Abstract
Purpose :
To optimize the surgical procedure and test the applicability of the Gyroscope Therapeutics Orbit SDS™ in normal adult canine retinas. This suprachoroidal approach to subretinal delivery eliminates the need for a vitrectomy and avoids the formation of a retinotomy.
Methods :
Right eyes of four adult mongrel dogs (age: ~ 129 weeks; axial globe length: 22 ± 1.3 mm) underwent subretinal injection of an AAV2/5-GRK1-GFP vector with the Orbit SDS™. A 3 mm wide scleral incision located 8 mm posterior to the limbus in the supero-temporal quadrant was performed. The flexible cannula of the device was then introduced into the suprachroidal space and its progression towards the central tapetal fundus monitored under direct visualization through a digital operating microscope with intraoperative OCT. The microneedle was advanced into the subretinal space. A ~10 µL injection of BSS enabled formation of a subretinal bleb which was further expanded by injection of 100 µL of the viral vector solution. cSLO/OCT imaging and OCT angiography (OCTA) were performed with a Spectralis HRA/OCT2 unit at 5 and 9 weeks post injection to monitor GFP expression and integrity of the retinal layers.
Results :
All 4 dogs (4 eyes) had successful subretinal injections in the tapetal fundus, and retinas reattached within 48 hours. No adverse effects nor signs of ocular discomfort were seen. cSLO (BAF mode) showed GFP expression that had expanded beyond the bleb borders identified during surgery. A focal dark spot was seen funduscopically in the tapetal area that corresponded to the site of entry of the microneedle. En face OCTA imaging of the choriocapillaris confirmed this was the site of puncture. No evidence of choroidal neovascularization was seen in any of the 4 eyes. OCTA segmentation at the level of the nerve fiber layer confirmed in 1 out of 4 eyes perforation of the neuroretina with the microneedle that had been suspected at the time of surgery.
Conclusions :
Preliminary results show that the off label veterinary use of the Orbit SDS™ is a viable surgical approach for subretinal injections in healthy adult canine retinas. The presence of tapetal cells in the canine choroid caused some resistance but did not impair advancement of the microneedle into the SRS. Further histologic examination of the choroid and neuroretina will examine structural integrity of these tissues.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.