Optic Neuritis

Introduction

Optic neuritis is inflammation of the optic nerve, usually demyelinating in origin. It typically affects women aged 20 to 45 and presents with subacute, painful, unilateral visual loss developing over hours to days and peaking within one to two weeks.¹

Its importance is out of proportion to its incidence of around 5 per 100,000 per year, for two reasons. It is the presenting feature of multiple sclerosis in around a fifth of cases and occurs at some point in perhaps half of all people with MS, so the eye clinic is frequently where the diagnosis begins. And it is one of the classic bedside demonstrations of a relative afferent pupillary defect, which makes it a favourite in clinical examinations.

Understanding the anatomy makes the presentation coherent. The optic nerve is not a peripheral nerve at all: it is a central nervous system tract, myelinated by oligodendrocytes and surrounded by meninges and cerebrospinal fluid. It is therefore susceptible to exactly the same demyelinating processes as the brain and spinal cord, and its sheath is continuous with the intracranial subarachnoid space - which is also why raised intracranial pressure produces papilloedema.

Aetiology

Demyelinating

• Multiple sclerosis-associated (typical) optic neuritis - by far the commonest cause in the UK, and the pattern described in most of this article
• MOG antibody-associated disease (MOGAD) - antibodies against myelin oligodendrocyte glycoprotein. Tends to cause bilateral, painful neuritis with marked disc swelling, is often steroid-responsive but steroid-dependent, and recovers well. Increasingly recognised and now routinely tested for.
• Aquaporin-4 antibody disease (neuromyelitis optica spectrum disorder, NMOSD) - causes severe, often bilateral or sequential optic neuritis with poor recovery, frequently with a longitudinally extensive transverse myelitis. This is the diagnosis not to miss, because it needs different long-term immunosuppression and because interferon beta used for MS makes it worse.
• Acute disseminated encephalomyelitis (ADEM) - typically post-infectious and in children, with bilateral neuritis and encephalopathy

Infective and para-infective

• Post-viral - particularly in children, following measles, mumps, varicella or a non-specific viral illness, and typically bilateral
• Syphilis, Lyme disease and tuberculosis
• Cat scratch disease (Bartonella henselae) - producing neuroretinitis with a macular star
• HIV, herpes zoster, cytomegalovirus and toxoplasmosis in immunosuppression
• Sinusitis with contiguous spread from a posterior ethmoid or sphenoid sinus

Inflammatory and other

• Sarcoidosis - often with a granulomatous, steroid-responsive but steroid-dependent course
• Systemic lupus erythematosus and other connective tissue disease
• Chronic relapsing inflammatory optic neuropathy (CRION) - recurrent, painful, highly steroid-dependent, antibody-negative
• Drugs and toxins - ethambutol, isoniazid, amiodarone, methanol and tobacco-alcohol amblyopia (which are optic neuropathies rather than true neuritis, but enter the differential)
• Vaccination - a rare and much-discussed association, and the absolute risk is very small

Clinical features

Symptoms

• Subacute unilateral visual loss developing over hours to days and worsening for up to two weeks before plateauing. Patients describe a central blur, a dark or grey patch, or a sense that the eye has been dimmed.
• Pain on eye movement - present in around 90%, and often preceding the visual loss by a day or two. It arises because the superior and medial recti take origin from the optic nerve sheath at the orbital apex, so contracting them tugs on the inflamed nerve.
• Reduced colour vision (dyschromatopsia) - reds in particular appear washed out, faded or brown. Patients often notice this before the acuity change, and it is disproportionate to the acuity loss.
• Reduced brightness - a light shone into the affected eye seems dimmer than in the other eye, which patients describe well if asked to compare directly
• Central scotoma - the commonest field defect, though almost any pattern can occur
• Uhthoff phenomenon - transient worsening with heat: a hot bath, exercise, a fever or hot weather
• Pulfrich phenomenon - a moving object appears to follow an elliptical path, because conduction is delayed in one nerve so the two eyes signal at different times
• Photopsias - flashes or sparkles of light, particularly on eye movement

Signs

• Reduced visual acuity - variable, typically 6/12 to 6/60, occasionally worse
• Relative afferent pupillary defect - present in essentially all unilateral cases, and the single most important objective sign. It may be absent if the disease is bilateral and symmetrical.
• Reduced colour vision on Ishihara plates, disproportionate to the acuity - a patient reading 6/9 may fail most of the plates
• Reduced contrast sensitivity and reduced brightness appreciation
• Central or centrocaecal scotoma on field testing
• A normal optic disc in about two thirds - retrobulbar neuritis, where the inflammation lies behind the globe. Hence the aphorism that the patient sees nothing and the doctor sees nothing.
• A swollen, hyperaemic disc in about a third - papillitis, more common in children and in MOG antibody disease
• Optic disc pallor developing at 4-6 weeks as axons are lost, which persists indefinitely and is the residual sign of a previous episode

Differential diagnosis

Investigations

In a young adult with a typical presentation, the diagnosis is clinical. Investigation is aimed at prognosis - determining the risk of multiple sclerosis - and at excluding the atypical causes.

• Visual acuity, Ishihara colour plates and formal visual fields - to document the deficit and track recovery
• MRI brain and orbits with gadolinium - the key investigation. It shows enhancement and T2 hyperintensity in the affected optic nerve, and critically demonstrates whether there are periventricular, juxtacortical, infratentorial or spinal demyelinating lesions, which determine the risk of conversion to MS.²
• MRI whole spine - if myelitis is suspected or NMOSD is being considered
• Aquaporin-4 (AQP4) and MOG antibodies - serum cell-based assays, indicated in atypical presentations and increasingly tested in all first episodes in many UK centres
• Optical coherence tomography - shows peripapillary retinal nerve fibre layer thinning and ganglion cell layer loss over subsequent months, quantifying axonal loss objectively
• Visual evoked potentials - characteristically show delayed latency with preserved amplitude, reflecting demyelination rather than axonal loss. Useful for confirming a past subclinical episode and thereby demonstrating dissemination in space.
• Bloods - FBC, CRP, ESR (to exclude giant cell arteritis in the over-50s), B12 and folate, ANA, ACE, and syphilis and Lyme serology where relevant
• Lumbar puncture - for oligoclonal bands, which support a diagnosis of MS and can now substitute for dissemination in time under the revised McDonald criteria. Not routinely required in typical cases with characteristic MRI findings.
• Chest radiograph - if sarcoidosis is suspected

Management

Acute treatment

The Optic Neuritis Treatment Trial defined practice here and its findings are frequently examined. High-dose intravenous methylprednisolone, typically 1 g daily for three days with or without an oral taper, speeds the rate of visual recovery by about two weeks but does not alter the final visual acuity at six months or one year.⁴

• Offer IV methylprednisolone where rapid recovery matters - a patient whose occupation or care responsibilities depend on vision, or where the fellow eye is already affected
• Observation alone is entirely reasonable in typical unilateral disease, since the final outcome is the same
• Never give oral prednisolone alone at standard doses - in the ONTT this group had a higher rate of recurrent optic neuritis than either the IV steroid or the placebo group. This is a classic exam point.
• Analgesia for the pain, which usually settles within a week or two
• Plasma exchange for severe, steroid-refractory cases, particularly in NMOSD
• Prolonged immunosuppression in MOG antibody disease and NMOSD, since both are steroid-dependent and relapsing

Longer-term management

• Neurology referral for anyone with demyelinating lesions on MRI, for counselling and consideration of disease-modifying therapy
• Disease-modifying therapy - early treatment after a clinically isolated syndrome with an abnormal MRI delays conversion to clinically definite MS, and NICE and the ABN support this in appropriate patients
• Explain the MS risk honestly and at the right pace - many patients have already searched the association online and are more frightened by evasion than by the actual figures
• Explain Uhthoff phenomenon, so that transient blurring in a hot bath or after exercise is not experienced as a relapse
• DVLA - patients must meet the visual standards, and MS itself is separately notifiable
• Follow-up at 4-6 weeks to confirm recovery is under way. Failure to recover, or progressive worsening, mandates re-imaging and reconsideration of the diagnosis.

Prognosis

The visual prognosis in typical demyelinating optic neuritis is good. Recovery usually begins within two to four weeks and continues over several months. In the ONTT, around 90% of patients had acuity of 6/12 or better at one year, and over 70% reached 6/6.

Nevertheless, many patients are left with subtle but persistent deficits that a Snellen chart does not capture: reduced contrast sensitivity, persistent colour desaturation, reduced brightness in the affected eye, impaired depth perception and the Pulfrich phenomenon, and permanent optic disc pallor with thinning of the retinal nerve fibre layer on OCT. Being told the vision is 6/6 while still perceiving the world differently through that eye is a common source of frustration, and it helps to acknowledge it explicitly.

The neurological prognosis dominates the long-term outlook and is determined largely by the baseline MRI. Roughly half of all patients with typical optic neuritis develop multiple sclerosis within 15 years, but that average conceals two very different groups: around a quarter of those with a normal MRI and around three quarters of those with lesions. Antibody-defined disease behaves differently again - MOG antibody disease relapses but generally recovers vision well, while aquaporin-4 antibody disease recovers poorly and carries a substantial risk of severe bilateral visual loss without long-term immunosuppression.⁵