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Novel Finding of Retinal Aneurysmal Alterations in Patients Undergoing Fingolimod Therapy for Multiple Sclerosis

Feliciana Menna,Lucilla Barbano,Carmen Dell’Aquila,Mattia D’Andrea,V. Parisi,L. Ziccardi

Published 2025 in Neurological Therapeutics

ABSTRACT

Fingolimod (Gilenya®), commonly used for relapsing-remitting multiple sclerosis (RRMS), is the first approved oral immunomodulatory agent. While its primary mechanism involves lymphocyte sequestration in lymphoid tissues, emerging studies report a potential link between fingolimod therapy and retinal vascular complications such as central serous chorioretinopathy and macular oedema. This study aims to describe the novel evidence on retinal aneurysmal alterations in patients receiving fingolimod, exploring possible mechanisms and clinical implications. Case series of five eyes of five patients with retinal aneurysmal alterations and in therapy with fingolimod for multiple sclerosis. Multimodal imaging scans and medical records of patients on fingolimod therapy were reviewed. Outcome measures included best-corrected visual acuity (BCVA), central subfield thickness (CST) on spectral-domain optical coherence tomography (SD-OCT), presence of retinal aneurysmal alterations and analysis of their change in appearance over time using OCT angiography (OCTA). Findings indicate a possible association between fingolimod therapy and unilateral retinal aneurysmal changes in certain patients. The proposed mechanisms include endothelial retinal dysfunction, altered retinal vascular permeability and immune modulation effects. The clinical significance of these changes remains uncertain, necessitating further investigation. Fingolimod may contribute to unilateral retinal aneurysmal vascular changes in a subset of patients. Clinicians should remain vigilant for potential retinal vascular complications, and further research is needed to clarify the underlying mechanisms, the evolution and the long-term risks associated with fingolimod therapy. Notably, in the reported cases, the retinal aneurysmal alterations showed regression following the discontinuation of fingolimod, suggesting a potential reversibility of these changes upon cessation of treatment.

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