of uveitis observed in MS patients seems to occur rather in the context of a general predisposition for autoimmune disorders. However, MS-associated uveitis can precede the onset of neurological symptoms by many years and shows response to treatment with steroids and interferons, suggesting the presence of similar underlying pathogenic mechanisms. Therefore, further studies are warranted in order to reveal whether administration of early immunomodulatory therapy can delay or even prevent the clinical manifestation of MS in a distinct subgroup of patients presenting with uveitis.

BACKGROUND: Interferons are a complex group of glycoproteins with antiviral, antiproliferative and immunomodulatory activity. They are used to treat different types of human neoplasms and chronic hepatitis C. Several case reports have described interferon-induced ocular side effects since the first case in 1990. PATIENT AND METHODS: We report about a 61-year-old female undergoing interferon 2alpha treatment who developed bilateral retinopathy during systemic therapy and provide a summary about ocular side effects and their consequences. CONCLUSIONS: Patients should be monitored by ophthalmologists before, during and after interferon therapy in order to avoid side effects like retinal neovascularisation and to prevent potential serious side effects.

The quality of an article depends first and foremost on its scientific content. However, the way in which the scientific material is presented may determine whether it will receive proper attention. The aim of this presentation is to point out general characteristics of good papers. The title can decide whether a potential reader will give your article a proper look. A good title is descriptive and may also give a statement if the journal style allows. The abstract is the most important part of your article. People will proceed to read the article only if they find the abstract interesting. Describe the material or patients and the methods in brief. It is advisable to specify the study design. Present the most important results in a brief manner. Give quantitative data with confidence limits whenever applicable. The reader wants to know what your results were, not just whether they were “statistically significant”. In the discussion, put your data into context with the clinical practice, literature or both. What have we learned? A common mistake is to include general conclusions which are not specifically supported by the data presented. Please check that the conclusions are in line with the stated aim of the study.

Objective and design: To examine the effects of the nitric oxide synthase (NOS) inhibitors aminoguanidine (AG) and L-NAME on leukocyte adhesion in endotoxin-induced uveitis (EIU).¶Material: Uveitis was induced in Lewis rats (n = 124) by LPS injection (Salmonella typhimurium).¶Treatment: Rats either (1) did not receive any LPS or other treatments (controls), received (2) only subcutaneous saline injections with LPS administration, (3) a single s.c. dose of AG (100 mg/kg body weight) at the time of LPS administration, (4) a single s.c. injection of AG 8 h after LPS injection, (5) s.c. injections of AG at the time of LPS administration and 8 h after LPS injection or (6) received a single dose of L-NAME (75 mg/kg body weight) at the time of LPS administration.¶Methods: Intravital microscopy (IVM) of iris vessels was performed at 2, 4, 8, 16, 24 and 48 h after endotoxin injection. Aqueous humor analysis for protein concentration and cell count was performed after IVM.¶Results: At 2 h after the induction of uveitis, significantly more rolling leukocytes were detected in the AG and L-NAME-treated group than in untreated EIU (4.8 ± 0.31 and 9.83 ± 0.64 vs. 2.85 ± 0.37 %, mean ± SEM, p < 0.01). However, at 16 h the percentage of rolling leukocytes was significantly reduced in all groups which had received AG (LPS: 8.08 ± 0.37 %; LPS/AG 0h: 3.78 ± 0.25 %; LPS/AG 8 h: 5.34 ± 0.3 %; LPS/AG 0 + 8 h: 3.86 ± 0.31 %). L-NAME enhanced leukocyte rolling even at 24 h after LPS (12.38 ± 0.64 %). Early treatment of EIU with AG significantly reduced the number of sticking leukocytes at 4, 8 and 24 h (306 ± 13 vs. 571 ± 41, 228 ± 12 vs. 345 ± 19 and 240 ± 14 vs. 469 ± 23 cells/mm2, respectively). L-NAME inhibited LPS-induced sticking of leukocytes at all observed time points and this effect was most pronounced at 24 h (147 ± 10 vs. 469 ± 23 cells/mm2).¶Conclusions: In EIU, administration of AG or L-NAME causes enhanced leukocyte rolling in the early inflammatory response. However, firm adhesion of leukocytes to the vascular endothelium decreases and this effect prevails, ameliorating leukocyte infiltration.

Purpose Identification of apoptotic or damaged human corneal endothelial cells (HCECs) is limited to morphological evaluation such as phase contrast microscopy and vital staining. The molecular mechanisms of corneal endothelial cell loss are not fully understood. Special investigations in cellular signalling and ion channel research are necessary to elucidate the mechanisms of corneal cell loss. In this context, it is known that this cell loss is often caused by apoptosis in oxidative stress. Methods Automated planar patch-clamp has become common in drug development and safety programs because it enables efficient and systematic testing of compounds against ion channels during voltage-clamp. A particularly successful automated approach is based on planar patch-clamp chips and this is the basis for the technology used here. Routine intracellular or extracellular perfusion opens possibilities for studying the regulation and pharmacology of ion channels. Previously, these studies were available only to highly skilled and dedicated experimenters. Results Notable, definite ion channel activities could be demonstrated by conventional as well as by planar patch-clamp in HCECs for the first time. In particular, temperature-sensing transient receptor potential (TRP)-like non-selective cation channel currents as well as capsaicin-sensitive ion channel currents could be detected. The expression of TRPV1-3 ion channels in HCEC could also be confirmed by RT-PCR, Western blot analysis and fluorescence cell imaging. Conclusion The administration of this novel measuring technology opens new perspectives in the investigation of the physiology of HCEC. The findings may have direct clinical implication (eye banking procedures, keratoplasty).

Zielsetzung: Das okulare Pemphigoid (OCP) ist eine Autoimmunerkrankung die durch Fibrosierung der Schleimhaute charakteristiert ist. Das Ziel unserer Studie war es, die klinischen Symptome, Risikofaktoren und die Immunpathologie bei Patienten mit OCP zu beschreiben. Methoden und Patienten: Die Diagnose OCP wurde uberwiegend klinisch gestellt und durch Nachweis linearer Antikorperablagerungen an der Basalmembran (BMZ) und/oder dem Vorhandensein zirkulierender Antikorper gegen Proteine der epithelialen BMZ erganzt. Ergebnisse: 38 Patienten mit klinischem Hinweis auf ein okulares Pemphigoid wurden eingeschlossen. Bei allen Patienten lag eine Beteiligung beider Augen vor. Extraokulare Manifestationen waren weit verbreitet (35%), wobei eine Beteiligung der Mundschleimhaut dominierte (31%). Bei Erstvorstellung hatten bereits ca. 50% aller Patienten ein fortgeschrittenes Stadium III (26%) oder IV (21%) erreicht. Als haufigste okulare Komorbiditat wurde ein Glaukom (28%) beobachtet. Die systemische Therapie mit Dapson (38%), oralen Steroiden (29%), Azathioprin (7%), Methotrexat (41%), Mycophenolatmofetil (41%), Cyclophosphamid (28%) und Rituximab (3%) erfolgte in einer Stufenleiter. Als Komplikationen des OCP wurden Entropiumbildung, rezidivierende Hornhauterosionen, und- ulzerationen bis hin zur Hornhautperforation beobachtet. Verschiedene chirurgische Interventionen mit Entropium-Korrektur (21%), Schleimhauttransplantation (3%), Amnionmembran-Transplantation (3%), tektonische Keratoplastik (3%), Keratoprothese (3%) oder Enukleation(3%) wurden daher notwendig. Schlussfolgernung: Die Moglichkeiten funktioneller Rehabilitation bei Patienten mit fortgeschrittenem OCP bleiben stark eingeschrankt. Deshalb sollten sich die Bemuhungen auf eine fruhere Diagnosestellung konzentrieren. Oft werden eingreifende systemische Therapien und operative Masnahmen notwendig um die Progredienz der Erkrankung und ein Erblinden zu verhindern.