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Purpose: To evaluate the clinical presentation, course, and outcomes of uveitis in paediatric patients with tubulointerstitial nephritis and uveitis syndrome (TINU)., Methods: Multicentric Retrospective Cohort Study 110 patients ≤21 years of age diagnosed with TINU from 10 sites across the United States and Canada. Clinical diagnosis of TINU required uveitis diagnosed by an ophthalmologist, elevated serum creatinine (SCr) and elevated urine β2-microglobulin (β2M) or abnormal urinalysis. Renal biopsy and systemic illness were not mandatory. Univariate and multivariate analysis was performed to analyse risk factors and treatment modalities., Results: Median age was 13 years (Range (5.9-18.4); 52% male); median follow-up, 1.6 years (IQR 0.98-4.02). Uveitis was symptomatic in 90%, with bilateral anterior uveitis in 94%. Ninety-two (84%) patients required immunomodulatory treatment (IMT). Methotrexate (n = 44) and mycophenolate mofetil (n = 39) were the first agents after oral corticosteroids. 45% required addition of biologic agents (Adalimumab [n = 33], Infliximab [n = 8]). Younger age (p = 0.018), male sex (p = 0.011), and higher uveitis grade at presentation (p = 0.031) were associated with greater IMT ( ≥ 2) requirement. 53% had uveitis recurrence compared to 16% with nephritis recurrence. At the most recent visit, nephritis was controlled in 90%, while uveitis in 74%. Four (4%) patients required glaucoma surgery. Nine (8%) patients had renal complications., Conclusions: Most patients with TINU require steroid-sparing IMT for control of uveitis, with nearly half requiring addition of biologic agents. Urinalysis, urine β2M and SCr testing should be considered in children presenting with uveitis, especially when the disease is bilateral and anterior., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Purpose: Autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV) is a rare genetic (CAPN5) autoimmune condition typically diagnosed in adulthood and characterized by a triad of inflammation, retinal degeneration, and neovascularization. We report novel multimodal imaging findings in children and young adults with ADNIV, and early treatment response to short-duration local and systemic corticosteroids., Design: Retrospective consecutive case series., Participants: Ten patients aged <25 years with ADNIV and available multimodal imaging., Methods: The medical records of patients aged <25 years with a diagnosis of ADNIV with ultrawidefield fluorescein angiography (UWFFA) and OCT data were reviewed., Main Outcome Measures: Ultrawidefield fluorescein angiography and OCT findings at baseline and after local corticosteroids., Results: Median age at presentation was 14 years (range, 9-24 years). OCT on presentation demonstrated cystoid macular edema in 8 of 20 eyes and symptomatic vitreoretinal interface disease in 2 of 20 eyes. Initial UWFFA demonstrated retinal vascular leakage (20/20 eyes, 100%), peripheral nonperfusion (13/20 eyes, 65%), and retinal neovascularization (6/20 eyes, 30%). Retinal vascular leakage improved with local corticosteroids, and neovascularization regressed with anti-VEGF therapy., Conclusions: Ultrawidefield fluorescein angiography findings of prefibrotic ADNIV reported in adults were also present in children and young adults. Early testing for a pathogenic CAPN5 variant in at-risk children and regularly scheduled screening for uveitis and retinal vasculitis with UWFFA and OCT may prompt earlier intervention. Short-duration local steroids are effective at treating retinal vascular leakage and macular edema but are not durable, suggesting a potential role for steroid-sparing immunosuppressive therapy. Early treatment may alter the natural history of disease., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: Chronic anterior uveitis (CAU) carries a significant risk for eye complications and vision loss. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) introduced consensus treatment plans (CTPs) to standardize treatment for CAU and facilitate future comparative effectiveness studies. Two CTPs were developed to address: 1) initiation of methotrexate (MTX) in patients with CAU naïve to steroid-sparing therapy, and 2) initiation of a TNF inhibitor (TNFi) in patients with severe uveitis or uveitis refractory to MTX. We evaluated implementation of the uveitis CTPs using existing CARRA Registry infrastructure and assessed feasibility of the CTPs for comparative effectiveness research., Methods: This prospective observational cohort study was conducted at nine pilot sites between February 2020 and August 2022. Patients with JIA-associated CAU (JIA-U) were treated according to either the MTX or TNFi CTP. Uveitis activity and medication use were recorded at 0, 3, and 6 months. We assessed patient enrollment rates, CTP arm selection, uveitis control, and quality of data collection. We also evaluated CTP arm selection in a retrospective cohort of similar JIA-U patients enrolled in the CARRA Registry during the same study period., Results: Seventeen patients were included in the pilot cohort. Eight were treated with the MTX CTP (4 oral MTX, 4 subcutaneous MTX), and 9 with the TNFi CTP (9 received standard-dose adalimumab, none selected high-dose adalimumab or infliximab). Uveitis was controlled in 13 of 17 patients by 6 months. Query of the CARRA-wide Registry identified 42 patients with JIA-U who were treated according to the MTX or TNFi CTPs. Among these, 26 were treated with MTX (8 oral, 18 subcutaneous) and 16 with TNFi (12 standard dose adalimumab, 2 high dose adalimumab, and 2 infliximab)., Conclusion: Both the MTX and TNFi uveitis CTPs can practically be implemented in clinical settings and are currently being utilized across Registry sites. However, in patients starting TNFi therapy, all pilot study participants and most patients across the CARRA Registry were treated with a standard dose of adalimumab. This consensus on the treatment approach underscores its broad acceptance but also limits the applicability of the uveitis TNFi CTP for comparative effectiveness research., (© 2024. The Author(s).)

Background: Autosomal dominant neovascular inflammatory vitreoretinopathy (NIV), formerly called "ADNIV," is a rare autoinflammatory condition mainly of adulthood caused by mutations in calcium-activated calpain-5 protease (CAPN5). Our aim is to report the treatment and visual outcomes of children newly diagnosed with NIV after systemic treatment., Methods: We reviewed charts of patients ≤18 years old with CAPN5 gene mutation, ocular findings consistent with NIV, and treated with systemic immunosuppression for a minimum of 6 months. Treatment response was based on ophthalmic examination, ultra-widefield fluorescein-angiography (UWFFA), and optical coherence tomography (OCT)., Results: Eight children (16 eyes) were diagnosed with NIV at a median age of 14 (Range [R] 9-16) years, with a median follow-up of 18 months (R6-20). At diagnosis, one patient had impaired visual acuity (VA > 0.4), eight had vascular leakage, two had neovascularization, and three had macular edema. All responded to oral or local glucocorticoids but was not sustained. Systemic immunosuppression was started in seven patients with methotrexate and infliximab after a median time from diagnosis of 1.5 months (R0.5-2) and 3.2 months (R2.5-3.1), respectively. Infliximab was discontinued in all after a median time of 7 months (R3.5-10) for ineffectiveness, and 5/7 switched to tocilizumab and 1 to adalimumab. Five failed to respond (4 tocilizumab, 1 adalimumab) and one had a minimal response to tocilizumab., Conclusions: We report on the systemic treatment response of seven children with ADNIV treated with methotrexate, infliximab, and tocilizumab. None were able to control disease. Further studies are needed to understand long-term outcomes and the utility of systemic immunosuppression.

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., (© 2022 American College of Rheumatology.)

Purpose: A significant number of children with noninfectious, chronic anterior uveitis (CAU) fail to respond to conventional therapy; however, successful alternative biologic treatments (ABT) have not been well described. This study aims to review the clinical and treatment characteristics of children with CAU who require ABT., Design: Retrospective, nonrandomized clinical study., Methods: Setting: Tertiary center., Study Population: Children with noninfectious CAU., Observation Procedures: Clinical characteristics, uveitis course, complications, and treatment were compared among patients treated with methotrexate (MTX) monotherapy, conventional TNFα inhibitors (cTNFi), and ABT for >3 months., Main Outcome Measure: Success of ABT (abatacept, tocilizumab, and/or golimumab) in children failing conventional treatment., Results: Of the 52 children with CAU, 75% had juvenile idiopathic arthritis. CAU was controlled in 15 children receiving MTX monotherapy, 28 receiving cTNFi, and 9 receiving ABT (n = 1, abatacept; n = 3, tocilizumab; n = 5, golimumab). Patients in the ABT group had a greater number of total ocular complications per person before ABT than those in the control groups (3.4 vs 0.7 [MTX], P < .001, and 1.5 [cTNFi], P < .001, respectively). In all 9 children on ABT, treatment led to control of CAU and topical glucocorticoids tapered to ≤2 drops/d with no new ocular complications., Conclusions: In this study, alternative biologics (abatacept, golimumab, and tocilizumab) were useful for treating CAU in children who fail MTX and cTNFi therapy. Patients who were controlled on ABT had more disease activity, ocular complications, and anti-cTNFi neutralizing antibodies (before ABT) than those managed with conventional therapy. Larger studies are required to confirm these findings., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: 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., Methods: 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., Results: 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., Conclusion: 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., (© 2021 American College of Rheumatology.)

Background: Ebola virus disease (EVD) outbreaks in West Africa (2013-2016) and the Democratic Republic of Congo (2018-2020) have resulted in thousands of EVD survivors who remain at-risk for survivor sequelae. While EVD survivorship has been broadly reported in adult populations, pediatric EVD survivors are under-represented. In this cross-sectional study, we investigated the prevalence of eye disease, health-related quality-of-life, vision-related quality-of-life, and the burden of mental illness among pediatric EVD survivors in Sierra Leone., Methods: Twenty-three pediatric EVD survivors and 58 EVD close contacts were enrolled. Participants underwent a comprehensive ophthalmic examination and completed the following surveys: Pediatric Quality of Life Inventory Version 4.0, Effect of Youngsters Eyesight on Quality-of-Life, and the Revised Child Anxiety and Depression Scale., Findings: A higher prevalence of uveitis was observed in EVD survivor eyes (10·8%) cohort compared to close contacts eyes (1·7%, p=0·03). Overall, 47·8% of EVD survivor eyes and 31·9% of close contact eyes presented with an eye disease at the time of our study (p=0·25). Individuals diagnosed with an ocular complication had poorer vision-related quality-of-life (p=0·02)., Interpretation: Both health related quality-of-life and vision-related quality-of-life were poor among EVD survivors and close contacts. The high prevalence of eye disease associated with reduced vision health, suggests that cross-disciplinary approaches are needed to address the unmet needs of EVD survivors., Funding: National Institutes of Health R01 EY029594, K23 EY030158; National Eye Institute; Research to Prevent Blindness (Emory Eye Center); Marcus Foundation Combating Childhood Illness; Emory Global Health Institute; Stanley M. Truhlsen Family Foundation., Competing Interests: The funding organizations highlighted above had no role in the design or conduct of this research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. The authors on this manuscript declare no financial conflicts of interest in relationship to the work presented., (© 2022 The Author(s).)

Objective: To provide recommendations for the management of juvenile idiopathic arthritis (JIA) with a focus on nonpharmacologic therapies, medication monitoring, immunizations, and imaging, irrespective of JIA phenotype., Methods: We developed clinically relevant Patient/Population, Intervention, Comparison, and Outcomes questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation approach was used to rate the quality of evidence (high, moderate, low, or very low). A Voting Panel including clinicians and patients/caregivers achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations., Results: Recommendations in this guideline include the use of physical therapy and occupational therapy interventions; a healthy, well-balanced, age-appropriate diet; specific laboratory monitoring for medications; widespread use of immunizations; and shared decision-making with patients/caregivers. Disease management for all patients with JIA is addressed with respect to nonpharmacologic therapies, medication monitoring, immunizations, and imaging. Evidence for all recommendations was graded as low or very low in quality. For that reason, more than half of the recommendations are conditional., Conclusion: This clinical practice guideline complements the 2019 American College of Rheumatology JIA and uveitis guidelines, which addressed polyarthritis, sacroiliitis, enthesitis, and uveitis, and a concurrent 2021 guideline on oligoarthritis, temporomandibular arthritis, and systemic JIA. It serves as a tool to support clinicians, patients, and caregivers in decision-making. The recommendations take into consideration the severity of both articular and nonarticular manifestations as well as patient quality of life. Although evidence is generally low quality and many recommendations are conditional, the inclusion of caregivers and patients in the decision-making process strengthens the relevance and applicability of the guideline. It is important to remember that these are recommendations. Clinical decisions, as always, should be made by the treating clinician and patient/caregiver., (© 2022 American College of Rheumatology.)

Objective: To provide updated guidelines for pharmacologic management of juvenile idiopathic arthritis (JIA), focusing on treatment of oligoarthritis, temporomandibular joint (TMJ) arthritis, and systemic JIA with and without macrophage activation syndrome. Recommendations regarding tapering and discontinuing treatment in inactive systemic JIA are also provided., Methods: We developed clinically relevant Patient/Population, Intervention, Comparison, and Outcomes questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation approach was used to rate the quality of evidence (high, moderate, low, or very low). A Voting Panel including clinicians and patients/caregivers achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations., Results: Similar to those published in 2019, these JIA recommendations are based on clinical phenotypes of JIA, rather than a specific classification schema. This guideline provides recommendations for initial and subsequent treatment of JIA with oligoarthritis, TMJ arthritis, and systemic JIA as well as for tapering and discontinuing treatment in subjects with inactive systemic JIA. Other aspects of disease management, including factors that influence treatment choice and medication tapering, are discussed. Evidence for all recommendations was graded as low or very low in quality. For that reason, more than half of the recommendations are conditional., Conclusion: This clinical practice guideline complements the 2019 American College of Rheumatology JIA and uveitis guidelines, which addressed polyarthritis, sacroiliitis, enthesitis, and uveitis. It serves as a tool to support clinicians, patients, and caregivers in decision-making. The recommendations take into consideration the severity of both articular and nonarticular manifestations as well as patient quality of life. Although evidence is generally low quality and many recommendations are conditional, the inclusion of caregivers and patients in the decision-making process strengthens the relevance and applicability of the guideline. It is important to remember that these are recommendations. Clinical decisions, as always, should be made by the treating clinician and patient/caregiver., (© 2022 American College of Rheumatology.)

Objective: 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., Methods: 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., Results: 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., Conclusion: 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., (© 2020 American College of Rheumatology.)