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.