Relapse of Juvenile Idiopathic Arthritis-Associated Uveitis after Discontinuation of Immunomodulatory Therapy

Purpose: To assess treatment outcomes in juvenile idiopathic arthritis (JIA)-associated uveitis and relapse rates upon discontinuation of immunomodulatory therapy (IMT). Methods: Medical records of patients with JIA-associated uveitis seen at the University of Illinois at Chicago and the F.I. Proctor Foundation uveitis clinics from September 14, 1988 to January 5, 2011 were reviewed. The main outcome was time to relapse after attempting to discontinue IMT.Results: Of 66 patients with JIA-associated uveitis, 51 (77%) received IMT as either sole or combination therapy. Of a total of 51, 41 (80%) patients achieved corticosteroid-sparing control. Attempts were made to discontinue treatment in 19/51 (37%) patients. Of a total of 19 patients, 13 (68%) attempting to discontinue IMT relapsed, with a median time to relapse of 288 days from the time of attempted taper/discontinuation (IQR: 108–338).Conclusions: Corticosteroid-sparing control of inflammation was achieved in the majority of patients; however, attempts to stop IMT were often unsuccessful. Close follow-up of patients after discontinuation of therapy is warranted.     

Chronic Non-infectious Uveitis in Patients with Juvenile Idiopathic Arthritis

Purpose: To describe clinical findings and analyze treatment evolution of chronic, non-infectious uveitis in patients with juvenile idiopathic arthritis (JIA).

Methods: A total of 82 patients (147 eyes) with JIA-related uveitis treated for ≥2 months were included (78% females; 79% bilateral uveitis; 74% anterior uveitis). Outcome measures were visual acuity (VA), inflammation control, side-effects, and surgical procedures.

Results: Mean ± SD age at diagnosis was 4.9 ± 3.8 years; mean ± SD follow-up time was 8.7 ± 7.8 years. Mean VA did not significantly change throughout the study. Three (2%) eyes resulted in no light perception (NLP) vision. Thirty (37%) patients underwent 69 procedures. In total, 41 (50%) patients achieved inflammation control. TNF-α inhibitors were significantly associated with inflammation control. Seven (8.5%) patients stopped treatment due to side-effects.

Conclusions: JIA is a cause of significant ocular morbidity. TNF-α inhibitor use was associated with inflammation control. Prospective, randomized, double blind clinical trials in this regard are warranted.     

Treatment Options for Juvenile Idiopathic Arthritis (JIA) Associated Uveitis

Purpose: To summarize the available published data regarding the treatment of JIA-associated chronic uveitis.

Methods: Available peer-reviewed publications regarding the treatments of JIA-associated uveitis were read by multiple authors (RMA, EM, JET, and DH) and the data from these reports were synthesized for this review.

Results: Juvenile idiopathic arthritis (JIA)-associated chronic uveitis is a significant cause of ocular morbidity and visual impairment in children, often resulting in more frequent complications and worse visual outcomes than other types of pediatric uveitis. Since not all patients respond to the first medication introduced, it is useful to have a wide range of available treatment modalities to address recalcitrant disease. Treatment options for JIA-associated uveitis have increased substantially over the past decade, particularly with the availability of newer biological agents in addition to established medication classes such as anti-inflammatories (including topical and systemic corticosteroids) and antimetabolites.

Conclusions: Although data are increasing regarding biologic agents, definitive randomized prospective clinical trials would be helpful to determine their optimal dose, frequency, treatment duration, and long-term safety in children.     

Long-term Follow-up of Patients with Uveitis Associated with Juvenile Idiopathic Arthritis: A Cohort Study

Purpose: To analyze the clinical and visual outcome of 55 consecutive patients with juvenile idiopathic arthritis (JIA)-associated uveitis examined 7 and 24 years after the onset of the eye disease. Methods: A retrospective study. Results: Fifty-five out of 350 patients with JIA developed uveitis (15.7%). Forty-six (84%) of these had oligoarthritis, 6 (11%) had polyarthritis, and 3(5%) had systemic disease. Cataract was present in 42% at 7 years and in 51% at 24 years. Uveitic glaucoma was present in 5% at 7 years and in 22% at 24 years. After 24 years, 27 patients (49%) still had active uveitis. Conclusions: In half of these patients the uveitis was still active after 24 years of eye disease. In the group of patients with active disease, cataract and secondary glaucoma increased significantly between years 7 and 24 of disease.     

托珠单抗治疗幼年特发性关节炎相关葡萄膜炎的研究进展

葡萄膜炎是幼年特发性关节炎（JIA）最常见的关节外表现,多表现为反复发作的慢性前葡萄膜炎,其发病隐匿、并发症多等特点可导致患者眼部结构损伤、视力丧失。白细胞介素6（IL-6）是一种多效性细胞因子,参与炎症反应和免疫调节等过程,而托珠单抗是一种人源性IL-6受体（IL-6R）单克隆抗体,通过竞争性与IL-6R结合从而抑制...     

Surgery for Hypotony in Patients with Juvenile Idiopathic Arthritis-Associated Uveitis

Purpose: To describe the clinical response to cyclitic membrane excision of eyes with juvenile idiopathic arthritis (JIA)-associated uveitis and hypotony. Methods: The clinical records of patients with JIA-associated uveitis in a tertiary referral center were reviewed. Those patients with JIA-associated uveitis and hypotony who underwent cyclitic membrane excision were included in the study. Patients with hypotony secondary to active inflammation, retinal detachment, and surgical intervention (filtering, cyclo-destructive procedures, and glaucoma valve implantation) were excluded. Results: Two pediatric and two adult patients (4 eyes) were identified. The range of pre-operative intraocular pressure (IOP) was 0–5 mmHg. The two adult patients were noted to have atrophic ciliary processes intra-operatively, while the two pediatric patients had normal ciliary processes. At six months follow-up, the adult patients had IOPs of 5 mmHg, while the two pediatric patients had IOPs of 16 mmHg. At last consultation (mean duration of follow-up: 3.6 years), IOP was normal in all eyes. None of the eyes had a decrease in vision. Conclusions: Release of traction on the ciliary body by inflammatory membranes may play a role in the management of hypotony in patients with JIA-associated uveitis. However, even though the IOP was successfully elevated, preventing phthisis, vision remained poor due to the long-standing complications secondary to chronic uveitis. This emphasizes the critical importance of early diagnosis and appropriate treatment of the inflammation before vision-robbing complications occur.     

Foveal Serous Retinal Detachment in Juvenile Idiopathic Arthritis-associated Uveitis

Purpose: In juvenile idiopathic arthritis (JIA)-associated uveitis complicated by foveal serous retinal detachment (FSRD), we documented the relationship between best corrected visual acuity (BCVA), level of anterior chamber flare and OCT features.

Methods: Nine children (15 eyes) with FSRD were identified among 38 children with JIA-associated maculopathy. Outcome measures included BCVA, ocular inflammatory activity quantified by laser flare photometry and the macular profile analyzed by OCT.

Results: The diagnosis of FSRD led to intensification of the treatment using subtenon’s injection of triamcinolone or systemic immunomodulatory therapy. The improvement of BCVA at presentation (0.46 logMAR) was significant at 36 months follow-up (0.15 logMAR). The resolution of FSRD along with visual improvement (p?=?0.0032) correlated with improvement in anterior chamber flare (p?=?0.01).

Conclusion: FSRD is a complication of chronic JIA-associated uveitis that responds well to intensification of immunomodulation. Visual improvement is correlated with FSRD resolution and with flare photometry values.     

ORIGINAL ARTICLE Visual Outcome of Juvenile Rheumatoid Arthritis-Associated Uveitis in Adults

Purpose: Juvenile rheumatoid arthritis (JRA) is the systemic disease most frequently associated in childhood uveitis. The disease may cause several ocular complications, visual impairment, and blindness. Recent studies revealed a more favorable ocular prognosis. Our purpose was to analyze the long-term visual outcome of JRA-associated uveitis. Methods: Ocular complications and visual outcome in adult patients with JRA-associated uveitis were evaluated. Among 18 patients included in the study, uveitis was bilateral in 12 (66.7%) and unilateral in six (33.3%), for a total of 30 eyes with ocular involvement. Results: The mean durations of JRA and its associated uveitis were 24.9 and 20.5 years, respectively. All eyes (100%) had at least one ocular complication. The most frequently observed ocular complications were cataract (83.3%), band keratopathy (60%), posterior synechia (46.7%), glaucoma (33.3%), hypotony (16.7%), and macular pathology (13.3%). Final visual acuity was impaired in 40% of the eyes, poor in 20%, and totally lost in 10%. Therefore, 70% of the eyes were either visually handicapped or totally blind. Most eyes underwent at least one surgical procedure. Inflammation was active at last examination in 63.3% of eyes. All patients were still treated topically and with systemic NSAID. Sixty-one percent of the patients were using an immunosuppressive agent. Conclusion: JRA-associated uveitis still has a severe course and blinding potential. Patients suffer from uveitis and its complications even during the adulthood period. However, because our series represents a more severe subset of the disease, the outcome may be poorer than that of some other outcome studies.     

Uveitis Related to Juvenile Idiopathic Arthritis: Familial Cases and Possible Genetic Implication in the Pathogenesis

Purpose: To describe four cases of familial Juvenile Idiopathic Arthritis (JIA) associated uveitis.

Design: Retrospective observational case series.

Methods: Clinical data from patients who present familial JIA-associated uveitis are described and possible genetic influence in disease etiology is reviewed.

Results: Two sisters, 6- and 7-year-old, developed bilateral anterior uveitis related to oligoarticular JIA. Arthritis in both began by the age of 18 months; uveitis developed simultaneously in one of them and less than one year after arthritis in the other one. Both received topical and systemic treatment to control the ocular disease. Glaucoma occurred in both cases and bilateral cataract in one case. In the other family, a 2-year-old girl developed unilateral uveitis in the context of oligoarticular JIA which was diagnosed by 1-year-old. The disease became soon bilateral and she received topical and systemic immunosuppressive treatment. Her mother suffered from bilateral anterior uveitis associated to oligoarticular inflammatory disease during her infancy, later diagnosed as JIA-associated uveitis.

Conclusions: Familial cases of JIA uveitis, although not very common, support the possible role of genetic influence in the pathogenesis of the disease, with horizontal and vertical inheritance being possible. The evolution of ocular disease is similar to the non-familial cases, except for an earlier age of onset.     

Juvenile Idiopathic Arthritis-associated Uveitis at an Italian Tertiary Referral Center: Clinical Features and Complications

Abstract

Purpose: To describe the frequencies and risk factors of ocular complications and poor visual outcomes in children with juvenile idiopathic arthritis (JIA).

Methods: Retrospective cohort study, including 69 consecutive children (116 eyes) affected by JIA-associated uveitis managed at a tertiary uveitis clinic.

Results: The incidence of visual loss to the 20/50 or worse threshold was 0.04/eye-year (EY) and to the 20/200 or worse threshold was 0.02/EY. The most common complications at baseline were posterior synechiae (52%), band keratopathy (38%), and cataract (12%). Risk factor for a visual acuity threshold of 20/50 or worse included hypotony (p?=?0.01; hazard ratio [HR] 3.7; 95% CI 1.3–10.4); anterior chamber flare >1 (p?=?0.04; HR 1.3; 95% CI 0.5–3.4); a positive antinuclear antibody (ANA) (p?=?0.02; HR1.4; 95% CI 0.8–2.4). Hypotony and positive ANA are also associated to the 20/200 or worse threshold (p?=?0.03; HR 5.1; 95% CI 1.1–23.9 and p?=?0.04; HR 1.0; 95% CI 0.4–2.3; respectively). Use of immunosuppressive drugs was associated with a reduced risk of visual loss of 20/200 or worse (odds ratio 0.14, 95% CI, 0.02–1.29; p?=?0.04).

Conclusions: Loss of vision and ocular complications still occur among children with JIA-related uveitis. Prompt diagnosis and a strict follow up associated to immunosuppressive therapy may decrease the poor visual outcome.     

Retinal Complications of Juvenile Idiopathic Arthritis-related Uveitis: A Microperimetry and Optical Coherence Tomography Study

Purpose: To evaluate ocular complications of juvenile idiopathic arthritis (JIA)-related uveitis; to study macular morphology and sensitivity.

Methods: Retrospective chart review of 67 patients. Fourteen consecutive patients (24 eyes) observed from January to December 2008 were submitted to optical coherence tomography study (OCT) and microperimetry MP-1 examination.

Results: Most frequent complications were posterior synechiae (63.0%), band keratopathy (53.9%), and cataract (31.8%). Posterior complications were documented in 37.0% of eyes: 13.8% macular edema, 12.0% papillitis, 6.8% epiretinal membranes, 2.5% retinal vasculitis, 1.7% retinal detachment. At OCT examination 25.0% of eyes presented macular edema; macular sensitivity by MP-1 was ≤16.5 dB in 25.0% of eyes.

Conclusions: Visual prognosis is good despite ocular complications. Incidence of macular edema seems to be higher when using OCT. Microperimetry may represent a useful tool in detecting alteration in retinal sensitivity that may supplement visual acuity in the follow-up of macular edema.     

幼年特发性关节炎患儿白内障术后眼内 炎症与血清细胞因子的关系

目的：探讨Th17、Th1和调节性T细胞相关促炎细胞因子在幼年特发性关节炎（JIA）患儿白内障术 后眼内炎症反应中的作用。方法：回顾性病例对照研究。收集2013年7月至2018年3月于内蒙古自 治区人民医院眼科就诊的32例JIA患儿（JIA组）和35例先天性白内障患儿（先天性白内障组）在白内 障手术前及术后1、7、30、90 d的血清以及手术开始时的房水。采用多组别免疫分析系统测定血清 和房水中白细胞介素-1β（IL-1β）、IL-6、IL-10、IL-23、IL-27、IL-17和干扰素-γ（IFN-γ）的蛋白水 平。激光蛋白细胞检测仪用于定量眼内炎症。采用重复测量方差分析对数据进行统计学分析,用 Spearman相关系数法计算JIA患者血清IL-6、IL-23和IFN-γ水平与房水闪辉值和细胞计数之间的相 关性。结果：JIA组术后1 d血清IL-23 [（612±190）pg/ml]、IL-6 [（305±82）pg/ml]、IFN-γ [（172± 43）pg/ml]、IL-10 [（202±114）pg/ml]、IL-27 [（110±43）pg/ml]和IL-1β [（106±27）pg/ml]均明显升 高,术后90 d逐渐恢复至术前水平。JIA组术前及术后1、7、30、90 d血清IL-1β、IL-6、IL-23、IL- 27、IL-10和IFN-γ均明显高于先天性白内障组。JIA患者血清的IL-6水平（r=0.085,P=0.002）、IFN-γ 水平（r=0.741,P=0.021）、IL-23水平（r=0.622,P=0.028）与房水闪辉值均有相关性,IL-6水平（r=0.729, P=0.006）、IFN-γ水平（r=0.669,P=0.019）与前房细胞数均有相关性,IL-23水平与前房细胞数无明显 相关性（r=0.646,P=0.051）。结论：Th17、Th1和调节性T细胞相关促炎细胞因子IL-6和IFN-γ在JIA 患儿血清中水平的升高可反映患者眼内炎症活动情况,血清IL-23、IL-10、IL-27和IL-1β的变化也可 以用于评估JIA患者白内障术后眼内炎症的情况。     

Occurrence of and Risk Factors for Ocular Hypertension and Secondary Glaucoma in Juvenile Idiopathic Arthritis-associated Uveitis

Purpose: To describe the incidence of ocular hypertension (OHT) and secondary glaucoma (SG) in JIA-associated uveitis, identify risk factors for development of these complications, and describe their effect on visual outcomes.

Methods: A retrospective cohort of 108 patients (196 eyes) with JIA-associated uveitis seen over 30 years at an academic practice.

Results: Of examined eyes, 40% had OHT or SG at presentation. These eyes had a nearly three-fold higher incidence of legal blindness during follow-up, compared with eyes without OHT or SG. An additional 41 eyes developed OHT or SG during follow-up. Presenting with anterior uveitis, active inflammation, and using systemic corticosteroids were risk factors for developing OHT, while use of immunosuppressive medication at presentation reduced this risk. Risk factors for developing SG included anterior uveitis and use of systemic corticosteroids.

Conclusions: OHT and SG were common in patients with JIA-associated uveitis. Use of immunosuppressive drugs may decrease the risk of developing OHT.     

Recent advances in uveitis of juvenile idiopathic arthritis

Chronic scarring-type uveitis is a frequent extra-articular manifestation of juvenile idiopathic arthritis. It occurs in about 20% of children with this disease, commencing typically within a few years from its onset. The risk of uveitis is greatest in antinuclear antibody-positive girls with early onset oligoarthritis. The classic clinical picture is chronic bilateral anterior uveitis, usually asymptomatic until substantial damage to intraocular structures occurs. In view of the asymptomatic nature of the condition, routine screening of juvenile idiopathic arthritis patients 2-4 times a year is crucial to prevent complications. The treatment consists of topical corticosteroids and mydriatics, in severe cases with immunosuppressive agents, and surgical management of complications. Although the prognosis of uveitis is improving, there are cases refractory to standard regimens. Patients in whom uveitis commences prior to the onset of arthritis present a special problem.     

Cataract Surgery with Primary Lens Implantation in Children with Chronic Uveitis

Purpose: To evaluate the evolution of chronic uveitis in children undergoing cataract surgery with primary intraocular lens (IOL) implantation.

Methods: Twelve children with chronic uveitis underwent cataract surgery with primary posterior chamber intraocular lens (IOL) implantation.

Results: Fourteen eyes were implanted with a foldable hydrophobic acrylic IOL. The mean follow-up was 35.39 months (8.72–69.57). The mean BCDVA before surgery and at the end of follow-up was 1.11 (0.40–2.30; SD: 0.57) and 0.48 (0–3; SD: 0.77; p=0.007) respectively. The mean oral corticosteroids dosage after surgery and at the end of follow-up was 0.80 mg/kg/day (SD: 0.37) and 0.17 mg/kg/day (SD: 0.24; p=0.001) respectively. All patients except one were treated with methotrexate. Four patients (5 eyes) were additionally treated with anti-tumor necrosis factor agent.

Conclusions: Cataract surgery with primary posterior chamber hydrophobic IOL implantation is possible and leads to a good visual recovery in cases of pediatric chronic uveitis. This surgery requires aggressive anti-inflammatory management with immunosuppressive drugs to control inflammation and reduce the corticosteroids dosage.     

Elevated laser flare values correlate with complicated course of anterior uveitis in patients with juvenile idiopathic arthritis

Purpose: To evaluate the prognostic value of anterior chamber (AC) laser flare (LF) in uveitis associated with juvenile idiopathic arthritis (JIA). Methods: Monocentre, retrospective study of 150 JIA children (girls n = 107, 71.3%) with unilateral or bilateral chronic anterior uveitis (statistical analysis of one eye per patient). LF values (KOWA FM‐500), visual acuity, intraocular pressure, glaucoma treatment and uveitis complications were investigated longitudinally. Results: Patients were followed up for a mean of 8.7 months (range 1–36). High LF values correlated with poor visual acuity (p < 0.0001). Patients with low LF values (LF ≤ 20 photon units per millisecond) less often required glaucoma medication (p = 0.0005) or surgery (p = 0.01) and showed a lower prevalence of cataract, band keratopathy, posterior synechiae, epiretinal membrane, optic disc oedema and glaucoma/ocular hypertension (p < 0.05, each). Baseline LF > 20 photon units per millisecond was a better prognosticator for the development of subsequent complications than baseline AC cells (p = 0.04). Conclusions: High LF values in patients with JIA uveitis are associated with poor vision and a higher prevalence of uveitis complications.     

幼年特发性关节炎并发葡萄膜炎的治疗新进展

近年来,幼年特发性关节炎并发葡萄膜炎的治疗取得了一定的进展,但由于疾病的复发率较高,病情较复杂,使该病较难控制.现有药物的副作用较多,难以有效地控制疾病的发展,探索新的治疗方案是目前的研究热点.本文我们就目前已知的治疗方案以及未来可能应用于临床的治疗方法进行综述.     

Juvenile Idiopathic Arthritis Associated Uveitis in Adults: A Case Series

Purpose: To report a series of adults with uveitis following juvenile idiopathic arthritis (JIA) and uveitis as children.

Methods: The clinical features, treatment, complications, and visual outcome were ascertained for 17 patients at a single centre.

Results: Seventeen adults with previously diagnosed JIA and ongoing uveitis (30 eyes) were identified. All required at least topical steroids. The complication rate was high (15 patients, 23 eyes), most frequently cataract (57%), glaucoma (33%), and posterior synechiae (30%). The rate of visual acuity loss to 6/12 threshold (6/12 or worse) for patients with uveitis?<?15 years (Group A) was 13.3%, (and 6.7% to 6/60 threshold) and for patients with uveitis >15 years (Group B) was 26.7% (and 20% to 6/60 threshold). Overall, the rate of visual acuity loss to 6/12 threshold was 20% (6 eyes) and to 6/60 threshold, 13.3% (4 eyes).

Conclusions: JIA may be associated with ongoing uveitis and complications in adulthood.