Treatment Efficacy of a Dual Release of Aflibercept and Dexamethasone From a Single Hydrogel Drug Delivery System in a Rodent Model.

Abstract

Purpose: Age-related macular degeneration (AMD) is the leading cause of vision loss for the elderly population. Wet AMD, which accounts for approximately 15% of AMD cases, is characterized by abnormal blood vessel growth from the choroid into the subretinal space. Although intravitreal anti-vascular endothelial growth factor (VEGF) agents have become the standard of care for wet AMD, there is a growing subset of patients who do not fully respond to monotherapy anti-VEGF treatment. In previously published reports, corticosteroids have shown improvements in treatment efficacy when administered with anti-VEGF in a subset of non-responders to anti-VEGF monotherapy.

Methods: A combination dexamethasone and aflibercept drug delivery system (Combo-DDS) was evaluated in a laser-induced rodent model of choroidal neovascularization (CNV). Longitudinal monitoring was done through week 22 using fluorescein angiography (FA) and spectral domain optical coherence tomography (SD-OCT). Multi-Otsu thresholding was used to quantify the lesion area based on late-phase FA images. In addition, preliminary safety and biocompatibility of the Combo-DDS were evaluated by intraocular pressure (IOP) measurements, electroretinogram (ERG), and histology (n = 6 eyes/group).

Results: In the laser-induced CNV model, CNV lesions (n = 28-36 lesions/group) were monitored longitudinally. Combo-DDS showed a regression in lesion size starting at week 2 that continued through the end of study. IOP, ERG, and histology showed preliminary safety and biocompatibility of the Combo-DDS.

Conclusions: This study demonstrated that Combo-DDS maintained treatment efficacy in a laser-induced CNV rodent model for 6 months.

Translational relevance: The Combo-DDS shows the potential to eliminate the need for separate dosing regiments of anti-VEGF and corticosteroids for non-responders to anti-VEGF monotherapy.