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Yoo C. Kim, Henry F. Edelhauser, Mark R. Prausnitz; Intracorneal Delivery Of Bevacizumab Using Microneedles To Treat Injury-induced Neovascularization. Invest. Ophthalmol. Vis. Sci. 2012;53(14):507.
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Corneal transplantation is the most commonly performed tissue transplantation. Neovacuarlization in the cornea after corneal transplant introduces a significant increase in risk of graft rejection. For this reason, aggressive treatment of neovascularization is necessary after corneal transplant surgery in order to prevent rejection of the implanted cornea. This study examines the use of solid microneedles, coated with bevacizumab, to reduce corneal neovascularization in a minimally invasive way.
Solid metal microneedles 400 μm in length were fabricated by microfabrication. Bevacizumab was coated onto the microneedles using a rapidly dissolving formulation. A 7-gauge silk suture was placed approximately 1 mm from the limbus to induce corneal neovascularization in the eyes of New Zealand White rabbits. The rabbits were then divided randomly into four groups: untreated (Group 1), microneedle delivery (Group 2), topical eye drop (Group 3), and subconjunctival injection (Group 4). All treatments were done at four days after placement of the suture. For Group 2, a single bolus of approximately 1.1 μg of bevacizumab was given using four coated microneedles. For Group 3, a topical eye drop of bevacizumab (25 mg/mL) was given three times per day for 14 consecutive days. For Group 4, 100 μL of bevacizumab (25 mg/mL) was given as a subconjunctival injection. Digital photographs were obtained and the area of neovascularization was measured for 18 days.
Untreated eyes exhibited neovascularization that increased in area for up to 10 days followed by decrease in vascularization until it plateaued. Eyes treated with 1.1 μg of bevacizumab using microneedles (Group 2) reduced neovascularization compared to the untreated eye (Group 1) by 67.7% (day 10) to 40.8% (day 18). Eyes treated with 2500 μg of bevacizumab using subconjunctival injection (Group 3) reduced neovascularization compared to the untreated eye (Group 1) by 61.8% (day 10) to 29.4% (day 18). Eyes treated with 1250 μg of bevacizumab by eye drops three times per day for 14 days (Group 4) reduced neovascularization compared to the untreated eye (Group 1) by 44.3% (day 10) to 5.56% (day 18).
This study shows that microneedles can deliver a protein therapeutic locally into the intrastromal space of the cornea in a minimally invasive way and demonstrates that this approach can be effective to suppress neovascularization after suture-induced injury using a much lower dose compared to other conventionally used methods.
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