A non-surgical method for subretinal delivery by trans-scleral microneedle injection

Novel therapeutics have emerged for treating neurodegenerative eye diseases but are limited by non-optimal methods of ocular administration. Subretinal injection is the preferred method of delivery for retinal gene and stem-cell therapies, but its invasive and complex surgical procedure is a major limiting factor in clinical investigations and practice. Here, we engineered a novel trans-scleral injection technique to safely administer to the subretinal space in a simple, non-surgical, and minimally invasive procedure. Subretinal injection using this technique in rodents and rabbits took <1 min per injection and did not require a surgical microscope. Extensive safety examinations in rats showed that the injection technique reliably administered into the subretinal space with no incidence of retinal perforation, little or no choroidal bleeding, and no evidence of retinal toxicity. We further found that repeated subretinal injection in the same eye, in rats, was well tolerated. The developed technique may enable non-surgical subretinal injection without vitrectomy, potentially increasing safety, efficacy, and access to ocular therapies.