Adverse Effect Profile of Topical Ocular Administration of Fingolimod for Treatment of Dry Eye Disease

Abstract

Fingolimod is a promising prodrug in attenuating multiple sclerosis and prolonging survival of organ allograft, with many other protective effects. Its mechanism of action is related to the internalization of sphingosine 1-phosphate receptors (S1PRs). Our previous study indicated that fingolimod eyedrops was efficacious in inhibiting ocular inflammation in a dry eye disease (DED) model of non-obese diabetic (NOD) mice. In the current study, we evaluated potential adverse effects of fingolimod eyedrops. Inbred 10-week-old BALB/c mice were randomly divided into four groups, fingolimod-treated groups at three different concentrations (0.01%, 0.1% and 0.5%) and a negative control group without intervention. Our results showed that in the 0.5% fingolimod group, adverse effects such as photophobia, catacleisis and corneal oedema were observed after 1 week of treatment. 1 month later, corneal opacity, oedema and neovascularization persisted till the mice were killed 2 months later. In contrast, there was no significant abnormality in the negative control group, and 0.01% and 0.1% fingolimod-treated groups. During a 2-month treatment period, we did not detect fingolimod, nor significant change in blood cells in peripheral blood, nor pathological changes in retina and systemic organs. Combined with our previous study and the current results, we recommend that an optimal range of safe and effective concentration of fingolimod as eyedrops is between 0.005% and 0.1%.

Ocular Effects of Sulfur Mustard and Therapeutic Approaches

“…It is also reported that cationic emulsion of cyclosporine A is very efficient in the management of corneal epithelium lesion [Daull et al, 2016]. Fingolimod is a systemic drug in the management of multiple sclerosis, suggested for controlling dry eye disease as well [Xiao et al, 2016]. Fingolimod is a systemic drug in the management of multiple sclerosis, suggested for controlling dry eye disease as well [Xiao et al, 2016].…”

“…Tacrolimus has been described as an effective drug in the treatment of keratoconjunctivitis, controlling the inflammation in ocular tissues, and improving the tear film stability [Moscovici et al, 2015;Chatterjee and Agrawal, 2016]. Fingolimod is a systemic drug in the management of multiple sclerosis, suggested for controlling dry eye disease as well [Xiao et al, 2016]. The safe concentrations of this drug are reported to be 0.005% and 0.1% based on a study on mice [Xiao et al, 2016].…”

“…Fingolimod is a systemic drug in the management of multiple sclerosis, suggested for controlling dry eye disease as well [Xiao et al, 2016]. The safe concentrations of this drug are reported to be 0.005% and 0.1% based on a study on mice [Xiao et al, 2016]. Ocular surface injuries have been reported in SM-exposed patients [Solberg et al, 1997] thus this new formulation could be another treatment option in these patients for long term use.…”

Ophthalmic Complications and Managements of Sulfur Mustard Exposure: A Narrative Review

“…This novel formulation may be a long-term therapeutic alternative. 86 In SM-exposed patients, dry eye treatment is vital for reducing ocular symptoms and enhancing quality of life.…”

Fingolimod Suppresses a Cascade of Core Vicious Cycle in Dry Eye NOD Mouse Model: Involvement of Sphingosine-1-Phosphate Receptors in Infiltrating Leukocytes

“…17 Moreover, both our pharmacology and toxicology studies indicated that a range of 0.005% to 0.1% fingolimod is preferable as a formulation of eye drop applied in ocular surface. 17,18 These beneficial effects of fingolimod in DED are interesting and encouraging. However, the detailed mechanisms remain unknown.…”