Key Facts

Optic neuritis is an inflammatory, demyelinating condition affecting the optic nerve. It is the most common cause of acute optic neuropathy in young adults and is strongly associated with multiple sclerosis. The Optic Neuritis Treatment Trial (ONTT) remains the landmark study guiding management.

Epidemiology

• Incidence: 1-5 per 100,000 per year in the UK
• Peak age: 20-40 years
• Female:male ratio 3:1
• More common in Caucasian populations and higher latitudes
• First presentation of MS in 20% of cases
• 50-70% of patients develop MS within 15 years (higher if MRI abnormalities at presentation)

Aetiology

• Demyelinating: MS (most common), neuromyelitis optica spectrum disorder (NMOSD/Devic disease), MOG antibody-associated disease
• Infectious: post-viral (measles, mumps, EBV), syphilis, Lyme disease, TB, toxoplasmosis
• Autoimmune: SLE, sarcoidosis, Behçet disease
• Drug-induced: ethambutol, isoniazid, chloroquine
• Idiopathic: no identifiable cause in some cases

Pathophysiology

• Autoimmune-mediated inflammatory demyelination of the optic nerve
• T-cell-mediated attack on myelin sheaths surrounding optic nerve axons
• Inflammation causes conduction block, resulting in acute visual loss
• Remyelination occurs during recovery, though may be incomplete
• Axonal loss can occur in severe or recurrent cases, leading to optic atrophy
• In NMOSD, AQP4 antibodies target astrocytes, causing more severe and bilateral disease

Typical Presentation

• Unilateral painful visual loss developing over hours to days (bilateral in children or NMOSD)
• Pain on eye movement (present in >90% of cases), typically periorbital
• Reduced visual acuity (ranges from mild blurring to complete loss of vision)
• Dyschromatopsia (impaired colour vision, particularly red desaturation) often disproportionate to acuity loss
• Central or centrocaecal scotoma on visual field testing
• Uhthoff phenomenon: worsening of symptoms with heat or exercise

Examination Findings

• Relative afferent pupillary defect (RAPD) on swinging light test (Marcus Gunn pupil)
• Reduced visual acuity (variable severity)
• Disc swelling in 35% (papillitis); disc appears normal in 65% (retrobulbar neuritis — 'the patient sees nothing and the doctor sees nothing')
• Reduced colour vision (Ishihara plates)

Red Flags

• Bilateral simultaneous optic neuritis (consider NMOSD or MOG)
• No pain (consider ischaemic optic neuropathy, compressive lesion)
• Progressive visual loss over weeks without recovery (consider compressive or infiltrative lesion)
• Age >50 years (consider giant cell arteritis, ischaemic optic neuropathy)
• Severe visual loss to no perception of light (consider NMOSD)

Bedside

• Visual acuity (Snellen chart)
• Colour vision testing (Ishihara plates) — often disproportionately impaired
• Pupil examination for RAPD (swinging light test)
• Visual field testing (confrontation and formal perimetry) — central/centrocaecal scotoma
• Fundoscopy: disc swelling (papillitis) or normal (retrobulbar)

Bloods

• FBC, ESR, CRP (exclude GCA in older patients)
• AQP4 antibodies (anti-aquaporin-4) if NMOSD suspected
• MOG antibodies if atypical features
• ANA, anti-dsDNA if SLE suspected
• Syphilis serology, ACE level (sarcoidosis) in atypical cases

Imaging

• MRI brain and orbits with gadolinium: gold standard
  • Optic nerve enhancement and swelling on T1 post-contrast
  • T2 hyperintensity of optic nerve
  • White matter lesions (periventricular) suggest MS risk
  • ≥1 T2 lesion: 72% risk of MS at 15 years; 0 lesions: 25% risk (ONTT)

Special Tests

• Visual evoked potentials (VEPs): delayed P100 latency (even after clinical recovery)
• OCT (optical coherence tomography): thinning of retinal nerve fibre layer (RNFL) indicates axonal loss
• Lumbar puncture: oligoclonal bands (if MS workup needed)

Non-pharmacological

• Reassurance that visual recovery typically occurs over 4-6 weeks
• Urgent ophthalmology referral
• Neurology referral for MS workup if MRI abnormalities

Pharmacological

• IV methylprednisolone 1g daily for 3 days (ONTT protocol):
  • Accelerates visual recovery by 2-3 weeks
  • Does NOT alter final visual outcome at 6-12 months
  • Indicated for severe visual loss, bilateral disease, occupational need for rapid recovery
• Oral prednisolone alone is CONTRAINDICATED — increased recurrence rate (ONTT finding)
• Optional: oral prednisolone taper (1mg/kg for 11 days) after IV methylprednisolone
• If NMOSD confirmed: plasma exchange, IV immunoglobulin, long-term immunosuppression (rituximab, azathioprine, mycophenolate)

Surgical

• Not applicable for optic neuritis

Referral Criteria

• Urgent ophthalmology assessment within 24 hours
• Neurology referral for all patients (MS risk stratification)
• Neuro-ophthalmology specialist if atypical features
• Consider disease-modifying therapy (DMT) if MS diagnosed (e.g. dimethyl fumarate, natalizumab, ocrelizumab)

• 95% recover visual acuity to 6/9 or better within 12 months
• Recovery typically begins within 2-3 weeks and continues over months
• Residual colour vision deficit and contrast sensitivity loss are common despite good acuity recovery
• Risk of MS: 25% at 15 years if normal MRI; 72% if ≥1 white matter lesion (ONTT)
• Recurrence of optic neuritis: 35% within 10 years
• NMOSD carries a worse prognosis with 50% legally blind within 5-10 years if untreated
• MOG antibody-associated disease generally has better recovery than NMOSD

Optic Neuritis Treatment Trial (ONTT) Key Findings

MS Risk Stratification by MRI

Comparison of Optic Neuropathies