Appendix E-1: Patient Population Supplemental Data

appendix e-1: Patient Population Supplemental Data

The diagnosis of optic neuritis (ON) required that patients demonstrate the following clinical features: pain at presentation, decreased visual acuity, a visual field defect that followed the topography of the retinal nerve fiber layer (RNFL), color vision loss, a relative afferent pupil defect, and either mild to moderate disc edema or a normal fundus in the affected eye at presentation.

Patients were excluded if they had other suspected causes of vision loss and/or atypical features of ON, because it is not known whether the course of RNFL loss after ON secondary other inflammatory or infectious conditions is comparable to ON associated with MS. Clinical features that were considered atypical of ON included:optic disc or retinal hemorrhages, retinal exudates, cellular reaction in the vitreous, optic nerve pallor or RNFL thinning at presentation, and worsening vision with steroid withdrawal. Patients that could not participate in OCT testing were excluded from the study. Patients who did not carry a confirmed diagnosis of MS [including patients with a normal baseline MRI (n = 33 women and 6 men)];patients who presented with bilateral simultaneous ON (n = 3 women); and patients who lacked the diagnosis of MS and manifested incomplete visual recovery (defined as ETDRS visual acuity worse than 20/25 measured 3-months after ON) (n = 9 women and 5 men)underwent additional testing to exclude other causes of optic neuropathy.

The battery of investigations used to investigate for other causes of optic neuritis and to exclude ON and MS mimics included: serum testing for: syphilis [Veneral Disease Research Laboratory (VDRL) and Fluorescent treponemal antibody absorbed FTS-ABS)]; Wegener’s granulomatosisand Churg Strauss Syndrome [anti-neutrophil cytoplasmic antibody (ANCA)]; sarcoidosis [angiotension converting enzyme (ACE), antinuclear antibody (ANA)]; anti-phospholipid antibody syndrome (lupus anticoagulant, anti-phospholipid antibody testing, complement levels), rheumatoid arthritis (rheumatoid factor), Sjogren’s syndrome (SS-A, SS-B antibodies); Lyme disease; NeuromyelitisOptica (anti-NMO IgG; Mayo Clinic and University of Calgary); vitamin B12 deficiency, the Human Immunodeficiency Virus HIV testing (Elisa HIV-1 and HIV-2), myeloproliferative disorders (serum protein electrophoresis); and specific mutation testing (11778, 14484, 3460) for Leber’s Hereditary Optic Neuropathy (LHON). Additional blood work also included cell count with differential, electrolytes, liver enzymes, renal screen, serum sedimentation rate and C-reactive protein testing. Forty twopatients agreed to undergo a lumbar puncture to assess cerebrospinal fluid constituents (cell count with differential; glucose and protein; culture and sensitivity; cytopathology; and oligoclonal band testing). None of these patients had CSF abnormalities, except for 9/30 patients with negative baseline MRI, who demonstrated positive oligoclonal bands in the CSF. All patients underwent computed tomography of the chest, abdomen and pelvis to exclude sarcoidosis and evidence of extrapulmonary lymphadenopathy. Patients with other suspected causes of optic neuropathy also underwent a dedicated magnetic resonance imaging (MRI) study of the orbits to exclude orbital inflammatory syndromes (particularly perineuritis) and compressive lesions. Full field electroretinogram (ERG) and multifocal ERG testing were performed to exclude primary retinal causes of vision loss.