Optic neuritis

Optic neuritis refers to inflammation of the optic nerve secondary to demyelination that leads to acute visual loss.

Optic neuritis is an inflammatory condition of the optic nerve that characteristically leads to acute, unilateral, central loss of vision. The visual loss usually occurs over hours to days and is associated with ocular pain that is worse on movement.

Optic neuritis may be isolated or part of a wider neurological disorder such as multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), or myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease. It is the presenting feature of MS in up to 20% of cases.

The diagnosis is clinical, although imaging with MRI is usually performed to look for other demyelinating lesions that are suggestive of MS. The principal treatment of optic neuritis is high dose corticosteroids.

Optic neuritis is most commonly seen in younger, female adults.

Optic neuritis is more common in females and most commonly occurs between 20-40 years of age. The incidence of the condition, similar to other demyelinating conditions, is higher the further the distance from the equator (i.e. higher the latitude).

Optic neuritis is due to demyelinating inflammation of the optic nerve.

Optic neuritis results from immune-mediated demyelination of the optic nerve. The exact cause of the demyelination is unknown but there is evidence of systemic T cell activation followed by B cell activation with development of antibodies to components of myelin within the central nervous system. Optic neuritis may be isolated, part of a wider demyelinating disorder, or the first presentation in a patient who will go on to develop a more systemic disorder like MS.

Optic neuritis is essentially an ‘acute version’ of multiple sclerosis. It is estimated that up to 50% of individuals with MS will have an episode of optic neuritis during the course of their illness. Optic neuritis is the presenting clinical manifestation of MS in 15-20% of cases.

Analysis of both demyelinating plaques and the immune response generated in the cerebrospinal fluid during an episode of optic neuritis is supportive of an aetiology similar to multiple sclerosis.

Association conditions

Optic neuritis is associated with several more systemic neurological disorders, which include:

• Multiple sclerosis: a chronic, immune-mediated inflammatory disease of the central nervous system, which is characterised by demyelination. Affects the optic nerve in up to 50% of patients. A wide range of clinical features can develop depending on the site of the central nervous system affected (e.g. brainstem, spinal cord, cerebellum).
• Neuromyelitis optica spectrum disorder (NMOSD): an autoimmune disorder of the central nervous system that is characterised by autoantibodies to aquaporin-4 (AQA-4) that causes a wide range of clinical features including optic neuritis. The optic neuritis in this disorder is usually more severe, and more likely to be bilateral
• Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease: an autoimmune, demyelinating central nervous system disorder characterised by ‘MOG’ autoantibodies and features of optic neuritis, disseminated encephalomyelitis, and transverse myelitis

‘Optic neuropathy’ is a broad term that refers to any condition affecting the optic nerve.

Optic neuritis is one specific cause of optic neuropathy secondary to demyelinating inflammation of the optic nerve. On the other hand, optic neuropathy is a broad term that encompasses all the different pathologies that can affect the optic nerve from inflammation to granulomatous infiltration.

In younger adults, the most common cause of optic neuropathy is optic neuritis, whereas in older adults ischaemic optic neuropathy is most common (e.g. secondary to giant cell arteritis).

Causes

Some of the main causes of optic neuropathy include:

• Optic neuritis
• Ischaemic optic neuropathy
• Infective optic neuritis (e.g. toxoplasmosis, cat-scratch disease, cryptococcus)
• Post-viral (e.g. mumps, influenza)
• Sarcoidosis
• Drugs and toxins (e.g. infliximab)
• Radiotherapy
• Compression (e.g. tumour)
• Genetic (e.g. Leber hereditary optic neuropathy)

Mnemonic

These causes are often grouped into a handy mnemonic called ‘NIGHT TIC’:

• N – Neuritis
• I – Ischaemic
• G – Granulomatous infiltration (e.g. sarcoid)
• H – Hereditary (e.g. Leber’s)
• T – Traumatic
• T – Toxins (e.g. drugs, methanol)
• I – Irradiation
• C – Compression

Damage to the optic nerve leads to acute, central vision loss.

The characteristic features of any pathology that affects the optic nerve includes relative afferent pupillary defect (RAPD), central vision loss, and loss of colour vision. Bilateral symptoms are uncommon and more suggestive of a systemic neurological disorder (e.g. NMOSD).

Symptoms

• Visual loss: the loss of vision is typically acute, central, and unilateral occurring over hours to days.
• Eye pain: worse on visual movement
• Reduced colour vision (particularly reds)
• Photopsia: this refers to flickering or flashes of light

Signs

• Relative afferent pupillary defect (RAPD): refers to asymmetrical pupillary reaction to light due to optic nerve disease. Tested using the ‘swinging light test’ (See below)
• Visual field defects: commonly a central scotoma (i.e. a partial loss of vision in an otherwise normal visual field), but many different visual field defects can be present
• Papillitis: seen in anterior optic neuritis. There is evidence of a swollen optic disc on fundoscopy that is similar to papilloedema but the key is that visual loss is markedly reduced in papillitis. In posterior optic neuritis the disc appears normal.
• Optic atrophy: this is a chronic sign of optic neuritis that can be seen following an acute episode. The optic disc appears shrunken and pale on fundoscopy. The degree of atrophy depends on the number of attacks and severity.

Swinging light test

The swinging light test is completed to assess for a RAPD. The examiner shines a light into one of the pupils. Light shone into the unaffected eye leads to bilateral pupillary constriction as the afferent pathway is unaffected. When the light source is swung across into the affected eye there is mild pupillary constriction as some light is still sensed (depending on severity), but the contralateral unaffected pupil dilates due to an abnormal afferent pathway. In other words, the consensual light reflux is reduced due to abnormal function of the optic nerve.

Optic neuritis is usually a clinical diagnosis based on typical signs and symptoms that should include fundoscopic assessment.

The diagnosis of optic neuritis is usually made clinically based on the presence of acute, severe, unilateral visual loss with minimal neurological or ocular findings. Direct ophthalmoscopy may show evidence of a mildly swollen optic disc.

The presence of central visual loss with pain on movement, a RAPD, and mildly swollen optic disc is essentially pathognomonic for optic neuritis. The diagnosis is further supported by younger age, no evidence of systemic disease and subsequent improvement.

MRI is the most important additional diagnostic test for two main reasons:

1. Confirm the presence of demyelinating optic neuritis
2. Assess for other neurological lesions (i.e. plaques) suggestive of a diagnosis of multiple sclerosis

Imaging

An MRI of the brain with or without the spine is important to look for any evidence of demyelinating lesions within the central nervous system. There are characteristic features of optic neuritis on MRI and these will be seen in ~95% of patients who undergo MRI with gadolinium contrast.

If MRI does not show any lesions suggestive of multiple sclerosis it is estimated up to 25% of patients presenting with optic neuritis will later develop the condition. This type of isolated clinical presentation of an acute demyelinating pathology is often known as ‘clinically isolated syndrome’

Lumbar puncture

A lumbar puncture involves insertion of a spinal needle into the subarachnoid space in the lower spine to take a sample of cerebrospinal fluid. It is not a routine test for optic neuritis but may be completed in atypical cases or when a systemic neurological condition such as MS or NMOSD is suspected.

Typical features of optic neuritis on LP include:

• Elevated protein
• Elevated lymphocytes
• Oligoclonal bands (OCB)

OCB are associated with white matter lesions of MRI imaging and thus imply an increased risk of developing MS.

Special tests

If a systemic neurological cause is suspected then a number of additional investigations including blood tests and special autoantibodies can be requested. These may include but not limited to:

• Full blood count
• CRP/ESR
• LFTs, U&Es, Bone profile
• Glucose, HbA1c
• TFTs
• Haematinics
• Blood-borne virus screen
• Autoantibodies: MOG, AQA-4

Treatment of optic neuritis is typically with high-dose intravenous steroids.

The principal treatment of optic neuritis is high-dose, intravenous corticosteroids with methylprednisolone. This treatment has been shown to hasten visual recovery and also delay the onset of MS in those who subsequently develop the condition. However, intravenous steroids are not associated with improved long-term visual outcomes.

Additional ‘disease modifying therapies’ may be considered in patients deemed to have a clinically isolated syndrome consistent with MS based on further investigations including imaging.

Visual recovery in optic neuritis is common.

The two major concerns following presentation with optic neuritis is visual recovery and risk of progression to multiple sclerosis.

Even without treatment, visual recovery usually begins within a few weeks of presentation. The majority of patients (>90%) will have at least 6/12 vision (i.e. they can see at 6 metres what someone with normal vision can see at 12 metres) by one year. There are various prognostic factors that will predict a worse visual outcome (e.g. Severe visual loss at one month, ethnicity, extent of inflammatory lesion on MRI).

Optic neuritis recurrence may be as high as 35% over 10 years. The recurrence of optic neuritis also confers a greater risk of MS. Over 5 years, the risk of MS following an acute episode of optic neuritis is 30% with a median time to diagnosis of three years. Those who present with optic neuritis at older age (e.g. >35 years) are less likely to develop MS overtime.