title: Ophthalmic evaluations in clinical studies of fingolimod (FTY720) in multiple sclerosis.
abstract: OBJECTIVE
  To report outcomes of ophthalmic evaluations in clinical studies of patients receiving fingolimod (Gilenya; Novartis Pharma AG, Basel, Switzerland) for multiple sclerosis (MS).
  
  
  METHODS
  Analysis done on pooled safety data (N = 2615, all studies group) from 3 double-masked, randomized, parallel-group clinical trials (phase 2 core and extension >5 years, and phase 3 FREEDOMS and TRANSFORMS core and extension studies).
  
  
  METHODS
  Patients aged 18 to 55 years (18-60 years in phase 2 study) diagnosed with relapsing-remitting MS were included. Patients with diabetes mellitus or macular edema (ME) at screening were excluded.
  
  
  METHODS
  Participants received fingolimod (0.5/1.25 mg), placebo, or interferon beta for the respective study durations. Ophthalmic examination included detailed eye history (at screening), visual acuity (VA) assessment, dilated ophthalmoscopy, optical coherence tomography (OCT), and fluorescein angiography (FA).
  
  
  METHODS
  Extensive ophthalmic monitoring was performed for all patients. While being studied, patients with abnormal findings on dilated ophthalmoscopy and OCT compatible with ME were further studied by FA. All locally diagnosed ME cases were centrally reviewed by the retina specialist (M.A.Z.) on the Data and Safety Monitoring Board.
  
  
  RESULTS
  Among 2615 patients assessed, 19 confirmed ME cases were observed in fingolimod-treated groups (0.5 mg: n = 4, 0.3%; 1.25 mg: n = 15, 1.2%). Most patients (n = 13, 68%) presented with blurred vision, decreased VA, or eye pain. Macular edema was diagnosed within 3 to 4 months of treatment initiation in most cases (n = 13, 68%); 2 patients had late onset (>12 months) ME. Of the 19 patients with ME, 5 (26%), all treated with fingolimod 1.25 mg, had a history of uveitis compared with 26 (1%) in the all studies group. In most cases (n = 16, 84%), ME resolved after discontinuing the study drug. Eleven patients required topical anti-inflammatory medications. No patient had further vision deterioration.
  
  
  CONCLUSIONS
  Fingolimod 0.5 mg is associated with a low incidence of ME in MS studies. Patients with a history of uveitis may be at an increased risk of developing ME. An ophthalmic examination before initiating fingolimod therapy and regular follow-up eye examinations during fingolimod therapy are recommended.
authors.affiliation: Institute of Ophthalmology & Visual Science, New Jersey Medical School, Newark, New Jersey 07103, USA. zarbin@earthlink.net
authors.forename: Marco A
authors.initials: MA
authors.lastname: Zarbin
authors.forename: Lee M
authors.initials: LM
authors.lastname: Jampol
authors.forename: Rama D
authors.initials: RD
authors.lastname: Jager
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Reder
authors.forename: Gordon
authors.initials: G
authors.lastname: Francis
authors.forename: William
authors.initials: W
authors.lastname: Collins
authors.forename: Dejun
authors.initials: D
authors.lastname: Tang
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D004311:Double-Blind Method; D005260:Female; D000068876:Fingolimod Hydrochloride; D005451:Fluorescein Angiography; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D008269:Macular Edema / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy*; D009887:Ophthalmoscopy; D011409:Propylene Glycols / Q000009:adverse effects* / Q000627:therapeutic use; D013110:Sphingosine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D041623:Tomography, Optical Coherence; D016896:Treatment Outcome; D014605:Uveitis / Q000150:complications; D014792:Visual Acuity / Q000502:physiology; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine