Optic neuritis

General characteristics

Optic neuritis is one of the most common presenting features of multiple sclerosis. Clinical involvement of the optic nerve occurs in more than 50 per cent of patients at some time, and the visual pathway is invariably affected at autopsy. These statistics lead to a high level of anxiety in the informed patient that an episode of optic neuritis is likely to be the first manifestation of multiple sclerosis.

Clinical symptoms

Optic neuritis usually presents with pain on eye movement, followed or accompanied by blurred vision . Many patients first notice the visual loss on waking, or on accidentally closing one eye. Some report selective impairment of central vision with preservation of the peripheral field and awareness of movement. The symptoms usually evolve over hours or days, and the degree of visual loss that accompanies the clinical nadir varies from slight blurring to blindness. A number of other visual symptoms are described. Some patients notice selective loss of colour intensity or perception, usually in the red range. Others describe disturbances of visual perception with persistence of images on re-fixation or flashes of light (phosphenes) provoked by eye movement. The usual pattern is that the pain disappears after a few days. Vision improves, rapidly at first and then more slowly, full recovery often taking several months. About 90 per cent of patients consider themselves to have made a full visual recovery, but more formal assessments indicate that up to 50 per cent have persistent defects of vision, and colour perception frequently remains impaired.

The symptoms of bilateral simultaneous optic neuritis do not differ from unilateral disease, but there is usually a marked disparity in the extent to which each eye is affected and the implications for recurrence of the neurological symptoms are not the same. The rate of onset varies, and in some cases the loss of vision is progressive. Particular care needs to be taken in this situation so as to exclude compression of the anterior visual pathway, but it is also the case that structural lesions of the optic nerve can manifest as relapsing visual failure, closely mimicking optic neuritis.

Differential diagnosis

The diagnosis is one of exclusion, and ischaemic optic neuropathy needs to be considered in older patients. Relapsing visual loss may be due to optic nerve sarcoidosis or Eales' disease, in young women and men, respectively. A careful family history should be taken, since the onset of visual failure in Leber's hereditary optic neuropathy (Section 8.5.2) can be confused with bilateral sequential optic neuritis in men. Mistakes may also occur in the context of toxic amblyopia. Recently, the syndrome of a multiple sclerosis-like illness associated with mutations of mitochondrial DNA and manifesting as central nervous system demyelination with disproportionate involvement of the optic nerves has been recognized (Harding et al. 1992; Riordan-Eva et al. 1995: this is now designated as Harding's disease). The variable density of the bony orbital walls means that sinus infection may spread to affect the optic nerve directly or as a consequence of local tissue oedema. The lesion responsible for optic neuritis can be imaged, the nerve appearing swollen and showing a focal increase in magnetic resonance signal. Inflammation within the intracanalicular portion of the nerve and long lesions are associated with delayed or incomplete recovery of vision (Miller et al. 1988).

The main factor determining the reported frequency of multiple sclerosis after optic neuritis is the duration of follow-up. The risk is highest in the first 5 years, but the proportion of cases with widespread demyelination increases steadily with time. Several retrospective and prospective series have been treated to life-table analysis in an attempt to compensate for the varying length of follow-up. This approach gives estimates of 38–78 per cent conversion, depending on the location and actuarial time point. Age at presentation influences the risk of multiple sclerosis developing after an attack of optic neuritis. In children, the disorder is commonly bilateral and further symptoms of demyelination affecting the visual pathways or other parts of the nervous system rarely occur. Bilateral simultaneous optic neuritis in adults, although much less common than in children, also carries a low risk of multiple sclerosis, and in both situations the likely explanation is that these are anatomically restricted forms of acute disseminated encephalomyelitis.

Optic neuritis recurred in 28 per cent of patients recruited for a recent treatment trial (Optic Neuritis Study Group 1997b). Recurrence carried an increased risk for multiple sclerosis and was also more common in those who did not convert if treated at presentation with oral prednisolone. However, most clinicians would not assign the same diagnostic significance to a second attack of optic neuritis as an episode of demyelination affecting another part of the central nervous system. Other factors reported at one time or another to increase the risk of progression include young age of onset, female sex, and recurrence of optic neuritis.

Parkin et al. (1984) reviewed a series of cases with bilateral optic neuritis 25 years after presentation. Of the six adults with acute simultaneous optic neuritis, one had died with Devic's disease and another was thought to have had early probable multiple sclerosis but died from other causes at the age of 76 years. No other patient developed multiple sclerosis. Conversely, 20 patients had bilateral sequential optic neuritis within 3 months and, of these, seven were known to have developed multiple sclerosis. A recent follow-up of 23 cases with acute or subacute simultaneous bilateral optic neuropathy revealed that, after a mean of 71 months, four were shown by genetic analysis to have a mutation in mitochondrial DNA typical of Leber's disease, and another five had developed multiple sclerosis; the rest remained undiagnosed (Morrissey et al. 1995). There is a confused literature on whether the treatment of acute optic neuritis, either with intravenous methylprednisolone or oral prednisolone, influences the risk of conversion to multiple sclerosis. In the most up-to-date analysis, 30 per cent of the 308 patients enrolled between 1988 and 1991 converted to clinically definite multiple sclerosis, but there was no difference in rate between the groups depending on treatment. Lesions on magnetic resonance imaging at presentation were a poor risk factor; all 185 patients with no prior symptoms of imaging abnormalities, lack of pain, relative preservation of acuity, and a swollen disc carried a relatively good prognosis for conversion to multiple sclerosis (Optic Neuritis Study Group 1997b).

Given these uncertainties, attempts have been made to determine whether laboratory indices which are characteristic of multiple sclerosis serve to identify patients with optic neuritis who are destined to develop widespread demyelination; the usefulness of each factor depends on the specificity and sensitivity of that marker for the diagnosis of multiple sclerosis (Soderstrom et al. 1998). The visual evoked response characteristically shows delay with preserved amplitude once the phase of inflammation has settled, and this feature has the same implications for conversion to multiple sclerosis as a second episode of optic neuritis when it is detected in a clinically unaffected eye. Retinal vascular sheathing, or the presence of inflammatory cells in the ocular vitreous, occur in 30 per cent of patients with optic neuritis and are associated with a slightly increased risk of multiple sclerosis at follow-up (Lightman et al. 1987).

Periventricular white matter abnormalities demonstrated by magnetic resonance imaging are found in 61 per cent of patients with optic neuritis, more of whom develop multiple sclerosis than those with normal brain scans (O'Riordan et al. 1998). HLA DR2 is present in a higher proportion of patients with optic neuritis who subsequently develop multiple sclerosis than isolated cases, but the relative risk is low and HLA typing is not a useful prognostic marker. A higher proportion of patients with optic neuritis shown to have oligoclonal bands on cerebrospinal fluid electrophoresis at presentation subsequently develop multiple sclerosis than those with normal spinal fluid. Fifty-two per cent of patients with oligoclonal bands had developed multiple sclerosis at early follow-up, compared with 24 per cent having normal spinal fluid; however, almost half the patients with abnormal magnetic resonance scans, most of whom had oligoclonal bands from presentation and were HLA DR2 positive, had not developed clinical evidence for widespread demyelination many years after the initial episode of optic neuritis (Sandberg-Wollheim et al. 1990). In patients who underwent spinal fluid analysis at presentation as part of the Optic Neuritis Treatment Trial (Optic Neuritis Study Group 1997b), the presence of oligoclonal bands slightly increased the relative risk for developing multiple sclerosis within 2 years, but imaging abnormalities were more discriminating predictors of widespread demyelination in this group.

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