Macular Thickness in Patients with Idiopathic Juvenile Rheumatoid Arthritis without Uveitis: Is There any Alteration?
Carmen L Soria-Orozco, Diana E Arevalo-Simental*, Enrique RoigMelo-Granados, Saúl Cortés Quezada, Cisneros-Gomez Sonia, Perla M Madrigal Ruiz
Antiguo Hospital Civil de Guadalajara, USA
Submission: February 20, 2017; Published: June 16, 2017
*Corresponding author: Diana E Arevalo Simental, MD, Retina Doctor at Antiguo Hospital Civil de Guadalajara, Mexico, USA.
How to cite this article:Carmen L S, Diana E A, Enrique R, Saúl C Q, Cisneros G S, et al. Macular Thickness in Patients with Idiopathic Juvenile
Rheumatoid Arthritis without Uveitis: Is There any Alteration?. Acad J Ped Neonatol. 2017; 5(2): 555713. DOI: 10.19080/AJPN.2017.05.555713
Introduction: The Juvenile Idiopathic Arthritis (JIA) is the most common rheumatic disease in children. One of the most common causes of Secondary Uveitis is JIA, in fact uveitis is the most common extraarticular manifestation in all groups of JIA [1-3]. The visual loss secondary to a complicated uveitis is a major concern and has resulted in recommendations to regulate ophthalmologic examination. Among the possible complications is clinical and subclinical macular edema [2,4,5]. It has been reported increase in Macular Thickness (MT) in eyes with Anterior Uveitis in JIA patients [5-7]. This observation was also found in the contralateral eyes even though they did not had a current episode of uveitis, suggesting that the increase in MT could be explained by the immune response to systemic inflammatory process .
Purpose:This study aims to document the MT in patients with JIA wich present a systemic inflammatory response, but unlike what has been done in previous studies, this research was performed in eyes that did not have uveitis at the time of ophthalmologic examination and therefore seeking changes in MT arising from systemic situation.
Results: In a 11-month period 14 patients with JIA, 7 female and 7 male were reviewed. With an average of 10.5 years (range 3-16 years) with a mean age at diagnosis of 7.8 years (range 2-4 years). The range of time between diagnosis of JIA and the first ophthalmologic examination was 0.5-9.0 years. The most common type of JIA was persistent oligoarticular in 14.3% of cases. Active disease in 4 patients (28.6%) and 10 patients (71.4%) was found. Optical coherence tomography (OCT) was performed in patients with JIA and 14 controls matched for age and sex The Mann-Whithney was performed without finding difference in central macular thickness JIA patients and control patients, with p=0.548 for the right eye (RE) and p=0.378 for the left eye (LE). There was no relationship between macular thickness and the presence of positive rheumatoid factor, erythrocyte sedimentation rate or C-reactive protein.
Conclusion:There was no statistically significant difference in macular thickness in JIA patients without prior or current episode of uveitis and control patients. Likewise, there was no relationship between the activity or inactivity of the disease and macular thickness in such patients. Further research would find association between macular thickness and probability of developing uveitis or impared vision.
Keywords: International league of associations for rheumatology (ILAR); Mean foveal thickness (MFT); C-Reactive protein (CRP)
The International League of Associations for Rheumatology (ILAR) defines Juvenile Idiopathic Arthritis as a group of chronic childhood arthropathies with no apparent cause, lasting for a minimum of 6 weeks and with disease onset prior to age 16 Although an incidence of just 3 to 23 per 100,000 children and a prevalence of 16 to 140 per 100,000 children, Juvenile Idiopathic Arthritis is the most common rheumatic disease in children. Uveitis is the most common extra-articular involvement found in patients
with Juvenile Idiopathic Arthritis [1,2] and Juvenile Idiopathic
Arthritis is the most common systemic cause of pediatric uveitis [3,4].
The cumulative incidence of Juvenile Idiopathic Arthritis associated uveitis is 8.3%  and it is reported that 13 - 36% of the patients with Juvenile Idiopathic Arthritis will develop uveitis .Thirty seven percent (37%) of these patients will present secondary ocular complications, with significant visual impairment in 3% to 66% .
Among the complications of uveitis is macular edema, which is
initially reported in 5% . In the other hand, with the use of the
Optical Coherence Tomography (OCT), it has been found that while
macular edema is clinically detected in 13%, by OCT examination
actually 25% of eyes with anterior uveitis of any origin present
macular edema and that macular alterations can be found in 84%
of the eyes of children with Juvenile Idiopathic Arthritis and uveitis.
Also, has been studied the macular thickness of the fellow eye in
patients with unilateral anterior uveitis of any cause, finding that
also in the quiet fellow-eyes there is subclinical macular alteration,
probably as a reflect of systemic immune-mediated response to
the inflammatory disorder in anterior uveitis and that this seems
to be larger in HLA-B27 positive patients .
The purpose of our study was to transversely analyze by
means of OCT scanning the macular thickness in children with
Juvenile Idiopathic Arthritis without current or previous episode
of uveitis in order to describe the measurements of macular
thickness resulting from the systemic condition.
This was a case-control study where 30 eyes of patients
with Juvenile Idiopathic Arthritis and 60 eyes of control subjects
matched by sex and age (2:1) underwent Macular Optical
Coherence Tomography. Twenty patients with Juvenile Idiopathic
Arthritis where transversally referred from Rheumatology service
and evaluated between November 2012 and December 2013
at the Hospital Civil Fray Antonio Alcalde, Guadalajara, Jalisco.
Subjects with current or previous ophthalmic history of Anterior
Uveitis, intraocular surgery or any ocular complication of previous
uveitis were excluded. Five patients were excluded: Three patients
for having complication of uveitis, two of them with previous
intraocular surgery, and 2 for having incomplete file.
The study of 30 eyes of 15 patients with Juvenile Idiopathic
Arthritis and 60 eyes of 30 control subjects matched by age and sex,
underwent a complete ophthalmological examination during their
first visit, including visual acuity assessed using HTOV charts, slitlamp
examination, aplanation tonometry, and fundoscopy with
dilated pupils. The informed consent of the parents was obtained
in each case before undergoing ophthalmic examination and OCT.
OCT scanning was performed with Cirrus OCT, Carl Zeiss
Meditec and comprised in all patients a 6mm mapping of the
macula. The retinal map analysis protocol was used, with numeric
averages of the measurements for each of the 9 map sectors as
defined by the Early Treatment Diabetic Retinopathy Study.
The regional variables that were analyzed were Mean Foveal
Thickness (MFT=F1); Mean Central Thickness, composed by
the inner ring of 3mm diameter (MCT= (F2+F3+F4+F5)/4); and
Mean Peripheral Thickness, the outer ring of 6mm diameter
Data was analyzed with T-Student test, two tail/two-sided
and p-value < 0.05 was set to be statistically significant. SPSS
v.17.0 was used for statistical analysis. Institutional review board
approval was obtained for the design of this study, conducted in
accordance with Declaration of Helsinki recommendations.
The sample group was composed by thirty eyes of 15 patients
with Idiopathic Juvenile Arthritis, eight (53.3%) female and seven
(46.7%) male, and the control group formed by 60 eyes of 30
subjects matched by sex and age. The mean age at the time of
ophthalmological examination was 10.6±3.5 years, ranging from 3
to 16 years. The mean age of the onset of symptoms of Idiopathic
Juvenile Arthritis was 6.2±3.4 years (range 2-13), while the mean
age of diagnosis of Idiopathic Juvenile Arthritis was 8.2±3.6
years (range 2-14).The average time from diagnosis of Idiopathic
Juvenile Arthritis to the first ophthalmological examination was
3.1±2.6 years (range 0-9).
The oligoarticular persistent type was the most frequent
with a 40%, the seronegative polyarticular with a 33% while the
oligoarticular extended and polyarticular seropositive arthritis
with a 13% each one. Non systemic, psoriatic or enthesitis related
was found. The 93.3% of the patients were under systemic
rheumatologic treatment, the majority received both sulfasalazine
and methotrexate in a 57%, sulfazalazine 36% and 7% with oral
steroids. Active disease was found in 26.6%. The mean erythrocyte
sedimentation rate (ESR) was 13.92mm/hr (0-10mm/hr). The
mean C-Reactive protein (CRP) was 1.37mg/L, (0-0.80) no
association was found between the ESR and CPR with macular
Mean Visual Acuity in LogMAR was +0.10 for right eye and
+0.20 for left eye with HTOV chart. Mean intraocular pressure was
11mmHg (range 10-21mmHg) in right eye and 15.2mmHg in left
eye. (Range 12-22mmHg). No posterior pole alteration was found
in fundoscopy. Macular OCT was done in 30 eyes of the 15 case
patients and in 60 eyes of the 30 patient’s age and sex matched
controls. Mean foveal thickness was 239±17microns while mean
thickness in control group was 238±25 microns with a p=0.80.
Mean central thickness was 311±14 microns and 313±19 in
the control group P=0.54. The mean peripheral thickness was
276±14 microns and 277±19 microns in control group. p=0.65. No
statistical significance was found between the two groups.
The incidence of macular edema in patients with Idiopathic
Juvenile Arthritis as a complication of a uveitic process is
approximately 3%, as reported in a retrospective study by Sylvia
R. Kodsi et al. In 2002, 158 patients were included, of which 25%
developed uveitis, 5% according to a 2007 publication in a cohort
of 1081 patients with Idiopathic Juvenile Arthritis, 13% had
uveitis, and 5% had macular edema [6-10].
In 2007, however, a cross-sectional study was conducted,
which showed that the incidence of maculopathy in patients with
JIA and uveitis was greater in 82% of patients with peripheral
thickening (73%), Macular edema (47%), foveal detachment
(18%) or atrophic changes (10%), these data being quite different from what was found only by clinical evaluation . Similarly,
in a retrospective series carried out in 2010, which included 67
patients with Idiopathic Juvenile Arthritis, 13.8% presented
macular edema secondary to a uveitic process. However, macular
edema incidence was documented at 25%. In 2012, a retrospective
study was carried out in which OCT was performed in 14 eyes
with unilateral anterior uveitis of non-infectious origin, finding a
statistically significant increase in macular thickness compared to
healthy contralateral eye thickness .
On the other hand, also in 2012 Alexandra Wexler carried
out a prospective study in which macular OCT was performed
on eyes with anterior uveitis and healthy contralateral eye in
patients with HLA-B27 positive and HLA-B27 negative compared
to control patients matched by age and sex. It was found that there
is an increase in macular thickness of both the uveitic process eye
and the healthy contralateral eye, in comparison to the control
eyes of patients without uveitis, suggesting that the anterior
uveitis episode is accompanied by an autoimmune systemic
response, it was also discovered that the increase in macular
thickness was greater in HLA-B27 positive patients . Likewise,
evidence from animal models supports that the non-infectious
uvetic inflammatory process is related to alteration in systemic
immunity, which leads to damage of ocular autoimmunity .
To date, there is no previous study that documents the
macular thickness of patients with Idiopathic Juvenile Arthritis
and without uvetic process, seeking to describe the incidence of
maculopathy and / or posterior pole pathology resulting from a
systemic inflammatory and systemic immune process.
According to our results, there is no alteration in the macular
thickness of patients with Idiopathic Juvenile Arthritis and no
ocular inflammatory process. However, it is important to note
that 73.4% of our patients had inactive and controlled Idiopathic
Juvenile Arthritis and that 93% were on rheumatologic medication.
Finally, it is important to note that in 86% of the patients the
ophthalmologic assessment performed in the present study was
the initial assessment, with a delay between the diagnosis of
Idiopathic Juvenile Arthritis and referral to the ophthalmologist
of 3 years on average, with guidelines indicating ophthalmologic
assessment at the time of diagnosis of Idiopathic Juvenile Arthritis
No differences were found in the macular thickness of the
eyes of patients with Idiopathic Juvenile arthritis and without
uveitic process and eyes of control subjects. Future research will
be required with a larger sample of patients with active disease
or who are not taking rheumatologic medication at the time
of macular OCT. It is important to promote and promote the
ophthalmologic assessment of the patient with Idiopathic Juvenile