Volume of therapeutics delivered into the subretinal space can be measured using swept-source microscope-integrated optical coherence tomography

Abstract

Purpose : Subretinal injections of therapeutics such as stem cells and viral vectors are being studied for the treatment of retinal degenerations. However, the inability to directly measure the volume delivered into the subretinal space presents a problem in advancing studies of potential treatments. To address this need, we propose an image-based method to measure the volume of therapeutics delivered into the subretinal space.

Methods : We used live swept-source microscope-integrated ocular coherence tomography (SS-MIOCT) to monitor and record ex vivo porcine subretinal injections (Figure 1). The surgeon first performed a pars plana vitrectomy with surgical induction of posterior vitreous detachment in a freshly enucleated porcine eye, then injected 50μL of diluted triamcinolone using a 1mL syringe and 25g/38g subretinal cannula calibrated to ensure delivery volume accuracy. The surgeon noted any observed triamcinolone leakage from the cannula or retinotomy. We then manually segmented the MIOCT image recordings to calculate the subretinal bleb volumes. Intrasession reproducibility was determined by segmentation of repeated OCT volumes taken at different scan angles.

Results : 13 subretinal blebs were created and imaged; of these, 3 were excluded from image analysis due to inadequate visualization of bleb margins in the images. In 3 of the 10 blebs analyzed, the surgeon observed “no leakage” of triamcinolone during the injection. The mean segmented subretinal volume of these was 52.1±3.9μL. In 6 cases in which “minimal leakage” was observed, the mean volume was 33.9±5.8μL. In 1 case of “significant leakage,” the measured bleb volume was 12.9μL. There was no significant difference in the intrasession bleb volumes calculated from repeated 0 and 90 degree scans (n=7 eyes, difference range: -1.9 to 1.2μL, p=0.908 by Wilcoxon signed-ranks test).

Conclusions : The volume of subretinally delivered therapeutics can be directly and reproducibly measured using SS-MIOCT. Use of this technique will contribute to the accurate assessment of subretinal dose delivered, which is important in studies of efficacy and toxicity of retinal therapies.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

 

Figure 1. Subretinal injection of 50μL of diluted triamcinolone with “no leakage” imaged using SS-MIOCT. Left column shows 3D volumes, and right column shows cross sections: (A) before, (B) during, and (C) after the injection.