In Vivo Efficacy of an Injectable Microsphere-Hydrogel Ocular Drug Delivery System.

Purpose: Demonstrate in vivo that controlled and extended release of a low dose of anti-vascular endothelial growth factor (anti-VEGF) from a microsphere-hydrogel drug delivery system (DDS) has a therapeutic effect in a laser-induced rat model of choroidal neovascularization (CNV).

Methods: Anti-VEGF (ranibizumab or aflibercept) was loaded into poly(lactic-co-glycolic acid) microspheres that were then suspended within an injectable poly(N-isopropylacrylamide)-based thermo-responsive hydrogel DDS.The DDS was shown previously to release bioactive anti-VEGF for ~200 days.

Quantitative retinal blood flow mapping from fluorescein videoangiography using tracer kinetic modeling.

Abnormal retinal blood flow (RBF) has been associated with numerous retinal pathologies, yet existing methods for measuring RBF predominantly provide only relative measures of blood flow and are unable to quantify volumetric blood flow, which could allow direct patient to patient comparison. This work presents a methodology based on linear systems theory and an image-based arterial input function to quantitatively map volumetric blood flow from standard fluorescein videoangiography data, and is therefore directly translatable to the clinic. Application of the approach to fluorescein retinal videoangiography in rats (4 control, 4 diabetic) demonstrated significantly higher RBF in 4-5 week diabetic rats as expected from the literature.

Inverse relationship between the intraretinal concentration of bioavailable nitric oxide and blood glucose in early experimental diabetic retinopathy.

Purpose: To directly measure in vivo retinal nitric oxide (NO) concentration in experimental early diabetic retinopathy and correlate measurements with blood glucose to determine how intraretinal NO changes with severity of diabetes.

Methods: Long-Evans rats were made diabetic with streptozotocin (STZ). Three weeks post STZ injection, intraretinal NO concentration profiles were recorded using a dual NO/electroretinogram microelectrode.

Objective area measurement technique for choroidal neovascularization from fluorescein angiography.

The purpose of this study was to develop a non-biased method of quantitatively measuring choroidal neovascularization (CNV) areas based on late-phase fluorescein angiography (FA) images. Experimental CNV was induced in Long Evans rats by laser disruption of the Bruch's membrane. FA was performed weekly for 5weeks.

Dual electroretinogram/nitric oxide carbon fiber microelectrode for direct measurement of nitric oxide in the in vivo retina.

Nitric oxide (NO) plays an important physiological role in normal and pathological retinas. Intraretinal NO concentrations have not been directly measured due to lack of NO electrodes capable of determining their location in the retina. The microelectrodes described here allow recording of the intraretinal electroretinogram (ERG) and NO concentration from the same location, with ERGs used to determine retinal depth.

The effects of cross-linked thermo-responsive PNIPAAm-based hydrogel injection on retinal function.

There is significant interest in biomaterials that provide sustained release of therapeutic molecules to the retina. Poly(N-isopropylacrylamide) (PNIPAAm)-based materials have received significant attention as injectable drug delivery platforms due to PNIPAAm's thermo-responsive properties at approximately 32 °C. While the drug delivery properties of PNIPAAm materials have been studied extensively, there is a need to evaluate the safety effects of hydrogel injection on retinal function.