R. D. Jager

Ophthalmic Evaluations in Clinical Studies of Fingolimod (FTY720) in Multiple Sclerosis

PURPOSE To report outcomes of ophthalmic evaluations in clinical studies of patients receiving fingolimod (Gilenya; Novartis Pharma AG, Basel, Switzerland) for multiple sclerosis (MS). DESIGN 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). PARTICIPANTS 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. INTERVENTION 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). MAIN OUTCOME MEASURES 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.

Short-term intraocular pressure trends following intravitreal injections of ranibizumab (Lucentis) for the treatment of wet age-related macular degeneration

Rosenfeld and colleagues reported that ranibizumab (Lucentis) had no long-term effect on intraocular pressure (IOP) as determined by monthly measurements during the 2-year MARINA study.1 We are unaware of previous studies examining the short-term effect on IOP by intravitreal ranibizumab in patients with wet age-related macular degeneration. We conducted a retrospective chart review of 50 ranibizumab injections from 23 patients. IOP was recorded using Goldmann applanation tonometry. All patients included in this series received ranibizumab injection as directed by the instructions provided in the package insert (volume …

Optical coherence tomography in Susac's syndrome

Susacs syndrome is an autoimmune endotheliopathy with predilection for brain, retina and cochlea (Susac, 1994). Optical coherence tomography (OCT) is a non-invasive method, which is increasingly used in the diagnosis of retinal as well as primary central nervous system diseases. OCT is suggested as a useful diagnostic tool in differentiating Susacs syndrome from multiple sclerosis (MS) (Brandt et al., 2012). This report demonstrates the OCT findings in 3 patients with Susacs syndrome in different stages of the disease. The OCT demonstrated decreased retinal nerve fiber layer (RNFL) thickness, which was patchy in nature and more prominent in the nasal quadrants. We also observed loss of the normal foveal contour, which is uncharacteristic for MS. The extent and degree of the OCT abnormalities in our patients correlated with the stage and severity of the disease and correlated with the findings on the visual field studies. We confirm that OCT is a useful diagnostic tool in Susacs syndrome and helps to differentiate it from MS. Furthermore, OCT may be a non-invasive alternative to fluorescein angiography in longitudinal follow up of these patients.