June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Subretinal delivery by non-surgical, transscleral injection using a microneedle
Author Affiliations & Notes
  • Amir Hejri
    Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States
  • Micah Chrenek
    Department of Ophthalmology, Emory University, Atlanta, Georgia, United States
  • Nolan T Goehring
    Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States
  • Jiong Yan
    Department of Ophthalmology, Emory University, Atlanta, Georgia, United States
  • John N. Nickerson
    Department of Ophthalmology, Emory University, Atlanta, Georgia, United States
  • Mark Prausnitz
    Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States
  • Footnotes
    Commercial Relationships   Amir Hejri None; Micah Chrenek None; Nolan Goehring None; Jiong Yan None; John Nickerson None; Mark Prausnitz Clearside Biomedical, Code C (Consultant/Contractor), Clearside Biomedical, Code I (Personal Financial Interest), Clearside Biomedical, Code P (Patent)
  • Footnotes
    Support  R01EY022097, T32EY007192, P30EY006360, R01EY028450, R01EY021592, a Challenge Grant from Research to Prevent Blindness, Inc. to the Emory Eye Center
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 2625. doi:
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      Amir Hejri, Micah Chrenek, Nolan T Goehring, Jiong Yan, John N. Nickerson, Mark Prausnitz; Subretinal delivery by non-surgical, transscleral injection using a microneedle. Invest. Ophthalmol. Vis. Sci. 2023;64(8):2625.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Injection into the subretinal space (SRS) enables targeted drug and gene delivery to diseased retinal cells for treatment of neurodegenerative retinal diseases. This approach, however, is limited by its highly invasive and complex surgical procedure, as well as the formation of a subretinal bleb that is associated with safety concerns and insufficient injection spread in the SRS. In this work, we aimed to improve subretinal injections by developing a transscleral microneedle injection method for safe and simplified delivery that spreads across the SRS.

Methods : We designed a microneedle injector to access the SRS via the transscleral route by precise control of needle penetration into ocular layers. Key design parameters were individually tested and optimized in animals in vivo to minimize the risk of tissue damage and choroidal bleeding during injection. Fluid formulation and flow rate were varied to better understand fluid interaction with the retina and control injection spread in the SRS.

Results : Reliable subretinal delivery, validated by fundoscopy and optical coherence tomography imaging, was achieved in mice, rats, guinea pigs and rabbits without retinal perforation. A detailed safety analysis revealed no notable procedure-related tissue complications in any ocular layers. Injections caused no choroidal hemorrhage and triggered only a mild, highly localized, transient immune response. This excellent safety profile further enabled repeated SRS injections in the same eye without compounded adverse effects. Moreover, the simplicity of the injection method facilitated detailed testing of numerous flow parameters in >100 subretinal injections, through which we achieved controlled SRS delivery with increased circumferential spread and suppressed bleb formation, an outcome that has not been reported before.

Conclusions : This study introduces a novel transscleral technique for safe and widespread subretinal delivery via a simple, one-step procedure. The proposed method lays the foundation for development of a robust and minimally invasive method of subretinal injection that does not require vitrectomy and may be routinely performed as an office procedure. Additionally, the increased spread while suppressing bleb formation could potentially improve both treatment efficacy and safety by widespread coverage and reduced mechanical strain on fragile retina.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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