To identify serum biomarkers associated with the development of uveitis in a German juvenile idiopathic arthritis (JIA) cohort. A convenience sample, enriched for uveitis cases, was drawn from a prospectively followed inception cohort of newly diagnosed JIA patients (ICON). Baseline serum samples were biobanked, and each was tested for conventional and novel autoantibodies using multi-analyte array technologies. Associations between uveitis occurrence, disease outcomes, and autoantibody profiles were examined. Fifty-two patients with and 141 patients without uveitis were included in the analyses. At first uveitis documentation, 26

PURPOSE:Cataract surgery in patients with chronic anterior uveitis may be associated with increased risk for complications and poor outcomes. This study analyses visual outcome, uveitis course and complications after cataract surgery with intraocular lens (IOL) implantation in adolescents and adults with juvenile idiopathic arthritis (JIA)-associated or antinuclear antibodies (ANA)-positive uveitis. METHODS:Data before and at 6 weeks, 1 and 2 years after surgery were retrospectively analysed according to Standardization of Uveitis Nomenclature (SUN) standards. Surgery was performed with small incisions, phacoemulsification and IOL implantation. Surgical technique was adapted to pre-existing uveitis-related morphological abnormalities. Predictors of visual outcome and vision-threatening complications at 2-year follow-up (FU) were analysed. RESULTS:93 surgeries of 83 patients (84% female; mean age 24.8±16.2 years) with JIA-associated (84%) or ANA-positive (16%) anterior uveitis were analysed. Preoperative treatment included topical steroids, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs; 72.0%) or biological (b) DMARDs (65.6%). Besides cataract, uveitis-related complications (eg, fibrotic lens membrane, posterior synechiae and pupil contraction) were present in 95.7% before surgery. Best-corrected visual acuity (BCVA) in logarithm of the minimum angle of resolution (logMAR) improved from 1.57±1.32 preoperatively to 0.42±0.83 at 2 years (p<0.001). Postoperative complications included posterior synechiae formation (30%), giant-cell deposits (35.7%), posterior capsule opacification (51.9%) and macular oedema (12.7%). Significant preoperative predictors of poor visual outcome included poor BCVA and high laser flare (LF) values, and those of postoperative ocular complications also included poor BCVA and a lack of systemic anti-inflammatory drug use (each, p<0.05). CONCLUSIONS:Beneficial outcomes can be achieved following cataract surgery with IOL implantation in adolescents and adults with JIA-associated or ANA-positive anterior uveitis. Important prerequisites include preoperative inactivity, appropriate surgical technique and sustained long-term uveitis inactivity with the use of DMARDs.

Purpose: Clinical presentation of anterior uveitis affecting the iris is nearly identical in patients with juvenile idiopathic-associated uveitis (JIAU) and patients with antinuclear antibody-positive anterior uveitis (ANA-U). This study investigates whether the iris transcriptomes of patients with JIAU or ANA-U differ or reflect the clinical homogeneity. Methods: Iris biopsies were obtained from patients with JIAU (n = 31) or ANA-U (n = 9) during trabeculectomy, iridectomy, or complex cataract surgery. Frozen iris tissues were homogenized, the RNA was isolated and analyzed using a bulk RNA sequencing approach. Genes with a Benjamini–Hochberg false discovery rate (FDR) p ≤ 0.05 and a log2 fold change (FC) of >1 or <−1 were defined as significantly differentially expressed genes (DEGs). Pathway enrichment analysis was subsequently performed to characterize these DEGs. Results: The JIAU group included nine male and 22 female patients (median age 10.2 [IQR 7.2, 13.7] years), while the ANA-U group consisted of one male and eight female patients (median age 10.2 years (IQR [6.1, 11.7]) years). No DEGs were identified when comparing the iris transcriptomes of JIAU and ANA-U directly. Subgroup analyses based on disease activity revealed 35 DEGs in ANA-U, one DEG in JIAU. Inter-group comparisons based on uveitis activity status yielded no DEGs. In the merged JIAU/ANA-U cohort, 28 DEGs were upregulated in the active vs. inactive uveitis. Regarding secondary glaucoma, 12 DEGs were identified in JIAU, and 15 DEGs were identified in the corresponding ANA-U subgroup. Inter-group comparisons based on glaucoma status yielded no DEGs. In the merged JIAU/ANA-U cohort, 20 DEGs were identified between patients with and without glaucoma. Conclusions: Our findings reveal only marginal differences in gene expression patterns in iris tissues from JIAU and ANA-U patients. These results suggest a high degree of similarity in the underlying inflammatory processes of both uveitis subsets.

Abstract Background Juvenile idiopathic arthritis-associated uveitis (JIAU) frequently follows a chronic and complicated course. Janus kinase inhibitors (JAKi) represent a promising new therapeutic option. Methods Retrospective monocentric analysis of 20 children with chronic anterior JIAU treated with tofacitinib ( n = 18), baricitinib ( n = 1) or upadacitinib ( n = 1). Outcome measures: uveitis or arthritis inactivity at any time during follow-up, recurrences after achieving inactivity, sparing of medication, occurrence of new ocular complications, resolution of preexisting macular edema. Results All patients had received methotrexate prior to baseline, and at least two biologics had been ineffective in 18/20 patients. Whilst receiving JAKi medication, uveitis was inactive in eight patients (anterior chamber cell count < 0.5+) at any time during follow-up (mean 9.2 ± 3.3 months), but uveitis relapsed in 6 of them subsequently. In 7 patients, treatment was terminated after ≤ 1 year due to inadequate response of ocular inflammation. During follow-up, new uveitis-related complications occurred in 7 patients (9 eyes), the most frequent were macular edema (8 eyes of 7 patients), and ocular hypertension (5 eyes of 3 patients). Reduction of concomitant systemic medication was possible in 3/14 patients. Any reduction of topical steroids during follow-up was possible in 24/30 eyes, and 23/30 eyes received a lower dose at the last follow-up than they did at baseline. Conclusions Our data show limited effectiveness of JAKi treatment in patients with chronic DMARD-refractory JIAU. The number of patients in whom uveitis quiescence could be observed was low, as was the possibility for reduction of concomitant medication, and the relapse rate was high. Clinical trial number Not applicable.

This in vitro study investigated the adhesion of human human monocytes / macrophages (MΦ) to poly(styrene-block-isobutylene-block-styrene) (SIBS)-based PreserFlo® MicroShunts, as macrophage interactions can significantly influence microimplant success. For this, purified human MΦ were cultured for 35 days on SIBS-based PreserFlo® MicroShunts and compared against control intraocular lens (IOL) materials (PMMA and hydrophilic acrylate). We found significantly higher MΦ adhesion on the PreserFlo® MicroShunts than on PMMA or hydrophilic acrylic IOLs (p < 0.05). These results indicate that the surface properties of the SIBS-based MicroShunt promote greater MΦ adhesion in vitro compared to commercial IOLs under the conditions tested. This differential adhesion could have implications for the long-term performance of the implant, particularly in uveitic eyes. While increased MΦ adhesion is a known component of the foreign body response, further functional analysis of the macrophage secretome and polarization state (M1 vs. M2) is required to confirm whether this leads to clinically significant fibrosis. Furthermore, in vivo studies are required to elucidate the specific impact of these interactions on long-term clinical performance in uveitic eyes.

In this study the retinal transcriptome was investigated during the development of experimental autoimmune uveoretinitis (EAU) in mice. EAU was induced by immunizing B10.RIII mice with human interphotoreceptor retinoid binding protein (hIRBP) 161–180 peptide. Genome-wide transcriptional profiles of EAU (day 7, 14 or 21 after immunization) and of control retinas were generated using DNA-microarrays and bioinformatic data mining. Microglia-associated transcripts were identified. Quantitative real-time polymerase chain reaction was performed to validate the expression of differentially expressed genes. Retinal transcript validation revealed that complement and interferon-related pathways, as well as gene clusters specific for antigen-processing and -presentation, and immunosuppression are involved during the course of the disease. Immunofluorescence analysis confirm that upregulated transcripts in EAU are also expressed by retinal microglia. Furthermore, the heterogenous expression patterns observed in retinal microglia, suggests the presence of different subpopulations of retinal microglia in EAU. This study expands our knowledge of the local immune processes involved in EAU pathology.

Die in Europa häufige Keratitis herpetischer Genese wird meist durch das Herpes-simplex-Virus Typ I (HSV) verursacht und ist in seiner Ausprägung ein Chamäleon. Sie kann in der Regel erfolgreich behandelt werden, wenn man die verschiedenen, typischerweise einseitigen Ausprägungsformen dieser Krankheit kennt: 1. epitheliale Keratitis (dendritica/geographica), 2. stromale Keratitis (nekrotisierend vs. nichtnekrotisierend = „interstitiell“), 3. Endotheliitis (= „disziforme Keratitis“), 4. sog. metaherpetische Keratitis (= neurotrophe Keratopathie), 5. (vaskularisierte) Hornhautnarben. Das Therapieschema wird bewusst auf die Ausprägungsform abgestimmt. Eine begleitende okuläre Hypertension sollte im Akutstadium vornehmlich medikamentös behandelt werden (auf Prostaglandinanaloga verzichten!). Nach Keratoplastik und bei häufigen schweren Keratitisschüben ist die systemische Aciclovir-Applikation (2 × 400 mg/Tag) für mindestens 1 Jahr aktueller Standard!

Juvenile idiopathic arthritis-associated uveitis (JIAU) typically takes a chronic course, frequently leading to ocular complications and often requiring long-term treatment. The present study assesses the 5-years outcome of JIAU by analyzing data from a prospective study initiated in 2010. Data from 75 patients with onset of uveitis after study enrollment, and with a documentation at 5-years follow-up (5yFU) were available for analysis of uveitis characteristics, frequency and predictors of „inactivity on medication “ (defined as inactive uveitis for ≥ 6 months) and „inactivity off medication “ (defined as inactive uveitis for ≥ 6 months off medication). At the 5yFU, visual acuity remained good in the majority of eyes (LogMAR < 0.1 in 65.5

Background: Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare autoimmune disorder, characterized by acute tubulointerstitial nephritis and uveitis. It poses diagnostic challenges due to the mostly asynchronous onset of renal and ocular manifestations, as well as the variety of differential diagnoses. This review provides an overview of the epidemiology, pathogenesis, clinical features, diagnostic criteria, and management strategies. Methods: A comprehensive review of the peer-reviewed literature, including studies and case reports, was conducted. Results: The etiology of TINU syndrome involves an autoimmune reaction to renal and ocular antigens, leading to interstitial inflammation and tubular damage in the kidneys, and anterior uveitis with acute onset of flares. Diagnostic criteria based on ocular examination, laboratory parameters, and renal biopsy emphasize the need to exclude other systemic diseases. TINU syndrome accounts for approximately 2% of all uveitis cases. Primary treatment consists of corticosteroids, while immunomodulatory therapies (methotrexate, azathioprine, mycophenolate mofetil, or biologic agents) are reserved for refractory cases. Recurrence of uveitis appears to be more common than that of nephritis. Conclusions: TINU syndrome is rare and requires clinical suspicion for accurate diagnosis. Early diagnosis and initiation of treatment are crucial for achieving favorable outcomes. Advances in the understanding of its pathogenesis and treatment have improved patient outcomes. Further research is needed to investigate the underlying triggers and mechanisms in order to develop targeted therapies.

PURPOSE:To investigate the clinical course and 2-year outcome after cataract surgery with implantation of intraocular lenses (IOL) in children with juvenile idiopathic arthritis (JIA)-associated uveitis or chronic antinuclear antibody (ANA)-positive uveitis. DESIGN:Retrospective interventional clinical study. SUBJECTS:Children with cataract surgery at ≤10 years of age. METHODS:Comprehensive uveitis-related data (defined by Standardization of Uveitis Nomenclature standards) were collected before, during and 6 weeks, 1 and 2 years after surgery. Surgical procedures involved small incision phacoemulsification, insertion of foldable acrylic IOLs with a sharp-edge design into the capsular bag, 25 G anterior vitrectomy, posterior capsulectomy, and intravitreal triamcinolone injection. Surgical technique was modified individually according to pre-existing uveitis-related morphological abnormalities. MAIN OUTCOME MEASURES:Best-corrected visual acuity (BCVA) and postoperative complications. RESULTS:All 100 surgeries (81 patients, 100% ANA-positive, 69% female, 90.1% JIA, mean age at JIA diagnosis 4.26 ± 2.35 years) involved insidious-onset anterior uveitis (mean age at uveitis onset 4.6 ± 2.1 years). Surgery was performed at a mean age of 8.2 ± 3.3 years (SD 3.2), and under treatment with conventional synthetic disease-modifying anti-rheumatic drugs (DMARD; 90%), or 45% biologicals. Prior to surgery, uveitis-related complications were present alongside cataract in 99% of patients (eg. lens fibrotic membrane and pupil contraction). BCVA (logMAR) was 1.57 ± 1.24 before surgery, and was 0.32 ± 0.51 and 0.3 ± 0.53 at 1 and 2 years after surgery, respectively (each, P < .001). Fibrin formation was present in 39.6% of cases on the first day after surgery. After 1 and 2 years of surgery, macular edema was present in 4.6% and 9.4%, and glaucomatous optic discs in 17.3% and 18.9%, respectively. Preoperative predictors of poor 2-year visual outcome included poor BCVA, high laser flare (LF) values, unilateral uveitis, and glaucoma medication. Preoperative predictors of 2-year postoperative ocular complications included band keratopathy and a lack of methotrexate or adalimumab use. CONCLUSIONS:According to our observations, IOL implantation can be considered for children with JIA-associated or ANA-positive uveitis, on the condition that their uveitis is well controlled with DMARD therapy and the surgical technique is appropriate. The long-term course of the inflammatory disease determines the occurrence of intraocular complications related to inflammation and the visual outcome.