Hydrodynamics of Intravitreal Injections into Liquid Vitreous Substitutes.

Christin Henein,Steve Brocchini,Nkiruka Ibeanu,Peng Tee Khaw,Stavros Vlatakis,Sahar Awwad,Yann Bouremel

doi:10.3390/pharmaceutics11080371

Abstract

Intravitreal injections have become the cornerstone of retinal care and one of the most commonly performed procedures across all medical specialties. The impact of hydrodynamic forces of intravitreal solutions when injected into vitreous or vitreous substitutes has not been well described. While computational models do exist, they tend to underestimate the starting surface area of an injected bolus of a drug. Here, we report the dispersion profile of a dye bolus (50 µL) injected into different vitreous substitutes of varying viscosities, surface tensions, and volumetric densities. A novel 3D printed in vitro model of the vitreous cavity of the eye was designed to visualize the dispersion profile of solutions when injected into the following vitreous substitutes—balanced salt solution (BSS), sodium hyaluronate (HA), and silicone oils (SO)—using a 30G needle with a Reynolds number (Re) for injection ranging from approximately 189 to 677. Larger bolus surface areas were associated with faster injection speeds, lower viscosity of vitreous substitutes, and smaller difference in interfacial surface tensions. Boluses exhibited buoyancy when injected into standard S1000. The hydrodynamic properties of liquid vitreous substitutes influence the initial injected bolus dispersion profile and should be taken into account when simulating drug dispersion following intravitreal injection at a preclinical stage of development, to better inform formulations and performance.

Highlights

Intravitreal therapy (IVT) is one of the most frequently performed procedures across all medical and surgical specialties [1,2]
To treat age-related macular degeneration (AMD), intravitreal injections are administered monthly, bimonthly, or as needed, depending on the anti-vascular endothelial growth factor (VEGF) agent, pathology, and progression of the condition. These injections come at a considerable financial burden to the National Health Service (NHS) due to their frequency and cost
We investigate the hydrodynamic effects, such as dynamic viscosity, surface tension, and volumetric density of simulated liquid vitreous and vitreous substitutes, which may influence the distribution profile of the initial bolus administered in IVT

Summary

Introduction

Intravitreal therapy (IVT) is one of the most frequently performed procedures across all medical and surgical specialties [1,2]. To treat AMD, intravitreal injections are administered monthly (e.g., ranibizumab [3]), bimonthly (e.g., aflibercept [4]), or as needed, depending on the anti-VEGF agent, pathology, and progression of the condition. These injections come at a considerable financial burden to the National Health Service (NHS) due to their frequency and cost. Ranibizumab and aflibercept are priced between £550 and £880 per injection respectively [7] This cost difference suggests there is significant overspending on registered drugs for AMD and that there is still an urgent need for longer-acting effective treatments with infrequent dosing at a reasonable price

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Results

Conclusion