Skip to main content

Advertisement

Log in

Clinical features and treatment status of antiacetylcholine receptor antibody-positive ocular myasthenia gravis

  • Clinical Investigation
  • Published:
Japanese Journal of Ophthalmology Aims and scope Submit manuscript

Abstract

Purpose

To clarify the factors predictive of progression from ocular myasthenia gravis (OMG) to generalized MG (GMG) among patients with positive antiacetylcholine receptor antibodies (AChRAb) and to evaluate the efficacy of our OMG treatment protocol including tacrolimus (TAC).

Study design

Retrospective study.

Methods

Fifty-two patients with AChRAb positivity and ptosis and/or eye movement disturbance showing diurnal fluctuation and fatigability were included. First, we compared the clinical characteristics of patients without OMG progression (p-OMG) with those of patients whose OMG transformed to GMG (TMG). Second, we subdivided the p-OMG patients according to the time of approval of TAC into the Before group and the After group. We compared the dosage and period of prednisolone administration (PSL) of the 2 groups. Third, we evaluated the responses to OMG treatment using the Myasthenia Gravis Foundation of America Postintervention Status (MGFA-PS) scale.

Results

Forty-one patients were classified into the p-OMG group, and 11, into the TMG group. The AChRAb level (P = 0.0006) and prevalence of thymoma (P = 0.001) were significantly higher in the TMG group than in the p-OMG group. In the p-OMG group, the MG composite score (P ≤ 0.0001) and AChRAb level (P = 0.005) improved after treatment. The periods of PSL administration at ≥ 20 mg/day (P = 0.009) and at 10 to 19 mg/day (P = 0.002) were significantly shorter in the After group. At the last follow-up, 78.0% of the p-OMG group patients had achieved MGFA-PS minimal manifestations or better status with PSL ≤ 5 mg/day.

Conclusions

The TMG cases were characterized by higher AChRAb levels and presence of thymoma. The P-OMG patients could be managed with our treatment protocol. Combined use of TAC was efficacious in patients with steroid-dependent p-OMG.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Murai H, Yamashita N, Watanabe M, Nomura Y, Motomura M, Yoshikawa H, et al. Characteristics of myasthenia gravis according to onset-age: Japanese nationwide survey. J Neurol Sci. 2011;305:97–102.

    Article  PubMed  Google Scholar 

  2. Evoli A, Batocchi AP, Minisci C, Di Schino C, Tonali P. Therapeutic options in ocular myasthenia gravis. Neuromuscul Disord. 2001;11:208–16.

    Article  CAS  PubMed  Google Scholar 

  3. Li F, Hotter B, Swierzy M, Ismail M, Meisel A, Ruckert JC. Generalization after ocular onset in myasthenia gravis: a case series in Germany. J Neurol. 2018;265:2773–822.

    Article  PubMed  Google Scholar 

  4. Antonio-Santos AA, Eggenberger ER. Medical treatment options for ocular myasthenia gravis. Curr Opin Ophthalmol. 2008;19:468–78.

    Article  PubMed  Google Scholar 

  5. Mossman S, Vincent A, Newsom-Davis J. Myasthenia gravis without acetylcholine-receptor antibody: a distinct disease entity. Lancet. 1986;1:116–9.

    Article  CAS  PubMed  Google Scholar 

  6. Drachman DB. Myasthenia gravis. N Engl J Med. 1994;330:1797–810.

    Article  CAS  PubMed  Google Scholar 

  7. Palace J, Vincent A, Beeson D. Myasthenia gravis: diagnostic and management dilemmas. Curr Opin Neurol. 2001;14:583–9.

    Article  CAS  PubMed  Google Scholar 

  8. Hoch W, McConville J, Helms S, Newsom-Davis J, Melms A, Vincent A. Auto-antibodies to the receptor tyrosine kinase MuSK in patients with myasthenia gravis without acetylcholine receptor antibodies. Nat Med. 2001;7:365–8.

    Article  CAS  PubMed  Google Scholar 

  9. O'Hare M, Doughty C. Update on ocular myasthenia gravis. Semin Neurol. 2019;39:749–60.

    Article  PubMed  Google Scholar 

  10. Mittal MK, Barohn RJ, Pasnoor M, McVey A, Herbelin L, Whittaker T, et al. Ocular myasthenia gravis in an academic neuro-ophthalmology clinic: clinical features and therapeutic response. J Clin Neuromuscul Dis. 2011;13:46–52.

    Article  PubMed  Google Scholar 

  11. Apinyawasisuk S, Chongpison Y, Thitisaksakul C, Jariyakosol S. Factors affecting generalization of ocular myasthenia gravis in patients with positive acetylcholine receptor antibody. Am J Ophthalmol. 2020;209:10–7.

    Article  CAS  PubMed  Google Scholar 

  12. Jaretzki A 3rd, Barohn RJ, Ernstoff RM, Kaminski HJ, Keesey JC, Penn AS, et al. Myasthenia gravis: recommendations for clinical research standards. Task Force of the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America. Neurology. 2000;55:16–23.

    Article  PubMed  Google Scholar 

  13. Burns TM, Conaway MR, Cutter GR, Sanders DB. Construction of an efficient evaluative instrument for myasthenia gravis: the MG composite. Muscle Nerve. 2008;38:1553–622.

    Article  PubMed  Google Scholar 

  14. Katzberg HD, Bril V. A comparison of electrodiagnostic tests in ocular myasthenia gravis. J Clin Neuromuscul Dis. 2005;6:109–13.

    Article  PubMed  Google Scholar 

  15. Hendricks TM, Bhatti MT, Hodge DO, Chen JJ. Incidence, epidemiology, and transformation of ocular myasthenia gravis: a population-based study. Am J Ophthalmol. 2019;205:99–105.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Ayzenberg I, Ellrichmann G, Schroeder C, Tonges L, Klasing A, Pappa V, et al. Brainstem encephalitis with low-titer acetylcholine receptor antibodies mimicking myasthenia gravis. Front Neurol. 2019;10:829.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Rajput R, Sachdev A, Din N, Damato EM, Murray A. False positive acetylcholine receptor antibodies in a case of unilateral chronic progressive external ophthalmoplegia: case report and review of literature. Orbit. 2018;37:385–8.

    Article  PubMed  Google Scholar 

  18. Tanaka Y, Satomi K. Overlap of myasthenia gravis and Miller Fisher syndrome. Intern Med. 2016;55:1917–8.

    Article  PubMed  Google Scholar 

  19. Plested CP, Tang T, Spreadbury I, Littleton ET, Kishore U, Vincent A. AChR phosphorylation and indirect inhibition of AChR function in seronegative MG. Neurology. 2002;59:1682–8.

    Article  CAS  PubMed  Google Scholar 

  20. Peeler CE, De Lott LB, Nagia L, Lemos J, Eggenberger ER, Cornblath WT. Clinical utility of acetylcholine receptor antibody testing in ocular myasthenia gravis. JAMA Neurol. 2015;72:1170–4.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Teo KY, Tow SL, Haaland B, Gosavi TD, Jing-Liang L, Yew Long LO, et al. Low conversion rate of ocular to generalized myasthenia gravis in Singapore. Muscle Nerve. 2018;57:756–60.

    Article  CAS  PubMed  Google Scholar 

  22. Mazzoli M, Ariatti A, Valzania F, Kaleci S, Tondelli M, Nichelli PF, et al. Factors affecting outcome in ocular myasthenia gravis. Int J Neurosci. 2018;128:15–24.

    Article  CAS  PubMed  Google Scholar 

  23. Aguirre F, Villa AM. Prognosis of ocular myasthenia gravis in an Argentinian population. Eur Neurol. 2018;79:113–7.

    Article  PubMed  Google Scholar 

  24. Lindstrom JM, Seybold ME, Lennon VA, Whittingham S, Duane DD. Antibody to acetylcholine receptor in myasthenia gravis: prevalence, clinical correlates, and diagnostic value. Neurology. 1976;26:1054–9.

    Article  CAS  PubMed  Google Scholar 

  25. Kupersmith MJ, Latkany R, Homel P. Development of generalized disease at 2 years in patients with ocular myasthenia gravis. Arch Neurol. 2003;60:243–8.

    Article  PubMed  Google Scholar 

  26. Kupersmith MJ. Ocular myasthenia gravis: treatment successes and failures in patients with long-term follow-up. J Neurol. 2009;256:1314–20.

    Article  PubMed  Google Scholar 

  27. Mullaney P, Vajsar J, Smith R, Buncic JR. The natural history and ophthalmic involvement in childhood myasthenia gravis at the hospital for sick children. Ophthalmology. 2000;107:504–10.

    Article  CAS  PubMed  Google Scholar 

  28. Kupersmith MJ, Ying G. Ocular motor dysfunction and ptosis in ocular myasthenia gravis: effects of treatment. Br J Ophthalmol. 2005;89:1330–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Ozawa Y, Uzawa A, Kanai T, Oda F, Yasuda M, Kawaguchi N, et al. Efficacy of high-dose intravenous methylprednisolone therapy for ocular myasthenia gravis. J Neurol Sci. 2019;402:12–5.

    Article  CAS  PubMed  Google Scholar 

  30. Komiyama A, Arai H, Kijima M, Hirayama K. Extraocular muscle responses to high dose intravenous methylprednisolone in myasthenia gravis. J Neurol Neurosurg Psychiatry. 2000;68:214–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Jaretzki A 3rd, Barohn RJ, Ernstoff RM, Kaminski HJ, Keesey JC, Penn AS, et al. Myasthenia gravis: recommendations for clinical research standards. Task Force of the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America. Ann Thorac Surg. 2000;70:327–34.

    Article  PubMed  Google Scholar 

  32. Gilhus NE. Autoimmune myasthenia gravis. Expert Rev Neurother. 2009;9:351–8.

    Article  CAS  PubMed  Google Scholar 

  33. Sanders DB, Evoli A. Immunosuppressive therapies in myasthenia gravis. Autoimmunity. 2010;43:428–35.

    Article  CAS  PubMed  Google Scholar 

  34. Grob D, Brunner N, Namba T, Pagala M. Lifetime course of myasthenia gravis. Muscle Nerve. 2008;37:141–9.

    Article  PubMed  Google Scholar 

  35. Masuda M, Utsugisawa K, Suzuki S, Nagane Y, Kabasawa C, Suzuki Y, et al. The MG-QOL15 Japanese version: validation and associations with clinical factors. Muscle Nerve. 2012;46:166–73.

    Article  PubMed  Google Scholar 

  36. Zhang Z, Yang C, Zhang L, Yi Q, Hao Z. Efficacy and safety of tacrolimus in myasthenia gravis: a systematic review and meta-analysis. Ann Indian Acad Neurol. 2017;20:341–7.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Nishida Y, Takahashi YK, Kanai T, Nose Y, Ishibashi S, Sanjo N, et al. Safety of tapering tacrolimus dose in patients with well-controlled anti-acetylcholine receptor antibody-positive myasthenia gravis. Euro J Neurol. 2020;27:100–4.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yoshihiko Isshiki.

Ethics declarations

Conflicts of interest

Y. Isshiki, None; O. Mimura, Lecture fee (Santen, Senju, Otsuka, Pfizer, Alcon, GSK); F. Gomi, Grant, Lecture fee (Pfizer, Novartis, Santen, Senju), Grant (Alcon), Lecture fee (Bayer).

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Corresponding Author: Yoshihiko Isshiki

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Isshiki, Y., Mimura, O. & Gomi, F. Clinical features and treatment status of antiacetylcholine receptor antibody-positive ocular myasthenia gravis. Jpn J Ophthalmol 64, 628–634 (2020). https://doi.org/10.1007/s10384-020-00770-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10384-020-00770-z

Keywords

Navigation