A 3-year Multi-center Study to Describe Changes of OCT Parameters Under Treatment With Gilenya®

Inclusion criteria

Patients eligible for inclusion in this study have to fulfill all of the following criteria:

• Written informed consent must be obtained before any assessment is performed.
• Male or female subjects aged 18-65 years.
• Subjects with relapsing remitting MS defined by 2010 revised McDonald criteria (see Appendix 4).
• Patients with Expanded Disability Status Scale (EDSS) score of 0-6.0 inclusive (see Appendix 6).
• Patients stable on immunomodulatory treatment with fingolimod for at least 1 month and at most 4 months prior to screening according to local label
• Neurologically stable with no evidence of relapse within 30 days prior to inclusion date
• Sufficient ability to read, write, communicate and understand

Exclusion criteria

Patients fulfilling any of the following criteria are not eligible for inclusion in this study:

• Patients who have been treated with:

• systemic corticosteroids or immunoglobulins within 1 month prior to screening;
• immunosuppressive medications such as azathioprine, cyclophosphamide, or methotrexate within 3 months prior to screening;
• monoclonal antibodies (including natalizumab) within 3 months prior to screening;
• mitoxantrone within 6 months prior to screening
• cladribine at any time.
• Patients with any medically unstable condition, as assessed by the primary treating physician at each site.
• Patients with any of the following cardiovascular conditions :

• history of myocardial infarction or with current unstable ischemic heart disease;
• Heart failure (NYHA III-IV) or any severe cardiac disease as determined by the Investigator (see Appendix 5);
• history or presence of a second-degree AV block, Type II or a third-degree AV block
• patients receiving Class Ia (ajmaline, disopyramide, procainamide, quinidine) or III antiarrhythmic drugs (e.g., amiodarone, bretylium, sotalol, ibulitide, azimilide, dofelitide);
• proven history of sick sinus syndrome;
• uncontrolled hypertension
• Patients with severe respiratory disease, pulmonary fibrosis, or chronic obstructive pulmonary disease (Class III-IV).
• Patients with history of specific MRI findings (tumor, subdural haematoma, post-contusional changes, territorial stroke, neurodegenerative disorders, aneurysm/arteriovenous malformation, evidence of past macroscopic haemorrhage, or other relevant MRI findings that would interfere with evaluation)
• Any severe disability or clinical impairment that can prevent the patient to meet all study requirements at the investigator's discretion
• History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin
• Patients who have received an investigational drug (excluding fingolimod) or therapy within 90 days or 5 half-lives of screening, whichever is longer.
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG test (serum)
• Patients with any ophthalmologic reason for RNFL pathology other than MS, such as: optic neuropathy, active advanced glaucoma, injury of the optic nerve based on the ophthalmologist's clinical judgment
• history or presence of severe myopia

• in patients who have not had refractive surgery, a refractive error of greater than 6.00 diopters
• pathologic fundus changes of high myopia, such as retinal pigmentary atrophy, besides peripapillary atrophy (atrophy involving the macula) or a staphyloma
• in patients that have had previous refractive surgery, an axial eye length of greater than 26 mm
• Acute optic neuritis within the past 6 months before screening
• Evidence of advanced, non-proliferative or proliferative diabetic retinopathy
• Presence of retinal conditions associated with edema, subretinal fluid, cysts, etc.
• Concomitant use of drugs that may directly affect retinal structure and function (e.g.

chronic systemic corticosteroids [>30 consecutive days; doses higher than Cushing threshold e.g. prednisone 7.5mg/d], intraocular anti-angiogenic drugs [ranibizumab, bevacizumab], intraocular steroids etc.)