PURPOSE: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.
RCT Entities:
PURPOSE: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.