Owing to the disseminated nature of the disease process in MS, there are several distinct neuro-ophthalmological syndromes that span both the visual sensory and the ocular motor systems. The principal objective of this review is to provide a framework for understanding the neuro-ophthalmic signs and symptoms that occur in patients with multiple sclerosis (MS). Particular emphasis is placed on understanding currently proposed mechanisms that give rise to disorders of visual processing and ocular motility.
Part I: the afferent visual system in MS
Optic neuritis
Acute idiopathic demyelinating optic neuritis is frequently the initial clinical manifestation of multiple sclerosis. Although there is a broad age range for onset, most patients with acute demyelinating optic neuritis are young, age 20-50 years. There is a gender difference: women are three times as likely as men to develop optic neuritis. The incidence of acute demyelinating optic neuritis is about three per 100 000 people in the USA; in low-risk regions such as Japan, the incidence approaches one per 100 000 population per year. 1,2
Clinical characteristics
The patient with typical demyelinating optic neuritis usually experiences a decline in vision over a 7-10-day period. The progression of visual loss beyond 2 weeks is distinctly unusual. 3 In the Optic Neuritis Treatment Trial, 4 92% of patients had pain, particularly with eye movements. In the patient with typical optic neuritis, some recovery of vision should occur within 30 days of onset. Clinical features that suggest non-typical optic neuritis include the presence of retinal haemorrhages, a markedly swollen nerve, retinal exudates, the absence of pain, and the presence of no light perception vision at onset. 5 These patients have a lower risk of developing MS, particularly when a baseline MRI scan is normal. 5,6
Diagnostic assessment
Patients with demyelinating optic neuritis should undergo a brain MRI scan to establish their risk of MS. According to the 10 year longitudinal optic neuritis study, even one white-matter lesion increases the risk of MS from 22% to 56%, which may have implications for therapy (see below). When the clinical course is typical, other diagnostic studies such as fluorescence treponemal antigen antibodies, anti-nuclear antibodies, angiotensin converting enzyme, Lyme titre, chest radiograph, and lumbar puncture are of limited use in eliminating other causes of optic neuropathy. 4 A more aggressive assessment should be considered when nontypical features of optic neuritis are present, including a very swollen optic nerve, retinal exudates, absence of visual recovery within 30 days, and absence of pain. Tests for Lupus, Lyme disease, sarcoid, syphilis, West Nile virus, 7 ehrlichiosis, 8 and Leber's optic neuropathy should be considered in the appropriate clinical setting.
Demyelinating optic neuritis can be occasionally difficult to distinguish from anterior ischaemic optic neuropathy (table 1). The two entities may have overlapping clinical features, including the rate and range of visual deterioration. [9][10][11] An altitudinal defect (visual field suppression either above or below the horizontal) alone may not be reliable in distinguishing optic neuritis from ischaemic optic neuropathy, since up to 10-15% of patients with optic neuritis may present with an altitudinal defect. [9][10][11] Although imaging is rarely necessary to distinguish these two entities, orbital MRI will show optic nerve enhancement in most patients with optic neuritis. 12 Subclinical or chronic forms of demyelinating optic neuritis-in which the patient notices a gradual decline in vision instead of acute vision loss followed by improvement-may also develop. These patients may show abnormalities on neuro-ophthalmological examination, including field loss, pupillary abnormalities, and disc pallor. 13 Diagnosis of chronic optic neuritis is based on exclusion and considerations could include superimposed glaucoma (either chronic or acute), an underlying mass lesion, or an infiltrative process.