Ocular myasthenia gravis
- Victoria S Pelak, MD
Victoria S Pelak, MD
- Associate Professor of Neurology and Ophthalmology
- Director, Neurology Residency Program
- University of Colorado Denver, School of Medicine, Department of Neurology
- Dianna Quan, MD
Dianna Quan, MD
- Associate Professor of Neurology
- University of Colorado Denver, School of Medicine
- Section Editors
- Paul W Brazis, MD
Paul W Brazis, MD
- Section Editor — Neuroophthalmology
- Professor of Neurology, Department of Ophthalmology
- Mayo Clinic College of Medicine
- Jeremy M Shefner, MD, PhD
Jeremy M Shefner, MD, PhD
- Section Editor — Neuromuscular Disease
- Professor and Chair of Neurology, Barrow Neurological Institute
- Professor of Neurology, University of Arizona, Phoenix
- Clinical Professor of Neurology, Creighton University
Myasthenia gravis (MG) is an autoimmune disorder characterized by weakness and fatigability of skeletal muscles. Muscle weakness due to dysfunction of the neuromuscular junction (myasthenia) may be an acquired disorder, and the vast majority of patients who develop generalized myasthenia in adolescence or adulthood have autoantibodies that play a pathogenetically important role. Such antibody-mediated disease is referred to as MG.
When the symptoms of MG are isolated to the levator palpebrae superioris, orbicularis oculi, and the oculomotor muscles, it is referred to as ocular MG (OMG). Over one-half of all patients with MG initially present with isolated ptosis, diplopia, or both, and no signs or symptoms of weakness elsewhere [1-3]. Approximately 15 percent of all patients with MG have isolated OMG as the only manifestation of their disease. Although the disease pathology at the neuromuscular junction is not known to be distinct from generalized MG (GMG), there are several important and unique differences between OMG and GMG with regard to diagnosis and treatment.
This topic will discuss OMG. Other aspects of MG are discussed separately. (See "Pathogenesis of myasthenia gravis" and "Clinical manifestations of myasthenia gravis" and "Differential diagnosis of myasthenia gravis" and "Diagnosis of myasthenia gravis" and "Treatment of myasthenia gravis".)
The pathophysiology of ocular myasthenia gravis (OMG) is not known to be different than that for generalized MG (GMG). (See "Pathogenesis of myasthenia gravis".)
It is uncertain why ocular muscles are frequently involved in myasthenia and why the disease stays localized to the ocular muscles in 15 percent of cases. It has been proposed that subtle alterations in the function of extraocular muscles are more likely to produce symptoms than in limb muscles, and that the levator palpebrae, under constant activation during eye opening, may be more susceptible to fatigue. Other factors may contribute to this phenomenon [4-6]:To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Simpson JF, Westerberg MR, Magee KR. Myasthenia gravis. An analysis of 295 cases. Acta Neurol Scand 1966; 42:Suppl 23:1.
- Grob D, Arsura EL, Brunner NG, Namba T. The course of myasthenia gravis and therapies affecting outcome. Ann N Y Acad Sci 1987; 505:472.
- Bever CT Jr, Aquino AV, Penn AS, et al. Prognosis of ocular myasthenia. Ann Neurol 1983; 14:516.
- Kaminski HJ, Maas E, Spiegel P, Ruff RL. Why are eye muscles frequently involved in myasthenia gravis? Neurology 1990; 40:1663.
- Kaminski HJ, Li Z, Richmonds C, et al. Susceptibility of ocular tissues to autoimmune diseases. Ann N Y Acad Sci 2003; 998:362.
- Sommer N, Melms A, Weller M, Dichgans J. Ocular myasthenia gravis. A critical review of clinical and pathophysiological aspects. Doc Ophthalmol 1993; 84:309.
- COGAN DG. MYASTHENIA GRAVIS: A REVIEW OF THE DISEASE AND A DESCRIPTION OF LID TWITCH AS A CHARACTERISTIC SIGN. Arch Ophthalmol 1965; 74:217.
- Averbuch-Heller L, Poonyathalang A, von Maydell RD, Remler BF. Hering's law for eyelids: still valid. Neurology 1995; 45:1781.
- Ohkawa S, Yamasaki H, Ohsumi Y, et al. Eyebrow lifting test: a novel bedside test for narrowing of the palpebral fissure associated with peripheral facial nerve palsy. J Neurol Neurosurg Psychiatry 1997; 63:256.
- Osher RH, Glaser JS. Myasthenic sustained gaze fatigue. Am J Ophthalmol 1980; 89:443.
- BAPTISTA AG, SILVA E SOUZA H. Pupillary abnormalities in myasthenia gravis. Report of a case. Neurology 1961; 11:210.
- Cooper J, Pollak GJ, Ciuffreda KJ, et al. Accommodative and vergence findings in ocular myasthenia: a case analysis. J Neuroophthalmol 2000; 20:5.
- Moorthy G, Behrens MM, Drachman DB, et al. Ocular pseudomyasthenia or ocular myasthenia 'plus': a warning to clinicians. Neurology 1989; 39:1150.
- Shams PN, Waldman A, Plant GT. B Cell lymphoma of the brain stem masquerading as myasthenia. J Neurol Neurosurg Psychiatry 2002; 72:271.
- Tummala RP, Harrison A, Madison MT, Nussbaum ES. Pseudomyasthenia resulting from a posterior carotid artery wall aneurysm: a novel presentation: case report. Neurosurgery 2001; 49:1466.
- Keane JR. Multiple cranial nerve palsies: analysis of 979 cases. Arch Neurol 2005; 62:1714.
- Sethi KD, Rivner MH, Swift TR. Ice pack test for myasthenia gravis. Neurology 1987; 37:1383.
- Golnik KC, Pena R, Lee AG, Eggenberger ER. An ice test for the diagnosis of myasthenia gravis. Ophthalmology 1999; 106:1282.
- Daroff RB. The office Tensilon test for ocular myasthenia gravis. Arch Neurol 1986; 43:843.
- Meriggioli MN, Sanders DB. Myasthenia gravis: diagnosis. Semin Neurol 2004; 24:31.
- Elrod RD, Weinberg DA. Ocular myasthenia gravis. Ophthalmol Clin North Am 2004; 17:275.
- Lindstrom JM, Seybold ME, Lennon VA, et al. Antibody to acetylcholine receptor in myasthenia gravis. Prevalence, clinical correlates, and diagnostic value. Neurology 1976; 26:1054.
- Ahlskog JE, Petersen RC, Waring SC, et al. Guamanian neurodegenerative disease: are diabetes mellitus and altered humoral immunity clues to pathogenesis? Neurology 1997; 48:1356.
- Sanders DB, Andrews PI, Howard JF, Massey JM. Seronegative myasthenia gravis. Neurology 1997; 48:40S.
- Vincent A, Newsom-Davis J. Acetylcholine receptor antibody as a diagnostic test for myasthenia gravis: results in 153 validated cases and 2967 diagnostic assays. J Neurol Neurosurg Psychiatry 1985; 48:1246.
- Evoli A, Tonali P, Bartoccioni E, Lo Monaco M. Ocular myasthenia: diagnostic and therapeutic problems. Acta Neurol Scand 1988; 77:31.
- Soliven BC, Lange DJ, Penn AS, et al. Seronegative myasthenia gravis. Neurology 1988; 38:514.
- Hoch W, McConville J, Helms S, et al. Auto-antibodies to the receptor tyrosine kinase MuSK in patients with myasthenia gravis without acetylcholine receptor antibodies. Nat Med 2001; 7:365.
- McConville J, Farrugia ME, Beeson D, et al. Detection and characterization of MuSK antibodies in seronegative myasthenia gravis. Ann Neurol 2004; 55:580.
- Ohta K, Shigemoto K, Kubo S, et al. MuSK antibodies in AChR Ab-seropositive MG vs AChR Ab-seronegative MG. Neurology 2004; 62:2132.
- Caress JB, Hunt CH, Batish SD. Anti-MuSK myasthenia gravis presenting with purely ocular findings. Arch Neurol 2005; 62:1002.
- Hanisch F, Eger K, Zierz S. MuSK-antibody positive pure ocular myasthenia gravis. J Neurol 2006; 253:659.
- Bennett DL, Mills KR, Riordan-Eva P, et al. Anti-MuSK antibodies in a case of ocular myasthenia gravis. J Neurol Neurosurg Psychiatry 2006; 77:564.
- Zisimopoulou P, Evangelakou P, Tzartos J, et al. A comprehensive analysis of the epidemiology and clinical characteristics of anti-LRP4 in myasthenia gravis. J Autoimmun 2014; 52:139.
- Tsivgoulis G, Dervenoulas G, Kokotis P, et al. Double seronegative myasthenia gravis with low density lipoprotein-4 (LRP4) antibodies presenting with isolated ocular symptoms. J Neurol Sci 2014; 346:328.
- AAEM Quality Assurance Committee. American Association of Electrodiagnostic Medicine. Practice parameter for repetitive nerve stimulation and single fiber EMG evaluation of adults with suspected myasthenia gravis or Lambert-Eaton myasthenic syndrome: summary statement. Muscle Nerve 2001; 24:1236.
- Younger DS, Worrall BB, Penn AS. Myasthenia gravis: historical perspective and overview. Neurology 1997; 48:S1.
- Costa J, Evangelista T, Conceição I, de Carvalho M. Repetitive nerve stimulation in myasthenia gravis--relative sensitivity of different muscles. Clin Neurophysiol 2004; 115:2776.
- Oh SJ, Kim DE, Kuruoglu R, et al. Diagnostic sensitivity of the laboratory tests in myasthenia gravis. Muscle Nerve 1992; 15:720.
- Sanders DB, Howard JF Jr. AAEE minimonograph #25: Single-fiber electromyography in myasthenia gravis. Muscle Nerve 1986; 9:809.
- AAEM Quality Assurance Committee. American Association of Electrodiagnostic Medicine. Literature review of the usefulness of repetitive nerve stimulation and single fiber EMG in the electrodiagnostic evaluation of patients with suspected myasthenia gravis or Lambert-Eaton myasthenic syndrome. Muscle Nerve 2001; 24:1239.
- Valls-Canals J, Povedano M, Montero J, Pradas J. Stimulated single-fiber EMG of the frontalis and orbicularis oculi muscles in ocular myasthenia gravis. Muscle Nerve 2003; 28:501.
- Rivero A, Crovetto L, Lopez L, et al. Single fiber electromyography of extraocular muscles: a sensitive method for the diagnosis of ocular myasthenia gravis. Muscle Nerve 1995; 18:943.
- Mercelis R, Merckaert V. Diagnostic utility of stimulated single-fiber electromyography of the orbicularis oculi muscle in patients with suspected ocular myasthenia. Muscle Nerve 2011; 43:168.
- Krendel DA, Sanders DB, Massey JM. Single fiber electromyography in chronic progressive external ophthalmoplegia. Muscle Nerve 1987; 10:299.
- Milone M, Monaco ML, Evoli A, et al. Ocular myasthenia: diagnostic value of single fibre EMG in the orbicularis oculi muscle. J Neurol Neurosurg Psychiatry 1993; 56:720.
- Weinberg DH, Rizzo JF 3rd, Hayes MT, et al. Ocular myasthenia gravis: predictive value of single-fiber electromyography. Muscle Nerve 1999; 22:1222.
- Benatar M, Kaminski HJ, Quality Standards Subcommittee of the American Academy of Neurology. Evidence report: the medical treatment of ocular myasthenia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2007; 68:2144.
- Kupersmith MJ, Ying G. Ocular motor dysfunction and ptosis in ocular myasthenia gravis: effects of treatment. Br J Ophthalmol 2005; 89:1330.
- Kupersmith MJ, Moster M, Bhuiyan S, et al. Beneficial effects of corticosteroids on ocular myasthenia gravis. Arch Neurol 1996; 53:802.
- Sommer N, Sigg B, Melms A, et al. Ocular myasthenia gravis: response to long-term immunosuppressive treatment. J Neurol Neurosurg Psychiatry 1997; 62:156.
- Allen JA, Scala S, Jones HR. Ocular myasthenia gravis in a senior population: diagnosis, therapy, and prognosis. Muscle Nerve 2010; 41:379.
- Agius MA. Treatment of ocular myasthenia with corticosteroids: yes. Arch Neurol 2000; 57:750.
- Kaminski HJ, Daroff RB. Treatment of ocular myasthenia: steroids only when compelled. Arch Neurol 2000; 57:752.
- Bhanushali MJ, Wuu J, Benatar M. Treatment of ocular symptoms in myasthenia gravis. Neurology 2008; 71:1335.
- Monsul NT, Patwa HS, Knorr AM, et al. The effect of prednisone on the progression from ocular to generalized myasthenia gravis. J Neurol Sci 2004; 217:131.
- Kupersmith MJ. Does early treatment of ocular myasthenia gravis with prednisone reduce progression to generalized disease? J Neurol Sci 2004; 217:123.
- Benatar M, Kaminski H. Medical and surgical treatment for ocular myasthenia. Cochrane Database Syst Rev 2006; :CD005081.
- Mee J, Paine M, Byrne E, et al. Immunotherapy of ocular myasthenia gravis reduces conversion to generalized myasthenia gravis. J Neuroophthalmol 2003; 23:251.
- Gronseth GS, Barohn RJ. Practice parameter: thymectomy for autoimmune myasthenia gravis (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2000; 55:7.
- Schumm F, Wiethölter H, Fateh-Moghadam A, Dichgans J. Thymectomy in myasthenia with pure ocular symptoms. J Neurol Neurosurg Psychiatry 1985; 48:332.
- Lanska DJ. Indications for thymectomy in myasthenia gravis. Neurology 1990; 40:1828.
- Roberts PF, Venuta F, Rendina E, et al. Thymectomy in the treatment of ocular myasthenia gravis. J Thorac Cardiovasc Surg 2001; 122:562.
- Huang CS, Hsu HS, Huang BS, et al. Factors influencing the outcome of transsternal thymectomy for myasthenia gravis. Acta Neurol Scand 2005; 112:108.
- Shrager JB, Deeb ME, Mick R, et al. Transcervical thymectomy for myasthenia gravis achieves results comparable to thymectomy by sternotomy. Ann Thorac Surg 2002; 74:320.
- Gilbert ME, De Sousa EA, Savino PJ. Ocular Myasthenia Gravis treatment: the case against prednisone therapy and thymectomy. Arch Neurol 2007; 64:1790.
- Chavis PS, Stickler DE, Walker A. Immunosuppressive or surgical treatment for ocular Myasthenia Gravis. Arch Neurol 2007; 64:1792.
- Castronuovo S, Krohel GB, Kristan RW. Blepharoptosis in myasthenia gravis. Ann Ophthalmol 1983; 15:751.
- Davidson JL, Rosenbaum AL, McCall LC. Strabismus surgery in patients with myasthenia. J Pediatr Ophthalmol Strabismus 1993; 30:292.
- Oosterhuis HJ. The natural course of myasthenia gravis: a long term follow up study. J Neurol Neurosurg Psychiatry 1989; 52:1121.
- CLINICAL FEATURES
- - Examination for eyelid fatigue
- Other findings
- DIFFERENTIAL DIAGNOSIS
- Thyroid ophthalmopathy
- Chronic progressive external ophthalmoplegia
- Muscular dystrophy
- Brainstem and motor cranial nerve pathology
- DIAGNOSTIC TESTS
- Ice pack test
- Tensilon test
- Serum antibody studies
- - Repetitive nerve stimulation
- - Single-fiber EMG
- DIAGNOSTIC EVALUATION
- Symptomatic management of ptosis and diplopia
- Anticholinesterase agents
- Immunosuppressive agents
- - Prednisone
- - Steroid sparing agents
- Surgery for ptosis and diplopia
- SUMMARY AND RECOMMENDATIONS