Clinical Challenge

Ophthaproblem

Stephanie Baxter, MD  Sanjay Sharma, MD, MSC, MBA, FRCSC

A 36-year-old man presents with a history of intermittently droopy eyelids and double vision. These symptoms seem to fluctuate throughout the day and are absent when he wakes up in the morning. He is otherwise well.

The appearance of the eye is compatible with the patient’s having which of the following?

1. Left third nerve palsy
2. Ocular myasthenia gravis
3. Thyroid ophthalmopathy
4. Multiple sclerosis

Dr Baxter is a fourth-year resident in the Department of Ophthalmology at Queen’s University in Kingston, Ont. Dr Sharma is an Associate Professor in the Department of Ophthalmology and an Assistant Professor in the Department of Epidemiology at Queen’s University.

Answer to Ophthaproblem

2. Ocular myasthenia gravis

Myasthenia gravis (MG) is an autoimmune disease characterized by weakness and fatigue of skeletal muscle. Patients with MG produce autoantibodies against the postsynaptic nicotinic acetylcholine receptor (Ach-R).

Myasthenia gravis is relatively common. Incidence is 3 to 5 per 100 000 people and prevalence is 40 per 100 000 people.1,2 It occurs in patients of all ages, both sexes, and all races, but there are two peaks in its distribution: younger women and older men tend to be more frequently affected.1

As many as 84% of myasthenia patients present with the ocular symptoms ptosis and diplopia.3 If the signs and symptoms are confined to the extraocular muscles, these patients are said to have ocular myasthenia gravis (OMG). In 30% to 51% of those with OMG at presentation, the disease will generalize to involve muscles throughout the body.3,4 Half the patients who progress this way do so within the first 2 years.4 Any skeletal muscle can be affected, including the muscles used for swallowing and respiration. When the respiratory muscles fail, patients are said to be in myasthenic crisis, indicating the severity of the condition.

Patients with MG sometimes have associated conditions, such as thymomas and other autoimmune disorders that can include thyroid disease, rheumatoid arthritis, diabetes mellitus, and systemic lupus erythematosus.1 Mediastinal imaging and serologic analysis should be used to test for these conditions. Medications, such as aminoglycosides, ciprofloxacin, and ß-blockers, can exacerbate the symptoms of MG.5

Ocular myasthenia gravis can be diagnosed with a variety of tests. Office tests include the ice test (improved ptosis after exposing the eyelids to ice), the rest test (fewer symptoms after a period of rest), and tensilon testing (pharmacologically induced improvement in symptoms using an anticholinesterase inhibitor).1 Results of serologic assays for Ach-R antibodies are positive in 90% of patients with systemic MG and in 70% of patients with OMG.6 Electromyographic testing can also assist in diagnosing OMG.1,7

The goals of therapy in patients with OMG are to relieve symptoms and prevent the spread of the condition. Mounting evidence suggests that immune modulating therapy reduces the risk of OMG patients’ developing systemic symptoms.4,8 Symptom management includes prisms or patching for the diplopia and eyelid crutches or taping the lid for ptosis.

Pyridostigmine, an anticholinesterase inhibitor, increases the amount of acetylcholine available in the synaptic cleft and has varying effects on patients with OMG.5 Additional immunosuppressive therapy is often needed for managing symptoms. Also, pyridostigmine does not modulate immunity, and thus does not reduce risk of disease progression.

Prednisone is the most commonly used immune modulator; azathioprine is used as a steroid-sparing agent.4,5,8 Other medications have been tried experimentally, most often for patients with severe, unresponsive, generalized MG. All patients with thymomas or thymic hyperplasia should have thymectomy, but it is unclear whether thymectomy benefits other patients with MG.9

Management

This patient was referred to an ophthalmologist for assessment. He was found to have variable ptosis and strabismus. He had positive results on ice, tensilon, and anti–Ach-R antibody testing. A computed tomography scan of his mediastinum revealed a thymoma, which was surgically excised.

He had an incomplete response to 60 mg of oral pyridostigmine four times daily and had only minimal side effects (diarrhea managed with 5 mg of oral diphenoxylate HCl and atropine sulfate as required). Prednisone was added to help control symptoms and as an immune modulator to prevent progression of disease. Two years later, he was doing well, and there was no evidence of generalization.

Recommendation

Patients presenting with variable ptosis and diplopia should be referred to an ophthalmologist or a neurologist for assessment and management. A diagnosis of OMG and the risk of systemic progression, including the risk of choking and respiratory failure, should be clearly explained to patients and their families.

References

1. Miller NR. Myasthenia. In: Albert DM, Jakobeic FA, editors. Principles and practice of ophthalmology. Vol 5. 2nd ed. Philadelphia, Pa: WB Saunders; 2000. p. 4051-65.
2. MacDonald BK, Cockerell OC, Sander JW, Shorvon SD. The incidence and lifetime prevalence of neurological disorders in a prospective community-based study in the UK. Brain 2000;123:665-76.
3. Bever CT, Aquino AV, Penn AS, Lovelace RE, Rowland LP. Prognosis of ocular myasthenia. Ann Neurol 1983;14:516-9.
4. Sommer N, Sigg B, Melms A, Weller M, Schepelmann K, Herzau V, et al. Ocular myasthenia gravis: response to long-term immunosuppressive treatment. J Neurol Neurosurg Psychiatry 1997;62:156-62.
5. Pelak VS, Galetta SL. Ocular myasthenia gravis. Curr Treat Options Neurol 2001;3:367-76.
6. Oda K, Ito Y. Myasthenia gravis: antibodies to acetylcholine receptor in ocular myasthenia gravis. J Neurol 1981;225:251-81.
7. Rivero A, Crovetto L, Lopez L, Maselli R, Nogues M. Single fibre electromyography of extraocular muscles: a sensitive method for the diagnosis of ocular myasthenia gravis. Muscle Nerve 1995;18:943-7.
8. Kupersmith MJ, Moster M, Bhuiyan S, Warren F, Weinberg H. Beneficial effects of corticosteroids on ocular myasthenia gravis. Arch Neurol 1996;53:802-4.
9. Lanska DJ. Indications for thymectomy in myasthenia gravis. Neurology 1990;40:1828-9.