Optic neuritis

Definition

• • Optic neuritis (ON) represents inflammation of the optic nerve

  • By far the most common form is idiopathic ON, which is a primary demyelinating disease occurring in isolation or as part of multiple sclerosis (MS)

  • When in isolation, primary demyelinating ON is considered a forme fruste of MS

  • ON manifests as:

    • subacute or acute onset of pain in the eye

    • pain with eye movements

    • loss of vision, typically with central or centrocaecal scotoma

    • usually reaches a nadir at approximately 1 to 2 weeks

  • ON recovers over several months, with ultimate visual acuity that is possibly reduced but seldom severely so

Risk Factors

• • Strong

    • age 30 to 50 years

    • female sex

    • white ethnicity

    • HLA DR(2)15 genetic mutation

  • Weak

    • EBV infection later in childhood

    • childhood in higher latitudes

    • presence of autoimmune disease

    • exposure to infectious diseases, such as Lyme disease and syphilis

Differential diagnosis

• Lyme disease

• Syphilis

• HIV infection

• Varicella-zoster

• Aspergillosis

• Cat-scratch disease

• SLE

  • Neuromyelitis optica (Devic's disease)

• Sarcoidosis

• Behcet's syndrome

• Sjogren's syndrome

• Giant cell arteritis

• Takayasu's arteritis

  • Non-arteritic anterior ischaemic optic neuropathy

  • Drugs and toxins

  • Leber's hereditary optic neuropathy

Epidemiology

• • The demographics and distribution of idiopathic optic neuritis (ON) reflect those of multiple sclerosis (MS)

  • The annual incidence varies between 1 and 5 per 100,000

  • The majority of patients with acute ON are aged 20 to 50 years

  • Females are more commonly affected than males

    • In the Optic Neuritis Treatment Trial (ONTT), 77% of patients were females, 85% were white, and mean age was approximately 33 years

  • As for MS, the geographic distribution follows a striking latitude gradient, with higher frequency the closer the location is to the poles

  • Within the same geographical distribution, white people are at higher risk than other ethnic groups such as black people

    • The latter group, although less susceptible, tends to have more severe disease

Aetiology

• • Idiopathic optic neuritis (ON) has no known aetiology

  • When ON occurs in isolation, it is considered a forme fruste of multiple sclerosis (MS), and the aetiology of ON is thought to be identical to that of MS

  • The most common view of this inflammatory, primary demyelinating disease is that it is the result of interplay between genetic susceptibility and an environmental factor, most probably a virus

    • Of the many viruses that have been implicated, the Epstein-Barr virus is the strongest contender for an aetiological role, based on both epidemiological and, to a lesser extent, biological studies

  • Inflammatory optic neuropathies outside the context of primary demyelinating diseases (ON in the wider sense) include:

    • systemic autoimmune diseases such as SLE (where up to 5% of patients may have optic neuropathy)

    • sarcoidosis

    • Sjogren's syndrome

    • Behcet's disease.

  • ON, typically bilateral, is also part of neuromyelitis optica (NMO, Devic's disease), where frequently there are some features of SLE and other autoimmune conditions (discussed below), chronic relapsing inflammatory optic neuropathy (CRION, where there is recent evidence of an overlap with NMO), and post-infection or post-vaccine conditions such as acute disseminated encephalomyelitis.

  • Infectious aetiologies are rare but include Lyme disease and syphilis

Clinical features

• • Common

    • peri-orbital/retro-ocular pain

    • loss of visual acuity with scotoma

    • colour desaturation/loss of colour vision

    • relative afferent papillary defect (RAPD)

    • optic disc swelling

    • neurological abnormalities of multiple sclerosis

  • Uncommon

    • phosphenes

    • Uhthoff's phenomenon

    • Pulfrich's phenomenon

    • peri-venous sheathing

Pathophysiology

• • The pathophysiological mechanisms of optic neuritis (ON) and multiple sclerosis (MS) are identical

    • MS and ON are thought to have autoimmune mechanisms triggered by an environment factor (such as a virus) in susceptible people

  • T-helper cells (CD4+) are key effector cells

    • These are activated in the periphery by an environmental factor and cross the blood-brain or blood-optic nerve barrier

    • Inside the CNS they encounter neural auto-antigens, proliferate, activate and recruit other inflammatory cells

    • CD4+ cells stimulate local immune and parenchymal cells such as microglia and astrocytes to produce pro-inflammatory cytokines

  • The neural damage involves complex pathways also involving CD8+ cells, B cells, antibody, and complement

  • This leads to the key pathological features of MS/ON

    • inflammation

    • demyelination

    • axonal loss

    • gliosis

  • The signals for resolution of inflammation are not well known

  • Neural recovery represents a combination of resolution of inflammation, re-myelination, and neural plasticity

  • The loss of axons, neurones, and myelin can be assessed using quantitative MRI and optical coherence tomography techniques

  • Free radical damage and glutamate excitotoxicity are thought to play an important role in the axonal and myelin damage, and have been linked to mitochondrial dysfunction

Investigations

• • MRI of the optic nerves

    • swelling of optic nerve

    • enhancement in optic nerve

    • white matter lesions in patients with multiple sclerosis (MS) or at risk of MS

  • FBC

    • high WBC (infection)

  • ESR

    • high in giant cell arteritis

  • C-reactive protein

    • high in infection/inflammation

  • VDRL

    • positive in syphilis infection

  • uric acid

    • Non-specific indicator of reduced anti-oxidant reserve

    • has been shown to be low in MS and in primary demyelinating ON

  • serum ACE

    • Elevated in patients with sarcoidosis, and responds to treatment

    • May be non-specifically elevated in other inflammatory diseases, including a proportion of patients with MS, although not at the high levels seen in sarcoidosis

  • ANA

    • Positive in patients with SLE

    • May be non-specifically elevated in other inflammatory diseases including a proportion of patients with MS, although not at the high titres seen in SLE

Management

a) conservative

b) medical

• • acute episode

    • pulsed methylprednisolone

    • oral prednisolone

    • gastrointestinal protection with H2 antagonists or proton pump inhibitors

  • co-existing inflammatory diseases (e.g., SLE or sarcoidosis)

    • immunosuppressive treatment

c) surgical

Prognosis

• • Optic neuritis (ON) recovers spontaneously, typically over several weeks or months

  • Generally the visual prognosis of ON is good, with only approximately 8% having a residually decreased visual acuity of less than 20/40

  • There is a certain risk of recurrence (30% over 5 years) in the affected or fellow eye

  • There is also a risk of conversion to clinically definite multiple sclerosis, which depends on the presence of an abnormal MRI at presentation