Restoring Color Perception to the Blind: An Electrical Stimulation Strategy of Retina in Patients with End-stage Retinitis Pigmentosa

Abstract

Purpose: Bioelectronic retinal prostheses that stimulate the remaining inner retinal neurons, bypassing degenerated photoreceptors, have been demonstrated to restore some vision in patients blinded by retinitis pigmentosa (RP). These implants encode luminance of the visual scene into electrical stimulation, however, leaving out chromatic information. Yet color plays an important role in visual processing when it comes to recognizing objects and orienting to the environment, especially at low spatial resolution as generated by current retinal prostheses. In this study, we tested the feasibility of partially restoring color perception in blind RP patients, with the aim to provide chromatic information as an extra visual cue.

Design: Case series.

Participants: Seven subjects blinded by advanced RP and monocularly fitted with an epiretinal prosthesis.

Methods: Frequency-modulated electrical stimulation of retina was tested. Phosphene brightness was controlled by amplitude tuning, and color perception was acquired using the Red, Yellow, Green, and Blue (RYGB) hue and saturation scaling model.

Main outcome measures: Brightness and color of the electrically elicited visual perception reported by the subjects.

Results: Within the tested parameter space, 5 of 7 subjects perceived chromatic colors along or nearby the blue-yellow axis in color space. Aggregate data obtained from 20 electrodes of the 5 subjects show that an increase of the stimulation frequency from 6 to 120 Hz shifted color perception toward blue/purple despite a significant inter-subject variation in the transition frequency. The correlation between frequency and blue-yellow perception exhibited a good level of consistency over time and spatially matched multi-color perception was possible with simultaneous stimulation of paired electrodes. No obvious correlation was found between blue sensations and array placement or status of visual impairment.

Conclusions: These findings present a strategy for the generation and control of color perception along the blue-yellow axis in blind patients with RP by electrically stimulating the retina. It could transform the current prosthetic vision landscape by leading in a new direction beyond the efforts to improve the visual acuity. This study also offers new insights into the response of our visual system to electrical stimuli in the photoreceptor-less retina that warrant further mechanistic investigation.

Keywords: Color vision; Retinal degeneration; Retinal stimulation; Vision restoration; Visual prosthesis.

Figure 1.

Demonstration of the importance of color in simulated prosthetic vision. A: colored and black-and-white presentations of a visual scene (371 × 456 pixels; adapted from http://webvision.med.utah.edu); B-C: images in A but downsampled to 14 × 18 pixels (B) and 7 × 9 pixels (C), respectively; D: colored and black-and-white presentations of an apple and an orange side-by-side (542 × 273 pixels); E-F: images in D but downsampled to 24 × 12 pixels (E) and 12 × 6 pixels (F), respectively.

Figure 2.

Color perceptions reported by test subjects under brightness control. A: stimulation waveform showing current amplitude (I), frequency (F) and pulse width (PW). B: current amplitude needed to maintain medium brightness (Im) with the increase of the frequency. Aggregate results obtained from 19 electrodes in 7 subjects. Fitting of the data with an exponential decay function shown in red, R² = 0.92. C: dominant colors reported and the number of electrodes that have generated each color (colors generated from less than 5 electrodes not shown). Data obtained from 29 electrodes across 7 subjects. D: plot of the dominant chromatic colors in the color space formed by blue-yellow and red-green axis. Color and size of the circles respectively represents the hue perceived and its frequency of occurrence.

Figure 3.

Changes of color perception with stimulation frequency and pulse width. A: representative colors perceived by Subject 2 under different combinations of frequency (6, 20, 40, 60, 120 and 200 Hz) and PW (0.2, 0.45, 0.6, 0.8, 1.0, and 1.5 ms). As the frequency increased, the subject’s perception changed from yellow (6 - 60 Hz) to blue (120 - 200 Hz) dominated colors. For the ease of illustration, if more than one colors were perceived in one phosphene, they are presented in concentric rings, each portraying the hue and saturation of one color reported. These rings do not depict the actual spatial relations of each color. B: representative colors perceived by another subject (Subject 4) under different combinations of frequency (6, 20, 40, 60 and 120 Hz) and PW (0.45, 0.6, 0.8, 1.0, and 2.0 ms). As the frequency increased, the subject’s color perception shifted from yellow and white (6 Hz) to purple (20-120 Hz). C: color perception obtained from 8 electrodes in different retinal locations of Subject 4 under variations of frequency (PW = 0.45 ms). D: Left: aggregate data of blue scores under variations of frequency; Right: the conversion scale from subjective descriptions of color perception to the blue scores. Data obtained from 20 electrodes in 5 subjects. E: aggregate data of blue scores under variations of PW at 20 Hz (black) and 120 Hz (red). Data obtained from 6 electrodes in 3 subjects for 20 Hz and 7 electrodes in 4 subjects for 120 Hz. Data presented in mean ± standard error.

Figure 4.

Stability of frequency-shifted yellow-blue perception over time. A: color perception under different frequencies in Subject 2. Data obtained from 4 electrodes at 10 months (left) and 19 months (middle) post-implantation. Right: locations of the electrodes in the array. B: average blue scores of the 4 electrodes at the two post-implantation time points. C: color perception under different frequencies in Subject 4. Data obtained from 4 electrodes at 7 months (left) and 14 months (middle) post-implantation. Right: locations of the electrodes in the array. D: average blue scores of the 4 electrodes at the two post-implantation time points. Data presented in mean ± standard error.

Figure 5.

Color perception with simultaneous stimulation of paired electrodes. A: color perception of Subject 1 when Electrode 1 was separately paired with Electrodes 2, 3, and 4. Data obtained at two frequencies (20 & 60 Hz for Pair 1 & 2 and Pair 1 & 3; 20 & 120 Hz for Pair 1 & 4). Left: locations of the electrodes in the visual field (labeled in red); Right: color percepts produced by activation of different electrode pairs and the relative locations of each color. B: color perception of Subject 4 when Electrode 1 was separately paired with Electrodes 2-6. Data obtained at 20 Hz. Left: locations of the electrodes in the visual field. Difference in the orientation of the visual field between Panel A & B reflects the array position in the right v.s. left eye. At 20 Hz, Electrode 1 consistently generated yellow percepts while other electrodes generated purple percepts (electrodes labeled by the corresponding colors). Edge-to-edge separation between Electrodes 1 & 3 is labeled by the dashed line with arrows. Right: relative locations of the yellow and purple percepts under activation of different electrode pairs.

Figure 6.

Fundus images and perceptual threshold of blue-sensing and non-blue-sensing subjects. A: Fundus images showing overall placement of the intraocular implant in Subject 3 (left) and the blown-up view of the retinal area nearby the electrode array (right). B-C: Fundus images obtained from the implant eye of Subjects 4 (B; OS) and 5 (C; OS). All 3 subjects reported blue/purple sensation at higher stimulation frequencies. D-E: fundus images obtained from the implant eye of Subjects 6 (D; OS) and 7 (E; OD). Neither subjects reported blue/purple sensation at higher stimulation frequencies. F: Perceptual threshold of 19 electrodes in the blue-sensing subjects v.s. that of 15 electrodes in the non-blue-sensing subjects.