Findings from a study published in Ophthalmology Science evaluated the efficacy and safety of the PRIMA (Pixium Vision) neurostimulation system for improving visual acuity (VA) in patients with geographic atrophy (GA) due to age-related macular degeneration (AMD) at 48 months following implantation.
Give me some background.
GA is associated with a gradual loss of photoreceptors of the macula, which can severely impair visual functions, including reading and facial recognition.
Low-resolution peripheral vision is retained in GA, and while photoreceptors are lost, the inner retinal neurons largely survive.
Consequently: PRIMA—a wireless subretinal prosthesis—was designed to convert projected light into patterns of electrical current to reintroduce visual information into the degenerating retina via electrical stimulation of second-order neurons (i.e., bipolar cells).
Talk about the PRIMA implant.
The first and current version of the PRIMA implant is a 2-mm wide (corresponding to about 7° of the visual angle in the human eye) and 30-μm thick microchip that contains 378 pixels of 100μm in width.
The PRIMA neurostimulation system also contains external components—namely augmented reality (AR) glasses and a pocket computer—that provide image-processing capabilities such as zoom.
How does the PRIMA neurostimulation system work?
Images captured by the camera on the AR glasses are processed and projected onto the implant using near-infrared (880 nm) light to prevent photophobic and phototoxic effects from bright illumination.
Then: Photovoltaic pixels convert this light into electric current flowing through the retina between the active and return electrodes, which stimulates the nearby inner retinal neurons.
Finally: These responses then pass through the retinal neural network to ganglion cells, harnessing the residual retinal signal processing.
Now talk about the study.
In this first-in-human clinical trial (NCT03333954) of the PRIMA subretinal prosthesis in patients with GA, investigators included five patients who had no foveal light perception and VA of logMAR 1.3-1.7 (20/400-20/1000) in their worse-seeing study eye.
What were the main outcome measures?
- VA using Early Treatment of Diabetic Retinopathy Study (ETDRS) charts with and without the system
- Light sensitivity in the central visual field, as measured by Octopus perimetry
- Anatomical outcomes demonstrated by fundus photography and optical coherence tomography (OCT) up to 48 months post-implantation
Findings?
All five subjects met the primary endpoint of light perception elicited by the implant in the scotoma area.
However, in one patient the implant was incorrectly inserted into the choroid and one patient died 18 months post-implantation due to reasons unrelated to the study.
Consequently, the ETDRS VA results were reported for three subjects.
How did PRIMA impact VA?
Without zoom: VA closely matched the implant's pixel size (1.17±0.13 pixels, mean logMAR 1.39, Snellen 20/500 [ranging from 20/438-20/565]).
With zoom: At 48 months, subjects improved their VA by 32 ETDRS letters versus baseline (standard error [SE] 5.1, 95% confidence interval [CI] 13.4-49.9, p<0.0001).
Natural peripheral visual function in the treated eye did not decline after surgery or during the 48-month follow-up period (p=0.08).
What about adverse events?
The majority of the device- and procedure-related non-serious adverse events (AEs) occurred within the first 6 months post-implantation; further, none of these events led to any long-term safety issues.
Reported AEs included:
- Microcysts discovered in three subjects (two happened 9 months post-implantation)
- Asymptomatic choroidal neovascular membrane (CNVM)
- Occurred in one patient, 31 months post-implantation
Expert opinion?
According to the study authors, “Unlike the current pharmacological treatments for GA, which aim to slow down the growth of atrophic lesions without any functional improvement in VA, our results demonstrate restoration of central vision in the former scotoma.”
Tie it all together for me.
These findings suggest that subretinal implantation of PRIMA in GA patients with profound vision loss due to AMD is feasible and well-tolerated, with no reduction of natural peripheral vision up to 48 months.
Prosthetic central vision provided by photovoltaic neurostimulation enabled patients to reliably recognize letters and sequences of letters, and with zoom it improved VA up to eight ETDRS lines.
Next steps?
The study authors noted that reduced pixel size in future implants may improve the prosthetic VA to significantly higher levels.