The investigation of acute optic neuritis: a review and proposed protocol

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Key Points

  • Optic neuritis is frequently but not always associated with multiple sclerosis (MS), and patients who present with optic neuritis will want to know about their risk of developing MS

  • Early recognition of optic neuritis not caused by MS is important to prevent severe visual loss, and to avoid inappropriate use of MS-targeted treatments

  • No international consensus exists on the nosology of optic neuritis: the aetiology remains idiopathic in many cases, and attempts at classification fall short, in part because we lack a uniform investigation protocol

  • This Review on established and emerging diagnostic tools proposes a consensus on the investigation of patients with suspected optic neuritis in both standard care and research

  • The aims are to aid recognition of patients at risk of severe visual loss, to contribute to future attempts at classification of optic neuritis, and to provide end points for clinical studies


Optic neuritis is an inflammatory optic neuropathy that affects many patients with multiple sclerosis (MS) at some point during their disease course. Differentiation of acute episodes of MS-associated optic neuritis from other autoimmune and inflammatory optic neuropathies is vital for treatment choice and further patient management, but is not always straightforward. Over the past decade, a number of new imaging, laboratory and electrophysiological techniques have entered the clinical arena. To date, however, no consensus guidelines have been devised to specify how and when these techniques can be most rationally applied for the diagnostic work-up of patients with acute optic neuritis. In this article, we review the literature and attempt to formulate a consensus for the investigation of patients with acute optic neuritis, both in standard care and in research with relevance to clinical treatment trials.

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Figure 1: Ophthalmological and MRI investigations in a 35-year-old woman with blurred vision in the right eye.
Figure 2: Minimal retinal OCT protocol—part I: peripapillary ring scan.
Figure 3: Minimal retinal OCT protocol—part II: macular volume scan.
Figure 4: MMO in a 44-year-old man with Harding disease (multiple sclerosis plus Leber hereditary optic neuropathy).

Change history

  • 18 July 2014

    In the version of the article originally posted online, Romain Marignier's surname was misspelt. The error has been corrected in the online PDF and HTML versions of the article.


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The MS Center VUMC is partially funded by a programme grant from the Dutch MS Research Foundation. K.F. is a recipient of Grants-in-Aid for Scientific Research from the Ministry of Education, Science and Technology and the Ministry of Health, Labour and Welfare of Japan. F.P. is supported by the German Research Council (DFG Exc 257) and the German Ministry for Education and Research Competence Network Multiple Sclerosis. S.S. is supported by the Clinical Research Priority Program of the University of Zürich and the Betty and David Koetser Foundation for Brain Research. G.T.P. is supported by the University College London Comprehensive Biomedical Research Centre and the Moorfields Biomedical Research Centre.

Author information

A.P. had the idea for this protocol, reviewed the literature, provided figures, wrote the first draft and finalized the manuscript. F.C., K.F., F.P., S.S. and C.S. revised the manuscript. M.P.W. performed an independent literature review and wrote the MRI section. C.L.F. performed an independent literature review and wrote the VEP/ERG section. B.W. and G.T.P. contributed to the conception and design of the protocol. All authors revised the final version of the manuscript.

Correspondence to Axel Petzold.

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The authors declare no competing financial interests.

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Investigation protocol for patients presenting with suspected optic neuritis (PDF 781 kb)

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Conversion of visual acuities (PDF 44 kb)

Microcystic macular oedema (MOV 762 kb)

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Petzold, A., Wattjes, M., Costello, F. et al. The investigation of acute optic neuritis: a review and proposed protocol. Nat Rev Neurol 10, 447–458 (2014) doi:10.1038/nrneurol.2014.108

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