Acute optic neuritis

Synonyms: retrobulbar neuritis, papillitis

What is optic neuritis?

Optic neuritis, or inflammation of the optic nerves, is a frequent cause of acute optic nerve injury in children and adults. Although optic neuritis is frequently associated with multiple sclerosis, there are many other causes of optic neuritis.¹ Classically there is a triad of clinical features - reduced vision (of varying severity), eye pain (particularly on movement) and impaired colour vision.

The term 'optic neuritis' means inflammatory optic neuropathy from any cause, but many other terms are used to differentiate subtypes of optic neuritis. Other terms used in the literature are papillitis (if the optic nerve head is affected) and retrobulbar neuritis (if the nerve is affected more posteriorly).

Demyelinating disorders are a common cause of ON in parts of the world where multiple sclerosis (MS) is common such as northern European countries. Multiple sclerosis associated optic neuritis as the first presentation of a clinical isolated syndrome with MRI or CSF findings compatible with multiple sclerosis. It can also occur as a
multiple sclerosis relapse. Isolated MS-ON is an atypical or attenuated manifestation of multiple sclerosis. There are many other possible causes of optic neuritis which must not be overlooked, as they may require different and urgent management.

Neuromyelitis optica spectrum disorder (NMOSD), is a rare condition in which there are recurrent and simultaneous optic neuritis and transverse myelitis of the spinal cord. Lesions are different from those observed in MS, and the condition requires a different course of treatment.²³

Presentation⁴⁵

The diagnosis of optic neuritis is based on clinical criteria with support from paraclinical tests (OCT, MRI and biomarkers). The onset is usually with pain on eye movement in one eye and subacute visual loss. In unilateral optic neuritis, the direct pupillary light reflex is weaker in the affected eye.

Other symptoms present in multiple sclerosis optic neuritis are:

• Varying degrees of vision reduction: from a mildly decreased visual acuity to complete vision loss.

  • Light flashes (phosphenes or photopsias).

  • Uhthoff's phenomenon - increased symptoms with raised body temperature (hot environment or exercise).

  • Pulfrich's phenomenon - altered perception of the direction of movement; objects moving straight appear to have a curved trajectory, presumably due to asymmetrical conduction in optic nerves.

  • Fatigue - fading of vision.

Typical signs

These include:

• Abnormal contrast sensitivity and colour vision: this is seen in almost all patients with adult ON with decreased visual acuity.

• Altitudinal field defects.

• Arcuate defects.

• Nasal steps.

• Scotoma.

• Papillitis is seen in one third of patients with ON.

One third of patients with optic neuritis have a mildly oedematous optic disc. The visual disturbance resolves in 95% of cases. A less favourable course may be evidence of neuromyelitis optica, and macular involvement may be evidence of neuroretinitis.⁶

Diagnostic criteria⁵

A) Monocular, subacute loss of vision associated with orbital pain worsening on
eye movements, and relative afferent pupillary deficit (or Marcus Gunn pupil), is commonly found.
B) Painless with all other features of (A).
C) Binocular loss of vision with all features of (A) or (B). In bilateral cases the RAPD may not be apparent.

Paraclinical criteria⁵

OCT: Corresponding optic disc swelling acutely or an inter-eye difference in the macular ganglion cell inner plexiform layer (mGCIPL) of >4% or >4 μm or in the peripapillary retinal nerve fibre layer (pRNFL) of >5% or >5 μm within 3 months after onset.

MRI: This shows contrast enhancement of the symptomatic optic nerve and sheaths acutely, or a signal looking brighter within 3 months. The sensitivity of MRI to detect optic neuritis is 20-44%, depending on the subtype.

Biomarkers: Aquaporin 4 (AQP4) specific to neuromyelitis optica spectrum disorders, myelin oligodendrocyte oligoprotein (MOG),⁷ or collapsin response mediator protein (CRMP5) antibody seropositive, or intrathecal CSF IgG (oligoclonal bands).

Other investigations depend on the clinical picture, and may include:

• Blood tests - for example, FBC, ESR, TFTs, autoantibodies and syphilis serology.

• Serological testing for neuromyelitis optica immunoglobulin G (NMO-IgG).

• CXR - for suspected sarcoidosis, tuberculosis or malignancy.

• Lumbar puncture - for suspected central nervous system infection or inflammatory ON (CSF is examined for immunoglobulins, oligoclonal bands and infection).

• Visual evoked potentials.

Assessment

• Full ophthalmological and neurological examination.

• The first step is to decide whether the diagnosis is definitely optic neuritis, or possibly (requiring further testing, or time).

• In practice, it is important to assess whether the clinical picture is of an autoimmune disorder that will require long-term immunomodulation or suppression, or that of an infectious or systemic cause (which may require different treatment). Whilst recognising there is overlap and exceptions, the suggested major difference between the two is that autoimmune diseases tends to be relapsing whilst other causes usually have a monophasic course.⁵

Application of the clinical and paraclinical criteria

A diagnosis of definite optic neuritis is made when:

(A) clinical criteria and one paraclinical test is positive.

(B) clinical criteria and two paraclinical tests of different modality are positive.

(C) clinical criteria and two different paraclinical tests (of which one is MRI) is positive.

A diagnosis of possible optic neuritis is made when:

(A), (B), or (C) are present (if seen acutely) but in absence of paraclinical tests, with fundus examination typical for optic neuritis and consistent with the natural history during follow-up.

Positive paraclinical test or tests, with a medical history suggestive of optic neuritis

Optic neuritis classification

The diagnosis of specific subtypes usually occurs in specialist centres and may facilitate access to specific treatments.

Autoimmune subtypes

These include aquaporin 4 optic neuritis (AQP4) neuromyelitis optica spectrum disorders, chronic relapsing isolated optic neuritis (CRION), collapsin response mediator protein 5 optic neuritis (CRMP5), myelin oligodendrocyte glycoprotein optic neuritis (MOG), multiple sclerosis, optic neuritis, relapsing isolated optic neuritis and single isolated optic neuritis.

Infectious subtypes

These include post vaccination and post-infectious subtypes. Causative infections include Bartonella, brucella, Chikungunya fever, cytomegalovirus, coronavirus, Coxiella burnetii, dengue, Epstein–Barr virus, echovirus, Henoch-Schönlein purpura, hepatitis B and C, herpes simplex, histoplasma, HIV, human herpesvirus 6, IgG subclass deficiency, leprosy, Lyme disease, measles, mumps, Mycoplasma pneumoniae, neurotoxocarosis, ocular cat-scratch disease, rubella, streptococcus, syphilis, tick-borne encephalitis, toxoplasmosis, tuberculosis, typhus, varicella zoster virus, West Nile virus, Whipple disease, and Zika virus.

Systemic disease subtypes

Those that may cause optic neuritis include allergic granulomatous angiitis, ANCA associated vasculitis, ankylosing spondylitis, Behçet’s disease, Churg–Strauss disease, Cogan syndrome, giant cell arteritis, granulomatosis with polyangiitis, IgG 4 disease, Kawasaki disease, microscopic polyangiitis, polyarteritis nodosa, primary antiphospholipid syndrome, rheumatic disease, sarcoidosis, Sjögren syndrome, systemic lupus erythematosus, systemic sclerosis, Takayasu arteritis, ulcerative colitis, and Wegener granulomatosis.

Differential diagnosis⁸

• Posterior scleritis.

• Acute idiopathic maculopathy.

• Acute macular neuroretinopathy.

• Acute retinal pigment epitheliitis.

• Retinopathy.

• Big blind spot syndrome.

• Multiple evanescent white dot syndrome.

Management

Acute management of optic neuritis

Refer to an ophthalmologist and/or neurologist. Usually, an ophthalmologist is involved in the initial assessment, diagnosis and treatment. Further management regarding the risk of MS (below) usually requires neurological expertise.

• Corticosteroids are generally used during the acute phase:

  • Treatment with methylprednisolone speeds up visual recovery in the acute phase, but has no effect on final visual acuity.^{6 9} Side-effects of corticosteroids can be serious. Therefore, they are usually reserved for patients who need to hasten visual recovery, such as those with poor vision in the fellow eye or bilateral visual loss, or for occupational reasons.

  • Dose recommendation is the bioequivalent of 1 g methylprednisolone intravenously or the bioequivalent of 1.25 g prednisone per day. The intravenous treatment dose varies from 0.5 to 1.0 g methylprednisolone. Recommended treatment duration is three- five days according to severity.⁵

  • Oral prednisolone is not recommended because of (uncertain) evidence that it may increase the recurrence rate.

• There is no treatment that can reverse poor visual outcome in the long term but many supportive aids are available.

• Information for patients is important.

• Consider referring to a neurologist for assessment of the patient's risk of developing MS, and the value of disease-modifying drugs in this context.

• For Pulfrich's phenomenon (disturbed perception of movement), symptoms may be helped by using spectacles with a tinted lens over the unaffected eye, to balance the delay in conduction from the other side.

• For Uhthoff's phenomenon symptoms (worsening vision with raised body temperature), avoid hot environments and take cool drinks; reassure patients that this symptom is reversible and does not damage vision.

• Plasma exchange can also be administered in severe refractory cases.¹⁰The presence of severe vision loss, older age, and longer delay to exchange predicted a worse outcome.

The further management of optic neuritis will depend on which subtype of optic neuritis is diagnosed. Those who have relapses after reduction of corticosteroids may need immunosuppression. There are several disease-modifying treatments approved for multiple sclerosis, and there are other immuno­suppressive strategies used to treat optic neuritis associated with antibodies to MOG or aquaporin 4 and chronic relapsing inflam­matory optic neuropathy; these include azathioprine, methotrexate, mycophenolate, rituximab and plasma exchange.

Prognosis of optic neuritis

Visual prognosis

• The prognosis for vision is generally good.¹¹

• The Optic Neuritis Treatment Trial (ONTT), was a large study with 15-year follow-up, and found that:

  • 93% of patients showed improvement within five weeks of onset; vision continued to improve for up to one year. One year after onset, 93% had visual acuity better than 6/12 in the affected eye. At 15-year follow-up, 92% had acuity better than 6/12 in the affected eye, and only 1% had vision worse than 6/60 in both eyes.

  • The severity of initial visual loss seems to be related to the final visual outcome; however, even with initial visual acuity of ≤6/60, 85% recover vision to 6/12 or better.¹²

  • More recent studies show most patients maintaining a visual acuity over 20/200 with a progressive visual loss over two weeks before stabilizing. Approximately 72% of patients are able to maintain visual acuity of 20/20 in both eyes at a 15-year follow-up.¹²

• Recovery in MOGAD has patients showing visual acuities with a median of 20/20 and a mean of 20/30 for visual recovery, although it was correlated to steroid treatment.¹²

• NMOSD displays the worst prognosis. NMOSD-related ON will lead to worsening results with each recurrent episode. The initial ON attack will leave 20%-30% of patients with 20/200 or worse visual acuity (functionally blind), and 70% of patients experiencing relapses will have a visual acuity of 20/200 or worse.¹²

Risk of recurrence

• ON can recur in either eye.

• The risk of recurrence was 35% over 10 years in the ONTT.

Risk of developing MS

• ON is associated with MS.

• In the ONTT, for adults with a single episode of unilateral ADON, the risk of MS was 38% at 10 years after onset, and 50% at 15 years.¹³

• MRI of the brain gives information about the risk of developing MS. The presence of white matter abnormalities increases the MS risk and their absence reduces it. In the ONTT, the risk of developing MS at 15-year follow-up was 25% for patients with no lesions on MRI, and 75% for those with white matter lesion(s).

• Prognostic models are better predictors compared with the standard practice relying on brain lesions on MRI. It can, therefore, help guide decision-making to initiate earlier disease-modifying therapy for patients with optic neuritis at risk of developing MS.¹⁴

Discussion with patients

• The association between ON and MS causes anxiety for patients and can impact on insurance policies.

• It is important to emphasise that many ON patients will not develop MS; even if they do, the prognosis regarding both vision and other disability can be good.

• Information about the prognosis can help patients to decide whether to undergo an MRI scan and whether to use beta interferon.

Dr Mary Lowth is an author or the original author of this leaflet.