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Approximately 0.5-1% of patients with multiple sclerosis (MS) have co-existing uveitis. Both intraocular inflammation and MS mainly affect women in younger adulthood. The MS in patients is most frequently associated with an often bilateral intermediate uveitis with typical concomitant retinal vasculitis. Both diseases share similar characteristics with chronic inflammatory diseases with a relapsing course and an immune-mediated pathogenesis; however, it is still unclear whether the co-occurrence of uveitis and MS in the same patient represents a coincidence of two separate disease entities or whether uveitis is a rare clinical manifestation of MS. In the differential diagnostics of intermediate uveitis, clinical symptoms and signs of MS should be considered. As both diseases are considered to be immune-mediated, immunotherapy is the main treatment option. In recent years the range of medications has expanded and includes several disease modifying drugs (biologics). When selecting the active substance it must be taken into account that tumor necrosis factor (TNF) alpha blockers are contraindicated in patients with MS., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

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.)

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.)

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.)

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.)

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.)

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.)

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.

Background: The standardization of uveitis nomenclature (SUN) working group is an international expert committee, which follows the aim to develop a standardized and internationally recognized terminology for the field of uveitis. This appears to be important in view of the demand for evidence-based medicine, especially for relatively rare diseases such as uveitis., Methods: A databank of > 4000 uveitis patients was compiled using formal consensus techniques, for whom a majority consensus was previously achieved in the diagnosis. The patient data were analyzed within the subclasses of uveitis and divided into a training set and a validation set. Multinomial logistic regressions with LASSO regularization were carried out on the training set with machine learning (ML). The accuracy of the rules that were developed to express the criteria of ML, were assessed by a masked observer in a random sample of 10%., Results: The estimations of total accuracy according to the uveitis classes in the validation set were high for all forms of uveitis: anterior uveitis 96.7% (95% confidence interval, CI 92.4-98.6%), intermediate uveitis 99.3% (95% CI 96.1-99.9%), posterior uveitis 98.0% (95% CI 94.3-99.3%), panuveitis 94.0% (95% CI 89.0-96.8%) and infectious posterior uveitis/panuveitis 93.3% (95% CI 89.1-96.3%)., Conclusion: Classification criteria are presented, which show a high degree of accuracy (low misclassification rates) and are therefore suitable for future clinical and translational research., (© 2021. The Author(s).)

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.

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.)

Background: Sympathetic ophthalmia (SO) is a rare inflammation of an operated or injured eye that spreads to the fellow eye. It is typically a bilateral granulomatous panuveitis. The traumatized eye is referred to as inciting eye and the fellow eye as sympathizing eye. The pathophysiology of the disease is not entirely understood, but there is strong evidence of an autoimmune genesis., Patients/material and Methods: A selective literature search on epidemiology, immunology, clinical features and risk factors of SO was carried out. In addition, our own experience using multimodal imaging for this clinical entity was introduced., Results: In the literature, the incidence after traumatic eye injuries is 0.1 - 3% and approximately 0.01% after intraocular surgery. Among the iatrogenic causes, vitreoretinal surgery has the highest rate of SO, presumably due to disruption of the blood-retinal barrier and involvement of retinal and choroidal tissue, which are susceptible to anterior traction, phthisis and chronic inflammation. In 90% of patients, the disease develops within a year following the eliciting event and is associated with a potentially bilateral risk of blindness. Typical symptoms include bilateral visual impairment with photophobia, dull pain and photopsia. The spectrum of clinical manifestations ranges from granulomatous anterior uveitis and vitritis, to choroiditis, serous retinal detachment and Dalen-Fuchs nodules in the context of posterior involvement. The diagnosis of SO is generally based on clinical presentation and is supported by imaging methods. These primarily comprise fluorescein and indocyanine green angiography, which are increasingly being supplemented by non-invasive methods such as optical coherence tomography. They can provide important information for assessment of severity, differential diagnosis as well as for disease monitoring. The differential diagnosis includes i. a. Vogt-Koyanagi-Harada syndrome, ocular sarcoidosis and the rare phacoanaphylactic endophthalmitis. Immediate systemic high-dose steroid therapy is used as initial treatment. The course of the disease is often relapsing to chronic progressive. Immunomodulators such as ciclosporine A, azathioprine, cyclophosphamide, mycophenolate mofetil, and biologics are increasingly being used and contribute to the significantly better prognosis of the disease. Generally, SO can be triggered by any kind of intraocular intervention., Conclusion: SO remains a threatening clinical diagnosis that poses diagnostic and therapeutic challenges. It can be triggered post-traumatic, but also any intraocular surgery. This should be taken into account when assessing the indication for intraocular eye surgery, especially in eyes with reduced visual outcome., Competing Interests: UP: Consultant: Abbvie, Allergan, Novartis, Santen, Thea; Section chair: Uveitis – German Society of Ophthalmology./UP: Berater Abbvie, Allergan, Novartis, Santen, Thea; Sprecher: Sektion Uveitis/DOG., (Thieme. All rights reserved.)

Anterior uveitis involves inflammation of the iris and/or ciliary body and is the most common intraocular inflammation in ophthalmological practice. It can be attributed to an infectious or immune-mediated genesis or be associated with systemic diseases. Anamnesis and (guiding) findings during the slit lamp examination often already provide important information on pathogenesis and thus on further diagnostic clarification and therapy. This includes the assessment of laterality, acute or chronic course of the disease and morphological criteria (granulomatous/non-granulomatous). The guideline-compliant procedure recommends further diagnosis with targeted laboratory diagnostics and, if necessary, consultative examinations if the disease recurs. This is important in order to pursue a targeted treatment approach and to recognize comorbidities., Competing Interests: Erklärung zu finanziellen Interessen Forschungsförderung erhalten: ja, von einer anderen Institution (Pharma- oder Medizintechnikfirma usw.); Honorar/geldwerten Vorteil für Referententätigkeit erhalten: ja, von einer anderen Institution (Pharma- oder Medizintechnikfirma usw.); Bezahlter Berater/interner Schulungsreferent/Gehaltsempfänger: ja, von einer anderen Institution (Pharma- oder Medizintechnikfirma usw.); Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an im Bereich der Medizin aktiven Firma: nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an zu Sponsoren dieser Fortbildung bzw. durch die Fortbildung in ihren Geschäftsinteressen berührten Firma: nein. Erklärung zu nichtfinanziellen Interessen U. Pleyer: DOG – Vorstand der Sektion Uveitis; DUAG – Vorstandsmitglied; IUSG – Mitglied, (Thieme. All rights reserved.)

Imaging is one of the key elements in the diagnosis and treatment of eye diseases. This is especially true for intraocular inflammation. In this article, the current imaging modalities such as optical coherence tomography (OCT), OCT angiography, fluorescein and indocyanine green angiography, fundus autofluorescence and wide-field imaging modalities are discussed. The use of these examination methods is illustrated, depending on the focus of intraocular inflammation. In addition, current and future options are presented for optimised, objective monitoring for these clinical entities., Competing Interests: Dr. Dominika Pohlmann ist Teilnehmerin des BIH Charité Clinician Scientist Programm der Charité Universitätsmedizin Berlin und des Berlin Institute of Health (BIH). DP: Allergan, Bayer; UP: Abbvie, Alcon, Alimera, Allergan, Dompé, Novartis, Santen, Shire und Thea; CH: Vortrag: AbbVie, Alimera, Novartis, Allergan; Advisory Board: Alimera. Keiner der Autoren weist Interessenkonflikte oder ein Eigentumsinteresse auf., (Georg Thieme Verlag KG Stuttgart · New York.)

Introduction : Uveitis is a leading cause of visual impairment and a significant burden of blindness. Although corticosteroids and conventional immunosuppressive agents have been successfully used, these are non-specific, and their long-term use may induce significant adverse effects. Areas covered : This article discusses existing local and systemic applied treatments for ocular inflammation including corticosteroids, non-biologic, and biologic disease-modifying anti-rheumatic drugs (DMARD). Potential drugs being studied in clinical trials are introduced for both local and systemic use. Expert opinion : Treatment options for uveitis continue to expand. Still, more efforts and research are needed to better understand the mechanisms potentially leading to clinical trials.

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., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To report the effectiveness of repeated intravitreal dexamethasone (DEX) inserts in noninfectious uveitis patients., Design: Prospective, single-center, interventional clinical trial between February 2010 and March 2015., Participants: Patients with noninfectious uveitis with cystoid macular edema and/or vitreitis., Methods: Patients were treated with a 700-μg intravitreal DEX insert (Ozurdex; Allergan, Inc., Irvine, CA). Follow-up visits were scheduled 1, 3, and 6 months after injection. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), vitreous haze (VH) score, intraocular pressure (IOP), and adverse events were recorded., Main Outcome Measures: Primary outcome was the reduction of CRT. Secondary outcome was the improvement in BCVA and reduction of VH., Results: In total, 109 eyes of 76 patients received 298 DEX inserts. Fifty-two patients were women (68%). The mean age of all participants was 57 years (range, 24-88 years). More than 3 DEX inserts were injected into 44% of eyes. Mean number of injections were 1.54±0.5 (standard deviation [SD]), 1.98±0.84, and 2.46±1.1 over 12, 18, and 24 months, respectively. Central retinal thickness decreased significantly (P < 0.001) from 465 μm at baseline to 318, 342, and 388 μm after 1, 3, and 6 months, respectively. Similar trends were seen in eyes receiving a second, third, and fourth DEX insert. Patients with idiopathic uveitis and sarcoidosis benefited well from DEX inserts. The greatest overall benefit was achieved in patients with no systemic treatment and patients receiving antimetabolites and cyclosporin A. A significant VH score reduction was documented in 44% of eyes after 1 month. A gain of more than 3 lines in BCVA was recorded in 31% to 37%, 26% to 39%, and 8% to 32% of eyes after 1, 3, and 6 months, respectively. A transient rise in mean IOP after 1 month (P < 0.001) and after 3 months (P = 0.001) was seen., Conclusions: The repeated longer-term administration of DEX inserts in noninfectious uveitis patients, either alone or in combination with other therapies, led to improved CRT, BCVA, and VH. Underlying diseases and concomitant systemic therapy seem to have an impact on overall treatment benefit. Ocular complications were reversible and were managed by local treatment, with exception of cataract formation., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Posner-Schlossman-Syndrome (PSS) is clinically characterized by acute, recurrent, mild, unilateral uveitis anterior accompanied by elevated intraocular pressure (IOP). Fuchs´ Uveitis (FU) is a chronic, low-grade-inflammatory disorder, involving anterior uvea and vitreous. The clinical findings show remarkable similarities as well as differences. In our study, we determine the composition of immune mediators in aqueous humor of patients with PSS and FU and evaluate if immune mediators play a crucial role in specific viral intraocular inflammation and IOP rises. Aqueous humor samples from 81 uveitis patients (= eyes) presenting with either PSS or FU were collected at one time point. Local intraocular antibody synthesis to rubella virus was confirmed in 65 patients, whereas 16 were tested positively for human cytomegalovirus. Thirteen patients with PSS and 10 patients with FU were treated with glaucoma medications. Additionally, 11 cataract patients acted as control group. Immune mediator concentrations were measured by Bio-Plex Pro assay. We observed in both PSS (IFN-γ: 174.9 pg/mL; TNF-α: 25.1 pg/mL) and FU (IFN-γ: 25.4 pg/mL; TNF-α: 27.2 pg/mL) groups a significantly increased level of T-helper 1 immune mediators compared to controls (IFN-γ, TNF-α: 0 pg/mL) [median]. Notably, PSS patients (IL-1RA: 73.4 pg/mL; IL-8: 199.4 pg/mL; IL-10: 33.4 pg/mL; IP-10: 126350 pg/mL) showed a stronger and more active ocular inflammatory response, than FU patients (IL-1RA: 4.3 pg/mL; IL-8: 72.4 pg/mL; IL-10: 1.6 pg/mL; IP-10: 57400 pg/mL). Furthermore, a negative correlation between mediators and IOP was seen in the PSS group, potentially caused by acetazolamide-treatment. Our findings show that immune mediators play a crucial role in specific viral intraocular inflammation and influence IOP levels. Remarkable similarities but also significant differences of immune mediator concentrations are apparent in PSS compared to FU. High concentrations of IL-1RA, IL-8, IL-10, and IP-10 correlate with active inflammation in PSS, while FU may trigger chronic inflammation. Our data also substantiated a very similar composition of cytokines in those patients from the PSS group suffering from ocular hypertension and thus offers a potential explanation model for a negative correlation between mediators and IOP., Competing Interests: DP has served as consult for Allergan. SW has served as consultant for: Allergan, Novartis, Bayer, MSD, Heidelberg Engineering. UP has served as principal investigator or consultant for: Abbvie, Alcon, Allergan, Novartis, Santen, Thea. None of the authors has a direct proprietary interest in any of the products used in this study. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Multiple sclerosis (MS) is a chronic inflammatory disorder of the brain and the spinal cord occurring mostly in young adults and is associated with temporary or permanent neurological deficits. An association between uveitis and MS has been recognized for a long time. Current data indicate an approximately 10 times higher prevalence of uveitis in patients with MS compared to the general population. In particular, MS is associated with intermediate uveitis and typically with concomitant retinal vasculitis. The treatment of uveitis should not only take the severity of intraocular inflammation into account but a coordination of the active agents must also consider the neurological manifestations. Since uveitis and MS are pathogenetically based on an immune-mediated genesis, immunomodulatory treatment approaches are dominant but it is important to bear in mind that tumor necrosis factor(TNF)-alpha blocking agents may worsen MS.

Cataracts are a frequent complication of uveitis, and their management can be challenging. Operation planning requires knowledge of the cause (e.g., infectious versus noninfectious) and course of uveitis, including any intraocular comorbidities (e.g., macular edema). Preoperative patient selection is particularly important in uveitis patients to achieve good surgical results. Steroid-sparing disease-modifying antirheumatic drugs (DMARDs) can reduce the rate of postoperative complications and can improve visual acuity. Before the operation, a stable inactivity of intraocular inflammation must be achieved. The surgical approach should be minimally invasive. Intraocular lens implantation should only be performed under stable inflammatory control. By using intraocular corticosteroids (e.g., dexamethasone acetonide implant, triamcinolone acetonide) the complication rate can be reduced. Postoperatively, the additional anti-inflammatory medication should be intensified and continued for up to 3 months. With careful patient selection, planning and execution of cataract surgery and postoperative care, satisfactory anatomical and functional outcomes can be achieved in uveitis patients., Competing Interests: AH: institutionell: BMBF, DFG; nicht institutionell: AbbVie, Alimera, Sciences, Allergan, MSD, Pfizer, Santen, Xoma. KW: keine. UP: institutionell: BMBF, EU, DFG; nicht institutionell: Abbvie, Alcon, Allergan, Bausch and Lomb, Bayer, Dompe, Novartis, Santen, Sanofi, Shire, Thea., (Georg Thieme Verlag KG Stuttgart · New York.)

Biologic disease modifying antirheumatic drugs (bDMARDs) can be highly efficient in the treatment of various non-infectious uveitis entities. Currently, the TNF-α-inhibitor Adalimumab is the only in-label therapeutic option, whereas, all other bDMARDs need to be given as an off-label therapy. bDMARDs are indicated in diseases refractory to conventional synthetic DMARD therapy and/or systemic steroids, or in patients in whom treatment with those is not possible due to side effects. Therapeutic mechanisms currently employed are cytokine-specific (interferons, inhibition of TNF-α or of interleukin [IL]-1-, IL-6- or IL-17-signalling), inhibit T cell costimulation (CTLA-4 fusion protein), or act via depletion of B cells (anti-CD20). All bDMARDs need to be administered parenterally, and therapy is initiated by the treating internal specialist only after interdisciplinary coordination of all treating subspecialties and after exclusion of contraindications. Regular clinical and laboratory monitoring is mandatory for all patients while under bDMARD therapy., Competing Interests: KW: keine. UP: institutionell: BMBF, EU, DFG; nicht institutionell: AbbVie, Alcon, Allergan, Bausch and Lomb, Bayer, Novartis, Santen, Sanofi, Thea. AH: institutionell: BMBF, DFG; nicht institutionell: AbbVie, Alimera, Sciences, Allergan, MSD, Pfizer, Santen, Xoma., (Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: To assess the efficacy and tolerability of intravitreal dexamethasone 0.7 mg sustained-release insert (Ozurdex ® ) in patients with sclerouveitis and recurrent cystoid macula edema (CMO) refractory to treatment., Methods: Interventional retrospective case series of five patients receiving 13 intravitreal dexamethasone inserts., Results: Three of five patients presented with an associated systemic disorder, whereas two patients had idiopathic sclerouveitis. All patients received immunosuppressive therapy. The CRT mean (SD) decreased in all eyes from 428 μm (137) (baseline) to 327 μm (149) (1 month), 342 μm (155) (3 months), 297 μm (99) (6 months) and reduced scleral inflammation. No morphologic adverse changes were noted, in particular, no scleral melting or necrosis occurred., Conclusions: Intravitreal dexamethasone may be an effective and safe therapeutic option in sclerouveitis with otherwise treatment-resistant CMO. It resolves not only CMO, but also provides a reduction of scleral inflammation and ocular pain. Nonetheless, adequate immunosuppressive treatment of an underlying disease must ensue.

Introduction: Intraocular inflammation (uveitis) remains a significant burden of legal blindness. Because of its immune mediated and chronic recurrent nature, common therapy includes corticosteroids, disease-modifying anti-rheumatic drugs and more recently biologics as immune modulatory agents. The purpose of this article is to identify the role of new treatment approaches focusing on small molecules as therapeutic option in uveitis. Areas covered: A MEDLINE database search was conducted through February 2017 using the terms 'uveitis' and 'small molecule'. To provide ongoing and future perspectives in treatment options, also clinical trials as registered at ClinicalTrials.gov were included. Both, results from experimental as well as clinical research in this field were included. Since this field is rapidly evolving, a selection of promising agents had to be made. Expert opinion: Small molecules may interfere at different steps of the inflammatory cascade and appear as an interesting option in the treatment algorithm of uveitis. Because of their highly targeted molecular effects and their favorable bioavailability with the potential of topical application small molecules hold great promise. Nevertheless, a careful evaluation of these agents has to be made, since current experience is almost exclusively based on experimental uveitis models and few registered trials.

Treatment of autoimmune diseases has undergone significant changes and developments in recent years. New classes of active substances, in particular biologics and small molecules have resulted in previously unknown success in the treatment of many diseases. In particular patients suffering from autoimmune rheumatic or dermatological diseases have benefited. For autoimmune uveitis there are numerous reports indicating excellent therapeutic and preventive effects; however, statutory approval for therapy in adults is still pending. This article outlines recent advances and future therapeutic options for the treatment of posterior segment noninfectious uveitis.

Introduction: Noninfectious posterior uveitis (NIPU) remains a significant burden of legal blindness. Because of its immune mediated and chronic recurrent nature, common therapy includes (systemic) corticosteroids and immune modulatory agents. Most treatments bear the risk of significant adverse effects. Therefore efforts are made to administer therapeutic agents directly into the vitreous cavity. The purpose of this article is to identify the role of intravitreally applied sirolimus as a recently approved therapeutic option in NIPU., Areas Covered: A MEDLINE database search was conducted through August 2015 using the terms: intravitreal injection, pharmacology, sirolimus, treatment and uveitis. To provide ongoing and future perspectives in treatment options, also clinical trials as registered at ClinicalTrials.gov were included. Sirolimus (Opsiria) was in licensed from SANTEN in 2015 and approved in Phase III registration trials in the US, Europe and other countries for NIPU. Current information results mainly from registration and Phase III trials., Expert Opinion: Intravitreal sirolimus appears to be an interesting option in the treatment algorithms of NIPU because of its highly targeted molecular effects, nonsteroidal nature and good safety profile. It has the advantage to avoid systemic side effects, but this has to be balanced against the fact that treatment covers one eye only and bears the risks of any intraocular procedure. Nevertheless a careful evaluation of this agent has to be made, as current experience is almost exclusively based on registration trials and long-term effects still have to be explored.

Purpose: Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, exhibited promising activity in a proof-of-concept study when administered in intravenous (IV) doses to patients with active, chronic, noninfectious uveitis. This study compared the efficacy and safety of different IV and subcutaneous (SC) doses of secukinumab in patients with noninfectious uveitis., Design: Multicenter, randomized, double-masked, dose-ranging, phase 2 clinical trial., Participants: Thirty-seven patients with active noninfectious intermediate uveitis, posterior uveitis, or panuveitis who required corticosteroid-sparing immunosuppressive therapy., Methods: Patients were randomized to secukinumab 300 mg SC every 2 weeks for 4 doses, secukinumab 10 mg/kg IV every 2 weeks for 4 doses, or secukinumab 30 mg/kg IV every 4 weeks for 2 doses. Intravenous or SC saline was administered to maintain masking. Efficacy was assessed on day 57 (2-4 weeks after last dose)., Main Outcome Measures: Percentage of patients with treatment response, defined as (1) at least a 2-grade reduction in vitreous haze score or trace or absent vitreous haze in the study eye without an increase in corticosteroid dose and without uveitis worsening or (2) reduction in corticosteroid dosages to prespecified levels without uveitis worsening. Percentage of patients with remission, defined as anterior chamber cell and vitreous haze scores of 0 or 0.5+ in both eyes without corticosteroid therapy or uveitis worsening., Results: Secukinumab 30 mg/kg IV and 10 mg/kg IV, compared with the 300 mg SC dose, produced higher responder rates (72.7% and 61.5% vs. 33.3%, respectively) and remission rates (27.3% and 38.5% vs. 16.7%, respectively). Statistical and clinical superiority for the 30 mg/kg IV dose compared with the 300 mg SC dose was established in a Bayesian probability model. Other measures, including time to response onset, change in visual acuity, and change in vitreous haze score, showed numeric trends favoring IV dosing. Secukinumab, administered in IV or SC formulations, appeared safe and was well tolerated., Conclusions: Intravenous secukinumab was effective and well tolerated in noninfectious uveitis requiring systemic corticosteroid-sparing immunosuppressive therapy. Greater activity with IV dosing suggests that patients may not receive sufficient drug with SC administration. High-dose IV secukinumab may be necessary to deliver secukinumab in therapeutic concentrations., (Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: Juvenile idiopathic arthritis (JIA) is the most common systemic disease causing uveitis in childhood, with a prevalence of 10 per 100 000 persons. JIA often takes a severe inflammatory course, and its complications often endanger vision., Methods: This review is based on pertinent articles retrieved by a selective literature search up to 18 August 2014 and on the current interdisciplinary S2k guideline on the diagnostic evaluation and anti-inflammatory treatment of juvenile idiopathic uveitis., Results: Uveitis arises in roughly 1 in 10 patients with JIA. Regular eye check-ups should be performed starting as soon as JIA is diagnosed. 75-80% of patients are girls; antinuclear antibodies are found in 70-90%. The risk to vision is higher if JIA begins in the preschool years. As for treatment, only a single, small-scale randomized controlled trial (RCT) and a small number of prospective trials have been published to date. Topical corticosteroids should be given as the initial treatment. Systemic immunosuppression is needed if irritation persists despite topical corticosteroids, if new complications arise, or if the topical steroids have to be given in excessively high doses or have unacceptable side effects. If the therapeutic effect remains inadequate, conventional and biological immune modulators can be given as add-on (escalation) therapy. Treatment lowers the risk of uveitis and its complications and thereby improves the prognosis for good visual function., Conclusion: Severely affected patients should be treated in competence centers to optimize their long-term outcome. Multidisciplinary, individualized treatment is needed because of the chronic course of active inflammation and the ensuing high risk of complications that can endanger vision. Future improvements in therapy will be aided by prospective, population-based registries and by basic research on biomarkers for the prediction of disease onset, prognosis, tissue damage, and therapeutic response.

Relapsing ocular involvement is one of the major manifestations in Behçet disease (BD). When ocular BD is left untreated, it often results in blindness in <5 years. Combining systemic corticosteroids with cyclosporine A and other conventional immune modulating agents has been the only choice for treatment. More recently, the introduction of 'biologics' seems to be an effective therapy in patients affected with BD, especially in those with ocular disease. Our purpose was to survey the current knowledge regarding the biological therapeutic approaches for Behçet uveitis. We focused on the most commonly used biological agents: 'tumor necrosis factor-alpha antagonists' and 'interferon alpha'. We attempted to compare the effectiveness of these two biologicals and tried to balance on the pros and cons of these agents in clinical practice. The impressive efficacy of both approaches in sight-threatening BD argues for their expanding role. Earlier introduction of these agents in the course of disease may prevent irreversible structural damage and may result in improved long-term prognosis., (© 2012 The Authors. Acta Ophthalmologica © 2012 Acta Ophthalmologica Scandinavica Foundation.)

Uveitis in juvenile idiopathic arthritis (JIA) is frequently associated with the development of complications and visual loss. Topical corticosteroids are the first-choice therapy, and immunosuppression is commonly used. However, treatment has not been standardized. Representatives from the German Ophthalmological Society, Society for Childhood and Adolescent Rheumatology, and the German Society for Rheumatology reached consensus on a standardized treatment strategy according to disease severity in the individual patient. The recommendations were based on a systematic literature analysis in MEDLINE and consensus expert meetings. Evidence and recommendations were graded, and an algorithm for anti-inflammatory treatment and final statements confirmed in a Delphi method. An interdisciplinary, evidence-based treatment guideline for JIA uveitis is presented.

The term uveitis encompasses a very diverse group of inflammatory ocular diseases that cause a significant burden of legal and economic blindness. Indeed, the socioeconomic impact of uveitis is at least as significant as that of diabetic retinopathy and, in the majority of cases, those affected are young individuals of working age. Significant progress has been made in our understanding of the mechanisms underlying the inflammatory process through the use of animal models, but correlation with human disease has proved elusive and many scientific approaches which appear highly effective in animal models prove to be less effective in patients. Nevertheless, effective, targeted treatments are needed in uveitis as current treatment is based on corticosteroids and immunosuppressive drugs whose usefulness is limited by their many side-effects. The aims of this review are to summarize the state of clinical research in uveitis, to identify gaps in our knowledge, and to propose new opportunities and methodologies for future developments in all aspects of uveitis research, including epidemiology, economic impact analysis, diagnosis, therapeutics, and clinical study design. Optimal patient management and efficient drug development depend on validated structured tools, such as those that have helped to drive a rapid acceleration in the means and methods available to assess and treat patients with rheumatoid arthritis and cancer. Uveitis care should witness a similar boom as the issues discussed are resolved., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Biologicals are selectively acting proteins that demonstrated high efficacy in the treatment of chronic disorders. In particular, biologicals blocking tumor necrosis factor α (TNF-α), an essential cytokine in chronic inflammatory diseases, have demonstrated great promise. Experimental and clinical data indicate that TNF-α plays an important role in intraocular inflammation. Neutralization of TNF-α might therefore be a promising strategy for prevention and treatment of uveitis. Here we review the principle effects, therapeutic value, and potential side effects of anti-TNF agents in uveitis.

Background: TNF-alpha inhibitory drugs are widely used with beneficial effect in the treatment of rheumatic diseases, such as juvenile idiopathic arthritis and ankylosing spondylitis. Due to the complex immune regulatory function of TNF-alpha, induction of inflammation in several organs including the eye, skin, and gastrointestinal tract has been reported. This report describes the occurrence of intraocular inflammation after treatment with the TNF-alpha antagonist etanercept., Methods: In this observational case series, we followed and examined six patients receiving etanercept for juvenile idiopathic arthritis, ankylosing spondylitis, adult Still's disease, or psoriasis., Result: All patients responded well to their joint affliction, but developed endogenous uveitis for the first time after application of etanercept. Following acute intervention with corticosteroids, etanercept was discontinued and instead an antibody-based anti-TNF treatment using infliximab was instituted. We documented visual acuity before and after change from etanercept to treatment with the anti-TNF-alpha antibody infliximab. Interestingly, prompt long-term remission (mean 34 months) of uveitis without recurrence could be induced in all patients., Conclusions: Our observations may indicate that immunodysregulatory and even proinflammatory effects of etanercept are of relevance in clinical practice. Further randomized controlled clinical trials are necessary to investigate possible side effects of anti-TNF therapy using etanercept and infliximab.

According to the World Health Organization, 60- 95 % of the population worldwide is infected by viruses of the herpes viridae family. Excellent adaptation of the organisms and host-related factors are probably predisposing for this global distribution. Herpes virus infections are probably the most common infectious cause of blindness in the Western world. Besides the well known manifestations of keratitis and anterior uveitis caused by HSV and VZV, new aspects have been discovered, in particular, in CMV-related disorders. Molecular biological methods have been instrumental to explore and discover herpes virus associated disorders and have provided new insights. Whereas keratitis and anterior uveitis are the most common clinical manifestations, more severe disorders such as posterior uveitis, panuveitis and acute retina necrosis syndrome have all been attributed to herpes virus infections. Since the therapeutic intervention greatly varies in these acute situations, identification of the causative agent is essential. Serology is rarely helpful, whereas analyses of aqueous humor or vitreous samples provide clues for the etiology. Aqueous humor antibody testing and PCR have demonstrated excellent diagnostic power with high sensitivity and high specificity. This review is intended to provide an overview on the diagnosis and differential diagnosis of this important disorder.

Glaucoma, a common and potentially devastating complication of intraocular inflammation, remains a considerable therapeutic challenge. During uveitis, breakdown of the blood-ocular barrier occurs with subsequent influx of proteins as well as inflammatory and immunocompetent cells. These mediators, including cytokines and chemokines, are considered to have a major impact on secondary elevated intraocular pressure (IOP). Several mechanisms are involved in the pathogenesis of inflammatory glaucoma, including obstruction of the trabecular meshwork by inflammatory cells and proteins, trabeculitis, formation of anterior and/or posterior synechiae, pupillary block, neovascularization, and anterior rotation of the lens-iris diaphragm. In addition, the use of steroids to control intraocular inflammation may cause secondary elevation of IOP.The management of uveitic glaucoma requires a careful balance between adequate anti-inflammatory therapy and appropriate lowering of IOP to prevent long-term visual loss. Despite the availability of many new medical treatments for both conditions, control of IOP in these patients remains challenging.

Ocular hypertension and secondary glaucoma are frequent and challenging complications in childhood uveitis. They are commonly found in patients with panuveitis or anterior uveitis and are often associated with juvenile idiopathic arthritis. Angle closure is rare, while secondary open angle glaucoma accounts for the majority of cases and often continues after the acute inflammation has healed. Monitoring should include tonometry, perimetry, and the objective assessment of the optic disc and nerve fibre layer. First-line therapy should consist of topical carbonic anhydrase inhibitors, followed by beta blockers, and then the alpha-2 agonists. Topical therapy must be monitored closely, as drug-related systemic side effects may preferentially occur in children. Because topical therapy in children is commonly ineffective, surgical interventions are often required. Reports on the use of trabeculectomy, goniosurgery, glaucoma drainage devices, and cyclodestructive procedures show higher failure rates than when used for primary open angle glaucoma in adults.

Background: Mycophenolate mofetil (MMF) has gained acceptance as an immune modulatory agent in the treatment of autoimmune disorders such as uveitis. It represented a major advance, although optimal use may be limited, in particular, by gastrointestinal (GI) side effects in up to 50 % patients. This prospective study was undertaken to evaluate the effect of conversion from mycophenolate mofetil (MMF) to an enteric-coated mycophenolate sodium (EC-MPS)., Patients and Methods: Within a cohort of 143 patients treated with MMF we prospectively followed 19 individuals who developed gastrointestinal side effects. Because of limited treatment alternatives, conversion to an enteric-coated mycophenolate sodium (EC-MPS) was undertaken. A standardised questionnaire (GSRS) was completed by each patient regarding GI adverse events, at predefined intervals during the study., Results: The spectrum of underlying disorders included uveitis (n = 16) and ocular cicatricial pemphigoid (n = 3) that were initially treated with MMF (1000 mg BID). All patients could be kept on EC-MPS treatment and followed with a mean follow-up of 44 weeks (median +/- 12). The maximum of scores on GSRS was reached at baseline (conversion to EC-MPS) in all but 3 patients. However, GSRS scores improved significantly between baseline and visit 4 (3 months) and remained stable further on (p < 0.03). In all but one (uveitis) patient the underlying disorders were under control demonstrating the similar efficacies of MMF and EC-MPS treatments., Conclusion: The use of EC-MPS appears to be a valid treatment option in ocular autoimmune disorders. In particular. patients with gastrointestinal problems may profit from a significantly reduced frequency of adverse events.

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.

Toxoplasmosis and toxocariasis are parasitic infections that are transmitted by cats and dogs, respectively, to humans, and which may induce posterior uveitis already in childhood. Toxoplasmosis presents as a congenitally or postnatally contracted infection whereas toxocariasis is always an acquired disease. The typical ocular sign of toxoplasmosis is retinochoroiditis, occurring as an active lesion, in most instances, associated with an inactive pigmented scar. In contrast, toxocariasis leads to a choroidal granuloma secondarily involving the retina or an endophthalmitis-like picture. Although toxoplasmosis represents the most common cause of posterior uveitis, there are uncertainties regarding the timing and specificity of the diagnosis, namely in atypical cases and those at risk of permanent severe loss of function. Antiparasitic treatment should be tailored to the severity of the inflammation and the risk of visual function loss. Concomitant steroids may be used to control the sequelae of unspecific inflammation, but should be used with caution and must be combined with an antimicrobial regimen. Because it is a rare disorder, one may not be familiar with the clinical presentation and suggested therapy for ocular toxocariasis. With this survey we, therefore, wish to provide a current, practice-oriented overview on the infection, ocular manifestations, diagnosis and treatment of ocular toxoplasmosis and toxocariasis in childhood.

Background: Intraocular inflammation in children differs considerably from that found in adults. Therefore the diagnostic work-up has to be adapted to the age and specific diseases., Materials and Methods: The published literature was reviewed for results of clinical trials and consensus meetings. In addition, the authors have incorporated their own experience., Results: Recommendations for a systematic and complete diagnostic work-up are given using tables where possible., Conclusions: A close cooperation between ophthalmologists and paediatricians is very important.

Infectious uveitis caused by Borrelia, tuberculosis or syphilis is a rare condition, even in childhood. Because these diseases can be treated successfully, knowledge of their diagnosis and therapy is highly important. The clinical aspects vary from simple conjunctivitis to endophthalmitis or neuro-ophthalmological diseases. The diagnosis of and therapy for borreliosis depend on the stage of the disease. The involvement of different organ systems or positive indirect tests (tuberculin skin test, interferon gamma assays) are important factors in the diagnosis of tuberculosis as the cause of a uveitis. Serology is essential for the diagnosis and monitoring of syphilis.

Purpose: The purpose of the study is to investigate whether analysis of specific antibody synthesis can aid the diagnosis of herpes keratitis., Methods: Aqueous humor was collected from 39 patients with presumed recurrent herpes keratitis, including 23 consulting for keratitis and 16 patients scheduled for penetrating keratoplasty. Local antibody production was ascertained by analysis of paired aqueous humor/serum samples, using a modified micro-ELISA technique., Results: Local production of antibodies was found in 32 patients (82%): anti-herpes simplex virus (HSV) antibodies in 26 (67%) and anti-varicella zoster virus (VZV) antibodies in 11 (28%). Twenty of 23 patients with active keratitis (87%), and 12 of 16 undergoing keratoplasty (75%), tested positive. Five patients had local production of both anti-HSV and anti-VZV antibodies, whereas seven patients tested negative. Local antibody production was significantly associated with intraocular inflammation (P<0.05), corneal neovascularisation (P<0.05), and positive response to anti-viral treatment (P<0.05). No complications were encountered in sampling aqueous humor., Conclusions: Assessment of local anti-HSV and -VZV antibody production is a safe and reliable diagnostic procedure for recurrent herpes keratitis. It might be particularly helpful in patients presenting with intraocular inflammation and neovascularisation since it discriminates between herpes and non-herpes pathologies and may therefore be useful for preventive and therapeutic strategies.

Background: Uveitis is a frequent and potentially vision-threatening manifestation of juvenile idiopathic arthritis (JIA). There are only a few population-based studies providing data on the frequency and severity of uveitis., Methods: Documentation of patients with JIA was collected in a national database. An analysis of the paediatric rheumatologic and ophthalmologic data collected from all patients that were included in 2002 was performed., Results: Uveitis was documented in 12 % of a total of 3271 JIA patients: extended oligoarthritis (25 %), persistent oligoarthritis (16 %), seronegative polyarthritis (4 %), seropositive polyarthritis (2 %), psoriatic arthritis (10 %), enthesitis-related arthritis (ERA) (7 %), systemic arthritis (1 %), other arthritis forms (11 %). Ophthalmologic data were available from 115 uveitis patients (28 %). Mean age at onset of uveitis was 5.2 (SD 3.2) years. JIA patients with uveitis were significantly younger at onset of arthritis (3.8 vs. 7.0 years), and were more often girls (74 vs. 63 %) or ANA-positive (86 vs. 42 %) than the patients without uveitis. Uveitis complications were present in 45 % at initial presentation of uveitis. After a mean duration of 5.6 years, complications were noted in 56 %, and included band keratopathy (29 %), posterior synechiae (27 %), cataract (26 %), glaucoma (8 %), and macula oedema (6 %). Final visual acuity was less than 20/50 in 31 % and less than 20/200 in 12 % of eyes. In patients with uveitis, immunosuppressive or immunomodulatory drugs were used significantly more often than in patients without uveitis (75 % vs. 43 %)., Conclusions: The nationwide data documents the spectrum of uveitis in patients with JIA, the complications and the therapy for uveitis. The high rate of uveitis complications at the time of diagnosis points out the need for early ophthalmologic screening and therapy, and for a close collaboration between ophthalmologist and paediatric rheumatologist.

Background: Cyclosporine (CsA) is a widely used drug in the treatment of posterior uveitis. Whereas treatment with CsA has considerably improved the visual prognosis of uveitis patients, the therapeutic benefits of CsA are partially outweighed by its adverse effects, most notably nephrotoxicity and hypertension. Recently, monitoring the CsA 2-h postdose level (C(2)) has been recommended as the most sensitive assay and predictor of clinical outcome in transplantation., Patients and Methods: This prospective clinical trial included 15 patients with posterior uveitis who received oral CsA (5 mg/kg BW b.i.d.). The relationship of C(2) to C0 blood levels was analyzed and correlated with clinical safety and efficacy., Results: A high intrapatient and interpatient variability was observed regarding the C0 values depending on several factors including comedication and intestinal resorption. C(2) values corresponded to control measurements of intraocular inflammation., Conclusions: C(2) monitoring offers a simple and accurate alternative for clinical monitoring of CsA. It allows the dose of CsA to be individualized effectively for each patient.

Purpose: Understanding of the role of cytokines in uveitis may provide new clues to its treatment. Therefore, the purpose of our study was to evaluate systemic cytokine receptor expression in patients with noninfectious uveitis., Method: Serum concentrations of soluble interleukin-2 receptor alpha (IL-2 s Ralpha) and soluble tumor necrosis factor receptor-1 (sTNF-R1) were measured in patients with intermediate uveitis (n = 26), posterior uveitis (n = 23) and healthy controls (n = 12) using ELISA. All patients were identified in a consecutive series of 996 uveitis patients who had been diagnosed between 1998 and 2002 and classified according to the recommendations of the International Uveitis Study Group. Inclusion criteria were idiopathic, active intraocular inflammation, uveitis as a primary process and no systemic anti-inflammatory treatment at the time of blood sampling. None of the patients had an underlying systemic disease., Results: Serum concentrations of IL-2 s Ralpha were significantly increased in patients with posterior (p < 0.005) and intermediate uveitis (p < 0.005) as compared to healthy controls. Similarly, concentrations of sTNF-R1 appeared to be increased in posterior (p < 0.005) and intermediate (p < 0.005) uveitis patients when compared to controls., Conclusions: Our results may suggest that patients with noninfectious uveitis express systemic cytokine receptors such as TNF-R1 and IL-2 Ralpha, which may have an important role in the immune response of the eye and may lead to new immunomodulatory approaches., (Copyright (c) 2005 S. Karger AG, Basel.)