Hindawi Publishing Corporation Journal of

Ophthalmology Volume 2016, Article ID

9167361, 7 pages
http://dx.doi.org/10.1155/2016/9167361

Research Article Clinical Features and

Visual Outcomes of Optic Neuritis in
Chinese Children

Huanfen Zhou,1,2 Wei Wang,3 Quangang Xu,2,4 Shaoying Tan,2

Shuo Zhao,5 Mo Yang,2 Chunxia Peng,2 and Shihui Wei2

1Department of Ophthalmology, The First Affiliated Hospital of Chinese People’s Liberation Army General Hospital, Beijing, China

2Department of Ophthalmology, Chinese PLA General Hospital, Beijing, China 3Zhongshan Ophthalmic Center, State Key Laboratory of

Ophthalmology, Sun Yat-sen University, Guangzhou, China 4Department of Neurology, Chinese PLA General Hospital, Beijing, China

5Department of Ophthalmology, Beijing Hospital, Beijing, China

Correspondence should be addressed to Shihui Wei; [email protected]

Received 28 April 2016; Revised 2 August 2016; Accepted 25 August 2016

Academic Editor: Terri L. Young

Copyright © 2016 Huanfen Zhou et al. This is an open access article distributed under the Creative Commons Attribution License, which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Purpose. Although optic neuritis (ON) in children is relatively common, visual outcomes and factors associated with the condition have
not been well documented. The aim of this study was to evaluate the clinical features and visual outcomes of ON in Chinese children.
Methods. Patients with a first episode of ON at a tertiary neuroophthalmic centre in China were assessed and followed up for at least three
months. Visual outcomes and clinical, laboratory, and neuroimaging findings were reviewed. In patients with bilateral ON, only the eyes
with worse visual acuity (VA) at presentation were used for statistical analysis. Results. Seventy-six children (76 eyes) with a first episode
of ON were included. The mean age was 11.8 years, 60.5% were females, and 48.7% had bilateral involvement. The children were
followed up for an average of 18.5 months (age range, 3–48 months). Vision loss at presentation was severe, with VA < 20/200 in 37 eyes
(48.7%). At the final visit, 3 (3.9%) eyes had VA of at least 20/20, and 41 (53.9%) eyes had VA of at least 20/40. The final VA in 35 eyes
(46.1%) was worse than 20/40. Children aged ≤ 10 years had better predicted visual outcomes when compared to children over 10 years
(odds ratio = 2.73, 95% confidential interval: 1.05–7.07, andP = 0.039). The other features of this cohort, such as sex, experienced
bilateral attack, VA at presentation, presence of optic disc edema, systemic diseases, magnetic resonance imaging (MRI) findings, and
aquaporin-4 (AQP-4) antibody status, were not significantly correlated with the final visual outcome. Conclusion. The data revealed the
clinical characteristics and visual outcomes of ON in Chinese children. ON in children was associated with severe vision loss and
relatively good visual recovery. The age at onset could predict the final visual function.

1. Introduction which may be isolated or closely correlated with sys- temic

demyelinating diseases such as multiple sclerosis (MS) and
Optic neuritis (ON) is an inflammatory process of the optic nerve, neuromyelitis optica spectrum disorders (NMOSDs) [1, 2].
Aquaporin-4 (AQP-4) antibody testing has been added to the 15-year follow-up [6, 7]. With regard to children with ON, a
diagnostic assessment for ON and has prognostic value [3, 4]. meta-analysis demonstrated that only 19% of the children
The prevalence of ON in children is lower than that in adults. developed MS after an average follow-up of 6.3 years [8].
Furthermore, ON in children is distinguished by greater bilateral The influence of race/ethnicity on features and outcomes
involvement, higher prevalence of optic disc edema (ODE), and of adults with ON has been well documented. In ONTT, people of
lower conversion into MS [5]. In the optic African American origin were found to have lower visual acuity
neuritis treatment trial (ONTT), 50% of adults with ON, 72% (VA) and contrast sensitivity at onset and faster vision recovery
patients with one or more lesions in brain MRI, and 25% of but worse final visual outcomes in com- parison with white
patients without lesion in brain MRI progressed to MS during the patients with ON [9]. Epidemiological
2 Journal of Ophthalmology

studies also showed that African Americans had more severe this study had to fulfil the following criteria: (1) the first episode
vision loss, worse disability scores, more retinal atrophy, and of ON with best corrected visual acuity (BCVA) loss; (2) age <
accelerated retinal nerve fibre-layer thinning compared to 18 years; (3) follow- up of ≥3 months; (4) no prior steroid
Caucasian Americans [10–12]. Furthermore, MS is rare in East treatment; and (5) objective evidence of visual abnormalities:
Asian populations such as Chinese, Korean, and Japanese relative afferent papillary defect (RAPD), visual field defects, and
populations, and the prognosis of ON in these populations differs abnormal visual evoke potential (VEP). Patients with any
from that in American and European pop- ulations. We evidence of the following conditions were excluded: (1)
previously demonstrated a higher prevalence of serum AQP-4 uncertainty in the diagnosis; (2) other types of optic neuropathy
antibody, severe vision loss, and poor vision recovery in Chinese such as compressive, hereditary, vascular, toxic, traumatic,
adults with ON, with only 26.1% of patients having VA of 20/20 metabolic, or infiltrative optic neuropathy; (3) other ocular
or better and 39.1% of patients having VA of 20/100 or worse at diseases such as amblyopia, uveitis, or glaucoma; (4) a previous
the final visit [13, 14]. episode of ON; and (5) systemic diseases, such as epilepsy and
Although the visual outcomes of adults with ON are malignancy. Patients diagnosed with MS, NMOSD, acute
well documented in the ONTT, there are few trials on the disseminated encephalomyelitis (ADEM), or systemic lupus
outcomes for children with ON. In 2014, Wan et al. reviewed 46 erythematosus (SLE) were not excluded.
American children (46 eyes) with a first episode of ON and
reported the vision in 35 of 36 eyes (97%) recovered to >20/40 2.2. Study Outcomes. The following data were extracted from the
after one year [15]. However, most of the children in their study medical records using a standardized form: age,
were white. Studies on other races are urgently needed. sex, laterality, ocular symptoms, pupil function test, fundus
Therefore, to fill the gap, we performed a retrospective study to findings, colour vision test, and laboratory findings including
investigate the clinical features and visual outcomes of ON in AQP-4 IgG status and cerebral spinal fluid (CSF) analy- sis, orbit
Chinese children. magnetic resonance imaging (MRI) information, treatment,
follow-up, best corrected visual acuity (VA) at presentation, and
2. Methods final VA. The serum AQP-4 antibody exam- ination was assessed
using the cell-based assay described previously by our group [31].
This was a retrospective observational cohort study on The VA in all the children was evaluated using the Snellen visual
hospitalized patients diagnosed with ON in the neurooph- chart, and the data were transformed as the logarithm of the
thalmology department of Chinese People’s Liberation Army minimum angle of resolution (logMAR) values [16]. The MRI
General Hospital (PLAGH). Patients were recruited between images were reviewed by the same experienced radiologist.
January 2012 and December 2014. The study protocol was Moreover, MS and NMOSD were diagnosed according to the
approved by the institutional review board at the Chinese PLAGH latest international criteria [17, 32]. In patients with bilateral ON,
and performed in accord with the tenets of the Helsinki only the eyes with worse BCVA at presentation were included in
Declaration. Informed consent was obtained from all the patients this study.
or their parents.

2.3. Statistical Analyses. Only one eye of each patient was used
2.1. Patients. Patients who presented with a first episode of ON
for statistical analysis. In patients with bilateral ON, only the eyes
were identified by searching electronic medical records. The
with worse visual acuity (VA) at presentation were used for
diagnosis of ON was confirmed by both an experienced
statistical analysis to exclude intereye correlations. All statistical
neurologist (QX) and ophthalmologist (SW). Patients included in
 analyses were performed using SPSS 20.0 soft- ware (IBM characteristics of these patients (unit of presenta- tion = person).
Corporation, New York, USA). Fisher’s exact test was used to 39 (51.3%) patients experienced unilateral involvement and 37
compare categorical variables between groups and determine the patients (48.7%) experienced bilateral involvement. The mean
predictors of a favourable visual outcome (final VA ≥ 20/40). No age at onset was 11.8 years (5–17 years). The follow-up duration
adjustment for multiple comparisons was made owing to the ranged from 3 to 48 months, with a mean of 18.5 months (median
exploratory nature of the study. In addition, logistic regression of 11 months). Eighteen patients who experienced bilateral ON
analyses were performed to calculate the odds ratio of poor visual had RAPD. Of the 47 patients who underwent AQP-4 IgG testing,
outcome as a function of age onset, sex, laterality, VA at 13 (27.7%) were seropositive and 34 (72.3%) were seronegative.
presentation, presence of ODE, systemic diseases, MRI findings, Of the 42 patients who underwent orbit MRI imaging, 35
and AQP-4 IgG status. A value of P < 0.05 was considered (83.33%) had optic nerve T2 lesions and 7 (16.67%) had normal
statistically significant. MRI findings. One patient was diagnosed with ADEM, one
patient was diagnosed with SLE, three patients were diagnosed
with MS, and 13 patients were diagnosed with neuromyelitis
3. Results optica spectrum disorders (NMOSDs) during the follow-up. ON
was the first symptom in all children and no prior myelitis
3.1. Demographic and Clinical Characteristics. Seventy-six attacked in children with seropositive AQP- 4 antibody. During
children were eligible for this study, with 30 male and 46 female the follow-up, none of the children with AQP-4 Ab seropositive
children. Table 1 summarized the demographic and clinical underwent attack of myelitis.
Journal of Ophthalmology 3

Table 1: Demographic and clinical characteristics of Chinese children To eliminate intereye correlations, data of only one eye
with optic neuritis. in each patient was included in the statistical analysis (unit of
analysis = eye). Twenty-two (28.9%) eyes had ODE. Of 55 eyes
Features Total Percent (%) Number of patients 76 100% Age at onset,
with colour vision test, 11 (22%) eyes had colour vision deficit.
year
Vision loss at presentation was severe, with
Mean 11.80 ± 3.87 Range 5–17 SexMale 30 39.5 Female 46 60.5 VA < 20/200 in 37 (48.7%) eyes. All patients received
Experience 76 intravenous methylprednisolone therapy (10–30 mg/kg/day) for
Unilateral attack 39 51.3 Bilateral attack 37 48.7 Pupillary function three days, followed by oral prednisolone (1 mg/kg/day for two
test 76 weeks).
RAPD positive in unilateral 39 100 RAPD positive in bilateral 18
48.65 AQP-4 IgG status 47 3.2. Visual Outcomes. VA was determined in the affected eyes in
Seropositive 13 27.7 Seronegative 34 72.3 Orbit MRI 42 unilateral ON and in the worse eyes at presentation in bilateral
Abnormal (T2 lesions) 35 83.33 Normal 7 16.67 Causes/associations ON. The VA at presentation of the patients aged ≤ 10 years was
76 not significantly different from that of the patients aged > 10
ION 58 76.3 ADEM 1 1.3 MS 3 4.0 SLE 1 1.3 NMOSD 13 17.1 years (Table 2). 13 (43.3%) patients aged ≤ 10 years and 24
Funduscopy∗ 76 (52.2%) patients aged > 10 years had VA < 20/200. At the final
visit, among those aged≤10 years, the VA of 21 (70%) patients
Optic disc edema 22 28.9 Normal 54 71.1 Colour vision test∗ 55
had improved to at least 20/40, as compared to that of 20 (43.5%)
Deficit 11 20 Intact 33 60 Vision too poor to test 11 20 Presenting patients aged < 10 years.
VA∗ 76
20/40 ≤ VA < 20/20 5 6.6 20/200 ≤ VA < 20/40 34 44.7 CF ≤ VA <
3.3. Predictors of Visual Outcomes. The age at onset was
20/200 6 7.9 NLP ≤ VA < CF 31 40.8 Treatment
significantly correlated with the final VA. The children aged ≤ 10
IV methylprednisolone 76 100 RAPD, relative afferent papillary years had better predicted visual outcomes when compared to
defect; AQP-4 IgG, anti-aquaporin-4 antibody IgG; ION, isolated optic neuritis;
ADEM, acute disseminated encephalomyelitis; MS, multiple sclerosis; SLE, those older than 10 years (odds ratio = 2.73, 95% confiden- tial
systemic lupus erythemato- sus; IV, intravenous; VA, best corrected visual acuity; interval: 1.05–7.07, and P = 0.039). The other features of this
CF, count finger; and NLP, no light perception. ∗Only one eye of each patient was
cohort, such as sex, experienced bilateral attack, VA at
presentation, presence of ODE, systemic diseases, MRI findings,
included in the statistical analyses. and AQP-4 IgG status, were not significantly correlated with the
final visual outcomes (Table 3).
 4. Discussion children to date. Brady et al. examined 25 children (39 eyes) with
ON and reported that 30 of 39 (76%) eyes recovered to 20/40 or
In this study, we described the clinical features and visual better after a follow-up of an average of 11 months [30]. Wilejto
outcomes of ON in Chinese children. The clinical features of this et al. reviewed 36 children (51 eyes) with ON in Canada and
cohort included female preponderance (60.5%), com- mon reported that the VA of 39 of 47 eyes (83%) recovered to ≥20/40
bilateral involvement (48.7%), and a high proportion of ODE after a follow-up of 2.4 years [26]. In Japanese children with ON,
(28.9%), which is consistent with previous reports of ON in Mizota et al. reported that 54 of 61 (95%) eyes recovered to 20/20
various ethnic groups (Table 4) [15, 18–30, 33–36]. The vision or better after a mean follow- up of 10.7 years [27]. A study of
loss was severe with 48.7% of patients having VA < 20/200. Korean children with ON reported that the VA recovered to
However, the visual recovery was favourable in the majority of ≥20/40 in 53.3%–80% of affected eyes but that it remained
children, with VA at least 20/40 in 53.9% of the patients. The ≤20/200 in 7.7%–13.3% of eyes at the final visit [18, 22, 25, 28].
only identified predictor of visual outcomes was the age at onset. A study of Malaysian children revealed that the final VA of 21 of
To the best of our knowledge, this is the first study to report the 28 (75%) eyes was ≥20/40 [21]. Among children with ON in
characteristics of ON in children in Mainland China and Taiwan, Sun et al. reported that the VA of 20 of 24 (83.3%) eyes
represents the largest cohort of children with ON. recovered to ≥20/40 after a mean follow-up of 14.01 months [23].
Few studies have reported the visual outcomes of ON in In the
4 Journal of Ophthalmology
Table 2: Visual outcomes of Chinese children with optic neuritis.
Age ≤ 10 years Age > 10 years
Visual outcomes (worse eye at onset if bilateral)
Initial Final Initial Final VA ≥ 20/20 0 3 (10%) 0 0 20/40 ≤ VA < 20/20 3 (10%) 18 (60%) 2 (4.4%) 20 (43.5%) 20/200 ≤ VA < 20/40 14
(46.7%) 7 (23.3%) 20 (43.5%) 22 (47.8%) CF ≤ VA < 20/200 1 (3.3%) 0 5 (10.9%) 0 NLP ≤ VA < CF 12 (40%) 2 (6.7%) 19 (41.3%) 4
(8.7%) Total 30 30 46 46 VA, visual acuity; CF, count finger; and NLP, no light perception.
Table 3: Factors for visual outcomes in Chinese children with optic neuritis.
Age ≤ 10 years 30 21 (70%)
Factors Total eyes Final VA ≥ 20/40 (%) P value Age at onset 0.039 Age > 10 years 46 20 (43.5%) Sex
Female 46 24 (52.17%) Unilateral attack 39 20 (51.3%)
0.701 Male 30 17 (56.7%) Experience 0.632 Bilateral attack 37 21 (56.8%) Initial
VA > CF 42 25 (59.5%) ODE 22 14 (63.6%)
VA 0.278 VA ≤ CF 34 16 (47.1%) Funduscopy 0.501 Normal 54 30 (55.6%) Systemic
ADEM/MS/SLE/NMOSD 18 8 (44.4%) Normal 7 4 (57.1%)
diseases 0.454 ION 58 32 (55.2%) Orbital MRI imaging 0.934 Abnormal
Seropositive 13 5 (38.5%)
(T2 lesions) 35 20 (58.8%) AQP-4 IgG status 0.374 Seronegative 34 18 (52.9%) VA, visual acuity; CF, count
finger; ODE, optic disc edema; ION, isolated optic neuritis; ADEM, acute disseminated encephalomyelitis; MS, multiple sclerosis; SLE, systemic lupus
erythematosus; AQP-4 IgG, anti-aquaporin-4 antibody IgG; and MRI, magnetic resonance imaging.
Table 4: Clinical features of children optic neuritis in previous published reports.
First author Year Location Patient (eyes) Female Mean age Bilateral ODE MS NMOSD Present China 76 (76) 60.5% 11.8 48.7% 36.7%
3.95% 17.1% Kim [18] 2015 Korea 26 (40) 54.0% 10.3 54.0% 77.0% 8.0% 0 Wan [15] 2014 USA 46 (46) 72.0% 12.6 41.0% 67.0%
39.0% NR Jayakody [19] 2014 USA 26 (38) 73.1% 4.5-19 46.0% 73.0% 7.7% 0 Shatriah [21] 2012 Malaysia 14 (28) 85.7% 11.1 100%
85.8% 14.3% NR Jo [22] 2011 Korea 20 (33) 85.0% 6.5 65.0% 75.8% 25.0% NR Sri-Udomkajorn [33] 2011 Thailand 31 65.0% 9.2
74.2% 55.0% 6.0% 6.5% Sun [23] 2011 Taiwan 24 (38) 58.3% 10.1 58.3% 63.2% 12.5% NR Hwang [25] 2007 Korea 10 (15) 50.0%
7.31 NR NR NR NR Wilejto [26] 2006 Canada 36 (51) 58.0% 12.2 42.0% 67.0% 36.0% 2.8% Mizota [27] 2004 Japan 41 (61) 56.0%
9.4 49.0% 74.0% 31.7% NR Hwang [28] 2002 Korea 23 (43) 43.0% 8.9 87.0% 51.0% 4.0% NR Morales [29] 2000 USA 15 60.0% 9.8
66.0% 64.0% 26.0% NR Brady [30] 1999 USA 25 (39) 52.0% 9.4 54.0% NR 16.0% NR Visudhiphan [34] 1995 Thailand 22 (41) 54.5%
7.1 86.3% 48.7% 9.1% NR Kriss [35] 1988 UK 39 74.0% 8.6 74.0% 74.0% 15.0% NR Riikonen [36] 1988 Finland 21 NR NR 62.0%
76.0% 43.0% NR ODE, optic disc edema; MS, multiple sclerosis; NMOSD, neuromyelitis optica spectrum disorders; and NR, not reported.
Journal of Ophthalmology 5

present study, the VA of 53.9% of the patients recovered to of children had VA of 20/40 or better at the one-year follow-up
≥20/40, which is similar to the visual outcomes reported in visit [15]. In this Chinese cohort, we also observed a favourable
Korean children [25]. visual prognosis in the majority of the population, thereby
The ONTT reported that 50% of patients had VA of indicating that children with ON have at least similar or better
20/20 or better and 68% of patients had VA of 20/40 or better visual outcomes compared to those in adults.
after one year [37]. In American children with ON, Wan et al. The identification of predictors of visual outcomes is
reported that 81% of children had VA of 20/20 or better and 89% essential for individualized treatment. The ONTT study
demonstrated that race significantly affected the visual prog- associations between certain factors and visual outcomes. Fourth,
nosis, but it found no associations between age, sex, treat- ment, we were not able to construct any useful statistics about MS-like
and visual outcomes in follow-up periods of 5, 10, or 15 years [6]. lesions or typical NMOSD lesions in brain MRI because only a
In this study, we found that the age at onset was significantly very small number of patients received the brain MRI or the spine
correlated with the visual outcome of the children. Brady et al. cord MRI. Furthermore, myelin oligodendrocyte glycoprotein
examined 25 children (39 eyes) with ON and reported a trend (MOG) antibody was not available in our department, which was
towards better final VA in patients aged < 6 years, but this did not reliably associated with a spectrum of demyelinating disor- ders
have statistical significance [30]. A study in Taiwan reported that including relapsing paediatric demyelination [41, 42]. Fifth, the
poor visual recovery (<20/40) in children was associated with follow-up was not standardized and relatively short, and analyses
younger age (≤10 years) but not with initial VA, sex, laterality, of the conversion rate of MS and NMOSD were not performed.
underlying diagnosis, and abnormalities of brain MRI [23]. Further, Sun et al. reported a relatively low conversion rate
However, two other studies found no association between the age (12.5%) of MS in children with ON in Taiwan and ADEM was
at onset and final VA [15, 21]. The discrepancy may be caused by reported to be the most common systemic cause [23]. In Korean
different ethnicities, small sample size, distribution of ages, children, Kim et al. showed that only two patients (7.7%)
various phenotypes of ON, or different follow-up times. Con- developed MS [18]. More studies with longer-term follow-up and
sistent with most previous studies, we confirmed that several standardized evaluations are necessary.
baseline parameters such as sex, laterality, initial visual acuity, In summary, the clinical features of ON in Chinese
appearance of ODE, MRI findings, and treatment did not affect children were similar to those of children in other Asian
the final visual function [15, 19, 23, 33]. countries. Paediatric ON was associated with severe vision loss
Severe vision loss, a high prevalence of AQP-4 IgG, and and relatively good visual recovery. The majority of this cohort
poor visual recovery were reported to be common in Chinese (53.9%) had final VA of at least 20/40. Age at onset of <10 years
adults with ON [38]. We performed AQP-4 IgG testing in 47 predicted better visual outcomes. No other clinical parameters
patients, and 13 (27.7%) were seropositive. However, we did not were significantly correlated with the final visual function.
observe any correlations between underlying diagnosis, AQP-4
IgG status, and final VA in this study. The small sample size in
Competing Interests
our subgroup analysis may explain the lack of correlations.
Banwell et al. found that AQP-4 IgG was seropositive in 78% of The authors declare that there are no competing interests.
children with recurrent NMO [39]. Absoud et al. reviewed 20
children with NMOSD in the UK and reported that the VA of 10
of 12 patients with seropositive AQP-4 IgG was <20/200 in at Authors’ Contributions
least one eye and the bilateral VA was <20/200 in 58% of the
patients after a mean follow-up of 6.1 years [40]. Most previous Huanfen Zhou and Wei Wang contributed equally to this work
studies of ON in children did not detect the serum AQP-4 IgG and share the first authorship. All the authors concur with the
status. In a Korean study by Kim et al. the status of AQP-4 IgG submission.
was only available in three patients [18]. Thus, prospective
studies with a large sample size and various ethnicities are Acknowledgments
required to clarify the influence of AQP-4 IgG on final visual
outcomes in children with ON. This work was supported by a grant from the National High
The strengths of this study included the uniform sample Technology Research and Development Program of China (863
of children with the first episode of ON, standardized treat- ment, Program) (no. 2015AAO20511).
and detection of AQP-4 IgG status. On the other hand, this study
also has a number of limitations. First, the nature of the
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