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An arched micro-injector (ARCMI) for innocuous subretinal injection.

You YS, Lee CY, Li C, Lee SH, Kim K, Jung H - PLoS ONE (2014)

Bottom Line: ARCMIs were fabricated using three major techniques: reverse drawing lithography, controlled air flow, and electroplating.These specific features were optimized via in-vitro experiments in artificial ocular hemispherical structures and subretinal injection of indocyanine green in porcine eye ex-vivo.We confirmed that the ARCMI was capable of delivering ocular drugs by subretinal injection without unusual subretinal tissue damage, including hemorrhage.

View Article: PubMed Central - PubMed

Affiliation: Nune Eye Hospital, Seoul, Republic of Korea.

ABSTRACT
Several critical ocular diseases that can lead to blindness are due to retinal disorders. Subretinal drug delivery has been developed recently for the treatment of retinal disorders such as hemorrhage because of the specific ocular structure, namely, the blood retinal barrier (BRB). In the present study, we developed an Arched Micro-injector (ARCMI) for subretinal drug delivery with minimal retinal tissue damage. ARCMIs were fabricated using three major techniques: reverse drawing lithography, controlled air flow, and electroplating. In order to achieve minimal retinal tissue damage, ARCMIs were fabricated with specific features such as a 0.15 mm(-1) curvature, 45° tip bevel, 5 mm length, inner diameter of 40 µm, and an outer diameter of 100 µm. These specific features were optimized via in-vitro experiments in artificial ocular hemispherical structures and subretinal injection of indocyanine green in porcine eye ex-vivo. We confirmed that the ARCMI was capable of delivering ocular drugs by subretinal injection without unusual subretinal tissue damage, including hemorrhage.

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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.
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pone-0104145-g005: 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.

Mentions: We next performed subretinal injections in porcine eyes to study whether ARCMIs can inject drugs into the subretinal space with minimal tissue damage in real eyes (Figure 5A). An ARCMI with a 0.15 mm−1 curvature, 5 mm length, and 45° bevel tip angle was applied onto the porcine retina surface obliquely (Figure 5B). The distance between the retinal surface and ARCMI could be determined using the shadow of the ARCMI tip. Indocyanine green (10 µL) could be smoothly injected via the ARCMI into the subretinal space with a pressure of 15 mmHg. Importantly, indocyanine green spread specifically in the subretinal space (dashed circle in Figure 5C), indicating successful subretinal injection with the ARCMI. Indocyanine green was predominantly present in the subretinal space after 5 minutes without fade away in vitreous cavity (Figure 5D).


An arched micro-injector (ARCMI) for innocuous subretinal injection.

You YS, Lee CY, Li C, Lee SH, Kim K, Jung H - PLoS ONE (2014)

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.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4128757&req=5

pone-0104145-g005: 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.
Mentions: We next performed subretinal injections in porcine eyes to study whether ARCMIs can inject drugs into the subretinal space with minimal tissue damage in real eyes (Figure 5A). An ARCMI with a 0.15 mm−1 curvature, 5 mm length, and 45° bevel tip angle was applied onto the porcine retina surface obliquely (Figure 5B). The distance between the retinal surface and ARCMI could be determined using the shadow of the ARCMI tip. Indocyanine green (10 µL) could be smoothly injected via the ARCMI into the subretinal space with a pressure of 15 mmHg. Importantly, indocyanine green spread specifically in the subretinal space (dashed circle in Figure 5C), indicating successful subretinal injection with the ARCMI. Indocyanine green was predominantly present in the subretinal space after 5 minutes without fade away in vitreous cavity (Figure 5D).

Bottom Line: ARCMIs were fabricated using three major techniques: reverse drawing lithography, controlled air flow, and electroplating.These specific features were optimized via in-vitro experiments in artificial ocular hemispherical structures and subretinal injection of indocyanine green in porcine eye ex-vivo.We confirmed that the ARCMI was capable of delivering ocular drugs by subretinal injection without unusual subretinal tissue damage, including hemorrhage.

View Article: PubMed Central - PubMed

Affiliation: Nune Eye Hospital, Seoul, Republic of Korea.

ABSTRACT
Several critical ocular diseases that can lead to blindness are due to retinal disorders. Subretinal drug delivery has been developed recently for the treatment of retinal disorders such as hemorrhage because of the specific ocular structure, namely, the blood retinal barrier (BRB). In the present study, we developed an Arched Micro-injector (ARCMI) for subretinal drug delivery with minimal retinal tissue damage. ARCMIs were fabricated using three major techniques: reverse drawing lithography, controlled air flow, and electroplating. In order to achieve minimal retinal tissue damage, ARCMIs were fabricated with specific features such as a 0.15 mm(-1) curvature, 45° tip bevel, 5 mm length, inner diameter of 40 µm, and an outer diameter of 100 µm. These specific features were optimized via in-vitro experiments in artificial ocular hemispherical structures and subretinal injection of indocyanine green in porcine eye ex-vivo. We confirmed that the ARCMI was capable of delivering ocular drugs by subretinal injection without unusual subretinal tissue damage, including hemorrhage.

Show MeSH
Related in: MedlinePlus