June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Optimizing Subretinal Gene Therapy Delivery with Microscope-Integrated Optical Coherence Tomography and Novel Suprachoroidal Delivery System
Author Affiliations & Notes
  • William Raynor
    Department of Ophthalmology, Duke University School of Medicine, Durham, North Carolina, United States
  • Jianwei David Li
    Department of Biomedical Engineering, Duke University, Durham, North Carolina, United States
  • Ananth Sastry
    Department of Ophthalmology, Duke University School of Medicine, Durham, North Carolina, United States
  • Christian Viehland
    Department of Biomedical Engineering, Duke University, Durham, North Carolina, United States
  • Al-Hafeez Dhalla
    Department of Biomedical Engineering, Duke University, Durham, North Carolina, United States
  • Joseph A Izatt
    Department of Biomedical Engineering, Duke University, Durham, North Carolina, United States
    Department of Ophthalmology, Duke University School of Medicine, Durham, North Carolina, United States
  • Cynthia Toth
    Department of Ophthalmology, Duke University School of Medicine, Durham, North Carolina, United States
    Department of Biomedical Engineering, Duke University, Durham, North Carolina, United States
  • Lejla Vajzovic
    Department of Ophthalmology, Duke University School of Medicine, Durham, North Carolina, United States
  • Footnotes
    Commercial Relationships   William Raynor, None; Jianwei Li, None; Ananth Sastry, None; Christian Viehland, None; Al-Hafeez Dhalla, Beyeonics (C), Leica (P), Leica (R); Joseph Izatt, Carl Zeiss Meditec (P), Carl Zeiss Meditec (R), Leica Microsystems (P), Leica Microsystems (R), St. Jude Medical (P), St. Jude Medical (R); Cynthia Toth, Alcon (F), EMMES (C), Hemosonics (F), unlicensed patents and patents pending on OCT technologies (P); Lejla Vajzovic, Alcon (C), Orbit Biomedical (C)
  • Footnotes
    Support  U01 EY028079, RO1 EY023039, P30 EY005722, VRSF Research Award, Orbit Biomedical Research Grant
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 4487. doi:
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      William Raynor, Jianwei David Li, Ananth Sastry, Christian Viehland, Al-Hafeez Dhalla, Joseph A Izatt, Cynthia Toth, Lejla Vajzovic; Optimizing Subretinal Gene Therapy Delivery with Microscope-Integrated Optical Coherence Tomography and Novel Suprachoroidal Delivery System. Invest. Ophthalmol. Vis. Sci. 2020;61(7):4487.

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

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Abstract

Purpose : Subretinal (SR) gene therapy administered via the trans-vitreal approach is becoming an effective treatment and delivery approach for various retinal diseases. However, it is difficult to assess needle penetration depth using this SR delivery technique guided by only en-face surgical views. This study aims to increase the depth-related feedback available to surgeons and introduce novel suprachoroidal delivery system for more accurate drug delivery into the SR space.

Methods : Ten ex-vivo porcine eyes each received a SR bleb injection via suprachoroidal delivery system (Orbit Biomedical, Ambler, PA) with a 35 G needle protracted into the SR space. A nominal amount of BSS was injected first to verify correct needle placement (entry bleb) followed by therapeutic injection (final bleb). Surgical images and OCT volumes were captured for both the entry and final blebs (Fig 1) via a surgical microscope with a custom 100 kHz swept-source MIOCT system and TrueVision unit (Goleta, CA). Cross-sectional areas from each bleb were manually segmented and volumes were computed using a calibrated optical model (Li et al, SPIE, 2020). Images were graded for needle visualization in the SR space. Agreement between 2 of 3 graders constituted the final grade for each eye.

Results : The mean intended injection volume from the suprachoroidal cannula was 66.44 ± 2.4μL. The mean injection volume as measured by MIOCT imaging method was 54.8 ± 12.3µL (range 32.8 - 69.6µL). Graders localized the needle in the SR space in 8 of 10 eyes (Fig 2).

Conclusions : MIOCT is useful tool for quantification of SR blebs and needle visualization in the SR space. Additionally, the novel suprachoroidal approach proved to be a reliable method of administering injections into the intended SR space. These may improve standards for SR therapy delivery and therefore treatment efficacy.

This is a 2020 ARVO Annual Meeting abstract.

 

Figure 1. The SR entry bleb (A, C, E) and final bleb (B, D, F) were created using a novel suprachoroidal injection system. The en-face surgical microscope views (A, B), the 3D MIOCT volume views (C, D) and the MIOCT B-scan cross-sectional images (E, F) were captured. The device and the needle (white arrows) in the SR space can be seen on the volume view (C) and the B-scan (E).

Figure 1. The SR entry bleb (A, C, E) and final bleb (B, D, F) were created using a novel suprachoroidal injection system. The en-face surgical microscope views (A, B), the 3D MIOCT volume views (C, D) and the MIOCT B-scan cross-sectional images (E, F) were captured. The device and the needle (white arrows) in the SR space can be seen on the volume view (C) and the B-scan (E).

 

Figure 2. The needle can be visualized using the B-scans of the entry SR bleb captured on MIOCT. Also, corresponding net injection volumes are shown.

Figure 2. The needle can be visualized using the B-scans of the entry SR bleb captured on MIOCT. Also, corresponding net injection volumes are shown.

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