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Original research
Diagnosing myasthenia gravis using orthoptic measurements: assessing extraocular muscle fatiguability
  1. Kevin R Keene1,2,
  2. Johan M de Nie3,
  3. Mechteld J Brink3,
  4. Irene C Notting3,
  5. Jan J G M Verschuuren2,
  6. Hermien E Kan1,
  7. Jan-Willem M Beenakker1,3,4,
  8. Martijn R Tannemaat2
  1. 1CJ Gorter MRI Center, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands
  2. 2Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands
  3. 3Department of Ophthalmology, Leiden University Medical Centrum, Leiden, The Netherlands
  4. 4Department of Radiation Oncology, Leiden University Medical Center, Leiden, Netherlands
  1. Correspondence to Kevin R Keene, Department of Radiology, CJ Gorter MRI Center, Leiden Universitair Medisch Centrum, 2333 ZA Leiden, Zuid-Holland, The Netherlands; K.R.Keene{at}lumc.nl

Abstract

Introduction Diagnosing ocular myasthenia gravis (MG) can be challenging because serum antibodies are often not detected. We aimed to explore whether determining extraocular muscle (EOM) weakness using orthoptic measures, including an adapted Hess chart examination, can aid in diagnosing MG.

Methods We conducted a prospective study among patients with acetylcholine receptor antibody positive MG (20 recently diagnosed, 19 chronic) and 14 seronegative MG patients. We compared orthoptic measures to 19 healthy and 18 disease controls with Graves orbitopathy, chronic progressive external ophthalmoplegia or oculopharyngeal muscular dystrophy. Maximal eye duction angles were measured using a synoptophore. Gaze deviations between eyes were measured using standard Hess chart examination with addition of 1 min persistent gaze to assess MG-associated fatiguability. Receiver operating characteristics curve analysis was performed.

Results For duction angles, the area under the curve (AUC) was 0.73 comparing MG to healthy, and 0.69 comparing to patient controls. For the outer field of the Hess chart, the AUC was 0.89 comparing to healthy and 0.54 to patient controls. For drift, the AUC was 0.93 comparing to healthy and 0.93 to patient controls. The sensitivity and specificity of the presence of drift was 81% and 100%.

Discussion Orthoptic measurements can be used to diagnose MG by quantifying EOM weakness and fatiguability. Drift during persistent gaze on a Hess chart is specific for MG and could be used for diagnostic purposes. The Hess chart examination is widely available, inexpensive and fast. Moreover, orthoptic measurements may be a clinically relevant outcome measure for clinical trials.

  • MYASTHENIA
  • EYE MOVEMENTS

Data availability statement

Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as online supplemental information. Anonymised data presented in this article will be made available at the request of a qualified investigator. Requests should be made to MRT (m.r.tannemaat@lumc.nl). Raw Hess charts and spider plots depicting the affected EOM per individual participant have been added as online supplemental data.

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Data availability statement

Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as online supplemental information. Anonymised data presented in this article will be made available at the request of a qualified investigator. Requests should be made to MRT (m.r.tannemaat@lumc.nl). Raw Hess charts and spider plots depicting the affected EOM per individual participant have been added as online supplemental data.

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Footnotes

  • Twitter @kan_hermien

  • J-WMB and MRT contributed equally.

  • Contributors KRK, MRT, J-WMB, HEK, ICN, JMdN, JJGMV and MJB have contributed to conception and design of the study. KRK, MRT, JJGMV and ICN have contributed to the acquisition of data. KRK performed the statistical analysis in this study. KRK, J-WMB, HEK, MRT have contributed by drafting a significant portion of the manuscript or figures. MRT is responsible for the overall content as guarantor. The guarantor accepts full responsibility for the finished work and/or the conduct of the study, had access to the data, and controlled the decision to publish.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests KRK reports involvement in myasthenia gravis research sponsored by Argenx, Alexion Pharmaceuticals, and the CHDR, with all reimbursements received by Leiden University Medical Center and research support from Philips Healthcare. JJGMV has been involved in MG research sponsored by the Princes Beatrix Fonds, NIH, FP7 European grant (#602420), consultancies for Argen-X, Alexion and Rapharma, and patents on the use of MuSK monoclonal antibodies. The LUMC receives royalties for MuSK antibody assays. MRT reports trial support from ArgenX and Alexion, consultancies for ArgenX and UCB Pharma and research funding from NMD Pharma, with all reimbursements received by Leiden University Medical Center. He is co-inventor on a patent describing a deep learning application to diagnose and monitor myasthenia gravis based on facial video data. J-WMB reports research support from Philips Healthcare. ICN reports no disclosures. HEK reports research Support from Philips Healthcare, Trial Support from Imaging DMD, no personal fees are received, all revenues go to the LUMC.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.