Abstract

Self-sealing hyaluronic acid (HA)-coated self-sealing 30-gauge needles exhibiting instant leakage prevention of intravitreal humor and injected drug were developed in this study. Ninety New Zealand rabbits were used in this study. We assessed dye regurgitation in intravitreal ICG dye injections using HA-coated needles (HA needle group) and conventional needles (control group). Vitreous humor levels of anti-vascular endothelial growth factor (VEGF) were compared between groups one, three, and seven days after intravitreal bevacizumab (0.016 mL) injections. Expression levels of inflammatory cytokines in the aqueous humor and vitreous humor, including prostaglandin E2 (PGE2), interferon-γ, tumor necrosis factor-α, interleukin (IL)-1β, IL-4, IL-6, IL-17, and IL-8, were compared between HA needle, control, and normal (in which intravitreal injection was not performed) groups following 12 intravitreal injections over a period of one week. In the HA needle group, HA remained at the injection site and blocked the hole after intravitreal injection. Dye regurgitation occurred significantly less frequently in the HA needle group (16.7%) than the control group (55.6%) after intravitreal ICG dye injection. Meanwhile, vitreous anti-VEGF levels were markedly higher in the HA needle group than the control group one and three days after intravitreal bevacizumab injections. After 12 intravitreal injections, expression levels of aqueous and vitreous IL-8 significantly increased in the control group compared to the HA needle and normal groups. Conversely, there were no significant differences in the expression of the other seven cytokines among the three groups. Intravitreal injections using HA-coated self-sealing 30-gauge needles can block the outflow of vitreous humor and drugs through the needle passage.

Highlights

  • Intravitreal injection is widely used for drug delivery in the treatment of various diseases of the posterior segment of the eye

  • We hypothesized that using needles coated with a substance such as Hyaluronic acid (HA), which can block the passage that forms after intravitreal injection, would prevent the outflow of vitreous humor and drugs, hindering introduction of pathogens through the needle passage site postinjection without causing inflammation

  • It is considered reasonable that no significant differences were observed in levels at seven days after injection. These results suggest that HA-coated needles immediately closed the fistulae produced in eyeballs by intravitreal injection, which maintained higher vitreous anti-vascular endothelial growth factor (VEGF) levels

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Summary

Introduction

Intravitreal injection is widely used for drug delivery in the treatment of various diseases of the posterior segment of the eye. Drugs injected into the vitreous cavity decrease in concentration according to their half-lives, which results in decreased efficacy over t­ime[8,9]. The beveled incision technique could reduce vitreous and drug reflux compared to a straight incision, maximizing the drug delivery and decreasing the risk of i­nfection[2,10]. Intravitreal injection using needles coated with a bio-inspired polymer could have the advantage of preventing the outflow of vitreous humor and drugs. We hypothesized that using needles coated with a substance such as HA, which can block the passage that forms after intravitreal injection, would prevent the outflow of vitreous humor and drugs, hindering introduction of pathogens through the needle passage site postinjection without causing inflammation. The purpose of this study was to verify the advantages and disadvantages of intravitreal injection using HA-coated needles in an animal study

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