Acute optic neuritis

Synonyms: retrobulbar neuritis, papillitis

Optic neuritis, or inflammation of the optic nerves, is a frequent cause of acute optic nerve injury in children and adults. Although optic neuritis is frequently associated with multiple sclerosis, there are many other causes of optic neuritis¹ . Classically there is a triad of clinical features - reduced vision (of varying severity), eye pain (particularly on movement) and impaired colour vision.

The term 'optic neuritis' means inflammatory optic neuropathy from any cause, but is sometimes used to refer to acute demyelinating optic neuritis. In this article, 'optic neuritis' (ON) refers to optic neuritis of any type, and 'acute demyelinating optic neuritis' (ADON) will be used for that specific form. Other terms used in the literature are papillitis (if the optic nerve head is affected) and retrobulbar neuritis (if the nerve is affected more posteriorly).

ADON is a common cause of ON in parts of the world where multiple sclerosis (MS) is common. However, there are many other possible causes which must not be overlooked, as they may require different and urgent management.

Neuromyelitis optica (NMO), also known as Devic's disease or Devic's syndrome, is a rare condition in which there are recurrent and simultaneous optic neuritis and myelitis of the spinal cord. Lesions are different from those observed in MS, and the condition requires a different course of treatment² .

The first part of this article discusses ON of any type: its causes, assessment and diagnosis. The second part gives more detail about ADON in adults, with a note on Devic's disease.

Aetiology³

Causes of optic neuritis (ON)⁴

Differential diagnosis

• Posterior scleritis.

• Maculopathy.

• Retinopathy.

• Big blind spot syndrome.

Presentation, assessment and diagnosis⁸

The diagnosis of optic neuritis is based on presenting symptoms and signs. The onset is usually with pain on eye movement in one eye and subacute visual loss. In unilateral optic neuritis, the direct pupillary light reflex is weaker in the affected eye. One third of patients with optic neuritis have a mildly oedematous optic disc. The visual disturbance resolves in 95% of cases. A less favorable course may be evidence of neuromyelitis optica, and macular involvement may be evidence of neuroretinitis⁹ .

Usual presentation

This is usually a triad of:

• Visual impairment (of varying severity, usually developing over a period of hours or days, and may typically be exaggerated by a hot bath or shower).

• Pain around the eye (retrobulbar or ocular, typically worse on eye movement).

• Dyschromatopsia (impairment of colour vision).

Other symptoms present in ADON are:

• Light flashes (phosphenes or photopsias).

• Uhthoff's phenomenon - increased symptoms with raised body temperature (hot environment or exercise).

• Pulfrich's phenomenon - altered perception of the direction of movement; objects moving straight appear to have a curved trajectory, presumably due to asymmetrical conduction in optic nerves.

• Fatigue - fading of vision.

Typical signs

These include:

• Decreased pupillary light reaction in the affected eye: a relative afferent pupillary defect (RAPD), or Marcus Gunn pupil, commonly is found; in bilateral cases, the RAPD may not be apparent.

• Varying degrees of vision reduction: from a mildly decreased visual acuity to complete vision loss.

• Abnormal contrast sensitivity and color vision: this is seen in almost all patients with adult ON with decreased visual acuity.

• Altitudinal field defects.

• Arcuate defects.

• Nasal steps.

• Scotoma.

• Papillitis is seen in one third of patients with ON.

Assessment

• Full ophthalmological and neurological examination.

• In practice, it is important to assess whether the clinical picture is typical of ADON, or whether there are atypical features suggesting another cause (see table).

Typical vs atypical features of optic neuritis (ON)⁴

Investigations¹⁰

The diagnosis of ADON is a clinical one. If the clinical picture is typical for ADON, initial assessment involves:

• Full ophthalmological examination.

• Testing of visual acuity, contrast and colour vision, visual field testing.

Further investigations

• MRI of the brain may be used to give information about the likelihood of developing MS.

• Some studies suggest that testing of contrast vision, using specific charts, may yield similar information to MRI in this scenario⁴ .

• If there are atypical features, investigations depend on the clinical picture, and may include:
  

  • Blood tests - eg, FBC, ESR, TFTs, autoantibodies and syphilis serology.

  • Serological testing for neuromyelitis optica immunoglobulin G (NMO-IgG)⁶ .

  • CXR - for suspected sarcoidosis, tuberculosis or malignancy.

  • CT or MRI of the brain and orbits.

  • Lumbar puncture - for suspected central nervous system infection or inflammatory ON (CSF is examined for immunoglobulins, oligoclonal bands and infection). CSF analysis is usually non-contributory to diagnosis. However, the presence of myelin basic protein, oligoclonal bands, and an elevated IgG index and synthesis rate in the CSF, supports the diagnosis of MS. Even in the absence of other signs of MS during the initial presentation, patients with positive findings of demyelination in the CSF are more likely to develop MS in the long term. NMO-IgG is a specific autoantibody marker for NMO.

  • Visual evoked potentials.

Acute demyelinating optic neuritis in adults⁴

Epidemiology

• ADON demographics closely follow those of MS, which has a higher frequency in Caucasian populations and at higher latitudes. Children who migrate before puberty take on the MS incidence of the area to which they migrate.

• Annual incidence of ADON is approximately 5/100,000; prevalence is 115 per 100,000.

Pathophysiology

The pathology of ADON involves demyelination and axonal loss, probably due to an inflammatory process and a delayed hypersensitivity reaction. Recovery is due to remyelination and compensatory neuronal recruitment.

Presentation, diagnosis and investigations

These are explained above (see clinical features, and 'Presentation, assessment and diagnosis' and 'Investigations' sections).

Management

• Refer to an ophthalmologist and/or neurologist. Usually, an ophthalmologist is involved in the initial assessment, diagnosis and treatment. Further management regarding the risk of MS (below) usually requires neurological expertise.

• Consider corticosteroids during the acute phase:
  

  • Treatment with methylprednisolone speeds up visual recovery in the acute phase, but has no effect on final visual acuity^{9 11} . Side-effects of corticosteroids can be serious. Therefore, they are usually reserved for patients who need to hasten visual recovery, such as those with poor vision in the fellow eye or bilateral visual loss, or for occupational reasons.

  • Recommended treatment is methylprednisolone 1 g daily for three days.

  • Oral prednisolone is not recommended because of (uncertain) evidence that it may increase the recurrence rate.

• There is no treatment that can reverse poor visual outcome in the long term.

• Information for patients is important (see 'Prognosis', below).

• Consider brain MRI, to give information about the risk of developing MS.

• Consider referring to a neurologist for assessment of the patient's risk of developing MS, and the value of disease-modifying drugs in this context (see 'Role of disease-modifying drugs', below).

• For Pulfrich's phenomenon (disturbed perception of movement), symptoms may be helped by using spectacles with a tinted lens over the unaffected eye, to balance the delay in conduction from the other side.

• For Uhthoff's phenomenon symptoms (worsening vision with raised body temperature), avoid hot environments and take cool drinks; reassure patients that this symptom is reversible and does not further damage vision.

• Intravenous immunoglobulin has generally been found to be of no benefit. One trial (small and non-randomised, using a different regimen) reported improved vision with immunoglobulin treatment¹² .

Prognosis

Visual prognosis

• The prognosis for vision in ADON is usually good¹³ .

• The Optic Neuritis Treatment Trial (ONTT), was a large study of ADON with 15-year follow-up, and found that:
  

  • 93% of patients showed improvement within five weeks of onset of ADON; vision continued to improve for up to one year. One year after onset, 93% had visual acuity better than 6/12 in the affected eye. At 15-year follow-up, 92% had acuity better than 6/12 in the affected eye, and only 1% had vision worse than 6/60 in both eyes.

  • The severity of initial visual loss seems to be related to the final visual outcome; however, even with initial visual acuity of ≤6/60, 85% recover vision to 6/12 or better.

• Although visual outcome is good in objective tests, many patients experience subjective reductions in vision, colour vision, contrast sensitivity or depth/movement perception after recovery from ADON.

Risk of recurrence

• ADON can recur in either eye.

• The risk of recurrence was 35% over 10 years in the ONTT.

Risk of developing MS

• ADON is associated with MS.

• In the ONTT, for adults with a single episode of unilateral ADON, the risk of MS was 38% at 10 years after onset, and 50% at 15 years¹⁴ . Another study found the MS risk was 54% after 30 years. The risk of developing MS is lower for children and for men.

• MRI of the brain gives information about the risk of developing MS. The presence of white matter abnormalities increases the MS risk and their absence reduces it. In the ONTT, the risk of developing MS at 15-year follow-up was 25% for patients with no lesions on MRI, and 75% for those with white matter lesion(s).

Role of disease-modifying drugs

• Interferon beta increases the time interval to relapse in MS. Trials suggest that, in a scenario such as a patient with ADON and white matter lesions on brain MRI, where the risk of developing MS is relatively high, interferon beta may similarly delay the onset of MS symptoms.

• However, bear in mind that:
  

  • Many patients with a first episode of ADON and an abnormal MRI scan will not develop MS.

  • Treatment is only partly effective - eg, six years of interferon beta treatment prevents one relapse.

  • The visual prognosis is good even if MS develops.

Discussion with patients

• The association between ADON and MS causes anxiety for patients and can impact on insurance policies.

• It is important to emphasise that many ADON patients will not develop MS; even if they do, the prognosis regarding both vision and other disability can be good.

• Information about the prognosis can help patients to decide whether to undergo an MRI scan and whether to use beta interferon.

Devic's disease¹⁵

• This is an idiopathic inflammatory demyelinating and necrotising disease mainly involving the optic nerves and spinal cord. In Asian countries relapsing NMO is known as opticospinal MS.

• NMO has a typically relapsing course. Distinctive pathological features of NMO distinguish NMO from other demyelinating diseases such as MS. An IgG antibody named NMO-IgG has high sensitivity and specificity.

• There is often a long spinal cord lesion that extends through three or more vertebral segments in length. Brain MRI lesions atypical for MS are found in the majority of cases.

• Treatment in the acute phase includes intravenous steroids and plasma exchange therapy. Immunosuppressive agents are recommended for prophylaxis of relapses.

Dr Mary Lowth is an author or the original author of this leaflet.