Abstract
Purpose :
The primary purpose of this work is to measure the effect on drug distribution due to syneresis combined with saccadic motion in an aged eye by simulating the corresponding motion and liquefaction in a mechanical model.
Methods :
A mechanical model using a motor controller was programmed to provide the motion equivalent to the sideways saccadic motion in human eyes. Based on preliminary experiments on ex vivo bovine eyes with mechanically liquefied pockets in the vitreous, it has been expected and observed that the effect of simulating eye motion on a deposited drug surrogate (Gd-DTPA) is much more significant within the liquefied regions than the intact gel regions. However, proper comparison of cases with and without saccadic motion are quite challenging because of difficulty in replicating the topography of the syneresis. Therefore, a simulation study using 3D-printed spherical liquid pockets was conducted. Density stratification within the liquid pocket results in relative motion due to inertial effects when saccadic oscillations take place, in addition to the gravitational effects. A spherical syneretic pocket is simulated as a 10 mm diameter saline-filled cavity off-center within a larger 38 mm sphere to represent the dimensions of a bovine eye.
Results :
A 100-microliter solution of colored nanoparticles 80 nm in diameter (NanoCym) was injected in solution form into the saline-filled spherical cavity and photographic images were obtained for the progression of the nanoparticle dispersion both with and without the simulated saccadic motion. Since the particle density was slightly higher than the saline, a slow downward drift was observed. Without saccadic motion (control), diffusion took place and an equilibrium distribution (a balance of gravity and diffusion) was achieved in about 10 hours. With simulated saccadic motion, the mixing was enhanced and highly dispersed distribution was observed after 3 hours. Repeating the experiments two more times showed similar results.
Conclusions :
The effect of saccadic motion on macromolecular and nanoparticulate drug distribution is not significant in the gel portion of the vitreous. However, within the liquid region, cases with and without the simulated saccadic motion have shown that such oscillatory motion enhances the distribution levels when the drug density is different from the liquid.
This is a 2020 ARVO Annual Meeting abstract.