Risk Factors for Loss of Visual Acuity
among Patients with Uveitis Associated with
Juvenile Idiopathic Arthritis: The Systemic
Immunosuppressive Therapy for Eye
Anthony C. Gregory II, MD, MPH,1John H. Kempen, MD, PhD,2,3Ebenezer Daniel, MBBS, MPH, PhD,2
R. Oktay Kaçmaz, MD, MPH,4,5C. Stephen Foster, MD,5,6Douglas A. Jabs, MD, MBA,7,8,9
Grace A. Levy-Clarke, MD,10Robert B. Nussenblatt, MD, MPH,10James T. Rosenbaum, MD,11,12
Eric B. Suhler, MD, MPH,11,13Jennifer E. Thorne, MD, PhD,1,7for the Systemic Immunosuppressive Therapy
for Eye Diseases Cohort Study Research Group
in patients with juvenile idiopathic arthritis (JIA)–associated uveitis.
Multicenter retrospective cohort study.
A total of 327 patients (596 affected eyes) with JIA-associated uveitis managed at 5 tertiary
uveitis clinics in the United States.
Participants were identified from the Systemic Immunosuppressive Therapy for Eye Diseases
(SITE) cohort study. Demographic and clinical characteristics were obtained for every eye of every patient at
every visit via medical record review by trained expert reviewers.
Main Outcome Measures:
Loss of VA to 20/50 or to 20/200 or worse thresholds and the development of
At presentation, 240 eyes (40.3%) had a VA of ?20/50, 144 eyes (24.2%) had a VA of ?20/200, and
359 eyes (60.2%) had at least 1 ocular complication. The incidences of VA loss to the ?20/50 and ?20/200
thresholds were 0.18 and 0.09 per eye-year (EY), respectively; the incidence of developing at least 1 new ocular
complication over follow-up was 0.15/EY (95% confidence interval [CI], 0.13–0.17). However, among eyes with
uveitis that had no complications at presentation, the rate of developing at least 1 ocular complication during
follow-up was lower (0.04/EY; 95% CI, 0.02–0.06). Posterior synechiae, active uveitis, and prior intraocular
surgery were statistically significantly associated with VA to the ?20/50 and ?20/200 thresholds both at
presentation and during follow-up. Increasing (time-updated) anterior chamber cell grade was associated with
increased rates of visual loss in a dose-dependent fashion. Use of immunosuppressive drugs was associated
with a reduced risk of visual loss, particularly for the ?20/50 outcome (hazard ratio, 0.40; 95% CI, 0.21–0.75;
Ocular complications and vision loss were common in our cohort. Increasing uveitis activity
was associated with increased risk of vision loss, and use of immunosuppressive drugs was associated with
reduced risk of vision loss, suggesting that control of inflammation and use of immunosuppression may be
critical aspects in improving the outcomes of patients with JIA-related uveitis.
The author(s) have no proprietary or commercial interest in any materials discussed
in this article. Ophthalmology 2013;120:186–192 © 2013 by the American Academy of Ophthalmology.
To describe the incidence of and risk factors for visual acuity (VA) loss and ocular complications
Juvenile idiopathic arthritis (JIA) refers to a group of het-
erogeneous arthritides that begin before 16 years of age and
may be associated with uveitis, most commonly in patients
who have antinuclear antibodies.1–3Uveitis related to JIA is
an important cause of childhood uveitis in North America,4
with an estimated incidence of approximately 4.9 to 6.9 per
100 000 person-years (PYs) and an estimated prevalence of
13 to 30 per 100 000 population.4–9
Because JIA-associated uveitis typically has an indolent
and chronic course, children with this condition are at risk
for ocular morbidity and visual loss, particularly if referred
to a tertiary care setting late in the disease course.10,11
Structural ocular complications of JIA-related chronic uve-
itis include band keratopathy, posterior synechiae, cataract,
glaucoma, hypotony, macular edema, epiretinal membrane,
and optic disc edema, many of which lead to visual
© 2013 by the American Academy of Ophthalmology
Published by Elsevier Inc.
ISSN 0161-6420/13/$–see front matter
loss.2,3,6–17The reported risks of reduced visual acuity (VA)
to 20/50 range from 13% to 26% and of reduction to 20/200
range from 5% to 9% depending on series and practice
type.6–10,16,17Reported rates of VA loss from small- to
medium-sized series range from 0.10 to 0.12 per eye-year
(EY) for ?20/50 vision and 0.08/EY to 0.09/EY for vision
loss to ?20/200.10,12,16Previous studies have suggested that
even low-grade active inflammation is associated with an
increased risk of developing visual loss over time and that
use of immunomodulatory therapy (IMT) may reduce this
risk, presumably by achieving better control of the intraoc-
ular inflammation and thereby reducing rates of complica-
tions that decrease vision. However, the sample sizes of
these studies were relatively low, which has limited the
precision of the results,10,12and groups with possibly het-
erogeneous risk were lumped together and analyzed as a
group, making it unclear whether very low levels of inflam-
mation are associated with increased risk of poor outcome.
The Systemic Immunosuppressive Therapy for Eye Dis-
eases (SITE) cohort study18is a retrospective cohort study
conducted at 5 referral-based uveitis practices in the United
States, which provides a more extensive experience with the
outcomes of JIA than has been reported. The purpose of our
study was to analyze the incidence of and risk factors for
vision loss among the 327 patients (596 eyes) with JIA-
associated uveitis in SITE, with a particular interest in
evaluating the effect of low-grade active intraocular inflam-
mation and treatment with IMT.
Materials and Methods
The methods of the SITE cohort study have been described.18For
the purposes of this analysis, all patients from the SITE cohort who
were diagnosed with JIA19(or oligoarticular and rheumatoid
factor–negative polyarticular juvenile rheumatoid arthritis before
the publication of the newer criteria) and had an associated chronic
uveitis were included. Enthesis-related acute or recurrent alternat-
ing anterior uveitis was not included. The patients reported in this
article had been examined between January 1978 and December
2007 inclusive. All participating centers had approval from their
institutional review boards for the study.18
Data had been entered into a database using a computer-based
standardized data entry form set specifically prepared for the SITE
Study.18The system included quality-control checks, requiring
correction of potential errors in real time. Data evaluated in this
report include demographic characteristics, ophthalmologic exam-
ination findings, and all medications that patients (or eyes) were
receiving at each clinic visit, including dose and route of admin-
istration. Ophthalmologic examinations included measurement of
VA, intraocular pressure (IOP) assessment, and details regarding
the activity and complications of the uveitis.
Main Outcome Measures
Incidence rates of and risk factors for the loss of VA were the
primary outcomes. Loss of VA was evaluated among those at risk
as the first measurement of a VA of ?20/50 (visual impairment) or
?20/200 (legal blindness), thresholds according to recommenda-
tions of the Standardization of Uveitis Nomenclature Working
Group.20Ocular complications evaluated included posterior syn-
echiae, band keratopathy, ocular hypertension (IOP ?21 mmHg
and IOP ?30 mmHg were assessed), hypotony (IOP ?5 mmHg),
epiretinal membrane, and macular edema. In addition, the history
of ophthalmic surgeries was assessed, including cataract and glau-
coma surgery. All outcomes were assessed at every clinical visit.
Measurements of prevalent reduction of VA or ocular complica-
tions of inflammation were based on the presence of these char-
acteristics at the first study visit.
The frequencies of patient- and eye-specific characteristics were
tabulated. Visual acuities, recorded in the SITE dataset as Snellen
equivalents, were transformed to logarithm of the minimum angle
of resolution scores to facilitate analyses. Incidence rates were
calculated as the number of events divided by the number of PYs
or EYs at risk; 95% confidence intervals (CIs) were calculated for
each rate. Crude and adjusted hazard ratios (HRs) using Cox
regression models were calculated to assess both baseline and
longitudinal risk factors for the incidence of reduced VA to
?20/50 and to ?20/200.21P values were nominal and 2-sided.
Time-updated multiple regression models containing all exposure
variables with statistically significant associations for each VA
outcome and models generated by stepwise procedures with the
cutoff for inclusion in the final model of P ? 0.05 were con-
structed. All multiple regression models controlled for demo-
graphic characteristics, including age, gender, race, bilateral dis-
ease, and uveitis duration. All analyses accounted for correlation
between eyes in patients with bilateral disease using robust tech-
niques.22Analyses were performed with the Stata 9.0 statistical
package (Stata Corporation, College Station, TX).
Characteristics of the Study Population at
The demographic and clinical characteristics of the study popula-
tion are summarized in Table 1. A total of 327 patients with
JIA-related uveitis were included in the study. The median age of
diagnosis of JIA was 4.1 years, with a range from 4 months to 16.9
years. The follow-up duration ranged from 0 to 24 years, with a
median follow up of 2.62 years among patients seen more than
once. The majority of the participants were white (85.3%) and
female (80.1%). At presentation, 269 patients (82%) had bilateral
uveitis. Of the 596 affected eyes, 240 (40.3%) initially had a VA
of ?20/50 and 144 (24.2%) had a VA of ?20/200. At presenta-
tion, 35% of the eyes in this study had at least 1? anterior chamber
cell, and 29% of eyes had posterior synechiae. Sixty percent of
affected eyes (59% of patients) had at least 1 ocular complication,
20.6% had 2 ocular complications, and 7.2% of eyes had more than
2 ocular complications at the time of presentation.
Incidence of Visual Loss and Ocular
Table 2 summarizes the incidence rates for structural ocular com-
plications and VA loss observed during the follow-up period
(median duration of follow-up, 2.6 years; range, 1 month to 24
years or 767 PYs [1448 EYs of follow-up]). The incidence of
visual loss to the ?20/50 threshold was 0.20/PY (for either eye or
Gregory et al ? Outcomes in Juvenile Idiopathic Arthritis
0.18/EY [for affected eyes]). The incidence of visual loss to
?20/200 was 0.14/PY or 0.09/EY. Among patients with new VA
loss to 20/50 and 20/200, 54% and 62%, respectively, maintained
vision loss to this level for at least 2 visits (data not shown). During
the observed follow-up time, 40% of patients (37% of eyes)
developed at least 1 new ocular complication (rate ? 0.17/PY and
0.15/EY). Ocular hypertension (rate ? 0.17/PY and 0.10/EY),
band keratopathy (0.14/PY and 0.14/EY), and posterior synechiae
(0.12/PY and 0.10/EY) were the most common complications
Because it is possible that eyes of patients with 1 or more
ocular complications at presentation had more severe disease, we
evaluated the incidence of developing the first ocular complication
among uveitic eyes that had no ocular complications when the
patient entered the study. Among these eyes, the rate of developing
a first ocular complication during follow-up was 0.04/EY (95% CI,
0.02–0.06). This result was statistically significantly lower than
the overall rate of developing an ocular complication among all
uveitic eyes (rate ? 0.15/EY; 95% CI, 0.13–0.17; P ? 0.01).
Risk Factors for Loss of Visual Acuity
Table 3 summarizes the risk factors for the development of loss of
VA across the ?20/50 and the ?20/200 thresholds. After control-
ling for demographic characteristics, bilateral uveitis, and duration
of uveitis, the presence of posterior synechiae, abnormal IOP,
active uveitis (as indicated by ?1? cells in the anterior chamber
or presence of ?0.5? vitreous haze), and history of intraocular
surgery were all statistically significantly associated with an in-
creased risk of developing ?20/50 vision during follow-up. In
addition, the time-updated evaluation of presence of anterior
chamber cell showed a dose-response–type relationship as dem-
onstrated by an increased risk of developing ?20/50 VA in both
the crude and adjusted regression models. The presence of any
band keratopathy at presentation was associated with an increased
risk of incident ?20/50 vision in the univariate analyses, but was
not statistically significant after adjusting for the other variables in
the multiple regression model (HR, 1.20; 95% CI, 0.97–1.49; P ?
0.10). Use of any corticosteroids over follow-up also was associ-
ated with visual loss to ?20/50 (adjusted HR, 1.38, 95% CI,
1.11–1.71; P?0.01), which arose from patients who were using
oral corticosteroids (adjusted HR for oral corticosteroids, 1.43;
95% CI, 1.15–1.79; P?0.01) rather than topical corticosteroids
(adjusted HR, 0.67; 95% CI, 0.17–2.70; P ? 0.57). Use of IMT
evaluated longitudinally over follow-up time was associated with
a statistically significant decrease in the risk of VA loss to ?20/50
after controlling for confounding variables (HR, 0.40; 95% CI,
For the ?20/200 VA outcome, risk factor analysis revealed that
the presence of posterior synechiae, active uveitis (as defined
previously), band keratopathy, oral corticosteroid use, and prior
intraocular surgery were associated with increased incidence (Ta-
ble 3). The presence of anterior chamber cells evaluated in a
time-dependent manner demonstrated a dose-dependent increase
in the risk of developing ?20/200 VA, whereas time-updated
abnormal IOP did not. When ocular hypertension and hypotony
were reevaluated as separate risk factors, neither was statistically
significantly associated with an increased risk of ?20/200 VA. In
the adjusted model (controlling for demographic characteristics,
duration of uveitis, VA at presentation, active uveitis, posterior
synechiae, history of surgery, and use of oral corticosteroids), use
of IMT evaluated longitudinally over follow-up time was associ-
ated with a tendency toward decreased incidence of ?20/200 VA
(adjusted HR, 0.80; 95% CI, 0.62–1.02; P ? 0.08).
Separate analyses evaluating risk factors only at the presenting
visit were performed for both VA outcomes and yielded similar
results. Furthermore, stepwise regression models also were per-
formed to evaluate the effectiveness of IMT, and these models did
not alter the results presented (data not shown).
Table 1. Characteristics of Patients with Juvenile Idiopathic
Arthritis and Uveitis at Presentation
Patient Characteristics (N?327)Median (yrs) Range (yrs)
Age at diagnosis of JIA
Age at first clinic visit
Eye-specific characteristics (N?596)
Prior eye surgery§
AC ? anterior chamber; JIA ? juvenile idiopathic arthritis; VA ? visual
*?20/50 ? logarithm of the minimum angle of resolution (logMAR)
?0.4, ?20/200 ? logMAR ?1.0; logMAR ? –log10(VA fraction mini-
mal angle of resolution).
†Vitreous haze gradings: 1? ? mild, 2? ? substantial, 3? ? partially
obscuring optic nerve, 4? ? unable to see optic nerve.
‡Any complication includes posterior synechiae, band keratopathy, mac-
ular edema, epiretinal membrane, hypotony, or ocular hypertension.
§Prior eye surgery includes cataract, glaucoma tube shunt, or trabeculec-
Volume 120, Number 1, January 2013
In this large retrospective cohort of patients with JIA-
associated uveitis, we assessed the incidence of VA loss and
ocular complications and found that the time-updated pres-
ence of posterior synechiae, active anterior chamber inflam-
mation, and intraocular surgery were associated with in-
creased risk of incident vision loss across both VA
thresholds (?20/50 and ?20/200) in a statistically signifi-
cant fashion. These findings are consistent with the pub-
lished literature.2,4,6–13,15,16Furthermore, our results dem-
onstrated a “dose-response” relationship between the
severity of anterior chamber cell grade and the risk for VA
loss during follow-up, particularly for anterior chamber cell
of 1? or greater. This finding remained statistically signif-
icant for both VA loss thresholds, for crude and adjusted
models, and for analyses using risk factors at presentation
and time-varying risk factors. The result suggests that the
presence and degree of intraocular inflammation are signif-
icant risk factors for visual loss among patients with JIA-
associated uveitis and that 1? or higher grade anterior
chamber cells are associated with an increased risk of visual
loss. Grade 0.5? anterior chamber cells were not associated
with a large or significantly higher degree of visual loss
after adjusting for other factors.
We observed that the use of immunosuppressive drugs
was associated with a statically significantly reduced risk of
at least moderate visual loss, a finding previously re-
ported.12However, because the patients reported by Thorne
et al12likely overlap with some of the patients in this current
cohort, we performed a subanalysis evaluating this associ-
ation in the SITE cohort with the Hopkins patients removed,
which demonstrated the same overall pattern as that re-
ported in this article including all patients. Indeed, the
results were similar in each center. Our results also sug-
gested that the use of immunosuppressive drugs was asso-
ciated with a reduced risk of developing blindness, although
our results did not achieve statistical significance. Never-
theless, avoidance of moderate vision loss provides an ad-
equate indication to advocate the use of immunosuppressive
therapy in patients with chronic uveitis related to JIA. Given
the evidence supporting the relative safety and effectiveness
of immunosuppressive drug therapy in the treatment of a
variety of ocular inflammatory diseases,23–33the threshold
for starting immunosuppression in cases that are not easily
and stably controlled by simpler means should be low. Our
ability to conduct subanalyses investigating various types of
IMT was limited by indication for treatment bias, because
drugs typically used for more severe cases would tend to
have worse outcomes. Indeed, because IMT generally is
used for more severe cases, our data likely underestimate
the benefits of IMT. It is possible that results would have
been even more favorable had tumor necrosis factor
inhibitors—believed to be effective for this condition34—
been widely used at the time that our patients were treated.
Furthermore, we lacked an adequate sample size to analyze
treatment outcomes according to the specific immunosup-
pressive agent used. The SITE Research Group is collecting
additional data on tumor necrosis factor inhibitors, so per-
haps we will have adequate power to perform these analyses
in the future.
We found that eyes of patients who presented to our
clinics without developing any ocular complications before
presentation were less likely to develop ocular complica-
tions during the observed follow-up (rate ? 0.04/EY vs.
0.15/EY, P ? 0.01). This observation may reflect a lesser
degree of severity in those cases without complications at
the time of presentation, a benefit of early successful treat-
Table 2. Incidence of Structural Ocular Complications and Loss of Visual Acuity in Juvenile Idiopathic Arthritis–Associated Uveitis
among Those at Risk
Event n/N* Rate/PY†
Ocular hypertension ?21
Ocular hypertension ?30
Any complication among naive¶
Any new complication#
CI ? confidence interval; EY ? eye-year; PY ? person-year; VA ? visual acuity.
*Number of events/number of persons at risk.
†Rate is number of events occurring per PYs at risk.
‡Number of events/number of affected eyes at risk.
§Rate is events occurring in affected eye per EY at risk.
¶Any complication among naive includes posterior synechiae, band keratopathy, macular edema, epiretinal membrane, hypotony, or ocular hypertension
among those with no ocular complications at presentation.
#Any new complication includes posterior synechiae, band keratopathy, macular edema, epiretinal membrane, hypotony, or ocular hypertension among
those eyes at risk for having any of these complications during follow up.
**Rate is number of events occurring in better-seeing eye of each patient at risk for VA loss per PYs or EYs of follow-up. Vision was assessed using logMAR
(?Log10Minimal Angle of Resolution) charts.
Gregory et al ? Outcomes in Juvenile Idiopathic Arthritis
ment, or both. If we assume that uveitis specialists are more
effective in preventing these complications, then these data
could support previous publications suggesting that early
referral to a uveitis specialist is associated with better clin-
ical outcomes.11,35The high risk of complications observed
even under tertiary care also suggests that these patients
may benefit from early tertiary management.
As with all retrospective studies, our results must be
interpreted with caution. Selection bias may be present in
the patients receiving immunosuppressive drugs, because
patients who are more reliable and compliant with treatment
and follow-up may be more likely to receive these drugs. It
is also possible that sicker patients seen in these tertiary care
centers are followed more closely than the general popula-
tion of those with JIA-associated uveitis. Referral bias likely
exists in this study because all participant centers are ter-
tiary, referral-based clinical centers, so the absolute risk of
adverse events may be higher than would be reported in less
specialized settings.36,37The risk factor associations re-
ported might have been less strong had a general population
sample been available, but it is unlikely that the pattern of
association would be qualitatively different. Furthermore,
the results of this study are consistent with other referral-
based studies, and therefore likely are generalizable to the
tertiary setting. Regional differences in follow-up and treat-
ment may exist between the different clinics, although pub-
lished guidelines38typically were used for the systemic
treatment for JIA-associated chronic uveitis in this cohort,
because the founders of the participating centers were lead-
ers in developing these guidelines. Indeed, practitioners in
the participating centers treated chronic uveitis, including
JIA uveitis, with immunosuppressive medications in a sim-
ilar manner as the guidelines that were published in 2000,
so although it is plausible that regional differences in
follow-up and treatment could exist, we do not believe they
would be significant. Further, analyses stratifying by clinic
did not reveal significant differences among the clinics.
For outcomes that may be reversible in some instances,
such as reduction in VA, the risk reported provides an upper
boundary of risk, under the assumption of survival analysis
that eyes never recover VA, which is not always the case.
We elected to analyze the data in a manner similar to
previous reports, following Standardization of Uveitis No-
menclature analysis guidelines,20to facilitate comparison
and because results are more readily interpretable. Given
that any visual loss is undesirable and that any imprecision
in measuring VA likely would be balanced across different
levels of covariates, it is unlikely that results would have
been qualitatively different had a more complicated ap-
proach been undertaken; although CIs might have been
Table 3. Risk Factors for Loss of Visual Acuity in Eyes with Juvenile Idiopathic Arthritis–Associated Uveitis
HR 95% CI
HR95% CIHR P ValueP ValueHR P ValueP Value
Age at diagnosis
Prior ocular surgery
0 AC cell grade
0.5? AC cell
1? AC cell
2? AC cell
3? AC cell
4? AC cell
Any vitreous cell or
Use of oral
Use of IMT?
AC ? anterior chamber; CI ? confidence interval; HR ? hazard ratio; IMT ? immunomodulatory therapy; logMAR ? logarithm of the minimum angle
*Characteristic was assessed as number of new events of vision loss per EY of follow-up. Vision was assessed using logMAR (?Log10Minimal Angle of
†Crude refers to univariate Cox regression analyses.
‡Adjusted refers to multivariate Cox regression analyses.
§An abnormal IOP was defined as ?21 mmHg (ocular hypertension) or ?5 mmHg (hypotony).
¶Per increase in 1 line of VA ?20/15 at initial visit.
Volume 120, Number 1, January 2013
wider with such an approach, the high degree of significance
suggests it is unlikely that our conclusions would have been
changed by such an approach. Indeed, the impact of immu-
nosuppression may be greater than we have estimated, be-
cause immunosuppression typically would have been used
for the most severe cases, such that our observation of its
benefit may be underestimated. Although the study’s power
is considerably more than in previous reports, small to
moderate effect sizes may not have been detectable with the
available study power. Although the study includes patients
whose outcomes have been reported,12the outcomes of the
remainder of the cohort were similar, justifying inclusion of
the previously reported cases to optimize the study’s statis-
tical precision. Strengths of the study include the large
sample size (327 patients, 596 affected eyes), the large
amount of follow-up time, and the standardized methods of
chart review across the multiple sites at each clinical visit.
We found at presentation that the frequencies of visual
impairment and blindness were similar to those reported by
other studies from tertiary care centers10–13,16,17,39but are
approximately 20% to 30% higher than what has been
reported in population-based registries,8,9,36,37and those
studies reported data from secondary and tertiary referral
centers combined,6,7as would be expected.
In conclusion, ocular complications and vision loss oc-
curred frequently among patients with JIA-related chronic
uveitis in the SITE cohort who were receiving tertiary care.
Active uveitis had a statistically significant dose-dependent
association with loss of VA for levels of anterior chamber
cell of 1? or higher. Use of immunosuppressive drugs was
associated with a reduced risk of vision loss by approxi-
mately 60%. These observations provide support of the
concept that aggressive treatment of intraocular inflamma-
tion is critical to the prevention of visual loss among pa-
tients with JIA-related uveitis.
1. American Academy of Pediatrics Section on Rheumatology
and Section on Ophthalmology: guidelines for ophthalmologic
examinations in children with juvenile rheumatoid arthritis.
2. Hahn YS, Kim JG. Pathogenesis and clinical manifestations
of juvenile rheumatoid arthritis. Korean J Pediatr 2010;53:
3. Ravelli A, Felici E, Magni-Manzoni S, et al. Patients with
antinuclear antibody-positive juvenile idiopathic arthritis con-
stitute a homogeneous subgroup irrespective of the course of
joint disease. Arthritis Rheum 2005;52:826–32.
4. Carvounis PE, Herman DC, Cha S, Burke JP. Incidence and
outcomes of uveitis in juvenile rheumatoid arthritis, a synthe-
sis of the literature. Graefes Arch Clin Exp Ophthalmol 2006;
5. Cassidy J, Kivlin J, Lindsley C, Nocton J, American Academy
of Pediatrics Section on Rheumatology, Section on Ophthal-
mology. Ophthalmologic examinations in children with juve-
nile rheumatoid arthritis. Pediatrics 2006;117:1843–5.
6. Edelsten C, Lee V, Bentley CR, et al. An evaluation of
baseline risk factors predicting severity in juvenile idiopathic
arthritis associated uveitis and other chronic anterior uveitis in
early childhood. Br J Ophthalmol 2002;86:51–6.
7. Edelsten C, Reddy MA, Stanford MR, Graham EM. Visual
loss associated with pediatric uveitis in English primary and
referral centers. Am J Ophthalmol 2003;135:676–80.
8. Saurenmann RK, Levin AV, Feldman BM, et al. Prevalence,
risk factors, and outcome of uveitis in juvenile idiopathic
arthritis: a long-term followup study. Arthritis Rheum 2007;
9. Sabri K, Saurenmann RK, Silverman ED, Levin AV. Course,
complications, and outcome of juvenile arthritis-related uve-
itis. J AAPOS 2008;12:539–45.
10. Woreta F, Thorne JE, Jabs DA, et al. Risk factors for ocular
complications and poor visual acuity at presentation among
patients with uveitis associated with juvenile idiopathic arthri-
tis. Am J Ophthalmol 2007;143:647–55.
11. Dana MR, Merayo-Lloves J, Schaumberg DA, Foster CS.
Visual outcomes prognosticators in juvenile rheumatoid
arthritis-associated uveitis. Ophthalmology 1997;104:236–44.
12. Thorne JE, Woreta F, Kedhar SR, et al. Juvenile idiopathic
arthritis (JIA)-associated uveitis: incidence of ocular compli-
cations and visual acuity loss. Am J Ophthalmol 2007;143:
13. Tugal-Tutkun I, Havrlikova K, Power WJ, Foster CS. Chang-
ing patterns in uveitis of childhood. Ophthalmology 1996;103:
14. Kanski JJ. Juvenile arthritis and uveitis. Surv Ophthalmol
15. Bowyer SL, Roettcher PA, Higgins GC, et al. Health status of
patients with juvenile rheumatoid arthritis at 1 and 5 years
after diagnosis. J Rheumatol 2003;30:394–400.
16. Kump LI, Cervantes-Castaneda RA, Androudi SN, Foster CS.
Analysis of pediatric uveitis cases at a tertiary referral center.
17. Smith JA, Mackensen F, Sen HN, et al. Epidemiology and
course of disease in childhood uveitis. Ophthalmology 2009;
18. Kempen JH, Daniel E, Gangaputra S, et al. Methods for
identifying long-term adverse effects of treatment in patients
with eye diseases: the Systemic Immunosuppressive Therapy
for Eye Diseases (SITE) Cohort Study. Ophthalmic Epidemiol
19. Petty RE, Southwood TR, Manners P, et al. International
League of Associations for Rheumatology classification of
juvenile idiopathic arthritis: second revision, Edmonton, 2001.
J Rheumatol 2004;31:390–2.
20. Jabs DA, Nussenblatt RB, Rosenbaum JT, Standardization of
Uveitis Nomenclature (SUN) Working Group. Standardiza-
tion of uveitis nomenclature for reporting clinical data. Results
of the First International Workshop. Am J Ophthalmol 2005;
21. Cox DR, Oakes D. Analysis of Survival Data. London: Chap-
man & Hall; 1984:xx–xx. Monographs on Statistics and Ap-
plied Probability 21.
22. Lin DY, Wei LJ. The robust inference for the Cox propor-
tional hazards model. J Am Stat Assoc 1989;84:1074–8.
23. Yu EN, Meniconi ME, Tufail F, et al. Outcomes of treatment
with immunomodulatory therapy in patients with corticosteroid-
resistant juvenile idiopathic arthritis-associated chronic iridocy-
clitis. Ocul Immunol Inflamm 2005;13:353–60.
24. Thorne JE, Jabs DA, Qazi FA, et al. Mycophenolate mofetil
therapy for inflammatory eye disease. Ophthalmology 2005;
25. Kempen JH, Gangaputra S, Daniel E, et al. Long-term risk of
malignancy among patients treated with immunosuppressive
agents for ocular inflammation: a critical assessment of the
evidence. Am J Ophthalmol 2008;146:802–12.
Gregory et al ? Outcomes in Juvenile Idiopathic Arthritis
26. GalorA,JabsDA,LederHA,etal.Comparisonofantimetabolite Download full-text
drugs as corticosteroid-sparing therapy for noninfectious ocular
inflammation. Ophthalmology 2008;115:1826–32.
27. Kempen JH, Daniel E, Dunn JP, et al. Overall and cancer
related mortality among patients with ocular inflammation
treated with immunosuppressive drugs: retrospective cohort
study. BMJ 2009;339:b2480.
28. Pasadhika S, Kempen JH, Newcomb CW, et al. Azathioprine
for ocular inflammatory diseases. Am J Ophthalmol 2009;148:
29. Gangaputra S, Newcomb CW, Liesegang TL, et al, Systemic
Immunosuppressive Therapy for Eye Diseases Cohort Study.
Methotrexate for ocular inflammatory diseases. Ophthalmol-
30. Daniel E, Thorne JE, Newcomb CW, et al. Mycophenolate
mofetil for ocular inflammation. Am J Ophthalmol 2010;149:
31. Kacmaz RO, Kempen JH, Newcomb C, et al. Cyclosporine for
ocular inflammatory diseases. Ophthalmology 2010;117:576–84.
32. Pujari SS, Kempen JH, Newcomb CW, et al. Cyclophosph-
amide for ocular inflammatory diseases. Ophthalmology 2010;
33. Multicenter Uveitis Steroid Treatment (MUST) Trial Research
Group, Writing Committee, Kempen JH, Altaweel MM, Hol-
brook JT, et al. Randomized comparison of systemic anti-
inflammatory therapy versus fluocinolone acetonide implant
for intermediate, posterior, and panuveitis: the Multicenter
Uveitis Steroid Treatment Trial. Ophthalmology 2011;118:
34. Mackensen F, Lutz T. Therapy for childhood uveitis:
biologics: too often–too late [in German]? Ophthalmologe
35. Dana MR, Merayo-Lloves J, Schaumberg DA, Foster CS.
Prognosticators for visual outcome in sarcoid uveitis. Oph-
36. Heiligenhaus A, Niewerth M, Mingels A, et al. Epidemiology
of uveitis in juvenile idiopathic arthritis from a national pae-
diatric rheumatologic and ophthalmologic database [in Ger-
man]. Klin Monbl Augenheilkd 2005;222:993–1001.
37. Chalom EC, Goldsmith DP, Koehler MA, et al. Prevalence
and outcome of uveitis in a regional cohort of patients with
juvenile rheumatoid arthritis. J Rheumatol 1997;24:2031–4.
38. Jabs DA, Rosenbaum JT, Foster CS, et al. Guidelines for the
use of immunosuppressive drugs in patients with ocular in-
flammatory disorders: recommendations of an expert panel.
Am J Ophthalmol 2000;130:492–513.
39. Wolf MD, Lichter PR, Ragsdale CG. Prognostic factors in the
uveitis of juvenile rheumatoid arthritis. Ophthalmology 1987;
Footnotes and Financial Disclosures
Originally received: March 1, 2012.
Final revision: July 17, 2012.
Accepted: July 18, 2012.
Available online: October 11, 2012.Manuscript no. 2012-303.
1Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins
University School of Medicine, Baltimore, Maryland.
2Department of Ophthalmology, Perelman School of Medicine, The Uni-
versity of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
3The Center for Clinical Epidemiology and Biostatistics, Department of
Biostatistics and Epidemiology, Perelman School of Medicine, The Uni-
versity of Pennsylvania, Philadelphia, Pennsylvania.
4Allergan, Irvine, California.
5The Massachusetts Eye Research and Surgery Institute, Cambridge, Mas-
6Department of Ophthalmology, Harvard Medical School, Boston, Mas-
7Department of Epidemiology, Center for Clinical Trials, the Johns Hop-
kins University Bloomberg School of Public Health, Baltimore, Maryland.
8Department of Ophthalmology, The Mount Sinai School of Medicine,
New York, New York.
9Department of Medicine, The Mount Sinai School of Medicine, New
York, New York.
10Laboratory of Immunology, National Eye Institute, Bethesda, Maryland.
11Department of Ophthalmology, Oregon Health and Science University,
12Department of Medicine, Oregon Health and Science University, Port-
13The Portland Veterans’ Affairs Medical Center, Portland, Oregon.
The author(s) have no proprietary or commercial interest in any materials
discussed in this article.
Supported primarily by Grant ey014943 from the National Eye Institute,
National Institutes of Health, Bethesda, Maryland (Dr. Kempen). Addi-
tional support was provided by the Paul and Evanina Mackall Foundation,
Philadelphia, Pennsylvania, and Research to Prevent Blindness Inc, New
York, New York. Dr. Kempen is a Research to Prevent Blindness James S.
Adams Special Scholar Award recipient. Dr. Thorne is a Research to
Prevent Blindness Harrington Special Scholar Award recipient. Drs. Jabs
and Rosenbaum are Research to Prevent Blindness Senior Scientific In-
vestigator Award recipients. Dr. Levy-Clarke was previously and Dr.
Nussenblatt continues to be supported by intramural funds of the National
Jennifer E. Thorne, MD, PhD, The Wilmer Eye Institute, 600 North Wolfe
St., Woods Building, Room 476, Baltimore, MD 21287. E-mail: jthorne@
Volume 120, Number 1, January 2013