OBJECTIVE: Semifluorinated alkanes (SFAs) are amphiphilic molecules with a fluorinated carbon segment (F) and a hydrocarbon segment (H). Perfluorohexyloctane ophthalmic solution (F6H8; MIEBO©) is an anti-evaporative agent for dry eye that forms a long-lasting layer on the surface of the tear film. This in vitro study evaluated the impact of SFA chain length on intermolecular interactions, evaporation rate (Revap), and inhibition of Revap of saline to compare the anti-evaporative properties of various SFAs.

METHODS: The SFAs F4H2, F4H5/CsA (cyclosporine ophthalmic solution 0.1 %; Vevye©), F6H7, F6H8, and F6H10 were evaluated. The Revap of 1 mL of each SFA and saline alone or saline with 11 or 100 µL of the SFA layered over top were evaluated gravimetrically at 35 ?C. Total sample weight was recorded every 10 min over 100 min, and Revap was obtained from the slope of the best-fit line obtained by least squares linear regression analysis. The relative order (fluidity) of the SFAs was evaluated using Fourier transform infrared spectroscopy.

RESULTS: The mean (SEM) inherent Revap (mg/min) was 102 (25), 6.0 (0.6), 0.58 (0.20), 0.15 (0.017), and 0.12 (0.09) for F4H2, F4H5/CsA, F6H7, F6H8, and F6H10, respectively (n = 3-9). The Revap of saline with a 100 µL F6H7, F6H8, and F6H10 layer was inhibited by 40 %, 80 %, and 66 %, respectively (p < 0.001 vs saline), and unchanged by F4H2 and F4H5/CsA. Only F6H8 had a significant inhibitory effect on Revap of saline when applying an 11 µL drop (p < 0.0001 vs saline; n = 10-25). The SFA-SFA intermolecular interactions were greater with longer H and F chain lengths.

CONCLUSIONS: SFA chain length and volatility correlated with inhibition of the Revap of saline with the longest chain length SFAs F6H8 and F6H10 having the maximal effect. These data support the suitability of F6H8 as a treatment for evaporative dry eye disease.