Acute Optic Neuritis

Optic neuritis (ON) is an inflammation of the optic nerve.¹ The term papillitis is used if the optic nerve head is affected and retrobulbar neuritis if the nerve is affected more posteriorly. It arises in a number of situations:

• Demyelinating ON - by far the most common cause of ON and shall be the main subject of this record.
• Non-Demyelinating ON
  • Parainfectious ON - occasionally occurs following a viral infection or immunisation.
  • Infectious ON - a variety of infections can uncommonly lead to ON.
  • Autoimmune ON - associated with systemic autoimmune diseases.

Demyelinating optic neuritis

There are a number of demyelinating diseases that can affect the optic nerve, the most common being multiple sclerosis (MS). There are cases of isolated optic nerve demyelination, although many subsequently go on to develop more wide-spread disease. Other demyelinating diseases affecting the optic nerve are:

• Devic disease (neuromyelitis optica) - a rare, bilateral optic neuritis which occurs at any age. Over days or weeks, there is development of transverse myelitis. It is distinct from MS in that the brain is spared.²
• Schilder disease - a rare and progressive, generalised demyelinating disease which arises in childhood and results in death within 1 to 2 years of onset.
• Guillain-Barré syndrome, Charcot-Marie-Tooth syndrome, multifocal demyelinating neuropathy and acute disseminated encephalomyelitis

Demyelinating lesions usually involve the optic nerves but occasionally, can occur at the level of the optic chiasm, optic tracts or optic radiations. Brainstem lesions can also affect the visual system through damage to nuclei subserving the cranial nerves involved in motor function, so resulting in gaze palsies, nystagmus and trigeminal and facial nerve palsies.

Association of optic neuritis (ON) and MS

• Some patients with ON have no apparent systemic disease but of those with a normal MRI, 16% go on to develop MS.³
• About 50% of patients presenting with a first episode of ON but no other signs of MS have demyelinating lesions on MRI.
• The cumulative risk of developing MS for asymptomatic patients with or without MRI abnormalities when they first present with ON is 30% over 5 years³ and 38% at 10 years.²
• The risk of developing MS is increased with winter onset of the ON, HLA-DR2 positivity and presence of the Uthoff phenomenon (worsening of symptoms on elevation of body temperature e.g. during a hot bath). This risk is decreased by lack of pain, the presence of optic disc swelling and mild visual acuity loss on presentation.³
• 15 to 20% of MS cases first present with ON.²
• There is evidence of ON in 70% of MS cases.

• Occurs in 1 to 5 individuals/100 000/year.⁴
• Caucasian northern Europeans are 8 times more likely to be affected as Afro-Caribbean and Asian individuals.
• It typically affects individuals between 18 and 45 years old; it is very rare in children in whom it tends to be an immunological reaction to a viral infection.⁵
• There is an increased risk in women (male:female = 1:1.8).
• ON unrelated to multiple sclerosis is higher in developing countries (particularly in tropical climates), where the prevalence of tuberculosis and syphilis is high.

Symptoms⁵

• Subacute visual impairment (deterioration is usually over days but rarely, may be over hours). The peak of impairment is about a week after onset.
• Discomfort in or around the eye (often exacerbated by ocular movements) in the absence of a red eye.
• Ocular symptoms are usually but not exclusively unilateral. It is more likely to be bilateral in children.
• Occasionally, patients report brief flashes of light (phosphenes) induced by eye/body movement or loud noises.
• More unusually, there may be a description of Pulfrich's stereo phenomenon (a beer-barrel appearance to the environment).
• Non-ocular complaints e.g. frontal headache, weakness, numbness, tingling in the extremities.
• There may have been an antecedent 'flu-like episode.

Assessment

Examination should include an assessment of the eye with a particular emphasis on optic nerve function. Please go to our dedicated record on examination of the eye for detail on examination techniques but points to cover should include both a physical examination (particularly the fundus and optic nerve) and an assessment of optic nerve function (visual acuity, check for an RAPD, check for colour impairment, assess brightness sensitivity and carry out a confrontational field test). It is important that both eyes are examined, regardless of the laterality of the symptoms. A full neurological examination is mandatory.

Signs

• The optic disc often looks normal (that of the fellow eye may look pale).
• Visual acuity tends to be somewhere between 6/18 and 6/60.
• An RAPD is present.
• There is impairment of brightness sensitivity.
• Visual fields may diffusely affected, partially affected (e.g. altitudinal defect) and occasional focal defects/arcuate scotomas.

• Ischaemic optic neuropathy (e.g. giant cell arteritis)
• Acute papilloedema
• Severe systemic hypertension
• Orbital tumour compressing the optic nerve
• Leber's optic neuropathy
• Toxic/metabolic optic neuropathy
• Intracranial mass compressing elements of the visual pathway

Diagnosis of demyelinating ON is often suspected clinically but confirmed with an MRI of the brain and orbits (with gadolinium).⁵ Atypical cases may need further investigation through blood tests (e.g. FBC, ESR, VRDL - or equivalent syphilis serology and ANA). Consider a chest XR if there is evidence to suggest sarcoidosis, syphilis, tuberculosis or vasculitis.

• Refer to neurological / ophthalmological team (depending on local referral policies).
• Treatment tends to be reserved for moderate to severe visual impairment (e.g. worse than 6/12 within a week of onset), for those with bilateral involvement and patients with poor vision in the fellow eye.
• Treatment is aimed at speeding up visual recovery in the acute phase but has no bearing on final visual acuity in the long run.⁶ There is, however, recent evidence that questions this fact and in the light of this, practice may change in the future.⁷ It is thought to delay further MS-related neurological events by up to 2 years¹ but it does not affect either the eventual risk of clinically definite multiple sclerosis or the development of disability.³
• The treatment regime involves 3 days of intravenous methylprednisolone (1 gm/day) followed by 11 days of oral prednisolone (1 mg/kg/day).
• Oral prednisolone alone is inappropriate as it has no proven benefit and doubles the recurrence rate of ON.¹
• Intramuscular interferon beta-1a may reduce the risk of clinical demyelination in patients presenting for the first time with ON, who are at high risk of developing MS based on their MRI (where there are 2 or more subclinical brain lesions). This needs to be given within 28 days.
• Patients with a normal MRI benefit from rescanning a year later.
• Patient education is also an important aspect of management - the association with MS clearly has long-term implications both directly for the patient's health and also the related impact it can have on insurance premiums for example.

ON is very rarely a disease entity in itself and the complications relate to the underlying disease process. The most common problem is recurrence which can be as high as 28% over 5 years and 35% over 10 years.²

The acute ON tends to last about 2 to 3 weeks before recovery begins. Maximal recovery tends to occur after about 6 months. 75% of patients recover a visual acuity to 6/9 or better and 85% to 6/12 or better, even if the acute attack was extremely severe. However, the other abnormalities seen (e.g. colour vision, visual field defects, RAPD etc) often persist to a certain degree. Repeated attacks will also eventually result in optic disc atrophy.

Parainfectious optic neuritis

This may follow viral infections (1 to 3 weeks later) such as measles, mumps, chickenpox, rubella, whooping cough and glandular fever. Children tend to be affected more often than adults and presentation is with severe uni- or bilateral visual loss ± headaches, seizures and ataxia. Although the prognosis is excellent in most patients, occasionally there is a need for intravenous steroids.

Infectious optic neuritis²

ON may occur where there is a sinus infection or in the context of cat-scratch fever, Lyme disease, syphilis, tuberculosis, cryptococcal meningitis and in AIDS patients suffering from herpes zoster ophthalmicus. Treatment of the offending organism is warranted and where it is sinus-related, drainage surgery is sometimes required.

Autoimmune optic neuritis

Granulomatous inflammation such as that found in sarcoidosis can result in ON.

Rare causes of ON²

These include:

• Complication of radiation therapy
• Drug induced, e.g. concurrent etanercept and isoniazid therapy, ethambutol in the context of end-stage renal disease and interferon alfa
• Gluten sensitivity
• Hypereosinophilic syndrome
• Vasculitis (giant cell arteritis)