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

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 eyedrop 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 eyedrop. 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 one week of treatment. One month later, corneal opacity, oedema and neovascularization persisted till the mice were euthanized two months later. In contrast, there was no significant abnormality in the negative control group, 0.01% and 0.1%fingolimod-treated groups. During a 2-month treatment period, we did not detect fingolimod, nor significant change of 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 eyedrop is between 0.005% and 0.1%. This article is protected by copyright. All rights reserved.