Diagnosis and Management of Fingolimod-Associated Macular Edema

Abstract

ObjectiveTo investigate the clinical features, treatment, and prognosis of fingolimod-associated macular edema (FAME) and to provide a reference for its rational management.MethodsFAME-related case reports were included in a pooled analysis by searching Chinese and English databases from 2010 to November 31, 2021.ResultsThe median age of 41 patients was 50 years (range, 21, 67 years), of whom 32 were women. The median time to onset of FAME was 3 m (range.03, 120), and blurred vision (17 cases) and decreased vision (13 cases) were the most common complaints. A total of 55 eyes were involved in FAME, including the left eye (14 cases), right eye (10 cases), and both eyes (15 cases), of which 46 eyes had best-corrected visual acuity close to normal (20/12-20/60) and 8 eyes had moderate to severe visual impairment (20/80-20/500). Fundus examination in 23 patients showed macular edema (11 cases). Optical coherence tomography (OCT) in 39 patients mainly showed perifoveal cysts (24 cases), ME (23 cases), and foveal thickening (19 cases). Fundus fluorescein angiography (FFA) in 18 patients showed vascular leakage (11 cases). Complete resolution of ME occurred in 50 eyes and recovery of visual acuity occurred in 45 eyes at a median time of 2 m (range 0.25, 24) after discontinuation of fingolimod or administration of topical therapy.ConclusionsMacular edema is a known complication of fingolimod. All patients using fingolimod require regular eye exams, especially those with a history of diabetes and uveitis and those undergoing cataract surgery.

Ponesimod-Associated Macular Edema: Onset and Resolution

“…Previous studies of FAME, which is physiologically similar to PAME, have shown prompt resolution after sub-Tenon corticosteroid injection, a treatment that can be considered in the setting of refractory or difficult-to-treat macular edema. 6,8 An alternate approach to treating our asymptomatic patient could have been to closely monitor her while continuing the ponesimod. An intervention could have then been made with topical medication, a sub-Tenon corticosteroid, and/or cessation of ponesimod if the PAME worsened or she developed visual symptoms.…”

“…Patients beginning ponesimod therapy should receive a pretreatment ophthalmic evaluation, including macular OCT scans as well as regular monitoring during the treatment course-a suggestion maintained by the US Food and Drug Administration for the less S1P 1 R-selective fingolimod and recommended by Janssen's ponesimod prescribing information. 8,11 Patients should further be informed that any painless vision loss during treatment requires urgent evaluation by their ophthalmologist. If macular edema is noted, transitioning patients from ponesimod treatment and starting supportive topical therapy with corticosteroids and NSAIDs is an effective PAME management algorithm.…”

“…Fingolimod, an S1P analogue, exerts a lymphocytic-trafficking blockade through an S1PR agonism. 8 Physiologically, S1P forms a concentration gradient used by immune cells in localizing to inflammation sites. 10 S1P analogues flood the existing gradient, resulting in lymphocytic cell stasis, and minimize inflammation, thereby aiding in symptomatic resolution.…”

“…Older S1P structural analogues, namely fingolimod, have similarly been implicated in ophthalmological pathologies, termed fingolimod-associated macular edema (FAME). [6][7][8] Fortunately, FAME occurs in only approximately 0.5% of patients and typically resolves after medication cessation. We report a case of macular edema in a patient with RRMS being treated with ponesimod.…”

Siponimod-Related Bilateral Macular Edema: A Transient and Completely Reversible Disorder

“…The iBRB, which regulates the movement of solutes from the retinal vasculature to the neuroretina, is composed of tight junctions located between retinal vascular endothelial cells, regulated by perivascular astrocytes, pericytes, and Müller cells. S1PR 1 was found highly expressed in endothelial cells and it is believed to play a role in the correct functioning of the intercellular tight junctions (4,5). Thus, siponimod may modulate S1PR1 on endothelial cells, resulting in the internalization of the receptors, transient dysfunction of the iBRB and impairment of retinal hydric homeostasis leading to intraretinal edema and foveal detachment.…”