A Second-Generation (44-Channel) Suprachoroidal Retinal Prosthesis: Interim Clinical Trial Results

Abstract

Purpose: To report the initial safety and efficacy results of a second-generation (44-channel) suprachoroidal retinal prosthesis at 56 weeks after device activation.

Methods: Four subjects, with advanced retinitis pigmentosa and bare-light perception only, enrolled in a phase II trial (NCT03406416). A 44-channel electrode array was implanted in a suprachoroidal pocket. Device stability, efficacy, and adverse events were investigated at 12-week intervals.

Results: All four subjects were implanted successfully and there were no device-related serious adverse events. Color fundus photography indicated a mild postoperative subretinal hemorrhage in two recipients, which cleared spontaneously within 2 weeks. Optical coherence tomography confirmed device stability and position under the macula. Screen-based localization accuracy was significantly better for all subjects with device on versus device off. Two subjects were significantly better with the device on in a motion discrimination task at 7, 15, and 30°/s and in a spatial discrimination task at 0.033 cycles per degree. All subjects were more accurate with the device on than device off at walking toward a target on a modified door task, localizing and touching tabletop objects, and detecting obstacles in an obstacle avoidance task. A positive effect of the implant on subjects' daily lives was confirmed by an orientation and mobility assessor and subject self-report.

Conclusions: These interim study data demonstrate that the suprachoroidal prosthesis is safe and provides significant improvements in functional vision, activities of daily living, and observer-rated quality of life.

Translational relevance: A suprachoroidal prosthesis can provide clinically useful artificial vision while maintaining a safe surgical profile.

Conflict of interest statement

Disclosure: M.A. Petoe, BI (P), BVT (F,R); S.A. Titchener, BVT (F); M. Kolic, BVT (F,R); W.G. Kentler, BVT (F); C.J. Abbott, BVT (F,R); D.A.X. Nayagam, BI (P), BVT (F); E.K. Baglin, BVT (F,R); J. Kvansakul, BVT (F); N. Barnes, ANU (P), BVT (F); J.G. Walker, BVT (F); S.B. Epp, BVT (F); K.A. Young, BVT (F); L.N. Ayton, none; C.D. Luu, BVT (F); P.J. Allen, BVT (F), CERA (P)

Figures

Figure 1.

(A) The implanted ocular electrode array (left eye variant) shown with two implantable stimulators (image courtesy of D.A.X. Nayagam). (B) External components including a spectacle-mounted CMOS video camera, head-worn magnetically coupled transmission coils, and a body-worn portable video processor (image courtesy of W.G. Kentler).

Figure 2.

Indicative ocular aspects of the surgical procedure: (A) The electrode array is inserted into the dissected suprachoroidal pocket. (B) The Dacron patch is sutured to the eye globe and the lead grommet is placed within the orbitotomy. (C) The lateral rectus muscle is replaced and the periosteum is closed over the lead.

Figure 3.

Study flowchart. All time points are relative to device switch-on and basic fitting in week 1. Weeks 2 to 16 included training on camera use, head scanning, mobility, and task familiarization. Functional assessments comparing device on versus device off occurred in week 17, with repeated assessments at week 20, 32, 44, and 56.

Figure 4.

(A) Screen-based tasks were performed on a 40-inch touchscreen at arm's length. Shown here is the square localization task. (B) Measuring fingertip distance to target in the modified door task. (C) Tabletop search task. (D) Obstacle avoidance task. The subjects are shown in (B) and (D) wearing a backpack containing wireless equipment for remote control of device parameters.

Figure 5.

Configuration of the modified door task. All measurements are in centimeters. A black high-contrast target, representing a darkened window or doorway, was randomly positioned at location A, B, or C. The target measured 54 × 70 cm (W × H) and the top-edge was approximately 2 meters above the floor. Subjects started each trial at a random selection of starting points 1, 2, or 3.

Figure 6.

(A) The six obstacles used to seed the obstacle course: (1) tall pole (17 × 230 × 17 cm); (2) small box – hanging (15 × 30 × 10 cm); (3) large box – hanging (33 × 30 × 10 cm); (4) short pole (34 × 107 × 34 cm); (5) large wastepaper basket (34 × 78 × 34 cm); (6) small wastepaper basket (28 × 34 × 28 cm). (B) An example configuration of the obstacle course. A random selection of five of the six obstacles were placed at 2.55-metre intervals along a 1.75 × 20.00 m corridor.

Figure 7.

(A) Fundus images of the electrode array at 12 weeks after surgery for a right eye implantation (S4), visualized using a CLARUS 500 in wide-field configuration (133° retinal field) with RGB illumination (left image) and infrared illumination (right image). A blue cross marks the fovea. The leading edge of the electrode array is surgically inserted toward the optic disc, with the trailing edge and lead wire (not shown) extending toward the periphery. (B) OCT image of the electrode array at 4 weeks after surgery (S2). (Left) The infrared image was used to orientate the B-scan position (green line) through the retina and electrode array. (Right) The retina and electrodes could be visualized on OCT B-scan. (C) Magnified view of the region in the orange box in (B), showing the inner retina, RPE, choroid, and suprachoroidal electrode. The yellow arrow demonstrates an example measurement of electrode-to-retina distance (200 µm), defined as the distance from electrode to the outer retina boundary.

Figure 8.

(A) Electrode to retina distances obtained from OCT images. Each different color (black, magenta, blue, red) indicates data for each subject. Individual electrode measurements are shown as dots. A solid line connects the median values between time points. A vertical line at −8 weeks indicates the date of surgery. A vertical line at 0 weeks indicates the date of device activation (‘switch-on’). (B) Device thresholds for a subset of five phosphenes per subject were assessed throughout the 56-week period. Phosphenes are typically in a single electrode configuration (open squares) for electrodes nearest the fovea and paired electrode configuration (solid dots) for electrodes at the periphery where higher charge requirements have been observed. Defined safe charge limits of 250 nC (single electrode) and 500 nC (paired electrode) are indicated with dotted horizontal lines. A solid line describes a linear regression for each subject. (C) Device thresholds for the same subset of five phosphenes per subject versus eccentricity from the fovea (degrees). A SOLID LINE describes a linear regression for each subject. (D) Device thresholds for the same subset of five phosphenes per subject versus electrode-to-retina distance (in micrometers). A solid line describes a linear regression for each subject.

Figure 9.

Results for the square localization task comparing device on (blue) versus device off (red) versus a scrambled condition (magenta). (A) Average pointing error (in degrees) from touch location to the target center for 24 trials of each condition. The boundary of the 10° wide square target is indicated by a dotted horizontal line. (B) Average response time (seconds) for 24 trials of each condition. Circles show the average of 24 trials at each time point, shaded progressively darker for later dates and labelled with week number. The height of the bar is each subject's average across all time points. Statistical significance of within-subject comparisons is shown; *** P < 0.001; ** P < 0.01.

Figure 10.

Results for the motion discrimination task comparing device on (blue) versus device off (red) versus a scrambled condition (magenta). (A) Success rate at 7°/s. (B) Success rate at 15°/s. (C) Success rate at 30°/s. Chance level (25%) is shown as a dotted horizontal line. Circles show the average of 24 trials at each time point, shaded progressively darker for later dates and labelled with week number. The height of the bar is each subject's average across all time points. Statistical significance of within-subject comparisons is shown; *** P < 0.001; ** P < 0.01; NS = not significant. Friedman tests for S3 at 7°/s were significant, but post hoc comparisons were not; hence, significance is not indicated for these data.

Figure 11.

Results for the spatial discrimination task comparing device on (blue) versus device off (red) for subjects S1 to S3. (A) Percentage correct of 24 trials. The passing criterion (75%) is shown as a dotted horizontal line. (B) Mean response time (seconds). Circles show the average of 24 trials at each time point, shaded progressively darker for later dates and labelled with week number. The height of the bar is each subject's average across all time points. Significance was not tested. Subject S4 did not attempt this task.

Figure 12.

Results for the modified door task comparing device on (blue) versus device off (red). (A) Rate of successful touches of target (%). (B) Touch distance from fingertip to target including successful touches. (C) Time taken to reach target. Circles show the average of 10 trials at each time point, shaded progressively darker for later dates and labelled with week number. The height of the bar is each subject's average across all time points. Statistical significance of within-subject comparisons is shown; *** P < 0.001; * P < 0.05; NS = not significant.

Figure 13.

Results for the tabletop search task comparing device on (blue) versus device off (red). (A) Success rate (%) for verbally indicating object location on a 3 × 3 grid. (B) Success rate (%) for identifying object type (1 of 6). (C) Success rate (%) for contacting the object. (D) Distance from fingertip to object including successful touches. Chance level is indicated as a horizontal dotted line in (A) and (B). Circles show the average of 20 trials at each time point, shaded progressively darker for later dates and labelled with week number. The height of the bar is each subject's average across all time points. Statistical significance of within-subject comparisons is shown; *** P < 0.001; ** P < 0.01; * P < 0.05; NS = not significant.

Figure 14.

Response matrices for tabletop object identification pooled from all time points. (A) Comparisons with device on for reported object versus actual object demonstrate low scores for object identification but also clustering of responses according to the size of the actual object. (B) Comparisons with device off for reported object versus actual object. Cell text indicates incidence percent and fraction of actual object incidence. Row numerator totals (n) are the response incidence. Column numerator totals (N) are the total object incidence. (C) Photos of the objects used for tabletop search (from left): placemat, plate, bowl, cup, can, and fork.

Figure 15.

Results for the obstacle avoidance task comparing device on (blue) versus device off (red). (A) Success rate (%) for verbally indicating object location on approach. (B) Walking speed for each trial, expressed as percent of preferred walking speed (PWS). (C) Collision rate (%) for each trial. (D) Percent of trials with zero collisions or contact. Circles show the average of 10 trials at each time point, shaded progressively darker for later dates and labelled with week number. The height of the bar is each subject's average across all time points. Statistical significance of within-subject comparisons is shown; *** P < 0.001; ** P < 0.01; NS = not significant.

Figure 16.

Group means and subject means for FLORA in four task categories: (A) orientation, (B) mobility, (C) activities of daily living, and (D) interacting with others. (E–H) The relative contribution of vision (with respect to other senses) was determined for these same tasks. One subject is excluded from this analysis (see text). Group averages are shown as blue lines (device on) and red lines (device off). Subject averages are shown as circles (device on) and squares (device off). The color key for individual subject data is described in the legend of (A) and (E).

Figure 17.

Subjects reported on the Impact of Vision Impairment (IVI-VLV) on their (A) emotional well-being and (B) activities of daily living, mobility, and safety in the month before each assessment. Subject averages are shown as solid lines. Assessments for subject S4 were markedly influenced by external stressors that were unrelated to the device or the study.