By: Edward J. Atkins, M.D.
At disease onset, individuals with MS might experience a variety of symptoms including numbness, tingling, pain, weakness, and balance problems, but visual symptoms are the presenting symptom up to 50% of the time. Over the course of the disease, virtually 100% of those with MS will have some visual problem, including visual loss and/or various distortions of vision. As with other neurological symptoms in MS, these visual problems can come and go, fluctuate in severity, or be permanent.
A helpful concept in understanding why MS causes visual problems is that we don’t actually see with our eyes. We see with our brains. In fact, two-thirds of our brain is involved in processing visual sensory input received through the eyes. The optic nerve is the cable that connects the eye to the brain, and it is this connecting structure that is often damaged in MS, giving rise to the well-recognized syndrome optic neuritis. In addition, there are several other pathways in the brain that send signals from the brainstem to the muscles of both eyes, allowing us to move our eyes in unison. These motor output pathways are also often affected in MS. If these pathways are damaged, then the eye muscles will not be able to move in a coordinated fashion, resulting in double vision, or involuntary movements of one or both eyeballs, giving rise to another well recognized visual syndrome seen in MS called internuclear ophthalmoplegia. Both visual sensory (input) and eye movement (output) abnormalities are common in MS.*
MS is a disease that causes brain tissue injury through multiple inflammatory demyelinating lesions. Most of these MS lesions involve areas of the brain that do not give rise to visual symptoms, unless they directly affect visual sensory input (optic nerve) or ocular motor output (brainstem). There are, however, several visual problems in MS that arise from multiple lesions that involve both the input and output systems, resulting in disorders of both visual processing and eye movements.
The word neuritis means inflammation of a nerve. In an attack of optic neuritis, the optic nerve is affected. Isolated acute optic neuritis is often the first sign of MS, and many individuals with MS develop optic neuritis during the course of their disease. This is the presenting syndrome in 20% of MS patients. Women are three times as likely as men to develop optic neuritis. Overall in North America, the incidence of optic neuritis is about 3 per 100,000 people per year. It is the most common cause of optic nerve disease in the young.
For many people, a diagnosis of optic neuritis is equivalent to having a high risk of MS. Large studies published within the past decade have clarified our understanding of the characteristics and outcome of optic neuritis, as well as its relationship to MS. We are now able to predict the risk of subsequent MS in selected individuals who present initially with optic neuritis; this allows us to discuss the use of disease-modifying drugs for the potential reduction of risk and severity of clinically definite MS in those people. Less than 20 years ago, neurologists had to decide whether or not they should reveal their suspicion of possible MS to optic neuritis patients. Today, the question of “to tell or not to tell?” has been replaced by “to treat or not to treat?”
We have a better understanding of the characteristics of optic neuritis from a major study called the Optic Neuritis Treatment Trial (ONTT), conducted by the Optic Neuritis Study Group. Optic neuritis presents with mild to severe visual loss associated with painful eye movements (92%) and impaired color vision. It most often affects only one eye. Typically, vision declines over a week to 10 days, then the amount of visual loss stabilizes, with some recovery of vision occurring within 30 days of onset. About 30% of those recovering from optic neuritis will experience positive visual phenomena such as seeing colors or flashing lights. These are more common with eye movements, exposure to loud noises, or when going from a well lit to a dark room. Disturbed perception of objects moving in space can also occur; this is known as the Pulfrich phenomenon.
Spontaneous visual recovery is a nearly universal feature of acute demyelinating optic neuritis, and the visual prognosis for patients is usually excellent, regardless of treatment. However, the risk of subsequent development of MS after an isolated attack of optic neuritis has been estimated as high as 75% at 15 years.
The natural history of optic neuritis has been clarified by a number of recent studies, of which the ONTT is the largest. The ONTT confirmed that spontaneous visual recovery begins rapidly (within 3 weeks) in about 80% of patients with demyelinating optic neuritis, and continues to improve for up to one year. The ONTT also emphasized that if at least some improvement does not occur within five weeks, the diagnosis of optic neuritis should be reconsidered. At one-year follow-up, at least 95% of patients had visual acuity better than 20/40 in the affected eye. Half the patients had visual acuity of at least 20/20 (normal) in the affected eye, although a majority still complained of permanent visual dysfunction such as impaired contrast sensitivity, decreased color vision, difficulty with motion perception, and diminished intensity of light. Following optic neuritis, individuals often also experience Uhthoff’s phenomenon, a transient visual decline following exposure to heat or exercise.
Outcome of Optic Neuritis
These recent studies have provided important information regarding 1) the visual outcome of patients with acute optic neuritis, 2) the risk of recurrence of optic neuritis, and 3) the risk of clinically definite MS in patients with a first episode of acute demyelinating optic neuritis. There has been renewed interest based on these trials in establishing the diagnosis of MS as early as possible. Starting therapy early has been shown to slow the time until the next relapse or MRI lesion. A recently published trial showed that early therapy with interferon beta 1b decreased the likelihood of disability three years after the first relapse.
All patients with demyelinating optic neuritis should have a brain MRI scan, since those with a normal MRI, showing no evidence of other MS lesions at the time of an attack of optic neuritis, have a lower chance of going on to develop MS. Around 50-70% of patients with optic neuritis will have other MS lesions on an initial MRI. Even one MS lesion in a part of the brain other than the optic nerve increases the risk of MS from 22% to 56%. MRI is therefore the most important test to guide treatment and to assess the risk of MS. Other diagnostic tests include visual fields, visual acuity, color vision, and examination with an ophthalmoscope and slit lamp. A test called visual evoked responses may also be arranged to demonstrate optic nerve dysfunction. (See photos below).
Treatment Options for Optic Neuritis
The ONTT concluded that the best acute treatment option for demyelinating optic neuritis was a 3-day course of high-dose (1 gram/day) intravenous steroid treatment (methylprednisolone) followed by a tapering dose of oral prednisone. This treatment hastens visual recovery, but has no effect on the final visual outcome. Intravenous methylprednisolone is generally well tolerated, but mild steroid-related side effects are common, including insomnia, weight gain, stomach upset, and mood alteration. The decision to use intravenous methylprednisolone should be a personal one. Discuss the risks and benefits of this therapy with your doctor and also consider other factors, such as visual function, MRI results and potential side effects.
The ONTT showed that oral prednisone in conventional lower doses of 1 mg/kg per day should not be used in the treatment of optic neuritis, as this led to a higher recurrence rate. Some MS specialists now use high dose oral prednisone, rather than high dose intravenous methylprednisolone, and a small trial investigating this alternative treatment approach did not demonstrate an increased rate of recurrent optic neuritis. Even without treatment, visual recovery occurs in almost all cases. Steroids are only given to shorten the duration of visual symptoms.
Recent studies have suggested that damage to nerve cells occurs early during the course of MS. It has been emphasized that once damage to the axon occurs, permanent neurological deficits may result. The issue of axonal damage is at the center of the ongoing debate over whether or not to treat patients with isolated optic neuritis (especially those predicted at high risk for the subsequent development of MS) with early intervention with disease-modifying drugs. Results of recent interferon trials suggest that patients with optic neuritis and an abnormal MRI should be considered for interferon therapy. The decision to treat optic neuritis patients with disease-modifying agents should be individualized. Some recommend immediate treatment to avoid further injury, while others suggest delaying long-term treatment, and repeating the MRI to prove definite MS prior to starting such serious and expensive treatment. This topic remains debated and recommendations vary among countries.
Choosing the Right Specialist
Choosing the right specialist for visual problems in MS can be confusing for both patients and family physicians. Patients may be referred to neuro-ophthal-mologists, neurologists, ophthalmologists, optometrists, and even neurosurgeons. For the visual sensory system, neurologists generally manage optic neuritis. Since visual loss is the primary symptom, these patients are more likely to initially present to ophthalmologists or optometrists. Management of optic neuritis has become complicated and remains controversial. It requires specialized knowledge of MS diagnosis and treatment. The decision-making process now involves spending more time with the patient and often results in lengthy discussions. Therefore, ophthalmologists may refer patients to neurologists or neuro-ophthalmologists without initiating treatment. For problems of the eye movement system (e.g., double vision), patients may also require input from a neurologist (MS specialist). However, ophthalmologists or optometrists may also become involved in providing prisms for the correction of double vision, or prescribing lenses that will optimize visual acuity. Neurologists who are MS specialists, or neurologists and ophthalmologists who have had additional training in neuro-ophthalmology, are the ideal choice for MS patients with visual problems. Neuro-ophthalmologists will be familiar with all aspects of both optic nerve and eye movement disorders, and will be able to provide up-to-date recommendations on complex treatment issues and follow-up.
Dr. Edward J. Atkins received his medical degree from McMaster University in Hamilton, Ontario, Canada, in 2003. He will begin a fellowship in Neuro-ophthalmology in 2008 with Dr. Nancy J. Newman and Dr. Valerie Biousse at the Emory University School of Medicine in Atlanta, GA.
(Last reviewed 7/2009)