Alteration of MCP-1 and MMP-9 in Aqueous Humor Is Associated with Secondary Glaucoma in Fuchs Uveitis Syndrome.

PURPOSE: To analyze changes in concentrations of pro- or anti-inflammatory cytokines, chemokines, or metalloproteinases (MMP) in the aqueous humor (AH) in Fuchs uveitis syndrome (FUS) patients with (FUSwG) or without (FUSwoG) secondary glaucoma. METHODS: AH samples were collected from 43 eyes of Caucasian subjects (FUSwoG: n = 11; FUSwG: n = 8; control eyes: n = 24). Concentrations of IL-8, MCP-1, MMP-1,-2,-3,-9, SAA, TGFß-1,-2,-3, and TNF-α were measured by multiplex bead assay analysis. RESULTS: Compared with the control group, levels of IL-8, MCP-1, MMP-3, and MMP-9 in the AH were significantly increased in FUSwG and FUSwoG patients. In contrast to FUSwoG patients, MCP-1 and MMP-9 level were lower in FUSwG, while expression of MMP-2, MMP-3, and TGFß-1 was increased. CONCLUSION: In our experiments, glaucoma in FUS patients was associated with low levels of MCP-1 and MMP-9 in the AH, while expression of MMP-2, MMP-3, and TGFß-1 increased. The alteration in these molecular patterns may contribute to the development of glaucoma in FUS.

[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.

[Diagnosis and treatment of episcleritis and scleritis]. / Diagnose und Therapie der Episkleritis und Skleritis.

Episcleritis is a benign and self-limiting disease, often with a recurrent course, manifesting mainly in young adults. In less than a third of patients, an associated systemic disease can be found. In contrast, scleritis is observed mainly in patients between the 4th and 6th decade of life, may lead to severe ocular complications, and is often associated with a systemic rheumatological disease. Diffuse, nodular, and necrotizing forms of scleritis can be differentiated. Necrotizing and posterior scleritis have a higher risk of complications and worse visual outcome. In most cases, medical history and slit lamp examination allow differentiation of episcleritis and scleritis. Whereas episcleritis is treated mainly symptomatically with artificial tears, topical corticosteroids, and potentially with systemic nonsteroidal anti-inflammatory drugs, scleritis requires early and aggressive anti-inflammatory treatment in a stepwise approach.

[Uveitis associated with juvenile idiopathic arthritis : Optimization of immunomodulatory therapy]. / Juvenile idiopathische Arthritis-assoziierte Uveitis : Optimierung der immunmodulierenden Therapie.

BACKGROUND: Uveitis associated with juvenile idiopathic arthritis (JIA-associated uveitis) is a vision-threatening disorder with a high complication rate. Besides early diagnosis within screening programs an adequate therapy is essential for improvement of the long-term prognosis. Corticosteroid therapy is often insufficient. In addition to conventional immunosuppression, immunomodulatory drugs, so-called biologicals, are novel highly effective treatment modalities. OBJECTIVE: A systematic search of the literature was carried out for biologicals currently used in the treatment of JIA-associated uveitis. MATERIAL AND METHODS: Review of current publications, summary of treatment guidelines and discussion of treatment options for therapy refractive patients. RESULTS: In accordance with the current recommendations tumor necrosis factor (TNF) inhibitors are administered if uveitis inactivity cannot be achieved with topical corticosteroids and in the next stage with immunosuppressants (methotrexate preferred). According to the currently available data adalimumab is then preferred. When the effectiveness of TNF inhibitors ceases during long-term administration and/or recurrences, other biological response modifiers are attractive treatment options (e. g. lymphocyte inhibitors or specific receptor antagonists). CONCLUSION: The TNF inhibitors are of major importance for the treatment of JIA-associated uveitis. Prospective studies and registries would be desirable in order to be able to compare the value of TNF inhibitors and other biologicals and for optimization of treatment recommendations.

[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.

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.