Simulation of Thermally-Driven Buoyant Convection for Ocular Drug Delivery Enhancement

Abstract

Purpose : The main purpose of this work is to computationally simulate the effect of thermal stimuli on fluid transport to enhance intravitreal drug delivery. The goal is to take into consideration the partial liquefaction of the vitreous due to syneresis.

Methods : In an earlier experimental investigation (Huang and M. Gharib), a thermal stimulus applied to an eye model showed an enhancement of fluid flow in the vitreous due to the density stratification resulting from thermal expansion. While this was done for a wholly liquid vitreous, in the current computational investigation the vitreous is considered to be partially liquefied due to syneresis. The vitreous is modeled as a Darcy fluid for the fibrous gel part and a Newtonian fluid for the liquefied part. A thermal stimulus consisting of a Peltier heater is applied over a 0.25-cm^2 circular area to provide a steady temperature of approximately 10C above the normal body temperature of 37C. The choroidal tissues and those surrounding the eye have been modeled with the Pennes bioheat equation for transport between the vitreous and the vasculature. The density changes in the ocular fluids due to heating create a gravitational body force and induces fluid motion over and above the normal physiological flow. The simulations were conducted for various eye orientations with respect to the direction of gravity. The liquefied region was kept as a simple spherical segment in the posterior region. The computational simulation was carried out using Star CCM+.

Results : The simulations show that after 5-10 minutes of heating at 10C above the body temperature at the cornea leads to fluid motion in the aqueous and the vitreous humors. As expected, the liquefied region within the vitreous experiences significant motion owing to the free mobility of the fluid therein. Fluid velocities up to 0.07 cm/s are predicted.

Conclusions : Thermal stimulation of the eye for approximately 10 minutes at the cornea by 10C elevation of the temperature provides substantial increase of the fluid velocity, particularly in the syneretic regions. This technique has the potential to significantly enhance intravitreal drug delivery to the retina. Detailed studies to further explore and quantify the degree of enhancement are needed along with clinical recommendations for ophthalmologists as well as patients.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

 

Fig 1. Simulation of velocity field after 5 mins