Optic Neuritis

Description

Optic neuritis refers to an inflammation of the optic nerve, which can lead to transient or lasting vision loss. The condition is often associated with autoimmune diseases, particularly multiple sclerosis (MS). Though it can affect individuals of any age, it is most prevalent amongst young adults.

Pathogenesis

Optic neuritis typically manifests as a consequence of an autoimmune reaction that results in inflammation and demyelination of the optic nerve. In most cases, the autoimmune response is an isolated incident, but it may also be a precursor or symptom of a systemic autoimmune disease like multiple sclerosis or neuromyelitis optica.

Epidemiology, Risk Factors & Associations

• Optic neuritis primarily affects young adults aged 20-45 years, with a peak incidence in the third decade.
• More common in women (ratio of 3:1 compared to men) and in individuals of Northern European descent.
• Risk factors include genetic susceptibility (e.g., certain HLA-DRB1 alleles), environmental factors such as exposure to certain viral infections, smoking, and vitamin D deficiency.

The condition can arise in the setting of various infective and non-infective conditions.

Non-infective causes

• Multiple sclerosis (MS) (33% of cases): It’s the most common cause of optic neuritis. About 50% of individuals with optic neuritis will develop MS within 15 years.
• Neuromyelitis optica (NMO) (1-2%): Less common than MS. Optic neuritis may occur concurrently with transverse myelitis.
• MOG antibody-associated disease (MOGAD) (less common): A small proportion of patients with optic neuritis have MOGAD.
• Sarcoidosis (rare, <1%).
• Acute disseminated encephalomyelitis (ADEM), Systemic lupus erythematosus (SLE), Behçet disease, Sjögren syndrome: These systemic autoimmune diseases can occasionally cause optic neuritis. The prevalence is low and varies by geographical location and population.
• Toxins and Radiation (rare)
• Chronic relapsing inflammatory optic neuropathy (CRION) (very rare, < 1%)

Infective causes

• Lyme disease: It’s an uncommon cause of optic neuritis and is more likely to occur in Lyme-endemic areas.
• Toxoplasmosis: It’s a rare cause of optic neuritis and typically occurs in immunocompromised individuals.
• Human immunodeficiency virus (HIV): HIV-associated optic neuritis is also rare and typically occurs in the advanced stages of the disease.
• Systemic viral diseases as varicella or herpes: These are rare causes of optic neuritis. The incidence is not well-established.

Clinical Features

Common symptoms of optic neuritis include sudden, unilateral, and painful loss of vision that worsens over a period of several days.

Other features may include impaired colour vision (dyschromatopsia), a central scotoma or ‘blind spot’, and pain with eye movement.

Complications

Optic neuritis can lead to permanent vision loss if not promptly treated. Furthermore, as a potential early manifestation of systemic autoimmune conditions such as multiple sclerosis and neuromyelitis optica, optic neuritis could herald the onset of more extensive neurological involvement.

Subtypes

Optic neuritis is broadly divided into two categories based on the underlying cause: idiopathic optic neuritis and secondary optic neuritis.

• Idiopathic optic neuritis occurs without any identifiable cause
• Secondary optic neuritis arises due to an underlying systemic disease such as multiple sclerosis, neuromyelitis optica, or systemic lupus erythematosus.

Pathological Features

Histopathology

The key pathological finding in optic neuritis is inflammatory infiltration of the optic nerve with lymphocytes, resulting in demyelination. In severe cases, there can be axonal loss leading to optic atrophy.

Serology

Serological tests may reveal the presence of anti-aquaporin-4 antibodies (common in neuromyelitis optica) or oligoclonal bands in the cerebrospinal fluid (indicative of multiple sclerosis).

Genetics

There’s no specific genetic marker for optic neuritis, but it is more common in individuals carrying certain HLA-DRB1 alleles, indicating a genetic predisposition.

Radiological Features

General Features

• In acute optic neuritis, the optic nerve appears swollen and enhances with contrast.
• In the chronic stage, optic nerve atrophy may be observed.

MRI

• T1WI: Normal or slightly increased signal in the affected optic nervee.
• T1WI C+: Enhancement of the optic nerve sheath or the nerve itself.
• T2WI: High signal intensity in the affected optic nerve.

May see concurrent features of multiple sclerosis:

• T2WI/FLAIR: Multiple periventricular, juxtacortical, infratentorial or spinal cord white matter lesions, which appear as high signal areas. The characteristic “Dawson’s fingers” sign might be seen, referring to perpendicular oriented demyelinating lesions along the lateral ventricles.
• T1WI: Lesions may appear as hypointense, or “black holes,” indicating areas of severe demyelination and axonal loss.
• T1WI C+: Active lesions can enhance, usually in a ring or open-ring pattern.
• DWI/ADC: MS lesions are typically isointense on DWI with no restricted diffusion.

Grading and Staging

There is currently no grading or staging system for optic neuritis.

Diagnosis

The diagnosis of optic neuritis is primarily clinical, based on symptoms and ophthalmological findings. MRI is often employed to identify optic nerve inflammation and to assess for possible underlying causes, such as multiple sclerosis.

Differential Diagnosis

Clinically-based

• Ischaemic optic neuropathy: Characterised by painless vision loss and optic disc pallor rather than swelling. It is more common in older adults with vasculopathic risk factors. MRI may show restricted diffusion at nerve head, however >75% of cases often normal.
• Compressive optic neuropathy: Often associated with slowly progressive visual loss and evidence of mass lesion on imaging.
• Leber’s hereditary optic neuropathy: This genetic condition usually affects young males with a history of smoking and alcohol use. It presents as bilateral, sequential vision loss.

Imaging-based

• Optic nerve meningioma – Tubular, fusiform mass surrounding the optic nerve, with calcification often seen. Demonstrates intense linear enhancement around the nerve giving a tramtrack sign. Optic nerve is not thickened or enhanced. Usually seen in middle-aged females.
• Optic nerve glioma – Most common cause of diffuse optic nerve enlargement (especially in childhood, seen in neurofibromatosis type 1). Low density than meningioma on CT. Fusiform enlargement with variable enhancement. May extend along optic pathway (chiasm, optic tracts, lateral geniculate body and optic radiation)

Management

• Patients with optic neuritis should be promptly referred to ophthalmology for assessment and management.
• The first-line treatment is intravenous corticosteroids (e.g., methylprednisolone) followed by oral corticosteroids. This treatment can hasten visual recovery but doesn’t significantly influence the final visual outcome or risk of developing multiple sclerosis.
• If a patient has recurrent optic neuritis, an underlying systemic condition should be suspected, and appropriate referrals made for further evaluation.