Ultrasound-activated perfluorocarbon nanodroplets in ophthalmology

Glaucoma, a leading cause of blindness, can result from increased intraocular pressure resulting from elevated outflow resistance. In this preliminary study, we consider the potential of ultrasound-activated perfluorocarbon nanodroplets (NDs) to increase the permeability of the outflow pathway. 100nm diameter NDs with a perfluoropentane core and lipid shell were introduced into the anterior chamber (AC) of ex vivo pig and in vivo rat eyes. Imaging (18 and 28 MHz) was performed with a weakly focused (F = 2.9) beam. Activation was induced by increasing the array sub-aperture to tighten the focus to F = 0.62 centrally. Images showed NDs to be distributed widely within the AC, from which they could enter the outflow pathway by virtue of their small dimension. At 28 MHz, NDs were activated at a peak negative pressure of 5 MPa, corresponding to a mechanical index of 1.8.Two days after treatment, rat eyes showed no sign of inflammation, but a few small gas bubbles were present in the AC. In this application, NDs are advantageous as cavitation nuclei with respect to conventional microbubble contrast agents because of their higher density and smaller diameter (<1/10th that of microbubble agents), which facilitate entry into the outflow channels. Future preclinical in vivo studies will assess the effect of treatment on IOP and outflow facility.