Abstract
Purpose: :
To compare the distribution of dye to the ocular posterior segment via an intravitreal (IV) or anterior suprachoroidal space (SCS) injection of free or microbubble-contained 1,1’-Dioctadecyl-3,3,3’,3’-tetramethylindocarbocyanine iodide (DiI).
Methods: :
Fresh canine cadaver eyes received either an IV or SCS injection (250 uL) of free or microbubble-incorporated DiI. Eyes injected with microbubbles were simultaneously imaged with ultrasound and either received 0, 1, or 3 pulses to destroy the microbubbles and release the incorporated Dil once they reached the ocular posterior segment. All eyes were frozen within 1 minute of injection using 2-methylbutane in liquid nitrogen, stored at -80°C until sectioned at 5-10 um at -30°C, and mounted on superfrost slides. Amount of dye in the retina as observed on a fluorescent microscope was semi-quantified using a score of 0 (none) to 4 (retina saturated with DiI) in representative areas of the superior, central, and inferior retina by two masked observers. Mean cumulative scores (of the 3 anatomic areas) were analyzed using Wilcoxon rank sum test and differences considered significant at P<0.05.
Results: :
Ultrasound imaging illustrated that microbubble contrast was present in the ocular posterior segment within 10 seconds of injection. Mean cumulative scores of retinal dye were similar between IV (2.0 +/- 1.7) and SCS (1.8 +/- 0.88) for free DiI, and slightly higher for 1 pulse microbubble delivery of DiI (IV: 2.9 +/- 1.4 ; SCS: 2.8 +/- 2.3). However, 3 pulse microbubble destruction resulted in significantly higher delivery of DiI to SCS (P=0.043) (4.1 +/- 0.8) compared to IV (2.7 +/- 1.1).
Conclusions: :
These results support the theory that microbubbles as a delivery vehicle and site-targeted ultrasound may improve drug delivery to the ocular posterior segment. Furthermore, these results suggest that the SCS may allow enhanced targeted drug delivery to the ocular posterior segment and use of these modalities together (i.e., microbubbles and SCS injections) may result in more effective drug delivery to the retina.
Keywords: injection • imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound)