Optogenetic Therapy for Restoring Aspects of Visual Function.

Retinitis pigmentosa is an inherited degenerative retinal disease that can lead to irreversible blindness. Optogenetic therapy has shown potential for restoring visual function at late stages of the disease. In this open-label study, we evaluated the safety of ganglion cell-directed optogenetic therapy in 10 participants with blindness due to advanced retinitis pigmentosa. Each participant received a single intravitreal injection of an adeno-associated viral (AAV) vector encoding the red-shifted channelrhodopsin ChrimsonR in the worse-seeing eye. The primary outcome was safety. Secondary outcomes included changes in light sensitivity as measured by full-field stimulus threshold (FST) testing conducted with the untreated eye patched and with the use of light-stimulating goggles designed to activate ChrimsonR. The definition of a clinically meaningful improvement in the FST (based on evidence from the literature and not prespecified in the protocol) was a decrease of at least 0.6 log units (i.e., an increase in light sensitivity by a factor of approximately 4). A total of 34 ocular adverse events occurred among 9 of the 10 participants, including 23 mild events and 10 moderate events. One severe event occurred: transient occlusion of the central retinal artery that occurred immediately after intravitreal injection and resolved within minutes after instillation of iopidine. Light sensitivity increased in 7 of the 10 participants, with increases ranging from a factor of 2.0 to a factor of 62.3; 6 participants had a clinically meaningful increase in light sensitivity. Within the limits of this small study, intravitreal administration of a ChrimsonR-expressing AAV vector targeting retinal ganglion cells combined with use of light-stimulating goggles was safe. Additional research is needed to further assess safety and efficacy. (Funded by GenSight Biologics; PIONEER ClinicalTrials.gov number, NCT03326336.).