Intraoperative Use of Microscope-Integrated Optical Coherence Tomography for Subretinal Gene Therapy Delivery.

Intraoperative Use of Microscope-Integrated Optical Coherence Tomography for Subretinal Gene Therapy Delivery With advances in gene therapy biotechnologies, ophthalmology entered a new era of potential prevention, arrest, or reversal of previously untreatable retinal diseases. Key gene therapy trials have focused on degenerative conditions, such as inherited retinal degenerations caused by RPE65 mutations, choroideremia, achromatopsia, age-related macular degeneration, and Stargardt disease.1–4 Adeno-associated virus or lentivirus vectors used in many ongoing trials do not penetrate the retina well because of the relatively impermeable internal limiting membrane and are preferentially delivered via subretinal injection to directly contact the outer retina and the retinal pigment epithelium (RPE). Selective surgical delivery into the sub-RPE or suprachoroidal space has not been attempted as far as we are aware. Confirming delivery to a predefined target zone for therapeutic product injection is desirable in clinical trials and may enhance efficacy. In addition, a means to confirm the volume of injected vector intraoperatively will help to minimize the risk of incomplete dose delivery.1,3 Intraoperative OCT allows visualization of retinal anatomy and provides the surgeon with real-time feedback on instrument–tissue interaction.5 Posterior segment MIOCT images are possible through direct contact lens or a noncontact viewing system. Inclusion of intraoperative OCT has been shown to alter surgeons’ understanding of underlying tissues and surgical approach in 43% of membrane peeling procedures.5 We describe our experience with a novel approach of using microscope-integrated optical coherence tomography (MIOCT) for real-time guidance of subretinal delivery of gene therapy products in clinical trials.