Visual consequences of medications for multiple sclerosis: the good, the bad, the ugly, and the unknown

Moss, Heather E.

doi:10.2147/eb.s140481

Cited by 16 publications

(8 citation statements)

References 43 publications

(49 reference statements)

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“…The time course informs monitoring and management. Our six patients fit previous studies which report the onset of Graves' disease ranging from 6 months to 7 years but with a peak at around 18-36 months [15,21] which coincides with when the B-cells are reconstituted and later peak.…”

Section: Discussionsupporting

confidence: 90%

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Immune reconstitution after alemtuzumab therapy for multiple sclerosis triggering Graves’ orbitopathy: a case series

Roos

Moran

Chatterjee

et al. 2018

Eye

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Alemtuzumab-a monoclonal antibody targeting the CD52 glycoprotein expressed by most mature leucocytes-effectively decreases relapse rate and disability progression in early, relapsing-remitting multiple sclerosis (MS). However, secondary autoimmune disorders complicate therapy in nearly 50% of treated patients, with Graves' disease being the most common. Rarely, thyroid eye disease (TED) ensues; only seven such cases have been reported. Our aim was to analyse the largest series of MS patients developing thyroid eye disease after alemtuzumab treatment. We performed a retrospective chart review of MS patients treated with alemtuzumab and subsequently identified by their treating physicians as having developed TED and referred to our ophthalmology service. As an original trial centre for alemtuzumab, our hospital has treated approximately 162 MS patients with this novel therapy. In total, 71 (44%) developed thyroid dysfunction, most of whom (87%) developed Graves' disease, with ten (16%) referred for ophthalmological evaluation. Two developed active orbitopathy following radioiodine treatment; one occurred after cessation of anti-thyroid drug treatment. Three developed sight-threatening disease requiring systemic immunosuppression, with one refractory to multiple immunosuppressants. The remaining patients were treated conservatively. TSH-receptor antibody (TRAb) levels were significantly raised in all cases, when ascertained. We report sight-threatening as well as mild TED in MS patients after treatment with alemtuzumab. Endocrine instability, radioiodine treatment and positive TRAb are all likely risk factors. The data support at least 6-monthly biochemical and clinical assessment with a low threshold for referral to an ophthalmologist, particularly for those with higher TRAb levels who may be at greater risk of orbitopathy.

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Section: Discussionsupporting

confidence: 90%

“…Development of thyroid eye disease is less common, occurring in less than 2% of alemtuzumab-treated MS patients [21]. Consequently, only a handful of cases have been reported in the literature (see Table 2) [22][23][24].…”

Section: Introductionmentioning

confidence: 99%

Immune reconstitution after alemtuzumab therapy for multiple sclerosis triggering Graves’ orbitopathy: a case series

Roos

Moran

Chatterjee

et al. 2018

Eye

View full text Add to dashboard Cite

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“…Altogether, based on available data, fingolimod seems to have some short-term benefit in T1D by downregulating the immune response against beta-cell, but long-term responses are missing as it fails to halt disease progression. Furthermore, it must be kept in mind that in diabetic patients the risk for developing macula edema under fingolimod is increased (Moss, 2017). This risk must be weighed against its rather limited benefit as an insulin sensitizer in diabetes.…”

Section: Insulin Resistancementioning

confidence: 99%

“…Those seen more frequently with fingolimod than with placebo included lymphopenia, increased liver transaminases, herpes viral infections, hypertension, and initial bradycardia and first degree AV block both as first-dose effects. Of note, analysis of pooled safety data from various phase 2 and phase 3 studies revealed that the risk for macular edema, which in FREEDOMS II occurred in 1% of the patients in both the fingolimod and the placebo group, was seven times more common in individuals with coexisting diabetes or history of uveitis when treated with 1.25 mg fingolimod (Moss, 2017;Zarbin et al, 2013).…”

Section: Other Potential Indications For Fingolimodmentioning

confidence: 99%

The sphingosine 1-phosphate receptor modulator fingolimod as a therapeutic agent: Recent findings and new perspectives

Huwiler

Zangemeister‐Wittke

2018

Pharmacology & Therapeutics

170

139

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The immunomodulatory drug fingolimod (FTY720, Gilenya) was approved for oral treatment of relapsing-remitting multiple sclerosis, due to its impressive efficacy and good tolerability. Pharmacologically, it acts as an unselective agonist of sphingosine 1-phosphate receptors (S1PR) and as a selective functional antagonist of the S1P subtype by induction of receptor downregulation. Since S1P is crucial for the regulation of lymphocyte trafficking, its downregulation causes redistribution of the immune cells to secondary lymphoid tissues, resulting in the depletion from the circulation and hence immunosuppression. Numerous preclinical studies have since been performed with the aim to increase the spectrum of potential indications for fingolimod with emphasis on other autoimmune disorders and diseases associated with inflammation and uncontrolled cell proliferation, including cancer. As an alternative to fingolimod, novel S1PR modulators with a more selective receptor activation profile and improved pharmacokinetic performance and tolerability have also been developed. Preclinical and clinical studies are ongoing to investigate their therapeutic potential. This review discusses the most relevant preclinical and clinical findings from S1PR-targeting and from less-well defined off-target effects reported in the literature, and reveals perspectives for using fingolimod and functionally-related derivatives and new formulations in the management of an increasing number of diseases.

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“…In fact, although corticosteroids may reduce inflammation and stimulate acute visual recovery, up to 60% of patients fail to normalize visual function (see [ 7 ]). Additional newer candidates to improve ON function have been recently established, although their benefit and harm remain to be determined (see [ 8 ]).…”

Section: Introductionmentioning

confidence: 99%

Fatty Acids Dietary Supplements Exert Anti-Inflammatory Action and Limit Ganglion Cell Degeneration in the Retina of the EAE Mouse Model of Multiple Sclerosis

et al. 2018

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Optic neuritis is an acute inflammatory demyelinating disorder of the optic nerve (ON) and is an initial symptom of multiple sclerosis (MS). Optic neuritis is characterized by ON degeneration and retinal ganglion cell (RGC) loss that contributes to permanent visual disability and lacks a reliable treatment. Here, we used the experimental autoimmune encephalomyelitis (EAE) mouse model of MS, a well-established model also for optic neuritis. In this model, C57BL6 mice, intraperitoneally injected with a fragment of the myelin oligodendrocyte glycoprotein (MOG), were found to develop inflammation, Müller cell gliosis, and infiltration of macrophages with increased production of oncomodulin (OCM), a calcium binding protein that acts as an atypical trophic factor for neurons enabling RGC axon regeneration. Immunolabeling of retinal whole mounts with a Brn3a antibody demonstrated drastic RGC loss. Dietary supplementation with Neuro-FAG (nFAG®), a balanced mixture of fatty acids (FAs), counteracted inflammatory and gliotic processes in the retina. In contrast, infiltration of macrophages and their production of OCM remained at elevated levels thus eventually preserving OCM trophic activity. In addition, the diet supplement with nFAG exerted a neuroprotective effect preventing MOG-induced RGC death. In conclusion, these data suggest that the balanced mixture of FAs may represent a useful form of diet supplementation to limit inflammatory events and death of RGCs associated to optic neuritis. This would occur without affecting macrophage infiltration and the release of OCM thus favoring the maintenance of OCM neuroprotective role.

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Visual consequences of medications for multiple sclerosis: the good, the bad, the ugly, and the unknown

Cited by 16 publications

References 43 publications

Immune reconstitution after alemtuzumab therapy for multiple sclerosis triggering Graves’ orbitopathy: a case series

Immune reconstitution after alemtuzumab therapy for multiple sclerosis triggering Graves’ orbitopathy: a case series

The sphingosine 1-phosphate receptor modulator fingolimod as a therapeutic agent: Recent findings and new perspectives

Fatty Acids Dietary Supplements Exert Anti-Inflammatory Action and Limit Ganglion Cell Degeneration in the Retina of the EAE Mouse Model of Multiple Sclerosis

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