JIA-associated Uveitis Research Articles

Early DMARD therapy in idiopathic pediatric uveitis

Scottish 2010 guidelines for JIA-associated and idiopathic paediatric uveitis recommended disease-modifying anti-rheumatic drugs (DMARD) if there was initial posterior involvement or lack of uveitis control at 4 month review. We sought to examine which patients went on to require DMARDs and whether this was associated with posterior disease at presentation.

Pediatric Noninfectious Uveitis in a Tertiary Referral Center in Jordan: Clinical Spectrum and Immunomodulatory Treatment.

ObjectivesThis study aims to describe the clinical, etiological, and treatment features of noninfectious uveitis in Jordanian children in a single center.MethodsA retrospective, observational analysis of medical records of pediatric patients who were diagnosed with noninfectious uveitis from 2015 to 2020 at pediatric rheumatology and ophthalmology clinics at Queen Rania Children’s Hospital, Amman, Jordan, was conducted. All patients were below 14 years of age at diagnosis. The collected data included age at diagnosis, anatomical location of uveitis, laterality, associated systemic disease, and used medications.ResultsOverall, 96 patients were included in this cohort (41 males and 55 females), with a mean age at diagnosis of 8.4±2.4 years. Anterior uveitis (44.8%) was the commonest anatomical location. Based on laterality, bilateral uveitis was reported in 59.3% of all patients. Idiopathic uveitis (46.9%) and juvenile idiopathic arthritis-associated uveitis (JIAU) (35.5%) were the most common diagnoses. Of the children with idiopathic uveitis, 47% had panuveitis, while 61.7% of the children with JIAU had chronic anterior uveitis. Posterior synechiae were the most common complication (12.5%). Patients with refractory uveitis received infliximab (29.1%) and adalimumab (4.1%).ConclusionTo the best of our knowledge, this is the first report on noninfectious uveitis in Jordanian children. Compared with other regional and international published reports, JIAU and idiopathic uveitis were the most common diagnoses. To obtain more details on noninfectious uveitis characteristics, a population-based rather than a single-center study is needed in Jordan.

Comprehensive Assessment of Quality of Life, Functioning, and Mental Health in Children With Juvenile Idiopathic Arthritis and Noninfectious Uveitis.

Pediatric uveitis can lead to sight-threatening complications and can impact quality of life (QoL) and functioning. We aimed to examine health-related QoL, mental health, physical disability, vision-related functioning (VRF), and vision-related QoL in children with juvenile idiopathic arthritis (JIA), JIA-associated uveitis (JIA-U), and other noninfectious uveitis. We hypothesized that there will be differences based on the presence of eye disease. A multicenter cross-sectional study was conducted at four sites. Patients with JIA, JIA-U, or noninfectious uveitis were enrolled. Patients and parents completed the Pediatric Quality of Life Inventory (PedsQL; health-related QoL), the Revised Childhood Anxiety and Depression Scale (RCADS; anxiety/depression), the Childhood Health Assessment Questionnaire (C-HAQ; physical disability), and the Effects of Youngsters' Eyesight on Quality of Life (EYE-Q) (VRF/vision-related QoL). Clinical characteristics and patient-reported outcome measures were compared by diagnosis. Of 549 patients, 332 had JIA, 124 had JIA-U, and 93 had other uveitis diagnoses. Children with JIA-U had worse EYE-Q scores compared to those with JIA only. In children with uveitis, those with anterior uveitis (JIA-U and uveitis only) had less ocular complications, better EYE-Q scores, and worse C-HAQ and PedsQL physical summary scores compared to those with nonanterior disease. In children with anterior uveitis, those with JIA-U had worse PedsQL physical summary and C-HAQ scores than anterior uveitis only. Further, EYE-Q scores were worse in children with bilateral uveitis and more visual impairment. There were no differences in RCADS scores among groups. We provide a comprehensive outcome assessment of children with JIA, JIA-U, and other uveitis diagnoses. Differences in QoL and function were noted based on underlying disease. Our results support the addition of a vision-specific measure to better understand the impact of uveitis.

Clinical Course and Outcome in Pediatric Idiopathic Chronic Anterior Uveitis

To examine the clinical course and outcome in children with idiopathic chronic anterior uveitis (iCAU), and to compare the results with those of age-matched children with juvenile idiopathic arthritis-associated uveitis (JIA-U). Retrospective cohort study. Data regarding ocular complications, visual acuity, and systemic treatment were retrospectively collected for 2 patient groups that were matched regarding age and year of uveitis diagnosis. Outcome was evaluated using survival analysis. The iCAU and JIA-U groups included 48 patients with 83 affected eyes and 48 patients with 73 affected eyes, respectively. Multivariate analyses showed that iCAU was associated with a higher prevalence of posterior synechiae (adjusted hazard rate [aHR]=3.63; P < .001) and cataract surgery (aHR=2.90; P=.006). Baseline visual acuity was worse in the iCAU group compared to the JIA-U group (20/25 vs 20/20, respectively; P < .001), but improved in the iCAU group after 5 years (20/20 vs 20/20, respectively; P=.052). At the 5-year follow-up, the younger children with iCAU (≤8 years of age at diagnosis) had a higher prevalence of posterior synechiae (aHR=2.56; P=.007), secondary glaucoma (aHR=16.0; P=.020), and cataract surgery (aHR=4.79; P=.004) compared to older children with iCAU (≥9 years at diagnosis). Vision-threatening ocular complications are more common in children with iCAU compared to children with JIA-U, particularly in cases in which the onset of uveitis occurred at ≤8 years of age. However, the long-term vision of these children can be improved with adequate treatment.

Management Strategies of Juvenile Idiopathic Arthritis-Associated Chronic Anterior Uveitis: Current Perspectives.

Juvenile idiopathic arthritis (JIA) is the most common extraocular disease associated with pediatric uveitis. Despite the growing knowledge about the pathogenetic and clinical characteristics of the disease, it still remains a challenge for both the pediatric rheumatologist and ophthalmologist. Since uveitis is asymptomatic in most cases, it is generally detected by parents in a late phase of the disease when complications have occurred with consequent severe vision loss. Improvement in attentive screening and early treatment initiation to suppress inflammation has considerably reduced the sight-threatening outcomes of JIA-associated chronic anterior uveitis (JIA-CAU). Initial treatment with topical steroids is effective in most cases. However, more severe cases require the use of periocular or systemic corticosteroids, possibly leading to long-term complications. These include growth retardation, cataract and glaucoma. Systemic immunosuppressive agents are then employed in patients resistant to first-line therapy or to reduce steroid-associated complications. In this review, we will discuss the immunosuppressant agents currently employed for the treatment of the disease, including anti-tumor necrosis factor (TNF)α biologics approved or not by the regulatory agencies. We will also highlight how new therapeutic options like biologic targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4) co-stimulatory molecule, interleukin-6 receptor (IL-6R) or B lymphocytes might represent exciting new options for patients resistant to conventional therapy. Finally, the potential use of janus kinase (JAK) inhibitors recently approved for the treatment of several inflammatory rheumatic diseases in adults will be also discussed.

Persistence of Juvenile Idiopathic Arthritis-Associated Uveitis in Adulthood: A Retrospective Study.

Background: Juvenile idiopathic arthritis (JIA) is a rheumatic condition of childhood that is frequently associated with anterior chronic uveitis. Evidence suggests that uveitis may persist up to adulthood in some cases, possibly causing severe visual impairment. Methods: We conducted a retrospective study on a series of patients aged 16 years or older with JIA-related active uveitis who were referred to the Uveitis Service of Sapienza University of Rome from 1990 to 2019 to evaluate the characteristics of ocular disease in patients with JIA-associated uveitis (JIA-U) who still exhibit uveitis in adulthood. Data on clinical features, treatment, complications and visual outcomes were collected. Results: Twenty adults (85% female; median age 23.4 ± 6.6 years, range 16–38 years) with ongoing uveitis (35 eyes) were identified. The median age at JIA onset was 6.15 ± 2.9 years (range 2–10), and uveitis onset was 8.7 ± 4.7 years (range 3–20). The patients were observed in a median follow-up of 16 ± 7.7 years (range 4–35). Fifty-seven percent of affected eyes (20 eyes) had good visual acuity (>0.4 logMAR), while eleven percent of affected eyes (4 eyes) were blind (≤20/200). Uveitis required topical steroids and mydriatic/cycloplegic in all cases. Orbital steroid injection was performed in 13 eyes. Systemic corticosteroids and biologic drugs were used in 14 patients. Conclusions: Although the visual prognosis of JIA-U has improved in recent years, persistent uveitis up to adulthood is still observed. Therefore, protracted follow-up of JIA-U patients is warranted because of the high burden of delayed visual complications.

Janus Kinase Inhibitors: Next-Generation Treatment for Uveitis.

A large proportion of patients with visual impairment secondary to non-infectious uveitis may require DMARDs. Although these are highly effective, some patients may require alternatives to the currently available immunomodulators due to an inadequate response or undesirable side effects. Janus Kinase Inhibitors (JAKi) are already approved for several autoimmune diseases in rheumatology, gastroenterology and dermatology. To date, JAKi have been studied in phase 3 trials in various types of uveitis. Mechanism of Action: JAKi work by inhibiting the phosphorylation of Janus kinases, which are transmembrane proteins. This blocks the activation of transcription factors, which in turn downregulates cytokine expression and inflammatory mediators. JAKi represent an extremely effective novel therapeutic approach in rheumatology, gastroenterology and dermatology. They have already been approved for the treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis and atopic eczema. In earlier comparative studies with conventional biologics, a better therapeutic response was reported in some cases. Several published case reports report reduced cortisone levels in patients with uveitis who had responded poorly to conventional and biological DMARDs. Approval studies are under way for JIA-associated and ANA-positive anterior uveitis. In summary, JAKi represent an innovative treatment option for patients with non-infectious uveitis in whom DMARDs are contraindicated or ineffective.

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

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. 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). 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. Angiogenesis-related factors could play a role in long-standing complicated JIAU, leading to clinically visible alterations in selected cases.

Evaluation of Patients with Juvenile Idiopathic Arthritis- Associated Uveitis from Rheumatology Perspective

Objective: Uveitis, the most common extra-articular manifestation of juvenile idiopathic arthritis (JIA), is most commonly found in children with oligoarticular type and polyarticular rheumatoid factor (-) JIA. Close follow-up of these children by pediatric rheumatologists and ophthalmologists is important because of the risk of blindness if these cases are untreated. This study aims to evaluate the frequency of uveitis, demographic characteristics, and complications in children with JIA. Material and Methods: Among the patients with JIA who were followed up at the Pediatric Rheumatology Clinic of Dr Sami Ulus Maternity, Child Health and Diseases Training and Research Hospital between January 2017 and July 2021, those with uveitis were included in the study. Location of uveitis, laterality, age at onset of uveitis, complications of uveitis, duration of follow up, laboratory findings, medications used, and status of uveitis at the time of data collection were obtained from the patients’ files. Results : Uveitis was observed in 34 (7.1%) of the 473 children with JIA included in the present study. Twenty three patients were female (67.6%). The age at diagnosis of JIA was 5.9±5.1 years, and the age at diagnosis of uveitis was 7.5±4.2 years. The most common form of JIA was the persistent oligoarticular form. Compared with the age of onset of arthritis in all JIA patients, the age of onset of arthritis was lower in patients with JIA-associated uveitis (7.8±4.6 years vs. 5.9±5.1 years). Anatomically, all patients had anterior uveitis. Antinuclear antibody positivity was more common in children with JIA-associated uveitis (47.1%) than all of our patients with JIA (19%). In one of the patients, arthritis and uveitis were diagnosed simultaneously. Posterior synechia was found in three patients (8.8%). Arthritis was the first symptom in 27 patients (79.4%) and uveitis in six patients (17.6%), cataract in five patients (14.7%), glaucoma in two patients (5.9%), and blindness in one eye (2.9%). Conclusion: Uveitis is the most common extra-articular complication of JIA and has sight-threatening complications which may lead to irreversible visual loss. The findings of this study suggest that the joint effort of pediatric rheumatologists and ophthalmologists is needed to diagnose these children promptly and treat them appropriately. Key Words: Eye diseases, Juvenile Idiopathic Arthritis, Uveitis

Assessing the Validity and Reliability of the Effects of Youngsters' Eyesight on Quality of Life Questionnaire Among Children With Uveitis.

The Effects of Youngsters' Eyesight on Quality of Life (EYE-Q) questionnaire measures vision-related functioning (VRF) and vision-related quality of life (VRQoL) in children with uveitis. Our aim was to revise the alpha version of the EYE-Q to refine VRF and VRQoL subscales and to assess the validity of the EYE-Q. Children with juvenile idiopathic arthritis (JIA), JIA-associated uveitis, and other noninfectious uveitis were enrolled. Patients and parents completed the EYE-Q, Pediatric Quality of Life Inventory (overall quality of life), and Childhood Health Assessment Questionnaire (physical functioning). The development site completed the alpha version of the EYE-Q, and the composite sites completed the beta version. We compared item-subscale correlations, internal consistency, and construct and discriminant validity among the different versions. Of the 644 patients enrolled, 61.6% completed the alpha version, and 38.4% the beta version of the EYE-Q. Mean ± SD patient age was 11.1 ± 4.2 years, and 70% were female. Fewer White patients (73.5%) completed the alpha version compared to the beta version (86.2%; P < 0.001). With the exception of patient-reported VRF, both versions had similar item-subscale correlations. Version comparisons on scale internal consistencies indicated significant differences for parent- and patient-reported VRF, but each scale had a Cronbach's α of >0.80 beta. When data were combined, the EYE-Q showed significant differences between JIA-only and uveitis patients on all parent and patient scores, except for patient-reported VRF. The EYE-Q appears to be a valid measure of VRF and VRQoL in pediatric uveitis. Our results suggest it may be used as an outcome measure in multicenter pediatric uveitis studies.

Temporal Relationship Between Juvenile Idiopathic Arthritis Disease Activity and Uveitis Disease Activity.

To determine whether there is a temporal association between arthritis and uveitis activity among children with juvenile idiopathic arthritis-associated uveitis (JIA-U). Uveitis and arthritis data from patients with JIA-U age ≤21 years were collected from July 2013 to December 2019 at a tertiary care center. Arthritis activity was assessed at each rheumatology visit, and the primary outcome was the presence of active uveitis at ophthalmologic examination within 45 days of the rheumatology visit. Repeated-measures logistic regression was used to evaluate the temporal association between any uveitis activity within 45 days of arthritis activity. Models were adjusted for demographic-, disease-, and treatment-related factors. A total of 98 patients were included: 81 (83%) female, 67 (69%) antinuclear antibody positive, 59 (60%) oligoarticular, and 13 (13%) enthesitis-related arthritis (ERA) subtypes. There were 1,229 rheumatology visits, with a median of 13 visits per patient (interquartile range 7-18). Concordance between arthritis and uveitis activity was observed 73% of the time (694 of 947). There was an independent temporal association between uveitis and arthritis activity (odds ratio 2.47 [95% confidence interval 1.72-3.54]; P < 0.01), adjusted for demographic and disease characteristics. Use of combination biologic and nonbiologic disease-modifying antirheumatic drugs, female sex, HLA-B27 positivity, and ERA and polyarticular (rheumatoid factor negative) subtypes were associated with decreased odds of active uveitis at any time point. In patients with JIA-U, there is a significant temporal association between arthritis and uveitis disease activity. These novel results suggest that an arthritis flare should prompt an expedited referral to the ophthalmologist.

Frequência de uveíte em pacientes pediátricos com artrite idiopática juvenil em hospital terciário

OBJECTIVE: Observe the profile and the frequency of juvenile idiopathic arthritis-associated uveitis (JIA-U) in patients followed at a tertiary pediatric hospital. METHODS: Retrospective study of patients with JIA attended from January to July 2019 at the pediatric rheumatology department. RESULTS: 41 charts were reviewed, from which four (9.75%) presented uveitis, all of them being diagnosed with JIA before seven years old and all of them with ocular complications. Concerning the subtype of JIA, two patients had persistent oligoarticular subtype and two had the negative rheumatoid factor poliarticular subtype. Three patients (75%) with JIA-U were antinuclear-antibody (ANA) positive. All patients presented uveitis within the first 4 years of JIA. CONCLUSION: Around 10% of the patients with JIA presented uveitis. In the JIA-U group, the following were observed: ANA positivity, JIA diagnosis before 7 years old and development of uveitis within the first 4 years of articular disease. The presence of ocular complications in all of the patients with JIA-U reveals the severity and the importance of tracking back this ocular manifestation.

Changes and significance of CDld(hi)CD5+CD19+ regulatory B cells in peripheral blood of children with juvenile idiopathic arthritis-associated uveitis

Changes and significance of CDld(hi)CD5+CD19+ regulatory B cells in peripheral blood of children with juvenile idiopathic arthritis-associated uveitis

Juvenile idiopathic arthritis-associated\xa0uveitis in the era of biological therapy: how the disease changed in more than 20\xa0years of observation in a tertiary referral center in Rome (Italy)

ObjectivesTo describe the ophthalmological characteristics in a Juvenile idiopathic arthritis (JIA) cohort and to evaluate how therapeutic advances have changed the course of the uveitis.MethodsAnalysis of a retrospective cohort study of consecutive JIA pediatric patients including JIA-associated uveitis (JIA-U) and comparison with a previous study in the same uveitis center assessed before the wide-spread of biological therapy.ResultsThe total of 49 JIA patients were analyzed, of whom 18 JIA-U, compared with a JIA-U past cohort of 66 patients. Systemic corticosteroids were used significantly less in the current JIA-U group (p = 0.008) than in the past one. JIA-U present cohort was on therapy more frequently with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) than the past group (p = 0.039), mostly treated with methotrexate (93.3%). Furthermore, a larger use of biologic disease-modifying anti-rheumatic drugs (bDMARDs) was described in the current JIA-U group (p = 0.005) also associated with csDMARDs (p = 0.003). Adalimumab was used more (72.7%) in the present JIA-U cohort compared to a larger treatment with infliximab (61.5%) in the past (p = 0.005). Higher number of uveitis recurrences was observed in the previous cohort compared to the current one (p = 0.005). Fewer complications were described in this study than in the previous: posterior synechiae (p = 0.007), cataract (p < 0.001), band keratopathy (p < 0.001), and elevated intraocular pressure (IOP) (p = 0.047).ConclusionCurrent therapies reduced the uveitis recurrences and ocular complications including cataract due also to the lower use of corticosteroids. The new close collaboration with the pediatric rheumatologic center in the same University has contributed to the care improvement and decrease of uveitis complications.

Clinical effectiveness and safety of baricitinib for the treatment of juvenile idiopathic arthritis-associated uveitis or chronic anterior antinuclear antibody-positive uveitis: study protocol for an open-label, adalimumab active-controlled phase 3 clinical trial (JUVE-BRIGHT)

BackgroundJuvenile idiopathic arthritis (JIA) is the most common pediatric rheumatic disease and the most common systemic disorder associated with uveitis in childhood. Uveitis is more common in JIA patients who are antinuclear antibody (ANA)-positive, have an early-onset disease, and have oligoarticular arthritis. JIA-associated uveitis (JIA-uveitis) is typically anterior, chronic, bilateral, nongranulomatous, and asymptomatic. Visual outcomes in JIA-uveitis have improved with current screening and treatment options; however, many patients fail to respond or do not achieve long-lasting remission. Baricitinib, an oral selective Janus kinase (JAK)1 and 2 inhibitor, may impact key cytokines implicated in the pathogenesis of JIA-uveitis or ANA-positive uveitis, representing a potential novel treatment option for disease management.MethodsThe multicenter, phase 3 trial will be conducted using an open-label Bayesian design. The study will enroll at least 20 and up to 40 patients aged 2 to <18 years with active JIA-uveitis or chronic ANA-positive uveitis without systemic features. At least 20 patients who have had an inadequate response or intolerance to methotrexate (MTX-IR), but not biologic disease-modifying antirheumatic drugs (bDMARDs), will be randomized (1:1) to open-label baricitinib or adalimumab. Approximately 20 additional patients who are MTX-IR or bDMARD inadequate responders will receive baricitinib treatment. Patients will be treated with once daily oral baricitinib at a fixed dose by age group (4 mg for patients aged ≥6 to <18 years and 2 mg for patients <6 years) or adalimumab (20 mg for patients weighing <30 kg and 40 mg for patients ≥30 kg) as a subcutaneous injection every 2 weeks. Treatment with stable background conventional synthetic DMARDs, low-dose corticosteroids, and/or nonsteroidal anti-inflammatory drugs is allowed. The primary endpoint is the proportion of patients with response at week 24. Patients may continue treatment for up to 5 years.DiscussionThis is the first pediatric clinical trial to assess the clinical effectiveness and safety of a JAK inhibitor in JIA-uveitis or chronic ANA-positive uveitis. A novel Bayesian design is used to assess the efficacy of baricitinib, including an adalimumab reference arm, in this small patient population with unmet medical need.Trial registrationEudraCT 2019-000119-10. Registered on January 4, 2019; NCT04088409. Registered on September 12, 2019

Knowledge about juvenile idiopathic arthritis-associated uveitis: more frequent reminders are associated with higher patient and family uveitis knowledge

BackgroundChronic anterior uveitis is a sight-threatening complication of juvenile idiopathic arthritis (JIA) and a primary contributor to long-term morbidity in people with JIA. Levels of knowledge about uveitis among JIA patients and their parents are unknown. A survey of JIA patients and parents was conducted to assess knowledge about uveitis complications and recommended screening.MethodsA survey was developed consisting of six demographic questions, six arthritis/uveitis history questions, and nine uveitis knowledge questions. The survey was administered to JIA patients age 14 and older and parents of patients with JIA at three pediatric rheumatology practices and online through the Patients, Advocates, and Rheumatology Teams Network for Research and Service (PARTNERS) network. ANOVA, chi-square and Fisher’s exact tests were used to look for relationships between survey questions and demographic variables.ResultsThirty-three patients and 111 parents completed the survey. Overall, 17.4% reported a history of uveitis, and 89.6% had heard of uveitis. The mean composite knowledge score was 6.46 ± 2.6 out of 9. Patients and parents with a history of uveitis had higher composite knowledge scores than their counterparts without a uveitis history (p = 0.01 and p < 0.01, respectively). Parents whose rheumatologist reminded them about eye exams at every visit had higher knowledge of the risk of blindness (p = 0.04), the risk for uveitis when arthritis is controlled (p = 0.02), the need for ongoing eye exams when off of medications (p = 0.01), and had a higher overall score (p = 0.02) than those who were reminded at some visits or not at all.ConclusionsJIA patients and parents report variable levels of knowledge regarding uveitis complications and recommended screening. Frequent discussion between the rheumatology provider and family about uveitis screening is associated with higher uveitis knowledge. Incorporating detailed and frequent education about uveitis into rheumatology clinic appointments may improve early uveitis detection and visual outcomes.

Occurrence and Risk Factors for Macular Edema in Patients with Juvenile Idiopathic Arthritis-Associated Uveitis.

Purpose: To analyze occurrence and risk factors for macular edema (ME) in juvenile idiopathic arthritis-associated uveitis (JIA-U). Methods: Retrospective analysis of patients with JIA-U at a tertiary referral uveitis center between 2000 and 2019. Epidemiological data and clinical findings before ME onset were evaluated. Results: Out of 245 patients, ME developed in 41 (18%) of the 228 JIA-U patients for whom data documentation was complete during the follow-up (mean 4.0 ± 3.8 years). Risk factors (univariable logistic regression analysis) at baseline for subsequent ME onset included older age at initial documentation at institution (hazard ratio, HR 1.19, p < 0.0001), longer duration of uveitis at initial documentation (HR 1.17, p < 0.0001), worse best-corrected visual acuity (BCVA; HR 2.49, p < 0.0001), lower intraocular pressure (IOP; HR 0.88, p < 0.01), band keratopathy (HR 2.29, p < 0.01), posterior synechiae (HR 2.55, p < 0.01), epiretinal membrane formation (HR 6.19, p < 0.0001), optic disc swelling (HR 2.81, p < 0.01), and cataract (HR 4.24, p < 0.0001). Older age at initial documentation at institution (HR 1.55, p < 0.001), worse BCVA (HR 28.56, p < 0.001), and higher laser-flare photometry (LFM) values (HR 1.003, p = 0.01) were independent risk factors for ME manifestation. Patients with ME revealed significant changes in BCVA, LFM, and IOP and new optic disc swelling at 6 and 3 months before ME onset compared to timepoint of ME occurrence (p < 0.05, each). Conclusion: ME is a common complication of JIA-U. Demographic risk factors and courses of IOP, BCVA, and LFM may indicate patients at risk for ME onset.

Immunomodulatory treatment and surgical management of idiopathic uveitis and juvenile idiopathic arthritis-associated uveitis in children: a French survey practice

BackgroundSurgeries for idiopathic uveitis and juvenile idiopathic arthritis-associated uveitis in children are complex because of the high risk of inflammatory postoperative complications. There is no consensus about treatment adaptation during the perioperative period. The objectives of this study are to report the therapeutic changes made in France and to determine whether maintaining or stopping immunosuppressive therapies is associated with an increased risk of surgical site infection or an increased risk of uveitis or arthritis flare-up.MethodsWe conducted a retrospective cohort study between January 1, 2006 and December 31, 2018 in six large University Hospitals in France. Inclusion criteria were chronic idiopathic uveitis or chronic uveitis associated with juvenile idiopathic arthritis under immunosuppressive therapies at the time of the surgical procedure, operated before the age of 16. Data on perioperative treatments, inflammatory relapses and post-operative infections were collected.ResultsA total of 76 surgeries (42% cataract surgeries, 30% glaucoma surgeries and 16% posterior capsule opacification surgeries) were performed on 37 children. Adaptation protocols were different in the six hospitals. Immunosuppressive therapies were discontinued in five cases (7%) before surgery. All the children in the discontinuation group had an inflammatory relapse within 3 months after surgery compared to only 25% in the other group. There were no postoperative infections.ConclusionsThe results of this study show varying practices between centres. The benefit-risk balance seems to favour maintaining immunosuppressive therapies during surgery. Further studies are needed to determine the optimal perioperative treatments required to limit post-operative inflammatory relapses.

Frequency of juvenile idiopathic arthritis and associated uveitis in pediatric rheumatology clinics in Turkey: A retrospective study, JUPITER

BackgroundJuvenile idiopathic arthritis (JIA), is the most common pediatric rheumatologic disorder with unknown etiology. Currently, no population-based data are available regarding the distribution of categories and frequency of uveitis in patients with JIA in Turkey. The purpose of this study was to evaluate the frequency of JIA-associated uveitis (JIAU) and distribution of JIA categories in a Turkish JIA cohort.MethodsThis was a retrospective study of 500 randomized patients in four pediatric rheumatology clinics in Turkey.ResultsOligoarticular JIA (oJIA) was the most common JIA disease category in this study cohort (38.8%). The frequencies of the other categories were as follows: enthesitis-related arthritis (ERA), 23.2%; rheumatoid factor (RF)–negative polyarthritis, 15.6%; systemic arthritis, 12.2%; juvenile psoriatic arthritis, 5.2%; undifferentiated arthritis, 2.8%; and RF-positive polyarthritis, 2.2%. JIA-associated uveitis was observed in 6.8% of patients at a mean (Standard Deviation, SD) age of 9.1 (3.8) years over a mean JIA disease duration of 4 (1.9) years. Uveitis developed after joint disease, with a mean (SD) duration of 1.8 (1.9) years. Patients with oJIA had the highest rate of uveitis (12.9%) followed by patients with ERA (5.2%) and polyarticular RF-negative disease (3.8%). Compared with persistent oJIA, the extended oJIA category had a > 3-fold higher risk of uveitis (11.3% vs 27.7%; odds ratio, 3.38 [95% Confidence Interval, 1.09–10.4]). The most frequently administered drug after development of uveitis was tumor necrosis factor–alpha inhibitors (38.2%). Five patients (14.7%) had uveitis-related complications that required surgical intervention.ConclusionsTurkish pediatric patients with JIA experience a lower frequency of oJIA and higher frequency of ERA than their white European counterparts; the occurrence of uveitis is also somewhat lower than expected. Geographic and ethnic factors may affect these differences and need further investigation.

Golimumab in juvenile idiopathic arthritis-associated uveitis unresponsive to Adalimumab

ObjectiveTo assess the efficacy of golimumab (GLM) as a treatment option for juvenile idiopathic arthritis (JIA)-associated uveitis refractory to adalimumab (ADA).MethodsRetrospective single-centre study including patients with JIA receiving GLM for active uveitis after failing ADA. JIA- and uveitis-related data, including intraocular inflammation, best-corrected visual acuity, corticosteroid-sparing potential, and ocular complications were evaluated at start of GLM treatment, at 1 month and 3 months, and every 3 months thereafter during GLM administration. We further investigated the association of response to GLM with primary and secondary failure of ADA treatment.ResultsTen patients were studied, all female (17 affected eyes, mean age 14.3 + 6.7 yrs., mean follow-up 25.2 + 21.7 mos). Two patients were switched to GLM because of primary non-response to ADA. Eight were switched because of loss of response (LOR).In 5 of the latter LOR was associated with neutralizing anti-ADA-antibodies. Response to GLM was observed in all 8 patients with LOR, while the 2 patients with primary non-response to ADA also did not respond to GLM. Three of the 8 responders experienced LOR. At the end of follow-up 4 of the 5 remaining responders had achieved complete response. One had achieved partial response.ConclusionGLM is an efficacious therapeutic option in patients who experience LOR to ADA. Our data indicate that patients without primary response to ADA should be rather switched to a biologic agent with a different mode of action instead of further blocking the TNF-alpha pathway.