Myasthenia gravis is an autoimmune-mediated disease of the neuromuscular junction with fluctuating, painless muscle weakness as its cardinal symptom. It is a generalized disorder that often manifests initially as focal weakness.1 The most common focal presentation involves weakness of the extraocular muscles, eyelid elevators, and orbicularis oculi with symptoms of ptosis and diplopia. These findings localized in the eye are defined as ocular myasthenia gravis.2 The estimated prevalence of myasthenia gravis is approximately 10 per 100,000 individuals, and approximately 60% to 85% of patients initially present with isolated ocular symptoms.3
Treatments proposed for ocular myasthenia gravis include drugs with purely symptomatic effects, such as cholinesterase inhibitors, and drugs that suppress the immune system, such as corticosteroids and immunosuppressives.4,5 The highest dose of prednisone had effects on the treatment of ocular myasthenia gravis.6 Proponents of steroids point to the limited efficacy of pyridostigmine, the possibility that cholinesterase inhibitor therapy may exacerbate the cholinergic deficit in myasthenia, the potentially greater beneficial effects of a corticosteroid, and the potential for corticosteroids to reduce the risk of progression from ocular to generalized myasthenia gravis.7,8 Opponents of corticosteroids emphasize the potential risk of serious side effects and question whether these risks are justified in the setting of purely ocular symptoms.9
Therefore, this study was conducted to evaluate the efficacy and safety of low-to-moderate dose oral corticosteroids in patients diagnosed as having ocular myasthenia gravis.
Patients and Methods
This retrospective, observational case series was performed at a single center. The study was approved by the institutional review board of Kim's Eye Hospital and was conducted in accordance with the tenets of the Declaration of Helsinki.
The current study included patients who complained of variable or fatigable ptosis and/or diplopia between January 2011 and September 2015 at Kim's Eye Hospital. Ocular myasthenia gravis was confirmed with an acetylcholine receptor binding antibody test (more than 0.5 nmol/L) and an ice test in patients with ptosis. Patients with a blowout fracture, hyperthyroidism, diabetes mellitus, hypertension, cardiovascular disease, or history of strabismus surgery were excluded. Patients who underwent any therapy for myasthenia gravis and had general weakness were also excluded to investigate the initial effect of a corticosteroid on ocular myasthenia gravis.
We performed a full ophthalmologic evaluation including a levator function test, orbicularis oculi weakness test, Hess screen test, alternate prism cover test, and ice test. All patients included in the study were initially treated with methylprednisolone (Methylon tab 4 mg; Alvogen Korea, Seoul, Korea). The initial dose of methylprednisolone ranged from 16 (4 tablets) to 32 (8 tablets) mg and the dose depended on the patient's status. When the symptoms disappeared, the dose was gradually reduced (8 mg/week). The success of treatment was defined as the disappearance of diplopia and ptosis for more than 6 months after remission. Complications resulting from corticosteroid medication were investigated.
During the study period, methylprednisolone therapy was administered to 29 patients as an initial treatment (Table 1). Six of 29 patients were lost to follow-up. As a result, 23 of the 29 patients (15 men and 8 women) were included. All 4 patients with ptosis showed a positive finding for the ice test. Acetylcholine receptor binding antibody was 3.615 ± 4.23 nmol/L. Patterns of clinical symptoms included 22 patients with diplopia, 5 patients with ptosis, and 2 patients with simultaneous diplopia and ptosis. Nineteen of the 23 patients demonstrated successful treatment with corticosteroids (Figure 1) and 4 patients remained symptomatic during the 8 weeks.
Characteristics of 29 Patients With Ocular Myasthenia Gravis
Outcomes of patients with ocular myasthenia gravis. F/U = follow-up
Among patients with ptosis and diplopia symptoms, 1 patient had symptomatic improvement after the oral corticosteroid regimen. All 3 patients who had only ptosis improved after oral corticosteroid therapy. Fifteen of 19 patients with symptoms of diplopia improved after oral steroid therapy. However, 4 patients with diplopia did not have improved symptoms (Figure 2). An initial worsening of symptoms was not found and the treatment response of oral steroid therapy was 82.6% at 8 weeks (Figure 3). After finishing corticosteroid therapy, 4 patients had recurrences during follow-up (mean follow-up time: 17 months; mean recurrence time: 9 months).
Treatment response from oral steroid therapy.
Success rate of corticosteroid treatment according to symptoms; 82.6% of the enrolled patients had relief of ocular problems.
Eight patients complained of adverse effects of steroid therapy such as constipation, insomnia, anorexia, myalgia, and weight gain. The most common side effect was insomnia (3 of 8 patients). There were no serious side effects such as gastritis, diabetes mellitus, worsened hypertension, avascular necrosis of the hip joint, or infectious disease.
The results of this study are important in confirming the therapeutic effect of using a low-to-moderate dose of an oral corticosteroid as a primary treatment rather than using a cholinesterase inhibitor. Although corticosteroid use in ocular myasthenia gravis is still debated,10 corticosteroid therapy should be considered because patients with ocular myasthenia gravis have relatively poor responses to a cholinesterase inhibitor alone.11
Lindberg et al.4 reported that single intravenous methylprednisolone was efficacious and safe in moderate myasthenia gravis. The dose of corticosteroid ranged from 16 to 32 mg in the current study. Ordinary oral steroids have a starting dose of 24 mg/d. The the dosage of oral steroid in our study was changed according to the status of ptosis or strabismus. Oral corticosteroid treatment is often administered at high doses (0.75 to 1.0 mg/kg/d) and tapered slowly for several days.12 In addition, a higher corticosteroid dose and longer treatment with a corticosteroid were not associated with a better outcome.13 Several studies suggest a gradual increase in dose from an initial relatively low dose (20 mg/d).14,15 The current study showed that a low-to-moderate dose of corticosteroid without a dose increase was effective in the treatment of ocular myasthenia gravis. Thus, relatively low-dose corticosteroid treatment in patients with ocular myasthenia gravis could be efficacious and 8 weeks might be enough to obtain a response from a corticosteroid in ocular myasthenia gravis.
There were no severe side effects from the corticosteroid treatment and none of the 23 patients stopped the medication because of side effects. The side effects of corticosteroid treatment depend on the dose and duration.16 This would be one of the benefits of a low-to-moderate dose of a corticosteroid.
Symptomatic improvement usually starts within 2 to 3 weeks after initiating therapy.1 In the current study, 10 of 23 patients (43.4%) showed recovery in 2 weeks. The successful remission rate was 82.6% in the current study. Previous studies reported similar results of 56% to 96% improvement.10,17,18 During follow-up, 4 of the 19 patients in remission (21%) had ocular myasthenia gravis recurrence. The total remission rate could be underestimated because of the short follow-up duration and because permanent remission can be induced by corticosteroids in only 10% of patients.19
Limitations of this study are as follows. First, the study was retrospective and conducted in a relatively small number of eyes. We did not compare effectiveness and efficacy between corticosteroid treatment and a cholinesterase inhibitor. Second, most patients suffered from diplopia because the study was performed in a neuro-ophthalmology clinic. In ocular myasthenia gravis, ptosis is the most common finding.20 Thus, there might have been selection bias. However, the study demonstrated the effectiveness of a low-to-moderate dose of a corticosteroid in ocular myasthenia gravis.
A low-to-moderate dose of an oral corticosteroid may be considered as a primary treatment in ocular myasthenia gravis because the treated patients had a favorable response to the corticosteroid without severe side effects.
- Elrod RD, Weinberg DA. Ocular myasthenia gravis. Ophthalmol Clin North Am. 2004;17:275–309. doi:10.1016/j.ohc.2004.05.014 [CrossRef]
- Tackenberg B, Hemmer B, Oertel WH, Sommer N. Immunosuppressive treatment of ocular myasthenia gravis. BioDrugs. 2001;15:369–378. doi:10.2165/00063030-200115060-00003 [CrossRef]
- Grob D, Brunner N, Namba T, Pagala M. Lifetime course of myasthenia gravis. Muscle Nerve. 2008;37:141–149. doi:10.1002/mus.20950 [CrossRef]
- Lindberg C, Andersen O, Lefvert AK. Treatment of myasthenia gravis with methylprednisolone pulse: a double blind study. Acta Neurol Scand. 1998;97:370–373. doi:10.1111/j.1600-0404.1998.tb05968.x [CrossRef]
- Tindall RS, Phillips JT, Rollins JA, Wells L, Hall K. A clinical therapeutic trial of cyclosporine in myasthenia gravis. Ann N Y Acad Sci. 1993;681:539–551. doi:10.1111/j.1749-6632.1993.tb22937.x [CrossRef]
- Kupersmith MJ, Moster M, Bhuiyan S, Warren F, Weinberg H. Beneficial effects of corticosteroids on ocular myasthenia gravis. Arch Neurol. 1996;53:802–804. doi:10.1001/archneur.1996.00550080128020 [CrossRef]
- Kupersmith MJ, Latkany R, Homel P. Development of generalized disease at 2 years in patients with ocular myasthenia gravis. Arch Neurol. 2003;60:243–248. doi:10.1001/archneur.60.2.243 [CrossRef]
- Zach H, Cetin H, Hilger E, et al. The effect of early prednisolone treatment on the generalization rate in ocular myasthenia gravis. Eur J Neurol. 2013;20:708–713. doi:10.1111/ene.12057 [CrossRef]
- Vaphiades MS, Bhatti MT, Lesser RL. Ocular myasthenia gravis. Curr Opin Ophthalmol. 2012;23:537–542. doi:10.1097/ICU.0b013e328358b94a [CrossRef]
- Hoffmann S, Kohler S, Ziegler A, Meisel A. Glucocorticoids in myasthenia gravis; if, when, how, and how much?Acta Neurol Scand. 2014;130:211–221. doi:10.1111/ane.12261 [CrossRef]
- March GA Jr, Johnson LN. Ocular myasthenia gravis. J Natl Med Assoc. 1993;85:681–684.
- Meriggioli MN, Sanders DB. Autoimmune myasthenia gravis: emerging clinical and biological heterogeneity. Lancet Neurol. 2009;8:475–490. doi:10.1016/S1474-4422(09)70063-8 [CrossRef]
- Imai T, Suzuki S, Tsuda E, et al. Oral corticosteroid therapy and present disease status in myasthenia gravis. Muscle Nerve. 2015;51:692–696. doi:10.1002/mus.24438 [CrossRef]
- Seybold ME, Drachman DB. Gradually increasing doses of prednisone in myasthenia gravis: reducing the hazards of treatment. N Engl J Med. 1974;290:81–84. doi:10.1056/NEJM197401102900204 [CrossRef]
- Benatar M, McDermott MP, Sanders DB, et al. Efficacy of prednisone for the treatment of ocular myasthenia (EPITOME): a randomized, controlled trial. Muscle Nerve. 2016;53:363–369. doi:10.1002/mus.24769 [CrossRef]
- Antonio-Santos AA, Eggenberger ER. Medical treatment options for ocular myasthenia gravis. Curr Opin Ophthalmol. 2008;19:468–478. doi:10.1097/ICU.0b013e328310da18 [CrossRef]
- Evoli A, Tonali P, Bartoccioni E, Lo Monaco M. Ocular myasthenia: diagnostic and therapeutic problems. Acta Neurol Scand. 1988;77:31–35. doi:10.1111/j.1600-0404.1988.tb06970.x [CrossRef]
- Evoli A, Batocchi AP, Minisci C, Di Schino C, Tonali P. Therapeutic options in ocular myasthenia gravis. Neuromuscul Disord. 2001;11:208–216. doi:10.1016/S0960-8966(00)00173-5 [CrossRef]
- Johns TR. Long-term corticosteroid treatment of myasthenia gravis. Ann N Y Acad Sci. 1987;505:568–583. doi:10.1111/j.1749-6632.1987.tb51325.x [CrossRef]
- Leeamornsiri S, Chirapapaisan N, Chuenkongkaew W. Clinical profiles of Thai patients with ocular myasthenia gravis in Siriraj Hospital. J Med Assoc Thai. 2011;94:1117–1121.
Characteristics of 29 Patients With Ocular Myasthenia Gravis
| Male||19 (66%)|
| Female||10 (34%)|
|Acetylcholine receptor binding antibody (nmol/L)||3.615 ± 4.23|
|Nature of the chief complaint|
| Diplopia||22 patients|
| Ptosis||5 patients|
| Diplopia & ptosis||2 patients|