Intrastromal delivery of bevacizumab using microneedles to treat corneal neovascularization.

Investigative Ophthalmology & Visual Science

PubMedID: 25212779

Prausnitz MR, Kim YC, Grossniklaus HE, Edelhauser HF. Intrastromal delivery of bevacizumab using microneedles to treat corneal neovascularization. Invest Ophthalmol Vis Sci. 2014;55(11):7376-86.
Purpose: This study tested the hypothesis that highly targeted intrastromal delivery of bevacizumab using coated microneedles allows dramatic dose sparing compared to subconjunctival and topical delivery for treatment of corneal neovascularization. Methods: Stainless steel microneedles 400 µm in length were coated with bevacizumab. A silk suture was placed in the cornea approximately 1 mm from the limbus to induce corneal neovascularization in the eyes of New Zealand White rabbits that were divided into different groups: untreated, microneedle delivery, topical eye drop, and subconjunctival injection of bevacizumab. All drug treatments were initiated four days after suture placement and area of neovascularization was measured daily by digital photography for 18 days. Results: Eyes treated once with 4.4 µg of bevacizumab using microneedles reduced neovascularization compared to untreated eyes by 44% (day 18). Eyes treated once with 2,500 µg of bevacizumab using subconjunctival injection gave similar results to microneedle-treated eyes. Eyes treated once with 4.4 µg of subconjunctival bevacizumab showed no significant effect compared to untreated eyes. Eyes treated with 52,500 µg of bevacizumab by eye drops three times per day for 14 days reduced neovascularization area compared to untreated eyes by 6% (day 18), which was significantly less effective than the single microneedle treatment. Visual exam and histological analysis showed no observable effect of microneedle treatment on corneal transparency or microanatomical structure. Conclusions: This study shows that microneedles can target drug delivery to corneal stroma in a minimally invasive way and demonstrates effective suppression of corneal neovascularization after suture-induced injury using a much lower dose compared to conventional methods.