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Description
Wet age-related macular degeneration (AMD) causes vision loss when vascular endothelial growth factor (VEGF) stimulates blood vessel growth into the light-sensitive retina. Anti-VEGF treatments such as ranibizumab are currently administered to treat wet AMD via intravitreal injections, which are unpleasant, expensive and risk complications. We explored the efficacy of topically administered ranibizumab, with cell penetrating peptides (CPPs).
Ex vivo pig eyes were divided into 3 groups and treated with 1. topical or 2. intravitreal ranibizumab and CPP, or 3. intravitreal ranibizumab. ELISAs measured ranibizumab and VEGF concentrations in the aqueous and vitreous at 20 min, 40 min, 1 hr and 3.5 hr (n = 3, per group). An ordinary differential equation model was formulated to describe the evolving concentrations of ranibizumab, VEGF and their compounds in the tear, aqueous and vitreal compartments.
CPP allows topical ranibizumab to penetrate the cornea but reduces ranibizumab availability and efficacy in neutralising VEGF for intravitreal treatment. Topical treatment may provide sustained, moderate suppression of vitreal VEGF levels, while intravitreal treatment provides strong suppression which lessens between treatments. Combined intravitreal/topical treatment presents a promising approach. Treatment efficacy would be enhanced if ranibizumab’s rate of binding to VEGF or tear residence time could be increased.
Bibliography
@Article{Roberts2025a,
author = {Roberts, P. A. and Thomas, C. N. and Bellamy Plaice, G. and Roberts, J. A. and Jones, M.-C. and Andrews, J. W. and Hill, L. J.},
journal = {Invest. Ophthalmol. Vis. Sci.},
title = {Mathematical Models of Topically and Intravitreally Applied Ranibizumab},
year = {2025},
number = {11},
pages = {45},
volume = {66},
doi = {10.1167/iovs.66.11.45}
}