Intraoperative Microscope-integrated Optical Coherence Tomography for Subretinal Gene Therapy Delivery



To report the novel use of microscope-integrated optical coherence tomography (MIOCT) as an adjunct to delivery of subretinal gene therapy.


The Bascom Palmer Eye Institute, Miami, FL, USA


The MIOCT was used intraoperatively during subretinal injections of adeno-associated viral serotype 2 vector (AAV2) encoding Rab-escort protein 1 (REP1) in 5 patients with choroideremia enrolled in a clinical trial. Retinal layers were visualized in real-time with MIOCT to assure the subretinal space was entered with balanced salt solution prior to injection of the viral vector, to visualize that the viral vector expanded the subretinal space, and to watch for macular hole formation.


Assuring entry into the subretinal space proved challenging in patients with advanced choroideremia and very thin retina. Utilization of intraoperative MIOCT allowed real-time confirmation of subretinal injection of balanced salt solution in 5 patients and subsequent avoidance of sub- retinal pigment epithelium or suprachoroidal delivery of the viral vector in 3 of 5 cases. Thin foveal tissue and preexisting macular holes were monitored during injection for hole formation or enlargement.


Utilization of intraoperative MIOCT allowed the surgeon to visualize retinal microanatomy in real-time in order to assure injection of viral vector into intended tissue plane. Development of intraoperative MIOCT for this indication may be helpful to the retina surgeons involved in gene therapy clinical trials. Use of this technique would likely make gene therapy accessible to more surgeons and clinical centers.



Ninel Z. Gregori
Miami, FL, United States
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