High-Frequency Ultrasound Activation of Perfluorocarbon Nanodroplets for Treatment of Glaucoma.

Abstract

Elevated intraocular pressure (IOP) is the most prevalent risk factor for initiation and progression of neurodegeneration in glaucoma. Ocular hypertension results from increased resistance to aqueous fluid outflow caused by reduced porosity and increased stiffness of tissues of the outflow pathway. Acoustic activation and resulting bioeffects of the perfluorocarbon (PFC) nanodroplets (NDs) introduced into the anterior chamber (AC) of the eye could potentially represent a treatment for glaucoma by increasing permeability in the aqueous outflow track. To evaluate the potential of NDs to enter the outflow track, 100-nm diameter perfluoropentane (PFP) NDs with a lipid shell were injected into the AC of ex vivo pig eyes and in vivo rat eyes. The NDs were activated and imaged with 18- and 28-MHz linear arrays to assess their location and diffusion. NDs in the AC could also be visualized using optical coherence tomography (OCT). Because of their higher density with respect to aqueous humor, some NDs settled into the iridocorneal angle where they entered the outflow pathway. After acoustic activation of the NDs at the highest acoustic pressure, small gas bubbles were observed in the AC. After two days, no acoustic activation events were visible in the AC of the rats and their eyes showed no evidence of inflammation.