Deciphering the action of perfluorohexyloctane eye drops to reduce ocular discomfort and pain

Perfluorohexyloctane (F6H8) eyedrops have been recently introduced in Europe as a product to treat dry eye disease, based on its ability to reduce tear film instability in Meibomian gland dysfunction and evaporative dry eye disease, although its mechanism of action is still unknown. In the present pilot study, we evaluated the effects of the ocular instillation of a single drop of commercial F6H8 eyedrops in 20 healthy humans (9 women/11 men), measuring: (a) Corneal surface temperature (CST) from infrared video images; (b) tear volume using phenol red threads; (c) blinking frequency; and (d) ocular surface sensations (cold, dryness, pricking, foreign body, burning, itching, gritty, eye fatigue, watering eyes, and light-evoked discomfort sensations; scored using 10 cm Visual Analog Scales), before and 5–60 min after F6H8 or saline treatment. CST decreased and tearing and blinking frequency increased significantly after F6H8 but not after saline solution. When applied unilaterally, CST decreased only in the F6H8-treated eye. No sensations were evoked after F6H8 or saline. The corneal surface temperature reduction produced by topical F6H8 does not evoke conscious ocular sensations but is sufficient to increase the activity of corneal cold thermoreceptors, leading to an increased reflex lacrimation and blinking that may relieve dry eye condition thus reducing ocular discomfort and pain.This work was funded by the Spanish Agencia Estatal de Investigación and the European Regional Development Fund grants SAF2017-83674-C2-1-R and SAF2017-83674-C2-2-R, the Generalitat Valenciana Excellence Program grant PROMETEO/2018/114, Predoctoral fellowships ACIF/2019/054 from GV (MD-M) and FPU16/00283 from Spanish Ministry of Universities (EV), and PID2020-115934RB-I00/AEI/10.13039/501100011033.Peer reviewe