Retinopathy: An Overlooked Adverse Effect of Interferon-beta Treatment of Multiple Sclerosis

Ohira, Masayuki; Ito, Daisuke; Shimizu, Toshihiko; Shibata, Mamoru; Ohde, Hisao; Suzuki, Norihiro

doi:10.2302/kjm.58.54

Cited by 12 publications

(5 citation statements)

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“…Alternatively, it has been suggested that dosing IFN less frequently, even if less antiinflammatory, may be more neuroprotective. [22][23][24] Interestingly, the IFN SC cohort exhibited a faster rate of GCIP atrophy during the first year of treatment, as compared to afterwards. A number of possibilities may explain this finding.…”

Section: Comparison Of Rates Of Gcip Thinning Between Rrmsmentioning

confidence: 99%

Disease-modifying therapies modulate retinal atrophy in multiple sclerosis

et al. 2017

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Objective: To retrospectively investigate whether disease-modifying therapies (DMTs) exert differential effects on rates of retinal atrophy in relapsing-remitting multiple sclerosis (RRMS), as assessed using optical coherence tomography (OCT).Methods: A total of 402 patients with RRMS followed at the Johns Hopkins MS Center who underwent Cirrus-HD OCT were assessed for eligibility. Inclusion criteria included at least 1 year of OCT follow-up and adherence to a single DMT during the period of follow-up. Combined thickness of the ganglion cell 1 inner plexiform (GCIP) and other retinal layers was computed utilizing automated macular segmentation. Retinal thickness changes were analyzed using mixed-effects linear regression.Results: The effects of glatiramer acetate (GA; n 5 48), natalizumab (NAT; n 5 46), and interferonb-1a subcutaneously (IFN SC ; n 5 35) and intramuscularly (IFN IM ; n 5 28) were assessed. Baseline analyses revealed no significant differences between groups in terms of age, sex, optic neuritis history, or follow-up duration. During follow-up, relative to NAT-treated patients, IFN SC -and GAtreated patients exhibited 0.37 mm/y (p , 0.001) and 0.14 mm/y (p 5 0.035) faster rates of GCIP thinning, respectively, adjusting for the interval between initiation of DMT and OCT monitoring (gap time), age, sex, relapses, and disease duration. In the IFN SC group, GCIP thinning was 1.53 mm/y faster during the first year of therapy vs during the time interval afterwards (p , 0.001).Conclusions: Rates of GCIP atrophy in patients with RRMS vary according to DMT utilization. Our findings support OCT for monitoring neurodegenerative treatment effects in the retina, an easily accessible tissue, and as a practical outcome measure in RRMS clinical trials. Neurology ® 2017;88:525-532 GLOSSARY AMT 5 average macular thickness; DMT 5 disease-modifying therapy; GA 5 glatiramer acetate; GCIP 5 ganglion cell 1 inner plexiform layer; HC 5 healthy control; IFN 5 interferon; IFN IM 5 intramuscular interferon-b-1a; IFN SC 5 subcutaneous interferon-b-1a; INL 5 inner nuclear layer; MME 5 microcystic macular edema; MS 5 multiple sclerosis; NAT 5 natalizumab; OCT 5 optical coherence tomography; ON 5 optic neuritis; ONL 5 outer nuclear layer; pRNFL 5 peripapillary retinal nerve fiber layer thickness; RRMS 5 relapsing-remitting multiple sclerosis.Although multiple sclerosis (MS) is conventionally regarded as an autoimmune, inflammatory, demyelinating disorder of the CNS, neurodegeneration resulting from these processes is recognized as the principal substrate of long-term disability.1,2 Currently available disease-modifying therapies (DMTs) for relapsing-remitting MS (RRMS) modulate or suppress the immune system, reducing the risk for future inflammation and associated neurodegeneration.3 Accordingly, the effect of DMTs on MRI-derived estimates of brain atrophy is a common outcome in MS trials. [4][5][6][7] Recent studies reveal that retinal atrophy mirrors brain atrophy over time in MS. 8 However, it remains unclear wh...

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Section: Comparison Of Rates Of Gcip Thinning Between Rrmsmentioning

confidence: 99%

Disease-modifying therapies modulate retinal atrophy in multiple sclerosis

et al. 2017

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“…Despite the retinopathy, most patients have had good visual acuity. Sommer et al [2] described the first case of IFNβ-1b associated retinopathy during treatment for MS. To our knowledge there are only eight cases reported in the international literature [2][3][4][5][6][7][8][9][10]. Consensus is lacking regarding treatment of IFN-retinopathy in a patient with MS due to its infrequency.…”

Section: Discussionmentioning

confidence: 99%

Retinal Lesions and Renal Impairment Associated with Interferon β1α Therapy for Multiple Sclerosis: A Case Report

Chelioti¹,

Theodoropoulou²

2018

J Clin Exp Nephrol

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Background: Recombinant interferon β is now the mainstay of maintenance therapy for multiple sclerosis in many countries. Retinal lesions are rarely related with subcutaneous interferon β1α in multiple sclerosis. Interferon nephrotoxicity is also an extremely rare side effect. We report a case of interferon-associated retinopathy and nephropathy in a patient with multiple sclerosis receiving subcutaneous interferon β1α.Case report: A 42 years old Caucasian female with a history of multiple sclerosis on continuous treatment with interferon β1α, presented with anemia, thrombocytopenia, albuminouria, mild elevation of liver enzymes, renal impairment and sudden hypertension without visual disorders. Ocular fundus exam showed several retinal cotton wool spots indicating interferon-retinopathy and the drug was discontinued. Biochemical and immunological analyses were negative for autoimmune renal diseases. The retinopathy disappeared without specific therapy 2 months after discontinuing interferon β1α and kidney function restored. Interferon β1α resumed 16 weeks after stopping treatment due to multiple sclerosis relapse. On an iterative fundus exam 3 months after resumption of interferon β1α, no further cotton wool spots have recurred. 6 and 12 months later, with the patient on interferon β1α treatment, the ocular fundus was free of lesions and kidney function was within normal range. Conclusions:In our patient, both complications resolved after drug cessation and the diagnosis of interferon β1α retinopathy and nephropathy was retained due to the lack of any other etiology.

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“…The majority of them complained about symptoms after 11 months since the initiation of the treatment. The TEAEs reported in these patients included unilateral/bilateral asymptomatic retinopathy (peripheral intraretinal hemorrhages and cotton wool spots), unilateral/bilateral symptomatic retinopathy (blurred vision, progressive visual field loss, and peripheral telangiectasia), central vein and arterial branch occlusions, Sicca syndrome, and recurrent idiopathic orbital inflammation [23, 28,29,31,36,39,40,42,43,46,47,50,51].…”

Section: Teaes Related To Interferon βmentioning

confidence: 99%

Ocular adverse events from pharmacological treatment in patients with multiple sclerosis—A systematic review of the literature

et al. 2021

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Purpose The aim of this study was to review the scientific evidence and describe the ocular treatment-emergent adverse events (TEAEs) related to pharmacological treatment in patients with multiple sclerosis. Methods A systematic review of literature was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines in the MEDLINE, LILACS, EMBASE, and COCHRANE databases. Articles were filtered based on title and abstract considering the selection criteria and subsequently filtered by full-text reading. The resulting articles were evaluated using the Joanna Briggs Institute Quality Tools. Study characteristics and results were extracted and presented in structured tables to conduct a narrative synthesis. Results A total of 2852 published articles were extracted using our strategy. After removing duplicates, 2841 articles were screened based on title and abstract, 102 articles were evaluated using quality tools, and 69 articles were filtered by full-text reading. Through this search strategy, 60 articles met all the inclusion criteria and seven articles, through a search update conducted in the same manner, were included. This resulted in 67 articles meeting the inclusion criteria, of which 11 were experimental and 56 were observational. The therapies related to ocular TEAEs were alemtuzumab, amantadine, fingolimod, steroids, CTLA-4 Ig, estriol, interferon β, natalizumab, hyperbaric oxygen, rituximab, siponimod, teriflunomide, and tovaxin. Fingolimod and siponimod were commonly associated with macular edema, interferon β was associated with retinopathy, alemtuzumab was associated with thyroid eye disease, amantadine was associated with corneal edema, and steroids were associated with acute retinal necrosis. Opportunistic infections were also found, and there was one life-threatening case. Conclusions Our search revealed different methodological assessments of the topic. However, longitudinal studies regarding ocular TEAEs related to multiple sclerosis therapy are necessary to provide evidence-based recommendations, especially in understudied regions such as Latin America and Africa. Physicians should monitor ocular symptoms in patients being treated for multiple sclerosis and consider an interdisciplinary approach. Systematic review registration PROSPERO ID CRD42020106886

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Retinopathy: An Overlooked Adverse Effect of Interferon-beta Treatment of Multiple Sclerosis

Cited by 12 publications

References 5 publications

Disease-modifying therapies modulate retinal atrophy in multiple sclerosis

Disease-modifying therapies modulate retinal atrophy in multiple sclerosis

Retinal Lesions and Renal Impairment Associated with Interferon β1α Therapy for Multiple Sclerosis: A Case Report

Ocular adverse events from pharmacological treatment in patients with multiple sclerosis—A systematic review of the literature

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