Loss to the choroidal circulation was small compared to loss from the scleral surface. Active transport was predicted to induce periscleral movement of the drug, resulting in more rapid distribution and elevated drug concentrations in the choroid and sclera.
Purpose-The vitreous humor liquefies with age and readily sloshes during eye motion. The objective was to develop a computational model to determine the effect of sloshing on intravitreal drug transport for transscleral and intra-vitreal drug sources at various locations Methods-A finite element model based on a telescopic implicit envelope tracking scheme was developed to model drug dispersion. Flow velocities due to saccadic oscillations were solved for and were used to simulate drug dispersion.Results-Saccades induced a three-dimensional flow field that indicates intense drug dispersion in the vitreous. Model results showed that the time scale for transport decreased for the sloshing vitreous when compared to static vitreous. Macular concentrations for the sloshing vitreous were found be much higher than that for the static vitreous. For low viscosities the position of the intravitreal source did not have a big impact on drug distribution.
Conclusion-Model resultsshow that care should be taken when extrapolating animal data, which are mostly done on intact vitreous, to old patients whose vitreous might be a liquid. The decrease in drug transport time scales and changes in localized concentrations should be considered when deciding on treatment modalities and dosing strategies.
Transscleral delivery is an emerging, high-potential method for delivering drugs to the posterior eye. If successful, it could offer non-invasiveness comparable to drops and delivery efficiency comparable to intravitreal injection. However, there are numerous challenges to be overcome before transscleral delivery will be a significant treatment option. The resistance of the sclera is extremely well understood, but the other tissues, especially the retinal pigment epithelium, clearly demand more attention and the effect of drug chemistry remains poorly understood. In this review, the major research on transscleral delivery with an emphasis on current understanding of these points and open questions for the field is summarized.
The vitreous is a transparent gel that fills the posterior segment of the eye. With aging, the vitreous undergoes progressive liquefaction and thus more readily sloshes during eye motion [1]. In addition to its relevance to the problem of vitreous detachment [1], increased motion of the vitreous could have a profound effect on transport of drugs used to treat posterior segment eye diseases.
Delivering drugs to the posterior eye has been a challenge for many years. Systemic delivery of drugs is not a viable option because the eye does not receive enough blood supply, because of its small size, for the drug delivery process to be effective. Topical delivery in the form of eye drops is also ineffective in generating therapeutic concentrations in the posterior eye, because of the resistance offered by the corneal epithelium to the transport of drugs, and rapid elimination due to aqueous humor flow and tear dilution. Intravitreal delivery of drugs through implants and injections has been associated with serious side effects like endophthalmitis, hemorrhage, and retinal detachment. In recent years, transcleral delivery of drugs has received attention due to the relatively high permeability of the sclera.
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