Differentiating Between Perfluorohexyloctane Ophthalmic Solution and Water-Free Cyclosporine Ophthalmic Solution 0.1% for Dry Eye Disease: A Review of Preclinical and Clinical Characteristics

Abstract Perfluorohexyloctane ophthalmic solution (Miebo) and water-free cyclosporine ophthalmic solution 0.1% (Vevye) are recently approved treatments for dry eye disease (DED). Perfluorohexyloctane (PFHO) uses a novel approach to treat evaporative DED, whereas water-free cyclosporine (CsA 0.1%) is formulated to increase ocular delivery of its active ingredient to improve tear production. The two medications utilize the distinctive properties of two different semifluorinated alkanes (SFAs) to elicit their therapeutic effects. PFHO consists of 100% active ingredient and forms a monolayer on the surface of the tear film to inhibit evaporation. CsA 0.1% utilizes a vehicle consisting of perfluorobutylpentane (PFBP) and ethanol to facilitate delivery of cyclosporine to ocular tissues. The structure of these SFAs determines their differing behaviors and functions. The longer chain length of PFHO results in a slower evaporation rate and facilitates formation of a stable monolayer on the ocular surface. In vitro, PFHO demonstrated a substantially lower evaporation rate versus PFBP or human meibum, as well as a significantly longer ocular surface residence time. Ex vivo, PFHO demonstrated a longer ocular surface residence time than PFBP. The shorter chain length of PFBP enables it to better solubilize cyclosporine and improve drug delivery to ocular tissues. Although both of these ophthalmic drops utilize SFAs, their differences—in physicochemical properties and the mechanisms by which they are understood to intervene in the DED cycle—are important considerations in treatment selection for patients with DED.