Fingolimod (Gilenya) is an oral immunosuppressant approved for the treatment of relapsing forms of multiple sclerosis. In clinical trials, macular edema (ME) was found to be a dose-dependent adverse effect, occurring in 0.4% to 1% of patients.1 Most cases develop within 3 to 4 months of initiation and improve or resolve with discontinuation of treatment.1-3 We describe a 58-year-old woman with bilateral fingolimod-associated ME (FAME) who was adamant that her medication be continued. We treated her successfully in both eyes with sub-Tenon triamcinolone acetonide injection without discontinuing fingolimod. Report of a Case A 58-year-old woman with a long-standing history of relapsing and remitting multiple sclerosis presented 2 months after switching from natalizumab infusions to oral fingolimod. Her chief concern at presentation was difficulty reading. Her ocular history included bilateral intermediate uveitis with associated posterior subcapsular lens opacities. Best-corrected visual acuity was 6/15 OD and 6/18 OS. Intraocular pressure (IOP) was 14 mm Hg OU. The anterior segment and anterior vitreous were unremarkable. Posterior segment examination revealed cystoid ME (CME) bilaterally with no other signs of inflammation. Optical coherence tomography and intravenous fluorescein angiography confirmed the presence of CME (Figure 1). The central subfield thickness was 506 μm OD and 282 μm OS. View LargeDownload Figure 1. Optical coherence tomographic images of the right (A) and left (B) eyes show cystoid macular edema. I indicates inferior; N, nasal; S, superior; and T, temporal. Intravenous fluorescein angiograms of the right (C) and left (D) eyes show bilateral foveal leakage in a petaloid pattern characteristic of cystoid macular edema. Because of the patient's insistence on continuing fingolimod, we offered her treatment with sub-Tenon triamcinolone injection. The right eye was initially treated with topical prednisolone acetate, 1%, and ketorolac tromethamine for 1 month to assess for steroid-induced IOP elevation. At follow-up, the central subfield thickness improved to 394 μm OD, while the untreated left eye worsened to 388 μm. With no steroid-induced IOP change, we proceeded with sub-Tenon injection of 40 mg of triamcinolone acetonide in her right eye. One month later, optical coherence tomography revealed complete resolution of CME in her right eye (Figure 2). We thus proceeded with the same treatment in her left eye. Follow-up optical coherence tomography 1 month later revealed complete resolution of CME in the left eye and no recurrence in the right eye. She achieved best-corrected visual acuity of 6/9 OU. Despite our prednisolone trial, acute intraocular hypertension developed, with a maximum IOP of 50 mm Hg OD and 28 mm Hg OS. The right eye required 360° selective laser trabeculoplasty, while the left eye responded to topical antiglaucoma therapy. The patient is continuing fingolimod treatment and was free of CME for 7 months before recurrence. View LargeDownload Figure 2. Optical coherence tomographic images of the right (A) and left (B) eyes show complete resolution of fingolimod-associated macular edema with sub-Tenon triamcinolone acetonide injection and continued use of fingolimod. I indicates inferior; N, nasal; S, superior; and T, temporal. Comment Fingolimod is a structural analogue of sphingosine-1-phosphate (S1P), a lysophospholipid that plays a key role in T-lymphocyte trafficking. When the active metabolite of fingolimod binds to the S1P receptor on the T-lymphocyte surface, the receptor is internalized and degraded. Because these T lymphocytes can no longer respond to S1P signaling, they remain sequestered in lymph nodes and cannot participate in the central nervous system autoimmune destruction that characterizes multiple sclerosis.1,4 The mechanism of FAME is believed to be related to an alternate function of the S1P receptor—promoting endothelial integrity.1 The S1P acts on the cytoskeleton and intercellular junctions of endothelial cells to enhance barrier function, and degradation of the receptor may lead to increased vascular permeability.1,5,6 Stabilization of the blood-retinal barrier by triamcinolone is the general proposed mechanism of effect in our case. It allowed continued use of fingolimod in our patient and may be an alternative to discontinuation in similar cases. The risk of elevated IOP is significant and must be discussed. Patients taking fingolimod should be screened at baseline and reassessed every 3 to 6 months for FAME.1,4 Those who develop FAME should discuss the risks and benefits of continued use of fingolimod with their neurologist and ophthalmologist. Back to top Article Information Correspondence: Dr Belliveau, Department of Ophthalmology, Hotel Dieu Hospital, 166 Brock St, Kingston, ON K7L 5G2, Canada (firstname.lastname@example.org). Published Online: April 18, 2013. doi:10.1001/jamaophthalmol.2013.2465 Conflict of Interest Disclosures: None reported. References 1. Jain N, Bhatti MT. Fingolimod-associated macular edema: incidence, detection, and management. Neurology. 2012;78(9):672-68022371414PubMedGoogle ScholarCrossref 2. Saab G, Almony A, Blinder KJ, Schuessler R, Brennan DC. Reversible cystoid macular edema secondary to fingolimod in a renal transplant recipient. Arch Ophthalmol. 2008;126(1):140-14118195237PubMedGoogle ScholarCrossref 3. Turaka K, Bryan JS. Does fingolimod in multiple sclerosis patients cause macular edema? J Neurol. 2012;259(2):386-38822231867PubMedGoogle ScholarCrossref 4. Cohen JA, Chun J. Mechanisms of fingolimod's efficacy and adverse effects in multiple sclerosis. Ann Neurol. 2011;69(5):759-77721520239PubMedGoogle ScholarCrossref 5. Wang L, Dudek SM. Regulation of vascular permeability by sphingosine 1-phosphate. Microvasc Res. 2009;77(1):39-4518973762PubMedGoogle ScholarCrossref 6. Dudek SM, Jacobson JR, Chiang ET, et al. Pulmonary endothelial cell barrier enhancement by sphingosine 1-phosphate: roles for cortactin and myosin light chain kinase. J Biol Chem. 2004;279(23):24692-2470015056655PubMedGoogle ScholarCrossref
JAMA Ophthalmology – American Medical Association
Published: Jun 1, 2013
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