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.
C hronic anterior uveitis (CAU) is the most common form of uveitis in children. This inflammatory intraocular disease can follow a severe, debilitating course with vision-threatening ocular complications. CAU can be associated with a variety of systemic conditions, among which juvenile idiopathic arthritis (JIA) is the most frequent and well studied. Up to 30% of children with JIA will eventually develop CAU. , In contrast, idiopathic CAU (iCAU) accounts for approximately 30% to 40% of pediatric anterior uveitis cases, but remains poorly understood. , ,
No clinical distinction can be made between iCAU and juvenile idiopathic arthritis−associated uveitis (JIA-U) based on ophthalmological characteristics. In addition, we recently found that these 2 uveitis subtypes have shared risk alleles. Therefore, it is not surprising that both the Childhood Arthritis and Rheumatology Research Alliance (CARRA) standardized consensus treatment plans for comparative effectiveness research and recent therapy recommendations indicate that iCAU and JIA-U should be treated using similar strategies. ,
Currently, the initial treatment for pediatric uveitis consists of topical corticosteroids. However, long-term use of topical corticosteroids can lead to sight-threatening complications such as cataracts and/or secondary glaucoma. , Moreover, systemic corticosteroids can have additional adverse effects on the child’s general health. Therefore, patients who do not respond to initial therapy, who develop corticosteroid dependency, or who present with a severe and/or persistent disease are typically switched to immunomodulatory therapy (IMT); however, IMT can fail in 25% to 50% of cases, leading to the need for additional treatment with biological agents. ,
Similar to uveitis in JIA-U, uveitis in iCAU is typically asymptomatic. In the case of JIA-U, however, routine ophthalmological screening of children with JIA can often reveal the presence of asymptomatic uveitis, and early detection and treatment can help prevent ocular complications such as cataracts, secondary glaucoma, and posterior synechiae. In contrast, children with iCAU and children with JIA who develop uveitis prior to the onset of arthritis are not typically subjected to routine screening for uveitis. We therefore hypothesized that children with iCAU are more likely to present with complications compared to children with JIA-U. To test this hypothesis, we conducted a retrospective cohort study in which we examined the medical records of children with iCAU and children with JIA-U and compared their clinical course, visual outcome, ocular complications, and treatment. Comparing these 2 patient groups can provide important insights into whether these 2 types of CAU can be treated using similar approaches. These findings can also be used to guide the treatment of pediatric CAU.
In this retrospective cohort study, the clinical data of pediatric patients with iCAU and a previously reported cohort of pediatric patients with JIA-U were obtained from a similar time period (from 1997 through 2020). Patients were included if they were diagnosed with uveitis before 16 years of age and had a minimum follow-up of 6 months. The initial diagnosis of uveitis was established by a trained uveitis specialist at the Department of Ophthalmology, University Medical Center Utrecht, in accordance with the Standardization of Uveitis Nomenclature (SUN) criteria. All patients with uveitis were screened by a pediatric rheumatologist, and JIA was diagnosed in accordance with the criteria established by the International League of Associations for Rheumatology. , The patients who were diagnosed with JIA were also screened for development of uveitis in accordance with the guidelines established by the American Academy of Pediatrics. , iCAU was defined as a diagnosis of uveitis in a patient for whom JIA was not documented during the study period. All patients were seen by a pediatric rheumatologist, and patients whose CAU was caused by infection, neoplasm, or trauma were excluded. The JIA-U patients were selected from a previously reported dataset , (for patients who were diagnosed with uveitis prior to 2010) and a new dataset (with patients who were diagnosed with uveitis from 2010 through 2020) and were age-matched and matched to the date of uveitis diagnosis in the iCAU cohort. The maximum time interval of the date of uveitis diagnosis between 2 matched patients was 2 years. Matching to the date of uveitis diagnosis is performed because literature demonstrates better visual outcomes in the “biologic era” compared to earlier studies. The study adhered to the tenets of the Declaration of Helsinki and was approved by the Medical Ethics Research Committee of the University Medical Center Utrecht (protocol number: 19/178).
Data extracted from the patients’ electronic medical records included: patient demographics, uveitis characteristics, age at onset of JIA, laboratory results for antinuclear antibody (ANA) testing, ocular complications, best-corrected visual acuity (BCVA), and anti-inflammatory therapy. The following clinical data were also extracted: posterior synechiae, band keratopathy, cataract requiring surgery, secondary glaucoma, glaucoma surgery, cystoid macular edema (CME), and papillitis. Systemic treatment with corticosteroids, IMT, and/or biological agents was also documented. Patients who received methotrexate (MTX) received a starting dose of 10 to 15 mg/m 2 per week orally or subcutaneously. Patients who were additionally treated with adalimumab received a dose of 20 mg or 40 mg (for patients weighing <30 kg or ≥30 kg, respectively) administered as a subcutaneous injection every 2 weeks, and the MTX dose was kept at 10-15 mg/m 2 per week. Prior to 2010, a grade of ≥1+ anterior chamber (AC) cells was used to intensify treatment in order to gain inflammatory control. From 2010 and onward, additional indicators were added, including adverse effects from topical corticosteroids at a dose of >2 drops and/or the presence of new inflammation-related complications. , Because of difficulties objectively measuring cataract formation, we used “cataract requiring surgery” to indicate the presence of cataract. Secondary glaucoma was defined using the international consensus established by the World Glaucoma Association and the Childhood Glaucoma Research Network. CME was defined as the presence of macular thickening with cyst formation visible on fundoscopy, fluorescein angiography (prior to 2003), and/or macular optical coherence tomography (OCT). Papillitis was defined as blurring of the optic disc margins visible on fundoscopy and/or the presence of optic disc hyperfluorescence on fluorescein angiography scored in accordance with the Angiography Scoring for Uveitis Working Group. Visual impairment was defined as BCVA between 20/50 and 20/200, and legal blindness was defined either as BCVA ≤20/200 or a visual field consisting of less than 10 degrees, in accordance with the definition established by the World Health Organization (WHO).
The primary outcome was the difference in the number of complications between the patients with iCAU and the patients with JIA-U at the diagnosis of uveitis and after 1 and 5 years of follow-up. The secondary outcomes were the differences in visual acuity and systemic treatment between the 2 groups.
Descriptive statistics are used to report baseline characteristics and treatment, and were analyzed per patient. Except where indicated otherwise, data are represented as the median and interquartile range (IQR). The Pearson χ 2 or Fisher exact test was used for the univariate analysis of categorical variables to test for differences between the 2 groups. The Wilcoxon rank-sum test was used for medians. Snellen BCVA was converted to the logarithm of minimal angle of resolution (logMAR) for statistical analysis and converted back to Snellen BCVA for data presentation. Statistical analysis of ocular complications and BCVA were performed “by eye”, including only affected eyes with 5-year follow-up data, with correction for paired eyes. A generalized estimating equation (GEE) was used to adjust for the correlation between 2 eyes in patients with bilateral disease (paired eyes). Cox proportional hazard regression was applied in multivariate analyses, including all affected eyes with a correction of standard error with clustering using a robust method. Differences with a P value of less than .05 were considered significant. All tests were 2-tailed, and all statistical analyses were performed using RStudio software version 4.0.3 (RStudio Inc, Boston, Massachusetts, USA).
A total of 48 patients with iCAU (with 83 affected eyes) and 48 age-matched patients with JIA-U (with 73 affected eyes) were included in our analysis. As shown in Table 1 , the 2 groups did not differ significantly with respect to general patient characteristics.
|Type of CAU|
|Patient Characteristic||iCAU||JIA-U||P Value|
|Total no. of patients||48||48|
|Total no. of eyes||83||73|
|Bilateral disease, n (%)||35 (73)||25 (52)||.058 a|
|Male sex, n (%)||14 (29)||15 (31)||1 a|
|ANA-seropositive, n (%)||30 (63)||37 (77)||.171 a|
|Age, y, at uveitis diagnosis, median (IQR)||7.8 (5.9-11.1)||7.8 (5.8-9.5)||.818 b|
|Follow-up time, y, median (IQR)||5.0 (2.5-8.4)||6.1 (3.5-9.0)||.524 b|
The number and percentage of ocular complications reported at the diagnosis of uveitis and after 1 and 5 years of follow-up are summarized in Table 2 . At diagnosis, the patients in the iCAU group had a generally more complicated presentation compared to the JIA-U group, with significant differences in posterior synechiae (45% vs 14%, respectively; P < .001) and band keratopathy (19% vs 7%, respectively; P < .05). At 5 years and after adjusting for the correlation of paired eyes, the patients in the iCAU group had a higher prevalence of posterior synechiae (68% vs 31%; P = .002) and a higher prevalence of cataract requiring surgery (51% vs 20%; P = .01); we found no other differences between the 2 groups with respect to complications at the 5-year follow-up.
|Type of CAU|
|At Diagnosis||No. of eyes||83||73|
|No complications||44 (53)||57 (78)||.001 a|
|Posterior synechiae, n (%)||37 (45)||10 (14)||<.001 a|
|Band keratopathy, n (%)||16 (19)||5 (7)||.432 a|
|Cataract surgery, n (%)||0||0||NA|
|Secondary glaucoma, n (%)||1 (1)||1 (1)||.927 b|
|Glaucoma surgery, n (%)||0||1 (1)||.468 b|
|CME, n (%)||3 (4)||4 (5)||.940 b|
|Papillitis, n (%)||7 (8)||6 (8)||.829 a|
|After 1 y of Follow-up||No. of eyes||79||71|
|No complications||39 (49)||39 (55)||.605 a|
|Posterior synechiae, n (%)||42 (53)||14 (20)||<.001 a|
|Band keratopathy, n (%)||18 (23)||7 (10)||.393 a|
|Cataract surgery, n (%)||11 (14)||5 (7)||.046 a|
|Secondary glaucoma, n (%)||4 (5)||1 (1)||.573 b|
|Glaucoma surgery, n (%)||1 (1)||3 (4)||.680 b|
|CME, n (%)||6 (8)||7 (10)||.979 b|
|Papillitis, n (%)||8 (10)||9 (13)||.751 a|
|After 5 y of Follow-up||No. of eyes||41||51|
|No complications||14 (34)||20 (39)||.525 a|
|Posterior synechiae, n (%)||28 (68)||16 (31)||.002 a|
|Band keratopathy, n (%)||14 (34)||11 (22)||.236 a|
|Cataract surgery, n (%)||21 (51)||10 (20)||.012 a|
|Secondary glaucoma, n (%)||12 (29)||10 (20)||.494 a|
|Glaucoma surgery, n (%)||13 (32)||12 (24)||.731 a|
|CME, n (%)||8 (20)||8 (16)||.982 a|
|Papillitis, n (%)||10 (24)||12 (20)||.951 a|