Subretinal Photovoltaic Implant to Restore Vision in Geographic Atrophy Due to AMD

Abstract

Background: Geographic atrophy due to age-related macular degeneration (AMD) is the leading cause of irreversible blindness and affects more than 5 million persons worldwide. No therapies to restore vision in such persons currently exist. The photovoltaic retina implant microarray (PRIMA) system combines a subretinal photovoltaic implant and glasses that project near-infrared light to the implant in order to restore sight to areas of central retinal atrophy.

Methods: We conducted an open-label, multicenter, prospective, single-group, baseline-controlled clinical study in which the vision of participants with geographic atrophy and a visual acuity of at least 1.2 logMAR (logarithm of the minimum angle of resolution) was assessed with PRIMA glasses and without PRIMA glasses at 6 and 12 months. The primary end points were a clinically meaningful improvement in visual acuity (defined as ≥0.2 logMAR) from baseline to month 12 after implantation and the number and severity of serious adverse events related to the procedure or device through month 12.

Results: A total of 38 participants received a PRIMA implant, of whom 32 were assessed at 12 months. Of the 6 participants who were not assessed, 3 had died, 1 had withdrawn, and 2 were unavailable for testing. Among the 32 participants who completed 12 months of follow-up, the PRIMA system led to a clinically meaningful improvement in visual acuity from baseline in 26 (81%; 95% confidence interval, 64 to 93; P<0.001). Using multiple imputation to account for the 6 participants with missing data, we estimated that 80% (95% CI, 66 to 94; P<0.001) of all participants would have had a clinically meaningful improvement at 12 months. A total of 26 serious adverse events occurred in 19 participants. Twenty-one of these events (81%) occurred within 2 months after surgery, of which 20 (95%) resolved within 2 months after onset. The mean natural peripheral visual acuity after implantation was equivalent to that at baseline.

Conclusions: In this study involving 38 participants with geographic atrophy due to AMD, the PRIMA system restored central vision and led to a significant improvement in visual acuity from baseline to month 12. (Funded by Science Corporation and the Moorfields National Institute for Health and Care Research Biomedical Research Centre; PRIMAvera ClinicalTrials.gov number, NCT04676854.).

Figure 1. Rendering of the PRIMA system components.

(A) The system includes the PRIMA glasses with a camera and projection module, a pocket processor, and the implant. The captured image (e.g., a letter R) is processed and projected onto the implant by NIR (880nm) light. (B) Projection of NIR light onto the implant. (C) The implant, activated by the NIR light, stimulates the remaining nerve cells, which process the information in the retina and then transfer it via the optic nerve to the brain. (D) Photodiodes in each pixel of the subretinal implant convert light into electric currents to stimulate the nearby inner retinal neurons. To utilize flicker fusion for stable perception, the projector operates at a 30Hz frame rate, and perceptual brightness is adjusted by controlling the pulse duration from 0.7 to 9.8ms at peak irradiance of 3.5mW/mm². Each pixel comprises the active electrode in the center, a hexagonal return electrode mesh, and two photodiodes filling the space between the active and the return electrode. (E) Fundus photograph of a participant’s retina with the PRIMA implant. The implant is 2×2mm in size, composed of 100μm pixels.

Figure 2. Subretinal implant in a study participant’s eye.

This participant had an atrophy size of 21.49 mm² at baseline and was implanted five years after AMD diagnosis. (A) Color fundus photograph demonstrates GA prior to implantation. (B) The same eye with a subretinal implant at 12 months post-implantation. The green arrows indicate the direction of OCT scanning. (C) OCT image of the eye pre-implantation. (D) OCT image demonstrating the implant under the degenerated retina in proximity to the inner nuclear layer.

Figure 3. Change of VA from baseline (ETDRS).

(A) Progression of VA over time, measured at baseline, 6 months, and 12 months under three conditions: without PRIMA glasses (blue line), with PRIMA glasses (grey line), and participant’s choice (green line). Change in VA is expressed in both logMAR (primary y-axis) and letters (secondary y-axis). Data points represent the mean, with error bars indicating the 95% confidence intervals. Negative logMAR values indicate improvement in VA. (B) Box plots depicting logMAR change from baseline at 12 months without PRIMA glasses, with PRIMA glasses and participant’s choice. Individual participants’ data are represented by black dots.