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BLOG: Is fluorometholone the magic mucin medicine?
Well now, what have we here? For years DED docs have lamented the absence of a medication that in some way improves the mucin part of tears. There has been lots of excitement, or at least lots of buzz, around tavilermide and the 2015 licensing deal signed between Allergan and Mimetogen. At the moment tavilermide is reported to be in phase 3 FDA trials. While surfing around the Dry Eyeosphere I stumbled upon a study that appears to show that we may have had a mucin-enhancing drug sitting on our shelf for a couple of decades.
Building on an “Aha!” moment published by Machida and colleagues in 2016 showing an increase in MUC gene expression in two patients treated for DED with fluorometholone, Taniguchi and Sharma studied cell cultures of corneal and conjunctival cells. When exposed to fluorometholone there was a dose- and time-responsive increase in the expression of MUC genes 1, 4, 16 and 19. Put simply, fluorometholone increases the production of mucin in both corneal and conjunctival epithelial cells. Of course the original fluorometholone medication is FML made by Allergan, the company now waiting with bated breath for the FDA to rule on tavilermide, and Alcon had a competing drug called Flarex (fluorometholone acetate ophthalmic suspension).
Could Allergan and Alcon unwittingly have had the magic bullet all along?
The up-regulation of the MUC genes involves the activation of a glucocorticoid receptor on those epithelial cells. It is therefore likely that any glucocorticoid could have a similar effect. This may explain why steroids in general are so effective in treating so many different types of DED if they all increase mucin production in addition to reducing surface inflammation. For my mind we all now have a much stronger case to make when we want to use steroids to treat our DED patients, and more so, this may very well prompt us to consider steroids both earlier and for longer courses of treatment.
Is there something special about fluorometholone? That remains for other researchers to investigate. If anyone is asking me (and thus far no one has), if I had a loteprednol product I’d be on the phone with Messrs. Taniguchi and Sharma asking them to test my potion in their crystal ball broth. For the rest of us my declaration that 2019 is the “Year of Steroids” in DED is looking better all the time. As of this moment my steroid of choice for DED is fluorometholone two to four times per day. FML and its generic equivalents will vie with the reborn Flarex in the marketplace (note: all are preserved with BAK, as are the loteprednol products). The references cited herein might help with pre-authorization.
It’s funny, isn’t it? Alcon buried Flarex and Allergan has largely ignored FML. How strange would it be if fluorometholone was the mucin-producing drug we’ve been looking for all these years, and it was there all along.
References:
Machida Y, et al. Case Rep Ophthalmol. 2016;doi:10.1159/000445371.
Taniguchi J, et al. Acta Ophthalmol. 2019;doi:10.1111/aos.14113.
Disclosure: White reports he is a consultant for Allergan and Eyevance.