Abstract
Purpose
Retinitis Pigmentosa (RP) is a group of inherited retinal degenerations leading to blindness due to photoreceptor loss. A rare disease, it affects about 100,000 people in the United States. There is no cure and no approved medical therapy to slow or reverse RP. The purpose of this clinical trial was to evaluate the safety, reliability, and benefit of the Argus® II Retinal Prosthesis System (Second Sight Medical Products, Inc., Sylmar, CA) in restoring some visual function to subjects completely blind from RP. Herein, we report clinical trial results at 1 and 3 years post-implant.
Design
The study is a multicenter, single-arm, prospective clinical trial.
Subjects
There were 30 subjects in 10 centers in the U.S. and Europe. Subjects served as their own controls – i.e., implanted eye vs. fellow eye, and System ON vs. System OFF (native residual vision).
Methods
The Argus II System was implanted on and in a single eye (typically the worse-seeing eye) of blind subjects. Subjects wore glasses mounted with a small camera and a video processor that converted images into stimulation patterns sent to the electrode array on the retina.
Main Outcome Measures
The primary outcome measures were safety (the number, seriousness, and relatedness of adverse events) and visual function, as measured by three computer-based, objective tests.
Results
Twenty-nine out of 30 subjects remained implanted with functioning Argus II Systems at 3 years post-implant. Eleven subjects experienced a total of 23 serious device- or surgery-related adverse events. All were treated with standard ophthalmic care. As a group, subjects performed significantly better with the System ON than OFF on all visual function tests and functional vision assessments.
Conclusions
The three-year results of the Argus II trial support the long-term safety profile and benefit of the Argus II System for patients blind from RP. Earlier results from this trial were used to gain approval of the Argus II by the FDA and a CE Mark in Europe. The Argus II System is the first and only retinal implant to have both approvals.
This work presents three-year results from the ongoing clinical trial of the Argus II Retinal Prosthesis System. The study’s purpose is to evaluate the safety and benefit of the Argus II System in providing functional vision to people blind from retinitis pigmentosa.
Several different approaches to restoring sight to those blind from retinal degeneration are currently under investigation, including stem cell therapy,1 gene therapy,2,3 as well as other approaches.4 Visual prostheses offer the possibility of restoring vision in patients who are severely blinded from retinitis pigmentosa and other retinal degenerations. Different visual prostheses have been explored, including visual cortex,5,6 optic nerve,7 epiretinal,8 and subretinal9 devices. While many approaches show promise, to date, retinal prostheses are the only therapy to have achieved market approval in the US and Europe.
A previous report8 presented data from this cohort when all subjects had reached 6 months follow-up. Herein, we present complete one-year and three-year data from the Argus II clinical trial.
Methods
Study Design
The study is a single-arm, prospective, unmasked clinical trial. Due to the rarity of the eligible patient population, the sample size was 30 subjects, which was determined, with guidance from regulatory agencies, to be reasonably achievable and of sufficient power to evaluate safety and probable benefit. These 30 subjects were enrolled at 10 centers in the United States and Europe. Subjects served as their own controls (i.e., tested with the Argus II System turned on vs. only using their residual vision). The trial was and continues to be conducted in accordance with the Declaration of Helsinki and the national regulations for medical device clinical trials in the respective countries in which the study is being conducted. The study has been approved by the national ministries of health in these countries and the ethics committees or institutional review boards of participating institutions. All subjects signed informed consent to participate. The clinical trial is posted on www.clinicaltrials.gov, trial registration number NCT00407602.
Inclusion and Exclusion Criteria
Subjects were eligible to enroll if they had a confirmed diagnosis of retinitis pigmentosa (U.S.) or outer retinal degeneration (Europe), bare or no light perception in both eyes, functional ganglion cells or optic nerve (confirmed by photoflash detection or measurable electrically evoked response), and a history of useful form vision. Age inclusion criterion was initially 50 years or older, and was later changed to 25 in the U.S. and Switzerland and 18 in France and the U.K.
Exclusion criteria included diseases or conditions that affected retinal or optic nerve function, ocular structures or conditions that could prevent successful implantation, and any inability to tolerate the implant surgery or medical/study follow-up. Full inclusion and exclusion criteria are listed at ClinicalTrials.gov.
Device
The Argus II System consists of an active device implanted on and in the eye and external equipment worn by the user.
The implanted portion of the System includes a receiving antenna and an electronics case that are fixed outside the eye with sutures and a scleral band, and an intraocular 6x10 electrode array that is tacked over the macula epiretinally (i.e., on the retinal ganglion cell side) (Figure 1A). The external portion of the System includes a glasses-mounted video camera and a small video processing unit (VPU, Figure 1B) that can be worn on a shoulder strap or belt (not shown). The camera collects visual information and sends it to the VPU, which down-samples and processes the image. Several buttons on the VPU allow user control of various image-processing algorithms, for example enhancing contrast. Data and power are sent wirelessly from a transmitting antenna on the glasses to the internal receiving antenna. The electrodes in the array emit pulses of electricity whose amplitude correspond to the brightness of the scene in that location. Stimulation of the remaining retinal cells induces cellular responses that travel through the proximal visual system, resulting in visual percepts that subjects learned to interpret.
Figure 1.
Panel A shows the implanted portions of the Argus II System (Second Sight Medical Products, Inc., Sylmar, CA). Panel B shows the external components of the Argus II System. Images in real time are captured by the camera mounted on the glasses. The Video Processing Unit (VPU) down-samples and processes the image, converting it to stimulation patterns. Data and power are sent via radio frequency link from the transmitter antenna on the glasses to the receiver antenna around the eye. A removable, rechargeable battery powers the System.
Surgical Procedure
Subjects were implanted with the Argus II Retinal Prosthesis System in one eye, typically the worse-seeing eye. The surgical procedure is summarized here; a more detailed description of the procedure and medication regimen is in the Supplementary Appendix (available at http://www.aaojournal.org).
To implant the device, a 360-degree limbal conjunctival peritomy was performed. The rectus muscles were isolated and the coil was inserted temporally on the globe and centered under the lateral rectus muscle. The electronics package was centered in the superotemporal quadrant. The inferior part of the scleral band was passed under the inferior and the medial rectus muscles, and the superior portion of the band under the superior rectus muscle. The implant was fixed to the eye via sutures passed through suture tabs on the implant in both temporal quadrants and a Watzke® sleeve (Labtician Ophthalmics, Inc., Oakville, Ontario, Canada) and mattress sutures or scleral tunneling were used to secure the scleral band in the nasal quadrants.
A core and peripheral vitrectomy were conducted. The array was then inserted through a temporal sclerotomy. The electrode array was placed onto the retina in the macular region and then tacked using a custom retinal tack (Second Sight Medical Products, Inc., Sylmar, CA). The extraocular portion of the cable was sutured to the sclera and all sclerotomies were closed.
An allograft (or suitable alternative in countries where allografts were not permitted) was fixed over the device to reduce the likelihood of conjunctival irritation. Finally, the Tenon’s capsule and the conjunctiva were closed.
Assessment of Safety – Primary Endpoint
All adverse events were collected and reported as necessary to the relevant authorities and ethics committees. Adverse events were classified as to relatedness (device- or surgery-related; or subject-related) and whether or not they met the regulatory definition of “serious” (i.e., adverse events that required medical or surgical intervention or hospitalization to prevent permanent injury). Serious adverse events were distinguished from those for which treatment was unnecessary or noninvasive (non-serious). Therefore, a particular type of adverse event, such as hypotony, may have been considered non-serious or serious, depending on how or whether that particular event was treated. All adverse events were subject to detailed review and adjudication by an Independent Medical Safety Monitor.
Assessment of Visual Function – Primary Endpoint
The primary endpoint for the evaluation of benefit was visual function. This was assessed with three computer-based, objective tests of basic visual skills developed by Second Sight with input from the low-vision research community to cover the range of low vision restored by a retinal implant.
In “Square Localization,” subjects had to locate and touch a white square in random locations on a black touchscreen monitor. The response error (the distance between the subject’s response and the center of the target square in centimeters) was recorded and averaged over 40 trials. The mean error with the System ON and OFF for each subject was evaluated with a two-tailed t-test assuming unequal variances to determine whether the ON and OFF results were significantly different.
In “Direction of Motion,” a white bar moved across the same black touch screen and subjects drew the direction they perceived the bar to be moving. The response error (the difference between the subject’s response angle and the target bar’s angle in degrees) was recorded and averaged over 80 trials. A two-tailed t-test was performed to determine whether the mean errors with the System ON and OFF were significantly different.
Finally, “Grating Visual Acuity” measured subjects’ visual acuity on a scale of 2.9 – 1.6 logarithm of the minimum angle of resolution (logMAR; 20/15887 – 20/796 in Snellen notation) using black and white gratings displayed for 5 seconds. In a four-alternative forced-choice test, subjects indicated the perceived orientation (horizontal, vertical, diagonal left/right); the program adaptively reduced or increased the spatial frequency of the gratings based on the number of correct and incorrect answers. Subjects whose performance was no better than chance were scored as acuity “worse than 2.9 logMAR.”
Assessment of Device Reliability – Secondary Endpoint
Device stability and reliability were tracked by two measures: number of explants (surgical removal of all or a portion of the implanted device) and number of device failures (inability of the device to function).
Assessments of Orientation and Mobility, Activities of Daily Living, and Quality of Life – Secondary Endpoints
Assessments of performance in more real-world conditions were made with indoor orientation and mobility tasks involving finding and touching a “door” and following a white line on the floor. In the “Door Task,” subjects walked across a room and tried to find and touch a simulated door (black cloth on a light wall, in one of 2 positions relative to the subject’s starting point). In the “Line Task,” subjects walked across a floor consisting of black rubber interlocking tiles. A 6″ wide white line painted on the tiles was configured to be straight or to have a 90° turn to the left or right. Six trials were performed with the System ON and OFF, and successes (touching the door or ending on the line at its endpoint) or failures as well as time to completion were recorded. Detailed methods were described previously8.
At the beginning of the study, assessments of patient-reported activities of daily living (ADL) and quality of life (QoL) were made with the VisQoL vision-related utility instrument10 and the Mass of Activity Inventory.11 These instruments were not fully validated in RP patients with minimal or no sight, and thus were used primarily for exploratory purposes in this study (data not shown). Patient reported outcomes (PROs) from this study will be reported elsewhere.
In order to evaluate the impact of the Argus II System on subjects’ everyday lives, the Functional Low-vision Observer Rated Assessment (FLORA) was developed at the request of and with input from the FDA and introduced partway through the trial. The FLORA was performed by independent visual rehabilitation experts to subjectively assess real-world benefit of the Argus II System. Assessors first performed an extensive interview to understand a subject’s self-reported experience with the Argus II System. Next, the assessors observed the subject performing visual tasks (System ON and OFF) in and around their home. Tasks were chosen by the assessors from a provided list, and included orientation and mobility tasks, activities of daily living, and social interactions. Finally, the assessor wrote a case study narrative to synthesize his or her judgment of the effect of the Argus II on that subject’s life, taking into account both real-world use and quality of life. All narratives then were rated by a single independent rater for the effect of the System on subjects’ lives: positive, mild positive (usually subjects who self-reported functional benefits that were not supported by assessors’ observations), prior positive (subjects who self-reported positive effects in the past that could not be demonstrated at the time of the assessment), neutral, and negative.
Performance was assessed on all subjects at months 3 & 6, and years 1–3, except the FLORA, which was performed at years 1 and 3. The number of subjects assessed on each test differed slightly due to the introduction of Square Localization and Direction of Motion tests partway through the trial, as well as some missed follow-up visits. Deviations were collected and reported to relevant regulatory agencies.
Results
Thirty subjects were implanted with the Argus II System between June 2007 and August 2009 at 10 different centers in the US and Europe. Twenty-nine subjects had retinitis pigmentosa (including one with Leber Congenital Amaurosis) and one had choroideremia. Twenty-nine subjects had bare light perception (i.e., the ability to detect very bright light) in both eyes, while one had no light perception (but was able to perceive light in response to transcorneal electrical stimulation). The age at time of implant ranged from 28 – 77 years (average 58, standard deviation 10). There were 9 females and 21 males. Median surgery time was 4:04 hours (range 1:53 – 8:32).
Safety
As of one year post-implant, 66.7% of subjects (20 out of 30) had experienced no device- or surgery-related serious adverse events (SAEs). There were 18 SAEs among 10 subjects. The SAEs fell into 10 types with hypotony, conjunctival dehiscence, conjunctival erosion, and presumed endophthalmitis (culture negative) being slightly more common than the others. There were also two subjects who underwent revision surgery to re-tack the array to the retina one week post-implant.
At three years post-implant, there were a total of 23 SAEs among 11 subjects, with two additional SAE types. One subject’s device was removed at 1.2 years to treat recurrent conjunctival erosion, as reported previously8. Table 1 shows the total percent of subjects experiencing each SAE type with the 95% confidence intervals for data through Year 1 and Year 3.
Table 1.
Percent of subjects (N=30) experiencing each SAE type with 95% confidence interval through year 1 and year 3 post-implant (cumulative).
| Year 1 | Year 3 | |||||
|---|---|---|---|---|---|---|
| Serious Adverse Event Type | N subjects with SAE | % subjects with SAE | 95% CI | N subjects with SAE | % subjects with SAE | 95% CI |
| Conjunctival erosion | 3 | 10.0% | 2.1 – 26.5% | 4 | 13.3% | 3.1 – 30.7% |
| Hypotony | 2 | 6.7% | 0.8 – 22.1% | 4 | 13.3% | 3.1 – 30.7% |
| Conjunctival dehiscence | 3 | 10.0% | 2.1 – 26.5% | 3 | 10.0% | 2.1 – 26.5% |
| Presumed endophthalmitis | 3 | 10.0% | 2.1 – 26.5% | 3 | 10.0% | 2.1 – 26.5% |
| Re-tack | 2 | 6.7% | 0.8 – 22.1% | 2 | 6.7% | 0.8 – 22.1% |
| Corneal Opacity | 1 | 3.3% | 0.1 – 17.2% | 1 | 3.3% | 0.1 – 17.2% |
| Retinal Detachment - Rhegmatogenous | 1 | 3.3% | 0.1 – 17.2% | 1 | 3.3% | 0.1 – 17.2% |
| Retinal detachment - tractional and serous | 1 | 3.3% | 0.1 – 17.2% | 1 | 3.3% | 0.1 – 17.2% |
| Retinal Tear | 1 | 3.3% | 0.1 – 17.2% | 1 | 3.3% | 0.1 – 17.2% |
| Uveitis | 1 | 3.3% | 0.1 – 17.2% | 1 | 3.3% | 0.1 – 17.2% |
| Keratitis - infective | 0 | 0.0% | 0.0% | 1 | 3.3% | 0.1 – 17.2% |
| Corneal Melt | 0 | 0.0% | 0.0% | 1 | 3.3% | 0.1 – 17.2% |
Serious adverse events were clustered toward the early post-operative period: 14 of 23 SAEs (61%) occurred within the first six months post-implant, and only five SAEs (among 4 subjects) occurred after month 12. These late SAEs were: two cases of hypotony, and one each of keratitis – infective, corneal melt, and conjunctival erosion. This trend held for non-serious adverse events as well; over half (53%) of all non-serious AEs occurred within the first 6 months. Events were also clustered within patients: three subjects (10%) accounted for over 55% of SAEs by 3 years post-implant; 19 subjects had experienced no SAEs by that time. Indeed, four of the SAEs that occurred after year 1 were part of cascades or recurrences of events in three subjects. Only 1 SAE after year 1, a case of hypotony, occurred in a subject that had not experienced any SAEs previously. All SAEs were treatable with standard ophthalmic approaches, and there were no lost eyes (enucleated) in the study. A full listing and percentages of non-serious adverse events are in the Supplementary Appendix (available at http://www.aaojournal.org). Of note are seven subjects who underwent elective revision surgeries, which involved attempts to improve the position of the array.
Visual Function
At both one and three years, in the Square Localization test, a large majority of subjects performed significantly better with the System ON than OFF; in the Direction of Motion test, over half of the subjects performed significantly better with the System ON; on Grating Visual Acuity, no subjects scored on the scale with their fellow eye (System OFF), while 33 – 48% of the subjects scored 2.9 logMAR or better with the System ON (year 3 and year 1, respectively; Table 2A). The mean acuity values of those who scored on the scale were: 2.5 (SD=0.3) logMAR at year 1 and 2.5 (SD=0.4) logMAR at year 3. The best score at these two time points was 1.9 logMAR (20/1588). (As previously reported8, one subject has scored 1.8 logMAR on this test at a different time point.)
Table 2.
Assessments of Benefit
| A | Year 1 | Year 3 | ||
|---|---|---|---|---|
| Outcome Measure | N | Percent sig. better ON than OFF | N | Percent sig. better ON than OFF |
| Square Localization | 16 | 93.8% | 28 | 89.3% |
| Direction of Motion | 16 | 62.5% | 27 | 55.6% |
| Grating Visual Acuity | 29 | 48.2% | 27 | 33.3% |
| B | Year 1 | Year 3 | ||||
|---|---|---|---|---|---|---|
| Outcome Measure | N | Mean % Success ON | Mean % Success OFF | N | Mean % Success ON | Mean % Success OFF |
| Find the Door | 28 | 53.0% (5.5%) | 30.8% (4.8%) | 28 | 54.2% (6.2%) | 19.0% (4.3%) |
| Follow the Line | 28 | 72.8% (5.7%) | 17.1% (4.2%) | 28 | 67.9% (6.5%) | 14.3% (3.8%) |
| C | Year 1 | Year 3 | ||||||
|---|---|---|---|---|---|---|---|---|
| Outcome Measure | N | % Positive and Mild Positive | % Prior Positive and Neutral | Negative | N | % Positive and Mild Positive | % Prior Positive and Neutral | Negative |
| FLORA | 15 | 80% | 20% | 0 | 23 | 65.20% | 34.80% | 0 |
Panel A shows visual function results (primary endpoint). Results for Square Localization and Direction of Motion indicate the percentage of subjects whose System ON results were significantly different from (better than) System OFF. Results for Grating Visual Acuity indicate the percentage of subjects who scored between 2.9 and 1.6 logMAR with the System ON. None of the subjects scored with the System OFF. The proportion of subjects with significantly better ON than OFF results was not significantly different between 1 and 3 years for any of the visual function tests (Z-test, p>0.05). Panel B shows the mean percent success on the Find the Door and Follow the Line orientation and mobility assessments. Panel C shows the results of the FLORA at Year 1 and Year 3.
Device Reliability
Twenty-nine subjects were still implanted with functioning devices 3 years after implant. The one explant was due to SAE management, rather than device failure. There were no device failures through the three-year follow-up.
Orientation and Mobility, Activities of Daily Living, and Quality of Life
On both the Door and Line tasks, subjects perform much better (higher mean percent success) when using their Argus II Systems (Table 2B). On the FLORA, the effect of the System was overwhelmingly rated as positive or mild positive compared to prior positive or neutral at both Year 1 and Year 3; there were no ratings of negative at either time point (Table 2C).
Discussion
The Argus II System was extremely reliable and stable, with no device failures within 3 years post-implant (a total of 88.2 subject-years). Some of the performance measures (Square Localization, Direction of Motion, Grating Visual Acuity, and the FLORA) appear to show a smaller percentage of subjects performing better with the System ON than OFF (Table 2A and C). It is unclear if this is a true performance decline but that is a possibility. Most of these measures (except Grating Visual Acuity) were introduced partway through the clinical trial, after year 1 for about half the subjects. Therefore, the year 3 results include more subjects who were implanted earlier in the trial; a possible explanation could be that subjects enrolled later (who received a slightly different array design) were better performers. This is supported by the results on the Find the Door and Follow the Line tasks (Table 2B), which show essentially equal performance at years 1 and 3 on the same group of 28 subjects.
Visual function results indicated that 89% of subjects performed significantly better with the System ON than OFF for Square Localization at 3 years post-implant; 56% for Direction of Motion; and 33% scored on the scale on Grating Visual Acuity with the System ON (no subjects scored with the System OFF). Similar proportions of System ON vs. OFF performance were reported from different datasets earlier in the clinical trial8,12,13; these latest results indicate that visual function benefit from the Argus II System is sustained out to at least 3 years post-implant. For the 33%–48% of subjects who scored on the Grating Visual Acuity scale with their Systems ON, the mean visual acuity was 2.5 logMAR. Since none of these subjects had visual acuity of 2.9 logMAR or better with the System OFF, this result would be equivalent to an average gain of at least 4 lines on the ETDRS chart for these patients.
Laboratory-based orientation and mobility tests (Find the Door and Follow the Line) provide additional evidence that the System provided long-term benefit; subjects were able to perform practical tasks with much more success with the System ON than OFF out to 3 years post-implant. Finally, an in-depth assessment of subjects’ functional vision and well-being (the FLORA), performed by independent rehabilitation specialists, found that 80% subjects received benefit from the System at 1 year post-implant, while none were affected negatively.
Results to date in the Argus II Retinal Prosthesis System trial have shown no adverse safety concerns in this group of 30 subjects. Most serious adverse events occurred within 6 months post-implant, and all were treatable with standard ophthalmic approaches. Most (4 of 5) late-occurring SAEs (after 1 year) were part of a cascade of events that had begun earlier, rather than newly-arising events. However, any implant intended to remain in the eye for many years carries a long-term risk. Events such as conjunctival erosion, hypotony, or endophthalmitis, could occur in the long term. Therefore, any patient considering such an implant should be counseled as to the need for regular (at least once a year) follow-up as long as the implant remains in the eye.
There was one explant due to adverse events within 3 years post-implant. In this small study of 30 subjects, it is difficult to complete a robust statistical analysis of the safety results due to limited power. There are no long-term data from other retinal prostheses to place Argus II system adverse event rates in context. However, the Argus II is implanted using a series of common vitreoretinal surgical techniques (e.g., pars plana vitrectomy), and has design elements in common with other ophthalmic devices, particularly glaucoma drainage devices and metallic tacks.14 A comparison can therefore be made between these devices and the Argus II regarding key adverse event rates as shown in Table 3, though it should be noted that the comparison studies included many more subjects in their analyses.
Table 3.
Serious adverse event rates for Argus II System and comparator devices
| Adverse Event | Comparator Device or Technique | ||
|---|---|---|---|
| Retinal tack | Glaucoma drainage device | Argus II | |
| Hypotony | 10% [5.1, 18.4]15 | 6.7% [0.8, 22.1] | |
| Conjunctival dehiscence | 11% [6.0, 19.1] 15 | 10.0% [2.1, 26.5] | |
| Conjunctival erosion | 5% [1.5, 10.6] 15 16% [5.4, 33.7]16 |
10.0% [2.1, 26.5] | |
| Presumed endophthalmitis (culture-negative) | 1% [0.03, 5.1] 15 5% [NR]17 |
10.0% [2.1, 26.5] | |
| Dislodged tack | 5.3% [1.1, 15.4]18 | 6.7% [0.8, 22.1] | |
Adverse event rates at 1 year (with 95% confidence intervals in brackets) as reported for retinal tacks or glaucoma drainage devices for each of five serious adverse events seen in more than one Argus II subject. The follow-up time reported for each published reference varies but is typically less than or equal to a mean of 12 months. NR = not reported.
The comparison indicates that Argus II rates are similar to glaucoma drainage devices and retinal tacks in most cases. The one exception was endophthalmitis, which was relatively high in Argus II (10%), although each of the three individual events was culture-negative, managed successfully by medical (non-surgical) means, not related to sterility of the device, and not associated with pre-existing conjunctival erosion or hypotony. Notably, two of the three endophthalmitis cases were operated on the same day at a single site. All three cases occurred early in the study (within 2 months post-implant for each case, and within the first year of the overall study start), and no further cases of endophthalmitis were reported up to three years post-implantation after several procedural changes aimed at reducing the risk of infection were implemented. Changes included adding a temporary cover over the array portion of the device during the attachment of the extra-ocular portion of the device on the globe; recommendations to strengthen the sterile procedures at all surgical centers; and the addition of prophylactic intravitreal antibiotics at the end of each case.
Seven subjects underwent elective revision surgeries to attempt to improve the position of the array. These were non-serious adverse events because they were not medically necessary; however, they were interventions intended to improve the benefit of the device for these early subjects. No further elective revision surgeries have been conducted among all new cases since the last of these in 2010.
It is difficult to reach definitive conclusions about safety from this small study. Retinitis pigmentosa is a rare disease, and patients with almost total loss of vision from RP are rarer still. With only 30 subjects, statistical power is low. Among those 30 subjects, however, there were no lost eyes, all events were treated with standard ophthalmological techniques, and there were no unexpected events. The risk presented by the Argus II must also be considered in the context of these patients’ profound blindness and lack of other treatment options. Their vision before the Argus II was in the range of bare light perception or less in both eyes. Generally, ophthalmic adverse events may be a concern due to the possibility of further vision loss; in these patients, residual vision is negligible, thus reducing the risk posed by these adverse events.
This study is the largest and longest-running clinical trial of a retinal prosthesis to date; as of September 1, 2014, the longest duration of implant was 7.2 years. The results in these 30 subjects indicate that the Argus II Retinal Prosthesis System has an acceptable risk profile and is a beneficial therapy for profoundly blind patients suffering from retinitis pigmentosa. Earlier results from this trial were the basis of CE Mark (commercial approval) in Europe. After an FDA-convened panel of 19 experts voted unanimously that the benefits outweighed the risks of the Argus II System, the FDA approved the System for market under the Humanitarian Device Exemption in the U.S.
Supplementary Material
Acknowledgments
Financial Support
NIH grant: 5R01EY012893-10 Greenberg (PI) 07/2000 – 02/2011 NEI, Research/Development of Artificial Retinas for the Blind.
NIH grant: 1RC3EY020778-01 Greenberg (PI), Development and Testing of Low Vision Assessment Tools for Retinal Prostheses.
The clinical trial was sponsored by Second Sight Medical Products, Inc.
The sponsor participated in the design and conduct of the study; data management, analysis, and interpretation; and preparation and review of the manuscript.
The authors would like to thank Suber Huang, M.D., who served as the Independent Medical Safety Monitor for the Argus II Clinical Trial. Some funding was provided by grants from the National Institutions of Health (R01EY012893, RC3EY020778).
Abbreviations
- VPU
Video Processing Unit
- logMAR
Logarithm of the minimum angle of resolution
- ADL
Activities of Daily Living
- QoL
Quality of Life
- PRO
Patient-Reported Outcome
- FLORA
Functional Low-vision Observer Rated Assessment
- SAE
Serious Adverse Event
- SD
Standard Deviation
Footnotes
Conflict of Interest
Jessy D. Dorn and Robert J. Greenberg are employees of and have financial interest in Second Sight Medical Products. Mark S. Humayun and Eugene de Juan have financial interest in Second Sight Medical Products.
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