CASE REPORT
Retinopathy: An Overlooked Adverse Effect of Interferon-beta
Treatment of Multiple Sclerosis
Masayuki Ohira,1 Daisuke Ito,1 Toshihiko Shimizu,1 Mamoru Shibata,3 Hisao Ohde2 and Norihiro Suzuki1

Department of Neurology, and 2Ophthalmology, School of Medicine,
Keio University, Tokyo, Japan
3
National Hospital Organization Tokyo Medical Center, Tokyo, Japan
1(Received for publication on May 30, 2008)(Revised for publication on June 27, 2008)(Accepted for publication on September 18, 2008)

Abstract
Interferon (IFN), which is an established maintaining therapy for multiple sclerosis (MS),has been reported various adverse effects. This paper describes a case of IFN-associatedretinopathy, representing an overlooked adverse effect in MS. A 46-year-old woman with diabetes mellitus was diagnosed with MS and treated with IFNβ-1b for three years. She displayed sudden defect of the visual field and ocular fundi showed retinal cotton wool spots indicating IFN-retinopathy, which resolved rapidly after IFN was discontinued. To evaluate
the prevalence of retinopathy in MS, we performed fundoscopic examination on twenty MS
patients treated with IFNβ-1b in our hospital. However, none of the patients displayed retinopathy. Only four other cases of IFN- retinopathy in MS have been reported in the literature. Therefore, IFN-retinopathy may be uncommon in MS, but neurologist should be mindful of this adverse effect and regularly check the fundus, particularly in patients with possible risk factor, diabetes mellitus. (Keio J Med 58 (1) : 54－56, March 2009)

Keywords: multiple sclerosis, interferon, retinopathy, adverse effectIntroduction

4 times, with mild spastic paraparesis and sensory disturbance of the limbs. Subcutaneous IFNβ-1b was started ateight million units 3 times/week in June 2003. The patient also had diabetes mellitus and hypertension and had
been under medication with voglibose, amlodipine besilate and candesartan cilexetil since 2004. In May 2006,
she suddenly displayed defect of the visual field in theright eye. CSF examination and MRI did not reveal any
evidence of relapse, and ocular fundi showed several retinal cotton wool spots (Fig. 1a). As the retinal lesion wassuspected to represent IFN retinopathy, administration ofIFNβ-1b was suspended. Visual disturbance graduallyimproved and retinal lesions had disappeared by 5 weeks
after cessation of the drug (Fig. 1b). We thus concluded
that IFN was a cause of retinopathy in this patient. To
evaluate the prevalence of retinopathy in MS, we subsequently performed fundoscopic examination in all otherMS patients (N=20) treated with IFN at our hospital. All
patients (mean age, 43.0±13.0 years) were receiving

In multiple sclerosis (MS), many clinical trials havedemonstrated ameliorating effects of interferon (IFN) on
disease activity, and recombinant IFNβ is now the mainstay of maintenance therapy for MS in many countries.
To date, a variety of adverse effects of IFN use havebeen described, and flu-like symptoms, inflamed injection sites, and depression are widelyknown as frequent
adverse effects in MS.1
Herein we report a case of IFN-associated retinopathy
in a patient with MS receiving subcutaneous IFNβ-1btreatment and reviewed the clinical properties of this adverse effect in MS.
Case Report
A 46-year-old woman, who was diagnosed with relapsing-remitting MS in May 2003, had experienced relapse

Reprint request to: Daisuke Ito M.D. Ph.D., Department of Neurology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582,
Japan, Tel: +81-3-5363-3788, Fax:+81-3-3353-1272, E-mail: d-ito@jk9.so-net.ne.jp54Keio J Med 2009; 58 (1):54－56

Fig. 1 Fundoscopic examination. a) Ocular fundi show several
cotton spots in May 2006. b) Cotton spots have largely recoveredby 2 months after discontinuation of IFN in June 2006.

eight million units of IFNβ-1b three times/week. Mean
duration of disease was 100.7±104.4 months and mean
period of IFNβ-1b administration was 37.1±23.0 months.
In our study series, no other patients exhibited retinopathy.
Discussion
This is the first neurological report to describe clinicalfindings of retinopathy in an MS patient during IFN
treatment. Moreover, we also examined the frequency ofIFN retinopathy in MS in a retrospective hospital-basedanalysis. Ophthalmological complications related to IFN
administration were first described in 1990 by Ikebe etal. in Japan and, since the introduction of IFN therapy
for viral hepatitis, retinopathy has been identified as animportant adverse effect of IFN therapy for this disease.1
Incidence varies according to country and study design,with a high frequency of >50% reported in Japan,1 suggesting that patients should be carefully monitored byophthalmological assessment during treatment for viralhepatitis. Retinopathy reportedly develops between 2
weeks to 5 months after initiation of IFN therapy, andprevalence may depend on dosage of IFN received.
Signs of retinopathy are cotton-wool spots and associated ischemic signs, such as papilledema, retinal artery occlusion and retinal vein thrombosis.2 Risk factors remain
unclear. Many authors believe that diabetes mellitus is astrong risk factor, and arterial hypertension and old age
are also suspected as possible risk factors.1
Consensus is lacking regarding treatment for IFN reti-55

nopathy. As described in previous studies of viral hepatitis, most cases of IFN retinopathy are asymptomatic, andspontaneously improve over a period of several weeks,
despite continued full-dose IFN treatment.2 Continuing
IFN without reducing dosage is thus more often chosen
to avoid secondary aggravation due to cessation of treatment. Indeed, regression of retinopathy has been described after completing IFN treatment for hepatitis.1
However, in some cases, severe retinal lesions are reportedly responsible for significant decreases in visual acuity. Some authors thus recommend continuing treatment
with reduced IFN dosages.
To date, only four other cases of IFN-associated retinopathy in MS have been reported by ophthalmologists.3-6 First case continued IFN therapy under strict
monitoring of ophthalmologic condition, and showed noserious visual deterioration.3 In contrast, IFN was discontinued for cases in Spain and the United States andchanged to other maintenance treatment with glatiramer
acetate, and then the retinopathy were reportedly improved.4, 5 IFN therapy was discontinued for the most recent case, reported from Japan, and retinopathy subsided
without specific therapy.6 In the present case, treatment
was stopped because the patient reported serious visual
disturbance with several risk factors for retinopathy, diabetes mellitus and arterial hypertension. Unfortunately,
because glatiramer acetate is not available in Japan, wecould not use that for her. The patient is still not receiving IFN therapy and has shown no serious relapse orneurological aggravation for 6 months.
Visual disturbance is one of the most common symptoms in MS patients. Based on our study series, IFN retinopathy may be an uncommon but potentially serious
adverse effect in MS patients. Our examination of twenty
MS patients identified no other cases with retinopathy.
Although further large-scale studies are necessary, prevalence of retinopathy seems to be much lower in MS thanin viral hepatitis. We speculate that this low occurrence
could be attributed to lower patient ages and lower IFN
dosage for MS. However, because diabetes mellitus issuggested as a strong risk factor for this adverse effect,
neurologists should thus be aware of this adverse effectdue to IFN and regularly perform retinal examinations,particularly for patients with risk factors for retinopathy,
diabetes mellitus or arterial hypertension.
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