Optic neuritis & Multiple Sclerosis (2018)

Slides include
Basic anatomy of optic nerves
Background & epidemiology of optic neuritis
Classification of optic neuritis
Clinical features
Investigations
Diagnosis
Differential diagnosis
Managements
Prognosis

1. Optic Neuritis
Prepared by:
Dr. Goh ch (mbbs, imu)
ophthalmology medical officer ud44
hospital pakar sultanah fatimah muar
malaysia
Supervisor:
Dr Fadzlina

2. OPTIC NERVE
Anatomy

3. •derived from retinal ganglion cells and project to 8 primary visual nuclei
•most synapse in lateral geniculate body, some reach other centre
Hypothalmus: suprachiasmatic nucleus, supraoptic nucleus, paraventricular nucleus
Mesencephalon: accessory optic system nucleus, pretectal area nucles, superior colliculus nucleus
Thalamus:: Pulvinar nucleus
•1/3 of fibres subserve central 5 degree of visual field

5. •50 mm Long from globe to chiasm
•4 segments:
1)Intraocular (optic disc and optic
nerve head, shortest=1mm deep,
1.5mm vertical diameter)
2)Intraorbital (globe to optic
foramen at orbital apex, 25-30mm
long, 3-4mm diameter. Addition of
myelin sheath)
3)Intracanalicular (traverses optic
canal, 5-9mm, fixed to canal)
4)Intracranial (joining chiasm, 5-
16mm)

6. •Conduction velocities
Large, myelinated fibers
(~20m/second)
Small, unmyelinated fibers
(1m/second)

7. •optic nerves carries 1.2 million
afferent nerve fibres which
originate in retinal ganglion cells
•each optic nerve = 600 bundles =
2000 fibres
•Pia Mater : Delicate, vascular
•Arachnoid Subarachnoid space is
continous with cerebral
subarachnoid space (contain CSF)
•Dura Mater : Tough, continous
with sclera

8. Each bundle separed by connective
tissue septa which run the smaller
blood vessels

10. OPTIC NEURITIS
Def: inflammatory, infective or demyelinating process affecting optic nerve

11. Epidemiology
•Incidence: 1-5 cases per 100,000/year
England  93 per 100,000
US  46 per 100,000
Eastern Countries  0.77-1.8 per 100,000
India  1.33 per 100,000
•Higher the latitude, higher incidence

12. Classification
Ophthalmoscopic
•Retrobulbar Neuritis
•Papillitis
•Neuroretinitis
Aetiological
•Demyelinating
•Parainfectious
•Infectious
•Non-infectious

13. OPHTHALMOSCOPIC
CLASSIFICATION

15. AETIOLOGICAL
CLASSIFICATION

16. Aetiological Classification
•Demyelinating
Most common
Nv conduction disrupted
•Parainfectious
may follow a virus infection or immunization
•Infectious
may be sinus related, cat scratch fevver, syphilis, Lyme disease, cryptococcal
meningitis, Herpes Zoster
•Non-infectious
sarcoidosis, systemic autoimmune disease (SLE, Polyarteritis nodosa & other
vasculitides)

17. •Menon V, Saxena R, Misra R, Phuljhele S. Management of optic neuritis. Indian Journal of Ophthalmology.
2011;59(2):117-122. doi:10.4103/0301-4738.77020.

18. Demyelinating
•Multiple sclerosis
oremitting idiopathic demyelinating disease involving white matter within CNS
•Neuromyelitis Optica (Devic Disease)
obilateral optic neuritis and subsequent development of transverse myelitis within
days or weeks
overy rare disease, any age
omay have autoantibodies against AQP4
•Schilder Disease (Diffuse cerebral sclerosis)
orelentlessly, progressive, generalized disease
obilateral optic neuritis without subsequent improvement
oAs the disease progresses, larger and larger patches of demyelination occur,
interfering with motor movement, speech, personality, hearing and vision,
ultimately affecting the vital functions of respiration, heart rate, blood pressure.
overy rare, onset before 10 years, death within 2 years

21. OPTIC NEURITIS

22. Clinical Features
Symptoms
•Typically age 20-50 (mean~30)
•Female (75%)
•Acute monocular vision loss (<7 days)
•Ocular pain
•Worsens on eye movement
•Several hours to days
•+/- Positive visual phenomena (phosphenes)
•+/- Pulfrich phenomenon (altered perception of moving object)
•+/- Uhthoff's sign (exercise or increased body temperature makes the sx worse)
•May have history of demyelinating symptoms

23. Signs
•VA= 6/18 with mild visual defects to NPL
•+ RAPD (all unilateral cases)
•Subnormal Colour vision
•Reduce colour saturation and light brightness
•Visual field defect (diffuse depression/altitudinal
defect/arcuate/centrocecal scotoma)
•Papillitis (disc edema without hemorrhage or exudates)
•1/3 = Swollen disc, 2/3 = Normal disc (retrobulbar)

24. Atypical features
•Absence of pain
•NPL vision
•Marked optic disc swelling with retinal exudates and
peripapillary hemorrhages
•Lack of recovery after 3/52
•Bilateral involvement

25. Diagnosis
•Clinical diagnosis
•Investigation done
to assess risk of MS
and rule out other disorders

26. Clinical testing
•complete ophthalmic & neurological examination
(Pupillary assessment, colour vision evaluation, vitreous cells, optic nerve
assessment)
•Visual field test (eg. Humphrey)
•Check BP
Blood Ix
•FBC
•ESR/CRP
•Mantoux test
•Blood culture
•CSF examination
•Serology for syphilis, bartonella and toxoplasmosis

27. Imaging
•MRI BRAIN + SPINE
•Baseline CXR (Before starting Steroid *TB)
•CT of orbit (bony orbital lesion)
•Orbital ultrasound (posterior scleritis)
•OCT
•FFA

28. MRI Brain and Spine (gadolinium enchanced)
•Indicated for first episode or atypical case
(all patient with acute monosymptomatic demyelinating optic neuritis)
•To determine risk of Clinically Define MS (CDMS)
** High risk for MS if MRI showing ≥ 2 white matter lesions
(≥ 3mm in diameter at least 1 lesion periventricular or ovoid)

30. Multiple lesions adjacent to the ventricles (red arrow).
Ovoid lesions perpendicular to the ventricles (yellow arrow).
Multiple lesions in brainstem and cerebellum.

31. MRI Brain
Typical for MS in this case is:
Involvement of the temporal lobe (red arrow)
Juxtacortical lesions (green arrow) - touching the cortex
Involvement of the corpus callosum (blue arrow)
Periventricular lesions - touching the ventricles

33. MRI can show multiple lesions (dissemination in space), some of which
can be clinically occult and MRI can show new lesions on follow up scans
(dissemination in time).

34. Miscellanous
•Toxin screen (Toxic optic neuropathy)
•Serum B12 (Toxic optic neuropathy)
•Autoimmune disease marker
•Antibody to aquaporin-4
•Genetic analysis for mitochondrial mutation (Leber’s
hereditary optic neuropathy)

35. Differential Diagnosis
•ISCHEMIC OPTIC
NEUROPATHY (ION)
sudden visual loss
typically no pain with ocular motility
NAION : older patient (40-60yrs)
optic disc swelling hyperemic
then became pallor
AION (GCA) : older patient (>55yrs),
diffuse and chalk white optic disc
swelling

36. •ACUTE PAPILLOEDEMA
Bilateral disc edema, no decreased
colour vision, no decrease visual
acuity, no pain, no vitreous cells
•SEVERE SYSTEMIC
HYPERTENSION
Bilateral disc edema, increased BP,
flamed shapred retinal
hemorrhages and cotton wool
spots
•ORBITAL TUMOUR
(Compressive)
Unilateral, often with proptosis or
restricted EOM

37. •LEBER OPTIC NEUROPATHY
Male, 20-30 yrs, with family history
rapid visual loss of one and then the
other eye within days to months
+/- peripapillary telangiecses
disc swelling then optic atrophy
•TOXIC or METABOLIC OPTIC
NEUROPATHY
progressive painless bilateral visual loss
(alcohol, malnutrition, anemia,
ethambutol, HCQ, heavy metal,
isoniazid....)

38. MANAGEMENT

39. Management
1) IV Methylprednisolone *Based on ONTT
- IV Methylprednisolne 1g/day x 3/7
(250mg every 6 hours)
- Then T. Prednisolone 1mg/kg for 11 days
- Then taper over 4 days
(20mg D1, 10mg D2 and D4)
Cleary PA, Beck RW et al. Optic Neuritis Study Group: Design, methods and conduct of the Optic Neuritis
Treatment Trial. Control Clin Trials. 1993;14:123-42.
2) Antiulcer medications
- T. Ranitidine 150mg BD
Cleary PA, Beck RW et al. Optic Neuritis Study Group: Design, methods and conduct of the Optic Neuritis Treatment Trial. Control Clin Trials. 1993;14:123-42.

40. 3) Refer Neurologist
for possible Interferon Beta-1alpha within 28 days
* if MRI shows 2 or more demyelinating lesions
From ONTT
•Periventricular white matter lesions demonstrating demyelination most
critical for assessing risk of developing M.S.
–Zero Lesions: 25% chance of developing M.S. within 5 years
–One Lesion or more: 72% chance of developing M.S. in 15
year period
Cleary PA, Beck RW et al. Optic Neuritis Study Group: Design, methods and conduct of the Optic Neuritis
Treatment Trial. Control Clin Trials. 1993;14:123-42.

41. Immunomodulating drugs
- reduce the development and severity of CDMS
- reduce antigen presentation, inhibit pro-inhibitory cytokines,
inhibit autoreactive T cell, induce immunosuppressive cytokines,
decrease migration of cells in CNS
- eg. Interferon Beta-1a (Avonex *refer CHAMPS study, Rebif), Interferon
Beta-1b (Betaseron *refer BENEFIT study) & Glatiramer acetate, or
intravenous immunoglobulin treatment

42. ONTT

43. Optic Neuritis Treatment Trial (ONTT)
•Initiated in 1988-2006, enrolled
454 patients, utilizing 15 clinical
centers throughout U.S.
•Patients randomized to one of
three regiments
A)Oral Prednisone (1mg/kg/day for
14 days followed by 3 day
tapering
B)IV Methylprednisolone (250mg
every 6 hours for 3 days,
followed by Oral Prednisone 1
mg/kg for 11 days and 3 days
tapering oral prednisolone
C)Oral Placebo for 14 days
•Eligible Patients
a)18 to 46 years of age
b)Acute unilateral optic
neuritis with visual
symptoms 8 days or less
c)+RAPD and Field Defect in
affected eye
d)No previous episodes of
Optic Neuritis in affected
eye
e)No previous corticosteroid
treatment for optic neuritis
or M.S.
f)No systemic dx other than
M.S. that could cause Optic
Neuritis

44. Key Findings of ONTT
•IV Methyprednsolone group recovered vision faster
(IV steroid sped up by 1-2 weeks)
•At 1 year follow up, noted no statistically significant difference
in visual function in all groups
(no long term beneficial effect on vision)
•Oral Prednisone regimens showed no benefit, but 2 fold
greater rate of recurrence
(oral prednisone greater recurrence rate)
•IV Methyprednisolone reuced the risk of developing MS
within first 2 years but this protective effect dissappeared
after 2 years
[IV Steroid protective for first 2 years)

45. Key Findings of ONTT
Lower risk of developing M.S. associated:
a)male sex
b)optic disc swelling
c)atypical features of optic neuritis (absence of pain, NLP vision,
peripapillary hemorrhages, retinal exudates)

46. Recommendations from ONTT
•CXR, blood test, lumbar puncture not indicated for typical
case of optic neuritis
•Treatment with oral prednisolone alone is contraindicated
•Consider treatment with IV steroid when ≥3 lesion on MRI
(reduce 2year risk of developing MS) or patient requiring
expedited recovery of vision (monocular patient, employment
demands, bilateral involvement or patient desired)

47. Latest Research
- Higher dose of IV Methylprednisolone showed no statistical benefits
- IV Dexamethasone equally effective as IV Methylprednisolone
(easier to administer (200mg OD dose) and 6 times cheaper )
- IV Methylprednisolone 500mg Monthly with 3 day oral tapering reduces inflammatory disease
activity without clinically relevant side effects. Noted reduction in number of gadolinium
enhanced lesion over 6 months follow up
Sellebjerg F, Nielson HS et al. A randomised controlled trial of oral high-dose methylprednisolone in acute optic neuritis. Neurology.
1999;52:1479-84
Sethi HS, Menon V, Sharma P et al. Visual Outcome after IV dexamethasone therapy for idiopathic optic neuritis in an Indian
population: A clinical case series. Indian J Ophthalmol. 2006;54:177-83.
Then Bergh F, Kumpfel T et al. Monthly intravenous methylprednisolone in relapsing-remitting multiple sclerosis-reduction of
enhancing lesions, T2 lesion volume and plasma prolactine concentrations. BMC Neurol. 2006;6:19.

48. Further follow up
•Reexamine patient 4-6weeks later then every
3-6 months
•Consider repeating MRI in 1 year if no MRI
lesion during first presentation

49. Prognosis
•vision worsens over few days to 2 weeks from onset
•after 2 weeks begins to improve
•>75% of patients - recover to VA at least 6/9 in 10years
follow up but other visual function may still be subnormal
•10% of patients - chronic optic neuritis (slow progressive or
step-wise visual loss)
•After first attack, risk of recurrence = 35% either in one or
both eyes in 10 years

50. MULTIPLE SCLEROSIS

52. Multiple Sclerosis
•remitting idiopathic demyelinating disease involving white matter within
CNS
•Close association with Optic neuritis
•20% of MS patients present with Optic Neuritis
•50% of MS patients had optic neuritis at some point
•After acute episode of optic neuritis [based on ONTT]
Overall 15 year risk in developing MS = 50%
Overall 15 year risk in developing Clinical Definite MS
= 25% if no lesion in MRI
= 50% if there is single lesion in MRI
= 75% if there is 3 or more lesions in MRI

53. •2 ways of presentation
1) : Relapsing/remitting episodes
with complete or incomplete recovery
* after 10 years, 50% of patients develop
continously progressive disease
2) Progressive (10%):
without remission

54. Spinal Cord
Brainstem
Cerebral Hemisphere
Psychological
Transient features
* Lhermitte sign - electrical sensatio non neck flexion
* dysarthria-dysequilibrium-diplopia syndome
* Uhthoff phenomenon
Sudden worsening of vision or other symptoms on
exercise or increase in body temperature

55. Ophthalmic features
•optic neuritis
•internuclear
ophthalmoplegia
•nystagmus
•uncommon:
skew deviation, ocular
motor nerve palsies,
hemianopia, intermediate
uveitis, retinal
periphlebitis & etc.

56. Investigations
•MRI
ovoid periventricular and corpus
callosum plaques with long axes
perpendicular to the ventricular
margins
•Lumbar Puncture
leucocytosis
IgG >70% of total protein
oligoclona bands on protein
electrophoresis

58. Treatment
•Systemic steroid
•Immunomodulator
eg. interferon beta-1a

59. Take Home Message

60. •Menon V, Saxena R, Misra R, Phuljhele S. Management of optic neuritis. Indian Journal of Ophthalmology.
2011;59(2):117-122. doi:10.4103/0301-4738.77020.

61. References
•Jack J Kanski, Ken Nischal, Andrew Pearson. Clinical Ophthalmology A Systematic
Approach 7th Edition. Elsevier Saunders Edinburg. 2011. ISBN-13 9780702040931
•Myron Yanoff MD, Jay S. Duker MD. Fourth Edition Ophthalmology. Elsevier
Saunders 2014. International Edition ISBN 978-1-4557-3983-7
•Vimla Menon, Rohit Saxena et al. Management of optic neuritis. Indian J
Ophthalmol. 2011 Mar-Apr;59(2):117-122. PMC3116540