One of the first symptoms of multiple sclerosis may be a problem with vision, and associated symptoms can range from diplopia, nystagmus, and retrobulbar eye pain to blurred vision. The symptoms result from damage due to inflammation of the optic nerve, known as optic neuritis, or as the result of a demyelinating lesion along one of the neural pathways that control ocular movement and visual coordination.
Treatment of Visual Symptoms of Multiple Sclerosis
The primary modality of treatment of visual symptoms of multiple sclerosis is treatment of the disease process itself, with a glucocorticoid agent or ACTH, or with a disease-modifying agent, which may include beta interferon, glatiramer acetate, dimethyl fumarate, or fingolimod. Other medications used in the treatment of MS include teriflunomide, mitoxantrone, and alemtuzumab. However, a number of comorbid symptoms mark the course of the disease, and symptomatic treatment and an acute course of symptomatic therapy may be necessary at those times.
A mainstay of treatment in exacerbations of multiple sclerosis are glucocorticoids, most commonly intravenous methylprednisolone, 500 to 1,000 mg per day, followed by an optional prednisone taper.1 Those patients with acute severe neurological deficits unresponsive to high doses of glucocorticoids as a result of an exacerbation of multiple sclerosis should be treated with plasma exchange.2
The Association of Optic Neuritis and Multiple Sclerosis
Optic neuritis is very highly associated with multiple sclerosis, and is sometimes the initial sign. As a clinically isolated syndrome, it has a high likelihood of progression to MS. Occurring in 50 percent of patients with multiple sclerosis at some point during the course of their disease, optic neuritis is typically monocular, although symptoms occur in approximately 10 percent of cases bilaterally or in quick succession. If bilateral optic neuritis does occur, other causes should be considered.3
Although the demyelination in optic neuritis is believed to be immune-mediated, the specific mechanism and target antigen are not well defined. The pathology of the inflammatory demyelination of the optic nerve sheath results in perivascular cuffing, edema in demyelinated nerve sheaths, and breakdown of myelin. Retinal vein sheathing may be visible before demyelination, as a result of inflammation of the retinal vascular endothelium.
Clinical Features of Optic Neuritis
The most common clinical features of optic neuritis are loss of vision and eye pain. The clinical features of optic neuritis characterized in the Optic Neuritis Treatment Trial included loss of vision over a period of hours to days, with symptoms peaking before self-resolution within one to two weeks.4 Significant loss of central visual acuity was present in more than 90 percent of patients in that study, with a median visual acuity of 20/60, although some patients retained 20/20 vision and others had no light perception.
Eye pain occurred in 92 percent of patients in the trial, and was often associated with ocular movement.5 Eye pain and visual loss often coincide in their onset and resolution.
Other visual signs and symptoms of optic neuritis include an afferent pupillary defect if one eye remains healthy, and a visual field defect known as a central scotoma is most commonly seen. However, in the Optic Neuritis Treatment Trial (ONTT), all types of visual field defects were seen. These defects normally resolve, and in the ONTT, 56 had resolved at one year, with 73 percent resolved at 10 years.6 Slit lamp or funduscopic examination may reveal perivenous sheathing or periphlebitis retinae.
A third of patients develop papillitis, characterized by hyperemia and swelling of the disk, with blurred disk margins and distended veins. Of those patients, two-thirds had retrobulbar neuritis, with normal funduscopic examination. Although not usually a feature of optic neuritis, peripapillary hemorrhages often accompany papillitis as a result of anterior ischemic optic neuropathy.
Other clinical features reported in optic neuritis include photopsias, or flashes of light that are precipitated by eye movement, and loss of color vision out of proportion to the loss of visual acuity. Chronic features that persist after clinical recovery may include persistent visual loss, color desaturation, relative afferent pupillary defects, optic atrophy, and pattern-shift visual evoked response.
The prognosis for patients with optic neuritis is good, with resolution without treatment within a few weeks and continued improvement over subsequent months.7 Recovery is measured by visual acuity in most cases.
Treatment of Optic Neuritis in MS
Treatment of optic neuritis is targeted at improving vision and preventing or slowing the development and progression of multiple sclerosis. There is evidence that intravenous corticosteroids delay onset of multiple sclerosis and improve the rate of visual recovery. It is typically given in 250 mg doses four times a day for three days followed by oral prednisone taper.8 Oral prednisone has been found to result in a higher two-year risk of recurrent optic neuritis in both eyes, compared with intravenous steroid therapy or placebo.9
Other therapeutic interventions for acute optic neuritis due to multiple sclerosis include intravenous immunoglobulin (IVIG) and plasma exchange. Two randomized trials studied the potential benefit of IVIG in patients with optic neuritis, and there was no apparent benefit in visual outcome at six months.10,11 A small study of IVIG therapy in patients refractory to treatment with corticosteroid therapy found significant improvement in visual acuity that was sustained at one year.12 A study of plasma exchange in 10 patients who were unresponsive to IV corticosteroid therapy resulted in visual improvements in seven of the 10 patients, but the benefit was not sustained in two patients.13
In patients with optic neuritis, the results of three randomized studies support the use of treatment with beta interferon or glatiramer acetate to prevent, delay, or ameliorate subsequent multiple sclerosis.13, 14 Chronic immunomodulatory therapy is a mainstay of treatment in patients with multiple sclerosis. Side effects of beta interferon treatment may include depression, reactions at the injection site, and flu-like symptoms. However, benefits of treatment include longer intervals of remission, reduction in demyelinating attacks, and delay of disability associated with MS.
Treatment of Children with Optic Neuritis
Finally, with respect to the treatment of children with optic neuritis, there are no clinical data available to guide therapy. Because children are at lower risk of development of multiple sclerosis, current recommendations include modification in treatment, withholding immunomodulatory agents in young children (younger than age 15) and giving consideration to the use of intravenous methylprednisolone for severe debilitating bilateral vision loss.15