Longitudinal quantitative assessment of macula during therapy with fingolimod in relapsing–remitting multiple sclerosis

Fruschelli, Mario; Capozzoli, Marco; Gelmi, Maria Chiara; Masi, Gianni; Annunziata, Pasquale

doi:10.1007/s10792-018-0870-x

Cited by 9 publications

(13 citation statements)

References 12 publications

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“…Among these, one of the most significant, in terms of the number of patients and duration of the follow-up, highlighted a higher rate of RNFL thinning in ON+ patients, as reported in our results. However, unlike our data, ON− patients presented statistically significant annual change rates [36].…”

Section: Discussioncontrasting

confidence: 99%

“…Regarding the BCVA in the whole sample, in accordance with previous studies [15,36], we observed a stability and an improvement rate that was not clinically significant, being less than 10 ETDRS letters (2 lines) on average, which is considered the cutoff for this test.…”

Section: Discussionsupporting

confidence: 90%

“…The present study has a longer follow-up compared to previous reported real-world studies, but similar to the latter, it reports no cases of ME [16,36].…”

Section: Discussionsupporting

confidence: 88%

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OCT Analysis in Patients with Relapsing-Remitting Multiple Sclerosis during Fingolimod Therapy: 2-Year Longitudinal Retrospective Study

et al. 2020

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Many studies have demonstrated the usefulness of some optical coherence tomography (OCT) parameters, like total macular volume (TMV) and retinal nerve fiber layer thickness (RNFL-T), for monitoring patients with multiple sclerosis (MS). However, there are no real-world, long-term studies on patients with relapsing-remitting MS (RR-MS) treated with fingolimod. Therefore, the purpose of this study was to describe retinal changes associated with fingolimod therapy during a two-year follow-up while considering previous episodes of optic neuritis (ON). Patients diagnosed with RR-MS and treated with fingolimod (46 in total) underwent a two-year follow-up. Based on previous ON history, we identified 16 ON+ and 30 ON− patients. The ophthalmological evaluations, including visual field (VF) examination and OCT, were performed at a baseline at 3–6, 12 and 24 months to evaluate the progression rate for each parameter. When analyzing the whole sample, OCT showed no cases of macular edema. Instead, we observed a significant reduction rate in the central retinal thickness (CRT) (p < 0.001), TMV (p < 0.001) and RNFL (p < 0.05). Moreover, we observed a significant difference in the progression rate between ON+ and ON− patients, relative to the VF and RNFL (p < 0.05) examinations. OCT highlighted a significant progression rate of retinal damage in MS patients despite fingolimod therapy, especially in MS ON+ patients.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 90%

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OCT Analysis in Patients with Relapsing-Remitting Multiple Sclerosis during Fingolimod Therapy: 2-Year Longitudinal Retrospective Study

et al. 2020

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“…Additionally, several studies reported a preserved macular structure and thickness over time in RR-MS patients treated with fingolimod (Fruschelli et al, 2019;d'Ambrosio et al, 2020). Worthy of note, although macular edema is reported as a side effect of fingolimod administration with an incidence of 0.3-1.2% (Nolan et al, 2013), two studies evidenced that RR-MS patients treated with fingolimod did not show any case of macular edema (Fruschelli et al, 2019;Rossi et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Fingolimod and Diabetic Retinopathy: A Drug Repurposing Study

et al. 2021

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This study aimed to investigate the interactions between fingolimod, a sphingosine 1-phosphate receptor (S1PR) agonist, and melanocortin receptors 1 and 5 (MCR1, MCR5). In particular, we investigated the effects of fingolimod, a drug approved to treat relapsing-remitting multiple sclerosis, on retinal angiogenesis in a mouse model of diabetic retinopathy (DR). We showed, by a molecular modeling approach, that fingolimod can bind with good-predicted affinity to MC1R and MC5R. Thereafter, we investigated the fingolimod actions on retinal MC1Rs/MC5Rs in C57BL/6J mice. Diabetes was induced in C57BL/6J mice through streptozotocin injection. Diabetic and control C57BL/6J mice received fingolimod, by oral route, for 12 weeks and a monthly intravitreally injection of MC1R antagonist (AGRP), MC5R antagonist (PG20N), and the selective S1PR1 antagonist (Ex 26). Diabetic animals treated with fingolimod showed a decrease of retinal vascular endothelial growth factor A (VEGFA) and vascular endothelial growth factor receptors 1 and 2 (VEGFR1 and VEGFR2), compared to diabetic control group. Fingolimod co-treatment with MC1R and MC5R selective antagonists significantly (p < 0.05) increased retinal VEGFR1, VEGFR2, and VEGFA levels compared to mice treated with fingolimod alone. Diabetic animals treated with fingolimod plus Ex 26 (S1PR1 selective blocker) had VEGFR1, VEGFR2, and VEGFA levels between diabetic mice group and the group of diabetic mice treated with fingolimod alone. This vascular protective effect of fingolimod, through activation of MC1R and MC5R, was evidenced also by fluorescein angiography in mice. Finally, molecular dynamic simulations showed a strong similarity between fingolimod and the MC1R agonist BMS-470539. In conclusion, the anti-angiogenic activity exerted by fingolimod in DR seems to be mediated not only through S1P1R, but also by melanocortin receptors.

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“…In the TRANSFORMS trial, ME was diagnosed in two out of the 429 patients treated with the approved FNG dosage of 0.5 mg (0.5%) [1]. In a longitudinal OCT study, over 12 months treatment with FNG, no cases of FNG- [10]. Probably due to the effect of FNG on its main target, the sphingosine-1phosphate (S1P) receptor, also expressed on the endothelium of the blood-retina barrier, an increase in TMV less than 0.05 mm 3 has been reported 3-5 months after starting FNG in RRMS patients [4,5].…”

Section: Discussionmentioning

confidence: 99%

Two-year macular volume assessment in multiple sclerosis patients treated with fingolimod

et al. 2020

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Background Fingolimod (FNG) is associated with the development of symptomatic macular edema (ME) in a small subset of multiple sclerosis (MS) patients. By using spectral domain optical coherence tomography (SD-OCT), an increase in the total macular volume (TMV) was rarely detected during the first months of treatment.Objectives The objective of this study is to assess whether FNG treatment leads to long-term macular changes in a real-life setting. Methods Sixty RRMS patients starting FNG, according to therapeutic indication, were enrolled at three Italian MS centers and followed for 2 years. Results The mean TMV did not change between baseline and the follow-up. No patients experienced visual acuity drop during the follow-up. Conclusions Initiation of FNG in MS is associated with a modest, not significant, increase in macular volume followed by no further significant changes over 2 years, highlighting the good safety profile of such treatment in MS.

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Longitudinal quantitative assessment of macula during therapy with fingolimod in relapsing–remitting multiple sclerosis

Abstract: In our cohort, therapy with fingolimod did not cause any change in CFT and TMV in MS patients during a 12-month follow-up independent of previous ON.

Cited by 9 publications

References 12 publications

OCT Analysis in Patients with Relapsing-Remitting Multiple Sclerosis during Fingolimod Therapy: 2-Year Longitudinal Retrospective Study

OCT Analysis in Patients with Relapsing-Remitting Multiple Sclerosis during Fingolimod Therapy: 2-Year Longitudinal Retrospective Study

Fingolimod and Diabetic Retinopathy: A Drug Repurposing Study

Two-year macular volume assessment in multiple sclerosis patients treated with fingolimod

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