Assessment of the Electronic Retinal Implant Alpha AMS in Restoring Vision to Blind Patients with End-Stage Retinitis Pigmentosa

Abstract

Purpose: To report the initial efficacy results of the Retina Implant Alpha AMS (Retina Implant AG, Reutlingen, Germany) for partial restoration of vision in end-stage retinitis pigmentosa (RP).

Design: Prospective, single-arm, investigator-sponsored interventional clinical trial. Within-participant control comprising residual vision with the retinal implant switched ON versus OFF in the implanted eye.

Participants: The Retina Implant Alpha AMS was implanted into the worse-seeing eye of 6 participants with end-stage RP and no useful perception of light vision. Eligibility criteria included previous normal vision for ≥12 years and no significant ocular or systemic comorbidity.

Methods: Vision assessments were scheduled at 1, 2, 3, 6, 9, and 12 months postimplantation. They comprised tabletop object recognition tasks, a self-assessment mobility questionnaire, and screen-based tests including Basic Light and Motion (BaLM), grating acuity, and greyscale contrast discrimination. A full-field stimulus test (FST) was also performed.

Main outcome measures: Improvement in activities of daily living, recognition tasks, and assessments of light perception with the implant ON compared with OFF.

Results: All 6 participants underwent successful implantation. Light perception and temporal resolution with the implant ON were achieved in all participants. Light localization was achieved with the implant ON in all but 1 participant (P4) in whom the chip was not functioning optimally because of a combination of iatrogenic intraoperative implant damage and incorrect implantation. Implant ON correct grating detections (which were at chance level with implant OFF) were recorded in the other 5 participants, ranging from 0.1 to 3.33 cycles/degree on 1 occasion. The ability to locate high-contrast tabletop objects not seen with the implant OFF was partially restored with the implant ON in all but 1 participant (P4). There were 2 incidents of conjunctival erosion and 1 inferotemporal macula-on retinal detachment, which were successfully repaired, and 2 incidents of inadvertent damage to the implant during surgery (P3 and P4).

Conclusions: The Alpha AMS subretinal implant improved visual performance in 5 of 6 participants and has exhibited ongoing function for up to 24 months. Although implantation surgery remains challenging, new developments such as OCT microscope guidance added refinements to the surgical technique.

Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

Implanting the subretinal chip. A fornix-based partial thickness scleral flap is constructed (A, B). After vitrectomy and localized retinal detachment, the guide foil is inserted through a full-thickness slit incision in sclera and choroid (C). Once the foil is positioned under the fovea, the chip is advanced along the same path before removal of the guide foil (D–F).

Figure 2

Integrated OCT microscope (Rescan 700, Carl Zeiss Meditec AG, Jena, Germany). The surgeon's perspective through the operating microscope eyepiece (i.e., superior retina is the lower half of the fundus image in each panel) of a left eye. Beside the fundus view is a real-time dual-plane OCT image. Before insertion of the guide foil, a 41-gauge subretinal injection cannula (DORC BV, Zuidland, the Netherlands) was used to induce a superotemporal retinal detachment that extended toward the posterior pole (A, B). The blue-colored guide foil was advanced under the detached retina (C). The retinal implant chip was then positioned under the fovea (D).

Figure 3

Color fundus photograph of P2 on day 10 postimplantation surgery showing an optimal subretinal chip position centered at the macula.

Figure 4

Activities of daily living and recognition tasks. A, B, The median number of correctly located tabletop items (maximum 4) for all follow-up visits to date, for each participant with implant ON versus OFF. Absent bars indicate that nothing was seen. Error bars show the range. Greyscale contrast discrimination was explored by testing participants' ability to discern a difference between 1 of 6 greyscale values on one half of a screen—from 0% (black) to 100% (white)—compared with 50% saturation on the adjacent half of the screen. The percentage of correctly detected contrast pairs is shown (C) for all participants except P4, whose implant had malfunctioned. Bars are shaded according to their respective greyscale value and presented on a 50% background to simulate the contrast shown on the screen. Analogue clock face identification was one of the most challenging tests (D). E, Dark-adapted achromatic full-field stimulus test (FST) (Espion, ColorDome, Diagnosys, Cambridge, UK) using implant gain and sensitivity settings optimized for tabletop testing (i.e., not for scotopic conditions) showed an overall improved threshold sensitivity with the implant ON versus OFF, although it did not reach statistical significance (P = 0.06, Wilcoxon matched-pairs, signed-rank test). A reliable threshold with the implant OFF could not be measured for P2. The test was not performed on P3 because of conjunctival erosion.

Figure 5

Basic vision assessments. Basic Light and Motion (BaLM) (A) and Basic Grating Acuity (BaGA) (B) assessments comparing the median response from all visits to date for each participant with implant ON versus OFF. Assessments were conducted as 8 repeated 2 or 4 alternate forced choice (AFC) test (the latter was used in the light localization component of BaLM), requiring a ≥75% or ≥62.5% pass rate. The default result was 50% due to random chance. The probability of a false-positive pass for the 2- and 4-AFC tests was 14% and 2.7%, respectively. No Basic Grating Acuity data were generated from P4 due to chip malfunction. Error bars display the range.

Figure 6

Modified Turano Independent Mobility Questionnaire. The degree of difficulty encountered when performing a range of activities was compared before and 2 months after implantation. “Walking in familiar areas” was the activity that changed most from baseline. The only baseline activity that did not improve was “Finding restrooms in public spaces.” P4 was not included in this analysis because device malfunction noted at switch on severely limited gain and sensitivity controls required to optimize its performance.

Figure S3

Optical coherence tomography scan (Heidelberg Engineering, Inc., Heidelberg, Germany) of P4 after reimplantation of a new Alpha AMS device (Retina Implant AG, Reutlingen, Germany).