Investigations

Treatment

Definition

Inflammation of the optic nerve (inflammatory optic neuropathy)

Clinical manifestations

• Subacute, painful visual loss

• Central vision

• Pain – usually worse on eye movements, may precede visual loss - present in 90%

• Reduction in colour vision – usually more severe/out of proportion to the acuity loss

Examination

• RAPD

• Fundoscopy

o Normal (2/3rds)

o Swollen optic disc (1/3rd)

o Haemorrhages rare in idiopathic optic neuritis

o Optic disc pallor 4-6 weeks after onset

o Retina normal in idiopathic optic neuritis, may be macula star in neuroretinitis

• Fields – often central scotoma, however any type of field loss can be present

DDx

• All forms of optic neuropathy should be considered (see Optic Neuropathy)

Optic Neuritis definitions

Isolated optic Neuritis	ION	Single and isolated episode of optic neuritis Brain MRI normal
Relapsing isolated optic neuritis	RION	Spontaneously relapsing and isolated episode of optic neuritis
Chronic relapsing inflammatory optic neuropathy	CRION	Relapses of isolated optic neuritis on steroid withdrawal
Neuromyelitis optica optic neuritis	NMO-ON	Spontanseously relapsing optic neuritis with other features meeting criteria for NMO
Multiple sclerosis associated optic neuritis	MSON	Optic neuritis in association with radiological (?or clinical) evidence of dissemination in space and time

Optic Neuritis – aetiology:

• Demyelinating disease

o Idiopathic

o MS

o NMO

o ADEM

• Infectious disease

o Bacterial - Syphilis, cat scratch (Bartonella), Mycoplasma pneumonia, TB

o Viral - VZV, HSV, EBV, HIV, Coxsackie, adenovirus, hepatitis A and B, measles, mumps, rubella, rubeola

o Parasitic – toxoplasmosis, cysticercosis, intra-ocular nematode infection

o Fungal – Cryptococcosis, aspergillosis, mucormycosis, candidosis, histoplasmosis

• Post-vaccination

• Other systemic inflammatory conditions

o Sarcoidosis, SLE, Wegener’s, Sjogren syndrome, PAN, Inflammatory bowel disease, Behcet’s

• Isolated recurrent optic neuritis (Autoimmune optic neuritis)

Autoimmune Optic Neuritis Terminology

Petzold/Plant have suggested the following terminology:

· Single episode of isolated optic neuritis (SION)

· Relapsing episodes of isolated optic neuritis (RION)

· Chronic relapsing inflammatory optic neuropathy (CRION)

· Optic Neuritis in Multiple Sclerosis (MSON)

· Neuromyelitis optica (NMO)

Incidence of alternative diagnosis

In Optic Neuritis Treatment Trial the following alternative diagnoses were found (out of 455 patients):

• 0.4% compressive

• 3.0% ANA positive (high titre) – one developed connective tissue disease

• 1.3% Syphilis antibody positive – none with active syphilis

• CXR did not reveal any cases of sarcoidosis or TB

• CSF performed in 131 cases – none revealed any unexpected diagnoses

The above has been used to argue against routine testing.

	Idiopathic	Ischaemic
Age
Pain	90%	10%
Field	Central	Altitudinal
Fundus	Retrobulbar 2/3	Swollen in majority

Red Flags - Clues that it is not idiopathic optic neuropathy

From Nancy Newman	From Petzold/Plant	From Pane
Atypical presentation
		Age <15 or >45yrs
Bilateral optic neuritis	Bilateral optic neuritis	Bilateral optic neuritis
Absence of pain	Absence of pain	Absence of pain
Worst VA – LP or NLP	Severe loss of vision
Progression of visual loss beyond 7 days	Progression of visual loss beyond 14 days	Progression of visual loss beyond 14 days
	Progression of pain beyond 14 days
No improvement by 30days	Absence of recovery for >3months	No improvement by 30days
	Worsening visual function after reducing or stopping steroids/immunosupression
	Past medical history of cancer	Medical history – cancer, vasculitis or autoimmune disease
		No diplopia or other cranial nerve signs or symptoms
Ophthalmoscopy
	Unexplained optic atrophy	Disc pallor
	Retinal abnormalities
Intra-ocular cells		Iritis, vitritis etc.
Disc swelling		Severe disc swelling
Haemorrhages		Haemorrhages
Exudates		Exudates, cotton wool spots

Investigations

All patients:	Reason for test
MRI – orbits and brain (with contrast)	Compressive lesion Other evidence of demyelination
FBC	Anaemia can cause or contribute to optic neuropathy
ESR, CRP	?GCA, ?systemic inflammatory disease
Visual fields	Occult bilateral disease Lesion
Atypical optic neuritis
Inflammatory antibodies – ANA, ENA, ANCA	SLE, Wegener’s, Sjogren’s
ACE	Sarcoidosis
Syphilis serology (RPR, TPA)	Syphilis optic neuropathy
NMO IgG	NMO
Bartonella serology	Cat scratch disease
B12, folate	Nutritional optic neuropathy
Leber’s mutations
CXR	Sarcoidosis
Lumbar Puncture:
Protein, M/C/S, cytology	Toxoplasmosis
NMO	Can pick up some extra cases not identified in serum
Herpes multiplex
Cryptococcal antigen
Consider:
Mycoplasma serology
TB testing (Quanterferon)	Sarcoidosis
EBV, CMV serology
HIV serology	Usually associated with syphilis or other infectious cause
Toxoplasmosis serology
Dominant optic atrophy gene testing
CAR antibodies
Retinal tests – ERG	Occult retinal disease
Fluorescein angiogram
OCT
VER	To confirm optic neuropapthy – may help differentiate demyelinating from axonal

MRI

• If MRI performed within 30days sensitivity is 80-94% (of detecting imaging evidence of ON)

• Need to obtain correct imaging – orbital views

OCT

• Thinning of the RNFL/GCL occurs in most patients after an episode of ON

o 74% of patients loose at least 20% of their RNFL

o Does not differentiate the cause

o Wedge shaped thinning might suggest a vascular aetiology or Susac syndrome

• Thickening

o Thickening of the Inner nuclear layer with Microcystic macula oedema may be seen

o This is no specific but is more common in NMO

• Potential advantages of OCT

o Confirm disc swelling

o Exclude other causes of visual loss

o Macula oedema may suggest neuroretinitis

o MMO should prompt NMO testing

o Pre-existing RNFL thinning on opposite side might indicate previous episode of ON

Association with MS

Risk of MS is 0% if MRI normal AND ANY of:

• No pain

• Severe disk oedema

• Disc Haemorrhage

• Macular exudate

• NLP vision

Treatment

Demyelinating optic neuropathy

Optic neuritis Treatment Trial (ONTT)

• NEJM 1992

• 450 patients divided into IV methylprednisolone (250mg QID for 3 days) , Oral prednisolone (1mg/kg/day for 14 days with 4 day taper) or Placebo

• Accelerated time to visual recovery with IV

• Reduced rate of conversion to MS at 2 years but effect disappeared by 5 years

• No difference in recurrence rate of optic neuritis compared to placebo, however oral prednisolone increased rate of recurrence

Other Treatment Trials

CHAMPS

ETOMS

BENEFIT

PRECISE

High dose oral steroids

RCT - JAMA neurology 2015

• 55 patients, 1000mg IV methylprednisolone vs oral prednisolone 1250mg (equiv to 50 x 35mg tablets)

• F/U at 1 and 6 months

• No difference in VEP latency, Visual acuity, Low contract visual acuity

• Similar side effects

Cochrane Review 2015

• Oral steroids (standard dose):

o No benefit in VA at 1 month and 6 months and 1 year

CRION

Proposed diagnostic criteria:

1. History: ON and at least one relapse;

2. Clinical: Objective evidence for loss of visual function;

3. Labor: NMO-IgG seronegative;

4. Imaging: Contrast enhancement of the acutely inflamed optic nerve

5. Treatment: Response to immunosuppressive treatment and relapse on withdrawal or dose reduction of immunosuppressive treatment.