Abstract
Purpose :
The primary treatment for posterior eye diseases is intravitreal (IVT) injection of anti-vascular endothelial growth factor (VEGF) antibodies. This is invasive and must be performed in a clinic, which is associated with patient discomfort and inconvenience. Eyedrop delivery of antibody therapeutics is non-invasive and can be performed at home but has been challenging due to size limitations of intraocular penetration. We developed ocular penetrating carrier (OPC) eyedrops that deliver anti-VEGF drugs into the posterior segment of the eye.
Methods :
We generated a library of OPCs and screened for ocular penetration via fluorescent dye labeled aflibercept-OPC eyedrop application in C57BL/6J mouse eyes. Select OPCs were validated in pig since pig eyes more closely resemble humans. OPCs exhibiting the highest intraocular penetration were used in a mouse model of laser induced choroidal neovascularization (CNV). Animals received eyedrops for 7 days immediately after laser treatment or 5-7 days post-laser in studies where lesions were analyzed point-to-point over time. Vascular leakiness was measured by fundus fluorescein angiography (FFA), lesion volume by optical coherence tomography (OCT), and CNV area by isolectin-B4 (IB4) staining and imaging. The decrease in CNV leakiness, volume, and area of aflibercept-OPC treatment was compared to buffer control. The eyedrop efficacy was compared to IVT injection of aflibercept. One-way ANOVA with Dunett’s multiple comparison test and two-tailed Student’s t-test were used for statistical analysis.
Results :
Several OPCs exhibited relatively high intraocular penetration delivery of aflibercept in mouse (Fig 1) and pig eyes. In a mouse model of laser induced CNV, aflibercept-OPC eyedrop treatment showed a decrease in leakiness, lesion volume and area after eyedrop treatment with efficacy similar to IVT injection (Fig 2).
Conclusions :
Aflibercept-OPC eyedrop treatment decreases vascular leakage and choroidal neovascularization in a mouse model of CNV. Our aflibercept-OPC eyedrops provide a non-invasive treatment for people suffering diseases of the eye posterior including AMD, DR, and DME.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.