A Second-Generation (44-Channel) Suprachoroidal Retinal Prosthesis: Long-Term Observation of the Electrode-Tissue Interface

Abstract

Purpose: To report the long-term observations of the electrode-tissue interface and perceptual stability in humans after chronic stimulation with a 44-channel suprachoroidal retinal implant.

Methods: Four subjects (S1-4) with end-stage retinitis pigmentosa received the implant unilaterally (NCT03406416). Electrode impedances, electrode-retina distance (measured using optical coherence tomography imaging), and perceptual thresholds were monitored up to 181 weeks after implantation as the subjects used the prosthesis in the laboratory and in daily life. Stimulation charge density was limited to 32 µC/cm2 per phase.

Results: Electrode impedances were stable longitudinally. The electrode-retina distances increased after surgery and then stabilized, and were well-described by an asymptotic exponential model. The stabilization of electrode-retina distances was variable between subjects, stabilizing after 45 weeks for S1, 63 weeks for S2, and 24 weeks for S3 (linear regression; Pgradient > 0.05). For S4, a statistically significant increase in electrode-retina distance persisted (P < 0.05), but by the study end point the rate of increase was clinically insignificant (exponential model: 0.33 µm/wk). Perceptual electrical thresholds were stable in one subject, decreased over time in two subjects (linear model; P < 0.05), and increased slightly in one subject but remained within the predefined charge limits (P = 0.02).

Conclusions: Chronic stimulation with the suprachoroidal retinal prosthesis over 3 years resulted in stable impedances, small individual changes in perceptual electrical thresholds, and no clinically significant increase in electrode-retina distances after a period of settling after surgery.

Translational relevance: Chronic stimulation with the 44-channel suprachoroidal retinal implant with a charge density of up to 32 µC/cm2 per phase is suitable for long-term use in humans.

Conflict of interest statement

Disclosure: S.A. Titchener, Bionic Vision Technologies Pty Ltd (F); D.A.X. Nayagam, Bionic Vision Technologies Pty Ltd (F, P); J. Kvansakul, Bionic Vision Technologies Pty Ltd (F); M. Kolic, Bionic Vision Technologies Pty Ltd (F, R); E.K. Baglin, Bionic Vision Technologies Pty Ltd (F, R); C.J. Abbott, Bionic Vision Technologies Pty Ltd (R, F); M.B. McGuinness, None; L.N. Ayton, None; C.D. Luu, Bionic Vision Technologies Pty Ltd (F); S. Greenstein, None; W.G. Kentler, None; M.N. Shivdasani, None; P.J. Allen, Bionic Vision Technologies Pty Ltd (F, P); M.A. Petoe, Bionic Vision Technologies Pty Ltd (F, R, P)

Figures

Figure 1.

Position of electrodes relative to the fovea in subject S3. (Left) Infrared fundus imaging showing the location of the stimulating electrodes (visible as bright circles) and the silicone substrate (dark shadow) behind the retina. Concentric circles indicate degrees of visual field relative to the fovea (red dot) according to the Drasdo and Fowler schematic eye., (Right) Electrode naming convention for a right eye implant. Electrode A06 in the inferior–nasal region is closest to the fovea for this subject (S3). The left eye implant is identical but mirrored horizontally. A and B refer to the stimulator unit that controlled that particular electrode (22 electrodes per stimulator).

Figure 2.

Longitudinal electrode–retina distance measures for all 44 stimulating electrodes for subjects S1 to S4. Data from all electrodes are included, but not all electrodes are represented at every time point. An asymptotic exponential model was fitted to the data (solid black line), suggesting an initial period of increasing distances that then settled to a stable value that was maintained for the rest of the study. The dashed black line indicates the switch-on date for each subject. There was no significant change in the average electrode-retina distance after 51 weeks postoperative for S1, 63 weeks postoperative for S2, and 17 weeks postoperative for S3, indicated by dashed red lines (linear model, Pgradient > 0.05). For S4, the electrode–retina distances continued to increase for the duration of the study, but seem to be approaching an asymptote.

Figure 3.

Heat maps showing electrode-retina distances across the electrode array for each subject (S1–S4) at device switch-on (left column) and at the study end point (right column). Color represents electrode to retina distance in microns. Black circles indicate electrode locations. A black cross marks the approximate location of the fovea for each subject. S1 received the implant in the left eye, and S2 to S4 received the implant in the right eye.

Figure 4.

Longitudinal impedance measures for subjects S1 to S4, showing only impedances measured before any other stimulation each day.

Figure 5.

Impedance decreased with increasing electrode-retina distance. The black line represents a mixed-effects linear model fitted to impedance versus electrode-retina distance with subject as a random variable (P < 0.001).

Figure 6.

Perceptual thresholds for a subset of five electrodes per subject. Circles represent single electrodes, and crosses represent electrodes that were operated as synchronous or shorted pairs, which were typically used in peripheral locations where higher charge levels were required. Regression models fitted to the data are represented by solid lines when the gradient was significantly different from zero (P < 0.05) and dashed lines otherwise. (A) Perceptual thresholds and exponential fit over time. (B) Perceptual thresholds and linear fit against electrode eccentricity from the fovea. For shorted/synchronous pairs, the eccentricity was calculated from the centroid of the two electrodes. (C) Perceptual thresholds and linear fit against electrode–retina distance. For shorted/synchronous pairs, the average distance for the two electrodes is shown.

Figure 7.

Impedance of electrodes decreased temporarily as they received stimulation. Changes in impedance from the start of each day to the end of each day for individual electrodes are plotted against the total charge delivered to the electrode over the course of the day. Data are excluded if the only stimulation delivered to an electrode was for impedance measurement. Note that the horizontal axis is logarithmic. A logarithmic function was fitted for each subject, represented by black lines, and the 95% CI indicated by gray lines.

Figure 8.

Stimulus-related changes in impedance were observed for a small number of electrodes. (A) Longitudinal impedance measures for S2 for electrodes A20 (blue) and B20 (red). (B) Electrode–retina distance for S2 electrodes A20 and B20. (C) Daily charge delivered to S2 electrodes A20 and B20. (D) Longitudinal perceptual threshold measures for S2 electrodes A20 and B20 (operated as a pair). (E) Longitudinal impedance measures for S3 A18 (blue) and B10 (red). (F) Electrode–retina distance for S3 electrodes A18 and B10. (G) Daily charge delivered to S3 electrodes A18 and B10. (H) Longitudinal perceptual threshold measures for S3 electrodes A18 and B10 (operated as a pair). Note that the vertical scales differ between subjects. Only impedance measures taken at the start of each day (before any other stimulation) are included. Impedance is smoothed using a median filter with a window width of 14 days. In both cases, the two electrodes occupy neighboring positions on the electrode array and were operated as a shorted pair, so the charge delivered to each electrode is the same.

Figure 9.

Changes in impedance that were apparently unrelated to stimulation were observed in S3 for a large number of electrodes between 115 and 140 weeks postoperatively. The affected electrodes are categorized into two distinct groups (blue and red) based on the shape of the impedance curve. (A) Longitudinal impedance measures for the first group of electrodes (blue). (B) Longitudinal electrode–retina distance measures for the first group of electrodes. (C) Schematic of the array showing the first group of electrodes highlighted in blue. The approximate location of the fovea is indicated by a black cross. (D) Longitudinal impedance measures for the second group of electrodes (red). (E) Longitudinal electrode–retina distance measures for the second group of electrodes. (F) Schematic showing the second group of electrodes highlighted in red. The approximate location of the fovea is indicated by a black cross. Impedance measures were smoothed using a median filter with a window width of 14 days. Note that these electrodes had been deactivated in the stimulation configuration deployed to the subject's device, and therefore received no stimulation except for impedance tests.