Fingolimod: ocular adverse effects
Reviewed by Sofia Rokerya

In this article the authors review the ocular side-effects of Fingolimod which is an oral immunomodulating drug used in the management of relapsing-remitting multiple sclerosis (RRMS). Fingolimod-associated macular oedema (FAME) is the most common ocular side-effect linked to this drug. FREEDOMS and TRANSFORMS trials are two useful sources of information, although this side-effect has also been reported in the drug marketing literature. The pathophysiologic mechanism responsible for FAME is thought to be due to an increased permeability of the retinal vessels because of the effect of fingolimod on retinal sphingolipid receptors. In an analysis of literature case reports of 15 patients (24 eyes) with FAME, the majority were symptomatic; the most common presenting complaint being painless blurred vision. One patient had metamorphopsia and another patient was asymptomatic but actually had reduced vision of 6/18. Presenting vision was mildly reduced (20/30 or better) in eight of 24 eyes and moderately reduced (20/30–20/80) in the remainder (16 of 24 eyes). The worst visual acuity reported in an eye with FAME was 6/24 or, approximately, 20/80. Both the FREEDOMS and TRANSFORMS studies had parallel extension studies to assess the long-term effects of fingolimod therapy. These studies found no further increased risk of FAME over a period of up to 4.5 years. The visual consequences appear to be mild and, in cases of FAME, resolution is often attained with discontinuation of therapy. However, in cases of retinal vein occlusion, due to the drug therapy discontinuation of fingolimod alone may not be sufficient and intravitreal therapy may be required. The authors propose a pragmatic service pathway for monitoring patients on fingolimod therapy, which includes stratifying them by risk and visual acuity. If there is a past history of uveitis or diabetic retinopathy, patients could be screened before commencement of fingolimod to rule out active maculopathy, as the addition of fingolimod may exacerbate pre-existing disease. In those patients with a history of ocular comorbidities but no active disease, review in eye clinic within the most likely time window for the development of FAME (three to four months) is suggested. However, in those with no significant ophthalmic history, it is proposed that a baseline visual acuity measurement is performed by the physician prescribing fingolimod followed by a further visual acuity test and OCT three to four months later in a virtual eye clinic. In the unlikely event that a patient with FAME is asymptomatic, there will still be an opportunity for such a patient to be detected in this screening pathway at the second contact in the virtual eye clinic. As the risk of FAME is low after four months, screening beyond this time is probably unnecessary. However, as patients on fingolimod therapy, regardless of duration, who undergo intraocular surgery are at an increased risk of FAME, it is suggested that this cohort of patients have a routine OCT at the pre- and postoperative check.

Fingolimod: therapeutic mechanisms ocular adverse effects.
Mandal P, Gupta A, Fusi-Rubiano W, et al.
EYE
2017;31:232-40.