Abstract
Purpose :
Primary open angle glaucoma (POAG) is the most common form of glaucoma worldwide. Increased stiffness and reduced porosity of Schlemm’s canal and juxtacanalicular tissues is known to play a key role in POAG pathogenesis. Ultrasound-induced cavitation has been used to increase porosity of tissues, especially when enhanced by the presence of microbubble contrast agents that serve as cavitation nuclei. In this preliminary study, we introduced PFC nanodroplets (NDs) into the anterior chamber (AC) and exposed eyes to focused ultrasound as a potential means for improving outflow in POAG.
Methods :
We synthesized NDs with a liquid perfluoropentane core and lipid shell. NDs averaged approximately 100 nm in diameter. Upon exposure to focused ultrasound of sufficient intensity, NDs undergo a transient phase change from liquid to gas. We introduced 0.1 ml of an ND emulsion into the AC of ex vivo pig eyes and 25 µl into 3 in vivo rat eyes. Using a Verasoncs Vantage-128 ultrasound system, eyes were then imaged and NDs activated with linear array ultrasound probes with center frequencies of 18 MHz and 28 MHz at a series of increasing acoustic intensities.
Results :
At diagnostic acoustic intensities, scanned focused ultrasound beams provided visualization of anatomy with minimal activation of NDs. At 28 MHz, NDs in the rat AC activated at a peak negative pressure of 5 MPa (mechanical index, MI=1.2), undergoing rapid phase transition from liquid to gas. Acoustic reflection from transient gas microbubbles produced high imaging contrast and microbubble collapse produced cavitation. Ultrasound and OCT Images showed NDs to be distributed widely within the AC, settling into the angle and entering Schlemm’s canal. Two days after treatment, rat eyes showed no sign of inflammation, but a few small gas bubbles were present in the AC.
Conclusions :
In this application, NDs are advantageous with respect to conventional microbubble ultrasound contrast agents because of their higher density and smaller diameter (< 1/10th that of microbubble agents), which facilitate entry into the outflow channels. ND activation occured at an MI of 1.2, which exceeds the diagnostic maximum of 0.23. Future preclinical in vivo studies using glaucoma models will assess safety and the effect of treatment on IOP and outflow facility.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.