Development of an image-guided non-vitrectomy subretinal access approach for trans-scleral cell and gene therapy delivery

PurposeRegenerative therapies for retinal diseases include cell and gene therapy modalities that are targeted to the subretinal space. Several recent clinical trials have shown that the morbidity of surgical access is the major limitation of safe subretinal space delivery. We aimed to develop an image-guided procedure for minimally invasive subretinal access (MISA) as a platform to deliver therapeutic agents for the treatment of degenerative retinal diseases. MethodsWe engineered prototypes of a novel common-path swept source optical coherence tomography (CP-SSOCT)-enabled needle, coaxial guide (COG), and subretinal access cannula (SAC). We pilot tested the MISA procedure in ex vivo bovine eyes and in vivo porcine ocular surgery. ResultsA- and M-mode scan recordings of ex vivo and in vivo animal eye models demonstrated that CP-SSOCT imaging from the scleral side (ab externo) was capable of identifying the retinal laminae and the sub-retinal space. We show results from in vivo porcine MISA surgeries (N=4) using the novel CP-SSOCT-enabled sub-retinal injection needle, COG, and SAC through the transscleral approach. The MISA approach enabled subretinal device placement in the posterior pole, however, cases of retinal incarceration and retinal perforation were encountered. ConclusionsWe describe a novel CP-SSOCT-guided subretinal access approach that, with further optimization, may be useful in regenerative retinal surgery.