528759
research-article2015
MSJ0010.1177/1352458514528759Multiple Sclerosis JournalS Thoo, S Cugati
MULTIPLE SCLEROSIS MSJ JOURNAL
Case Report
Successful treatment of fingolimod-associated macular edema with intravitreal triamcinolone with continued fingolimod use
Multiple Sclerosis Journal 2015, Vol. 21(2) 249–251 DOI: 10.1177/ 1352458514528759 © The Author(s), 2015. Reprints and permissions: http://www.sagepub.co.uk/ journalsPermissions.nav
Sophie Thoo, Sudha Cugati, Andrew Lee and Celia Chen
Abstract: The occurrence of macular edema as an adverse effect of fingolimod is well documented. Treatment modalities used to manage fingolimod-associated macular edema (FAME) have included nonsteroidal anti-inflammatory agents and sub-tenon injection. We describe two cases where intravitreal injection is used to successfully treat FAME in patients who were previously unsuccessfully treated with topical nonsteroidal anti-inflammatories.
Keywords: Fingolimod, multiple sclerosis, edema, steroid Date received: 1 October 2013; revised: 4 January 2014; accepted: 24 February 2014
Introduction Fingolimod, a sphingosine 1-phosphate (S1P) receptor modulator, is the first oral medication to receive Federal Drug Administration approval for treatment of relapse–remitting multiple sclerosis (MS).1–3 While fingolimod, by virtue of being an oral as opposed to an injectable agent, has the advantage of patient comfort and ease of administration, nevertheless potential serious adverse events such as bradycardia and macular edema may limit its use. The incidence of fingolimod-associated macular edema (FAME) is three per 1000 and is usually seen within three months of fingolimod administation.3 Cessation of fingolimod results in resolution of the macular oedema. In those who elect to continue the medication, the macular edema is treatable.4–7 We describe two cases of FAME that were successfully treated with intravitreal triamcinolone. Case 1 A 59-year-old woman was diagnosed with MS in 2012 following an episode of left sensory symptoms. Her Expanded Disability Status Scale (EDSS) was 2 and she was commenced on fingolimod 0.5 mg/day as her first immunomodulator. She had no other significant past medical or ophthalmic history. Her baseline eye examination was normal with unaided vision of 6/6 OD and 6/7.5 OS and normal macula confirmed
on ocular coherence tomography (OCT) (Figures 1A and B). Three weeks after starting the medication she noted bilateral central blurring of vision. Vision was reduced to 6/15 in the right and 6/12 in the left and OCT confirmed bilateral macular edema (Figures 1C and D). The patient wished to continue on fingolimod due to personal preference. Her macular edema (ME) was initially treated with topical steroid eye prednefrine forte drops QID OU for two weeks with no change to vision and persistent ME seen clinically and on OCT. She was then treated with 0.1 ml intravitreal triamcinolone 40 mg/ml. She noted subjective improvement in vision from one week, and at one month after treatment her vision had returned to 6/6 OD and 6/7.5 OS. OCT confirmed resolution of her macular edema (see Figures 1E and F). Her vision remained the same and her OCT was normal at a subsequent review 12 months after the treatment for FAME.
Correspondence to: Celia Chen Department of Ophthalmology, Flinders Medical Centre and Flinders University, Flinders Drive, Bedford Park, SA 5042 Australia. [email protected] Sophie Thoo Sudha Cugati Department of Ophthalmology and the Division of Medicine, Flinders University, Australia Andrew Lee Flinders Medical Centre and Flinders University, Australia
Case 2 A 66-year-old woman had stable relapsing–remitting multiple sclerosis diagnosed in 2000. She was immunomodulator-naïve till she developed a relapse with left hemisensory deficits in 2011. She was started on interferon beta-1b then and was symptomfree for five months when she developed a left optic neuritis. She was then switched to oral fingolimod
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Multiple Sclerosis Journal 21(2)
Figure 1. Optical coherence tomographic images showing initially normal macular appearance (A, B), macular edema which developed after fingolimod treatment (C, D) and resolution after intravitreal injection with triamcinolone (E, F).
0.5 mg/day in August 2011. She remained symptomfree for one year with normal sequential eye examinations. She had no diabetes and no other ophthalmic history other than the optic neuritis. She developed a cataract in the right eye in August 2012 and underwent a cataract extraction with intraocular lens implantation. Her post-operative unaided visual acuity (VA) was 6/6 on Day 1 post-op. Four days later she noted a decline in her vision with distortion. Her VA reduced to 6/12 OD and an OCT confirmed ME. Standard topical nonsteroidal anti inflammatory Acular eyedrops combined with prednefrine forte drops failed to resolve the ME at one month. Intravitreal triamcinolone 2 mg/0.05 ml was administered to the right eye and within one week the ME had settled and the vision improved to 6/7.5. She continued on fingolimod. Her vision maintained at the same level with normal macula OCT at the last review in November 2013, 14 months after the FAME treatment.
Discussion The current accepted treatment for FAME is ceasing fingolimod.2,3,5 These two cases presented demonstrate that FAME can be successfully treated with intravitreal triamcinolone and may be preferable to ceasing fingolimod in some patients. Although FAME is accepted as an adverse event, there have been reports of increases in the total macular volume in fingolimod-treated MS patients compared to untreated controls.8 This may imply that fingolimod has neuroprotectant qualities or, alternatively and more likely, there may be a subclinical phase of macular edema that in only some individuals, progresses to full-blown macular edema.9 Confounding the matter further is the observation that macular edema can occur in MS independent of fingolimod use and may be associated with disruption of the blood retinal barrier due to a more active disease.10 Therefore the appearance of FAME may reflect
250 http://msj.sagepub.com
Downloaded from msj.sagepub.com at NORTH CAROLINA STATE UNIV on April 15, 2015
S Thoo, S Cugati et al. disease activity and not necessarily be primarily due to fingolimod use alone. Clearly more work in this area needs to be done.
References
Other treatment options for FAME that are described include topical nonsteroidal anti-inflammatories and sub-tenon injection.6,11 Afshar et al. demonstrated that topical anti-inflammatories may hasten resolution of FAME. However in three of four eyes, the cessation of fingolimod was a confounding factor.11 Minuk et al. described a case of where sub-tenon injection of triamcinolone was successfully used to treat FAME.6 As there has only been one case reported, this treatment modality will need to be investigated further.
2. Cohen JA, Barkhof F, Comi G, et al. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. 2010; 362(5): 402–4015.
The patients described in this series were unresponsive to topical anti-inflammatories while continued on fingolimod suggesting that intravitreal injection may be a suitable treatment option for patients with FAME refractory to topical treatment. Treatment with intravitreal injection confers high risk of elevated intraocular pressure and cataract formation.12 This should be discussed with patients and patients will require ongoing monitoring. To our knowledge, this is the first report of intravitreal injection to treat FAME. Our series illustrates that intravitreal traimcinolone injection may be a suitable treatment option in patients who wish to continue taking fingolimod, and in whom topical anti-inflammatory treatment has been unsuccessful.
1. Yeh EA and Weinstock-Guttman B. Fingolimod: An oral disease-modifying therapy for relapsing multiple sclerosis. Adv Ther 2011; 28(4): 270–278.
3. Kappos L, Radue EW, O’Connor P, et al. A placebocontrolled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med 2010; 362(5): 387–401. 4. Chui J, Herkes GK, Chang A. Management of fingolimod-associated macular edema. JAMA 2013; 131(5): 694–696. 5. Jain N and Bhatti MT. Fingolimod-associated macular edema: Incidence, detection, and management. Neurology 2012; 78(9): 672–680. 6. Minuk A, Belliveau MJ, Almeida DR, et al. Fingolimod-associated macular edema: Resolution by sub-tenon injection of triamcinolone with continued fingolimod use. JAMA 2013; 131(6): 802–804. 7. Cugati S, Lee AW, Lake S, et al. Fingolimod and macular edema – pathophysiology, diagnosis and management. Curr Opin Neurol 2013; (In Press). 8. Nolan R, Gelfand JM and Green AJ. Fingolimod treatment in multiple sclerosis leads to increased macular volume. Neurology 2013; 80(2): 139–144. 9. Dinkin M and Paul F. Higher macular volume in patients with MS receiving fingolimod: Positive outcome or side effect? Neurology 2013; 80(2): 128–129. 10. Gelfand JM, Nolan R, Schwartz DM, et al. Microcystic macular oedema in multiple sclerosis is associated with disease severity. Brain 2012; 135(Pt 6): 1786–1793.
Conflict of interest None declared. Funding This research received no specific grant from any funding agency in the public, commercial, or not-forprofit sectors.
11. Afshar AR, Fernandes JK, Patel RD, et al. Cystoid macular edema associated with fingolimod use for multiple sclerosis. JAMA 2013; 131(1): 103–107. 12. Sampat KM and Garg S. Complications of intravitreal injection. Cur Opin Opthalmol 2010; 21(3): 178–183.
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research-article2015
MSJ0010.1177/1352458514528759Multiple Sclerosis JournalS Thoo, S Cugati
MULTIPLE SCLEROSIS MSJ JOURNAL
Case Report
Successful treatment of fingolimod-associated macular edema with intravitreal triamcinolone with continued fingolimod use
Multiple Sclerosis Journal 2015, Vol. 21(2) 249–251 DOI: 10.1177/ 1352458514528759 © The Author(s), 2015. Reprints and permissions: http://www.sagepub.co.uk/ journalsPermissions.nav
Sophie Thoo, Sudha Cugati, Andrew Lee and Celia Chen
Abstract: The occurrence of macular edema as an adverse effect of fingolimod is well documented. Treatment modalities used to manage fingolimod-associated macular edema (FAME) have included nonsteroidal anti-inflammatory agents and sub-tenon injection. We describe two cases where intravitreal injection is used to successfully treat FAME in patients who were previously unsuccessfully treated with topical nonsteroidal anti-inflammatories.
Keywords: Fingolimod, multiple sclerosis, edema, steroid Date received: 1 October 2013; revised: 4 January 2014; accepted: 24 February 2014
Introduction Fingolimod, a sphingosine 1-phosphate (S1P) receptor modulator, is the first oral medication to receive Federal Drug Administration approval for treatment of relapse–remitting multiple sclerosis (MS).1–3 While fingolimod, by virtue of being an oral as opposed to an injectable agent, has the advantage of patient comfort and ease of administration, nevertheless potential serious adverse events such as bradycardia and macular edema may limit its use. The incidence of fingolimod-associated macular edema (FAME) is three per 1000 and is usually seen within three months of fingolimod administation.3 Cessation of fingolimod results in resolution of the macular oedema. In those who elect to continue the medication, the macular edema is treatable.4–7 We describe two cases of FAME that were successfully treated with intravitreal triamcinolone. Case 1 A 59-year-old woman was diagnosed with MS in 2012 following an episode of left sensory symptoms. Her Expanded Disability Status Scale (EDSS) was 2 and she was commenced on fingolimod 0.5 mg/day as her first immunomodulator. She had no other significant past medical or ophthalmic history. Her baseline eye examination was normal with unaided vision of 6/6 OD and 6/7.5 OS and normal macula confirmed
on ocular coherence tomography (OCT) (Figures 1A and B). Three weeks after starting the medication she noted bilateral central blurring of vision. Vision was reduced to 6/15 in the right and 6/12 in the left and OCT confirmed bilateral macular edema (Figures 1C and D). The patient wished to continue on fingolimod due to personal preference. Her macular edema (ME) was initially treated with topical steroid eye prednefrine forte drops QID OU for two weeks with no change to vision and persistent ME seen clinically and on OCT. She was then treated with 0.1 ml intravitreal triamcinolone 40 mg/ml. She noted subjective improvement in vision from one week, and at one month after treatment her vision had returned to 6/6 OD and 6/7.5 OS. OCT confirmed resolution of her macular edema (see Figures 1E and F). Her vision remained the same and her OCT was normal at a subsequent review 12 months after the treatment for FAME.
Correspondence to: Celia Chen Department of Ophthalmology, Flinders Medical Centre and Flinders University, Flinders Drive, Bedford Park, SA 5042 Australia. [email protected] Sophie Thoo Sudha Cugati Department of Ophthalmology and the Division of Medicine, Flinders University, Australia Andrew Lee Flinders Medical Centre and Flinders University, Australia
Case 2 A 66-year-old woman had stable relapsing–remitting multiple sclerosis diagnosed in 2000. She was immunomodulator-naïve till she developed a relapse with left hemisensory deficits in 2011. She was started on interferon beta-1b then and was symptomfree for five months when she developed a left optic neuritis. She was then switched to oral fingolimod
http://msj.sagepub.com 249
Downloaded from msj.sagepub.com at NORTH CAROLINA STATE UNIV on April 15, 2015
Multiple Sclerosis Journal 21(2)
Figure 1. Optical coherence tomographic images showing initially normal macular appearance (A, B), macular edema which developed after fingolimod treatment (C, D) and resolution after intravitreal injection with triamcinolone (E, F).
0.5 mg/day in August 2011. She remained symptomfree for one year with normal sequential eye examinations. She had no diabetes and no other ophthalmic history other than the optic neuritis. She developed a cataract in the right eye in August 2012 and underwent a cataract extraction with intraocular lens implantation. Her post-operative unaided visual acuity (VA) was 6/6 on Day 1 post-op. Four days later she noted a decline in her vision with distortion. Her VA reduced to 6/12 OD and an OCT confirmed ME. Standard topical nonsteroidal anti inflammatory Acular eyedrops combined with prednefrine forte drops failed to resolve the ME at one month. Intravitreal triamcinolone 2 mg/0.05 ml was administered to the right eye and within one week the ME had settled and the vision improved to 6/7.5. She continued on fingolimod. Her vision maintained at the same level with normal macula OCT at the last review in November 2013, 14 months after the FAME treatment.
Discussion The current accepted treatment for FAME is ceasing fingolimod.2,3,5 These two cases presented demonstrate that FAME can be successfully treated with intravitreal triamcinolone and may be preferable to ceasing fingolimod in some patients. Although FAME is accepted as an adverse event, there have been reports of increases in the total macular volume in fingolimod-treated MS patients compared to untreated controls.8 This may imply that fingolimod has neuroprotectant qualities or, alternatively and more likely, there may be a subclinical phase of macular edema that in only some individuals, progresses to full-blown macular edema.9 Confounding the matter further is the observation that macular edema can occur in MS independent of fingolimod use and may be associated with disruption of the blood retinal barrier due to a more active disease.10 Therefore the appearance of FAME may reflect
250 http://msj.sagepub.com
Downloaded from msj.sagepub.com at NORTH CAROLINA STATE UNIV on April 15, 2015
S Thoo, S Cugati et al. disease activity and not necessarily be primarily due to fingolimod use alone. Clearly more work in this area needs to be done.
References
Other treatment options for FAME that are described include topical nonsteroidal anti-inflammatories and sub-tenon injection.6,11 Afshar et al. demonstrated that topical anti-inflammatories may hasten resolution of FAME. However in three of four eyes, the cessation of fingolimod was a confounding factor.11 Minuk et al. described a case of where sub-tenon injection of triamcinolone was successfully used to treat FAME.6 As there has only been one case reported, this treatment modality will need to be investigated further.
2. Cohen JA, Barkhof F, Comi G, et al. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. 2010; 362(5): 402–4015.
The patients described in this series were unresponsive to topical anti-inflammatories while continued on fingolimod suggesting that intravitreal injection may be a suitable treatment option for patients with FAME refractory to topical treatment. Treatment with intravitreal injection confers high risk of elevated intraocular pressure and cataract formation.12 This should be discussed with patients and patients will require ongoing monitoring. To our knowledge, this is the first report of intravitreal injection to treat FAME. Our series illustrates that intravitreal traimcinolone injection may be a suitable treatment option in patients who wish to continue taking fingolimod, and in whom topical anti-inflammatory treatment has been unsuccessful.
1. Yeh EA and Weinstock-Guttman B. Fingolimod: An oral disease-modifying therapy for relapsing multiple sclerosis. Adv Ther 2011; 28(4): 270–278.
3. Kappos L, Radue EW, O’Connor P, et al. A placebocontrolled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med 2010; 362(5): 387–401. 4. Chui J, Herkes GK, Chang A. Management of fingolimod-associated macular edema. JAMA 2013; 131(5): 694–696. 5. Jain N and Bhatti MT. Fingolimod-associated macular edema: Incidence, detection, and management. Neurology 2012; 78(9): 672–680. 6. Minuk A, Belliveau MJ, Almeida DR, et al. Fingolimod-associated macular edema: Resolution by sub-tenon injection of triamcinolone with continued fingolimod use. JAMA 2013; 131(6): 802–804. 7. Cugati S, Lee AW, Lake S, et al. Fingolimod and macular edema – pathophysiology, diagnosis and management. Curr Opin Neurol 2013; (In Press). 8. Nolan R, Gelfand JM and Green AJ. Fingolimod treatment in multiple sclerosis leads to increased macular volume. Neurology 2013; 80(2): 139–144. 9. Dinkin M and Paul F. Higher macular volume in patients with MS receiving fingolimod: Positive outcome or side effect? Neurology 2013; 80(2): 128–129. 10. Gelfand JM, Nolan R, Schwartz DM, et al. Microcystic macular oedema in multiple sclerosis is associated with disease severity. Brain 2012; 135(Pt 6): 1786–1793.
Conflict of interest None declared. Funding This research received no specific grant from any funding agency in the public, commercial, or not-forprofit sectors.
11. Afshar AR, Fernandes JK, Patel RD, et al. Cystoid macular edema associated with fingolimod use for multiple sclerosis. JAMA 2013; 131(1): 103–107. 12. Sampat KM and Garg S. Complications of intravitreal injection. Cur Opin Opthalmol 2010; 21(3): 178–183.
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