[Uveitis in juvenile idiopathic arthritis]. / Uveitis bei juveniler idiopathischer Arthritis.

BACKGROUND: Uveitis is the most common extra-articular manifestation of juvenile idiopathic arthritis (JIA). It occurs, according to German registry data, in around 12% of JIA patients and can lead to a loss of vision, especially in cases of delayed diagnosis and/or inadequate therapy. OBJECTIVE: A review of current aspects of diagnosis and therapy was carried out. MATERIAL AND METHODS: This is a review article of the current literature. RESULTS: The risk of uveitis is significantly elevated in patients with an oligoarticular course of JIA, ANA positivity and young age at onset of JIA. During the mostly asymptomatic course of uveitis severe complications, such as cataracts, glaucoma or macular edema can occur, limiting visual acuity. Early detection of uveitis and interdisciplinary cooperation of uveitis specialists and pediatric rheumatologists is of major importance to ensure a favorable long-term prognosis. The initial therapy consists of topical steroids; however, in cases of insufficient response or complicated course of uveitis, conventional synthetic (mainly methotrexate) or biological disease-modifying antirheumatic drugs (bDMARDs) are required. In respect to bDMARDs, the highest evidence exists for treatment with adalimumab; however, depending on the clinical course of disease, other bDMARDs, such as infliximab, golimumab, tocilizumab, abatacept or rituximab may also have a beneficial effect. Despite these treatment options, uveitis or arthritis may frequently persist into adult age. Adequate and early recognition and treatment of uveitis-related complications is of major importance to ensure a good long-term visual prognosis. CONCLUSION: Early diagnosis of JIA-associated uveitis and early implementation of effective treatment, especially steroid-sparing DMARD therapy, aims at achieving uveitis inactivity and prevention of ocular damage.

[Uveitis in spondyloarthritis]. / Uveitis bei Spondyloarthritiden.

Acute anterior uveitis (AAU) is the most frequent uveitis subtype. It is often associated with HLA-B27 and with inflammatory rheumatic diseases, in particular with spondyloarthritis (SpA), which itself is strongly associated with HLA-B27. About 40-60% of patients with AAU have an associated spondyloarthritis, and 20-40% of patients with spondyloarthritis also have uveitis. The incidence of AAU in patients with SpA clearly correlates with disease duration. The AAU has an acute onset, usually affects only one eye at a time, and shows a tendency for recurrence. Early therapy of AAU with topical steroids is relevant for good visual outcomes. Minimum duration of therapy of flares of AAU is 6-8 weeks in order to prevent early recurrency. The rate of local complications correlates with the rate of AAU flares and the visual outcome is often good. Refractory uveitis and frequent recurrencies of AAU may be treated with conventional disease-modifying antirheumatic drugs (DMARDs, such as sulfasalazine and methotrexate) and biologicals (e.g. TNF-alpha inhibitors). Any first episode of AAU diagnosed by an ophthalmologist should prompt referral to rheumatology for suspected SpA, particularly if rheumatic symptoms are present.

[Social Medical Consequences of Uveitis in Childhood and Adolescence: Results of a Pilot Study]. / Sozialmedizinische Folgen bei Uveitis im Kindes- und Jugendalter: Ergebnisse einer Pilotstudie.

Background Chronic illness - such as uveitis - may lead to socio-economic consequences, and poorer quality of life. Objective To study the influence of uveitis on quality of life and professional development. Material and Methods Prospective evaluation of juvenile patients with uveitis (age < 18 years, classification of uveitis as in Standardization of Uveitis Nomenclature [SUN] criteria, duration of disease ≥ 12 months) seen in a tertiary referral centre. Influence of uveitis on quality of life, recreational activities, educational training and development of severe disability were analysed. Results were correlated to clinical data, and analysed by descriptive statistics. Results 39 patients of 49 (80 %) had anterior uveitis (69.4 % in both eyes), of which 34 (69 %) presented with associated systemic disease (juvenile idiopathic arthritis, n = 28). 33 (80 %) had developed complications caused by uveitis. 15 patients (31 %) had undergone ophthalmic surgery due to these complications. Many patients were treated with conventional (n = 37; 76 %) and biological (n = 18; 37 %) disease-modifying antirheumatic drugs (DMARDs). In 41 % of the cases, quality of life and recreational time (23 %) were markedly reduced. Sick leave from pre-school or school because of uveitis (mean 12.5 days/year; 15 % > 20 days) was recorded in 32 patients (65 %). Uveitis negatively influenced school education in 29 %, and resulted in the necessity to repeat class (n = 3) or to change school (n = 3). Severe disability due to uveitis was found in 30 % of the patients. Conclusions Uveitis in childhood and adolescence may have a substantial impact on social and professional perspectives. Uveitis may result in severe disability even in early childhood.

[Ocular Manifestations in Sarcoidosis]. / Augenbeteiligung bei Sarkoidose.

Sarcoidosis is an inflammatory multi-organ disease of unknown pathogenesis, characterised by non-necrotising granulomata. Sarcoidosis predominantly manifests in the lung, but any other organ may be affected. Ocular involvement is present in about 25 to 50 % of patients. The most common ocular manifestation is uveitis, especially of the anterior eye segment. If ocular sarcoidosis is suspected, interdisciplinary assessment of the patient is mandatory, including laboratory tests, chest X-ray, assessment by a specialist in internal medicine and, ideally, histological evidence of granuloma formation in a tissue specimen. Other (infectious) causes of granulomatous inflammation need to be excluded, especially tuberculosis or syphilis. For the ophthalmological assessment, detection of granulomatous lesions is of particular importance, especially by visualising chorioretinal granuloma by fluorescein and indocyanin green angiography. Cystoid macular oedema and glaucoma are the most frequent complications limiting visual acuity. Corticosteroids, which can be administered either locally or systemically, are the mainstay of therapy. Depending on the clinical course and the development of ocular complications, systemic steroid-sparing immunosuppressive medication may be indicated.

[Efficacy of a Dexamethasone Implant for the Treatment of Refractory Cystoid Macular Oedema in Non-Infectious Uveitis]. / Intravitreales Dexamethason-Implantat zur Behandlung des therapierefraktären zystoiden Makulaödems bei nicht infektiöser Uveitis.

PURPOSE: To evaluate the efficacy of an intravitreal dexamethasone implant (Ozurdex®) in patients with cystoid macular oedema (CME) suffering from non-infectious uveitis. METHODS: Monocentric, retrospective, single-arm analysis in 49 patients (59 implanted eyes) with inactive uveitis, in whom CME had been unresponsive to corticosteroids and/or immunosuppressants and systemic acetazolamide, and who received a dexamethasone implant. Patients were followed up at 6, 12 and 24 weeks after unilateral (n = 39)/bilateral (n = 10) implantation. The primary outcome measure was central foveal thickness (CFT), as measured by Spectralis optical coherence tomography (OCT); secondary outcome measures were improvement in best-corrected visual acuity (BCVA), laser flare photometry and safety measures, including intraocular pressure (IOP) and cataract progression. RESULTS: At 6, 12 and 24 weeks, mean CFT was reduced (≥ 20 %) in 68, 44 and 45 % and BCVA improved (≥ 2 lines) in 47, 40 and 26 %, respectively, as compared to baseline. At 6, 12 and 24 weeks, significant flare reduction was observed in 70, 41, and 42 %, respectively. Cumulative cataract progression was observed in 12, 18 and 31 % at 6, 12 and 24 weeks, respectively. IOP ≥ 22 mmHg was noted in 5 % at baseline and in 21, 3, and 0 % at 6, 12 and 24 weeks, respectively. CONCLUSIONS: In uveitis patients with CME refractory to systemic anti-inflammatory drugs, the dexamethasone implant improves CME transiently. However, IOP increase and cataract progression are common side effects.

Temporal change in prevalence and complications of uveitis associated with juvenile idiopathic arthritis:data from a cross-sectional analysis of a prospective nationwide study.

OBJECTIVES: To analyse the nationwide prevalence of uveitis in JIA and its complications over a whole decade. METHODS: We conducted a prospective, observational and cross-sectional study including all JIA patients from a National Paediatric Rheumatological Database (NPRD) with a uveitis add-on module in Germany (2002-2013). Temporal changes in uveitis prevalence, related secondary complications and anti-inflammatory medication were evaluated. RESULTS: A total of 60 centres including 18,555 JIA patients (mean 3,863 patients/year, SD=837) were documented in the NPRD between 2002 and 2013. The mean age of the patients was 11.4 ± 4.6 years, their mean disease duration 4.4 ± 3.7 years. Among them, 66.9% were female and 51.7% ANA positive. Patients' mean age at arthritis onset was 6.9 ± 4.5 years. Treatment rates with synthetic and biological DMARDs increased during the observation period (sDMARD: 39.8% to 47.2%, bDMARD: 3.3% to 21.8%). Uveitis prevalence decreased significantly from 2002 to 2013 (13.0% to 11.6%, OR = 0.98, p=0.015). The prevalence of secondary uveitis complications also decreased significantly between 2002 and 2013 (33.6% to 23.9%, OR=0.94, p<0.001). Among the complications, the most common ones were posterior synechiae, cataract and band keratopathy. A significant increase in achieving uveitis inactivity was observed at 30.6% in 2002 and 65.3% in 2013 (OR=1.15, p<0.001). CONCLUSIONS: Uveitis prevalence and complications significantly decreased between 2002 and 2013. This may be associated with a more frequent use of DMARDs.

[The Chameleon of Herpetic Keratitis - Diagnosis and Therapy]. / Das Chamäleon der Keratitis herpetischer Genese - Diagnose und Therapie.

In Europe, herpes simplex virus type I (HSV) is a common cause of keratitis. The disease may be well treated if the ophthalmologtist is aware of the various types of clinical expressions of this typical unilateral chameleon, and treatment is adjusted accordingly. Types of expression include: (i) epithelial keratitis (dendritica/geographica), (ii) stromal keratitis (necrotising vs. non-necrotising = "interstitial keratitis"), (iii) endotheliitis (= "disciform keratitis"), (iv) so-called "metaherpetic keratitis" (= neurotrophic keratopathy), (v) (vascularised) corneal scars. In the acute phase, concomitant ocular hypertension should be treated predominantly without surgery (no prostaglandin analoga!). After keratoplasty and in cases of severe recurrences of herpetic keratitis, systemic aciclovir administration (2 × 400 mg/day) for at least one year is indispensable!

[Vernal keratoconjunctivitis]. / Keratoconjunctivitis vernalis.

Vernal keratoconjunctivitis (VKC) belongs to the group of allergic eye diseases. The incidence varies considerably, depending on the climate zone. In temperate climates VKC occurs only seasonally, while in hot climates it is mostly all year-round and rather more severe. Most commonly boys are affected in the first decade of life. Pathophysiological feature is a dense mixed cellular infiltrate with sometimes extremely thickened epithelium. It shows pronounced capillary proliferation, fibrosis and a thickened extracellular matrix. Inflammatory responses can be divided into IgE-mediated and non-IgE mediated inflammation. The clinical picture is characterised by pronounced subjective symptoms and the emergence of giant papillae, mostly on the upper tarsal conjunctiva. Distinction can be made into a limbal form and a palpebral form. Corneal changes are the most threatening complications with development of corneal erosions and shield ulcers. The therapeutic approach uses mainly drugs to block the release of inflammatory mediators such as histamine. These are usually local antihistamines and dual action preparations. Topical steroids or topical calcineurin inhibitors are only used in more severe situations. The same applies for the use of systemic corticosteroids or new biologics e.g., IgE inhibitors. Surgical therapy is predominantly required for the treatment of corneal complications. In general, VKC usually has a self-limiting course. However, during phases of inflammation with the risk of developing vision-threatening complications therapy is always indicated.

Everolimus improves experimental autoimmune uveoretinitis.

The efficacy and action mechanism of everolimus in the treatment of experimental autoimmune uveoretinitis (EAU) was analyzed. Disease was induced in B10.RIII mice by immunization with human interphotoreceptor-retinoid-binding protein peptide 161-180 (hIRBPp161-180). Everolimus was administered by oral gavage (5 mg/kg/d) beginning either two days before or 14 days after immunization. Everolimus significantly reduced the histopathological uveitis score compared to sham-treated mice. To examine the effect on the antigen-specific immune response, proliferation ([(3)H]-thymidine test) and delayed-type hypersensitivity (DTH) response were measured. Furthermore, content of T-helper-1, -2, and -17 cytokines were analyzed intraocularly (Bead Array) and in cell culture supernatants from splenocytes (sandwich ELISA). To study the effect on the humoral immune response the presence of antigen-specific serum antibodies was tested (indirect ELISA). The DTH, the humoral immune response, the proliferation of splenocytes and the intraocular Th1, Th2, Th17 cytokine content and in vitro production of Th1 and Th17 cytokines were impaired after everolimus treatment. The study of CD4+CD25+FoxP3+ regulatory T cells (T(reg)) in peripheral blood, draining lymph nodes, and spleen by flow cytometry showed an increased number of splenic T(reg) in mice of the everolimus therapy group. Furthermore the T(reg) of these mice had a higher suppressive capacity than cells from sham-treated mice. These results indicate that the immunosuppressive effect of everolimus on EAU was associated with the suppression of pathogenic effector responses and induction of regulatory T cells.

Evidence-based, interdisciplinary guidelines for anti-inflammatory treatment of uveitis associated with juvenile idiopathic arthritis.

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.

[Infections after intraocular lens surgery: implications for refractive surgery]. / Infektionen nach Linsenchirurgie: Implikationen für die refraktive Chirurgie.

Apart from the classical indication of removing an opaque lens that is compromising vision, extraction of the crystalline lens is gaining increasing importance as a refractive procedure. This literature review which considers the present guidelines of various ophthalmological societies and recently published studies is intended to give an estimate of the incidence of postoperative endophthalmitis and evidence-based recommendations for its prophylaxis, diagnosis, and therapy. The incidence of endophthalmitis after cataract extraction is reported to be 0.04% to 0.3% in most sizeable studies. Immediate sequential bilateral cataract surgery is internationally gaining popularity. It remains difficult to estimate whether or not the risk of endophthalmitis is affected with this approach. A toxic anterior segment syndrome (TASS) needs to be differentiated from postoperative endophthalmitis. TASS is an acute sterile inflammation after cataract surgery. Remnants of detergents and antiseptics on the surgical instruments are supposed to be main triggers. Additionally, the inappropriate preparation of solutions and antibiotics for intracameral use is considered to be a major cause. A case of TASS was also reported after implantation of an iris-fixated anterior chamber lens in a phakic eye. The cefuroxime solution that was prophylactically used in the ESCRS study and that is recommended for routine cataract surgery is not commercially available in Germany as a ready preparation for intraoperative application. Different measures are undertaken in different countries to prevent postoperative endophthalmitis, whose values are not exactly quantifiable. Antisepsis with povidone-iodine is still considered to be the component with the best evidence. For management of acute postoperative endophthalmitis, the systemic application of antibiotics is recommended in addition to their intravitreal injection. Few case reports have been published describing an infection after the implantation of refractive intraocular lenses (IOLs) in a phakic eye. However, we could not find meaningful information regarding the incidence of endophthalmitis after implantation of refractive IOLs. Based on the fact that these IOLs are not implanted into the capsular bag but in front of the crystalline lens or into the anterior chamber, and the presumably better anti-microbial immunity of this younger population compared to cataract patients, one may assume that the infection rate is lower than after cataract surgery. Nevertheless, a prospective register to document all endophthalmitis cases is desirable.

[Evidence and consensus based treatment guidelines 2010 for juvenile idiopathic arthritis by the German Society of Paediatric Rheumatology]. / Interdisziplinäre S2-Therapieleitlinie der Juvenilen Idiopathischen Arthritis (2. Auflage).

BACKGROUND: Treatment of Juvenile Idiopathic Arthritis (JIA) has improved quality of life in children and adolescents with JIA. Standardisation of care offers the chance to improve the quality of care of those patients. New studies have been published after completion of our last treatment guideline (2007). An updated consensus process is mandatory. METHODS: A systematic literature analysis in PUBMED (key words: juvenile idiopathic (rheumatoid) arthritis, therapy; limits: humans, published in the last 3 years, all child 0-18 years, clinical trial) revealed 17 relevant studies. Studies relating to diagnosis of JIA, Uveitis, vaccination, transition were excluded. Representatives nominated by scientific societies and organisations were invited to consensus conferences which were hosted by a professional moderator. The following societies were invited: Berufsverband der Kinder- und Jugendärzte (BVKJ), Deutsche Gesellschaft für Kinder- und Jugendmedizin (DGKJ), Deutsche Gesellschaft für Rheumatologie (DGRh), Deutsche Ophthalmologische Gesellschaft (DOG), Deutsche Rheuma-Liga Bundesverband, Verein zur Förderung und Unterstützung rheumatologisch erkrankter Kinder und deren Eltern, Vereinigung für Kinderorthopädie, Zentraler Verband der Physiotherapeuten und Krankengymnasten (ZVK). Consensus conferences were each attended by more than 95% of the nominated representatives. Consensus statements were confirmed by nominal group technique and Delphi method. RESULTS AND CONCLUSION: Updated consensus statements regarding drug therapy, symptomatic and surgical management of JIA were compiled and judged strictly by the criteria of Evidence-Based Medicine (EBM).

[Diagnosis and treatment of scleritis associated to inflammatory systemic diseases]. / Diagnose und Therapie der Skleritis bei entzündlichen Systemerkrankungen.

Because of potential vision-threatening complications and the association to inflammatory systemic diseases with an increased mortality, scleritis patients need an adequate diagnostic work-up and early and aggressive anti-inflammatory systemic treatment. New therapeutic options (such as biologicals) help to achieve remission in otherwise refractory cases.

[Canaloplasty and transient anterior chamber haemorrhage: a prognostic factor?]. / Kanaloplastie und transiente Vorderkammerblutung: ein prognostischer Faktor?

OBJECTIVE: An attempt has been made to evaluate transient anterior chamber haemorrhage after canaloplasty. METHOD: In the period from November 2008 to October 2009 a total of 21 eyes in 17 patients underwent canaloplasty for primary open angle glaucoma in our clinic. At the end of surgery all eyes left the surgical table with an intraocular pressure (IOP) of 5 - 10 mmHg and a deep anterior chamber without any bleeding. RESULTS: The IOP on day 1 after surgery was 9.6 mmHg in average. By that time 15 of 21 eyes showed anterior chamber haemorrhage with a hyphaema between 0.5 - 2 mm in height. Eyes without hyphaema showed an IOP of > 15 mmHg at the same time. In no case was there further haemorrhage, the blood was absorbed in all cases within a maximum of 1 week without further complications. CONCLUSION: In contrast to trabeculectomy, where the natural anterior chamber water outflow is by-passed via an artificial fistula, canaloplasty attempts to re-establish the physiological anterior chamber water draining system by means of a 360 degree viscocanalostomy and a thread mediated dilation of Schlemm's canal and its collector channels. If the anterior chamber pressure temporarily lowers the level of the venous capillary pressure, it is consistent with a patent piping system when a reverse flow with blood reflux into the anterior chamber can be observed as long as a minimal physiological pressure gradient from the anterior chamber in the direction of channel Schlemm's canal has been restored. Thus, in the authors opinion, anterior chamber haemorrhage shows the desired consistency of the water draining system and should therefore logically be expected after each successful operation in all cases where hypotony in the postoperative period occurs.

[Uveitis in juvenile idiopathic arthritis]. / Uveitis bei juveniler idiopathischer Arthritis.

Anterior uveitis usually occurs in the context of juvenile idiopathic arthritis in about 10% of patients. Frequency is dependent on JIA subtype. Uveitis is most commonly found in patients with extended oligoarthritis (up to 25%) and early-age onset of arthritis. As the uveitis is usually without externally recognisable signs and often leads to ocular complications, all JIA patients should undergo regular ophthalmological examinations to ensure the promptest possible diagnosis and therapy. About 25% of uveitis patients have a complicated clinical course and require systemic immunosuppression. Immunosuppressive therapy should be started as early as possible if the dosage of topical glucocorticoids is not less than 3 drops per day and systemic glucocorticoid therapy is not less than 0.1 mg / kg body weight after 12 weeks. Methotrexate is commonly started as a first line immunosuppressive therapy. In the case of treatment failure, additional therapy can consist of combination therapy with cyclosporine A and biologicals. The main therapeutic goal is to achieve remission. Management of the typical vision-threatening complications such as cataract, glaucoma, ocular hypotension, and macular edema is particularly challenging.

[Clinical presentation of zoster ophthalmicus]. / Klinik des Zoster Ophthalmicus.

BACKGROUND: Zoster ophthalmicus (ZO) is a common disease, in particular in elderly and immunocompromised patients. In addition to the characteristic dermal lesions and to the postherpetic neuralgia, the clinical appearance may include very different forms of eye involvement. METHODS: This article reviews the clinical features of ZO as well as the typical eye complications and therapy. RESULTS: 50 % of ZO patients have eye involvement. The acute phase of ZO is characterised by lid exanthema, conjunctivitis and epithelial keratitis (up to 65 %). In the late phase, stromal keratitis (up to 25 %), anterior uveitis (up to 50 %), and acute retinal necrosis (ARN) may occur. Typical complications are eyelid malposition, neurotrophic keratopathy (up to 25 %) and glaucoma. The diagnosis is usually based on the characteristic dermal lesions. In atypical cases, immunohistochemistry and PCR are tools for virus detection. All ZO patients should immediately receive systemic antiviral therapy. Corticosteroid therapy is essential for the management of the concomitant immune reaction that is relevant for the long-term prognosis, especially in stromal keratitis, uveitis, scleritis and ARN. CONCLUSIONS: All patients should receive systemic antiviral treatment to avoid complications and visual impairment. With appropriate medical and surgical therapy the prognosis is usually good. Postherpetic neuralgia is often the major issue in the later course. For the prevention of ZO and its complications, a vaccination is useful.

[Corticosteroid therapy and secondary elevated intraocular pressure in patients with Fuchs heterochromic cyclitis and idiopathic chronic anterior uveitis]. / Kortikosteroidtherapie und sekundäre Augeninnendruckerhöhung bei Fuchs-Heterochromiezyklitis und idiopathischer chronischer anteriorer Uveitis.

BACKGROUND: Due to different influences on anterior chamber angle structures, corticosteroids have a significant impact on secondary elevated intraocular pressure. This study examines the influence of corticosteroid therapy on the incidence of secondary elevated intraocular pressure in patients with Fuchs heterochromic cyclitis (FHC) and chronic anterior uveitis. MATERIALS AND METHODS: Retrospective chart analyses of patients undergoing topical and systemic corticosteroid therapy were carried out. RESULTS: Overall, data of 54 FHC and 49 CAU patients were analysed. Patients did not differ with respect to age, gender distribution and follow-up period. Seventeen (37 %) of the FHC patients and eight (18 %) of the CAU patients had secondary elevated intraocular pressure (p = 0.08). Number of months with topical therapy (54 vs. 20 months, p = 0.025) and number of months multiplicated with the frequency of topical maintenance therapy (158 vs. 61 p = 0.027) were significantly higher in the FHC patients. Only in the FHC group was an association with age (OR 1.16; 95 % CI 1.03 - 1.2; p = 0,006) and in the CAU group with the number of topical corticosteroid therapies (OR 1.15; 95 % CI 0.99 - 1.34; p = 0.03) evident in the multivariate analysis. CONCLUSIONS: Pathomechanisms, resulting in secondary elevated intraocular pressure in patients with FHC and CAU, must be different as only in CAU patients was an association to corticosteroid therapy found.