Clinical & Experimental
Neuroimmunology
REVIEW ARTICLE
Clinical characteristics of autoimmune optic neuritis
Izumi Kawachi
Department of Neurology, Brain Research Institute, Niigata University, Niigata, Japan
Keywords
multiple sclerosis; neuromyelitis optica spec-
trum disorders; optic neuritis
Correspondence
Izumi Kawachi, MD, PhD, Department of
Neurology, Brain Research Institute, Niigata
University, 1-757 Asahimachi, Chuo-ku, Niigata
951-8585, Japan.
Tel: +81-25-227-0666
Fax: +81-25-223-6646
Email: ikawachi@bri.niigata-u.ac.jp
Received: 30 October 2016; accepted: 7
November 2016.
Introduction
Autoimmune disorders of the central nervous system
(CNS), which include multiple sclerosis (MS) and
neuromyelitis optica spectrum disorders (NMOSD),
often involve autoimmune inflammation of the
anterior visual pathways (AVP). Patients with these
diseases and optic neuritis often suffer from acute
visual impairments with pain during eye
movement.1 Studies of the serum autoantibodies,
aquaporin-4 (AQP4) and myelin oligodendrocyte
glycoprotein (MOG), have elucidated several charac-
teristic clinical, radiological, immunological and
pathological features of each form of optic neuritis.
The present review will focus on the AVP structure
and summarize the current understanding of
autoimmune optic neuritis.
8 © 2017 Japanese Society for Neuroimmunology
Clinical and Experimental Neuroimmunology 8 (Suppl. 1), (2017) 8–16
Abstract
Autoimmune disorders of the central nervous system often involve autoim-
mune inflammation of the anterior visual pathways. Autoimmune optic
neuritis can be categorized as: (i) isolated optic neuritis; (ii) relapsing iso-
lated optic neuritis: (iii) chronic relapsing inflammatory optic neuropathy;
(iv) neuromyelitis optica spectrum disorders-associated optic neuritis; or (v)
multiple sclerosis-associated optic neuritis. Studies of serum-specific autoan-
tibodies, such as aquaporin-4 and myelin oligodendrocyte glycoprotein,
have revealed some underlying mechanisms of autoimmune optic neuritis.
However, the etiology and pathogenesis of most cases of autoimmune optic
neuritis remain unclear. The following clinical features of autoimmune optic
neuritis are profoundly affected by the unique structure of the human ante-
rior visual pathways: (i) vulnerability to swelling of the intracanalicular optic
nerve as a result of the limited space within the bony canal; (ii) inflamma-
tory cell infiltration through the subarachnoid space, pia and pial septa; (iii)
compartmentalized dynamics of cerebrospinal fluid as a result of the cul-
de-sac anatomy of the optic nerve; (iv) permeability of the prelaminar optic
nerve head as a result of the lack of classical blood–brain barrier characteris-
tics; and (v) retinal abnormalities, which are a diagnostic window of neu-
rodegenerative processes of the optic nerves and/or brain. Future studies
are required to configure a systemic nosology for optic neuritis with interna-
tional consensus, elucidate specific diagnostic biomarkers, carry out clinical
trials of the acute and chronic phases of the disease etiologies, and
elucidate possible neuroprotective and remyelinating treatments.
Anatomy of the AVP
The AVP, which includes the retinas, optic nerves,
chiasma and tracts, has anatomical features that are
unique in the CNS. The retina consists of over 60
neuronal types including rod and cone photorecep-
tors that capture light and convert it into electrical
signals,2 which are transmitted through the axons of
the optic nerves.3,4 The neural retina can be parti-
tioned into the following nine layers: photoreceptors
(rod and cones photoreceptors); external limiting
membrane (attachment sites of adjacent photorecep-
tors and M€ uller cells); outer nuclear layer (photore-
ceptor nuclei); outer plexiform layer (photoreceptor
axonal extensions), which contains the middle limit-
ing membrane (desmosome-like attachments of
photoreceptor synapse expansions); inner nuclear
I. Kawachi
layer (bipolar, horizontal, amacrine and M€ uller cell
nuclei); inner plexiform layer (mostly the synapses
of bipolar cells, ganglion cells and amacrine cells);
ganglion cell layer (GCL); retinal nerve fiber layer
(RNFL; ganglion cells axons); and internal limiting
membrane (basement membrane of M€ uller cells).
Importantly, the human retina is devoid of myelin,
whereas astroglia and microglia are evident in the
inner retina.5
Axonal projections from the retina travel through
the optic nerves, chiasma and tracts, and terminate
in several sites, including the lateral geniculate body
(Fig. 1). The optic nerves, which include the
1 158 000  222 000 myelinated axons,4 consists of
the following four parts: (i) optic nerve head (length,
1 mm), including the prelaminar, laminar and retro-
laminar regions; (ii) intraorbital segment (25 mm);
(iii) intracanalicular segment (4–10 mm); and (iv)
intracranial segment (10 mm; Fig. 1).6 The nerve
fibers in the optic nerve head, which are derived
from ganglion cells, project to the optic disc, where
nerve bundles are formed that pass through the
openings of the lamina cribrosa, and evolve into the
extraocular optic nerve.7 The optic nerve contains
the connective tissue, including the lamina cribrosa
and pial septa.8 The lamina cribrosa, which bridges
the scleral canal through which the axons from the
ganglion cells exit the eye, protects the optic nerve
fibers in the scleral canal from the intraocular pres-
sure.8 Lamina cribrosa that is deformed by high
A. Optic nerve head
Brain
B. Intraorbital segement
Optic nerve
C. Intracanalicular segement
D. Intracranial segement
Dura
Arachnoid
Eye A B
Bone
Optic nerve
Astrocytes
Central retinal artery
Subarachnoid space
T cells, B cells, antibodies
Arachnoid
Axon bundles
Pial septa
Figure 1 Schematic of anatomy of optic nerve and optic neuritis.
© 2017 Japanese Society for Neuroimmunology
Autoimmune optic neuritis
intraocular pressure injures the optic nerve and
might cause glaucomatous damage.9 The pial septa,
which arises from the pia mater and enters the optic
nerves, arranges the optic nerves into the axon bun-
dles. The pial septa might provide the required ten-
sile strength for maintaining the optic nerve
configuration and protecting the optic nerves from
mechanical damage by eye movement.8 Fine glial
fibers run perpendicular to the pial septa, and astro-
cyte processes compartmentalize the ganglion cell
axons into bundles of glial tubes.10 Observations of
dense inflammatory infiltrates of mononuclear cells,
including T cells, in the pial septa of the optic nerves
of patients with optic neuritis suggest that inflamma-
tory cells pass through the pial septa and alter the
axon bundles of the optic nerves.11 The optic nerve
head, especially the prelaminar region, lacks
microvessels with classical blood–brain barrier
characteristics and exhibits non-specific permeabil-
ity,12–14 whereas the pial septa of the optic nerve
shows no leakage.15 Therefore, the optic nerve head
might be damaged more by inflammatory stimuli
than other parts of the optic nerve are.12,14 The
intracanalicular segment of the optic nerve, which is
located within the bony canal, is also extremely deli-
cate, and swelling of the nerve might cause optic
nerve compression because of the limited space
there.16,17
The subarachnoid space of the optic nerve has
unique and distinct features (Fig. 1). In contrast to
other cranial nerves in the CNS, the optic nerve is
enveloped in cerebrospinal fluid (CSF) throughout
its entire length.18 The space, which contains a vari-
ety of trabeculae, septa and stout pillars that are
arranged between the arachnoid and pia of the
meninges around the optic nerves and lymphatic
vessels in the dura mater, might have a role in CSF
dynamics because of the cul-de-sac anatomy of the
C D
optic nerve.18–20 The CSF flows from the intracranial
subarachnoid space to the orbital subarachnoid space
as a result of a CSF volume gradient. In certain dis-
eases, the orbital subarachnoid space can become
separated from other CSF compartments.20 Inflam-
mation of the optic nerve might also contribute to
the changes in the arachnoid apertures that drain
the CSF into the meningeal lymphatics,18,20 because
distention of the sheath and inflammatory changes
in the orbital subarachnoid space are sometimes seen
in patients with optic neuritis.21
The key molecules in NMOSD, the AQP4 water
channels, are expressed in the optic nerves, chiasma
and tracts, with prominent expression in the astro-
cytic end-feet around the capillaries and the pia.5,22
9
Autoimmune optic neuritis
In the retinas, AQP4 expression is also present in
M€ uller cells and retinal astrocytes in the RNFL.5,22
In summary, autoimmune optic neuritis is pro-
foundly affected by the unique structure of the
human AVP in the following ways: (i) vulnerability
to swelling of the intracanalicular optic nerve as a
result of the limited space within the bony canal; (ii)
inflammatory cell infiltration through the subarach-
noid space, pia and pial septa; (iii) compartmental-
ized CSF dynamics as a result of the cul-de-sac
anatomy of the optic nerve; (iv) permeability at the
prelaminar optic nerve head as a result of the lack of
classical blood–brain barrier characteristics; and (v)
the lack of myelin and absence of demyelinated
lesions in the retina, and the retinal abnormalities
that are a diagnostic window of the neurodegenera-
tive processes in the optic nerves and/or brain. The
RNFL thinning and loss of ganglion cells result from
retrograde degeneration after damage of the optic
nerve, or trans-synaptic degeneration after damage
to the brain.
Clinical features of autoimmune optic neuritis
Classification of autoimmune optic neuritis
Autoimmune optic neuritis is an inflammatory disor-
der of the optic nerves that results from several
autoimmune processes including MS, NMOSD and
other systemic disorders. However, no international
consensus exists for a nosology system of optic neu-
ritis, which results in confusion in the interpretation
of the results of clinical studies due to the different
definition and classification algorithms used by dif-
ferent researchers.1,3 Traditionally, optic neuritis has
been categorized into typical or atypical clinical phe-
notypes, because of the lack of exact definitions and
diagnostic biomarkers, except for AQP4 autoantibod-
ies for patients with NMOSD.1 Typical optic neuritis
is considered as MS-related diseases that result from
MS or clinically isolated syndromes with the risk of
conversion to MS. In contrast, atypical optic neuritis
results from other autoimmune disorders or systemic
disorders, such as NMOSD, sarcoidosis, vasculitis and
lupus. Patients with atypical optic neuritis often
have red flags, including atypical clinical presenta-
tions, such as pain or vision loss for over 2 weeks,
absence of pain, retinal abnormalities, unexplained
optic atrophy, severe vision loss in patients of non-
white ethnic backgrounds, severe vision loss without
early recovery, bilateral optic neuritis, and past med-
ical history of cancer; and atypical courses, including
progressive vision loss, lack of recovery for over
3 months and visual function worsening after
10
I. Kawachi
reduction/stop of steroids or immunosuppression.3
The presence of red flags suggests other etiologies,
such as NMOSD, rather than MS or clinically iso-
lated syndrome, and the early recognition and
prompt treatment of these patients with atypical
optic neuritis with red flags are beneficial.
Another nosology system categorizes optic neuritis
as follows: (i) isolated optic neuritis (single and iso-
lated episode of optic neuritis); (ii) relapsing isolated
optic neuritis (RION; spontaneously relapsing and
isolated episode of optic neuritis); (iii) chronic RION
(CRION; relapses of isolated episodes of optic neuritis
with steroid withdrawal and seronegativity of AQP4
autoantibodies); (iv) NMOSD-associated optic neuri-
tis; and (v) MS-associated optic neuritis.3 In particu-
lar, patients with CRION and NMOSD need to be
recognized as early as possible, because they have a
high risk of severe visual loss and poor
prognoses.3,5,23,24
Epidemiology of autoimmune optic neuritis
The incidence of optic neuritis has been reported as
0.94–2.18 per 100 000 person-years (1.62 per
100 000 in Japan and 1.46 per 100 000 in Swe-
den).1,25,26 A female predominance is present in
European cohorts (males:females, 1:3),1,26 but not in
Japanese cohorts (1:1.22).25 Recent results have
showed that ethnic differences might reflect an asso-
ciation between optic neuritis and MS, and this asso-
ciation is lower in Asian patients compared with
Caucasian patients.23 Conversely, compared with
Caucasian patients, NMOSD seems more frequent in
Asian, African or African Caribbean patients, and
CRION seems more frequent in African or African
Caribbean patients.23,27,28 In European countries,
the incidence of optic neuritis is related to evidence
of past Epstein–Barr viral infections or the HLA-
DRB1*1501 genotype.29 Because most of these stud-
ies were retrospective and not population-based,
future studies are required to confirm these findings.
Clinical signs, including visual phenomena, in
autoimmune optic neuritis
Patients with typical autoimmune optic neuritis usu-
ally exhibit acute/subacute visual impairments with
pain during eye movement, which often develops
over hours or days.1 The visual impairments include
the following: (i) decreased visual acuity; (ii) defects
of the visual fields; (iii) phosphenes, such as bright
flashes of light during eye movement; (iv) dyschro-
matopsia with mixed defects in red–green; (v)
© 2017 Japanese Society for Neuroimmunology
I. Kawachi
Uhthoff’s phenomenon, which is a worsening of
vision by increased body temperature during hot
baths, exercises or other conditions; (vi) the Pulfrich
phenomenon, which is anomalous stereoscopic per-
ception of objects in motion as a result of asymmet-
rical conduction of the optic nerves; and (vii) ocular
pain during eye movement.1 Optic neuritis with no
ocular pain or no headache might indicate inflam-
matory processes within the optic canal or intracra-
nial space.3 These atypical signs or red flags suggest
diagnoses with other etiologies, such as NMOSD,
with severe and poor prognoses rather than MS. The
recovery of typical autoimmune optic neuritis is usu-
ally good, and it begins within a few weeks of dis-
ease onset. However, patients with optic neuritis and
NMOSD often have poor prognoses.5 In particular,
male patients in the UK with NMOSD and disease
onset at a young age have a high risk of poor visual
disabilities.30 Interestingly, 25% of NMOSD attacks
and 8% of MS attacks are associated with chronic
progressive visual deterioration, which is defined as
progressive abnormalities in visual acuity (+0.3 log-
MAR or more) and/or visual fields for more than
2 months.5
Neuro-ophthalmological findings in autoimmune optic
neuritis
The following neuro-ophthalmological investigations
of patients with autoimmune optic neuritis are
required: (i) direct and indirect ophthalmoscopic
examinations of the retinal and/or optic disc; (ii)
high- and low-contrast visual acuity examinations;
(iii) clinical treatment of impaired color vision with
Ishihara pseudoisochromatic plates; (iv) static
perimetry (e.g. Humphrey field perimetry) of visual
field defects; and (v) swinging light tests for the rela-
tive afferent pupillary defect (Marcus Gunn pupil).
Low-contrast visual acuity charts are more sensitive
than high-contrast charts.1,3 More severe visual acu-
ity impairments are evident in patients with optic
neuritis and NMOSD compared with patients with
optic neuritis and MS.5 Visual field morphological
analyses using the Optic Neuritis Treatment Trial
classification have shown central abnormalities in
patients with optic neuritis and MS, whereas neuro-
logical abnormalities, total vision loss, and altitude
abnormalities are prominent in patients with optic
neuritis and NMOSD.5,31
Optical coherence tomography (OCT) has emerged
as a non-invasive and reproducible tool for in vivo
studies of retinal neuroaxon damage.32,33 A meta-
analysis of the time domain (TD)-OCT data of 2063
© 2017 Japanese Society for Neuroimmunology
Autoimmune optic neuritis
eyes has reported highly significant RNFL loss in
patients with MS and optic neuritis ( 20.38 lm;
95% CI, 22.86 to 17.91) compared with healthy
controls.33 Furthermore, a meta-analysis of the TD-
OCT data of 3154 eyes has shown greater RNFL
thinning in patients with MS without optic neuritis
compared with individuals with normal aging
( 7.08 lm; 95% CI, 8.65 to 5.52), and decreased
thinning compared with patients with MS and optic
neuritis ( 20.38 lm; 95% CI, 22.86 to 17.91).33
Without optic neuritis, the retrograde trans-synaptic
degeneration of retinal ganglion cells that results
from the MS lesions within the posterior optic path-
ways might cause RNFL thinning.33,34 The recently
developed technique of Fourier/Spectrum
domain-OCT (F/SD-OCT) dramatically improves the
sensitivity and imaging speed of OCT,35 and has
axial resolutions that are twice as high (5–7 lm) as
those of the classical TD-OCT (approximately
10 lm).36 The data suggest that the estimated yearly
thinning of the overall RNFL (roughly 2 lm)37 of
patients with MS without optic neuritis is below the
detection limit of TD-OCT systems, whereas the
F/SD-OCT systems should be able to detect thinning
at this resolution level.33 Monitoring of peripapillary
RNFL thickness in eyes without optic neuritis with
F/SD-OCT might allow predictions of the risk of dis-
ability worsening over time in patients with MS, and
this thickness might be a biomarker of neurodegen-
eration in patients with MS.38 The degree of RNFL
thinning correlates with cognitive disability and the
results of the symbol digit modality test in patients
with MS.39
TD-OCT and F/SD-OCT studies have shown that
the mean RNFL thickness is significantly reduced in
patients with NMOSD compared with controls,40
and that patients with NMOSD have more severe
retinal damage after optic neuritis episodes compared
with patients with MS.5,41,42 For optic neuritis-
unaffected eyes, previous TD-OCT studies have
shown that the mean RNFL thickness in patients
with NMOSD is mildly, but non-significantly, thin-
ner compared with controls.40–42 However, F/SD-
OCT studies have identified retinal damage in optic
neuritis-free eyes of patients with NMOSD.5,43
Neuroradiological findings in autoimmune optic neuritis
Contrast enhancement might provide evidence of
acute optic neuritis in fat-suppressed T1-weighted
images.3 The distribution of the abnormal intensity
in double inversion recovery images shows the accu-
mulation of archival lesions throughout the disease
11
Autoimmune optic neuritis
course.5 Magnetic resonance imaging findings of T1-
weighted images with contrast enhancement have
shown that the length of abnormally enhanced
lesions in patients with optic neuritis and NMOSD is
longer than those in patients with optic neuritis and
MS.5,44 Furthermore, a number of studies, including
double inversion recovery imaging studies, have
shown that the optic chiasma and intracranial optic
nerve are often involved in the optic neuritis of
patients with NMOSD compared with the optic neu-
ritis of patients with MS.5,45 The orbital optic nerve
is the most frequently involved site in optic neuritis
in patients with both MS and NMO.5
Pathology in autoimmune optic neuritis
Pathological studies have shown that the lesions of
the optic nerves, chiasma, and tracts are basically
identical to those of the spinal cord and brain in
optic neuritis in patients with MS or NMOSD.5,46–49
The lesions in patients with NMOSD are character-
ized by a pattern-specific loss of AQP4 immunoreac-
tivity that shows a vasculocentric pattern of
complement depositions in the spinal cord, brain
and optic nerves, whereas the lesions of patients
with MS do not show this pattern throughout the
CNS. These results suggest that the complement-
dependent cytotoxicity of the AQP4 autoantibodies
and activated complements is an important effector
mechanism in the pathogenesis of optic neuritis in
patients with NMOSD and not in patients with
MS.5,46,50,51 Furthermore, the infiltration of inflam-
matory cells, including CD45RO+ T cells and Iba-1+
microglia/macrophages, is evident around the thick-
ening of the perioptic meninges, and it extends into
the pial septa and parenchyma of the optic nerves in
patients with NMOSD,5 which suggests that optic
neuritis and/or perioptic neuritis are present in
NMOSD.5,52 Interestingly, more severe neuroaxonal
degeneration, and the axonal accumulation of
degenerative mitochondria and the transient recep-
tor potential melastatin 4 channel are evident in
optic neuritis lesions in patients with NMOSD com-
pared with those in patients with MS. These results
might be associated with the more severe visual
impairments and poor prognoses in patients with
NMOSD compared with patients with MS.5
A few studies have described the retinal pathology
in optic neuritis in patients with MS and
NMOSD.5,53,54 Their retinal pathology in the optic
neuritis of patients with MS is characterized by sev-
ere atrophy of the RNFL and GCL, and atrophy of
the inner nuclear layer, which predominantly
12
I. Kawachi
consists of horizontal and bipolar cells, with gliosis
and inflammation, which suggests that the retinal
damage is more widespread than previously
thought.54 Patients with optic neuritis and NMOSD
exhibit severe atrophy of the RNFL and GCL with
gliosis, mild atrophy of the inner nuclear layer, and
unique AQP4 dynamics, including scattered losses of
AQP4 immunoreactivity on M€ uller cells with no
deposition of complement and densely packed AQP4
immunoreactivity on astrocytes in the RNFL.5 The
atrophy of the RNFL and GCL, and the densely
packed AQP4 immunoreactivity in astrocytes in the
RNFL, which indicates secondary retrograde degen-
eration after the optic neuritis, are worse in the optic
neuritis of patients with NMOSD rather than in
patients with MS. The observations of the scattered
loss of AQP4 immunoreactivity in M€ uller cells and
no deposition of complement might be unique to
patients with NMOSD and not be found in patients
with MS.5 These pathological changes of the RNFL
and GCL are consistent with retinal abnormalities
that are found by OCT assessments in the optic
neuritis of patients with MS and NMOSD.
Immunological features of autoimmune optic neuritis
The effects of immunological-specific autoantibodies
have remained unclear for most types of autoim-
mune optic neuritis. However, findings of autoanti-
bodies, such as AQP4 autoantibodies and MOG
autoantibodies, are revealing some of the underlying
causes of autoimmune optic neuritis.
AQP4 autoantibodies are the most important
pathogenic immune elements and specific diagnostic
biomarkers of optic neuritis in patients with
NMOSD.55–57 The two main lesion sites in patients
with NMOSD are the optic nerves and spinal cord.57
Patients with NMOSD, optic neuritis and seropositiv-
ity for AQP4 autoantibodies are characterized by
more severe visual impairments, poor prognoses,
bilateral and simultaneous optic neuritis,58 and thin-
ner RNFL, which suggest more widespread axonal
damage5,40,41 compared with patients with MS.
Several studies involving rodent models and in vitro
assessments have reported indirect evidence that the
basic effector mechanisms of AQP4 autoantibody
binding to its cellular target, the AQP4 water
channel, in the pathogenesis of NMOSD might
be complement-dependent cytotoxicity,59 anti-
body-dependent-cell-mediated cytotoxicity60 and
internalization of the AQP4 channels.61 Comple-
ment-dependent cytotoxicity is the main important
immune mechanism in the lesions of the spinal cord
© 2017 Japanese Society for Neuroimmunology
I. Kawachi
and optic nerves in patients with NMOSD, because
these lesions show a pattern-specific loss of AQP4
immunoreactivity in astrocytes with complement
activation. In contrast, other immune mechanisms,
including the internalization of AQP4 channels,
might contribute to the pathology in the retina and
cortical gray matter, because these lesions show
decreased AQP4 immunoreactivity in astrocytes and
M€ uller cells, and no deposition of activated
complements.
The MOG autoantibody, which is specifically
detected with a cell-based assay, is another interesting
immune marker.62 Early western blots or enzyme-
linked immunosorbent assay using recombinant
MOG or MOG peptides examined MOG immunoreac-
tivity in patients with MS and in healthy con-
trols,63,64 but the results of these studies could not be
confirmed in two replication cohorts.62,65,66 Recent
assessments of the conformational epitopes of native
MOG with cell-based assay or radioimmunoassays of
in vitro translated and radiolabeled MOG tetramers
have provided indirect evidence that the MOG
autoantibody is associated with pathogenic CNS
lesions.67–72 Seropositivity for MOG autoantibodies,
which was determined with a cell-based assay, is pre-
sent in patients with several CNS autoimmune disor-
ders, including optic neuritis,73–75 acute disseminated
encephalomyelitis,69 multiphasic disseminated
encephalitis,69 NMOSD with AQP4 antibody serone-
gativity70–72 and anti-NMDA receptor encephalitis.62,76
Among these, patients with optic neuritis who are
positive for MOG antibodies are characterized by an
equal gender ratio, younger onset age, longer lesions
with swelling on magnetic resonance imaging and
better prognoses of visual function, compared with
patients with optic neuritis who are positive for AQP4
autoantibodies.75 Further studies are required to elu-
cidate the pathogenic roles of MOG autoantibodies in
CNS autoimmune disorders.
Diagnosis and treatments of autoimmune optic neuritis
Acute/subacute monocular/bilateral visual impair-
ments can derive from autoimmune optic neuritis,
which can mimic several disorders, including
ischemic optic neuropathy, infectious optic neuropa-
thy and Leber’s hereditary optic neuropathy. Diag-
noses of optic neuritis are usually made with the
patient history, clinical signs and results of paraclini-
cal tests, including neuro-ophthalmic and magnetic
resonance imaging examinations, after exclusion of
the optic neuritis-mimicking syndromes. Then, atyp-
ical optic neuritis should be distinguished from
© 2017 Japanese Society for Neuroimmunology
Autoimmune optic neuritis
typical optic neuritis as described above. Further-
more, atypical optic neuritis should be categorized
into optic neuritis with NMOSD, CRION or other
disorders including systemic disorders, such as sar-
coidosis, lupus or vasculitis, with assessments of
serum autoantibodies, including AQP4 antibodies, or
systemic investigations, including chest/abdominal
computed tomography.1,3
For the acute phase of optic neuritis, a number of
studies have assessed treatments, including corticos-
teroids,77–80 plasmapheresis81–85 and intravenous
immunoglobulins.86–88 For the long-term manage-
ment of optic neuritis, the treatment options need to
be profoundly affected by the underlying causes.1
The early recognition of optic neuritis and prompt
choice of treatment that is based on the underlying
causes of the acute and chronic phases are required
to prevent severe visual impairments.
Future directions
Future studies are required to configure a nosology
system for optic neuritis with international consen-
sus, elucidate specific diagnostic biomarkers, carry
out clinical trials of the acute and chronic phases
according to the disease etiologies, and examine pos-
sible neuroprotective and remyelinating treatments.
Conflict of interest
IK has received funding for travel/speaker honoraria
or for serving on scientific advisory boards from
Novartis, Biogen, Bayer, Mitsubishi Tanabe, Takeda
and Astellas.
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