Fingolimod-Associated Macular Edema in the Treatment of Multiple Sclerosis

Abstract

Multiple sclerosis is a neurological disorder categorized by inflammatory processes with a high prevalence worldwide. It affects both motor and sensory pathways and is also associated with the visual pathway. Fingolimod is a commonly used drug for relapsing-remitting multiple sclerosis. It is a sphingosine 1-phosphate modulator acting on its receptors for immune cell accumulation, neuronal function, embryological development, vascular permeability, smooth muscle cell function, and endothelial barrier maintenance. This review aims to understand the processes, mechanisms, risks, and management of fingolimod-associated macular edema. Due to the anti-inflammatory properties of fingolimod, it decreases various cytokines, including interleukin (IL)-1B and IL-6, spike wave, and spike amplitude, in electrophysiological activities and decreases insoluble receptors for advanced glycation end product ligand. A daily dosage of 0.5 mg of fingolimod has an increased association with macular edema. The serious adverse events of fingolimod are lymphopenia, cardiovascular events, ocular events, and carcinoma. Fingolimod decreases brain volume and increases vascular permeability, resulting in increased macular volume and damage to the blood-retinal barrier, which causes an increased risk for macular edema. Cystoid macular edema is more common in older individuals suffering from comorbidities affecting the retina, such as diabetes, or those undergoing ophthalmological surgeries. This review also highlights the importance of regular ophthalmology examinations on patients consuming fingolimod both in the initial stages and chronic use. The treatment options for macular edema include nonsteroidal anti-inflammatory drugs, acetazolamide, triamcinolone, ketorolac, corticosteroids, and intravitreal procedures.

Potential adverse events associated with sphingosine-1-phosphate (S1P) receptor modulators in patients with multiple sclerosis: an analysis of the FDA adverse event reporting system (FAERS) database

“…According to our analysis, the most common serious adverse events (SAEs) caused by all the S1PR modulators were associated with ocular events, which was consistent with previous safety data ( Khan et al, 2023 ; Li et al, 2023 ). Among the related IMEs, macular oedema was reported frequently.…”

“…Nearly all the approved MS disease-modifying therapies have demonstrated a treatment effect on brain atrophy, which could result in an increase in retinal volume. Additionally, macular edema is also associated with the fingolimod modulation of S1PRs on the action of tight junctions of the blood-brain barrier and neurons ( Khan et al, 2023 ). Coppes et al reported a patient clinically presented with bilateral blurred central vision, painless, and no eye pain with eye movement after 10 days of fingolimod treatment ( Coppes, Gutierrez, Reder, Ksiazek & Bernard, 2013 ).…”

Current and Emerging Treatment Options in Pediatric Onset Multiple Sclerosis

“…INFβ and glatiramer acetate have favourable safety profiles in the pediatric population, as no malignancies or life-threatening events were reported [45][46][47][48][49]63]. On the other hand, newer DMTs have a reported risk for malignancies and serious adverse effects, such as hepatotoxicity or life-threatening PML [51,77,83,85,94,95,106,[143][144][145]. The daily need for subcutaneous drug administration for INFβ and glatiramer acetate is particularly distressing in both the pediatric and adolescent population and could lead to poor treatment compliance.…”

“…It is believed that leukopenia and lymphopenia, as a result of fingolimod's mechanism of action, increase infection risks [51]. Looking at the literature data of both POMS and AOMS treatment groups of fingolimod, several adverse effects are reported only in adults, such as melanoma, breast cancer, and macular edema [77].…”