Ocular Myasthenia Gravis Treatment

Abstract

M YASTHENIAGRAVIS (MG) is an autoimmunedisorder that affects the postsynapticneuromuscular junctionmembrane.Acetylcholine receptor (AChR) antibodiesare frequentlypresent, andthe numberoffunctioningpostsynapticreceptors isreduced.Muscle-specifickinaseantibodiesmaybeidentifiedinindividuals with and without AChR antibodies. Ptosis or diplopia due to ocular muscle involvement are frequently the first symptomsof thedisease. Approximately half of the patients are first seen with purely ocularMG(OMG);of these,53%develop generalizedMG(GMG)within2years ( 80% in the first year). Furthermore,aspontaneousremissionrateof 30%hasbeenreportedinpatientswith OMG during a 15-year period. Both AChRandmuscle-specifickinaseantibodies may be present in OMG. The goal of therapy for OMG and GMG is to minimize the patient’s symptoms. Another recently discussed goal is to prevent the progression of OMG to GMG. Symptomatic treatment may be as simple as observation for patients with minimal symptoms, but some patients are uncomfortable owing to diplopia or ptosis and desire a more definitive treatment. The choice of the initial medication in patients with OMG depends on each drug’s efficacy, adverse effects, contraindications, availability, and cost. Classically, the mainstay of pharmacotherapy is acetylcholinesterase inhibitors (eg, pyridostigmine bromide). However, there is evidence that pyridostigmine may not be as effective in treating purely OMG. The clinical response is variable, but approximately 50% of patients with OMG have a good response. Ptosis tends to respond better than diplopia. The most common adverse effect is diarrhea. Very large doses occasionally lead to increased weakness from cholinergic crisis. The drug should be used with caution in patients with asthma, cardiac arrhythmia, or urinary obstruction. If treatment with this agent is unsuccessful, other approaches, such as immunosuppressive agents (typically corticosteroids) or thymectomy, may be used. Prednisone is the immunosuppressive agent most frequently used in the treatment of OMG. Most patients experience relief from ptosis and diplopia within weeks of starting prednisone therapy. The typical approach is to titrate the dose up to 1.0 mg/kg per day over several weeks. Maintenance doses at this level are continued for 6 to 12 weeks and are followed by a slow taper over several months. Treatment with prednisone longer than 2 to 4 weeks can have significant morbidity. Patients require careful monitoring for development of peptic ulcer disease, diabetes mellitus, hypertension, psychosis, insomnia, myopathy, hypokalemia, hypocalcemia, osteoporosis, cataracts, glaucoma, masking of infections, and worsening MG symptoms. The failure of OMG-related ptosis and diplopia to improve after corticosteroid therapy ranges from as low as 8 of 89 patients (9%) in one study to as high as 6 of 18 (33%) in another. Somestudies suggest thatthe useofcorticosteroidsor thymectomy astheprimarytreatmentofOMGmay decrease theriskofdevelopingGMG. The firstof thesestudies summarized 32patientswhoweretreatedforOMG with prednisone for 2 months to 1 year. Only 3 of the 32 patients (9%) went on to develop GMG, a significantlylowerpercentagethanexpected fromthenaturalhistorystudiesof the disease. How long these 3 patients who progressed to GMG had symptomsbeforestartingtreatmentwasnot specified. This is critical information because patients with ocular symptoms for more than a year are less likelytodevelopGMGwhetherornot they are treated. The majority of patients who progress to GMG do so within the first year of OMG symptom onset. Two subsequent studies included patients from a myasthenia database anddidnot specifyhowlongpatients hadsymptomsbeforestartingtherapy. Therefore,patientswhohadbeen followed up for more than 2 years with onlyocularsymptomsmayhavebeen included, skewing the likelihood of progression. Amorerecent study included only patients with ocular symptoms for less than 2 years. Thirteen of 31 patients (42%) did not progress to GMG, and 10 of these patientsunderwentimmunosuppressive therapy. Two of the 10 patients receivedazathioprinesodiuminaddition to prednisone, 3 underwent prednisoneandazathioprinetherapyplusthymectomy,and3receivedimmunosupAuthor Affiliations: Neuroophthalmology Service, Wills Eye Institute (Drs Gilbert and Savino), and Department of Neurology, Thomas Jefferson University (Dr De Sousa), Philadelphia, Pennsylvania. Dr Gilbert is now with the Department of Neuro-Ophthalmology, Illinois Eye and Ear Infirmary, Chicago.