Optic neuritis and risk of MS: Differential diagnosis and management

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ABSTRACTOptic neuritis, a cause of sudden vision loss, often heralds the onset of multiple sclerosis (MS) within the next few years. It is important to distinguish optic neuritis from other types of optic neuropathy so that treatment can be started promptly, possibly delaying the onset of MS.


  • Optic neuritis is most common in women in their 20s and 30s, whereas ischemic optic neuropathy, which is more common, primarily affects older people.
  • The diagnosis of optic neuritis is primarily clinical, but magnetic resonance imaging confirms the diagnosis and, more importantly, assesses the risk of MS.
  • Intravenous methylprednisolone (Solu-Medrol) does not affect the long-term visual outcome, but it speeds visual recovery and reduces the risk of MS. Surprisingly, oral prednisone seems to increase the risk of recurrent optic neuritis and is therefore contraindicated.
  • Early treatment with interferon beta reduces the risk of MS and should be considered in patients at high risk.



Two days ago, a 27-year-old woman noticed that her vision was blurry in her right eye. She has come to see her primary care physician for advice. This is the first time this has happened to her. She describes seeing a grayish blur over the center of her vision, but she has not noted any other symptoms except for some soreness around the right eye, which is worse with eye movements.

How should she be assessed and treated?


Sudden vision loss is one of the more common problems encountered in ophthalmology and neurology.

Optic neuritis, a demyelinating inflammatory condition that causes acute vision loss, is associated with multiple sclerosis (MS), and recognizing its classic clinical manifestations early is important so that appropriate diagnostic testing (magnetic resonance imaging [MRI]) and treatment (corticosteroids and immunomodulators) can be started.

Although a comprehensive review of all the optic neuropathies is beyond the scope of this paper, in the pages that follow we review some of the most common causes, which may be first seen by the general internist.


There are four subtypes of optic neuritis:

  • Figure 1. In retrobulbar optic neuritis, the inflammation and demyelination occur behind the globe of the eye. The optic disc appears normal with no signs of swelling or pallor.

    Retrobulbar neuritis (Figure 1), or inflammation of the optic nerve behind the eye, is the form most commonly associated with MS.
  • Papillitis (Figure 2), or inflammation of the optic disc, can also be associated with MS.
  • Perineuritis is inflammation of the optic nerve sheath, sparing the optic nerve itself. Usually, patients are older, and vision loss is mild to moderate. Perineuritis is commonly due to infectious or inflammatory conditions, eg, syphilis or sarcoidosis.
  • Figure 2. In papillitis, mild swelling and elevation of the optic disc can be seen. The small splinter hemorrhage seen at 10 o’clock is not typical of optic neuritis associated with multiple sclerosis.

    Neuroretinitis may occur at any age. There is concomitant swelling of the optic nerve and macula. Exudates that form around the macula give the appearance of a star.

Perineuritis and neuroretinitis are not associated with MS, and if they are found they suggest another etiology. In the rest of this review, “optic neuritis” means retrobulbar optic neuritis, the form most commonly seen in clinical practice.


Acute demyelinating optic neuritis most often affects women in their 20s and 30s.1–3 Studies in the United States have estimated its annual incidence to be 5.1 to 6.4 per 100,000.4,5 The incidence is higher in populations at higher latitudes and lower near the equator. It is less common in blacks than in whites.6

In children, optic neuritis is not as strongly associated with MS, especially when there is optic disc swelling or bilateral involvement. Most children have a good visual outcome, although approximately 20% may be visually disabled.7–9


Most of our current knowledge of the clinical features of optic neuritis comes from the Optic Neuritis Treatment Trial (ONTT),10 conducted in the 1990s. This trial enrolled 457 patients 18 to 46 years old who had acute unilateral optic neuritis. The patients had to have symptoms consistent with acute unilateral optic neuritis for 8 days or less. They could not have evidence of any systemic disease (except for MS) or have received prior treatment for MS. Therefore, this study was quite representative of the patients with optic neuritis that one might encounter in the clinic and is highly important in both characterizing optic neuritis and defining its treatment.

The study found that the two most common symptoms are vision loss and eye pain.

Vision loss in optic neuritis typically occurs over several hours to days, and vision reaches a nadir within 1 to 2 weeks. Typically, patients begin to recover 2 to 4 weeks after the onset of the vision loss. The optic nerve may take up to 6 to 12 months to heal completely, but most patients recover as much vision as they are going to within the first few months.11 More than two-thirds of patients have at least 20/20 vision once they have fully recovered from the optic neuritis. Only 3% of patients become completely blind.

Eye pain is very common in optic neuritis (it affected 87% of patients in the ONTT) and typically worsens with eye movement. The eye is also sore to touch. The pain generally begins at the same time as the visual loss and improves along with it. Eye movements also may bring about photopsia (flickering or flashes of light), a symptom reported by 30% of the ONTT participants.

Loss of color vision out of proportion to the loss of visual acuity is characteristic of optic neuropathies. In the ONTT, 88% of the involved eyes had abnormal color vision as assessed by the Ishihara test (using pseudoisochromatic plates), and 94% as assessed by the Farnsworth-Munsell 100 hue test, which is more sensitive but cumbersome. The most common patterns of color vision loss in optic nerve disease are loss of red (protanopia) and green (deutranopia).

A good way to screen for loss of color vision is to test for color desaturation. First, ask the patient to fixate with the normal eye on a bright red object (for example, the cap from a bottle of ophthalmic mydriatic drops or a pen cap). Then ask the patient to compare the intensity of the redness between the good eye and the affected eye. The patient can quantify the color desaturation by rating what percentage of red is lost in the affected eye compared with the normal eye.

Temporary exacerbations of visual problems during fever (the Uhthoff phenomenon) can occur in patients who have had optic neuritis. These transient pseudoexacerbations are not new episodes of optic neuritis and should resolve after the body temperature returns to normal.

A relative afferent pupillary defect should be seen in the involved eye in all patients with optic neuritis if the other eye is uninvolved and healthy.12 The best way to elicit this sign is to perform the swinging light test in a dark room with the patient fixating at a distant target, which prevents miosis due to accommodation. When the light is swung to the involved eye, the pupil dilates because less light stimulus reaches the midbrain through the affected optic nerve. As the optic nerve heals and recovers, this sign may become subtle, but it persists in more than 90% of cases.12

Findings on funduscopy

Examination of the fundus is helpful in the clinical diagnosis of optic neuritis.

Two-thirds of the ONTT patients had retrobulbar neuritis, and one-third had papillitis. If optic nerve swelling is present, it is typically mild.

Peripapillary hemorrhages were exceedingly rare in the cases of papillitis (only 6%) and were associated with a very low to zero risk of developing MS. If peripapillary hemorrhages are found on examination, one should consider another diagnosis, such as anterior ischemic optic neuropathy.11


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