Repurposing verteporfin and hyaluronic acid gel for ocular surface treatment to prevent corneal scarring

Abstract

There is an unmet need for point-of-care therapies to prevent scarring and promote corneal clarity after injury, which is essential for maintaining vision. Verteporfin, an inhibitor of Yes-associated protein (YAP), has been shown to prevent fibrosis in several organs. Visudyne (VP) is an FDA-approved liposomal formulation of verteporfin used to treat abnormal blood vessels in the eye. Here, we showed that VP reduces myofibroblast formation in corneal stromal fibroblasts. To prolong the residence time of verteporfin on the ocular surface, the cohesive viscoelastic ProVisc® hyaluronic acid (HA) gel was hybridized to VP. This formulation is readily translatable because both VP and ProVisc® HA gel are FDA-approved agents. The ProVisc® HA gel increased the residence of subconjunctivally injected verteporfin 12-fold at 24 h after injection compared with pure VP. A single subconjunctival administration of VP hybridized within ProVisc® HA gel (VP/HA hydrogel) significantly reduced YAP activation, corneal fibrosis, neovascularization, and inflammation, leading to reduced opacity without compromising epithelial wound healing in mechanically injured rat corneas. This work demonstrated that VP hybridized with a viscoelastic HA gel can be readily repurposed to promote scar-less healing in the cornea.

Keywords: Corneal scar prevention; Corneal wound healing; Fibrosis; Hyaluronic acid; Verteporfin.