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.

Effect of Janus Kinase Inhibitor Treatment on Anterior Uveitis and Associated Macular Edema in an Adult Patient with Juvenile Idiopathic Arthritis.

Purpose: To report a case of effective Janus kinase inhibitor treatment in a case of anterior uveitis complicated by macular edema in a patient with juvenile idiopathic arthritis.Case report: A 22-year-old woman suffering from JIA-associated anterior uveitis since the age of 2 years presented with recurrent active uveitis and macular edema in both eyes responding only to intraocular dexamethasone implants in the past while several other DMARD therapies including biologicals failed to control activity and edema. After starting treatment with tofacitinib 5 mg twice daily arthritis, uveitis, and macular edema were controlled without any further steroid implants.Conclusion: In this case, Janus kinase inhibitor represented a successful strategy for severe refractory uveitis and ME and therefore Janus kinase inhibitor may be an option in selected cases not responding properly to conventional synthetic and biologic DMARDs or to intraocular steroid implants.

Update of the evidence based, interdisciplinary guideline for anti-inflammatory treatment of uveitis associated with juvenile idiopathic arthritis.

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.

[Management of anticoagulants in ophthalmic surgery-a survey among ophthalmic surgeons in Germany]. / Umgang mit gerinnungshemmenden Substanzen in der Ophthalmochirurgie ­ eine Umfrage unter Ophthalmochirurgen in Deutschland.

INTRODUCTION: As our population ages and comorbidities rise, ophthalmic surgeons are increasingly faced with patients on anticoagulant therapy or with clotting disorders. The ophthalmic surgeon has to weigh the perioperative risk of haemorrhage when anticoagulation continues against the risk of thromboembolism caused by discontinuation or changing the patient's medication (bridging, switching, cessation). There are currently no guidelines or recommendations. METHODS: A survey was sent to the DOG (German Ophthalmologic Society) divisions and associated surgical organizations to determine the status quo. A questionnaire was sent out and filled out by the different groups of specialists. RESULTS: All four divisions of the DOG and four associated organizations returned completed questionnaires. Surgical interventions were listed that are carried out during anticoagulant therapy without exceptions, as well as interventions that were classified to require medical adjustment. Although the assessments varied, general consensus was achieved regarding interventions not requiring adjustments due to anticoagulants (i. e., intravitreal injection, cataract surgery, laser and corneal operations, simple muscle surgery), and those interventions requiring adjustments in medications (glaucoma operations, complex retina surgery, eye socket surgery, complex surgery of the lid). CONCLUSION: Main result of this survey was the specification of serious bleeding complications which are permanent vision loss and re-operation. They could serve as endpoint parameters for essential future investigations. Nevertheless, this survey makes clear that the decision about an adjustment of anticoagulant medication in ophthalmic surgery is currently made individually and not based on established standards.

[Goodpasture syndrome: ocular manifestation in a young man]. / Goodpasture-Syndrom: Okuläre Manifestation bei einem jungen Mann.

Goodpasture syndrome (GS) is a rare organ-specific autoimmune disease that may consist of glomerulonephritis and pulmonary hemorrhage. Only few case reports have been published on ocular symptoms in the context of GS. This is a case report of a 22-year-old male with GS who was referred to our practice because of visual disturbances. The anamnesis revealed pulmonary hemorrhage, acute renal failure and nephrotic syndrome, which was treated by immunosuppressive therapy with additional plasmapheresis. Ophthalmoscopically, bilateral cotton wool spots were found along the vessels and bilateral retinal hemorrhages predominantly at the posterior pole. By intensifying the existing antihypertensive therapy the eyesight showed significant improvement. Although infrequently seen in Goodpasture syndrome it is important to be aware of ocular symptoms as they may be the initial signs of GS.

[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.

[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.

[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!