Optimizing Subretinal Gene Therapy Delivery with Microscope-Integrated Optical Coherence Tomography and Novel Suprachoroidal Delivery System

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 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.