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Mary Graver* was looking forward to starting high school. There was just one problem: Her left upper eyelid was blocking her vision. The pleasant 14-year-old told us that she was concerned with the appearance of her eyelid, and she made sure we understood that she was eager to have surgery to correct the ptosis before she started ninth grade in the fall.
Mary was accompanied to our oculoplastics clinic by her mother, who told us that she first noticed the eyelid droopiness when Mary was about 4 years old and that it seemed to have become progressively worse over the years. The eyelid also appeared to droop more when Mary was tired, Mrs. Graver said. When this happened, Mary had to tilt her head up to see things. This was beginning to bother Mary to the extent that she had her hair styled into asymmetric bangs to hide her left eye.
Our Patient’s History
Mary’s history included myopia, for which she wore glasses and contacts, and a lazy eye. Although her lazy eye was evident when she was an infant, she had not been consistently followed by an ophthalmologist. One of Mary’s three sisters also had a lazy eye but no eyelid abnormalities. Mary’s mother had a history of depression and thyroid disease, but she was not forthcoming about the details.
Mary was first examined by an ophthalmologist when she was 7. At that time, she voiced similar complaints of a droopy left upper eyelid. The ophthalmologist noted that she had left upper lid ptosis and severely restricted ocular movement. Given her age and ocular motility abnormalities, he expressed concern regarding potential chronic progressive external ophthalmoplegia, and he referred Mary to a pediatric ophthalmologist for further evaluation. However, Mrs. Graver did not follow through with this recommendation, and we were the next ophthalmologists to examine Mary.
Mary was otherwise healthy and not on any medications.
We Get a Look
When we examined her, Mary’s visual acuity with correction was 20/15 in her right eye and 20/70 with pinhole improvement to 20/40 in her left. Her pupils were briskly reactive with no relative afferent pupillary defect. Her ocular movements were limited in the right eye to 20 percent in all directions of gaze. In the left eye, the limitation was more severe—no supraduction or adduction was noted, but 20 percent of infraduction and 60 percent of abduction remained (Fig. 1).
|What's Your Diagnosis?
|ALL DIRECTIONS. The patient’s ocular movements were severely limited.
There was 2 mm of ptosis in the right eye and 7 to 8 mm of ptosis in the left eye, with intact levator function on the right side and minimal function on the left. In addition, Mary had significant brow elevation on both sides. The remainder of her exam appeared unremarkable.
Pinning It Down
At this point, our differential diagnosis included chronic progressive external ophthalmoplegia, myasthenia gravis, orbital fibrosis syndrome, and thyroid eye disease. We undertook further testing in the clinic and noted a positive Cogan lid twitch in both eyes as well as worsening of ptosis in upgaze. Mary’s ptosis also improved bilaterally after the application of ice for two minutes.
We referred Mary to pediatric neurology for further evaluation and management. Her thyroid-stimulating hormone results came back within normal limits, but blood serology for the acetylcholinesterase receptor binding antibody was positive. Electromyography (EMG) showed a decreased response with repetitive nerve stimulation, confirming the diagnosis of ocular myasthenia gravis.
Mary was to return to the neurology clinic in order to start pyridostigmine (Mestinon). She did not keep her appointment either with them or with us and was lost to follow-up.
Myasthenia gravis can mimic other clinical entities, resulting in a delay in diagnosis and treatment. It is important to note that ophthalmologists are often the first physicians to diagnose this disease, as half of affected patients present with ocular manifestations at onset. Thus, we must be highly sensitive to the possibility of this diagnosis.
Signs and symptoms. The most common ocular sign is unilateral or bilateral ptosis, followed by diplopia and ocular movement abnormalities. Many of these symptoms worsen with fatigue. In addition, weakness of the orbicularis oculi muscle may occur; the presence of this symptom should help differentiate myasthenia gravis from other conditions.
Thyroid eye disease occurs in about 5 percent of myasthenia gravis patients, and 10 percent of patients have thymomas.1 The pupil is never involved in myasthenia gravis; any pupil abnormalities require an investigation of other disease processes.
Systemic involvement. Nearly 85 percent of patients with ocular myasthenia gravis go on to develop systemic disease over the next two years. Systemic involvement leads to difficulty chewing, swallowing, breathing, and extending proximal muscles.
The dysphagia and dyspnea can be life threatening and require prompt medical attention.
Pediatric issues. Myasthenia gravis in patients under age 19 usually presents with symptoms similar to those seen in our patient, notably ptosis and asymmetric ophthalmoplegia. Children are less likely than adults to progress to systemic disease, particularly if they are initially affected prior to puberty.2
Many diagnostic tests for myasthenia gravis exist, and diagnosis and treatment is similar in children and adults.
Noninvasive tests. A simple and common in-office test with high specificity and sensitivity is the ice test, in which an ice pack is applied to the closed eyes for two minutes. If the ptosis improves, the test is considered positive. Similarly, another simple test, the rest test, assesses ptosis after the patient has rested quietly with eyes closed for 30 minutes. These tests are most useful when the patient presents with ptosis.3
Edrophonium. IV administration of acetylcholinesterase inhibitors can also be done in the clinic. Edrophonium (Tensilon, Reversol) and neostigmine methylsulfate (Prostigmine) are commonly used. These tests are useful for patients who present with ocular movement abnormalities.
Common side effects of the drugs include increased salivation and diarrhea. Rare, serious side effects include bradycardia, respiratory arrest/bronchospasm, and cholinergic crisis. IV atropine sulfate is an effective antidote and should be readily available when these tests are performed.4
Blood serology. Blood tests may be performed to detect one of the three anti-acetylcholine receptor antibodies: binding, blocking, or modulating. Binding antibodies are present in 90 percent of patients with generalized myasthenia and 50 percent with ocular myasthenia. If results for binding antibodies are negative, the other types of receptor antibodies can be tested. If all the receptor antibodies are negative, testing can be done for anti-MuSK (muscle-specific kinase) antibodies.
Nerve stimulation. Electromyographic repetitive nerve stimulation shows a classic decremental response, particularly in patients with systemic disease. Single-fiber EMG is a similar, very sensitive test for myasthenia gravis. Both can be used to confirm a clinical diagnosis.
Treatment varies according to symptoms and includes acetylcholinesterase inhibitors (such as Mestinon, as was recommended for our patient); corticosteroids, with or without steroid-sparing immunosuppressants; and immune-modulating agents. If a thymoma is present, it can be surgically excised, although the benefit is unclear in ocular disease.
* Patient’s name is fictitious.
1 Basic and Clinical Science Course, Section 5: Neuro-ophthalmology. San Francisco; AAO; 2010: 328-331.
2 Finnis MF, Jayawant S. Autoimmune Dis. Epub 2011 Nov. 1. doi: 10.4061/2011/404101.
3 Kubis KC et al. Ophthalmology. 2000;107(11):1995-1998.
4 Benatar M. Neuromuscul Disord. 2006;16(7):459-467.
Dr. Muthappan is a third-year ophthalmology resident and Dr. Mahoney is assistant professor of oculoplastics; both are at the Wilmer Eye Institute in Baltimore. The authors report no related financial interests.