Figure 1.
A comprehensive process of subretinal injection via the arched micro-injector (ARCMI).
(A) The ARCMI penetrates the ocular curves by passing through a trocar cannula, which is used as a surgical aid for protection from ocular tissue damage in ophthalmology. The ARCMI can then be glided up to the target site at the retinal region of posterior segment of the eye. (B) Magnified image of subretinal insertion of indocyanine green via ARCMI. ARCMI slides along the retinal surface to reduce retinal tissue damage. Indocyanine green was injected into the subretinal target site.
Figure 2.
Illustration of the fabrication method for the arched micro-injector (ARCMI).
(A) A straight SU-8 mold was formed at the end of blunt hollow metallic cannula (e.g., hypodermic needle) by reverse drawing lithography. (B) A flow of controlled air from a centrifugal fan produced the curved structure on the tip of the SU-8 mold of the ARCMI. (C) Hollow metallic walls on the mold surface were adopted by nickel sputtering and electroplating. (D) A hollow beveled tip was fabricated via tip polishing and removal of the SU-8 mold. (E) The hollow metallic structure of ARCMI formed after washing the mold.
Figure 3.
Different curvatures of SU-8 mold of Arched Micro-injector (ARCMI) produced by increasing airflow rate.
(A) The ARCMI curvature was defined as the inverse of the radius of a circle fitting the inner ARCMI curve (Inset). The radius of this circle was measured by photo analysis with real-time microscope. ARCMIs were fabricated with different curvatures and lengths (A). Image of ARCMI molds with various curvatures for lengths of (B) 10 mm length and (C) and 5 mm. ARCMI curvatures depended on both the mold length and rate of airflow. Scale bar: 1 millimeter.
Figure 4.
Subretinal injection of indocyanine green using the ARCMI in an artificial eye.
(A) The artificial eye was hemispherical composed of two layers consisting of an artificial retina (agarose gel) layer and artificial choroid (polydimethylsilane; PDMS) layer. (B) A straight needle ARCMI (curvature = 0) was difficult to insert into the subretinal space without incurring tissue damage. (C) An ARCMI with a curvature of around 0.15 mm−1 could be inserted into the artificial subretinal space through the agarose gel layer without damaging the PDMS layer. (D) Insertion of a needle with a curvature over 0.3 mm−1 was difficult because of the large surface of contact area with the artificial retina (D). Scale bar: 1 millimeter.
Figure 5.
Ex-vivo test of subretinal injection of indocyanine green via ARCMI in porcine eye.
(A) The ex-vivo test of the subretinal injection was performed using a standard 3-port pars plana vitrectomy, which is a widely used ocular surgical procedure for retinal disorder treatment. (B) All procedures were performed by ophthalmologists. The ARCMI reached on to the surface of the porcine retina, and the distance between retinal surface and ARCMI was determined using the shadow of the injector. (C) Indocyanine green with 10 µL was injected into subretinal space via ARCMI. (D) Subretinal injection of indocyanine green spread specifically in the subretinal space.
Figure 6.
Histological analysis of porcine eyes after subretinal injection.
Cryosection and tissue staining (Hematoxyline and Eosin) of the retina-choroid tissue of porcine was performed after subretinal injection with various tip form of Arched Micro-injector such as (A) no curved tip with large outer diameter (200 µm), (B) small outer diameter (100 µm) tip, (C) a 0.15 mm−1 curvature with 100 µm outer diameter and no beveled tip, and (D) a 45° bevel angle tip with 0.15 mm−1 curvature and 100 µm outer diameter. The straight tip caused damage to the retina as well as choroid surface. Lack of a beveled tip tore the retina surface resulting in a larger hole on the retina.