Purpose
To analyze visual outcome in uveitis associated with juvenile idiopathic arthritis (JIA) according to age of onset of uveitis, gender, and initial manifestation of JIA.
Design
Retrospective nonrandomized interventional case series.
Methods
Visual outcome of 117 affected eyes (65 patients) with JIA-associated uveitis was noted at onset of uveitis and after 1, 3, and 5 years. Visual outcome was analyzed according to gender, age of onset of JIA-associated uveitis (<7 years and >7 years), and initial manifestation of JIA (as uveitis or as arthritis). Linear and logistic regression with generalized estimating equation (GEE) was performed.
Results
Median age of onset of uveitis was 4.2 years (range 1.5–16). Female-to-male ratio was 3:1. In 15 children (23%) uveitis was diagnosed before arthritis. Visual acuity of boys was significantly worse at 1 and 3 years of follow-up (both P ≤ .03) but not at 5 years of follow-up ( P = .45). Until 3 years after the diagnosis of uveitis, children with atypical initial manifestation of JIA (uveitis before arthritis) had significantly worse visual acuity compared with children in whom uveitis debuted after arthritis (all P ≤ .05). No difference in vision between younger-onset (<7 years) and older-onset (>7 years) groups was noted. Blindness was independently associated with male gender (odds ratio [OR] = 6.61; 95% CI: 1.02–42.98; P = .048).
Conclusions
Male gender was an independent risk factor for poor visual prognosis in JIA-associated uveitis. Children in whom uveitis is being diagnosed before arthritis have significantly worse vision until 3 years after uveitis onset.
Uveitis associated with juvenile idiopathic arthritis (JIA) is the most common form of uveitis in childhood. JIA-associated uveitis typically has an asymptomatic, insidious onset and a potentially severe and complicated course. The complications during the course of JIA-associated uveitis can be sight-threatening. The risk of amblyopia development attributable to vision-disturbing complications and media opacities deserves a special awareness in this group of young patients.
Despite the current guidelines for the screening program and administration of new immunosuppressive agents, JIA-associated uveitis continues to be a potentially blinding condition. Although some centers report very good visual outcome, some of the recent studies still show that up to 24% of patients end up blind or with severe visual impairment.
Several authors contributed to the identification of early prognostic factors associated with poor visual outcome in JIA-associated uveitis. Although the results of the studies are not always conclusive, the following risk factors were pointed out as negative for visual outcome: young age of onset of uveitis, severity of uveitis at first examination, signs of vitreous involvement, and short interval between the diagnosis of arthritis and uveitis.
The prognostic role of gender in visual outcome of JIA-associated uveitis is still controversial. In this study we evaluate the role of gender, age of onset of uveitis, initial manifestation of JIA, and other early prognostic factors for visual outcome in JIA-associated uveitis.
Patients and Methods
The same database as our other study on complications in JIA-associated uveitis. The medical records of 65 pediatric patients (117 affected eyes) with uveitis associated with JIA or ANA-positive anterior uveitis were reviewed. The diagnosis of JIA was based on the criteria of the International League against Rheumatism. All patients were examined by a pediatric rheumatologist who confirmed the diagnosis of JIA in 65 patients.
Evaluation of uveitis was made according to the criteria of the International Uveitis Study Group. In addition to examination by an ophthalmologist who is specialized in childhood uveitis, all children in our clinics were being examined by an orthoptist at the initial visit and regularly during the follow-up for screening of amblyopia. In this study amblyopia was scored only if a decrease in vision could not be clinically explained by vision-threatening complications of uveitis (media opacities and macular edema) at that moment.
In addition to the data gathered in our work on complications in JIA-associated uveitis, best-corrected visual acuities (BCVAs) at standard points of time were assessed. Duration of uveitis was calculated from the date of diagnosis of uveitis.
The BCVAs were noted at the first presentation and after 1, 3, and 5 years of follow-up. We have categorized BCVAs according to definitions that are used as guidelines for obtaining a driver’s license in various countries. These definitions are similar to definitions used by other studies: BCVA of 20/40 or better was defined as good, BCVA between 20/50 and 20/100 was defined as impaired, and BCVA of 20/200 or worse was defined as blindness. Additionally we scored a visual field of less than 10 degrees as blindness.
We converted Snellen BCVAs into the logarithm of the minimal angle of resolution scale (logMAR) for statistical analysis and converted it back to Snellen BCVAs for data presentation. In the analysis of visual outcome, only the eyes with vision loss attributable to uveitis or related complications were included.
Patients were subdivided according to their age at onset of uveitis, into a young-onset (uveitis onset <7 years of age) or old-onset group (uveitis onset >7 years of age). This cut-off was chosen because of the higher likelihood of amblyopia developing before the age of 7. Two different types of initial manifestation of JIA were distinguished: initial manifestation as arthritis with later diagnosis of uveitis (classic); and initial manifestation with uveitis followed later by development of arthritis, making the diagnosis of JIA possible. Children in whom the signs of uveitis were present at the initial eye screening after the diagnosis of JIA were considered as classic presentation.
Statistical analysis of the data was performed with SPSS 15.0.1 (SPSS Inc, Chicago, Illinois, USA). We performed the analysis “by eye” including all affected eyes in the analysis. Correction for analysis of paired eyes was performed using generalized estimating equations (GEE). However, analysis “by patient” was used in comparison of baseline constant host characteristics between subgroups: laterality, antinuclear antibody (ANA) status, administration of systemic therapy, duration of follow-up. The Pearson χ 2 test or Fisher exact test was used for univariate analysis of categorical variables. LogMAR BCVAs at different points in time were compared using linear regression with GEE as adjustment for paired eyes in the analysis. Binary logistic regression with GEE was applied for multivariate analysis to identify independent predictive factors of blindness. In the multivariate analysis we entered baseline variables with P ≤ .05 in univariate analysis and clinically significant potential confounders. Baseline variables that were associated with blindness in univariate analysis included gender, initial manifestation of JIA, and initial visual acuity. The model was additionally adjusted for age of onset of uveitis (as numeric variable) and duration of uveitis. P values of less than .05 were considered statistically significant. All significances were 2-tailed. In the presentation of the results we used the mean if the data were normally distributed (by Kolmogorov-Smirnov test; P > .05) and the median if not normally distributed.
Results
General Characteristics of the Study Population
One hundred seventeen eyes (65 patients) were affected by JIA-associated uveitis, with available data of BCVA over a period longer than 1 year of follow-up. Table 1 presents general clinical characteristics of the whole study population with analysis of subgroups, according to age of onset of uveitis, gender, and initial manifestation of JIA. The typical manifestation of JIA-associated uveitis as chronic or recurrent anterior uveitis was observed in 116 eyes (99%), and in 1 eye (1%) panuveitis was present. Bilateral disease was more frequent in the younger-onset group: 43 of 48 patients (88%), versus 10 of 17 patients (59%) in the older-onset group ( P = .03). Time between the diagnosis of arthritis and uveitis ranged from 0 to 12.3 years with a median of 0.7 years ( Table 1 ). This interval was significantly shorter in the younger-onset group compared with the older-onset group and in boys compared with girls (both P = .02; Table 1 ). Children initially presenting with uveitis were less frequently ANA positive compared to children who presented with arthritis (73% vs 94%; P = .05). Follow-up was significantly longer in boys compared to girls (median 11.0 vs 7.2 years; P = .05).
| Characteristics | Age of Uveitis Onset | P Value | Gender | P Value | Initial Manifestation of JIA | P Value | |||
|---|---|---|---|---|---|---|---|---|---|
| 0–7 Years N = 48 (%) | 7–16 Years N = 17 (%) | M N = 18 (%) | F N = 47 (%) | Uveitis N = 15 (%) | Arthritis N = 50 (%) | ||||
| Female subjects, n (%) | 35 (73) | 12 (71) | >.99 | NA | 47 (100) | NC | 7 (47) | 40 (80) | .02 b |
| Age of onset, median (range) | NC | NC | NC | 4.3 (1.7–13.8) | 4.2 (1.7–16.0) | .48 | 4.0 (1.7–12.1) | 4.5 (1.5–16.0) | .68 |
| Bilateral (%) | 42 (88) | 10 (59) | .03 b | 16 (89) | 36 (77) | .33 | 14 (93) | 38 (76) | .27 |
| Time between diagnosis of arthritis and uveitis, a median (range) | 0.7 (0–6.7) | 2.0 (0–12.3) | .02 b | 0.3 (0–5.0) | 1.0 (0–12.3) | .02 b | 0.3 (0.1–7.3) | 0.8 (0–12.3) | .86 |
| Uveitis as initial manifestation of JIA | 12 (25) | 3 (18) | .74 | 8 (44) | 7 (15) | .02 b | 15 (100) | NA | NC |
| Follow-up, a median (range) | 8.3 (1.1–27.5) | 7.2 (1.2–23.1) | .51 | 11.0 (1.1–27.5) | 7.2 (1.1–22.9) | .05 b | 12.6 (1.1–27.5) | 6.1 (1.1–23.1) | .07 |
| ANA-seropositive | 42 (91) | 13 (81) | .36 | 16 (94) | 39 (87) | .66 | 11 (73) | 44 (94) | .05 b |
| Systemic corticosteroids | 18 (38) | 8 (47) | .53 | 8 (44) | 18 (39) | .78 | 10 (67) | 16 (33) | .02 b |
| Immunomodulatory therapy | 39 (81) | 12 (71) | .49 | 15 (83) | 36 (77) | .74 | 12 (80) | 39 (78) | >.99 |
Visual Outcome
Median BCVAs at standard points of follow-up, analyzed according to the age of uveitis onset, gender, and initial manifestation of JIA, are presented in Table 2 . Categorized BCVAs for the whole study population and the subgroups at standard points of follow-up are presented in Table 3 .
| BCVA | Total | Age of Uveitis Onset | P Value b | Gender | P Value b | Initial Manifestation of JIA | P Value b | |||
|---|---|---|---|---|---|---|---|---|---|---|
| 0–7 Years | 7–16 Years | M | F | Uveitis | Arthritis | |||||
| At onset | ||||||||||
| No of eyes/patients = 108/59 | ||||||||||
| Median a | 0.8 | 0.8 | 0.8 | .66 | 0.6 | 0.8 | .06 | 0.4 | 0.9 | <.01 c |
| 1 year of follow-up | ||||||||||
| No of eyes/patients = 101/56 | ||||||||||
| Median a | 1.0 | 1.0 | 1.0 | .27 | 0.9 | 1.0 | .02 c | 0.7 | 1.0 | .01 c |
| 3 years of follow-up | ||||||||||
| No of eyes/patients = 79/43 | ||||||||||
| Median a | 0.8 | 0.8 | 1.0 | .07 | 0.5 | 1.0 | .03 c | 0.5 | 1.0 | .05 c |
| 5 years of follow-up | ||||||||||
| No of eyes/patients = 60/33 | ||||||||||
| Median a | 0.7 | 0.7 | 0.6 | .50 | 0.6 | 0.7 | .45 | 0.6 | 0.8 | .67 |
a To compute the median of VAs all decimal Snellen BCVAs were transformed to their logMAR equivalents and afterwards back to decimal BCVAs, which are presented.
b P values are adjusted for the usage of paired eyes in the analysis.
| BCVA | Total Number of Affected Eyes (%± 95% CI) | Age of Uveitis Onset | P Value a | Gender | P Value a | Initial Manifestation of JIA | P Value a | |||
|---|---|---|---|---|---|---|---|---|---|---|
| 0–7 Years | 7–16 Years | M | F | Uveitis | Arthritis | |||||
| At onset | ||||||||||
| Number of eyes = 103 | ||||||||||
| Number of patients = 59 | ||||||||||
| ≤20/200 (%) | 11 (11 ± 5.7) | 10 (13) | 1 (4) | .31 | 6 (18) | 5 (7) | .11 | 7 (25) | 4 (5) | <.01 b |
| 20/100–20/50 (%) | 18 (17 ± 7.4) | 12 (15) | 6 (25) | 8 (24) | 10 (15) | 9 (32) | 9 (12) | |||
| ≥20/40 (%) | 74 (72 ± 8.6) | 57 (72) | 17 (71) | 20 (59) | 54 (78) | 12 (43) | 62 (83) | |||
| 1 year of follow-up | ||||||||||
| Number of eyes = 95 | ||||||||||
| Number of patients = 56 | ||||||||||
| ≤20/200 (%) | 9 (10 ± 5.9) | 8 (11) | 1 (4) | .60 | 7 (22) | 2 (3) | .01 b | 6 (23) | 3 (4) | .02 b |
| 20/100–20/50 (%) | 9 (10 ± 6.1) | 6 (8) | 3 (13) | 4 (13) | 5 (8) | 3 (12) | 6 (9) | |||
| ≥20/40 (%) | 77 (80 ± 7.9) | 58 (81) | 19 (83) | 21 (66) | 56 (89) | 17 (65) | 60 (87) | |||
| 3 years of follow-up | ||||||||||
| Number of eyes = 78 | ||||||||||
| Number of patients = 43 | ||||||||||
| ≤20/200 (%) | 3 (4 ± 4.3) | 3 (5) | 0 (0) | .51 | 2 (7) | 1 (2) | .01 b | 2 (11) | 1 (2) | .06 b |
| 20/100–20/50 (%) | 6 (8 ± 6.0) | 6 (10) | 0 (0) | 5 (19) | 1 (2) | 3 (16) | 3 (5) | |||
| ≥20/40 (%) | 69 (89 ± 6.9) | 53 (86) | 16 (100) | 20 (74) | 49 (96) | 14 (74) | 55 (93) | |||
| 5 years of follow-up | ||||||||||
| Number of eyes = 58 | ||||||||||
| Number of patients = 33 | ||||||||||
| ≤20/200 (%) | 4 (7 ± 6.5) | 3 (7) | 1 (8) | >.99 | 0 (0) | 4 (10) | .37 | 0 (0) | 4 (9) | .68 |
| 20/100–20/50 (%) | 10 (17 ± 9.5) | 8 (18) | 2 (15) | 4 (21) | 6 (15) | 3 (19) | 7 (17) | |||
| ≥20/40(%) | 44 (76 ± 10.7) | 34 (76) | 10 (77) | 15 (79) | 29 (74) | 13 (81) | 31 (74) | |||
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