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Susan S Lee, Michael Robinson, Mohammad Kazemi, Anita Nikolova Penkova, Satwindar Singh Sadhal, Mayssa Attar, Julie Elizabeth Whitcomb; The effect of elevated intraocular pressure on convective flow in the vitreous. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):234.
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© ARVO (1962-2015); The Authors (2016-present)
Intravitreal injections of corticosteroids and anti-vascular endothelial growth factor (VEGF) molecules are currently the standard of care for sight threatening retinal conditions such as diabetic macular edema and neovascular age-related macular degeneration. To understand the effect of intraocular pressure (IOP) changes on convective flow in the vitreous, we conducted computational fluid dynamic (CFD) simulations of molecules that model corticosteroids and anti-VEGF.
A 3D axisymmetric CFD model of the human eye was developed and solved for diffusion and convection using ANSYS Fluent. Simulations of a pars plana intravitreal injection of a small molecular weight molecule similar to a corticosteroid (vitreous diffusion coefficient 9.9E-10 m2/s) were conducted with IOPs of 10, 15, and 30 mmHg. Similarly, simulations of a pars plana injection of a large molecular weight biologic molecule similar to an anti-VEGF (vitreous diffusion coefficient 7.6E-11 m2/s) were also conducted at the same IOPs. The volume-averaged drug concentrations were determined over a month duration and the vitreous half-lives for each drug at the different IOPs were determined.
The volume-averaged velocity magnitude in the aqueous humor (2.37E-06, 2.29E-06, 2.06E-06 m/s) and trabecular meshwork (1.15E-06, 1.11E-06, 9.80E-07 m/s) decreased with increasing IOP (10, 15, 30 mmHg) (Figure 1). Velocity in the cornea, sclera, vitreous, retina, and choroid increased with increasing IOP. The vitreous half-life of the small molecule was 1.25 days for all 3 IOPs tested, whereas the biologic molecule vitreous half-life was 12 days at 10 and 15 mmHg and decreased to 8 days at 30 mmHg.
CFD modeling of intravitreal injections of surrogate corticosteroids and anti-VEGFs help to understand the effect of IOP on convective flow in the vitreous. Based on the CFD simulation, elevated IOP appears to increase the velocity in the vitreous and may result in an increase of drug clearance of large molecular weight compounds; however, this observation requires further study to understand relevance.
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