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Re-evaluating the treatment of acute optic neuritis
  1. Jeffrey L Bennett1,
  2. Molly Nickerson2,
  3. Fiona Costello3,
  4. Robert C Sergott4,
  5. Jonathan C Calkwood5,
  6. Steven L Galetta6,
  7. Laura J Balcer6,
  8. Clyde E Markowitz7,
  9. Timothy Vartanian8,
  10. Mark Morrow9,
  11. Mark L Moster4,
  12. Andrew W Taylor10,
  13. Thaddeus W W Pace11,
  14. Teresa Frohman12,
  15. Elliot M Frohman12,13
  1. 1Departments of Neurology and Ophthalmology, University of Colorado, Denver, Colorado, USA
  2. 2Department of Medical Affairs, Questcor Pharmaceuticals, Inc., Hayward, California, USA
  3. 3Departments of Clinical Neurosciences and Surgery, University of Calgary, Hotchkiss Brain Institute, Alberta, Canada
  4. 4Neuro-Ophthalmology Service, Wills Eye Institute, Thomas Jefferson University Medical College, Philadelphia, Pennsylvania, USA
  5. 5Minneapolis Clinic of Neurology, Minneapolis, Minnesota, USA
  6. 6Department of Neurology, Division of Neuro-Ophthalmology, NYU Langone Medical Center, New York, USA
  7. 7Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
  8. 8Rockefeller University and Memorial Sloan-Kettering Hospital, Weill Cornell Medical College, New York, USA
  9. 9Department of Neurology, Harbor-University of California Los Angeles Medical Center, Torrance, California, USA
  10. 10Department of Ophthalmology, Boston University School of Medicine, Boston, Massachusetts, USA
  11. 11College of Nursing at the University of Arizona, Tucson, Arizona, USA
  12. 12Departments of Neurology & Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, Texas, USA
  13. 13Departments of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
  1. Correspondence to Dr Elliot M Frohman, Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., Dallas, Texas 75235, USA; elliot.frohman{at}


Clinical case reports and prospective trials have demonstrated a reproducible benefit of hypothalamic-pituitary-adrenal (HPA) axis modulation on the rate of recovery from acute inflammatory central nervous system (CNS) demyelination. As a result, corticosteroid preparations and adrenocorticotrophic hormones are the current mainstays of therapy for the treatment of acute optic neuritis (AON) and acute demyelination in multiple sclerosis.

Despite facilitating the pace of recovery, HPA axis modulation and corticosteroids have failed to demonstrate long-term benefit on functional recovery. After AON, patients frequently report visual problems, motion perception difficulties and abnormal depth perception despite ‘normal’ (20/20) vision. In light of this disparity, the efficacy of these and other therapies for acute demyelination require re-evaluation using modern, high-precision paraclinical tools capable of monitoring tissue injury.

In no arena is this more amenable than AON, where a new array of tools in retinal imaging and electrophysiology has advanced our ability to measure the anatomic and functional consequences of optic nerve injury. As a result, AON provides a unique clinical model for evaluating the treatment response of the derivative elements of acute inflammatory CNS injury: demyelination, axonal injury and neuronal degeneration.

In this article, we examine current thinking on the mechanisms of immune injury in AON, discuss novel technologies for the assessment of optic nerve structure and function, and assess current and future treatment modalities. The primary aim is to develop a framework for rigorously evaluating interventions in AON and to assess their ability to preserve tissue architecture, re-establish normal physiology and restore optimal neurological function.


This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:

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