Vesna Zderic

Objectives Topically applied macromolecules have the potential to provide vision‐saving treatments for many of the leading causes of blindness in the United States. The aim of this study was to determine if ultrasound can be applied to increase transcorneal drug delivery of macromolecules without dangerously overheating surrounding ocular tissues. Methods Dissected corneas of adult rabbits were placed in a diffusion cell between a donor compartment filled with a solution of macromolecules (40, 70 kDa, or 150 kDa) and a receiver compartment. Each cornea was exposed to the drug solution for 60 minutes, with the experimental group receiving 5 minutes of continuous ultrasound or 10 minutes of pulsed ultrasound at a 50% duty cycle (pulse repetition frequency of 500 ms on, 500 ms off) at the beginning of treatment. Unfocused circular ultrasound transducers were operated at 0.5 to 1 W/cm 2 intensity and at 600 kHz frequency. Results The greatest increase in transcorneal drug delivery seen was 1.2 times ( P < .05) with the application of pulsed ultrasound at 0.5 W/cm 2 and 600 kHz for 10 minutes with 40 kDa macromolecules. Histological analysis revealed structural damage mostly in the corneal epithelium, with most damage occurring at the epithelial surface. Conclusions This study suggests that ultrasound may be used for enhancing transcorneal delivery of macromolecules of lower molecular weights. Further research is needed on the long‐term effects of ultrasound parameters used in this study on human ocular tissues.