JIA-associated Uveitis Research Articles

Successful resolution of refractory cystoid macular edema following tocilizumab therapy in a case of severe recalcitrant juvenile idiopathic arthritis-associated uveitis

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children, with JIA-associated uveitis being the most frequent extra-articular manifestation. If inadequately treated, JIA-associated uveitis can lead to persistent macular edema, potentially causing blinding complications. Tocilizumab, a humanized monoclonal antibody against IL-6, binds to its receptors and inhibits the pro-inflammatory effects of IL-6. This study reports the case of a 30-year-old female with polyarticular JIA-associated uveitis for 24 years, suffering from bilateral refractory cystoid macular edema (CME) resistant to treatments such as corticosteroids, methotrexate, infliximab, adalimumab, and tofacitinib. She received an intravitreal dexamethasone implant in her right eye. Remission of JIA and resolution of CME were achieved with tocilizumab 162 mg subcutaneous injections, combined with low-dose corticosteroids. After 12 doses of tocilizumab, there was no evidence of active uveitis in either eye.

Evaluation of postoperative outcomes after cataract surgery in patients with Juvenile Idiopathic Arthritis-Associated Uveitis.

To evaluate the postoperative outcomes of cataract surgery and intraocular lens (IOL) implantation on visual outcomes and complications in pediatric patients with Juvenile Idiopathic Arthritis-Associated Uveitis. This study included 25 patients (30 eyes) with uveitis and cataracts who underwent cataract surgery. The study was conducted as a retrospective study. Patients were divided into two groups based on their preoperative treatment: those who received immunomodulatory therapy (IMT) along with systemic corticosteroids and those who received IMT in combination with a biologic therapy. Best corrected visual acuity (BCVA), intraocular pressure (IOP), central macular thickness (CMT), macular volume (MV), and postoperative complications were assessed at various time points up to 12 months. All surgeries were performed by a single surgeon. Significant improvement in BCVA were observed postoperatively in both study groups, with approximately 80% of eyes showing improvement. Mean BCVA improved from 0.89 ± 0.63 to 0.37 ± 0.33 in group 1and from 0.82 ± 0.68 to 0.35 ± 0.31 in group 2 after 12 months. Postoperatively, there was a decrease in mean IOP, with no significant variance observed between the two groups. Complications were observed in 73% of cases, including posterior capsular opacification (PCO), secondary glaucoma, and macular edema (ME), but did not significantly differ between groups. Cataract surgery in children with uveitis associated with JIA presents significant challenges due to the risk of postoperative complications, even with adequate preoperative and postoperative care. The similar improvement in BCVA observed in both groups suggests that different systemic therapies were sufficient for satisfactory control of inflammation before and after surgery.

Visual Impairment at Presentation in Pediatric Uveitis: A Multicentric Study in 477 Children Across Southern and Eastern India

ABSTRACT Objective To evaluate visual impairment (VI) at presentation in pediatric uveitis cases in southern and eastern India. Methods Retrospective analysis of 477 children across four tertiary centers (2015–2020). Best-documented visual acuity (ETDRS letters) in the better eye was used to categorize VI. Results Mean age at presentation was 11 ± 3.7 years; 43.8% were females, and 64.8% bilateral. Of 205 patients with complete investigations, 32.7% were undifferentiated uveitis, 31.7% infectious, 25.7% juvenile idiopathic arthritis-associated uveitis, and 10.2% other non-infectious uveitis. At presentation, 79.0% had none to mild VI, 12.6% moderate VI, and 8.4% severe VI to blindness. On generalized estimating equations analysis for individual eyes, prior oral steroids and older age were risk factors, while female gender, prior topical corticosteroids and immunosuppressive therapy were protective against moderate and/or severe VI. Conclusions Over a fifth of pediatric uveitis cases present with moderate/severe VI, especially in older age or with prior oral corticosteroid therapy.

Outcomes of Micropulse Transscleral Cyclophotocoagulation in Uveitic Glaucoma.

To report a case series of patients with uveitic glaucoma who were treated with micropulse transscleral cyclophotocoagulation (mpCPC). This retrospective case series consists of patients from the University of Colorado Sue Anschutz-Rodgers Eye Center from 2015 to 2020 who were diagnosed with uveitic glaucoma. Information collected includes demographic data, type of uveitis, glaucoma severity, and prior glaucoma surgeries. Pre- and postoperative best corrected visual acuity, intraocular pressure (IOP), glaucoma medications, degree of inflammation, and uveitis therapies were included up to 36months postoperatively. Surgical success was defined as an IOP reduction of 30% with achievement of IOP goal using the same number of glaucoma medications or less at 6months or 1year. Uveitis success was defined as the absence of persistent anterior uveitis at 3months. Six patients and seven eyes with uveitic glaucoma underwent mpCPC. Types of uveitis included idiopathic anterior uveitis, HLA-B27-associated anterior uveitis, varicella zoster virus anterior uveitis, juvenile idiopathic arthritis-associated chronic anterior uveitis, lichen planus-associated intermediate uveitis, and sarcoidosis-associated panuveitis. Two of six eyes (33.3%) at 6months and three of five eyes (60%) at 1year achieved surgical success. Around 6months postoperatively, two out of seven eyes (28.6%) required Ahmed glaucoma valve placement (n = 1) or repeat mpCPC (n = 1). One eye (14.3%) required phacoemulsification with goniotomy followed by an Ahmed glaucoma valve 18months after mpCPC. There were no cases of persistent anterior uveitis, hypotony, or phthisis after mpCPC in this cohort. Micropulse transscleral cyclophotocoagulation may safely reduce intraocular pressure in some patients with uveitic glaucoma without exacerbation of intraocular inflammation. Multiple treatments may be required to achieve longer-term success.

Intravenous Golimumab in the Treatment of Juvenile Idiopathic Arthritis and Its Associated Uveitis

ABSTRACT Purpose To demonstrate the efficacy and safety of intravenous golimumab infusion in treating juvenile idiopathic arthritis-associated anterior uveitis. Methods This study was a retrospective observation case series. Electronic records of patients diagnosed with juvenile idiopathic arthritis-associated anterior uveitis who received intravenous golimumab infusion were examined. Results A total of 24 eyes of 13 patients were included in this study. During 12 months before starting intravenous golimumab, the median grade of anterior chamber reaction was 1 (range: 0.5–3), and the median number of flare-ups was 1 (1–3). During 12 months following the start of intravenous golimumab, the median grade of anterior chamber reaction was 0 (range: 0–1), and the median number of flare-ups was 0 (range: 0–1). Before starting intravenous golimumab, the average number of immunomodulatory agents was 2.6 ± 1.0 with a range of 2 to 5. The average age of patients at the time of starting intravenous golimumab was 13.69 ± 5.23 years (range between 5 and 22). A total of 11 (84.6%) patients responded to intravenous golimumab. The medication was discontinued in one patient due to ineffectiveness and in another patient due to the development of psoriasis as an adverse effect. Cystoid macular edema was present in six eyes of three patients which resolved in all six eyes after starting intravenous golimumab. Conclusion Intravenous golimumab proves to be efficacious and safe for inducing and sustaining remission in JIA and JIA-associated uveitis. Nonetheless, further robust studies with larger sample sizes are needed to substantiate our findings.

Integration of genetic and clinical risk factors improves the risk classification of uveitis in patients with juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA)-associated uveitis (JIAU) is a serious JIA comorbidity that can result in vision impairment. This study aimed to identify genetic risk factors, within the major histocompatibility complex , for JIAU and evaluate their contribution for improving risk classification when combined with clinical risk factors. Data on single nucleotide polymorphisms, amino acids and classical human leukocyte antigen (HLA) alleles were available for 2,497 JIA patients without uveitis and 579 JIAU patients (female=2060, male=1015). Analysis was restricted to patients with inferred European ancestry. Forward conditional logistic regression identified genetic markers exceeding a Bonferroni corrected significance (6x10-6). Multivariable logistic regression estimated the effects of clinical and genetic risk factors and a likelihood ratio test calculated the improvement in model fit when adding genetic factors. Uveitis risk classification performance of a model integrating genetic and clinical risk factors was estimated using area under the receiver operator characteristic curve and compared to a model of clinical risk factors alone. Three genetic risk factors were identified mapping to HLA-DRB1, HLA-DPB1 and HLA-A. These markers were statistically independent from clinical risk factors and significantly improved the fit of a model when included with clinical risk factors (P = 3.3x10-23). The addition of genetic markers improved the classification of JIAU compared to a model of clinical risk factors alone (AUC 0.75 vs. 0.71). Integration of a genetic and clinical risk prediction model outperforms a model based solely on clinical risk factors. Future JIAU risk prediction models should include genetic risk factors.

Childhood-Onset Non-Infectious Uveitis in the “Biologic Era”. Results From Spanish Multicenter Multidisciplinary Real-World Clinical Settings

ABSTRACT Objective To characterize and describe clinical experience with childhood-onset non-infectious uveitis. Study Design A multicenter retrospective multidisciplinary national web-based registry of 507 patients from 21 hospitals was analyzed. Cases were grouped as immune disease-associated (IMDu), idiopathic (IDIu) or ophthalmologically distinct. Characteristics of juvenile idiopathic arthritis-associated (non-HLA-B27-related) uveitis (JIAu), IDIu, and pars planitis (PP) were compared. Results IMDu (62.3%) and JIAu (51.9%) predominated in young females; and IDIu (22.7%) and PP (13.6%) in older children, without sex imbalance. Ocular complications occurred in 45.3% of cases (posterior synechiae [28%], cataracts [16%], band keratopathy [14%], ocular hypertension [11%] and cystoid macular edema [10%]) and were associated with synthetic (86%) and biologic (65%) disease-modifying antirheumatic drug (DMARD) use. Subgroups were significantly associated (p < 0.05) with different characteristics. JIAu was typically anterior (98%), insidious (75%), in ANA-positive (69%), young females (82%) with fewer complications (31%), better visual outcomes, and later use of uveitis-effective biologics. In contrast, IDIu was characteristically anterior (87%) or panuveitic (12.1%), with acute onset (60%) and more complications at onset (59%: synechiae [31%] and cataracts [9.6%]) and less DMARD use, while PP is intermediate, and was mostly bilateral (72.5%), persistent (86.5%) and chronic (86.8%), with more complications (70%; mainly posterior segment and cataracts at last visit), impaired visual acuity at onset, and greater systemic (81.2%), subtenon (29.1%) and intravitreal (10.1%) steroid use. Conclusion Prognosis of childhood uveitis has improved in the “biologic era,” particularly in JIAu. Early referral and DMARD therapy may reduce steroid use and improve outcomes, especially in PP and IDIu.

Sociodemographic and Visual Outcomes of Juvenile Idiopathic Arthritis Uveitis: IRIS® Registry Study.

Understanding sociodemographic factors associated with poor visual outcomes in children with juvenile idiopathic arthritis-associated uveitis may help inform practice patterns. Retrospective cohort study on patients <18 years old who were diagnosed with both juvenile idiopathic arthritis and uveitis based on International Classification of Diseases tenth edition codes in the Intelligent Research in Sight Registry through December 2020. Surgical history was extracted using current procedural terminology codes. The primary outcome was incidence of blindness (20/200 or worse) in at least one eye in association with sociodemographic factors. Secondary outcomes included cataract and glaucoma surgery following uveitis diagnosis. Hazard ratios were calculated using multivariable-adjusted Cox proportional hazards models. Median age of juvenile idiopathic arthritis-associated uveitis diagnosis was 11 (Interquartile Range: 8 to 15). In the Cox models adjusting for sociodemographic and insurance factors, the hazard ratios of best corrected visual acuity 20/200 or worse were higher in males compared to females (HR 2.15; 95% CI: 1.45-3.18), in Black or African American patients compared to White patients (2.54; 1.44-4.48), and in Medicaid-insured patients compared to commercially-insured patients (2.23; 1.48-3.37). Sociodemographic factors and insurance coverage were associated with varying levels of risk for poor visual outcomes in children with juvenile idiopathic arthritis-associated uveitis.

Predictors of lack of response to methotrexate in juvenile idiopathic arthritis associated uveitis

Abstract Objectives To investigate clinical features associated with lack of response to MTX in juvenile idiopathic arthritis associated uveitis (JIA-U). Methods Clinical records of JIA-U patients were retrospectively reviewed. Differences among variables were assessed by Mann–Whitney and χ2 or Fisher’s exact tests as appropriate. Association between predictors and requirement of a biological disease-modifying antirheumatic drug (bDMARD) was evaluated by univariate Cox regression analysis and Kaplan–Meier curves. A multivariable logistic model was applied to estimate strength of association, adjusting for potential confounders. Results Data from 99 JIA-U patients treated with MTX were analysed (82.8% female), with a mean follow up of 9.2 years and a mean age at uveitis onset of 5.7 years. In 65 patients (65.7%) at least one bDMARD to control uveitis was required. Children requiring a bDMARD for uveitis had lower age at JIA and uveitis onset, more frequent polyarticular course, higher frequency of bilateral uveitis at onset and higher prevalence of systemic steroids’ use. Despite similar frequency of ocular damage at onset, MTX non-responders showed a higher percentage of ocular damage at last visit. Younger age at JIA onset, polyarticular course and a history of systemic steroids’ use resulted independent factors associated to lack of response to MTX at Cox regression analysis. Kaplan–Meier curves and the multivariate model confirm the independent role of both polyarticular course and systemic steroids’ use. Conclusions Younger age at JIA onset, polyarticular course and a history of systemic steroids’ use are predictors of a worse response to MTX in JIA-U.

Causal inference between serum bilirubin levels and juvenile idiopathic arthritis-associated uveitis: A bidirectional Mendelian randomization study.

Several observational studies have suggested an association between low serum bilirubin levels and Behçet's disease uveitis. However, the causal inference between bilirubin level and juvenile idiopathic arthritis-associated uveitis (JIAU) remains ambiguous. We investigated the potential causal relationship between serum bilirubin levels and JIAU using a bidirectional two-sample Mendelian randomization (MR) framework. We systemically integrated summary-level data from published large-scale genome-wide association studies on bilirubin level and JIAU in a Caucasian British population. To determine the causal effect of bilirubin level on JIAU, we constructed strong instrumental variables using 47 and 80 single-nucleotide polymorphisms (SNPs) specific to direct bilirubin and total bilirubin levels, respectively. For reverse causal inference, seven SNPs associated with JIAU were included in our study. Multiple complementary methods were further performed to evaluate the robustness of MR estimates. The inverse-variance weighted estimate did not show any significant causal associations of genetically predicted serum direct or total bilirubin level with the risk of JIAU (odds ratio [OR]: 1.010, 95% confidence interval [CI]: 0.750-1.359, p = 0.947; OR: 0.867, 95% CI: 0.688-1.093; p = 0.227, respectively). MR-Egger and weighted median methods also obtained similar associations. Additionally, the results of reverse MR analyses using JIAU as exposure showed no associations of genetically predicted risk of JIAU with serum bilirubin levels (p > 0.05). In sensitivity analysis, the causal estimate between serum bilirubin levels and JIAU did not differ when SNPs associated with possible confounders were omitted. Genetic evidence from our bidirectional analysis did not support a causal association between serum bilirubin levels and JIAU risk in the Caucasian British population. Future large-scale studies should be conducted to validate these findings and explore any causal effects on the disease process.

Screening for juvenile idiopathic arthritis associated uveitis with laser flare photometry in the pediatric rheumatology office: a prospective observational study

BackgroundJuvenile Idiopathic Arthritis (JIA) Associated Uveitis (JIA-U) remains one of the most serious complications of JIA in children. Historically, pediatric JIA is diagnosed by an Optometrist or Ophthalmologist; however, barriers to scheduling increase wait times that may delay diagnosis and treatment. The purpose of this study was to evaluate laser flare photometry (LFP) use to diagnose JIA-U in the Pediatric Rheumatology clinic for patients with JIA.MethodsThis prospective, observational study assessed pediatric patients diagnosed with JIA without a previous history of uveitis between January 2020 and September 2022. All patients underwent at least one evaluation of both eyes using a Kowa FM-600 laser flare photometer during a routine Rheumatology appointment, as well as a standard slit lamp examination (SLE) by optometry or ophthalmology during routine clinical care. Data collected at patient visits included demographics, JIA characteristics, treatment, LFP readings, and anterior chamber (AC) cell grade score utilizing the SUN grading system. Data were summarized using descriptive analyses and the uveitis false positive rate was calculated.ResultsThe study cohort included 58 pediatric patients diagnosed with JIA. The mean age was 8.4 years (1.2–16.3 years) at diagnosis and 11.9 (4.8–16.5 years) at enrollment. The mean duration of disease at time of enrollment was 42 months (range; 0-157 months). Participants were predominantly female (n = 43, 74.1%) and white/Caucasian race (n = 37, 63.8%). The most common JIA subtypes included persistent oligoarticular JIA (n = 19, 32.8%), and RF negative polyarticular JIA (n = 12, 20.7%). There were 12 ANA positive patients (20.7%). At enrollment, 16 patients (27.6%) were not on medications, with 20 (34.5%) on methotrexate, 20 (34.5%) on adalimumab, 6 (10.3%) on tocilizumab, and 5 (8.6%) on etanercept. During the study period, no eye exams detected active uveitis based on SLE with a SUN grade over 0. However, of the 135 LFP readings, 131 (97.0%) were normal, yielding a false positive rate of 3% (95% CI: 0.8%, 7.4%).ConclusionsLFP is a non-invasive tool that can be utilized in the pediatric rheumatology clinic to evaluate for JIA-U. There is a low false positive rate of LFP when compared with standard slit lamp exam.

Beyond Diagnosis: Preliminary Study of Impact on Children and Parents in Neurodevelopmental Disorders and Juvenile Idiopathic Arthritis-Associated Uveitis

Chronic diseases are a growing problem for global health due to the large number of people they involve, the repercussions they have on the mental and physical well-being of those affected, and the costs to society. Particularly, chronic illnesses of childhood have important psychological implications, not only for affected children but also for their parents. Among these pathologies, neurodevelopmental disorders (NDDs) and uveitis associated with juvenile idiopathic arthritis (JIA-U) may affect mental and physical health, emotions, memory, learning, and socializing. This study evaluates the psychological and behavioral/emotional impact of NDDs and JIA-U on children and parents. Specifically, 30 children with active JIA-U and 30 children with NDDs and their parents completed the Child Behavior Checklist (CBCL) and Parent Stress Index—Short Form (PSI) questionnaires. Children with NDDs have statistically significant differences in all the emotional and behavioral variables compared to JIA-U children, and parents of children with NDDs experience an increased stress load compared to parents of children with JIA-U. This study emphasizes the wide range of emotional and behavioral challenges that parents face with NDDs. This study emphasizes that parents of children with NDDs not only experience higher levels of stress compared to parents of normally developing children but also experience higher levels of stress compared to parents of children with potentially debilitating chronic diseases such as JIA-U.

A clearer vision: insights into juvenile idiopathic arthritis–associated uveitis

The aim of this narrative review is to synthesize existing evidence-based knowledge on juvenile idiopathic arthritis–associated uveitis (JIA-U). We highlight epidemiology, pathophysiology, causes and genetics, risk factors, clinical features, diagnosis and screening, laboratory biomarkers, treatment options, trials with recent advances, and research challenges pertaining to JIA-U. The prevalence of JIA-U varies with different JIA subtypes, most frequently associated with the oligoarticular subtype. The risk factors involved in the development of JIA-U include younger age, antinuclear antibody (ANA) positivity, and the oligoarticular subtype of JIA, along with some specific major histocompatibility complex genes. Certain laboratory biomarkers, such as ANA, rheumatoid factor, interferon-λ, erythrocyte sedimentation rate, and transthyretin, have been used in JIA-U diagnosis, progress monitoring, and prognostication. Clinical features of JIA-U can range from asymptomatic to ophthalmic symptoms like redness, blurred vision, decreased visual acuity, hypopyon, and posterior uveitis, which can lead to retinal detachment and macular edema. The management protocol involves topical and systemic steroids, cycloplegics, disease-modifying antirheumatic drugs, biologic drugs, and surgical options. Early detection combined with prompt treatment is crucial to preventing irreversible vision loss in JIA-U.

Perinatal events and development of juvenile idiopathic arthritis-associated uveitis

Uveitis is one of the most common manifestations of juvenile idiopathic arthritis (JIA). Currently, JIA is associated with decreased gut microbiota diversity. Studies confirm that perinatal events can cause aberrant microbial colonization. The objective of this study is to determine if JIA is associated with perinatal events with a secondary focus on these variables to the development of JIA-uveitis. 369 patients with strabismus (n = 200) or JIA (n = 196) were included in the study. Completed surveys (JIA 37; strabismus 18) collected data about birth route, pregnancy and labor complications, JIA medications, and the presence of eye disorders. Analysis indicates that there is no relationship between JIA development and the perinatal events investigated. Similarly, no significance was found between JIA-uveitis and birth route or labor complications. Pregnancy complications, namely gestational diabetes (GD), were statistically higher in the JIA group with uveitis compared to JIA without uveitis. The data from this survey study showed that JIA-uveitis was highly associated with pregnancy complications, particularly with GD. However, no statistically significant association was found between JIA and route of delivery, labor complications, or pregnancy complications. Further studies are needed to understand the ways that GD interrelates with the development of uveitis in JIA patients.

Laser Flare Photometry to Monitor Childhood Chronic Uveitis: A Preliminary Report of a Monocentric Italian Experience.

Background: Childhood chronic non-infectious uveitis (cNIU) is a challenging disease that needs close monitoring. Slit lamp evaluation (SLE) is the cornerstone of ophthalmological evaluation for uveitis, but it is affected by interobserver variability and may be problematic in children. Laser flare photometry (LFP), a novel and objective technique, might be used in children with uveitis. Aim: The aim of this study was to attempt the use of LFP in cNIU clinical practice. Methods: Children, attending the Rheumatology Unit and who were scheduled to receive ophthalmological evaluation, were prospectively enrolled to concomitantly receive SLE and LFP. SLE was performed blind to LFP measure. Demographic, laboratory, clinical, and ophthalmology data were collected. Results: A total of 29 children (58 eyes) were enrolled, including 3 with juvenile idiopathic arthritis without uveitis (JIA-no-U), 15 with JIA-associated uveitis (JIA-U), and 11 with idiopathic chronic uveitis (ICU). We observed significantly higher LFP values in the eyes of children with uveitis compared to the others (10.1 IQR 7.1-13.6 versus 6.2 IQR 5.8-6.9, p = 0.007). Accordance between the SLE and LFP measures, at baseline (ρ.498, p < 0.001) and during the follow-up (LFP II ρ 0.460, p < 0.001, LFP III ρ 0.631, p < 0.001, LFP IV ρ 0.547, p = 0.006, LFP V ρ 0.767, p = 0.001), was detected. We evaluated significant correlation between LFP values and the presence of complications (ρ 0.538, p < 0.001), especially with cataract formation (ρ 0.542, p < 0.001). Conclusions: In this cohort, LFP measurements showed a good correlation with SLE. LFP values showed a positive correlation with the presence of complications. LFP might be considered as a reliable objective modality to monitor intraocular inflammation in cNIU.

Subcutaneous tocilizumab in the management of non-infectious uveitis in children: a brief report

BackgroundTocilizumab is a humanized monoclonal antibody that acts as an IL-6 receptor antagonist. Intravenous tocilizumab is considered an option for children with anti-TNF refractory juvenile idiopathic arthritis-associated uveitis. In contrast, the potential of subcutaneous drug use with this indication is more controversial. Due to the decreased availability of intravenous tocilizumab during the COVID-19 pandemic, we started using the subcutaneous formulation of the drug in children with anti-TNF refractory uveitis. The study analyzes the serum concentration of tocilizumab and its clinical response in patients with anti-TNF refractory uveitis who started or switched to subcutaneous administration from intravenous use.MethodsFive patients with non-infectious uveitis were treated with subcutaneous tocilizumab. Ocular inflammation was evaluated on slit lamp examination during clinical control. Serum tocilizumab concentrations were determined by ELISA.ResultsThe mean blood concentration of tocilizumab was 61.4 µg/mL (range 2.7–137.0.), with higher values than levels recorded in adult patients with rheumatoid arthritis treated with intravenous tocilizumab. Three patients entered clinical remission. One patient developed a mild relapse and was treated with topical steroids. Only one patient did not respond to therapy. The medication was well tolerated without severe infection or other adverse events.ConclusionOur results support a possible role of subcutaneous tocilizumab in anti-TNF refractory uveitis.

Evaluation of Uveitis Induced in Rats by a Type I Collagen Peptide as a Model for Childhood Arthritis-associated Uveitis.

Chronic asymptomatic and acute symptomatic anterior uveitis are forms of ocular inflammation associated with juvenile idiopathic arthritis (JIA) Chronic JIA-associated uveitis is characterized by young age of onset, female predilection, oligoarthritis, and antinuclear antibody (ANA) positivity. Acute JIA-associated uveitis predominantly affects older male juveniles who also develop enthesitis. A type I collagen-derived peptide (melanin-associated antigen [MAA]) induces anterior uveitis in rodents. In this study, we evaluated MAA-induced uveitis in rats as a potential model for JIA-uveitis. We characterized MAA-induced uveitis by assessing its relationship to age and sex; tracking the occurrence of arthritis, enthesitis, and ANA positivity; and measuring vitreous fluid inflammatory biomarkers. Juvenile and adult and male and female Lewis rats (Rattus norvegicus) were inoculated with MAA. Slit-lamp biomicroscopy, indirect ophthalmoscopy, and joint examinations were performed 3 times weekly. Rats were euthanized at 4 wk after MAA inoculation, and plasma ANA testing, vitreous inflammatory biomarker assays, and globe histopathology assessments were conducted. Uveitis, arthritis, ANA status, levels of inflammatory biomarkers, histopathology, and joint tomographic images were assessed in relation to age and sex and compared with nonuveitic controls. All MAA-immunized rats developed uveitis characterized by anterior chamber fibrin, iridal vessel dilation, and miosis, and uveal and choroidal lymphocytic infiltration. Levels of the vitreous fluid biomarker CCL5 were higher in uveitic rats compared with control rats. Time to uveitis onset, clinical uveitis scores, and biomarker levels did not differ based on age or sex. None of the MAA-exposed rats had arthritis, enthesitis, or ANA. None of the rats inoculated with MAA that had been treated with matrix metallopeptidase 1 had clinical, histologic, or immunohistochemical evidence of ocular inflammation. In contrast to JIA-associated uveitis in humans, MAA-induced uveitis in rats is not associated with age or sex predilections and MAA is not arthritogenic.

Encouraging visual outcomes in children with idiopathic and JIA associated uveitis: a population-based study

BackgroundPediatric uveitis is typically asymptomatic and may become chronic affecting ocular structures and vision. We evaluated visual outcomes, clinical features, medication, and uveitis activity in children with either idiopathic uveitis (idio-U) or juvenile idiopathic arthritis associated uveitis (JIA-U).MethodsA longitudinal, population-based cohort study of children with uveitis in 2008–2017. The data included parameters for age, gender, age at diagnosis, laterality, chronicity, anatomical distribution, etiology, systemic association, uveitis activity, medication, and visual outcomes.ResultsA total of 119 patients aged < 16 years with uveitis were included. Uveitis was idio-U in 23% and associated with JIA in 77% of cases. 37% of the patients in the idio-U group and 65% in the JIA-U were girls (p = 0.014). The mean age at first uveitis was 10.0 (SD 3.4) years in idio-U and 5.5 (SD 3.3) years in JIA-U (p < 0.001). Anterior location of uveitis was noted in 74% in idio-U and 99% in JIA-U (p < 0.001). Mostly, uveitis was chronic (59% in idio-U and 75% in JIA-U) and bilateral (56% in idio-U and 64% in JIA-U). Topical corticosteroids were initially used by 89% and 100%, systemic corticosteroids by 30% and 27% in some extent during the follow-up, disease-modifying antirheumatic drugs (DMARDs) by 33% and 85% (p < 0.001) of the patients in idio-U and JIA-U, respectively. Biologic disease-modifying antirheumatic drugs (bDMARDs) were more common in JIA-U (55% vs. 15% in idio-U, respectively, p < 0.001). Most patients had normal visual acuity (Snellen > 0.8, [6/7.5]) in the affected eye and bilaterally in 85% idio-U and 70% JIA-U. Only 5 patients (4%) had visual impairment in one, but none in both eyes. Uveitis activity by SUN classification was 0 + in 81% and 72%, 0.5 + in 19% and 25%, and 1 + in 0% and 3% in the idio-U and JIA-U, respectively.ConclusionsChildren with uveitis have good visual acuity and a low rate for visual impairment. In addition, modern treatment with DMARDs and bDMARDs seems to save vision.

The other side of the coin: Uveitis in patients with juvenile idiopathic arthritis

Objective: Juvenile idiopathic arthritis (JIA) is a childhood rheumatic disease that causes joint inflammation and tissue damage. Non-infectious uveitis is the most common extra-articular manifestation of JIA.The aim of this study is to evaluate the risk factors that play a role in occurrence and recurrence of uveitis and, to determine the relationship between arthritis and uveitis activity in patients with JIA. Material and Methods: This retrospective, cross sectional study included JIA patients with/without uveitis from a referral center in Turkey. The Juvenile Arthritis Disease Activity Score was used to evaluate the disease activity and calculated for arthritis and uveitis separately. Results: Uveitis was seen in 26 (13.3%) of 195 JIA patients. Of 26 JIA associated uveitis (JIA-U) patients, 19 (73%) had an oligoarticular subtype. The median age at diagnosis of JIA with uveitis was younger than without uveitis (p=0.015). Oligoarticular JIA was found to be associated with recurrence of uveitis (p=0.021). The occurrence age of arthritis and uveitis was significantly younger in patients with recurrent uveitis (p=0.041, p=0.002, respectively). The median JADAS27 score at the onset of uveitis was lower in the recurrent group (p=0.038). Conclusion: Early age is a significant risk factor for occurrence and recurrence of uveitis. It is important to remember that, during the disease course, patients with low disease activity may also develop uveitis.

Clinical Features and Risk Factors of Uveitis in Korean Children with Juvenile Idiopathic Arthritis: A Retrospective Cohort Study.

This study aimed to investigate the clinical features and risk factors of uveitis in Korean children with juvenile idiopathic arthritis (JIA). The medical records of JIA patients diagnosed between 2006 and 2019 and followed up for ≥1 year were retrospectively reviewed, and various factors including laboratory findings were analyzed for the risk of developing uveitis. JIA-associated uveitis (JIA-U) developed in 30 (9.8%) of 306 JIA patients. The mean age at the first uveitis development was 12.4 ± 5.7 years, which was 5.6 ± 3.7 years after the JIA diagnosis. The common JIA subtypes in the uveitis group were oligoarthritis-persistent (33.3%) and enthesitis-related arthritis (30.0%). The uveitis group had more baseline knee joint involvement (76.7% vs. 51.4%), which increased the risk of JIA-U during follow-up (p = 0.008). Patients with the oligoarthritis-persistent subtype developed JIA-U more frequently than those without it (20.0% vs. 7.8%; p = 0.016). The final visual acuity of JIA-U was tolerable (0.041 ± 0.103 logMAR). In Korean children with JIA, JIA-U may be associated with the oligoarthritis-persistent subtype and knee joint involvement.