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Samirkumar R. Patel, Eric Powers, Mark R. Prausnitz, Henry F. Edelhauser; Fluid Infusion Into the Corneal Stroma Using a Microneedle. Invest. Ophthalmol. Vis. Sci. 2012;53(14):482.
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Corneal infections, especially deep stromal infections, can require an aggressive therapy regimen using topically applied agents. It would be ideal to have a delivery method that can administer drug directly to the stroma to stop spread of the infection quickly without relying on patient compliance. Here, we investigate the capability of a microneedle to infuse a fluid into the corneal stroma and study the volume that can be delivered, the pressures needed for injection and the spread of injected material.
Enucleated porcine eyes were placed in a holder and microneedles (700-800 µm in length) were inserted perpendicularly into the cornea. The needles were attached to tubing with an in-line pressure transducer connected to a computer for continuous pressure monitoring. The tubing was attached to a 1 mL syringe that was mounted onto a syringe pump. The needle was inserted near the central cornea and the pump was used to inject a target volume of sulforhodamine B into the stroma at a flow rate of 100 µL/min. Images of the cornea were taken to measure the spread of the colored dye.
Intrastromal injections of up to 300 µL were achieved in all attempts using a microneedle. The spread of the injection was radial from the site of injection and the injection of 50, 80, 100, 200 and 300 µL resulted in a spread diameter of 6.3±0.5, 6.9±1.0, 8.2±0.1, 10.0±0.5 and 11.4±0.7 mm, respectively. The pressure profile during injection reached a peak within 25-35 s after the injection was started and then dropped off. The peak pressure during all injections was between 27-32 psi. During injection of volumes between 100-300 µL, the pressure leveled off before injection was stopped. In these cases the pressure averaged between 15-20 psi. All volumes caused the cornea to expand and injection of 200-300 µL resulted in a 3-4 mm increase in thickness.
This study demonstrated that a microneedle can inject up to 300 µL of fluid directly into the corneal stroma of porcine eyes. The injected fluid spread radially and a volume as small as 50 µL was able to spread significantly. Large volumes, however, caused significant corneal thickening. As a result, if minimal corneal thickening is desired, small volumes, < 50 µL should be used. This approach could be used to deliver drugs to the cornea for the treatment of corneal infections.
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