Optic Neuritis Recovery After Oral or IV Corticosteroids
Condition: Optic Neuritis
MeSH terms: Neuritis; Optic Neuritis
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      Patients aged 18-65 with acute demyelinating optic neuritis where treatment with high dose
      corticosteroids are already been chosen by the patient and the diagnosing physician will be
      contacted for screening and enrollment. Patients will then be randomized to receive
      equivalent doses of either intravenous (IV) or oral corticosteroid treatment. Optic nerve
      function assessments will be compared at baseline, prior to treatment, one and six months
      post corticosteroid treatment. This will allow for a comparison on whether the route of
      medication plays a role in the effectiveness of treatment with high dose corticosteroids.
    

Detailed description: 
      This will be a single-blind, randomized comparison study between 1000mg IV methylprednisolone
      daily for three days and 1250mg oral prednisone daily for three days of the recovery of optic
      nerve function in acute demyelinating optic neuritis. We will be comparing assessments at
      baseline, prior to corticosteroid treatment, with assessments at one and six months post
      corticosteroid treatment.

      Patient Population

      We propose to study patients with acute demyelinating optic neuritis where treatment with
      high dose corticosteroids is being considered. This presentation can be either the first
      presentation of a demyelinating event (CIS) or in a patient with a previous diagnosis of CIS
      or MS but must be the first presentation of ON in the affected eye.

      Subjects will be recruited from out-patients assessed for acute demyelinating optic neuritis
      by neurology, ophthalmology, neuro-ophthalmology at London Health Sciences Center and St.
      Joseph's Health Care Center in London, Ontario. Subjects will be included only if the first
      visit takes place within 14 days of symptom onset. Only subjects where the physician who
      identifies/diagnoses the optic neuritis is considering corticosteroid treatment will be
      contacted for potential screening and enrollment. To ensure treatment is chosen based on the
      clinical judgement of physician diagnosing ON, the investigators will only contact potential
      subjects after the decision to use corticosteroids has been made by the patient's treating
      physician.

      Primary and Secondary Endpoints

      The primary measure will be the P100 latency of the Visual Evoked Potential in the affected
      eye at six months. Secondary measures will include high contrast visual acuity and contrast
      sensitivity at one and six months post corticosteroid treatment and the P100 latency at
      one-month post corticosteroid treatment.

      Visual Evoked Potentials VEPs will be recorded with Teca Synergy equipment (Viasys
      Healthcare). To ensures consistency in technique, the same technician will perform all three
      assessments (day 0, 30 and 180) on the same patient. The subject's skin will be cleaned for
      electrode placement. The scalp electrodes will be placed relative to bony landmarks, as per
      International Society for Clinical Electrophysiology of Vision (ISCEV) standards (40). The
      electrodes will be positioned 5 cm above the inion for Oz (active), mid-forehead for Fz
      (reference) and on the right arm for the ground, following ISCEV guidelines. The patient will
      be positioned comfortably in a chair with the eye at a distance of 1 meter from a 17-inch
      cathode ray tube (CRT) monitor, which has been found to be superior to an LCD monitor as the
      latter can cause a delay in the latency. The room will be darkened to minimize extraneous
      light that produce responses in the visual cortex and interfere with the VEP response. The
      same room will be used for every VEP in this study. The subject will be monitored for
      fixation as poor fixation can affect the P100 peak time and an eye patch used to isolate
      vision from one eye only. Monocular stimulation will occur at a frequency of 2 Hz, beginning
      with the unaffected eye, averaging 200 individual responses for each trial. A minimum of two
      trials per eye will be performed as per ISCEV guidelines. Further averaging of additional
      trials may be done if there are obvious technical problems (with visual fixation for
      instance). As the test is dependent on subject compliance, the following will take place to
      maximize compliance and technical aspects of the recording: talking and gum chewing will be
      prohibited; the subject will be instructed to relax all muscles of the head and neck
      specifically the jaw; feet will be resting flat on the floor with hands relaxed in the
      subject's lap; coaching will take place to help diminish any anxiety; the importance of
      fixation will be emphasized and the need to resist following the changes in colour of the
      checkerboard pattern and to continue fixating on the red fixation square in the centre of the
      monitor will be explained. The interpretation of the VEPs will be done by an assessor blinded
      to the treatment arm received.

      Visual Acuity Visual acuity will be measured using the Early Treatment Diabetic Retinopathy
      Study (ETDRS) charts and standard protocol as it the gold standard for ophthalmology clinical
      trials using visual acuity as an outcome. Testing acuity occurs initially at 4 meters
      initially and only testing at 2 meters if there are no abnormalities noted at 4 meters.

      Contrast Sensitivity Contrast sensitivity will be measured using the Low Contrast Sloan
      Letter Charts that was found to be valid and reliable for the MS population
    

Intervention name(s): corticosteroids; corticosteroids
Intervention type(s): Drug; Drug
Intervention description(s): 1250mg of oral prednisone daily for 3 days; 1000mg IV methylprednisolone daily for 3 days
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Multiple Sclerosis; relapse; demyelination; treatment; corticosteroids