Central Serous Chorioretinopathy Associated With Fingolimod Treatment

Clinical Correspondence Central Serous Chorioretinopathy Associated With Fingolimod Treatment Karima S. Khimani, BS, Rod Foroozan, MD F ingolimod is the first oral drug approved by the Food and Drug Administration for the treatment of multiple sclerosis (MS) and is indicated in patients with highly active relapsing-remitting MS (1). Treatment with fingolimod has been associated with macular edema that is known to take on a cystoid appearance (2). We describe a patient who developed central serous chorioretinopathy associated with fingolimod. We are unaware of similar reports of this adverse effect of fingolimod treatment. A 34-year-old man with a history of MS noted blurry vision in his right eye for 1 week. He had been treated with fingolimod 0.5 mg once daily for the past 18 months. He had no previous history of ocular problems and was not taking any concurrent medications. Six months before beginning fingolimod, the patient's visual acuity was 20/20 bilaterally with normal slit-lamp and fundus examinations. Optical coherence tomography (OCT) of each macula was unremarkable (Fig. 1A). At the time of presentation, visual acuity was 20/200 in the right eye and 20/25 in the left eye. OCT showed subretinal fluid below the right macula (Fig. 1B). The patient was advised to discontinue fingolimod. Two weeks later, acuity in the right eye had improved to 20/20 with a decrease in the subretinal fluid (Fig. 1C) and by 3 months, the fluid had completely resolved (Fig. 1D). The patient's vision remained stable over the next year, and he was restarted on fingolimod. He returned 2 months later complaining of "darker vision" in his right eye, although his acuity was 20/20. OCT showed recurrence of subretinal fluid in the right eye (Fig. 2A), and the medication was discontinued. By 5 weeks, there was improvement in the subretinal fluid (Fig. 2B) and by 5 months, the subretinal fluid had nearly completely resolved but there was slight retinal wrinkling (Fig. 2C). Visual acuity stabilized at Baylor College of Medicine, Houston, Texas. The authors report no conflicts of interest. Address correspondence to Rod Foroozan, MD, Baylor College of Medicine, 1977 Butler Boulevard, Houston, TX 77030; E-mail: [e-mail] Khimani and Foroozan: J Neuro-Ophthalmol 2018; 38: 337-338 20/20, and the patient was prescribed dimethyl fumarate. Fingolimod is a structural analog of sphingosine1-phosphate (S1P) and acts as an antagonist to the S1P receptors on endothelial cells that regulate vascular permeability (2). The resulting endothelial damage is believed to cause an accumulation of intraretinal fluid in the inner nuclear and outer plexiform layers around the fovea, designated as fingolimod-associated macular edema (FAME). FAME typically begins within the first 3-4 months of initiating fingolimod treatment. Patients complain of loss of central vision, and symptoms tend to resolve with cessation of the drug (2). Our patient's maculopathy differed from FAME in that it showed subretinal fluid with a central serous-type appearance and absence of cystic intraretinal changes. Although the pathophysiologic mechanism of central serous chorioretinopathy (CSR) is unknown, it is believed to be the result of a dysfunctional retinal pigment epithelium or a hyperpermeable choriocapillaries (3). S1P is a signaling lipid circulating in the plasma and mediates the activation of 5 high-affinity G-protein coupled receptors (S1P; S1Ps) found on endothelial cells (4). The stimulation of S1P receptors, in response to an S1P gradient, promotes the organization and redistribution of vascular endothelial cadherin and ß-catenin in the cytoskeletal and junctional complexes of the endothelium (4). Thus, S1P maintains capillary integrity and has been associated with vascular maturation. S1P antagonists such as fingolimod disrupt the barrier integrity of the endothelium in a dosedependent manner, resulting in edema. Typically, in CSR, the subretinal fluid resolves spontaneously within 2-3 months (4,5). Failing this, treatment options include photodynamic therapy, intravitreal injection of vascular endothelial growth factor inhibitors, and laser photocoagulation (5). We are unaware of previous reports of CSR being associated with fingolimod use. The timing of onset of symptoms and the resolution of the maculopathy after discontinuation of fingolimod as seen on challenge- dechallenge-rechallenge, strongly suggest that the medication caused the subretinal fluid. Alternatively, if our patient had idiopathic CSR, perhaps fingolimod helped precipitate it. 337 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 2. Optical coherence tomography of the right macula 2 months following re-starting fingolimod (A) and 5 weeks (B) and 5 months (C) after discontinuing the medication. REFERENCES FIG. 1. Optical coherence tomography of the right macula 6 months before fingolimod use (A), at presentation (B), and 2 weeks (C) and 3 months (D) after stopping the drug. 338 1. Cohen JA, Barkhof F, Comi G. Hartung HP, Khatri BO, Montalban X, Pelletier J, Capra R, Gallo P, Izquierdo G, Tiel-Wilck K, de Vera A, Jin J, Stites T, Wu S, Aradhys S, Kappos L; TRANSFORMS Study Group. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med. 2010;362:402-415. 2. Zarbin MA, Jampol LM, Jager RD, Reder AT, Francis G, Collins W, Tang D, Zhang X. Ophthalmic evaluations in clinical studies of fingolimod (FTY720) in multiple sclerosis. Ophthalmology. 2013;120:1432-1439. 3. 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