Journal of Ophthalmology
Volume 2017 (2017), Article ID 3458356, 7 pages
https://doi.org/10.1155/2017/3458356

Research Article

Optic Neuritis in the Older Chinese Population: A 5-Year Follow-Up Study

Junqing Wang,¹ Huanfen Zhou,1,2 Limin Qin,¹ Chunxia Peng,¹ Jie Zhao,¹ Da Teng,¹ Dahe Lin,¹ Nanping Ai,¹ Quangang Xu,1,3 and Shihui Wei¹

¹Department of Ophthalmology, Chinese PLA General Hospital, Beijing, China
²Department of Ophthalmology, The First Affiliated Hospital of Chinese People’s Liberation Army General Hospital, Beijing, China
³Department of Neurology, Chinese PLA General Hospital, Beijing, China

Correspondence should be addressed to Shihui Wei; weishihui58@126.com

Received 15 June 2017; Revised 26 September 2017; Accepted 9 October 2017; Published 11 December 2017

Academic Editor: Biju B. Thomas

Copyright © 2017 Junqing Wang 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.

Abstract.

Objective. This study aims to describe the clinical manifestations and outcomes in a cohort of older Chinese patients. Method. A retrospective study of patients aged ≥ 45 years who had a first episode of optic neuritis (ON) between May 2008 and November 2012. Clinical features at onset and last follow-up were analyzed within subgroups (age 45–65 years and age ≥ 65 years). Results. 76 patients (99 eyes) were included, of which 58% were females. The mean age at presentation was 55.53 ± 8.29 years (range: 45–83 years). Vision loss was severe at presentation, with initial best corrected vision activity (BCVA) < 20/200 in 93% and final BCVA < 20/200 in 53% of patients at 5-year follow-up. Final BCVA significantly correlated with the initial BCVA and peripapillary retinal nerve fiber layer. At last follow-up, 14.5% were diagnosed with neuromyelitis optica spectrum disorder (NMOSD), 1.3% were diagnosed with multiple sclerosis (MS), 5.2% with chronic relapsing inflammatory optic neuropathy, 1.3% with infectious ON, and 19.7% with autoimmune ON. None of the elderly group (≥65 years) developed NMOSD or MS. Conclusion. Chinese patients in the age group ≥ 65 years with ON are less likely to develop NMOSD or MS. Notwithstanding, they had more severe visual loss at onset and poor recovery.

1. Introduction

Optic neuritis (ON) is the most common inflammatory demyelinating neuropathy [1]. It can manifest as either an isolated episode or be caused as a result of the patient suffering from multiple sclerosis (MS) or neuromyelitis optica spectrum disorders (NMOSD) [2, 3].

The optic neuritis treatment trial (ONTT) studied patients between 18 and 45 years old with acute, unilateral optic neuritis; most of whom had good vision recovery [4]. This has been classified as typical ON [5]. In ON patients, ethnicity has been documented as an important factor influencing clinical features and the outcome [6]. It has been identified that NMOSD is more likely to develop in Asia, whereas MS is more prevalent in western countries [7]. Previously, we reported a cohort of Chinese ON patients with atypical clinical features and poor recovery [8]. African-American patients were also found to have more severe vision loss and less vision recovery [9].

Although, the ONTT is the largest study to date of ON; it included only patients between 18 and 45 years. There are, currently, only a limited number of studies on the clinical features of ON in the older population. We previously reported a cohort of Chinese ON patients of all ages [10]. We observed less vision recovery in patients older than 45 years, compared to patients younger than 45 years. However, we could not divide patients into more specific age groups for analysis due to the small number of patients. We therefore carried out this study to describe the clinical manifestations and investigative outcomes in two age groups, middle-aged patients (45–65 years) and elderly patients (>65 years).

2. Patients and Methods

This retrospective study included patients evaluated for a first episode of optic neuritis in the Neuro-ophthalmology Clinic of the Chinese PLA General Hospital (PLAGH) in Beijing between May 2008 and November 2012. Only patients who had a first episode of ON were included in the study. To compare clinical features, we divided patients into two groups, middle-aged group (45–65 years) and elderly group (older than 65 years).

Inclusion criteria are the following: (i) the first episode ON with BCVA loss; (ii) older than 45 years; (iii) follow-up of ≥5 years; (iv) no prior steroid treatment; (v) objective evidence of visual abnormalities: relative afferent papillary defect (RAPD), visual field defects, and abnormal visual evoke potential (VEP).

Exclusion criteria are the following: (i) nonarteritic anterior ischemic optic neuropathy (NAION), (ii) disorders other than ON, including compressive, hereditary, vascular, toxic, traumatic, metabolic, or infiltrative neuropathy, (iii) ocular comorbidity including uveitis or glaucoma, and (iv) amblyopia.

To exclude a diagnosis of NAION, known risk factors for ischemic disease were evaluated, including [11] (i) systematic conditions: hypertension, diabetes, hyperlipidaemia, sleep apnoea syndrome, and nocturnal hypotension; (ii) medical history: erectile dysfunction drugs, amiodarone, and cataract surgery; (iii) “crowded” optic disc.

The protocol of the study was approved by the institutional review board at the Chinese PLAGH and performed in accordance with the tenets of the Helsinki Declaration. Informed consent was obtained from all the patients.

2.1. Clinical, Immunological, and Radiological Assessment

All patients underwent the ophthalmic exam, including ocular symptoms, best corrected visual acuity (BCVA), pupil function test, optic disc appearance, colour vision test, optical coherence tomography (OCT), and fluorescence angiography (FFA). The BCVA in all patients was evaluated using the Snellen visual chart, and the data was transformed as the logarithm of the minimum angle of resolution (logMAR) values [12]. In patients with bilateral optic neuritis, only the eyes presenting the worst BCVA at onset were included in this study.

Because of the retrospective nature of the study, some investigation results were unavailable for a number of patients. Orbital magnetic resonance imaging (MRI) and head MRI were used to detect the Gd-enhancement in the optic nerve or in any brain lesion. The MR images were reviewed by the same experienced radiologist to ensure consistency of the results. Serums were screened for antinuclear antibody (ANA), antineutrophil cytoplasmic antibodies (ANCA), extractable nuclear antigen antibodies (SSA and SSB), anticardiolipin antibodies (ACLs and β2-GPI), rheumatoid factor (RF) and major histocompatibility complex-B27 (HLA-B27), and aquaporin-4 antibody (AQP4-Ab) status. The serum AQP4-Ab level was assessed using the cell-based assay [13].

2.2. Statistical Analyses

All statistical analyses were performed using SPSS 22.0 software (IBM Corporation, New York, USA). Chi-squared Pearson test was applied for categorical variables and Mann–Whitney U test for quantitative variables. The Pearson correlation test was also used to determine the relationships between the recovery indices. A value of was considered statistically significant.

3. Results

3.1. Demographic and Clinical Characteristics

76 patients (99 eyes) were included in this study, of which 44 were females (57.9%). The mean age at onset was 55.5 ± 8.3 (range: 45–83) years. The follow-up duration ranged from 5–8 years, with a mean of 5 ± 1.49 years. There were 53 (69.7%) patients with unilateral disease and 23 (30.3%) with bilateral disease. The average relapse rate was 0.46 ± 0.23/year (range: 0.14–1/year). The details of the demographic and clinical characteristics of middle-aged and older patients are summarized in Table 1. All patients received intravenous methylprednisolone therapy (1 g/day) for three days, followed by oral prednisolone (1 mg/kg/day) for two weeks, in keeping with the recommendations of the ONTT [4].

Table 1: Baseline characteristics of middle-aged and older patients.

Baseline characteristics
Frequency
Middle-aged group (age < 65 years)
Elderly group (age ≥ 65 years)
value

Total patients
76
68
8
—

Age at onset (years)
Average
55.53 ± 8.29 (45–83)
53.28 ± 5.05 (45–65)
74.75 ± 4.56 (72–83)
NS

Gender n (%)
Male
44 (57.9)
30 (44.1)
2 (25)
NS

Female
32 (42.1)
38 (55.9)
6 (75)

Laterality, n (%)
Unilateral
53 (69.7)
49 (72.1)
4 (50)
NS

Bilateral
23 (30.3)
19 (27.9)
4 (50)

Pain, n (%)
Present
25 (53.2)
22 (50.0)
3 (100)
NS

Absent
22 (46.8)
22 (50.0)
0 (0)

Initial disc appearance, n (%)
Present
30 (40.5)
29 (50.0)
1 (87.5)
NS

Absent
44 (59.5)
37 (50.0)
7 (12.5)

Autoimmune antibodies, n (%)
Normal
43 (67.2)
38 (67.9.0)
5 (67.2)
NS

Abnormal
21 (21.8)
18 (32.1)
3 (32.8)

AQP4 antibody, n (%)
Seropositive
10 (20.4)
10 (22.2)
0 (0)
NS

Seronegative
39 (79.6)
35 (77.8)
4 (100.0)

CSF study, n (%)
Normal
23 (50.0)
23 (51.1)
0 (0)
NS

Abnormal
23 (50.0)
22 (48.9)
1 (100.0)

Orbit MRI, n (%)
Normal
9 (17.0)
7 (14.9)
2 (33.3)
NS

Abnormal
44 (83.0)
40 (85.1)
4 (66.7)

Head MRI, n (%)
Normal
26 (52.0)
25 (55.6)
1 (20.0)
NS

Abnormal
24 (48.0)
20 (44.4)
4 (80.0)

Relapse rate (N/Y)
Average
0.46 ± 0.23 (0.14–1)
0.46 ± 0.23
0.44 ± 0.18
NS

CSF: cerebrospinal fluid; AQP4-Ab: anti-aquaporin-4 antibody; MRI: magnetic resonance imaging.

3.2. Visual Acuity

Vision loss was severe at onset, with BCVA < 20/400 in 74 (74.8%) eyes. 49 (72.06%) patients aged ≤ 65 years and 8 (100%) patients aged ≥ 65 years had BCVA < 20/400. At the last follow-up, 30 (44.12%) patients aged ≤ 65 years and 7 (87.5%) patients aged ≥ 65 years had BCVA < 20/400. The initial BCVA of the patients aged < 65 years was significantly better from that of the patients aged ≥ 65 years (); however, there was no difference in final BCVA (). There was also no significant difference between initial BCVA and final BCVA in patients < 65 or ≥65 years (, ). The detailed comparison is summarized in Table 2.

Table 2: Factors for visual prognosis in middle-aged and elderly patients with optic neuritis.

Factors

Number of patients with final VA < 20/400
Number of patients with final VA ≥ 20/400
value

Initial BCVA
>20/400
3
16
0.001

<20/400
35
22

Sex
Male
15
17
NS

Female
23
21

Age
<65
31
37
NS

≥65
7
1

Laterality
Unilateral
24
29
NS

Bilateral
14
9

Initial disc appearance
Normal
23
21
NS

Swollen
14
16

Systemic association
Normal
20
23
NS

Abnormal
10
11

CSF
Normal
10
12
NS

Abnormal
13
11

Serum AQP4-Ab status
Seropositive
7
3
NS

Seronegative
17
22

Orbital MRI
Normal
4
5
NS

Abnormal
22
22

Brain MRI
Normal
11
15
NS

Abnormal
13
11

pRNLF
Average
64.00 ± 12.91
68.58 ± 18.70
NS

Superior
69.52 ± 20.72
79.23 ± 32.63
NS

Nasal
59.60 ± 9.39
60.35 ± 10.00
NS

Inferior
72.88 ± 23.53
83.88 ± 30.37
NS

Temporary
50.85 ± 15.81
52.92 ± 10.15
0.045

BCVA: best corrected visual acuity; CF: count finger; CSF: cerebrospinal fluid; AQP4-Ab: anti-aquaporin-4 antibody; MRI: magnetic resonance imaging; pRNLF: peripapillary retinal nerve fibre layer, NS: nonsignificant; .

3.3. Immunological Findings

Of the 76 patients, 49 patients had AQP4-Ab test, of which 11 (22.4%) were seropositive and 38 (77.6%) were seronegative. 64 patients had autoimmune antibody screening test, and 21 (21.6%) were abnormal, including antinuclear antibody (ANA), anticardiolipin antibody (ACA), double-stranded DNA (dsDNA), anti-Ro antibody (SS-A), anti-La antibody (SS-B), anti-β-glycoprotein antibody, rheumatoid factor (RF), and HLA-B27. The positive rate was not related to AQP4-Ab rate. There was no significant difference between patients < 65 years and ≥65 years.

3.4. MR Imaging Findings

Of the 76 patients, 53 patients had orbital MRI at presentation, of which 44 (83.0%) had optic nerve T2 lesions or optic nerve enhancement. 50 patients had head MRI imaging at the onset, 5 (10%) had demyelinating lesions, 8 (16%) had T2 lesions, and 9 (18%) had ischemic foci. The abnormal to normal ratio was not significantly different between patients < 65 years and ≥65 years.

3.5. OCT Imaging Findings

Of the 76 patients, OCT was performed in 51 patients, with the average time from the onset being 22.75 ± 23.00 months. Of the 51 patients, 45 patients were <65 years and 6 were ≥65 years. The peripapillary retinal nerve fibre layer (pRNFL) thickness (μm) was measured at the final follow-up. The thickness of pRNFL was not significantly different between patients < 65 years and ≥65 years, but the temporal thickness was significantly reduced in those with BCVA < 20/400 compared to ≥20/400 () (Figure 1). Thinning of the pRNFL was also found in those with positive AQP4-Ab ().

Figure 1: Peripapillary retinal nerve fibre layer (pRNFL) thickness measured by OCT. Temporal pRNFL was significantly reduced in eyes with BCVA < 20/400, ().

3.6. Correlation of Final BCVA with Other Parameters

The final BCVA was found to be significantly correlated only with the initial BCVA and temporal RNFL thickness (, ). Other variables examined in this patient cohort, such as sex, age, laterality, initial disc appearance, systemic association, orbital MRI findings, head MRI, AQP4-Ab status, and average thickness of pRNFL, were not significantly correlated with the final visual outcomes (Table 3).

Table 3: Visual outcomes Of Chinese middle-age and elder patients with optic neuritis.

Visual outcomes (worse eye at onset if bilateral)
Initial BCVA
Final BCVA

Age < 65 years
Age ≥ 65 years
Age < 65 years
Age ≥ 65 years

NLP ≤ BCVA < CF
31 (45.6)
8 (100)
16 (23.5)
2 (25.0)

CF ≤ BCVA < 20/400
18 (26.5)
0
14 (20.6)
5 (62.5)

20/400 ≤ BCVA < 20/66
14 (20.6)
0
17 (25.0)
0

20/66 ≤ BCVA < 20/20
3 (4.4)
0
17 (25.0)
1 (12.5)

BCVA ≥ 20/20
2 (2.9)
0
4 (5.9)
0

Total
68
8
68
8

Average LogMar BCVA
1.94 ± 0.86
2.63 ± 0.30
1.28 ± 0.98
1.72 ± 0.83

value
0.006
NS

NLP: light perception; LP: light perception; BCVA: best corrected visual activity; .

3.7. Final Diagnosis

At the last follow-up, there are 11 patients diagnosed with NMOSD, 4 with CRION, 1 with MS-ON, 1 with infectious ON, and 15 with autoimmune ON. None of the elderly group developed NMOSD or MS.

4. Discussion

Only a few cases of ON in middle-aged or elderly patients have been reported to date. In our study, the principal findings in ON patients ≥45 years were predominantly unilateral disease, severe reduction in visual acuity at presentation, and little recovery at 5-year follow-up.

The ONTT reported good recovery of BCVA in younger patients (18–45 years), with 36% having initial BCVA ≤ 20/200 and 8% with final BCVA ≤ 20/200 [4]. Other studies which included ON patients of all ages also reported better outcomes than our observation. A study of 27 native African patients conducted in Nigeria reported initial BCVA ≤ 20/200 in 60% and only 9% at 12-week follow-up [7]. However, the study only included 1 patient who was older than 50 years.

In the first ON study in older patients reported in 1988, outcomes were worse compared to the above two studies, with 61% having initial BCVA ≤ 20/200 and 17% final BCVA ≤ 20/200 [14].

A recent study, which is conducted in Korea, reported that patients > 50 years recovered well from ON attacks; all affected eyes had final BCVA > 20/40 within two months [15]. However, the small sample size, eight patients in total, may result in increase of the bias. In our study, we divided patients into two subgroups, one middle-aged group (45–65 years) and one elderly group (age ≥ 65 years). In comparison with the above studies, 64% of the middle-aged group and 100% of the elderly group had initial BCVA < 20/200 and 43% of the middle-aged group and 88% of the elderly group had final BCVA < 20/200, showing that visual recovery correlated inversely with age, that is, older patients recovered less vision in this cohort.

The first identified predictor of visual outcomes in this study is initial BCVA. ONTT reported a significant correlation between initial and final BCVA, consistent with our observations [6]. Other predictor in this study is the changes of pRNFL thickness in the temporal. pRNFL thinning manifested within 3 to 6 months after acute ON attack, then remained stable [16]. At 5-year follow-up, we observed particularly thinning in the temporal in patients with final BCVA < 20/400, compared to patients with final BCVA ≥ 20/400. Similar findings have been previously reported in ON patients by Pro et al. [17].

At 5-year follow-up, there were 11 patients diagnosed with NMOSD, 4 with CRION, and 1 with MS-ON. None of the elderly patients developed NMOSD or MS. Despite severe visual loss, elderly patients were less likely to have a diagnosis of NMOSD or MS. ONTT concluded that the risk of developing to MS is heavily dependent upon the MRI findings at onset [6]. For those patients with a normal brain MRI, a 15-year MS risk was 25%. In contrast, those with one or more MRI lesions consistent with demyelination had a 72% risk, with a higher lesion count conferring an even greater risk [18]. It has also been recognized that the risk of developing to NMOSD is higher in patients of Asian origin [19]. This may be associated with the high detection rate of AQP4-Ab in Asia (32.6%) compared to western countries (5.8%) [20, 21].

Myelin oligodendrocyte glycoprotein antibody (MOG-Ab) is also found associating with ON [22–24]. It was initially reported in a study of paediatric demyelinating disease and further reported in a series of related disorders: NMOSD, acute disseminated encephalomyelitis (ADEM), cortical encephalitis, Hashimoto’s encephalopathy, epilepsy, LETM, recurrent ON, and MS [25–27]. However, because this is a retrospective study, MOG antibody test was not available at the time. The strength of our study is that we carefully excluded the diagnosis of NAION in this cohort. NAION constitutes one of the major causes of blindness or seriously impaired vision among the middle-aged and elderly population [28]. Previous study on patients older than 50 years concluded that 6.25 patients per 100000 inhabitants were affected with NAION per year in Beijing [29]. NAION and ON patients share many symptoms and signs [30]. In this study, we did not only exclude patients with the risk factors for NAION, but also used MRI and FFA to further confirm the diagnosis, in order to obtain the uniform sample of the first episode of optic neuritis.

5. Conclusions

In summary, ON in the older population is less likely to develop to NMOSD or MS, especially in elderly patients (≥65 years), even though patients tend to present with more severe visual loss and poor recovery following classic steroid treatment. Further prospective studies are needed to confirm our observations and find an optimal treatment strategy for this population.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

Authors’ Contributions

Junqing Wang and Huanfen Zhou contributed equally.

Acknowledgments

This work was supported by a grant from the National High Technology Research and Development Program of China (863 Program) (no. 2015AAO20511).

References

A. Petzold, M. P. Wattjes, F. Costello et al., “The investigation of acute optic neuritis: a review and proposed protocol,” Nature Reviews Neurology, vol. 10, no. 8, pp. 447–458, 2014.

C. Eckstein and M. Tariq Bhatti, “Currently approved and emerging oral therapies in multiple sclerosis: an update for the ophthalmologist,” Survey of Ophthalmology, vol. 61, no. 3, pp. 318–332, 2016.

B. G. Weinshenker and D. M. Wingerchuk, “Neuromyelitis spectrum disorders,” Mayo Clinic Proceedings, vol. 92, no. 4, pp. 663–679, 2017.

R. W. Beck, P. A. Cleary, M. M. Anderson et al., “A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. The optic neuritis study group,” New England Journal of Medicine, vol. 326, no. 9, pp. 581–588, 1992.

M. Rodriguez, A. Siva, S. A. Cross, P. C. O'Brien, and L. T. Kurland, “Optic neuritis: a population-based study in Olmsted County, Minnesota,” Neurology, vol. 45, no. 2, pp. 244–250, 1995.

Optic Neuritis Study Group, “Visual function 15 years after optic neuritis: a final follow-up report from the optic neuritis treatment trial,” Ophthalmology, vol. 115, no. 6, pp. 1079–1082.e5, 2008.

C. N. Pedro-Egbe, B. Fiebai, and C. S. Ejimadu, “Visual outcome following optic neuritis: a 5-year review,” Nigerian Journal of Clinical Practice, vol. 15, no. 3, pp. 311–314, 2012.

H. Zhou, Q. Xu, S. Zhao et al., “Distinct clinical characteristics of atypical optic neuritis with seronegative aquaporin-4 antibody among Chinese patients,” British Journal of Ophthalmology, vol. 101, no. 12, pp. 1720–1724, 2017.

H. E. Moss, W. Gao, L. J. Balcer, and C. E. Joslin, “Association of race/ethnicity with visual outcomes following acute optic neuritis: an analysis of the optic neuritis treatment trial,” JAMA Ophthalmology, vol. 132, no. 4, pp. 421–427, 2014.

H. Zhou, S. Zhao, D. Yin et al., “Optic neuritis: a 5-year follow-up study of Chinese patients based on aquaporin-4 antibody status and ages,” Journal of Neurology, vol. 263, no. 7, pp. 1382–1389, 2016.

T. Chen, D. Song, G. Shan et al., “The association between diabetes mellitus and nonarteritic anterior ischemic optic neuropathy: a systematic review and meta-analysis,” PLoS One, vol. 8, no. 9, article e76653, 2013.

N. Z. Gregori, W. Feuer, and P. J. Rosenfeld, “Novel method for analyzing snellen visual acuity measurements,” Retina, vol. 30, no. 7, pp. 1046–1050, 2010.

S. Mader, A. Lutterotti, F. Di Pauli et al., “Patterns of antibody binding to aquaporin-4 isoforms in neuromyelitis optica,” PLoS One, vol. 5, no. 5, article e10455, 2010.

D. M. Jacobson, H. S. Thompson, and J. J. Corbett, “Optic neuritis in the elderly prognosis for visual recovery and long-term follow-up,” Neurology, vol. 38, no. 12, pp. 1834–1837, 1988.

J. Choi, S.-J. Kim, J. W. Chang, J. H. Kim, and Y. S. Yu, “Clinical characteristics of optic neuritis in Koreans greater than 50 years of age,” Korean Journal of Ophthalmology, vol. 26, no. 2, pp. 111–115, 2012.

E. H. Martinez-Lapiscina, M. Sepulveda, R. Torres-Torres et al., “Usefulness of optical coherence tomography to distinguish optic neuritis associated with AQP4 or MOG in neuromyelitis optica spectrum disorders,” Therapeutic Advances in Neurological Disorders, vol. 9, no. 5, pp. 436–440, 2016.

M. J. Pro, M. E. Pons, J. M. Liebmann et al., “Imaging of the optic disc and retinal nerve fiber layer in acute optic neuritis,” Journal of the Neurological Sciences, vol. 250, no. 1-2, pp. 114–119, 2006.

M. J. Morrow and M. W. Ko, “Should oral corticosteroids be used to treat demyelinating optic neuritis?” Journal of Neuro-Ophthalmology, vol. 37, no. 4, pp. 444–450, 2017.

M. Etemadifar, Z. Nasr, B. Khalili, M. Taherioun, and R. Vosoughi, “Review article epidemiology of neuromyelitis optica in the world: a systematic review and meta-analysis,” Multiple Sclerosis International, vol. 2015, Article ID 174720, 8 pages, 2015.

H. Kang, T. Chen, H. Li, Q. Xu, S. Cao, and S. Wei, “Prognostic factors and disease course in aquaporin-4 antibody-positive Chinese patients with acute optic neuritis,” Journal of Neurology, vol. 264, no. 10, pp. 2130–2140, 2017.

S. Jarius, J. Frederikson, P. Waters et al., “Frequency and prognostic impact of antibodies to aquaporin-4 in patients with optic neuritis,” Journal of the Neurological Sciences, vol. 298, no. 1-2, pp. 158–162, 2010.

A.-K. PrŁbstel, “Anti-MOG antibodies are present in a subgroup of patients with a neuromyelitis optica phenotype,” Journal of Neuroinflammation, vol. 12, no. 1, pp. 46-47, 2015.

K. Chalmoukou, H. Alexopoulos, S. Akrivou, P. Stathopoulos, M. Reindl, and M. C. Dalakas, “Anti-MOG antibodies are frequently associated with steroid-sensitive recurrent optic neuritis,” Neurology-Neuroimmunology Neuroinflammation, vol. 2, no. 4, article e131, 2015.

R. Höftberger, M. Sepulveda, T. Armangue et al., “Antibodies to MOG and AQP4 in adults with neuromyelitis optica and suspected limited forms of the disease,” Multiple Sclerosis Journal, vol. 21, no. 7, pp. 866–874, 2015.

Y. Nakamura, H. Nakajima, H. Tani et al., “Anti-MOG antibody-positive ADEM following infectious mononucleosis due to a primary EBV infection: a case report,” BMC Neurology, vol. 17, no. 1, pp. 1–4, 2017.

K.-A. Chen, F. Brilot, R. C. Dale, A. R. Lafferty, and P. I. Andrews, “Hashimoto’s encephalopathy and anti-MOG antibody encephalitis: 50 years after Lord Brain’s description,” European Journal of Paediatric Neurology, vol. 21, no. 6, pp. 898–901, 2017.

R. Ogawa, I. Nakashima, T. Takahashi et al., “MOG antibody–positive, benign, unilateral, cerebral cortical encephalitis with epilepsy,” Neurology-Neuroimmunology Neuroinflammation, vol. 4, no. 2, article e322, 2017.

S. S. Hayreh, “Ischemic optic neuropathies–where are we now?” Graefe's Archive for Clinical and Experimental Ophthalmology, vol. 251, no. 8, pp. 1873–1884, 2013.

L. Xu, Y. Wang, and J. B. Jonas, “Incidence of nonarteritic anterior ischemic optic neuropathy in adult Chinese: the Beijing eye study,” European Journal of Ophthalmology, vol. 17, no. 3, pp. 459-460, 2007.

J. F. Rizzo and S. Lessell, “Optic neuritis and ischemic optic neuropathy. Overlapping clinical profiles,” Archives of Ophthalmology, vol. 109, no. 12, pp. 1668–1672, 1991.