Pixel size limit of the PRIMA implants: from humans to rodents and back

Abstract

Objective. Retinal prostheses aim at restoring sight in patients with retinal degeneration by electrically stimulating the inner retinal neurons. Clinical trials with patients blinded by atrophic age-related macular degeneration using the PRIMA subretinal implant, a 2 × 2 mm array of 100 µm-wide photovoltaic pixels, have demonstrated a prosthetic visual acuity closely matching the pixel size. Further improvement in resolution requires smaller pixels, which, with the current bipolar design, necessitates more intense stimulation. Approach. We examine the lower limit of the pixel size for PRIMA implants by modeling the electric field, leveraging the clinical benchmarks, and using animal data to assess the stimulation strength and contrast of various patterns. Visually evoked potentials measured in Royal College of Surgeons rats with photovoltaic implants composed of 100 µm and 75 µm pixels were compared to clinical thresholds with 100 µm pixels. Electrical stimulation model calibrated by the clinical and rodent data was used to predict the performance of the implant with smaller pixels. Main results. PRIMA implants with 75 µm bipolar pixels under the maximum safe near-infrared (880 nm) illumination of 8 mW mm−2 with 30% duty cycle (10 ms pulses at 30 Hz) should provide a similar perceptual brightness as with 100 µm pixels under 3 mW mm−2 irradiance, used in the current clinical trials. Contrast of the Landolt C pattern scaled down to 75 µm pixels is also similar under such illumination to that with 100 µm pixels, increasing the maximum acuity from 20/420 to 20/315. Significance. Computational modeling defines the minimum pixel size of the PRIMA implants as 75 µm. Increasing the implant width from 2 to 3 mm and reducing the pixel size from 100 to 75 µm will nearly quadrupole the number of pixels, which should be very beneficial for patients. Smaller pixels of the same bipolar flat geometry would require excessively intense illumination, and therefore a different pixel design should be considered for further improvement in resolution.