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Clinical characteristics and prognosis of myelin oligodendrocyte glycoprotein antibody-seropositive paediatric optic neuritis in China
  1. Honglu Song1,
  2. Huanfen Zhou1,
  3. Mo Yang1,
  4. Shaoying Tan1,2,
  5. Junqing Wang1,
  6. Quangang Xu1,
  7. Hongjuan Liu1,
  8. Shihui Wei1
  1. 1 Department of Ophthalmology, Chinese PLA General Hospital, Beijing, China
  2. 2 Joint Shantou International Eye Center, Shantou University and Chinese University of Hong Kong, Shantou, China
  1. Correspondence to Professor Shihui Wei, Department of Ophthalmology, Chinese PLA General Hospital, Beijing 100853, China; weishihui58{at}


Background/Aims To investigate clinical characteristics and prognosis of paediatric optic neuritis (PON) in patients seropositive for myelin oligodendrocyte glycoprotein antibody (MOG-Ab) in China.

Methods Children displaying initial onset of optic neuritis (ON) were recruited from the Neuro-ophthalmology Department in the Chinese People’s Liberation Army General Hospital from January 2016 to August 2017. They were assigned into three groups based on antibody status: MOG-Ab-seropositive ON (MOG-ON), aquaporin-4 antibody-seropositive ON (AQP4-ON) and double seronegative ON (seronegative-ON).

Results Totally 48 patients were assessed, including 25 MOG-ON (52.1%), 7 AQP4-ON (14.6%) and 16 seronegative-ON (33.3%). The MOG-ON and seronegative-ON cohorts had equal ratios of female/male, but the AQP4-ON cohort was predominantly females (100%). The patients with MOG-ON were significantly younger at onset compared with the AQP4-ON group. Of the MOG-ON eyes, 97.6% had good recovery of visual acuity (VA) (≥0.5) compared with33.3% of AQP4-ON eyes (p<0.001). However, there was no significant difference compared with the seronegative-ON eyes (82.6%, p=0.052). Two children in the MOG-ON group ended up being diagnosed with acute disseminated encephalomyelitis, while only one patient in the AQP4-ON group developed neuromyelitis optica during follow-up. Patients with MOG-ON had thicker peripapillary retinal nerve fibre layers overall and in the superior and inferior quadrants than in patients with AQP4-ON (p=0.005, p=0.002 and p=0.024, respectively). In addition, the macular ganglion cell-inner plexiform in MOG-ON eyes became significantly thicker than in AQP4-ON eyes (p=0.029). Orbital MRI revealed a larger proportion of patients with MOG-ON had intracranial optic nerve involvement than patients with seronegative-ON (51.2% vs 17.4%, p=0.009).

Conclusion MOG-ON was the most common PON subtype in China. MOG-ON had different clinical features including earlier age of onset, equal female/male ratio, better recovery of VA and thicker peripapillary retinal nerve fibre and macular ganglion cell-inner plexiform layers. MOG-Abs may be a potential biomarker for determining visual prognosis with PON.

  • pediatric optic neuritis
  • myelin oligodendrocyte glycoprotein antibody
  • aquaporin-4 antibody
  • neuromyelitis optica.

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Optic neuritis (ON) is a disorder characterised by inflammatory demyelination of the optic nerve and predominantly affects young adults between ages of 18 and 45 years. Much of our understanding of ON comes from the Optic Neuritis Treatment Trial (ONTT), which focused on ON in adult Caucasians.1 Paediatric optic neuritis (PON) has different clinical features and a better prognosis than adult ON.2 3 PON occurs in 23% of Canadian children presenting with an initial demyelinating event.4 PON may be an idiopathic isolated event, but it also occurs in conjunction with multifocal inflammatory conditions of the central nervous system, such as acute disseminated encephalomyelitis (ADEM), multiple sclerosis and neuromyelitis optica (NMO).3

In the Chinese population, NMO is the more common central nervous system inflammatory demyelinating disorder.5 The presence of aquaporin-4 (AQP4) antibody is an important biomarker for neuromyelitis optica spectrum disorders (NMOSDs).6 7 Recent evidence suggests that some patients with NMO seronegative for AQP4-antibody are seropositive for antibodies against myelin oligodendrocyte glycoprotein (MOG).8 In recent years, accumulating evidence has increased awareness of the potential value of MOG antibody in differentiating between ON phenotypes.9 10

The aetiologies and clinical characteristics of ON in Asians have not been characterised as well as those in Caucasians, especially for children. In addition, the prevalence and incidence of PON in the African-American population has been determined to be 3.2 and 0.09–0.18, respectively, per 100 000 people.11 However, there have only been a few reports on PON in Asia2 12–14 and the number of cases assessed in these reports was too small to draw clear conclusions. Therefore, the clinical characteristics of MOG-Ab-positive PON remain unclear. To date, little is known about the frequency of MOG-ON and its characteristics in Chinese children with PON. Therefore, this retrospective observational study recruited Chinese children with ON, including those with MOG-ON, AQP4-ON and seronegative-ON. The clinical characteristics and prognosis of patients with MOG-Ab-positive PON in China were then assessed.

Materials and methods

Patient enrolment

Clinical data were retrospectively collected from hospitalised patients (<18 years) diagnosed with PON at the Neuro-ophthalmology Department of the Chinese People’s Liberation Army General Hospital (PLAGH) from January 2016 to August 2017. This study protocol was approved by the Ethics Committee at the Chinese PLAGH and met the tenets of the Declaration of Helsinki and applicable Chinese laws. Informed consent was obtained from the patients and their parents. All children were treated with intravenous methylprednisolone (20 mg/kg with a total dose of not more than 1000 mg/day) for 3 days followed by a taper of oral prednisone (starting dose 1 mg/kg/day) with variable durations, based on the subtype of and recovery from PON. Follow-up data were obtained through clinical examinations during return visits and surveys over the telephone with the parents of the patients. All patients were followed for at least 6 months.

Diagnostic criteria

ON was diagnosed in accordance with ONTT guidelines.1 The detailed inclusion criteria were (1) the patient presented with their first ON episode with acute loss of visual acuity (VA) or visual field in the presence or absence of eye pain, (2) the age at disease onset was <18 years and (3) the patient presented with at least one visual abnormality of abnormal visual evoked potential, visual field defect and relative afferent pupillary defect.

Exclusion criteria included (1) the patient presented with any other type of optic neuropathy, such as metabolic, vascular, toxic, hereditary, infiltrative or compressive optic neuropathy, (2) the presence of craniocerebral lesions other than those from demyelinating diseases involving the optic chiasm or optic pathway downstream of the optic chiasm and optic cortex, (3) the presence of anterior segment, ametropia, glaucoma or retinal or macular diseases, (4) the patient having an unknown serum MOG or AQP4 antibody status and (5) incomplete patient clinical or follow-up data.

Laboratory examinations

Serum and cerebrospinal fluid (CSF) samples were obtained from each patient within 1 month after the ON attack. Serum samples were tested for the presence of MOG and AQP4 antibodies using a cell-based assay (Euroimmun, Lübeck, Germany). Based on their serum antibody status, the enrolled children were categorised as either MOG-ON, AQP4-ON or seronegative-ON.

All patient sera were tested for autoantibodies, including antinuclear antibody, anti-Sjögren’s-syndrome-related antigen A, anti-Sjögren’s-syndrome-related antigen B, human leucocyte antigen-B27, rheumatoid factor, anticardiolipin antibodies (ACLs and b2-GPI), anti-thyroglobulin antibodies, antithyroid peroxidase autoantibody and antineutrophil cytoplasmic antibody in the Examination Center for Biomedical Research of PLAGH. Additionally, the CSF was also tested for white blood cell count and protein and IgG levels.

Neuro-ophthalmology examinations

Best-corrected visual acuity was evaluated as the main outcome based on the standard table of vision logarithms at a distance of 5 m. Subjects who were unable to read any letters at a distance of 1 m were further examined by finger count, hand movements or light perception.

Peripapillary retinal nerve fibre layers (pRNFLs) and macular ganglion cell-inner plexiform layers (mGCIPLs) were assessed at least 3 months after the ON attack using high-definition spectral domain optical coherence tomography (OCT; Carl Zeiss Meditec, Dublin, California, USA).

All enrolled children underwent orbital MRI with T2-weighted image and gadolinium-enhanced T1 sequences. The anterior visual pathways were divided into five segments: orbital, canalicular, intracranial and the optic chiasm and tract.15 Head or spinal MRIs were performed in patients with myelitis or systemic symptoms.

Statistical analysis

Demographic parameters were described and compared between different patient cohorts. Statistical analyses were conducted using SPSS V.20.0 software (IBM, New York, USA). Categorical data were analysed using χ² or Fisher’s exact tests where appropriate and quantitative data were analysed with independent sample t-tests. All probability values were two-tailed and considered to be significant at p<0.05.


Demographics and clinical characteristics

Table 1 summarises the demographics and clinical characteristics of the paediatric patients enrolled in the present study. Forty-eight cases (73 eyes) were assessed in this study cohort, of which, 27 were female (56.3%). The mean age at onset was 10.6±4.4 years (range of 3–17 years). Twenty-five patients (52.1%) experienced bilateral involvement, while 23 (47.9%) experienced unilateral involvement. The follow-up duration ranged from 6 to 30 months with a mean time of 16.10±6.13 months. All patients underwent serum MOG-Ab and AQP4-Ab testing, which revealed 25 patients had MOG-ON (52.1%), 7 had AQP4-ON (14.6%) and 16 had seronegative-ON (33.3%). No patients were found to be both MOG-Ab and AQP4-Ab seropositive. In this study cohort, 58 eyes (79.5%) were 0.1 or worse at the initial attack and 62 eyes (84.9%) were 0.5 or better at the final visit.

Table 1

Patient demographics and clinical characteristics in this study

Table 2 presents the demographics and clinical characteristics of the different PON subgroups. In the MOG-ON group, the mean age at onset was 9.7 years (range of 3–17 years) compared with 14.1 years (range of 8–17 years) for the AQP4-ON group and 10.5 years (range of 3–17 years) for the seronegative-ON group. Patients with MOG-ON were significantly younger than the patients with AQP4-ON (p=0.012). The MOG-ON cohort had an equal ratio of females/males (1:1.1), similar to the seronegative-ON cohort (1:1), but distinct from the predominance of females (100%) in the AQP4-ON cohort. The frequencies of ocular pain, bilaterality, optic disc swelling and presence of abnormal autoimmune antibodies were not significantly different among the three groups. The levels of protein, IgG and white cells in the CSF were also not significantly different.

Table 2

Demographics and clinical characteristics of different paediatric ON patient subgroups

Visual outcomes and clinical prognosis

Table 3 compares the visual outcomes and clinical prognosis of children in the MOG-ON, AQP4-ON and seronegative-ON groups. After treatment of the initial attack, 37 eyes (97.4%) in the MOG-ON group had good visual recovery (≥0.5) compared with the eyes in the AQP4-ON (4, 44.4%) and seronegative-ON groups (19, 82.6%) (p<0.001 and p=0.062, respectively). At the final visit, 40 eyes (97.6%) had a better visual recovery (≥0.5) in the MOG-ON group compared with the AQP4-ON (3, 33.3%) and seronegative-ON groups (19, 82.6%; p<0.001 and p=0.052). During follow-up, 12 patients (25.0%) experienced at least one episode of recurrence of ON. The MOG-ON and AQP4-ON groups had similar recurrence rates (32 vs 42.9%, p=0.667). The MOG-ON group had a higher recurrence rate than the seronegative-ON group (32 vs 6.2%, respectively, p=0.066). Only one patient in the AQP4-ON group developed NMO over the course of the follow-up. Two children in the MOG-ON group had an ON attack concurrently with an episode of ADEM and received a final diagnosis of ADEM-ON.

Table 3

Comparison of visual outcomes and clinical prognosis in MOG-ON, AQP4-ON and seronegative-ON groups

OCT measurements

Table 4 presents the pRNFL and mGCIPL thicknesses as measured by spectral domain-OCT. OCT measurements were taken in 24 MOG-ON, 6 AQP4-ON and 14 seronegative-ON eyes. The MOG-ON eyes were found to have less loss of pRNFL than the AQP4-ON group (p=0.005). We also found the MOG-ON eyes experienced less thinning of the superior and inferior quadrants compared with AQP4-ON eyes (p=0.002 and p=0.024; table 4). The pRNFL thinning did not display a quadrant predisposition in the MOG-ON and seronegative-ON groups.

Table 4

Comparison of pRNFL and macular GCIPL thickness in patients with MOG-ON, AQP4-ON and seronegative-ON

The mGCIPL measurements are shown in table 4. There was a less reduction in the average mGCIPL thickness (mean±SD) in the MOG-ON group than in the AQP4-ON group (62.08±7.56 vs 54.67±4.18 µm, respectively, p=0.029). Furthermore, we found a significant difference in the superior (63.97±8.56 and 54.17±5.00 µm, respectively, p=0.014), temporal inferior (63.83±6.89 and 55.67±6.89 µm, respectively, p=0.015) and temporal superior quadrants (64.17±7.88 and 53.33±6.35 µm, respectively, p=0.017). There were no differences in mGCIPL thickness in any quadrant between the MOG-ON and seronegative-ON groups (62.08±7.56 and 60.86±7.90 µm, respectively, p=0.638; table 4).

MRI manifestation

Table 5 presents the optic nerve MRI T2 hyperintensity (with or without enhancement) results. No significant differences were noted in the MRIs concerning the proportion of orbital segment lesions in MOG-ON children compared with AQP4-ON and seronegative-ON children (p>0.999 and p=0.240, respectively). The proportion of patients experiencing intracranial optic nerve involvement was higher in the MOG-ON cohort than the seronegative-ON cohort (51.2 vs 17.4%, respectively, p=0.009). The MOG-ON and AQP4-ON cohorts had almost the same incidence of chiasma involvement based on MRI imaging (4.9 vs 11.1%, respectively, p=0.456). Furthermore, none of children displayed optic tract involvement.

Table 5

Comparison of optic nerve MRIs in patients with MOG-ON, AQP4-ON and seronegative-ON


In this single-centre study, we evaluated the MOG-Ab status of Chinese paediatric patients with ON using a cell-based assay and found 52.1% (25/48) of all patients with PON were seropositive for MOG-Ab. A higher prevalence of MOG-Ab seropositivity was found in patients with a paediatric demyelinating disease, particularly ADEM.16 In another study, similar to our results, MOG-Abs were detected in 21 of 37 patients (56.8%) with an acute episode of PON at 6 paediatric hospitals in Germany and Austria.17 The presence of serum MOG-Abs has been proposed to indicate a specific subtype of ON, as it is becoming clear that this biomarker is associated with specific disease features and may be a novel serodiagnostic biomarker of demyelination.18 Zhou et al 13 tested the serum of 47 Chinese children patients and determined that among them, 13 (27.7%) were AQP4-Ab-positive; however, MOG-Abs were not tested for in this study. To our knowledge, the present study is the first report on the proportion of paediatric MOG-ON in China.

In our MOG-ON paediatric cohort, there was a frequency of females similar to that in the seronegative-ON group (48% vs 50%), but lower than that of the AQP4-ON group (100%). This is supported by data from previous studies, which reported patients with MOG-ON had a prevalence in females of 448% and 75%19 compared with AQP4-ON, which had a high female preference (90%).8 Previous studies have shown that MOG-Abs are prevalent in younger patients (4–8 years) with encephalopathy, while older patients (13–18 years) present almost exclusively with ON.20 Our previous study21 reported the onset in MOG-ON occurs at a younger age than AQP4-ON (range: 5–63 years vs 8–72 years, respectively). However, this study was biased by a mixed population that included both adults and children. PON is well known to have different clinical features than ON in adult patients. The clinical features of MOG-ON in Chinese children have remained elusive and should be studied as a separate entity. In this study focusing on only children, we found patients with MOG-ON were significantly younger at onset compared with patients with AQP4-ON.

In our study, 97.4% of the eyes in the MOG-ON children as well as 82.6% of the seronegative-ON eyes, had good recovery of VA, while patients with AQP4-ON had worse VA outcomes (44.4%), which is consistent with other studies on Asian populations.22 23

MOG-Abs can be detected in children with AQP4-Ab seronegative NMOSD, recurrent ON, transverse myelitis and multiphasic ADEM24 25; a proportion of these children will develop a relapsing type of disease.26 27 In our study, 32% of the children in the MOG-ON cohort presented with the relapsing form of disease. ADEM followed by ON is a rare, but distinct, clinical phenotype in children.28 In our cohort, two children had an ON attack during an episode of ADEM. MOG-Abs may play an important role in ADEM clinically29 and the MOG-Ab titre is associated with ADEM severity.30 However, due to the low number of ADEM cases, we were unable to identify a relationship between the titre and severity of ADEM-ON. Finally, only one patient in the AQP4-ON group developed NMO during follow-up. Because the follow-up duration was relatively short, the conversion rate for ADEM and NMO should be confirmed in further longitudinal studies.

OCT measurements, such as of pRNFL and mGCIPL thickness, are extensively used as structural markers of axonal loss in patients with ON and to differentiate between subtypes of ON.5 31 Our study found significant differences between the MOG-ON and AQP4-ON groups in terms of OCT measurements. The superior and inferior quadrants of pRNFL were preferentially damaged in AQP4-ON eyes compared with the MOG-ON eyes, which is consistent with previous studies. This may be because AQP4 is strongly expressed in the superior and inferior quadrants of the pRNFL with plenty of vessels and facing vitreous bodies, which can cause parallel and more severe injury and induce more pRNFL thinning in AQP4-ON eyes.5 Our study also found damage preferentially occurred in the superior, temporal inferior and temporal superior quadrants of the mGCIPL in AQP4-ON eyes compared with MOG-ON eyes. The mechanism underlying these distinct types of mGCIPL injury remains unclear.

Some studies have found similar results for pRNFL and mGCIPL , where they are better preserved in patient with MOG-ON eyes than AQP4-ON eyes; however, the number of patients enrolled in this study was small.23 Another study yielded32 controversial results, where patients who were MOG-Ab-positive had more retinal atrophy than patients with AQP4-Ab-positive NMOSD. The mechanism of this paradox is unknown. Zhao et al.31 presumed that the myelin sheath of ganglion cells of the optic nerve, which is the target of MOG-Abs, is injured severely during the acute attack of ON, where the axons are well preserved and VA improves after repair of the myelin sheath, but there is still pRNFL thinning on the OCT.

In our cohort, optic nerve orbital segment involvement occurred in 92.7% of children with MOG-ON, whereas the intracranial portion of the optic nerve was involved in more patients with MOG-ON than patients with seronegative-ON (51.2% vs 17.4%, p=0.009). Furthermore, 4.9% of children with MOG-ON had an optic chiasm lesion, indicating the MRI manifestation of MOG-ON can be longitudinally extensive. No differences were found in the MRI features of the AQP4-ON and MOG-ON groups, which is in contrast to the study by Ramanathan et al,33 where MRI lesions in patients with MOG-ON tended to involve the anterior optic nerve segment and AQP4-ON lesions were in the posterior optic nerve segment.

This study had several limitations. First, this was a retrospective single-centre study, which can introduce selection bias, precluding the confirmation of the cause and effect relationship. Second, MOG-Ab titres were measured within 1 month after onset of ON, but no relationship between titre and prognosis was discerned. Third, the follow-up was not standardised and relatively short. Therefore, prospective studies with a large sample size and involving patients of varied ethnicities are required to clarify the influence of MOG-Abs and AQP4-Abs on the final prognosis of patients with PON.


Based on the results of the present study, MOG-ON is the most common PON subtype identified in Chinese children. MOG-ON had clinical features distinct from AQP4-ON, including earlier age of onset, equal female/male ratio, better recovery of VA and a thicker pRNFL and mGCIPL. MOG-Abs may be a potential biomarker for determining visual prognosis with PON.



  • HS, HZ and MY are joint first authors.

  • HS, HZ and MY contributed equally.

  • Contributors Study was designed and conducted by HS, HZ, MY, QX and SW. Collection, analysis, management and interpretation of the data were performed by HS, HZ, MY, QX and HL. Manuscript was prepared by HS, HZ and MY. Critical revision of the manuscript was performed by ST and JW. Review and final approval of the manuscript was performed by all the authors.

  • Funding This study was supported by the 863 Plan Biological and Medical Technology project of China (No: 2015AA020511).

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval The Institutional Review Board at the Chinese PLAGH.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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