Table 4: Validation method and main results for 3D physiological models of drug delivery to the PSE.
Reference | Validation method | Main results |
[16] | Gd-DTPA data from MRI in vivo and ex vivo | estimate of lumped posterior membrane (6.0 × 10-8 cm2/s) and vitreous (2.8 × 10-6 cm2/s) diffusivity coefficient |
[21] | fluorescein data from in vivo IV injection | comparison between IV injection and implant; influence of vitreous drug diffusivity as a surrogate for drug molecular weight; influence of changes of the proportion of fluid loss by vitreous and aqueous outflows |
[18] | validation from GFP data in mouse after periocular injection | estimation of resistances (RPE: 9 × 105, periocular: 1.6 × 10-1 and choroid: 3.5 × 10-3), estimation of clearance rates from fitting of experimental data; sensitivity analysis on resistance, clearance rates, diffusivities, void volume for peak concentration, peak time and total integrated concentration |
[13] | validation from experimental data for systemic administration | study of the influence on drug levels of RPE active pumping, episcleral losses and choriocapillary clearance |
[15] | comparison with experimental data in rabbit eye after intravitreal injection | estimate of the hydraulic resistance of the trabecular meshwork by fitting procedure; comparison of solutions (fluid flow and drug) in different geometries; parametric study of clearance from the ASE; methodology to excerpt results for one species (human, rabbit, monkey) from different species |
[14] | transient mean plasma concentration and contours of anecortave acetate for different blood velocities; mean concentration in the choroid as indicator of the drug bioavailability at the retina | |
[17] | validation from fluoroscein data (IV injection, systemic) | effect of spatial inhomogeneities on episcleral drug delivery (to be compared with compartmental model by) [27], estimate of time duration of therapeutic drug levels for the igG1 Fab molecule |
[19] | effect drug mobility in sclera due to diffusion and permeability and of the partition coefficient at retina/vitreous interface and at retina/choroid interface | |
[12] | validation from experimental data for systemic (intravenous) administration | study of the effect of injection time and needle gauge/angle; study of the effect of implant position/type |
[20] | comparison with results obtained from recent models [13,18,27] | sensitivity analysis on diffusivity, clearance rates, permeability coefficient for drug concentration; sensitivity analysis on filtration velocity and fictitious-active velocity at RPE; theoretical analysis on lower and upper bound of drug concentration in the retina |
[22] | influence of vitreous liquefaction on velocity and on drug concentration in the retina; effect of implant position; influence on retinal drug concentration of the partition coefficient at vitreous/retina interface and of the rate of clearance at the retinal boundary; influence of intraocular pressure value on the drug concentration level in the retina |