The PIONEER study is an open-label Phase I/IIa clinical trial assessing the safety and efficacy of optogenetic vision restoration in patients with advanced nonsyndromic retinitis pigmentosa (RP). Subjects are injected with a genetic vector that encodes a light-sensing protein and then wear a pair of light-stimulating goggles. The hope is that stimulation of the protein can restore photoactivating properties to damaged photoreceptors.
The intravitreal injection is administered into the eye with the least vision to target the foveal retinal ganglion cells.
The light-stimulating goggles worn by the patient use a special camera to detect changes in intensity in the visual world as distinct events. They then render these events in monochromatic images and project them in real time onto the retina in 595-nm light pulses to activate optogenetically transduced retinal ganglion cells.
The patient reported in the paper is a 58-year-old male, diagnosed with RP 40 years ago. Visual acuity was light perception and the worse-seeing eye was treated with the optogenetic vector. The researchers assessed retinal anatomy on OCT, color fundus photographs and fundus autofluorescence over 15 visits spanning 84 weeks before and after the injection.
The patient performed three functional vision tests. The first two involved verbal descriptions of object locations and the third involved object placement without direction and with behavioral and electroencephalogram recordings.
Before the injection with or without goggles or after the injection without goggles, the patient couldn’t visually detect any objects. With the therapy, the patient was able to perceive, locate, count and touch various objects—but only by using the vector-treated eye while wearing the goggles.
“The results of all three visual and visuomotor tests suggest that optogenetic retinal stimulation triggered by the visual scene induced visual perception,” the researchers wrote in their paper. “Moreoever, the visual process leading to the percept was effective enough to enable the patient to orient toward the object and perform the visuomotor task of reaching for it. The first and second tests were performed five months before the third visual test, suggesting that the gain in visual function was stable over the period.”
The researchers reported that “this is the first case of partial functional recovery in a neurodegenerative disease after optogenetic therapy.”
Sahel J, Boulanger-Scemama E, Pagot C, et al. Partial recovery of visual function in a blind patient after optogenetic therapy. Nature Medicine 2021. [Epub May 24, 2021].