Ocular Myasthenia Gravis

Robert H. Spector, M.D.

Myasthenia Gravis
And Health Resources

Select: Myasthenia Gravis Foundation of America (MGFA)

Permission was granted for Reprint of this Article

Ocular Myasthenia Gravis

Robert H Spector, MD.

Introduction

Much has been written about myasthenia gravis (MG) in recent years, because there now seems to be
a plausible, scientific explanation for the cause of this disease. The word "gravis" seems no longer
appropriate, as current forms of treatment virtually have allowed patients to live fully functional
and independent lives. This review will summarize the therapeutic advances that have been made in the
ocular form of MG, stressing the most effective and practical ways to manage double vision (diplopia)
and droopiness of one or both lids (ptosis).

MG is the paradigm of an autoimmune disorder, i.e., it is caused by an antibody which attacks
and diminishes the integrity of one of the body's own components. Making antibodies is a normal daily
process from the moment we're born and exposed to such foreign proteins as viruses and bacteria, or
even snake venom. When a patient makes an antibody against themselves, as in MG in which there is an
anomalous antibody produced against the receptor end plate of voluntary muscles, it is referred to as
autoimmune. This autoimmune attack on the muscles end plate accounts for the symptoms and signs of
ocular and generalized MG.

All the muscles in our body are activated by nerve impulses which travel along nerve trunks emanating
from the brain and spinal cord. When these nerve impulses reach the neuromuscular junction, the point
at which a nerve fiber synapses with or terminates on a muscle fiber, a chemical is released called
acetylcholine (AcH), which attaches to a receptor on the muscle membrane, resulting in a muscular
contraction.

Patients with MG enigmatically produce a blocking antibody which deposits on the receptor muscle
membrane and prevents the entry of AcH molecules. The resulting attenuation of neuromuscular
transmission leads to muscular fatigue and sometimes frank paralysis. Characteristic of MG is the
randomness of neuromuscular blockade. It may be confined only to a small muscle which moves one eye
upward, outward, downward or laterally; or to one of the larger muscles which moves the face, arm or
leg or breathing muscles. Regardless of the muscles involved, the goal of effective treatment is to either
reduce the concentration of the blocking antibody or to increase the concentration of AcH at the
neuromuscular junction.

Ocular MG is characterized by the abrupt or insidious onset of weakness and fatigability of one or both
lids or the eye muscles. If the lid is involved it droops otherwise known as ptosis; with extraocular muscle
involvement the patient sees double looking in the direction of the weak muscle. For instance, they may
see well in all directions except upward, which tells the examiner that one of the elevator muscles is weak.
To compensate for the weakness, the patient can tilt their head or turn their face to allow the relatively
stronger eye muscles to work. In the above example, the patient would tilt their head back, thus throwing
their eyes relatively downward out of the field of action of the relatively weak elevator muscle.

Because of the frequency with which eye muscles are involved in MG, droopiness of one or both upper eyelids
(ptosis) and double vision (diplopia) are common impediments. Diplopia or ptosis eventually occur in 90% of
patients with MG and account for the initial complaint in 75%. About 80% of patients with ocular onset MG will
progress to involvement of other muscle groups within the first two years; thus only 20% of patients have pure
ocular MG. Patients in whom the disease has been confined to the ocular muscles for three or more years seem
unlikely to progress to generalized disease.

Eye muscle strength in MG, similar to swallowing, speech, and leg strength may be normal or mildly affected in
well rested patients, but weakness can usually be elicited with exercise. For instance, if a patient is asked to
look upward for 60 seconds, thereby testing the endurance of the vertical eye muscles and the upper lid which
concomitantly rises, the patient may evolve from a normal state to extreme weakness with flagrant diplopia or
ptosis.

Although upward eye movements are said to be involved earliest, extraocular muscle involvement does not follow
any set pattern. In my experience, weakness of medial eye movement along the horizontal plane is equally as
common. Essentially any pattern of dysfunctional ocular movement may develop so that isolated muscle palsies
or total immobility of the eyes will accrue, sometimes mimicking other medical conditions such as strokes, tumors,
thyroid eye disease, infections and multiple sclerosis

The natural history of ocular myasthenia has been well studied. Of 168 patients with generalized MG, in whom the
average follow-up was twelve years, and the last examination was compared with the initial examination, 68% were
unchanged, 14% improved, 14% in complete remission and 5% were worse. Most of the worsening seemed to
occur during the first 3-5 years of illness during which time the incidence of a severe exacerbation is highest. More
specifically, of those patients who present with ocular manifestations alone, i.e., pure ocular MG, 58% will show
symptoms of generalized muscular weakness during the first seven months of their illness, another 29% between
7 months and 13 months, 7% during the 2 and 3 years and only 6% after the third year. Therefore, if a patient with
ocular MG continues to have only ocular symptoms after three years, there is a 94% chance that his symptoms
will not increase.

The salient symptoms of ocular MG, double vision and droopiness of one or both lids, are frequently influenced by
environmental, emotional and physical factors. Bright sunlight, emotional stress, viral illness, surgery, menstruation,
pregnancy, immunizations and other physical factors all may precipitate a change in the expression of ocular MG,
although not in a predictable direction.

Spontaneous remissions can occur in any patient and sometimes persist for years. Most patients with MG show a
fluctuating course, often with a particular muscle group (e.g., ocular, speech, swallowing, arm or leg strength) being
maximally involved. Fortunately MG only rarely follows an acutely or chronically progressive course. Age, sex and
pattern of onset are not used to predict the eventual course of the disease.

It used to be felt that MG has no racial or geographic predilection. However in 1981 a number of interesting
observations were made regarding difference in ocular and generalized MG. In ocular MG, equal numbers of
males and females are affected, the Chinese race has an unusually high incidence, and patients with ocular MG
often have abnormal levels of autoantibodies against the thyroid gland and show concomitant disorders of thyroid
function. Victims of generalized MG, in contrast, are more commonly female, ethnically more likely to be Italian
and show much fewer abnormalities of thyroid function.

The diagnosis of ocular MG depends heavily on the patient's history, physical findings and their response to
intravenously administered edrophonium chloride (Tensilon). Falsely negative or equivocal tensilon tests are
annoyingly common and represent a distinct problem in the diagnosis and subsequent management of MG.

When weakness of lid elevation or eye movement is moderate or marked, evaluation of tensilon responsiveness
is usually a simple response can be difficult to evaluate. The patient's history is often the critical determinant of
accurate diagnosis. Alternating ptosis, i.e., unilateral ptosis that remits and is followed a variable interval by
ptosis of the other eye, is highly suggestive, as is diurnal fatigue of an extraocular muscle causing diplopia to
develop and worsen as the day progresses. Unfortunately, in the mild or incipient cases, the patient may give
a strongly suggestive history, but have no physical findings on examination to confirm the diagnosis. In such
cases the most practical approach is to invite the patient back for follow-up later in the day or after exposure
to bright sunlight to provoke their symptoms.

With the development of an assay for measuring the amount of blocking antibody, the diagnosis cam sometimes
be confirmed by blood work. However, there are both false positive and false negative blood test results. Active
antibodies may be present even in patients in clinical remission. Furthermore, only about 70% of patients with
ocular myasthenia have detectable antibody levels while 90% of patients with generalized MG have elevated
antibody titre. Although the blood tests when positive is highly specific, it is not particularly sensitive. In my
practice I do not rely upon the results of blood acetylcholine receptor levels to establish a diagnosis. The diagnosis
is based purely on clinical observations and the response to intravenous tensilon.

Treatment