Peripheral Ulcerative Keratitis: Clinical Characteristics, Differential Diagnoses and Therapeutic Concepts. / Periphere ulzerative Keratitis: Klinik, Differenzialdiagnosen und Therapiekonzepte.

Peripheral ulcerative keratitis (PUK) is an inflammatory disease of the peripheral cornea, which may frequently be associated with several rare, but potentially life-threatening systemic diseases. The inflammatory pathogenesis of PUK results from humoral and cell-mediated inflammation. The diagnosis is usually based on the typical clinical findings and always requires detailed diagnostic testing to identify a potential systemic underlying disease. Treatment includes topical and systemic immunosuppressive and immunomodulatory therapeutic strategies and, in the event of impending or existing perforation, also various surgical interventions. PUK is a potentially blinding disease that initially affects the periphery, but, if left untreated, can lead to destruction of the entire cornea. Interdisciplinary diagnostic testing and therapy are crucial to preserve vision in the affected patients and reduce morbidity and mortality. The following article provides an overview of the pathophysiology, clinical findings, possible underlying systemic diseases, relevant differential diagnoses and therapeutic strategies.

Ocular Involvement in Selected Rheumatic Diseases - Clinical Manifestation in Adulthood. / Augenbeteiligung bei ausgewählten rheumatischen Erkrankungen ­ Klinik im Erwachsenenalter.

Ocular manifestations of rheumatic diseases are common and contribute significantly to the morbidity and reduced quality of life of affected patients. Knowledge of typical clinical manifestations is important for the rheumatologist in order to support the reference of patients with corresponding symptoms for ophthalmological consultation at an early stage of disease, or to initiate regular screening examinations (e.g. in patients with Behçet's syndrome). Conversely, a (possibly urgent) rheumatological assessment is crucial for certain ophthalmological diseases, in order not to overlook a (possibly fatal) systemic associated disease. Patients with rheumatic or inflammatory ocular diseases should always be informed by the treating physician about possible symptoms of other organ manifestations, in order to avoid a delayed diagnosis. "Classic" associations for uveitis are (HLA-B27-associated) spondyloarthritis and acute anterior uveitis, as well as retinal vasculitis with or without panuveitis and Behçet's syndrome. In patients with rheumatoid arthritis or ANCA-associated vasculitis, however, scleritis (with or without peripheral ulcerative keratitis) typically occurs, but a variety of other findings are also possible. Close interdisciplinary collaboration, particularly regarding therapeutic decisions, is crucial to ensuring a good prognosis for the patient.

[Intermediate and Posterior Uveitis - Disease entities]. / Intermediäre und posteriore Uveitis ­ Teil 2.

Intermediate and posterior uveitis can have multiple infectious and noninfectious causes, and posterior uveitis in particular is clinically multifaceted. Some entities require prompt initiation of therapy to ensure visual prognosis. This article presents typical characteristics of intermediate and posterior uveitides and explains special features of their treatment.

[Intermediate and Posterior Uveitis - Classification, diagnostics, complications, and therapeutic algorithms]. / Intermediäre und posteriore Uveitis ­ Teil 1.

Intermediate and posterior uveitis describes a broad variety of different types of intraocular inflammation. Before starting treatment of intermediate or posterior uveitis, a differentiation between infectious or non-infectious uveitis must always be made. Pathognomonic symptoms do not exist, visual loss and vitreous floaters are the most common symptoms. The indication for therapy is influenced by the anatomical localization, the degree of inflammation, an association, complications and the activity of the inflammation. In addition to clinical ophthalmological standard examination, angiography and OCT are the most important investigations to classify and assess the course of inflammation. Macular edema is the most common complication of intermediate or posterior uveitis and should be treated at first onset, recurrence, or worsening. Oral, intravenous, or intravitreal corticosteroids are usually the primary therapy for intermediate or posterior uveitis. Systemic immunosuppression is indicated after steroid failure in non-infectious uveitis.

Surgical Glaucoma Treatment in Patients with Juvenile Idiopathic Arthritis-Associated Uveitis: Results after Trabeculectomy or Ahmed Glaucoma Valve Implantation.

PURPOSE: Patients with juvenile idiopathic arthritis (JIA) associated uveitis (JIAU) are at risk for secondary glaucoma, frequently requiring surgical management. We compared the success rates for trabeculectomy (TE) and Ahmed glaucoma valve (AGV) implantation. METHODS: We conducted a retrospective analysis of TE (45 eyes), primary AGV (pAGV) (7 eyes), or secondary AGV (sAGV) implantation after TE (11 eyes) in JIAU at the 2-year follow-up. RESULTS: All groups achieved significant pressure reduction. After 1 year, the overall success rate was higher in the Ahmed groups (p = 0.03). After adjusting the p-value according to Benjamin Hochberg, there is no significant difference between the groups in the Kaplan-Meier, despite a significant logrank test between all groups (p = 0.0194) and a better performance in the Ahmed groups. CONCLUSION: Slightly better success rates were achieved with pAGV in managing JIAU patients with glaucoma refractory to medical treatment.

New and Updated Recommendations for the Treatment of Juvenile Idiopathic Arthritis-Associated Uveitis and Idiopathic Chronic Anterior Uveitis.

OBJECTIVE: The Multinational Interdisciplinary Working Group for Uveitis in Childhood identified the need to update the current guidelines, and the objective here was to produce this document to guide clinicians managing children with juvenile idiopathic arthritis-associated uveitis (JIAU) and idiopathic chronic anterior uveitis (CAU). METHODS: The group analyzed the literature published between December 2014 and June 2020 after a systematic literature review conducted by 2 clinicians. Pediatric rheumatologists were paired with ophthalmologists to review the eligible 37 publications. The search criteria were selected to reflect those used for the 2018 Single Hub and Access point for pediatric Rheumatology in Europe (SHARE) recommendations, in order to provide an update, rather than a replacement for that publication. The summary of the current evidence for each SHARE recommendation was presented to the expert committee. These recommendations were then discussed and revised during a video consensus meeting on January 22, 2021, with 14 voting participants, using a nominal group technique to reach consensus. RESULTS: JIAU treatment was extended to include CAU. Fourteen recommendations regarding treatment of JIAU und CAU with >90% agreement were accepted. CONCLUSION: An update to the previous 2018 SHARE recommendations for the treatment of children with JIAU with the addition of CAU was created using an evidence-based consensus process. This guideline should help support clinicians to care for children and young people with CAU.

Beneficial Effect of Upadacitinib in an Adult Patient with Juvenile Idiopathic Arthritis-associated Uveitis after Unsatisfactory Response to Tofacitinib: A Case Report.

OBJECTIVE: Several case reports have been published on the effect of janus kinase inhibitors (JAK-I) on juvenile idiopathic arthritis-associated uveitis (JIAU). Both tofacitinib and baricitinib have been described as therapeutically effective in JIAU. METHODS: We here present a case of a 24-years-old female with refractory course of JIAU receiving upadacitinib therapy. RESULTS: After failing multiple conventional and biologic disease-modifying antirheumatic drugs, the patient finally achieved clinical remission on upadacitinib monotherapy, despite a previously unsatisfactory clinical response of both arthritis and uveitis to tofacitinib monotherapy. CONCLUSION: This case suggests that switching JAK-I might be a successful strategy in the treatment of JIAU, despite previously incomplete response to other preparations.

Beneficial Effect of Upadacitinib in a Refractory Course of Scleritis: A Case Report.

Noninfectious scleritis typically takes a chronic course, and systemic corticosteroids or disease-modifying anti-rheumatic drug (DMARD) treatment may be inevitable for a prolonged period. Janus kinase (JAK) inhibitors are a relatively new therapeutic option for inflammatory diseases, and three cases of successful treatment of scleritis with tofacitinib, a substance targeting JAK-1 and -3, have been published up to now. We here describe the case of a 51-years-old female patient with bilateral anterior and posterior scleritis who, after treatment failure of multiple DMARDs, finally achieved clinical quiescence of disease under treatment with upadacitinib, a selective JAK-1 inhibitor.

Assessment of angiogenesis-related parameters in juvenile idiopathic arthritis-associated uveitis.

PURPOSE: Juvenile idiopathic arthritis-associated uveitis (JIAU) may run a chronic and treatment-resistant course, and occasionally, alterations of the iris vasculature may be observed clinically. METHODS: Iris tissue (IT), aqueous humor (AH) and serum samples from patients with clinically inactive JIAU (n = 30), acute anterior uveitis (AAU; n = 18), and primary open angle glaucoma (POAG; n = 20) were obtained during trabeculectomy or cataract surgery. Samples were analyzed by RNA-Seq, qRT-PCR, LC-IMS, Western-Blot, and LEGENDplex™ analysis. Pattern of iris vasculature in JIAU patients was assessed qualitatively via fluorescein and indocyanine green angiography (FLA/ICGA). RESULTS: RNA-Seq of IT showed significantly differential expression (DE) of 136 genes between JIAU and POAG, of which 15 were associated with angiogenesis. qRT-PCR, performed to validate RNA-Seq results, showed upregulation of the angiogenesis-related genes Kdr, Angpt-1, Tie-1, Tie-2 and Mmrn2 in IT (JIAU vs POAG, p > 0.05). LC-IMS of IT revealed a total number of 56 DE proteins (JIAU vs POAG), of which Angiopoetin, Lumican and Decorin were associated with angiogenesis and showed increased (p > 0.05) expression on Western-Blot analysis. LEGENDplex™ analysis showed upregulation of ANGPT-2 in AH from JIAU compared to AAU and POAG, whereas VEGF was upregulated in AAU. Iris vascular leakage, hypoperfusion and neovascularization were observed by FLA/ICGA in JIA patients with treatment-refractory complicated course of uveitis. CONCLUSION: Angiogenesis-related factors could play a role in long-standing complicated JIAU, leading to clinically visible alterations in selected cases.

Viral Anterior Uveitis. / Virale anteriore Uveitis.

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.

Occurrence and Risk Factors of Uveitis in Juvenile Psoriatic Arthritis: Data From a Population-based Nationwide Study in Germany.

OBJECTIVE: Data on uveitis in juvenile psoriatic arthritis (JPsA), a category of juvenile idiopathic arthritis (JIA), are scarce. We describe prevalence and risk factors for JPsA-associated uveitis (JPsA-U). METHODS: Cross-sectional data from the German National Pediatric Rheumatological Database (2002-2014) were used to characterize JPsA-U and assess risk factors for the development of uveitis. RESULTS: Uveitis developed in 6.6% of 1862 patients with JPsA. Patients with JPsA-U were more frequently female (73.0 vs 62.9%, P = 0.03), antinuclear antibody (ANA) positive (60.3 vs 37.0%, P < 0.001), younger at JPsA onset (5.3 ± 4.1 vs 9.3 ± 4.4 yrs, P < 0.001), and treated with disease-modifying antirheumatic drugs (DMARDs) significantly more frequently compared with JPsA patients without uveitis. On a multivariable analysis of a subgroup of 655 patients enrolled in the study ≤ 1 year after arthritis onset, mean clinical Juvenile Arthritis Disease Activity Score for 10 joints during study documentation was significantly associated with uveitis development. Children with early onset of JPsA (aged < 5 yrs vs ≥ 5 yrs) were significantly more frequently ANA positive (48.4% vs 35.7%, P < 0.001), affected by uveitis (17.3% vs 3.8%, P < 0.001), and treated with DMARDs (52.9% vs 43.8%, P < 0.001), but less often affected by skin disease (55.3% vs 61.0%, P = 0.03). CONCLUSION: The characteristics of patients with JPsA developing uveitis are similar to those of patients with uveitis in other JIA categories, such as oligoarticular JIA. Children with early-onset JPsA are at a higher risk for ocular involvement. Our data support the notion of a major clinical difference between those patients with early vs late onset of JPsA.