Saccade movements effect on the intravitreal drug delivery in vitreous substitutes: a numerical study

Abstract

In this study, the distributions of intravitreal injected drugs in post-vitrectomy human eyes, which are subjected to periodic saccade movements, are investigated. The computational model for the vitreous cavity of human eye is a sphere with one side truncated by the eye lens. A dynamic mesh technique was used to model the eye motion and the unsteady 3-D forms of continuity; Navier-Stokes and concentration transport of drug equations were solved numerically. The numerical model was validated earlier for the vitreous liquid flow field. The predicted drug concentration for idealized geometry was compared with the available analytic solution and excellent agreement was observed. The validated computer model was then used to simulate a real vitreous cavity filled with Balanced Salt Solution or aqueous humor as a vitreous substitute in order to obtain distribution of drugs in the post-vitrectomy eyes or liquefied vitreous. Additionally, effects of locations of drug injection, drug diffusion coefficients and saccade amplitude on the drug distribution and its uniformity were investigated. Although the earlier findings in the literature reported a day or a week as a needed time for drug uniform distribution in the vitreous substitutes, the present work depicts that saccade movements augment the transport of the drug in a way that the uniformity of the drug distribution can be achieved in a matter of minutes. Furthermore, in a vitreous cavity subjected to the saccade movements, the diffusion coefficient of drugs does not significantly affect their distribution after a few minutes. Even the injection location does not matter as uniform distribution is achieved after some time.

Macro- and Microscale Properties of the Vitreous Humor to Inform Substitute Design and Intravitreal Biotransport

“…10,16,18,[168][169][170][171][172][173][174][175][176][177][178][179][180][181][182][183] The motion of fluid inside the vitreous (intact or liquefied) due to eye rotation or saccadic eye movement has been investigated by many groups, 168,169,171,180,183 with particular implications shown for drug delivery and pharmacokinetics in the vitreous. 170,172,173,178,184 A model of enzymatic degradation of the vitreous was created and used to study the mobility of intravitreal nanoparticles, which could better simulate the biotransport of a therapeutic injected into aged and liquefied vitreous. 18 An in vitro ocular flow model called the PK-Eye was proposed for use in preclinical drug development, 175 which can allow for testing of therapeutics in vitreous substitutes.…”

Precision Intravitreal Chemotherapy for Localized Vitreous Seeding of Retinoblastoma

“…The P-IVitC technique is based primarily on fluid dynamics principles from computational modeling and in vitro experiments that show drug dispersion following intravitreal injection is largely driven by advective mass transport, such as natural saccadic movement, rather than molecular diffusion [10, 11]. In other words, injected drugs remain localized at the injection site unless perturbed by movements of the globe.…”

Preclinical challenges for developing long acting intravitreal medicines

“…Whereas, a more dominant effect for drug with low diffusivity coefficients, such as macromolecules, is seen with convection. 322,323 Significant differences in drug distribution for both large and small molecules are seen with the effects of geometry, diffusion and convection. 324 Convection effects has been reported to have a bigger influence to mixing than saccades.…”