Long-term Repeatability and Reproducibility of Phosphene Characteristics in Chronically Implanted Argus II Retinal Prosthesis Subjects


Previously published literatures of acute studies on few subjects have shown contradictory evidence on the reproducibility and characteristics of the elicited phosphenes, despite using the same stimulating parameters with epiretinal electrode arrays. In this study, we set out to investigate the long-term repeatilibity and reproducibility of phosphenes in subjects chronically implanted with the Argus II retinal prosthesis (Second Sight Medical Products, Inc., Sylmar, CA, USA).


Retrospective interventional case series and reliability study.


Six Argus II subjects of >5 years implantation from a single site participated. The 4-electrode cluster (“quad”) closest to fovea was stimulated in each subject with a fixed biphasic current. Perceived phosphenes were depicted relative to subjective visual field center. The stimulus was applied at reducing time intervals from 20 minutes to 1 second. Two sets of stimulations were performed on the same day and 2 further sets repeated on a separate visit >1 week apart.


Each subject depicted phosphenes of consistent shapes and sizes, and reported seeing the same colors with the fixed stimulating parameters, irrespective of the interstimuli intervals. However, there is a wide intersubject variation in the phosphene characteristics. Four subjects drew phosphenes in the same visual field quadrant, as predicted by the quad-fovea location. Two subjects depicted phosphenes in the same hemifield as the expected locations.


Phosphenes for each subject were consistently reproducible in all our chronically implanted subjects. This has important implications in the development of long-term pixelated prosthetic vision for future devices.

Since entering the commercial market as a retinal prosthetic device for the treatment for end-stage retinitis pigmentosa (RP), the Argus® II (Second Sight Medical Products Inc., Sylmar, CA, USA) retinal prosthesis system has been implanted in an increasing number of patients. However, despite this growing clinical use, data describing the features of artificial vision perceived by the users remain scarce in the published literature. The idea of developing useful vision by epiretinal electrical stimulation hinges on the premise that stimulation with a single electrode gives rise to a discrete focal percept in a retinotopic manner. Simultaneous stimulation with multiple electrodes therefore theoretically leads to perception of a pattern in concordance with the pattern defined by the stimulating electrodes.

In earlier studies, Rizzo and associates have called into question the consistency and reproducibility of phosphenes elicited by patterned epiretinal microelectrode stimulation. In a study involving 5 end-stage RP patients and 1 patient with normal retina, only 48% of the single-electrode stimulations and 32% of the multielectrode stimulations elicited visual percepts that matched the electrical stimulation patterns. Of the single-electrode stimulations, 3 subjects reported “a line” on some occasions, while “clusters of 2 or 3 images” were seen on other occasions. In particular, the authors reported that only 66% (out of 99 stimulations) of the elicited visual percepts were reproducible in 3 RP patients on 2 separate trials, despite using the same stimulating parameters to activate the same electrodes. Such inconsistencies in the form and reproducibility of phosphenes would seriously undermine the formation of pixelated vision.

In this study, we set out to investigate the consistency and reproducibility of phosphenes elicited in a cohort of subjects chronically implanted with the Argus II system at a single site. All of the subjects described have had the device implanted and functioning for more than 5 years.


Subject Inclusion/Exclusion Criteria

This is a single-center prospective study. All but 1 subject from our center implanted with the Argus II retinal prosthesis system as part of the phase I/II clinical trial ( clinicaltrials.gov identifier: NCT00407602 ) took part in the study (n = 6). One subject was excluded, as his device ceased to function after he developed retinal detachment and thick macular pucker as a result of a fall. The participating subjects’ demographics and operation dates are shown in Table 1 . The study was approved by the institutional review boards and ethics committee, and adhered to the tenets of the Declaration of Helsinki.

Table 1

Demographics and Operation Dates of the Participating Chronically Implanted Argus II Retinal Prosthesis Subjects

Subject ID Diagnosis Year of Operation Age at Time of Operation (y)
001 Retinitis pigmentosa 2008 70
003 Retinitis pigmentosa 2008 72
005 Retinitis pigmentosa 2009 55
006 Choroideremia 2009 66
007 Retinitis pigmentosa 2009 63
009 Retinitis pigmentosa 2009 45

Selection of Stimulating Electrodes and Parameters

For each subject, a cluster of 4 electrodes (hereinafter referred to as a “quad”) closest to the fovea, which were functioning with thresholds within the safety charge density limit, was selected for stimulation, and the elicited phosphenes characterized for the purpose of this study ( Figure 1 ).

Figure 1

Red-free fundus photograph of the microelectrode array of a chronically implanted Argus II retinal prosthesis subject (ID: 007). The designated quad for stimulation consisted of electrodes E07E08F07F08 (enclosed in white square). The fovea location is estimated to be 15.5 degrees temporal and 1.5 degrees inferior to the center of the optic disc. The quad-fovea relation is calculated from the estimated fovea location, to the center of the stimulated quad.

An estimated location of the fovea was made on the fundus photograph (taken at the outset of the study) and was used for each subject as a reference point, measuring 15.5 ± 1.1 degrees from the center of the optic disc horizontally and −1.5 ± 0.9 degrees vertically. The foveal position was estimated, as there were no remaining features of the fovea on color photographs, fluorescein angiograms, or optical coherence tomography (OCT) scans owing to severe end-stage RP.

Once the designated quad was chosen, the stimulating current for each subject was arbitrarily set to be 100 μA above the threshold (measured within the last 6 months) initially, and then adjusted according to the strength of response and comfort level reported by the subject. We aimed to elicit a clear, definite visual percept without causing any discomfort or physical “tingling” sensation for each subject. Default settings for the Argus II retinal prosthesis system Clinical Fitting System (CFS) employed for device fitting and standard testing were likewise used for this study, which generate cathodic-first, charge-balanced biphasic square waves to avoid tissue damage from charge build-up. These default waveform parameters were as follows: phase width of 0.46 ms, interphase duration of 0 seconds, and total stimulation duration of 250 ms at the frequency of 20 Hz. Swept-source OCT (DRI OCT-1 Atlantis; TOPCON, Topcon Medical Systems, Tokyo, Japan) imaging through the chosen quad for each subject was performed, to assess the contact between the stimulating electrodes and the retinal surface. The selected quad, quad-retina relation, quad threshold, and stimulating current for each subject were as shown in Table 2 .

Table 2

Phosphene Features Described by Each Chronically Implanted Argus® II Retinal Prosthesis Subject, From Stimulating the Designated Quad With the Above Parameters

Subject ID Quad Quad-Retina Relation (on OCT) Threshold (μA) Stimulating Current (μA) Phosphene Features Phosphene Duration, t (s)
001 C07C08
In contact no significant ERM a 137 277 White filled-in circle 0.5 < t < 1
003 A07A08
In contact no significant ERM a 250 350 Electric blue filled-in circle t < 0.5
005 E05E06
In contact no significant ERM a 137 237 Bluish-gray vertical line, with fizzy vertical edges t < 0.5
006 A07A08
Quad-retina separation = 377 μm; no ERM visible 371 552 Yellow “7” shape 0.5 < t < 1
007 E07E08
In contact no significant ERM a 24 124 Orange filled-in ring that ripples out 0.5 < t < 1
009 E07E08
In contact no significant ERM a 97 124 Orange horizontal lines x2, with fizzy brightness in between the lines 0.5 < t < 1

ERM = epiretinal membrane; OCT = optical coherence tomography.

a In images where the electrode array is in direct contact with the retinal surface, owing to the artefact caused by the acoustic shadow of the array, it is difficult to ascertain the presence, if any, of mild epiretinal membrane.

Phosphenes Depiction

To record the phosphenes perceived by each subject, we constructed a wall covered with smooth-surface black mats. The subjects were first asked to stand up and stretch out both arms fully to touch the black wall, so that their shoulders were square, facing the wall. The standing position of each subject was then adjusted so that the distance between the front of their eyes and the wall equaled 30 cm. Next, the subjects were asked to point with the index finger of both hands simultaneously on the black wall, to where they believed the center of their visual field was, while keeping their head and eyes pointing straight ahead. A stack of white A4-size papers (in landscape layout) was then placed underneath the index fingers of each subject and pinned to the wall, so that the index fingers were pointing at the center of the top sheet of paper (ie, the center of the paper was approximating the proclaimed center of each subject’s visual field). A drawing pin with a protruding cylindrical head was then inserted at the point where their index fingers contacted with the wall, so as to mark the location of the proclaimed visual field center.

During the experiment, the subjects were asked to position themselves according to the setup above, hold onto the preplaced drawing pin head, and adjust their head and eye position until they felt the center of their visual field was in alignment with the drawing pin. With each quad stimulation, the subjects were instructed to keep their nondominant hand on the drawing pin as a point of reference, while drawing on the paper with a marker pen the outline of the phosphene they perceived in relation to their visual field center. A fresh sheet of paper was used for each phosphene depiction ( Figure 2 ).

Jan 5, 2017 | Posted by in OPHTHALMOLOGY | Comments Off on Long-term Repeatability and Reproducibility of Phosphene Characteristics in Chronically Implanted Argus II Retinal Prosthesis Subjects

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