A novel method to evaluate residence time in humans using a nonpenetrating fluorescent tracer

The purpose of these investigations was to develop an improved method for measuring precorneal residence time (RT) and to demonstrate its efficacy with novel formulations.

A biomicroscope was adapted for use as a clinical fluorometer. Using a nonpenetrating fluorescent probe (FITC-dextran, 70,000-73,000 molecular weight [MW]), RT was estimated as the time to return to baseline (gross RT) and from parameters derived from least-squares regression fits to the decay data (area under the curve [AUC], elimination rate, and time for 50% of the signal to be eliminated [T(50)]). One rabbit and two human studies were conducted. The studies were randomized, double-masked, and controlled. Repeatability in humans was examined in 15 subjects (six determinations per subject, n = 90 total).

The FITC-dextran tracer did not penetrate into corneal tissue. The rabbit gross RTs were 14.5, 15.0, and 16.0 minutes for three low-viscosity solutions (eta = 2.7-7.7 mPa/sec) and 22.5 minutes for a more viscous solution (eta = 357 mPa/sec). For a high-viscosity (eta approximately equal 30,000 mPa/sec) gel in humans, the method demonstrated approximately a twofold increase in gross RT and AUC compared with buffered saline. Repeatability of the method appeared acceptable, with intersubject variability the most significant factor affecting precision.

The new method is safe and convenient and offers comprehensive RT data. Furthermore, it appears to differentiate among formulations. However, as with other tear-influenced parameters, there is significant variability. Thus, sufficient sample sizes are necessary for meaningful comparative investigations.