Delivery Routes of Topical Eyedrops Reaching the Posterior Segment of the Eye-Recent Advances

Current topical eyedrop treatments for posterior segment diseases face significant challenges, including rapid tear clearance and ocular barrier limitations, which hinder effective drug delivery to target tissues in the posterior segment. To date, no eyedrop formulation has been clinically approved for the treatment of ocular fundus diseases. Eyedrops reach the posterior segment via two primary routes: the corneal route and the conjunctival routes, the latter comprising the conjunctival-vasculature route and the conjunctival-scleral route. This review summarizes recent advances in topical eyedrop therapies for ocular fundus diseases, with a focus on their delivery routes and the mechanisms by which they reach the posterior segment of eye. The cell-penetrating homing peptides and lipid nanoparticle-encapsulated eyedrops primarily reach the posterior segment via the corneal route; cell-penetrating peptides and PepT-1-targeting ligands mainly utilize the conjunctival route; whereas chitosan nanoparticles, polymeric micelles, and supramolecular peptide-based eyedrops can access the posterior segment via both routes. By systematically clarifying the pathways and mechanisms by which eyedrops formulations traverse ocular barriers, this review aims to provide a rational foundation for future research and development in posterior segment drug delivery.