Interim Results of a Multicenter Trial with the New Electronic Subretinal Implant Alpha AMS in 15 Patients Blind from Inherited Retinal Degenerations

Katarina Stingl, Ruth Schippert, Karl U Bartz-Schmidt, Dorothea Besch, Charles L Cottriall, Thomas L Edwards, Florian Gekeler, Udo Greppmaier, Katja Kiel, Assen Koitschev, Laura Kühlewein, Robert E MacLaren, James D Ramsden, Johann Roider, Albrecht Rothermel, Helmut Sachs, Greta S Schröder, Jan Tode, Nicole Troelenberg, Eberhart Zrenner, Katarina Stingl, Ruth Schippert, Karl U Bartz-Schmidt, Dorothea Besch, Charles L Cottriall, Thomas L Edwards, Florian Gekeler, Udo Greppmaier, Katja Kiel, Assen Koitschev, Laura Kühlewein, Robert E MacLaren, James D Ramsden, Johann Roider, Albrecht Rothermel, Helmut Sachs, Greta S Schröder, Jan Tode, Nicole Troelenberg, Eberhart Zrenner

Abstract

Purpose: We assessed the safety and efficacy of a technically advanced subretinal electronic implant, RETINA IMPLANT Alpha AMS, in end stage retinal degeneration in an interim analysis of two ongoing prospective clinical trials. The purpose of this article is to describe the interim functional results (efficacy). Methods: The subretinal visual prosthesis RETINA IMPLANT Alpha AMS (Retina Implant AG, Reutlingen, Germany) was implanted in 15 blind patients with hereditary retinal degenerations at four study sites with a follow-up period of 12 months (www.clinicaltrials.gov NCT01024803 and NCT02720640). Functional outcome measures included (1) screen-based standardized 2- or 4-alternative forced-choice (AFC) tests of light perception, light localization, grating detection (basic grating acuity (BaGA) test), and Landolt C-rings; (2) gray level discrimination; (3) performance during activities of daily living (ADL-table tasks). Results: Implant-mediated light perception was observed in 13/15 patients. During the observation period implant mediated localization of visual targets was possible in 13/15 patients. Correct grating detection was achieved for spatial frequencies of 0.1 cpd (cycles per degree) in 4/15; 0.33 cpd in 3/15; 0.66 cpd in 2/15; 1.0 cpd in 2/15 and 3.3 cpd in 1/15 patients. In two patients visual acuity (VA) assessed with Landolt C- rings was 20/546 and 20/1111. Of 6 possible gray levels on average 4.6 ± 0.8 (mean ± SD, n = 10) were discerned. Improvements (power ON vs. OFF) of ADL table tasks were measured in 13/15 patients. Overall, results were stable during the observation period. Serious adverse events (SAEs) were reported in 4 patients: 2 movements of the implant, readjusted in a second surgery; 4 conjunctival erosion/dehiscence, successfully treated; 1 pain event around the coil, successfully treated; 1 partial reduction of silicone oil tamponade leading to distorted vision (silicon oil successfully refilled). The majority of adverse events (AEs) were transient and mostly of mild to moderate intensity. Conclusions: Psychophysical and subjective data show that RETINA IMPLANT Alpha AMS is reliable, well tolerated and can restore limited visual functions in blind patients with degenerations of the outer retina. Compared with the previous implant Alpha IMS, longevity of the new implant Alpha AMS has been considerably improved. Alpha AMS has meanwhile been certified as a commercially available medical device, reimbursed in Germany by the public health system.

Keywords: RETINA IMPLANT Alpha AMS; artificial vision; hereditary retinal disease; neuroprosthetics; photoreceptor degeneration; retinitis pigmentosa; subretinal implant.

Figures

Figure 1
Figure 1
(A) Subretinal Implant RETINA IMPLANT Alpha AMS with (a): Polyimide foil and attached CMOS chip; (b): Sclera patch on ceramic chip; (c): Silicone cable; (d): Subdermal ceramic housing; (e): Return electrode. (B) View of silicone-power-cable routed on top of skull bone (below periost) and return electrode at temple area.
Figure 2
Figure 2
Summary (mean + SD) of scores for the ADL tasks shapes (A–C) and table set-up (D–F) for all time points tested (month 1, 2, 3, 6, 9, 12) for the conditions implant ON vs. implant OFF. (A,D) show the scores for detection of the item on the table, (B,E) show the scores for the localization of the item and (C,F) show the scores for recognition of the item. The number of participants with available data is indicated below the x-axis for both implant ON/implant OFF. Significant differences as analyzed via the Wilcoxon test are shown in the figures with *p < 0.05, **p < 0.01, and ***p < 0.001. As data for one patient at month 1 and for another patient at month 12 was only available for the condition “implant ON,” these data were excluded from the Wilcoxon analysis, but included in the summary statistics (mean + SD).
Figure 3
Figure 3
Shown are the percentages of patients passing the Eye-Hand Coordination test successfully at each time-point. Significant differences as analyzed via the 2-sided Fisher's exact test are shown in the figures with *p < 0.05 and **p < 0.01. The number of patients performing the test is indicated below the x-axis for implant ON/implant OFF. Except for one patient at month 9, none of the patients was able to position the object correctly when the implant was switched OFF.
Figure 4
Figure 4
Shown are the mean + SD of correctly distinguished gray levels out of 6 combinations tested. The number of patients performing the test is indicated below the x-axis for implant ON/implant OFF. Significant differences as analyzed via the Wilcoxon test are shown in the figure with *p < 0.05 and **p < 0.01. As data of 2 patients at month 1 and 3 and of 1 patient at month 6 for was only available for the condition “implant ON,” these data were excluded from the Wilcoxon analysis, but included in the summary statistics (mean + SD).
Figure 5
Figure 5
Shown are the percentages of patients passing the BaLM light perception test (A) and the BaLM light localization test (B) successfully at each time-point. Significant differences as analyzed via the 2-sided Fisher's exact test are shown in the figures with *p < 0.05, **p < 0.01, and ***p < 0.001. The number of patients performing the test is indicated below the x-axis for implant ON/implant OFF.
Figure 6
Figure 6
(A) shows the percentages of patients passing the basic grating acuity test successfully at each time-point for the conditions implant ON and implant OFF with significant differences as analyzed via the 2-sided Fisher's exact test shown in the figures with *p < 0.05, **p < 0.01, and ***p < 0.001. The number of patients performing the test is indicated below the x-axis for implant ON/implant OFF. (B) shows the data of patients in cycles per degree (cpd) with implant ON with the bottom white and top gray box representing the first and third quartile, and the band inside the box representing the median. The ends of the whiskers represent the minimum and maximum values. For failed tests, a value of “0 cpd” was noted. Please note the broken y-axis. The number of patients performing the test is indicated below the x-axis.
Figure 7
Figure 7
Overview of data available at the time of this report for the time points studied with solid lines indicating available data, dotted lines indicating that no visit occurred despite implant working properly (RIAG-TU-18, month 6 and 9; RIAG-KI-04, month 6) and arrowheads indicating a functioning implant. The blunt ends indicate that the implant stopped functioning; a detailed explanation for implant failures is given in the text.

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