Argus® II Retinal Stimulation System Feasibility Protocol
Phase: NA
Conditions: Retinitis Pigmentosa
Sponsor: Second Sight Medical Products

Extended Follow-Up of Argus™ II System Feasibility Protocol 
Revision O (January 15, 2013) 
Protocol Title:  Extended Follow-Up of the Argus™ II 
Retinal Stimulation System Feasibility Protocol 
Protocol Number:  CP-003-001-US 
 
 
Current Revision: 
O (January 15, 2013) 
 
 
Sponsor: 
Second Sight Medical Products, Inc. 
12744 San Fernando Road, Building 3 
Sylmar, CA 91342 
 
 
 
Revision History 
Revision 
Date Issued 
 
N 
M 
L 
January 23, 2012 
August 25, 2010 
March 1, 2010 
 
K 
February 25, 2009 
 
J 
June 17, 2008 
 
I 
Not issued 
 
H 
Not issued 
 
G 
Not issued 
 
F 
9/7/07 
 
E 
Not issued 
 
D 
11/22/06 
 
C 
10/17/06 
 
B 
8/18/06 
 
A 
8/8/06 
 
This protocol contains confidential information for use by the 
Investigators and their designated representatives participating in 
this clinical investigation.  It must be held confidential and 
maintained in a secure location. 
Do not copy or distribute without written permission. 

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 Protocol Synopsis 
 
Study Element 
Description 
Title: 
Extended Follow-Up of Argus II Retinal Stimulation 
System Feasibility Protocol 
Protocol Number: 
CP-003-001 
Device: 
Argus II Retinal Stimulation System 
Intended Use: 
The Argus II Retinal Stimulation System is 
intended to provide electrical stimulation of the 
retina to elicit visual perception in blind subjects 
with severe to profound retinitis pigmentosa. 
Diagnosis and Main 
Criteria for Eligibility: 
Retinitis pigmentosa with remaining vision of bare 
light perception or worse in both eyes. 
Study Phases: 
This study is being conducted in 2 phases:  
Investigational phase (i.e. up to 7 years of study 
participation) and Post-Approval phase (i.e. years 
7-10 of study participation).  These two study 
phases are summarized on the following pages. 
Sponsor: 
Second Sight Medical Products, Inc. 
12744 San Fernando Road, Building 3 
Sylmar, CA 91342 
+1-818-833-5000 

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Study Element 
Description 
Investigational Phase: 
 
Primary Objective: 
The objective of this feasibility study is to evaluate 
the safety and utility of the Argus II Retinal 
Stimulation System in providing visual function to 
blind subjects with severe to profound retinitis 
pigmentosa. 
Study Design: 
Single-armed feasibility study 
Primary Endpoints: 
The primary effectiveness endpoint is the subject’s 
visual acuity. 
The primary safety endpoint is the evaluation of 
the safety profile in this population.   
Secondary 
Endpoint(s): 
Secondary endpoints in this study relate to the 
subject’s ability to perform orientation and 
mobility tasks, their perceived quality of life and 
ability to undertake activities of daily living. 
Secondary safety endpoints are related to the 
stability of the device and sensitivity of the 
underlying retinal tissue to electrical stimulation. 
These will be qualitatively evaluated using optical 
coherence tomography, fluorescein angiography, 
retinal photography, CT scan and perceptual 
thresholds for electrical stimulation over time. 
The set-up, optimization and functionality of the 
Argus II System will be evaluated based on the 
tests performed and the feedback from the 
investigators and the subjects. 

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Study Element 
Description 
Length of Follow-Up:  
Subjects initially enrolled in the study for 3 years.  
Following completion of 3 years follow-up, 
subjects may consent to extended follow-up for up 
to an additional 4 years (years 4-7) in the 
investigational phase and another 3 years in the 
post-approval phase.  This provides for a total 
duration of follow-up in the study of 10 years per 
subject.   
 
Average length of follow-up in the investigational 
phase will be 5 years, and will range from 
approximately 3.5 – 5.5 years per subject 
depending on when the subject initially enrolled in 
the study.   
Number of Centers:  
Up to ten (10) centers within the U.S. 
Number of Subjects: 
Up to twenty (20) in the U.S.   
 
 
Study Element 
Description 
Post-Approval Phase: 
 
Post-Approval Study 
Questions: 
1.  Are there any significant changes in the 
device-related adverse events in the late 
follow-up period in subjects implanted with the 
Argus II device?   
2.  What is the long-term reliability of the implant? 
Study Design: 
Extending the Single-armed feasibility study 
Study Hypothesis: 
There is no study hypothesis 
Study Population: 
Subjects who have completed participation in the 
Investigational Phase of this study and who have 
the Argus II device still implanted are eligible for 
enrollment in the Post-Approval Phase of this 
study. 

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Study Element 
Description 
Sample Size: 
N=29. Fourteen (14) subjects were enrolled in the 
Investigational Phase of the study.  One of these 
14 subjects was explanted, which leaves a 
maximum of 13 subjects in the U.S. eligible for 
the post-approval phase of this study. 
An additional 16 subjects were enrolled in a 
similar study in Europe.  All 16 of these subjects 
are eligible for participation in the post-approval 
phase of the study. 
Study Endpoints: 
The primary endpoint of the post-approval phase 
is safety (i.e. the rates of adverse events).  The 
secondary endpoint of the post-approval phase 
the long-term reliability of the Argus II implant. 
Enrollment Plan and 
Follow-up Measures: 
As with all protocol amendments, IRB approval will 
be obtained at each site prior to adding the post-
approval phase to the protocol. 
At the completion of the 7 year follow-up visits, all 
eligible subjects will be offered the option of 
participating in the post-approval phase of the 
study.  Subjects who consent to the post-approval 
phase will be enrolled in this extended follow-up 
portion of the study.   
During the post-approval phase, subjects will 
undergo annual eye exams, assessments of 
medical status and adverse events, and 
measurement of stimulation thresholds.  In 
addition, at the mutual agreement of the 
investigator and the subject, subjects will have the 
option of participating in psychophysical research 
which could occur as frequently as monthly.  
Functional tests at 10 years:  photographic flash, 
square localization, direction of motion and grating 
visual acuity.   
Length of Follow-up: 
Extend the subjects’ overall participation in the 
study to 10 years post-implant. 

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Study Element 
Description 
Frequency of Follow-
up Assessments 
During year 5 to 7, every six month; from year 8 
to 10 annually. Note the examinations are not 
exactly the same prior to year 7 and thereafter, 
because the study undergoing was extended to 
year 7. 
Statistical Plan: 
Descriptive statistics will be used to report data 
collected in the Post-Approval Phase of the study.  
The proportion of subjects experiencing adverse 
events will be calculated along with the 95% 
confidence intervals.   

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This protocol should be read in conjunction with the latest revisions of: 
• Clinician’s Manual (090201) 
• Patient’s Manual (090101) 
• Procedures and Operations Manual (POM) (CP-003-007) 
• Investigator Agreement (CP-003-008) 
• Clinical Trial Agreement 
 

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Table of Contents 
 
1 
INTRODUCTION AND RATIONALE ......................................................................................................... 12 
2 
SYSTEM DESCRIPTION ............................................................................................................................... 14 
2.1 
INTRODUCTION .............................................................................................................................................. 14 
2.2 
PRINCIPLE OF OPERATION .............................................................................................................................. 14 
2.2.1 
Stand-Alone Mode ............................................................................................................................... 14 
2.2.2 
Communication Mode .......................................................................................................................... 14 
2.3 
ARGUS II IMPLANT ......................................................................................................................................... 15 
2.3.2 
Implant Placement ............................................................................................................................... 16 
2.3.3 
Packaging and Sterilization of Argus II Implant ................................................................................. 17 
2.4 
EXTERNAL SYSTEM ........................................................................................................................................ 17 
2.4.1 
Argus II Video Processing Unit (VPU) ................................................................................................ 18 
2.4.2 
Argus II Glasses ................................................................................................................................... 19 
2.4.3 
Argus II Clinical Fitting System .......................................................................................................... 20 
3 
STUDY DESIGN .............................................................................................................................................. 22 
3.1 
STUDY OBJECTIVES ........................................................................................................................................ 22 
3.2 
STUDY OVERVIEW ......................................................................................................................................... 22 
3.3 
JUSTIFICATION FOR THE STUDY DESIGN......................................................................................................... 26 
3.4 
STUDY ENDPOINTS ......................................................................................................................................... 26 
3.4.1 
Primary Effectiveness Endpoint ........................................................................................................... 26 
3.4.2 
Primary Safety Endpoint ...................................................................................................................... 27 
3.4.3 
Secondary Endpoints ........................................................................................................................... 28 
3.4.4 
Endpoints for the Post-Approval Phase of the Study ........................................................................... 29 
4 
STUDY POPULATION................................................................................................................................... 29 
4.1 
INCLUSION CRITERIA ..................................................................................................................................... 29 
4.2 
EXCLUSION CRITERIA .................................................................................................................................... 30 
5 
STUDY PROCEDURES .................................................................................................................................. 33 
6 
SCREENING, BASELINE AND ENROLLMENT PROCEDURES .......................................................... 38 
6.1 
SCREENING .................................................................................................................................................... 38 
6.1.1 
Informed Consent ................................................................................................................................. 38 
6.1.2 
Screening Log ...................................................................................................................................... 38 
6.1.3 
Screening Tests and Exams .................................................................................................................. 38 
6.2 
ENROLLING A SUBJECT .................................................................................................................................. 42 
6.3 
BASELINE TESTING ........................................................................................................................................ 42 
7 
PERI-OPERATIVE STUDY PROCEDURES .............................................................................................. 43 
7.1 
PRE-OPERATIVE MEDICATION REGIMEN ....................................................................................................... 43 
7.2 
ARGUS II RETINAL PROSTHESIS IMPLANTATION ............................................................................................ 43 
7.2.1 
Post-Operative Medication Regimen (starting on Day 1) ................................................................... 43 
8 
FOLLOW-UP STUDY PROCEDURES ........................................................................................................ 45 
8.1 
CLINICAL FOLLOW-UP ................................................................................................................................... 45 
8.2 
ENDPOINT ASSESSMENTS ............................................................................................................................... 46 
8.2.1 
Visual Acuity ........................................................................................................................................ 46 
8.2.2 
Orientation and Mobility Task ............................................................................................................. 48 
8.2.3 
Quality of Life and Activities of Daily Living ...................................................................................... 48 

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8.2.4 
Functional Low Vision Observer-Rated Assessment (FLORA) ........................................................... 48 
8.2.5 
Spatial Vision Tests .............................................................................................................................. 48 
8.2.6 
System Performance ............................................................................................................................ 48 
8.3 
ARGUS II SYSTEM FITTING AND PSYCHOPHYSICAL TESTING ......................................................................... 49 
8.3.1 
Argus II System Fitting ........................................................................................................................ 49 
8.3.2 
Psychophysical Testing ........................................................................................................................ 50 
8.3.3 
Training and Rehabilitation ................................................................................................................. 50 
8.4 
HOME USE ..................................................................................................................................................... 50 
8.5 
EXPLANTATION OF THE IMPLANT ................................................................................................................... 52 
8.6 
REVISION OF THE IMPLANT ............................................................................................................................ 52 
8.7 
MEDICATION REGIME FOR EXPLANT OR REVISION SURGERY ........................................................................ 53 
8.8 
EXTENDED FOLLOW-UP (YEARS 4-10) .......................................................................................................... 54 
9 
STUDY COMPLETION ................................................................................................................................. 54 
10 
WITHDRAWAL AND REPLACEMENT OF SUBJECTS ......................................................................... 55 
11 
STATISTICAL METHODS ........................................................................................................................... 55 
11.1 
SAMPLE SIZE ESTIMATE AND JUSTIFICATION ............................................................................................ 55 
11.2 
ELIGIBILITY OF SUBJECTS, EXCLUSIONS, AND MISSING DATA .................................................................. 55 
11.3 
PRIMARY ANALYSIS POPULATION ............................................................................................................. 56 
11.4 
SECONDARY ANALYSIS POPULATION ........................................................................................................ 56 
11.5 
STATISTICAL ANALYSIS ............................................................................................................................ 56 
12 
DATA MANAGEMENT ................................................................................................................................. 56 
12.1 
DATA COLLECTION ................................................................................................................................... 56 
12.2 
DATA PROCESSING .................................................................................................................................... 57 
13 
MONITORING PROCEDURES .................................................................................................................... 57 
13.1 
MONITORING ............................................................................................................................................. 57 
13.1.1 
Site Qualification ............................................................................................................................ 58 
13.1.2 
Site Initiation/Training .................................................................................................................... 58 
13.1.3 
Interim Monitoring .......................................................................................................................... 58 
13.1.4 
Site Closure ..................................................................................................................................... 59 
13.2 
DEVICE ACCOUNTABILITY ........................................................................................................................ 59 
13.3 
PROTOCOL VIOLATIONS AND DEVIATIONS ................................................................................................ 59 
14 
ADVERSE EVENTS ........................................................................................................................................ 59 
14.1 
RECORDING ADVERSE EVENTS ................................................................................................................. 60 
14.1.1 
Anticipated Adverse Events ............................................................................................................. 61 
14.1.2 
Anticipated General Adverse Events ............................................................................................... 64 
14.1.3 
Unanticipated Adverse Events ........................................................................................................ 65 
14.2 
REPORTING ADVERSE EVENTS .................................................................................................................. 65 
14.2.1 
Unanticipated, Serious, Device Related Adverse Events ................................................................ 65 
14.2.2 
Serious Adverse Events ................................................................................................................... 66 
14.2.3 
Other Adverse Events Requiring Immediate Notification ............................................................... 66 
14.2.4 
Other Adverse Events ...................................................................................................................... 66 
14.3 
INDEPENDENT MEDICAL SAFETY MONITOR .............................................................................................. 66 
15 
DEVICE FAILURES AND MALFUNCTIONS ............................................................................................ 66 
16 
ETHICAL CONSIDERATIONS .................................................................................................................... 67 
16.1 
DECLARATION OF HELSINKI ...................................................................................................................... 67 
16.2 
ETHICS COMMITTEE/INSTITUTIONAL REVIEW BOARD............................................................................... 67 
16.3 
EMERGENCY ACTIONS............................................................................................................................... 67 
16.4 
INFORMED CONSENT FORM ....................................................................................................................... 67 

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16.5 
AMENDING THE PROTOCOL ....................................................................................................................... 68 
17 
STUDY ADMINISTRATION ......................................................................................................................... 68 
17.1 
STUDY TIMELINES FOR THE POST-APPROVAL PHASE OF THE STUDY ........................................................ 68 
17.2 
STUDY REPORTING SCHEDULE .................................................................................................................. 69 
17.3 
RECORD RETENTION ................................................................................................................................. 69 
17.4 
CRITERIA FOR TERMINATING THE ENTIRE STUDY ..................................................................................... 69 
17.5 
CRITERIA FOR TERMINATING THE STUDY AT AN INVESTIGATIONAL SITE.................................................. 70 
17.6 
SPONSOR RESPONSIBILITIES AND COMMITMENTS ..................................................................................... 70 
17.7 
INVESTIGATOR QUALIFICATIONS/RESPONSIBILITIES ................................................................................. 70 
18 
PUBLICATION POLICY ............................................................................................................................... 70 
APPENDIX A - SPONSOR RESPONSIBILITIES ................................................................................................ 71 
APPENDIX B - CLINICAL RISK/BENEFIT ASSESSMENT ............................................................................. 72 
APPENDIX C - BIBLIOGRAPHY .......................................................................................................................... 83 
  

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Table of Tables 
 
Table 3.1 
Visual Acuity Scores ........................................................................................................................ 27 
Table 5.1 
Study Event Schedule ....................................................................................................................... 33 
Table 5.2 
Post-Explant Schedule ...................................................................................................................... 34 
Table 5.3 
Study Procedures and Tested Eyes ................................................................................................... 35 
Table 5.4 
Extended Follow-Up Schedule (Years 4-7) ...................................................................................... 36 
Table 5.5 
Post-Approval Phase Follow-Up Schedule (Years 8-10) .................................................................. 37 
Table 11.1 Monitoring Visit Schedule .................................................................................................................. 57 
3.11.1. 
Radiofrequency Transmission Standards .............................................................................................. 79 
 
Table of Figures 
 
Figure 2.1 
Schematic Overview of the Argus II System ........................................................................................ 15 
Figure 2.2 
Illustration of Argus II Implant ............................................................................................................. 16 
Figure 2.3 
Argus II Implant in Position on a Right Eye  (Conceptual Temporal Side View) ................................ 17 
Figure 2.4 
Argus II Video Processing Unit (VPU) ................................................................................................ 19 
Figure 2.5 
Argus II Glasses.................................................................................................................................... 20 
Figure 3.1 
Study Flow Chart .................................................................................................................................. 25 
Figure 6.1 
Visual Acuity Testing at Screening ...................................................................................................... 41 
Figure 8.1 
Visual Acuity Testing at Follow-Up ..................................................................................................... 47 
 
 

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1 Introduction and Rationale 
“In outer retinal degeneration, such as retinitis pigmentosa 
(RP), the photoreceptors and their supporting retinal pigment 
epithelium are impaired.  In RP (incidence 1:4000) legal 
blindness is reached after 25 years.  In many RP patients over 
sixty years of age, elementary vision with only gross movement 
or bright light perception remains, with little or no appreciable 
peripheral vision.  Eventually, even light perception may 
recede.  Currently, there is no treatment that stops or reverses 
the loss of photoreceptors in retinitis pigmentosa”.1 
Traditionally, the approach to vision rehabilitation in subjects with retinitis 
pigmentosa has been to use the remaining vision with optical aides.  If no 
useful vision is achieved, auditory or tactile information is substituted (e.g. 
Braille, cane travel, etc.).  Attempts to remedy or alleviate vision loss have 
been made by replacing damaged cells or by electrically stimulating an 
undamaged proximal level, bypassing impaired cells.  Replacement of 
damaged photoreceptors has been studied in animals through 
transplantation.2  Although there are indications that transplanted 
photoreceptors can make functional connections, many questions remain 
about the optimal methods to achieve long term graft survival and 
functionality in a human eye. 
More recently, visual prostheses have been developed to address the 
extreme low vision population with retinal degeneration.3  Electrical 
stimulation at the primary visual cortex has been attempted and has the 
advantage of not requiring a viable optic nerve.4  However, such cortical 
stimulation has its own risks, such as exposing the brain to surgical 
complication and infection. 
Stimulation at more distal neuronal locations has received recent attention 
and may provide an alternative in an outer retinal degenerative disease such 
as retinitis pigmentosa.5,6,7,8,9,10,11,12  Electrical stimulation of the optic nerve 
has been used to elicit a sensation of streaks or dots (phosphenes).  Also, 
electrical stimulation through a contact lens electrode elicits phosphenes in 
subjects with advanced photoreceptor degeneration.  These perceptual 
responses, and the electrically evoked responses recorded from the scalp in 
response to such stimuli, have been interpreted as evidence that inner 
retinal cells in subjects with photoreceptor degeneration retain at least 
partial function.  However, the phosphenes elicited with a contact lens 
electrode or by electrical stimulation of the optic nerve lack well defined 
shape or localization. 
The production of a small localized visual percept that might allow the 
generation of a two-dimensional array of phosphenes to provide “pixelized 

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visual input” has been explored in both acute and chronic studies of blind 
subjects. Even partial restoration of vision in subjects blind from 
photoreceptor degeneration has been shown to be 
important.13,14,15,16,17,18,19,20,21,22,23,24,25,26  Second Sight has undertaken the 
development of a Retinal Stimulation System intended for use in subjects 
with retinitis pigmentosa.  The earlier generation device (Argus 16 Retinal 
Stimulation System) has been implanted in six subjects in an Investigational 
Study.   The Argus 16 Study has demonstrated that subjects have the ability 
to perceive phosphenes generated by epi-retinal electrical stimuli and 
perform simple tasks such as: 
• Determine the position, orientation and direction of motion of objects,  
• Locate doorways   
Based on the results of the study, the current system has incorporated 
several improved features: 
• Increased number of electrodes.  Up to sixty electrodes will be used to 
increase visual resolution up to a theoretical limit of 2.1 logMAR based 
on a 575µm spacing of the electrodes. 
• Increased field of view.  The electrodes will cover an area of the retina 
corresponding to a 20 degree diagonal field of view, 
• Thin Film Electrode Array and cable.  The thin film cable replaces the 
round cable to reduce the risk of conjunctival erosion by the cable. 
• Extra-ocular placement.  The Argus II implant electronics are placed 
on the outer surface of the eye, removing the need for a tunneled 
cable and the implanting of the case in the skull of the subject.  The 
new implant procedure this affords reduces operative duration 
significantly and should also reduce post-operative complications. 
This feasibility study will utilize an array with up to sixty independently 
controllable electrodes implanted epiretinally to provide visual input via an 
external camera system and seeks to evaluate the utility of this system for 
safety, improvement in visual acuity, orientation and mobility, activities of 
daily living, and quality of life in subjects with retinitis pigmentosa. 
 

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2 System Description 
2.1 
Introduction 
The Argus II Retinal Stimulation System developed by Second Sight is a 
second generation system following the first generation Argus 16.  The main 
differences are that the Argus II provides more independent channels for 
stimulation and that the Argus II Implant (including the Internal Coil) is 
attached to the outside of the eye.  Like the Argus 16 System, the Argus II 
system comprises three sub-system components: the Argus II Implant, the 
Video Processing Unit (Argus II VPU) and the Argus II Glasses, and the 
Clinical Fitting System.  The principle of operation and a description of each 
of the Argus II sub-system components (Implant, VPU, and the Clinical 
Fitting System) are provided below. 
2.2 
Principle of Operation 
The principle of operation of the Argus II System is shown schematically in 
Figure 2.1.   
2.2.1 
Stand-Alone Mode 
In Stand-Alone Mode (inset in Figure 2.1), the camera, which is attached to 
eye-glasses worn by the subject, captures a video image (Argus II Glasses). 
The camera signal is sent to the Argus II VPU (powered by a rechargeable 
battery), which processes the camera image and transforms it into electrical 
stimulation patterns. The electrical stimulation data are then sent to the eye-
glasses mounted coil which sends both data and power via radio-frequency 
(RF) telemetry to the Argus II Implant. The implant coil receives the radio-
frequency commands which control an application-specific integrated circuit 
which in turn delivers stimulation to the retina via an electrode array.  
2.2.2 
Communication Mode 
When parameters are being adjusted to tailor the system to a subject or to 
do psychophysical testing with a subject, the Argus II VPU is connected to a 
dedicated fitting system (Clinical Fitting System), as seen in (Figure 2.1) via 
a cable between the VPU and the Communications Adapter.  In this mode, 
computer generated stimuli may be presented to the subject and 
programming parameters may be adjusted. In addition, a second computer 
(Psychophysical Test System) may be utilized to perform more sophisticated 
testing and analysis. 
 

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Figure 2.1 
Schematic Overview of the Argus II System 
 
2.3 
Argus II Implant 
A diagram of the Argus II Implant is provided in Figure 2.2.  The implant 
consists of four components: 
1. A small hermetic case that contains the electronics to receive power 
and communicate with the external system, and to drive the electrical 
stimulation of the electrodes. 
2. An internal coil that receives power and data from the external primary 
coil.   

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3. An electrode cable ending in an array that is electrically connected to 
the case and transmits the stimulation signals to the retina via the 
exposed electrodes. It is secured to the retina with a retinal tack.   
4. A scleral band that allows the implant to be secured to the outside of 
the eye. 
 
Figure 2.2 
Illustration of Argus II Implant 
 
 
2.3.2 
Implant Placement 
A conceptual side view illustrations of the Argus II Implant on a right eye is 
provided in Figure 2.3. The array enters the eye through a pars plana 
incision and the array is placed on the retina over the macula using a retinal 
tack.  The extra-ocular portion of the Argus II Implant is secured to the eye 
by means of a scleral band held in place by a Watzke sleeve (typical of 
scleral buckling procedures), and also by suture tabs. The inferior and 
superior implant suture tabs can be seen in Figure 2.3.  Additionally, the 
surgeon may elect to place a suture around the scleral band in the inferior 
medial quadrant. A description of the surgical implantation procedure is 
provided in Chapter 3 of the Clinician’s Manual. 
 
Electrode cable 
ending in an array 
Internal 
Coil 
Case 
Scleral Band 

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Figure 2.3 
Argus II Implant in Position on a Right Eye  
(Conceptual Temporal Side View) 
 
 
2.3.3 
Packaging and Sterilization of Argus II Implant 
The Argus II implant is individually packaged in a sealed tray with two 
Second Sight retinal tacks and provided sterile. The method of sterilization is 
ethylene oxide and the process has been validated for ocular use.  
2.4 
External System 
The External System consists of a pair of glasses with a video camera 
mounted above the nose piece and a RF coil that provides power and sends 
and receives data from the implant and the Video Processing Unit.  The 
purpose of the Argus II Video Processing Unit is to convert the input video 
Array in 
position over 
the fovea 
Superior 
suture tabs 
Inferior  
suture tab 

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signal to a pattern of electrical stimulation to be sent to the implant.  The 
VPU also allows the subject to turn the system on and off, and to manually 
adjust settings within pre-determined safe limits.  This section describes the 
main components of the Argus II External system.  A detailed description of 
these components is provided in Chapter 2 of the Clinician’s Manual. 
2.4.1 
Argus II Video Processing Unit (VPU) 
The Argus II VPU comprises a case, buttons, connectors, rechargeable 
battery and digital circuit boards.  The buttons are large and shaped so that 
they can be easily identified by touch.  There is one connector that connects 
the Argus II VPU to the Argus II Glasses.  The Argus II VPU can also be 
connected to the Argus II Clinical Fitting System during subject testing and 
fitting using a specialized connector that is covered by a rubber seal when 
the Argus II VPU is used in stand-alone mode.  An illustration of the Argus II 
VPU is provided in Figure 2.4. 
 

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Figure 2.4 
Argus II Video Processing Unit (VPU) 
 
 
The Argus II VPU is in constant communication with the implant.  The Argus 
II VPU transmits null frames (containing no stimulation information) until it 
synchronizes with the implant.  Stimulation can then occur.  Any loss of 
synchronization causes an alarm. 
The Argus II VPU acquires video input from the camera and converts it into a 
digital format.  Filters, such as edge detection, may be then applied.  The 
image is then reduced to sixty channel resolution using a downscaling filter.  
This representation of the image is then mapped to stimulation intensity 
using customized look-up tables that have been derived from testing of 
individual subjects.  A check is performed to assure that the overall current 
and the maximum charge per phase are within safety limits.  The stimulation 
parameters are then sent via telemetry to the implant in frames that employ 
an error detection scheme. 
The Argus II VPU is battery powered and has no “mains” connection.  As will 
be discussed below, when the Argus II VPU is connected to the Argus II 
Clinical Fitting System, it is optically isolated.  This removes the risk of 
electrical shock that can be associated with medical equipment. 
2.4.2 
Argus II Glasses 
The Argus II Glasses provide a convenient and discreet way to house the 
video camera and radio-frequency system needed to power and 
communicate with the implant.  A photograph of a sample design of the 
Argus II Glasses is shown in Figure 2.5 below. 

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Figure 2.5 
Argus II Glasses 
 
 
 
 
A small, light-weight color video camera is mounted in the center of the 
frame above the nose-piece. The telemetry coils and radio-frequency board 
are mounted on the ear piece.  The position of the coil housing is adjustable 
to provide comfort to the subject and to allow the external coil assembly to 
be optimally positioned relative to the implant coil to achieve a good 
communication link for subjects with different facial structure.  
2.4.3 
Argus II Clinical Fitting System  
The Argus II Clinical Fitting System consists of software with a graphical 
user interface running on a laptop computer.  This computer is connected to 
the Argus II VPU using an optically isolated serial connection (Argus II 
Communication Adapter).  Being optically isolated, the serial connection 
assures that no electric leakage current can flow from the Argus II Clinical 
Fitting System to the Argus II VPU in the event of a fault condition.   
The Argus II Clinician Fitting System is used to configure the Argus II 
system stimulation parameters and video processing strategies for each 
subject. The fitting application, operating system, laptop, isolation unit and 
Argus II VPU are tested and configuration controlled as a system. The 
RF board 
Coil  
Camera 

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software provides modules for electrode control, permitting the clinicians to 
interactively construct test stimuli with control over amplitude, pulse-width, 
and frequency of the stimulation waveform of each electrode. These 
parameters are checked to ensure that the maximum charge per phase is 
not exceeded, the charge in each biphasic pulse is balanced, and power 
limitations are not surpassed before the test stimuli are presented to the 
subject.  In addition, these parameters are checked a second time by the 
Argus II VPU firmware.  The fitting system also allows the clinician to control 
the spatial relationship between the video input and the electrodes, and to 
apply image processing filters to the video input.   
The Argus II Clinician Fitting System software provides a psychophysical 
software module that allows the clinician to quickly administer pre-
programmed test protocols.  Responses to these test protocols may be 
verbal or may be recorded by a keypad, or by other computer input devices.  
Using this module, important perceptual parameters, such as electrical 
stimulation threshold, can be reliably measured. Based on these perceptual 
parameters, the fitting software allows the clinician to custom configure the 
transformation between the video image and electrode stimulation 
parameters thereby optimizing the effectiveness of the retinal prosthesis for 
each subject.  Multiple transformation strategies may be downloaded to the 
VPU and stored in non-volatile memory.  The software can also load a 
previously used transformation strategy from the VPU for adjustment.  
To enable customized psychophysical testing, an Argus II Psychophysical 
Test System is connected to the Argus II Clinician Fitting System.  This 
system utilizes MatLAB® to develop, perform and analyze results of subject 
testing.  During such testing, the safety checks for charge balance, current 
density and total charge in the Argus II Clinician Fitting System and Argus II 
VPU will continue to operate to protect subject safety. 

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3 Study Design 
3.1 
Study Objectives 
Investigational Phase of the Study 
The objective of this feasibility study is to evaluate the safety and utility of 
the Argus II Retinal Stimulation System in providing visual function to blind 
subjects with retinitis pigmentosa.   
Post-Approval Phase of the Study 
To collect post-approval data in order to monitor the ongoing safety and 
reliability of the Argus II System 
3.2 
Study Overview 
The Argus II chronic retinal stimulation system is an implantable electronic 
device designed to provide chronic electrical stimulation of the retina in 
order to elicit visual percepts in blind subjects with retinitis pigmentosa.   
The Argus II Implant has a theoretical equivalent acuity (or Nyquist limit) of 
approximately 2.1 logMAR.27,28  To ensure that subjects will enter the study 
with worse acuity than a conservative estimate of the potential afforded by 
the Argus II System, we will initially only enroll subjects with bare light 
perception or worse, in both eyes.  These subjects will be at the least visual 
risk, since they have very progressed disease and almost no usable spatial 
vision. 
Visual acuity will be measured with a test that uses high contrast square 
wave gratings.  High contrast square gratings can be calibrated using a 
photometer, which can directly compare the luminance of the light and dark 
areas, whereas sinusoidal gratings require a more complex calibration 
procedure. Campbell showed that in subjects with low vision square gratings 
yield similar results to sinusoidal ones, due to the limited visual frequency 
response of these subjects.29  The test requires subjects to report the 
orientation of the grating in each trial (horizontal, vertical, oblique left or 
oblique right).  The visual acuity score is defined as the highest level at 
which the subject guesses the orientation correctly at a rate that is half way 
between chance and perfect performance. 
To facilitate a more targeted screening population, only adults (twenty-five 
years of age or older) will be evaluated.    
Prior to formal enrollment, subjects will be screened for inclusion by 
undergoing a series of interviews and tests including a complete ophthalmic 
examination, a medical history interview, a psychological evaluation and 

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visual acuity testing.  Once enrolled, subjects will undergo additional testing 
and diagnostic imaging to gather baseline data.  It is estimated that 
screening and baseline testing will each last less than six hours. 
This study evaluates the impact of the Argus II system on subjects’ quality 
of life and activities of daily living.  Quality of life will be assessed in all 
subjects using the VisQOL instrument.  The VisQOL is a validated instrument 
for the evaluation of the quality of life in visually impaired subjects.30  The 
VisQOL scores will serve as a baseline means of comparison for the 
implanted population, pre- and post-operatively.  The difficulty and 
importance of daily activities will be assessed using portions of the self-
reported questionnaire developed by Massof.31,32    
To evaluate the utility of the Argus II System for orientation and mobility, 
each subject will be asked to complete a mobility tasks modeled after that 
used by Turano but greatly simplified for the extreme low vision 
population.33,34  The tasks will use high contrast targets and the subject’s 
accuracy and time taken to complete the tasks will be evaluated. 
A functional low-vision observer rated assessment (FLORA) will be 
performed by a certified low vision therapist to evaluate how the Argus II 
System affects subjects’ everyday lives. 
The implant position, proximity to the retina and the retina under and 
around the array will be evaluated using retinal photography, optical 
coherence tomography (OCT) and fluorescein angiography.  An ultrasound 
B-scan will be obtained to measure the posterior coats thickness in the 
region where the array is placed. The extra-ocular placement of the device 
will be documented by CT scan. 
Subjects may be hospitalized for up to one day after surgery as needed.  
Post-operatively, study subjects will be treated and monitored per routine 
hospital post-operative procedure for ophthalmic surgery. 
Post-operative visits to evaluate and optimize the parameters of the Argus II 
will occur up to twice weekly and will last up to 4 hours at each visit.  As 
with the model A16 implant, subjects will be allowed to use the system 
outside the clinic.  Home use will only be permitted after system 
configuration and adequate training.  
Subjects will be followed post-operatively for 36 months.  Whether the 
subject completes the study or withdraws from the study, the subject will 
have the option to either keep the device implanted, or have it surgically 
removed.   
Following completion of 36 months follow-up, subjects may consent to 
extended follow-up for up to an additional 7 years.  Subjects will be asked to 

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consent for extended follow-up in 3 increments (i.e. years 4-5, then years 6-
7, then years 8-10).  During this time, subjects will be allowed to continue 
using their system and they will undergo periodic clinical follow-up and 
optional testing in the clinic.  
The device will be explanted if the subject experiences unresolved 
intraocular infection, clinically significant retinal detachment, unexplained or 
known device failure that may pose a risk to the subject, or intractable pain. 
All surgically removed devices will be returned to Second Sight for 
examination. 
This study is designed to enroll up to twenty (20) subjects in the U.S. and 
will require approximately 48 months to complete 3 years follow-up on all 
subjects.  If subjects consent to participate in extended follow-up, the study 
will continue for up to an additional 7 years. 
A flow chart of a subject’s participation in the study follows in Figure 3.1 
below. 

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Figure 3.1 
Study Flow Chart 
Subject 
presentation
Subject signs 
Screening 
Informed Consent
Perform Screening
Subject meets 
selection criteria?
Document on 
Screening Log
Exclude From 
Study
Subject signs Baseline 
Informed Consent
(if both a screening and 
main informed consent 
form are being used)
Perform Baseline 
Testing and 
Exams
Enroll Subject
Day 0:  
Surgically Implant 
Device
Day 1 Through 
Month 36:  
Follow-up
Study Conclusion
No
Yes
Subject consents to Years 4-5 
Extended Follow-up?
Years 4-5  Follow-Up
No
Yes
Subject consents to Years 6-7
Extended Follow-up?
Years 6-7 Follow-Up
Yes
No
Subject consents to Years 8-10
Extended Follow-up?
Years 8-10 Follow-Up
Yes
No

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3.3 
Justification for the Study Design 
This is a feasibility study to evaluate the safety and utility of the Argus II 
Retinal Stimulation System and to evaluate the methods used for optimizing 
programmable parameters.  Measurements taken with the device both off 
and on will serve as internal controls in each subject.  The risks involved 
with the implantation of the Argus II System are justified by the lack of 
alternate treatments for retinitis pigmentosa.1   In addition, the subjects for 
this feasibility study will have only bare light perception, minimizing the risk 
due to loss of residual vision.   Edwards, et.al. and Gartner, et.al. indicate 
that advanced retinitis pigmentosa provides a protective effect against 
possible retinal detachment.35,36  A detailed clinical risk assessment is 
attached in Appendix B. 
This study will not be masked to the subjects or the investigators. 
3.4 
Study Endpoints 
3.4.1 
Primary Effectiveness Endpoint 
The primary effectiveness endpoint is determined by objective measurement 
of visual acuity, the finest detail a subject can see. Visual acuity in the 
treated eye is quantified over a wide range of spatial vision with a high 
contrast grating acuity test and a full field stimulus threshold test.  Subjects’ 
visual acuity will be scored according to Table 3.1. 
Effectiveness will be analyzed by comparing the subject’s visual acuity score 
at enrollment and at follow-ups after implant.  Control will be established 
using the subject’s fellow eye and the implanted eye with the device OFF. 
Methods for performing the visual acuity tests are provided in the 
Procedures and Operations Manual. 

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Table 3.1 Visual Acuity Scores 
 
Visual Acuity 
log MAR 
Snellen 
European 
1.6 
20/796 
6/239 
1.7 
20/1002 
6/301 
1.8 
20/1262 
6/379 
1.9 
20/1589 
6/477 
2.0 
20/2000 
6/600 
2.1 
20/2518 
6/755 
2.2 
20/3170 
6/951 
2.3 
20/3991 
6/1197 
2.4 
20/5024 
6/1507 
2.5 
20/6325 
6/1898 
2.6 
20/7962 
6/2389 
2.7 
20/10024 
6/3007 
2.8 
20/12619 
6/3786 
2.9 
20/15887 
6/4766 
N/A  
Bare Light Perception 
(BLP) 
N/A 
No Light Perception  
(NLP) 
3.4.2 
Primary Safety Endpoint 
The primary safety endpoint is the evaluation of the safety profile in this 
population. 

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3.4.3 
Secondary Endpoints 
Orientation and Mobility 
Geruschat, Turano et al have used a simple mobility task consisting of a 
corridor with high contrast obstacles to evaluate the orientation and mobility 
of low vision subjects.33,34  It was found that the time to traverse the course 
was correlated with visual acuity and visual field.  This study will use a 
greatly simplified course.  Each subject will be asked to walk to a high-
contrast target on the wall and in a second test asked to follow a straight 
line on the floor.  The subject’s time and accuracy will be measured.  This 
instrument will be given to the subject pre-implant, then at prescribed 
intervals post-operatively. 
Subjects’ use of the Argus II System for orientation and mobility in their 
everyday lives will be assessed by an independent, certified low-vision 
therapist (e.g. CLVT, OTR/L, COMS, etc.) using commonly accepted 
techniques for performing such assessments and an instrument (Functional 
Low-Vision Observer Rated Assessment [FLORA]) designed specifically for 
this study. 
Quality of Life and Activities of Daily Living  
These secondary endpoints are the subject’s perceived quality of life and 
ability to undertake activities of daily living.  These endpoints will be 
measured using: 
a) the VisQOL survey,  
b) the Massof Activity Inventory 
c) Functional Low-Vision Observer Rated Assessment [FLORA] 
(mentioned above) 
The VisQOL Health Survey is a health-related quality of life instrument that 
has been validated and used in low vision subjects.30  The use of this 
instrument will provide a baseline for the general quality of life for these 
subjects and the impact of a retinal implant on their outlook.  This 
instrument will be given to the subject pre-implant, then at prescribed 
intervals post-operatively. 

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The Massof Activity Inventory is a series of activity related questionnaires 
that allow discrimination of both the usefulness and the difficulty of each 
task.31,32  Through the evaluation of tasks the subject finds useful or 
pleasurable, the inventory provides a measure of the “real-world” daily living 
changes, rather than artificial constructs.  This yields a meaningful measure 
without the risks of the subject “training to the test.” 
Spatial Vision 
Two additional spatial vision tests will be performed to supplement the 
Grating Visual Acuity test.  These tests, Square Localization and Direction of 
Motion, are designed to provide an objective measure of spatial vision in 
subjects who cannot reach the lowest level of the Grating Acuity scale (2.9 
logMAR).  These tests are similar to two of the procedures included in the 
Basic Light and Motion (BaLM) test developed by Michael Bach (U. of 
Freiburg, Freiburg, Germany).   
 
Stability of the Implant 
The stability of the array will be qualitatively evaluated using electrode 
impedances, stimulation thresholds, optical coherence tomography (OCT), 
CT scan and retinal photography. 
System Functionality 
The set-up, fitting and functionality of the Argus II System will be evaluated 
via psychophysical testing and feedback from the investigators and the 
subjects via the customer contact system. 
3.4.4 
Endpoints for the Post-Approval Phase of the Study 
The primary endpoint of the post-approval phase is safety (i.e. the rates of 
adverse events).  The secondary endpoint of the post-approval phase the 
long-term reliability of the Argus II implant by calculating the rate of implant 
failure over time. 
4 Study Population 
All subjects who are referred to the investigator with retinitis pigmentosa 
with significant visual loss are potential study candidates and may be 
screened for eligibility.  Eligibility of the subject must be established before 
enrollment.  Subjects who do not meet all selection criteria will not be 
enrolled.   
4.1 
Inclusion Criteria 
Each enrolled subject must: 

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1.  
Have a confirmed history of retinitis pigmentosa and have a visual 
acuity of Bare Light Perception or worse in both eyes (see Table 3.1).  
NOTE:  The implant should be implanted in the worse-seeing eye.  If 
there is no significant difference in vision between the two eyes, then 
the investigator will ask the subject which eye is his/her worse eye to 
determine which eye should be implanted.   
2.  
Have functional ganglion cells and optic nerve in the implanted eye 
as determined by documented light perception or a measurable 
electrically evoked response. 
3.  
Have a history of useful form vision in the worse-seeing eye. 
4.  
Be twenty-five (25) years or older at the time of enrollment. 
5.  
Reside within two (2) hours distance (by ground transportation) of 
the investigational site. 
6.  
Be willing and able to comply with the protocol testing and follow-up 
requirements. 
4.2 
Exclusion Criteria 
Each enrolled subject must NOT have or be: 
1. 
Optic Nerve disease 
a. History of glaucoma 
b. Optic neuropathy or other confirmed damage to optic nerve or 
visual cortex  
2. 
Diseases or conditions that affect retinal function including but not 
limited to: 
a. Central retinal artery/vein occlusion (CRAO or CRVO) 
b. End-stage diabetic retinopathy 
c. Retinal detachment or history of retinal detachment 
d. Trauma 
e. Infectious or inflammatory retinal diseases 
3. 
Diseases or conditions that prevent adequate visualization of the 
retina including, but not limited to cataract or corneal degeneration 
that cannot be resolved before baseline testing. Cataracts that permit 
visualization of the retina are NOT exclusive and will be removed at 
the time of implant surgery. 

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4. 
Diseases or conditions of the anterior segment that prevent the 
ability to adequately perform the physical examination including but 
not limited to trauma or lid malpositions. 
5. 
Diseases of the ocular surface including but not limited to keratitis 
sicca and corneal ulcers. 
6. 
An ocular condition that predisposes the subject to eye rubbing. 
7. 
Any disease or condition that prevents understanding or 
communication of informed consent, study demands, and testing 
protocols, including: 
a. Cognitive decline including diagnosed forms of dementia and/or 
progressive neurologic disease 
b. Psychiatric disease including diagnosed forms of depression 
c. Does not speak a principal language associated with the region 
d. Deafness or selective frequency hearing loss that prevents 
hearing device alarms and alerts 
8. 
Pregnancy. 
9. 
Any metallic or active implantable device (e.g. cochlear implant) in 
the head. 
10. Conjunctival thinning which may predispose the subject to 
conjunctival erosion in the area where the implant will be installed 
extra-ocularly (Note:  this is generally associated with a history of 
tobacco use greater than twenty pack-years.*) 
11. Participating in another investigational drug or device study that may 
conflict with the objectives, follow-up or testing of this study 
12. Any health concern that makes general anesthesia inadvisable.  
13. Unrealistic expectations of the system. 
14. Known allergy or contraindication to anticipated pre-operative, intra-
operative and post-operative medications.  Refer to Section 7 for a 
description of these medications. 
15. Conditions likely to limit life to less than 1 year from the time of 
screening. 
                                    
*  Pack-years is the number of packs per day times the number of years smoked.  For 
example two packs a day for ten years is 20 pack-years.  Also one pack per day for 15 
years is 15 pack-years. 

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16. Diseases or conditions that, in the judgment of the surgeon, impede 
the ability to implant the device or would prevent the system from 
functioning for the duration of the study (e.g. strabismus). 
17. An axial eye length <21.5 mm or >26.0 mm in the implanted eye as 
measured by ultrasound. 
 

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5 Study Procedures 
Table 5.1 Study Event Schedule 
Evaluation or Test 
Screening 
(-60 days – BL) 
Baseline (BL) 
(-60 days – day 
0)
Implant 
(Day 0) 
1 Day 
(12-36 hours) 
1 Week 
(5-9 days) 
2 Weeks 
(12 – 16 days) 
4 Weeks 
(24- 32 days) 
3 Months 
(75-105 days) 
6 Months 
(170-200 days) 
9 Months 
(250 – 290 
days)
12 Months 
(330-390 days) 
18 Months 
(525-565 days) 
24 Months 
(700-740 days) 
30 Months 
(890 – 930 
days)
36 Months 
(1065-1125 
days) 
Informed Consent 
x 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical Evaluation 
x† 
x 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Psychological Evaluation 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Complete Eye Exam 
x 
  
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Visual Field 
 
x 
 
 
 
 
 
 
x 
 
x 
 
x 
 
x 
Retinal Photography 
 
x 
 
 
x 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Fluorescein Angiogram 
 
x 
 
 
x 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Optical Coherence Tomography 
 
x 
 
 
x 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Ultrasound A- and B-scans 
x 
 
 
 
 
 
x (B- 
only) 
If subject was enrolled before March 2010, B-scan 
should be performed at next available clinic visit. 
CT Scan 
 
 
 
 
x 
 
 
 
 
 
 
 
 
 
 
Document Fixation Position and Eye Movement Range 
 
x 
 
 
Performed on an as-needed basis. 
Visual Acuity, including 
   Grating Acuity 
   Full Field Stimulus Threshold 
   (Electrically Evoked Response (EER)‡ 
X§ 
 
 
 
 
 
 
x 
x 
 
x 
x 
x 
 
x 
Orientation and Mobility Tasks 
 
x 
 
 
 
 
 
x 
x 
 
x 
x 
x 
 
x 
Massof Activity Inventory 
 
x 
 
 
 
 
 
x 
x 
 
x 
x 
x 
 
x 
VisQOL 
 
x 
 
 
 
 
 
x 
x 
 
x 
x 
x 
 
x 
Functional Low-Vision Observer Rated Assessment (FLORA) 
 
 
 
 
 
 
 
 
 
 
X*** 
 
 
 
X*** 
Square Localization & Direction of Motion 
 
x 
 
 
 
 
 
x 
x 
 
x 
x 
x 
 
x 
Perceptual Thresholds for Electrical Stimulation  
 
 
 
 
 
 
x 
x 
x 
 
x 
x 
x 
 
x 
System Fitting and Psychophysical Testing 
 
 
 
 
Ongoing. **  Typically 1-2 times per week. 
Home Use 
 
 
 
 
Ongoing after subjects meets home use criteria. 
                                    
† If the subject is female and capable of giving birth, this evaluation must include a pregnancy test 
‡ EER is only performed at screening and only if the subject has no light perception 
§ These tests are to be performed twice, on different days 
** Testing commences at latter of the following:  (a) 1 week post-implant, or (2) when the conjunctiva is sufficiently healed in the opinion of the clinician. 
*** For subjects enrolled in the study prior to August 2010, the FLORA should be performed as soon as possible after the subject consents to the test.  The 
assessment will be counted toward the closest follow-up visit (i.e. 1 or 3 years) even if it is performed outside that visit window. 

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Table 5.2 Post-Explant Schedule 
Evaluation or Test 
Explant 
(Day 0) 
1 Day 
(12-36 
hours) 
1 Week 
(5-9 
days) 
4 Weeks 
(24- 32 
days) 
3 Months 
(80-100 
days) 
6 Months 
(170-200 
days) 
12 Months 
(340-380 
days) 
Medical Interview, 
Complete Eye exam and 
Review for AE 
 
X 
X 
X 
X 
X 
X 
Retinal Photography  
 
 
X 
X 
X 
X 
X 
Optical Coherence 
Tomography 
 
 
X 
X 
X 
X 
X 
Fluorescein Angiogram  
 
 
X 
X 
X 
X 
X 
The post–explant schedule should be followed ONLY in the event that the device is explanted and the 
subject consents to post-explant follow-up.  Unless otherwise indicated, the device will remain implanted 
at the conclusion of the study. 

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Table 5.3 Study Procedures and Tested Eyes 
Evaluation or Test 
Screening & Baseline 
Follow-up 
Eye Tested 
Eye Tested 
System ON/OFF 
Complete Eye Exam   
Both, separately 
Both, separately 
OFF 
Visual Field 
Both, separately 
System OFF - Both, 
separately 
System ON – Both, 
together 
ON and OFF 
Retinal Photography  
Both, separately 
Both, separately 
OFF 
Fluorescein Angiogram  
Both, together 
Both, together 
OFF 
Optical Coherence Tomography  
Both, separately 
Both, separately 
OFF 
Ultrasound A- and B-scans 
Both, separately 
N/A 
N/A 
CT Scan 
N/A 
Implanted only 
OFF 
Document Fixation Position and Eye 
Movement Range 
Both, together 
Both, together 
OFF 
Visual Acuity Tests 
 
 
 
Grating Acuity 
Both, separately 
Both, separately 
ON and OFF 
Full Field Stimulus Threshold 
Both, separately 
Both, separately 
OFF 
Electrically Evoked Response 
Implanted only 
N/A 
N/A 
Orientation & Mobility Tasks 
Both, together 
Both, together 
ON and OFF 
Massof Activity Inventory 
N/A 
N/A 
N/A 
VisQOL 
N/A 
N/A 
N/A 
Square Localization & Direction of 
Motion Test 
Both, together 
Both, together 
ON and OFF 
Perceptual Thresholds for Electrical 
Stimulation  
N/A 
Implanted Only 
ON 
FLORA 
N/A 
Both, together 
ON and OFF 
 

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Table 5.4 Extended Follow-Up Schedule (Years 4-7) 
 
Evaluation or Test 
Enrollment in 
Years 4-5 
Extended 
Follow-up 
 
(After 36 Month 
follow-up) 
3.5 Years 
 
(40.5 – 
43.5 
Months) 
4 Years 
 
(46.5 – 
49.5 
Months) 
4.5 Years 
 
(52.5 – 
55.5 
Months) 
5 Years 
 
(58.5 – 
61.5 
Months) 
Enrollment 
in Years 6-7 
Extended 
Follow-up 
 
(After 5 Year 
follow-up) 
5.5 Years 
 
(64.5 – 
67.5 
Months) 
6 Years 
 
(70.5 – 
73.5 
Months) 
6.5 Years 
 
(76.5 – 
79.5 
Months) 
7 Years 
 
(82.5 – 
85.5 
Months) 
Informed Consent 
x 
 
 
 
 
x 
 
 
 
 
Medical Follow-Up, including: 
Complete Eye Exam 
Current Medical Status 
Adverse Events 
 
x 
x 
x 
x 
 
x 
x 
x 
x 
Retinal Photography 
 
 
x 
 
x 
 
 
 
 
 
Optical Coherence Tomography 
 
 
x 
 
x 
 
 
 
 
 
Visual Function 
Full-Field Stimulus Threshold (FST)* 
Photographic flash test 
Grating Visual Acuity 
Square Localization 
Direction of Motion 
 
 
x 
 
x 
 
 
 
 
 
Orientation and Mobility Tasks 
 
 
x 
 
x 
 
 
 
 
 
Massof Activity Inventory 
 
 
x 
 
x 
 
 
 
 
 
Functional Low-Vision Observer Rate 
Assessment (FLORA) 
 
If not performed in years 1-3, perform as soon 
as practical following subject consenting to this 
additional assessment.  This assessment will 
serve at the 3 year FLORA. 
 
 
 
 
 
Perceptual Thresholds for Electrical 
Stimulation  
 
 
x 
 
x 
 
 
X 
 
X 
System Fitting and Psychophysical Testing 
Optional at the joint discretion of subject and investigator.   
May occur as frequently as 1x/week, but usually occurs no more than 1x/month. 
Home Use 
Optional at the discretion of the subject.  Ongoing. 
* FST is only required at those centers that have a Diagnosys Espion System 

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Table 5.5 Post-Approval Phase Follow-Up Schedule (Years 8-10) 
 
Evaluation or Test 
Enrollment in Years 8-
10 Extended Follow-up 
 
(After 7 Year follow-up) 
8 Years 
 
(± 1.5 Mo) 
9 Years 
 
(± 1.5 Mo) 
10 Years 
 
(± 1.5 Mo) 
Informed Consent 
x 
 
 
 
Medical Follow-Up, including: 
Complete Eye Exam 
Current Medical Status 
Adverse Events 
 
x 
x 
x 
Photographic Flash* 
 
 
 
x 
Square Localization Test* 
 
 
 
x 
Direction of Motion Test* 
 
 
 
x 
Grating Visual Acuity* 
 
 
 
x 
Perceptual Thresholds for Electrical Stimulation* 
 
x 
x 
x 
Transfer VPU data to sponsor* 
 
x 
x 
x 
System Fitting and Psychophysical Testing* 
Optional at the joint discretion of subject and investigator.   
May occur as frequently as 1x/week, but usually occurs no more than 1x/month. 
Home Use 
Optional at the discretion of the subject.  Ongoing. 
 
* These tests are only required for subjects who are using the System at home. 
.

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6 Screening, Baseline and Enrollment Procedures 
The schedule of observations and assessments to take place during 
screening and baseline testing is summarized in Table 5.1.   
To determine which eye should be tested during screening and baseline 
testing, refer to Table 5.3.   
Methodologies for all screening and baseline testing procedures are detailed 
in the Procedures and Operations Manual. 
6.1 
Screening 
6.1.1 
Informed Consent 
Screening is intended to determine whether a subject meets the selection 
criteria defined in Section 4 of this protocol.  Prior to undergoing any 
screening procedures, each subject must sign the Screening Informed 
Consent Form.  Since potential subjects are severely visually impaired, the 
informed consent should be read to the subject in addition to providing them 
with a printed copy of the document as well as an audio version. 
6.1.2 
Screening Log 
All subjects screened must be recorded on the screening log regardless of 
whether they are subsequently enrolled or not.  Subjects who continue to 
meet the subject selection criteria after screening will be asked to review 
and sign a second Informed Consent Document (the Baseline Informed 
Consent Form) prior to beginning participation in the study. 
6.1.3 
Screening Tests and Exams 
Screening consists of the following tests and exams: 
1. Medical Evaluation 
This evaluation is performed to: 
a. Evaluate the subject’s expectations of the system   
b. Review the subject’s ophthalmic history and records  
c. Review the subject’s general medical history 
d. If the subject is female and is capable of becoming 
pregnant, administer a pregnancy test to ensure the 
subject is not pregnant.  Also, advise the subject of 
appropriate birth control measures that must be 
maintained during the course of the study. 

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e. Review of all the subject’s chronic and acute medications  
2. Psychological Evaluation 
This evaluation is performed to confirm that the subject: 
a. Seeks participation in the study primarily to contribute to 
the development of effective retinal prosthesis technology, 
rather than with the expectation of a substantial 
improvement in his or her level of vision, and is willing and 
able to commit to a lengthy rehabilitation process with 
limited benefits. 
b. Does not have any underlying psychological condition that 
would impede the study evaluations and follow-up such as:  
i. Cognitive decline including diagnosed forms of 
dementia and/or progressive neurologic disease 
ii. Psychiatric Disease including diagnosed forms of 
depression 
3. Complete Eye Exam 
4. Ultrasound A- and B-Scans 
An ultrasound A-scan is performed to determine the axial length of 
the eyes.  A B-scan is performed to determine the posterior coats 
thickness (i.e. the retina, sclera, choroid complex) in the region 
where the array will be implanted. 
5. Visual Acuity Testing  
Visual acuity testing will be performed at screening to confirm that 
the subject meets the first two inclusion criteria:   
1.  Have a confirmed history of retinitis pigmentosa with a visual 
acuity of Bare Light Perception or worse in both eyes.  
2.  Have functional ganglion cells and optic nerve in the 
implanted eye as determined by documented light perception 
or a measurable electrically evoked response. 
Refer to Figure 6.1 for the visual acuity procedure.   
Visual Acuity must be measured in full, on both eyes, on two 
separate days.  If the subject fails to meet visual acuity criteria on 
any of the tests in either of the eyes, they may not participate in 
the study.   
Following completion of each visual acuity screening test, a visual 
acuity score will be assigned for each eye using Figure 6.1 and 

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represents the highest acuity a subject attains in a particular 
session.   
In the event that the subject is eligible for inclusion in the study, 
the highest visual score measured from the two days of screening 
tests will be used as the baseline value. 

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Figure 6.1 
Visual Acuity Testing at Screening 
 
Start testing first eye 
(each eye is tested separately)
Perform Grating 
Acuity Test
Is subject’s acuity 2.9 logMAR or better?
Exclude subject.
Yes
Perform Full Field Stimulus 
Threshold Test (FST)
Perform Electrically Evoked 
Response Test
(Only performed in eye 
intended for implant)
Subject meets visual acuity criteria for this eye. 
Classify visual acuity of eye as Bare Light Perception
Subject perceives 
light in all FST test 
runs?
Yes
Subject perceives 
light?
No
Exclude subject. 
No
Repeat Process in Other Eye
NOTE:  Subject 
must be meet the 
visual acuity 
criteria in both eyes 
on 2 separate days 
to be a candidate 
for the study.
No
Subject meets visual acuity criteria for this eye. 
Classify visual acuity of eye as No Light Perception
Yes
Subject meets visual acuity criteria for this eye. 
Classify visual acuity of eye as Bare Light Perception
Subject perceives light in 
at least 9/20 blocks?
Yes
If FST does not use a Xenon 
Flash, Perform Photographic 
Flash Detection Test
No
 

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6.2 
Enrolling a Subject 
Subjects who meet all the patient selection criteria are eligible for enrollment 
in the study.  Interested subjects must sign the Baseline Informed Consent 
Form.  Once again, the Baseline Informed Consent form should be read to 
the subject in addition to providing the subject with a printed copy of the 
document and an audio version of the document.   
Subjects meeting all the patient selection criteria and who sign the Baseline 
Informed Consent form will be considered to be enrolled and will be formally 
assigned their study number.  Subjects will be numbered sequentially within 
each site upon enrollment.  Subject numbers contain the prefix of the site 
number to allow unique identification. 
6.3 
Baseline Testing 
Baseline testing consists of the following: 
1. 
Medical Evaluation. 
2. 
Visual Field 
3. 
Retinal Photography  
4. 
Fluorescein angiogram (FA) 
5. 
Optical Coherence Tomography (OCT)  
6. 
Documentation of Fixation Position and Eye Movement Range 
7. 
Orientation and mobility tasks 
8. 
Massof Activity Inventory questionnaire 
9. 
VisQOL questionnaire 
10. Square Localization and Direction of Motion tests 
 
Baseline testing may reveal that a subject no longer meets the subject 
selection criteria (e.g. imaging reveals that the subject has a condition that 
could prevent the system from functioning for the duration of the study).  In 
this situation, the subject would be withdrawn from the study.  Refer to 
Section 10 for instructions on subject withdrawal. 
 

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7 Peri-Operative Study Procedures 
7.1 
Pre-Operative Medication Regimen 
Subjects will be treated pre-operatively with Ciprofloxacin (or an equivalent 
dosage of another quinolone family antibiotic) 500mg BID for 48 hours 
before implant.  
7.2 
Argus II Retinal Prosthesis Implantation 
Refer to the Clinician’s Manual, Chapter 3 (Surgical Procedures) for 
instructions for how to implant the Argus II Retinal Prosthesis, including 
intra-operative medications.   
If there is a significant difference in vision between the two eyes, the device 
should be implanted in the worse eye.  This decision will be made by the 
clinician, in consultation with the subject, as necessary. 
If the subject is phakic in the eye intended for implant, the lens will removed 
at the beginning of the implant procedure to either remove an existing 
cataract or prevent the formation or progression of a cataract during follow-
up which could impair the ability to visualize the implant and the retina. 
The day of implant is considered Day 0. 
7.2.1 
Post-Operative Medication Regimen (starting on Day 1) 
 
1. Antibiotics 
o Ciprofloxacin:  500mg BID for 14 days  
o Gatifloxacin (Zymar) eye drops:  1 drop QID for at least 14 days 
 
2. Steroids 
o Prednisolone 60mg daily PO for two weeks, immediately followed by a 
Methylprednisolone (Medrol) taper pack (8mg), until the pack is 
completed 
o If Medrol pack is unavailable, reduce Prednisolone by 10mg 
per day  
o Pred Forte 1% – 1 drop QID for 2 weeks.  Continue prn. 
 
NOTE:  If the subject experiences low intraocular pressure (IOP) post-
operatively, then the steroid regimen should be as follows: 
 
o Halve the oral Prednisolone dose if IOP mmHg reaches 5 or less 
o Reduce Pred Forte 1% to 1 drop daily 

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o Once IOP has reached 10 mmHg or higher, increase the oral 
Prednisolone dose as clinically indicated 
o Continue Pred Forte drops as clinically indicated 
 
3. Mydriatics 
o 1 drop topical Atropine 1% once daily for 2 weeks 
 
NOTE 1: 
Investigators should direct subjects taking chronic or acute 
medication to make their primary physician aware of the 
medications anticipated for pre and post management of the 
implant and that these may affect their pre-existing medical 
conditions and/or interact with the medications they are taking.     
NOTE 2: 
Modifications to the medication regime should be made where 
necessary to optimize subject care. 

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8 Follow-Up Study Procedures 
Postoperative follow-up provides the data necessary to monitor system 
safety, including medical/surgical risks or complications and adverse events, 
and to monitor system effectiveness over time. Subjects will be followed 
post-operatively for 36 months. At the end of 36 months, subjects will be 
offered the opportunity to extend their follow-up for up to an additional 7 
years (Refer to Section 8.8, Extended Follow-Up (Years 4-10)). 
The schedule of observations and assessments to take place during follow-
up and the appropriate time intervals during which each visit should occur 
are summarized in Table 5.1.  Postoperative evaluations are counted from 
the date of the surgery, with the day of surgery being Day 0.  
To determine which eye should be tested during follow-up, refer to Table 
5.3.  Methodologies for clinical follow-up, endpoint testing procedures, and 
certain system fitting and psychophysical testing procedures are detailed in 
the Procedures and Operations Manual.  
8.1 
Clinical Follow-Up 
Clinical follow-up consists of the following: 
1. 
Medical Evaluation, including a review for adverse events, current 
medications and other relevant clinical findings 
2. 
Complete eye exam 
3. 
Visual Field 
4. 
Retinal photography 
5. 
Fluorescein angiography 
6. 
Optical coherence tomography (OCT) 
7. 
Ultrasound B-scan – If the subject was enrolled prior to March 2010, 
this test should be performed at the next available clinic visit. 
8. 
CT-Scan 
9. 
Documentation of Fixation Position and Eye Movement Range – This 
is only performed on an as-needed basis. 
If a portion of the subject’s implant array overlaps the optic nerve head, 
clinicians should carefully monitor the optic nerve head during the follow-up 
eye exams and review serial photographs from retinal photography, 
fluorescein angiography and OCT to confirm that the array is a safe distance 
from the optic nerve head surface and does not appear to be damaging this 
structure. 

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8.2 
Endpoint Assessments 
8.2.1 
Visual Acuity 
Follow-up visual acuity testing should be performed and scored according to 
Figure 8.1.   

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Figure 8.1 
Visual Acuity Testing at Follow-Up 
 
Perform this test in both eyes, separately.   
Refer to Table 5.3 for instructions about performing the test with the  
System ON or OFF. 
 
Start testing
Perform Grating 
Acuity Test
Perform Full Field Stimulus 
Threshold Test (and 
Photographic Flash 
Detection, if applicable)
Was eye assigned a 
logMAR score of 2.9 or 
better by the grating acuity 
test?
Assign this score 
as the eye’s Visual 
Acuity.
Yes
No
Did subject perceive light with 
the Full Field Stimulus 
Threshold Test or Photographic 
Flash Test?
Yes
Score eye as Bare 
Light Perception
No
Score eye as 
No Light 
Perception
 

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8.2.2 
Orientation and Mobility Task 
Once the subject has been successfully fitted with the external system (i.e. 
the subject’s VPU has been loaded with a Video Configuration File), the 
subject will be asked to perform the orientation and mobility tasks per the 
schedule in Table 5.1. 
8.2.3 
Quality of Life and Activities of Daily Living  
Commencing at three months post-implant, the VisQOL and Massof Activity 
Inventory will be administered to each subject. 
8.2.4 
Functional Low Vision Observer-Rated Assessment 
(FLORA) 
This assessment will be performed at 1 and 3 years post-implant.  For 
subjects enrolled in the study prior to August 2010, who may have already 
passed one or both of these time points, this assessment will be performed 
as soon as can be scheduled after the subject has consented to this 
additional assessment.  For these subjects, the assessment will be counted 
toward the closest required follow-up visit (i.e. 1 or 3 years) even if it is 
performed outside that test window.  
8.2.5 
Spatial Vision Tests 
Commencing at three months post-implant, the Square Localization and 
Direction of Motion tests will be administered to each subject per the 
schedule in Table 5.1. 
8.2.6 
System Performance 
System performance will be evaluated using two measures: 
• Electrode impedance will be recorded to ensure continued function of 
the electrodes in the array. Electrode impedance measurements will be 
taken at the beginning and, if possible, at the end of each testing 
session. 
• Perceptual Thresholds for Electrical Stimulation will be recorded to 
document the level at which electrical stimulation produces a 
phosphene (the perception of a spot of light). Threshold testing will be 
performed according to the schedule in Table 5.1. 

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8.3 
Argus II System Fitting and Psychophysical Testing 
Subjects will be scheduled for fitting and psychophysical testing sessions up 
to twice weekly, with sessions lasting up to four (4) hours.  A Second Sight 
Field Clinical Engineer may assist the investigator during these test sessions. 
8.3.1 
Argus II System Fitting 
Fitting refers to the procedure for establishing the most effective Visual 
Processing Unit (VPU) settings for subjects implanted with a retinal 
prosthesis.  Psychophysical testing will be used to establish the electrical 
pulse parameters for stimulating retinal neurons and to determine the 
optimal method for transforming the video input signal to a useful pattern of 
electrical stimulation.  
The procedure for converting video camera input to a pattern of electrical 
stimulation can be broken down into two general parts: the video chain and 
the Video Configuration File (VCF).  
The Video Chain 
The image is captured by a video camera mounted on the glasses. This video 
image is sent to the VPU, where the video input signal is processed by a 
series of digital filters. The goal of these operations is to construct the 
inferred “neural image” best suited for presentation to the retinal circuitry 
through electrical stimulation. The image should consist of intensity values 
that are scaled to maximize the dynamic range for perceived brightness. 
Video Configuration File (VCF) 
The Video Configuration File specifies the method for converting the output 
of the video chain to electrode stimulation values. The perceptual brightness 
produced by an electrode can be manipulated by changing the electrical 
pulse parameters, such as the pulse amplitude. The VCF contains a look-up 
table that specifies the mapping between the video image intensity values 
and the pulse parameter values. The file also specifies which spatial sections 
of the video image are sent to each electrode. 
Constructing the Video Configuration File 
The video configuration file will be constructed based on measurements of 
the percepts produced by patterned electrical stimulation. The experimental 
data required to construct a video configuration file may vary from subject 
to subject, and the design and execution of these experiments is referred to 
as fitting. During the course of this feasibility study, we will refine and 
evaluate our fitting procedures to determine the most efficient and effective 
method of optimizing system parameters. 
Video Configuration File Refinement 

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Based on the subjective feedback from the subject and any subsequent 
testing, the VCF may be altered to improve the subject’s perception.  For 
example, if a subject’s performance is hindered by the perception of flicker, 
the frequency of stimulation may be increased. 
8.3.2 
Psychophysical Testing 
During some fitting and testing sessions, we will conduct various non-
invasive objective tests (“psychophysical testing”) to monitor the progress of 
the fitting procedure and to determine the most appropriate testing to 
optimize system parameters. The specific psychophysical tests to be 
performed may vary from subject-to-subject and additional tests will be 
developed as the study progresses.  Results will be summarized in the 
annual report. 
8.3.3 
Training and Rehabilitation 
Throughout the study, subjects will receive training on how to use the Argus 
II System.  This training will typically take place during the weekly System 
Fitting and Psychophysical Testing Sessions at the clinic.  Subjects may also 
receive some vision rehabilitation to enhance their ability to receive benefit 
from the Argus II System.  Qualified vision rehabilitation specialists (e.g. 
CLVT, OTR/L, COMS, etc.) may assist with this training and rehabilitation.  
At the discretion of the investigator and with the agreement of the subject, a 
certain amount of training and rehabilitation may take place at the subject’s 
home and/or immediate environs or in an environment outside of the clinic. 
8.4 
Home Use  
As soon as possible after implant, subjects will be trained to use the Argus II 
system at home. After meeting the requirements for home use (see below), 
they will be allowed to take their system home and will be instructed to use 
it for approximately 4 hours/day, 28 hours a week.  
Subject and caregiver (if applicable) are instructed that the system may not 
be used as the primary mechanism for mobility. 
Subjects will report the details of their home use to the investigator during 
their fitting and testing sessions.  
Criteria for Home Use 
Before being allowed to use the Argus II System at home, subjects must 
demonstrate the ability to set-up and use the system and respond to audible 
alarm states without trainer intervention.   In addition, the subjects and 
their caregivers (if applicable) will be provided with a Patient’s Manual (hard 
copy and audio version) for information regarding the operation the Argus II 

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system. Subjects and their caregivers (if applicable) will be specifically 
trained on the following:  
1. System Set-up and Operation 
1.1. The Patient Manual will be used to instruct the subject to set-
up and operate the system.     
1.2. The Patient Manual will be used to review all safety information 
related to the system, including the Warnings and Precautions 
section, the significance of audible alerts and how to respond to 
them, any Caution statements that are included throughout the 
manual, and how to troubleshoot problems.   
2. “Real World” Training 
2.1. Tasks, such as the ones listed below, will be used to familiarize 
the subject with operation of the system in real world 
environments. 
a. Identify and localize a combination of fluorescent lights that 
are switched on and off.  
b. Identify the locations of doors or windows. 
c. Find the position of a dark colored chair against a white 
background. 
d. Identify whether a person passed by in front of them and 
the direction of travel. 
Equipment for Home Use 
Each subject will be furnished with the following: 
1. 
Argus II Video processing unit 
2. 
Argus II Glasses 
3. 
Argus II VPU Pouch to hold the Argus II VPU. 
4. 
Two Argus II VPU Batteries. 
5. 
Argus II VPU Battery Charger. 
6. 
Argus II Traveling Case. 
7. 
Patient User manual (hardcopy and audio version). 
8. 
Tactile targets to practice using the system. 

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8.5 
Explantation of the Implant  
The Argus II implant will be explanted at any time during the study (i.e. 
either during the initial 36 month follow-up period or during extended follow-
up in years 4-10) if any of the following conditions occur: 
1. Subject requests explant either upon study termination or subject 
withdrawal. 
2. Device becomes compromised in any way that compromises the 
subject’s safety. 
3. Unresolved infection. 
4. Clinically significant retinal detachment that does not respond to 
treatment. 
5. Unexplained device failure that places the subject at risk. 
6. Intractable pain. 
All surgically removed devices will be returned to Second Sight for analysis.  
Second Sight will provide a procedure for treatment and shipping of returned 
devices. 
Subjects will be followed post-explant per the schedule in Table 5.2 unless 
they have withdrawn from study and refuse further follow-up. 
Refer to the Clinician’s Manual, Chapter 3 (Surgical Procedures) for 
instructions for how to surgically remove the Argus II Retinal Prosthesis.  
The pre-, Intra-Op and Post-Explant medication regimen is provided below 
(Section 8.7).  
8.6 
Revision of the Implant  
The position of the Argus II implant may be revised during the study to 
address a variety of situations including, but not limited to: 
1. Correct the position of the implant due to movement. 
2. Reposition extra-ocular parts of the implant to improve functionality of 
the system. 
The revision may include replacing or adding materials that were used in the 
original surgery to better secure the implant (i.e. sutures and metal tacks).  
The decision to revise an implant will be made by the surgeon, in 
consultation with the Second Sight.  The procedure for performing the 
revision surgery will vary from subject-to-subject.  It is recommended that 
the surgeon consult with Second Sight as to how to perform the revision 
surgery.  The pre-, Intra-Op and Post-revisions surgery medication regimen 
is provided below (Section 8.7). 

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The short-term follow-up schedule following revision surgery should be 
directed by the nature of the surgery and determined by the surgeon.  The 
Revision Surgery Case Report Form provides general guidelines for post-
revision surgery follow-up.  In general, subjects should resume their normal 
follow-up schedule after about 1 month post-revision surgery. 
8.7 
Medication Regime for Explant or Revision Surgery 
Pre-Surgical 
Two days (48 hours) prior to the planned surgery, start the subject on 
Ciprofloxacin (or an equivalent dosage of another quinolone antibiotic) 
500mg BID. 
Intra-Operative 
Intra-operative medications should follow the same regime as for the initial 
surgery.  
Post-Operative (starting the day after surgery) 
 
1. Antibiotics 
o Ciprofloxacin:  500mg BID for 14 days  
o Gatifloxacin (Zymar) eye drops:  1 drop QID for at least 14 days 
 
2. Steroids - Steroids should be prescribed according to clinician 
judgment.  Oral steroids are not required for subjects whose device is 
explanted.  Below is a potential regime for consideration. 
 
o Prednisolone 60mg daily PO for up to two weeks, immediately 
followed by a Methylprednisolone (Medrol) taper pack (8mg), until 
the pack is completed.   
o If Medrol pack is unavailable, reduce Prednisolone by 10mg 
per day  
 
NOTE:  The requirement for and duration of oral steroids should be 
adjusted based on the duration and nature of the surgery. The full 
fourteen days of oral steroids should be administered before 
tapering in cases where the surgery is extensive and/or involves 
manipulation of the extra-ocular parts of the device. 
 
o Pred Forte 1% – 1 drop QID for 2 weeks.  Continue prn. 
 
NOTE:  If the subject experiences low intraocular pressure (IOP) post-
operatively, then the steroid regimen should be as follows: 
 

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o Halve the oral Prednisolone dose if IOP mmHg reaches 5 or less 
o Reduce Pred Forte 1% to 1 drop daily 
o Once IOP has reached 10 mmHg or higher, increase the oral 
Prednisolone dose as clinically indicated 
o Continue Pred Forte drops as clinically indicated 
 
3. Mydriatics 
o 1 drop topical Atropine 1% once daily for 2 weeks 
8.8 
Extended Follow-Up (Years 4-10) 
Following completion of the 36 months follow-up, subjects will be offered the 
opportunity to extend their participation in the study for up to an additional 
7 years, to provide a maximum follow-up duration of 10 years.  Subjects still 
implanted with the Argus II device will be asked to consent for extended 
follow-up in the following increments: 
• Years 4-5 
• Years 6-7 
• Years 8-10  
If subjects consent to extend their follow-up, they may continue to use the 
Argus II System at home and they will be required to undergo clinical follow-
up.  During the extended follow-up period, testing in the clinic (i.e. 
psychophysical testing and system fitting) will be optional and will be 
scheduled at the joint discretion of the subject and investigator.  The 
schedule for the extended follow-up for years 4-7 is provided in Table 5.4 
(page 36).  The schedule for the extended follow-up for years 8-10 is 
provided in Table 5.5 (page 37). 
9 Study Completion 
Subjects will be considered to have completed the study when they have 
been followed through 36 months post-implant (if the subject does not 
consent to extended follow-up), or through 5, 7, or 10 years post-implant (if 
they consent to extended follow-up), at the time of withdrawal, or 12 
months post explant, whichever is the longest.  One exception to this is 
when a subject has an unresolved adverse event at the end of the study.  
Refer to Section 14.1 for instructions for how to handle this situation. 
At the completion of the study, subjects will be allowed to continue use of 
the system with prior government regulatory and institutional review 
board/ethics committee approval. 
The study will be complete when all subjects have completed the study. 

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10 Withdrawal and Replacement of Subjects 
Subjects are at liberty to withdraw from participation in the study at any 
time without penalty or prejudice. Any subject who withdraws will be given 
the option of keeping the Argus II implant or having the device explanted. 
If a subject does not return for a scheduled visit, every effort will be made to 
contact her/him.  In any circumstance, every effort must be made to 
document subject outcome, if possible. 
If the subject becomes pregnant, she must be withdrawn from the study. 
Such subjects may elect to rejoin the study at the completion of pregnancy 
and lactation if the study is still open. 
In all cases, the reasons for withdrawal must be recorded on the case report 
form and in the subject’s medical records.  If possible, a complete, final 
examination should be performed on all subjects who intend to withdraw 
from the study. 
If the Argus II Implant is explanted, the subject will be followed post-
surgery for twelve months to allow evaluation of adverse events related to 
the explant procedure unless they have withdrawn and refuse further follow-
up. 
Any subject who has been implanted with the study device and withdrawn 
from the study will not be replaced. Subjects withdrawn prior to implant may 
be replaced. 
11 Statistical Methods 
11.1 
Sample Size Estimate and Justification 
As the objective of the study is to evaluate the safety of the implanted 
system and the utility of the study measures in this population, a maximum 
of twenty (20) subjects are to be enrolled in this feasibility study in the U.S. 
This number of subjects will allow evaluation of the basic performance of the 
system, an estimate of the level of vision provided and the safety profile of 
the system in the specified patient population.   
11.2 
Eligibility of Subjects, Exclusions, and Missing Data 
All subjects enrolled according to the entry criteria in Section 4 will be 
eligible for evaluation, regardless of the sequence of treatment that ensues.  
All subjects enrolled in the study are considered eligible for follow-up and 
will be required to adhere to the follow-up schedule outlined in Table 5.1 and 
Table 5.2. 

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Management of dropouts and missing data will depend on their frequency 
and the nature of the outcome measure.  Adjustments for missing data will 
be performed only if deemed necessary and will be described completely.   
Outlier values will be evaluated for their validity; all data will be included 
unless judged to be invalid. 
11.3 
Primary Analysis Population 
The primary analysis sample will be based on the principle of intention-to-
treat.  All subjects who sign the written Informed Consent form, meet the 
study entry criteria, and are enrolled will be included in the analysis sample, 
regardless of whether or not the device was implanted. 
11.4 
Secondary Analysis Population 
A secondary analysis will be performed to evaluate the results of device 
placement and consist of subjects on an “as treated” basis. 
11.5 
Statistical Analysis 
Subject demographics, clinical history, risk factors, preoperative, and 
procedure data will be summarized using descriptive statistics for continuous 
variables (e.g. mean, standard deviation) and frequency tables or 
proportions for discrete variables.   
Post-procedure information will be collected at regularly scheduled follow-up 
examinations according to the clinical study schedule.  Estimates of primary 
and secondary endpoints will be reported along with their 95% confidence 
intervals.  The Kaplan-Meier product limit method will be used to determine 
rates of events for time-to-event endpoints such as retinal detachment. 
Where testing is conducted with the system on and off, comparison will be 
made between subject performance under both conditions.  Where testing is 
conducted with the implanted and non-implanted eyes separately, 
comparison will be made between subject performances using each eye. 
12 Data Management 
12.1 
Data Collection 
Case Report Forms (CRF) are required and must be completed in black or 
blue ink for each subject enrolled. The authorized site representative signs 
and dates the case report forms on the specified pages to assure the 
accuracy and completeness of the recorded data. 

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Some data may be collected from the output of the clinical fitting system or 
ophthalmic diagnostic equipment.  In such cases, a signed and dated 
printout, de-identified images or encrypted electronic media may be used in 
place of the case report form pages.   
Some data may be collected directly onto the case report forms, e.g. subject 
questionnaires and tests that are not standard for retinitis pigmentosa 
patients.  In such instances, the case report form will constitute source 
documentation. 
12.2 
Data Processing 
Second Sight Medical Products is the responsible coordinating center for data 
management. 
All case report forms, images and data electronically captured by the Argus 
II System will be sent to the Second Sight for entry into a database.  Visual 
and computer error checks will be carried out.  The Investigator will be 
queried on discrepancies concerning completeness and consistency.   
All above-mentioned tasks will be performed according to relevant Standard 
Operating Procedures.  Audits may be performed for quality assurance of 
data handling.  
13 Monitoring Procedures 
Second Sight Medical Products, Inc will be the study monitor. 
13.1 
Monitoring 
Second Sight personnel will monitor all clinical studies in a manner 
consistent with applicable health authority regulations and the clinical 
research standards adopted by Second Sight. Site monitoring includes a site 
qualification visit, initiation/training visit, interim monitoring visits, and a 
study closure visit.  Monitoring visits will occur according to the schedule in 
table 11.1 at a minimum. Additional interim visits will be conducted 
according to subject number and site performance in regard to accuracy and 
completion of data and compliance to the protocol. 
Table 11.1 Monitoring Visit Schedule 
Monitoring Visit 
Number 
of Visits 
Frequency 
Timing 
Qualification 
1 
Once 
Before IRB 
submission. 
Initiation/Training 
1 
Once 
Before first subject 
enrollment. 

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Training may be 
repeated. 
Interim 
Ongoing 
At least every six 
months, and within 
one month of first 
implant. 
Commencing within 
one month of first 
implant. 
Closure 
1 
Once 
Within 3 months of 
study closure at 
site. 
13.1.1 Site Qualification 
A site qualification visit will be conducted to determine the adequacy of 
subject population, clinical facilities/equipment and the adequacy of the 
investigator and additional staff’s credentials, availability and resources to 
conduct the study.   
13.1.2 Site Initiation/Training 
A site initiation/training visit will be performed to train the investigational 
staff on the investigational plan, which includes, but is not limited to, 
confidentiality, consenting process, enrollment, device accountability, study 
deviations, subject testing, product training, adverse event reporting, data 
collection, and study documentation.  In addition, the implanting surgeon 
will receive training in how to implant the Argus II system. 
13.1.3 Interim Monitoring 
Interim monitoring visits will be conducted to evaluate study progress, 
continued acceptability of the facility, staff, and equipment, adherence to the 
protocol, maintenance of records, verification of case report form data to 
source documentation, verification of adverse event data to source 
documentation, collection of case report forms, and affirmation of 
investigational product/device inventory control.  
All investigative sites will be monitored for deviations related to protocol test 
procedures, exams, missed or out of window visits and subject 
noncompliance with study requirements. If a significant deviation/violation 
from the protocol is noted such as Inclusion/Exclusion violation, consent 
violation, or system misuse, the investigator must notify the Sponsor and 
the IRB immediately so that appropriate action can be taken.  If the 
investigator fails to implement the corrective action, the Sponsor may cease 
shipment of supplies, discontinue the investigation and/or notify the 
appropriate agencies.   

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13.1.4 Site Closure 
Site/Study Closure Visit will focus on device inventory/reconciliation, 
adequacy of space for retention of study records, re-verification that the 
investigator study file contains all appropriate documentation, and 
verification that the investigator’s final study report is in progress.  
13.2 
Device Accountability 
Device accountability records must be maintained at each study center. The 
number of devices delivered to and/or returned to SSMP and assigned to 
individual subjects by the Investigator will be registered.  Any accountability 
discrepancy at the end of the study needs to be explained in writing by the 
Investigator. 
13.3 
Protocol Violations and Deviations 
All violations and deviations related to study inclusion or exclusion criteria, 
conduct of the study, subject management, or subject assessment are to be 
documented on the case report form provided for that purpose. 
14 Adverse Events  
Adverse Events (AE) are to be monitored from the time of enrollment 
through the last follow-up visit.   
An adverse event is defined as any undesirable clinical occurrence in a 
subject whether it is considered system related or not.  This definition 
includes events occurring during surgery or the follow-up period.  Events 
may be: 
1. Observed or volunteered problems 
2. Physical signs and symptoms 
3. Medical condition(s) which occurs during the study, having been 
absent at baseline 
4. Medical condition(s) present at baseline, which appear to worsen 
during the study 
Excluded from the definition of adverse event are normal post-operative 
occurrences (e.g. inflammation, pain, etc.) that are routinely observed and 
managed medically.  Post-operative occurrences that are more severe than 
those normally observed would be considered adverse events. 

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14.1 
Recording Adverse Events 
All AEs must be recorded on the case report forms provided.  Each event 
must be on a separate form, regardless of whether one event may be 
secondary to another. 
The following data are required for each AE: 
1. Reportable term (name of the AE) 
2. Seriousness and reason for being serious. 
Serious Adverse Event Definition – United States 
A Serious Adverse Event (SAE) for subjects enrolled in the US is 
defined as one that causes/is any one of the following: 
• death 
• life threatening 
• permanent impairment of a body function or permanent damage 
to body structure 
• necessitates medical or surgical intervention to preclude 
permanent impairment of a body function or permanent damage 
to a body structure 
Permanent means irreversible impairment or damage to a body 
structure or function, excluding trivial impairment or damage. 
3. Relatedness to the subject’s disease, a procedure or the system.  
Some adverse events may be unrelated.  Relatedness is based on 
likelihood of the causal relationship 
4. Anticipated (anticipated or AEs are listed in section 14.1.1 of the 
protocol). All others are ‘unanticipated’ 
5. Start and resolution dates 
6. Description of the event, commentary on interventions (actions, 
procedures, medications) and outcomes  
AE forms are to be completed at the time of the event regardless of all data 
being available.  In cases where not all data are available, follow-up and 
final AE forms are to be completed as significant new data become available 
and when the event resolves. 
The need to capture adverse events is not dependent upon whether or not 
the clinical event is associated with the use of the study product. 
All adverse events occurring during the course of the study will be followed 
through to their resolution, even if this extends the subject’s participation 

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beyond the normal end of the study (i.e. 36 months).  If an AE is unresolved 
at the subject’s final study visit, the investigator should continue to follow 
and treat the adverse event as is clinically indicated, and report the follow-
up information on an adverse event form.   
14.1.1 Anticipated Adverse Events 
1. 
Infection 
• If an infection is presumed, attempt to confirm with microbiological 
testing 
2. 
Inflammation is not an AE if it is < Kimura class 2 and lasts for < 1 
month unless it raised IOP above 30mmHg. 
3. 
Hypopyon 
4. 
Hyphema is an AE if it: 
• Occurs in the immediate post-operative period and lasts > 1 month 
post surgery OR 
• Occurs later than one month post surgery , is mild (or worse) and 
lasts > 1 month OR 
• Is ‘8-ball hyphema’ OR 
• Causes high IOP (>30 mmHg). 
5. 
Vitreous hemorrhage is an AE if it: 
• Occurs in the immediate post operative period and lasts > one 
month post surgery OR 
• Occurs later than one month post surgery, is mild (or worse) and 
lasts ≥ 1 month  OR 
• Obscures the view of the retinas such that ultrasound is needed to 
assess OR  
• Leads to IOP >30mmHg 
6. 
Retinal Folds are AEs if the affect the array placement or the tack. 
7. 
Vascular Congestion/Occlusion 
8. 
Cystoid Macular Edema/Choroidal Hemorrhage  
9. 
Conjunctival Erosion is an AE if there is device exposure. 
10. Suture irritation is an AE if it requires surgical intervention. 
11. Scleral Erosion  
12. Choroidal detachment is an AE if –  
• It is ≥to 4 disc diameters OR 
• It displaces the array OR 
• Choroidals are ‘kissing’ OR 

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• It lasts for longer than 1 month OR 
• It is associated with a flat anterior chamber. 
13. Conjunctival congestion is an AE if it: 
• Occurs in the immediate post-operative period (within 1 month post-
operative) and lasts > 1 month OR 
• Occurs later than one month post surgery, is mild (or worse) and 
lasts > 1 month. 
14. Scleral Perforation – unintended perforation of the sclera  
15. Scar or fibrosis formation, including epiretinal membrane 
16. Ocular fibrin (anterior or vitreous) is an AE if it 
• Occurs in the immediate post-operative  period   and lasts >1month 
post surgery OR 
• Occurs later than one month post surgery, is mild (or worse) and 
lasts > 1 month  OR 
• Obscures the view of the retina 
• Raises IOP above 30mmHg. 
17. Retinal Tear or retinal break is an AE 
18. Retinal Detachment should be classified as: 
• Rhegmatogenous  (AE) OR 
• Subretinal fluid 
o Subclinical - ≤1 disc diameter and well demarcated is not an 
AE. 
o Clinical - >1 disc diameter  is an AE classified as either 
rhegmatogenous or tractional 
19. Retinal edema  
20. Retinal/subretinal hemorrhage is an AE only if it causes dislocation of 
the array. 
21. Cataract  
22. Corneal Opacity is an AE if it: 
• Covers the visual axis OR  
• Is infectious in nature. 
23. Corneal degeneration 
24. Corneal vascularization is an AE if it covers the visual axis. 
25. Corneal epithelial defect is an AE if it persists > 2 weeks post-surgery. 
26. Iris/Pupil changes are AEs if they 
• Lead to atrophy associated with significant functional or structural 
defects of the iris OR 

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• Lead to high IOP. 
27. Increased intra-ocular pressure (IOP) 
• Intra-ocular pressure increase more than 10 mmHg above baseline 
or intraocular pressure greater than 30 mmHg  
28. Hypotony (<5mmHg) is an AE if it 
• Persists  for > 2weeks OR 
• Is associated with kissing choroidals OR 
• Is associated with a flat anterior chamber. 
29. Ptosis  
30. Ocular pain or discomfort in the implanted eye 
31. Disturbed/difficult eye movement 
32. Dry eye 
33. Extrusion of band   
34. Intrusion of band  
35. Dislodgement of human sclera or equivalent allograft 
36. Electric Shock 
37. Migration of array  
38. Loosening/extrusion of device  
39. Increase in photophobia 
40. Side effects of medications and/or interactions with concurrent 
mediations and underlying medical conditions 
41. Respiratory failure – fail to wean from ventilator post-surgically 
42. Blood loss requiring active intervention such as transfusion 
43. Allergic reaction to anesthesia 
44. Loss of light perception in eyes having pre-operative light perception 
The following are not AEs: 
• Corneal dryness 
• Descemets Folds 
• Retinal pigmentary changes 

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14.1.2 Anticipated General Adverse Events 
These are normal events or health issues common to the general population. 
The following list is provided as general guidance but is not intended to be 
inclusive.   
Neurologic 
• Depression 
• Degeneration of cognition 
• Vertigo 
Cardiovascular 
• Stroke/Transient Ischemic Attack 
• Cardiac arrhythmia 
• Cardiac arrest 
• Hypertension 
Musculo-Skeletal 
• Arthritis 
• Fracture 
• Gout 
Gastro-Intestinal 
• Ulcer 
• Mesenteric ischemia 
Endocrine 
• Diabetes 
• Thyroid disorders 
• Hormonal changes 
Systemic 
• Infection unrelated to the implant site. 
Mobility 
• Falls 
• Bumps 
• Minor injury 

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14.1.3 Unanticipated Adverse Events 
An adverse event that occurs which is not listed above will be considered 
unanticipated.   
Both anticipated and unanticipated adverse event information will be 
collected throughout the study 
14.2 
Reporting Adverse Events 
14.2.1 Unanticipated, Serious, Device Related Adverse Events 
Any unanticipated, serious, device related adverse event must be reported 
to the Sponsor within 24 hours. This must be done by telephone and by 
scanning/emailing or faxing the completed Adverse Event Form to the 
address below. In addition, the Sponsor recommends any such adverse 
events also be reported to the Institutional Review Board within ten working 
days of learning of the event or in accordance with the IRB terms of 
approval. 
 
Second Sight Medical Products 
Attn: Clinical Affairs 
12744 San Fernando Road, Building 3 
Sylmar, CA 91342 
eFax:  +1-818-698-8168  
Scan and email to:  safety@2-sight.com 
Phone:  +1-818-833-5039 
 
The sponsor and investigator shall immediately conduct an evaluation of any 
unanticipated, serious, system related adverse events.  A report of the 
results of such evaluation shall be submitted to FDA and to all reviewing 
Institutional Review Boards/Ethics Committees and all participating 
investigators within 10 working days after the Sponsor first receives notice 
of the adverse system event. 
Reports relating to the subject’s subsequent medical course must be 
submitted to the study Sponsor until the event has subsided or, in case of 
permanent impairment, until the event stabilizes and the overall clinical 
outcome has been ascertained. 

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14.2.2 Serious Adverse Events 
Serious Adverse Events should also be reported immediately to the Sponsor 
and to the IRB in compliance with the terms of study approval, regardless of 
system relatedness or if they are anticipated. 
14.2.3 Other Adverse Events Requiring Immediate Notification 
The following events should also be reported immediately to the Sponsor, 
regardless of their system relatedness or if they are anticipated: 
• Endophthalmitis 
• Rhegmatogenous retinal detachment requiring laser treatment or 
surgical intervention to repair 
• Hypotony requiring surgical intervention to treat 
14.2.4 Other Adverse Events 
All other adverse events will be documented in annual reports. 
14.3 
Independent Medical Safety Monitor 
An Independent Medial Safety Monitor (IMSM) has been appointed to 
oversee this study. The IMSM is independent of the study and has no real or 
apparent conflict of interest.  The IMSM is responsible for: 
• Reviewing individual serious adverse events (SAEs) submitted by the 
Sponsor in real time to ensure good clinical practice and to quickly 
identify safety concerns 
• Suggesting protocol modifications to prevent the occurrence of 
particular adverse events 
• Serving as a resource to the clinical investigators for advice about 
management of SAEs  
• Preparing regular reports concerning AEs.  Such reports will be 
submitted on a regular basis (at least) once per year.  
In the event of unanticipated SAEs or an unduly high rate of AEs, the 
Medical Safety Monitor will promptly contact the Sponsor to consider the 
concerns and plan appropriate action. 
15 Device Failures and Malfunctions 
All device failures and malfunctions are reported to the Sponsor via the 
complaint handling process, and the investigational device is returned to 

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Sponsor for analysis if necessary.  The final report on the study results will 
include information on device failures and malfunctions.  Instructions for 
returning the investigational device will be provided by Second Sight. 
16 Ethical Considerations 
16.1 
Declaration of Helsinki 
The study will be performed in accordance with the relevant parts of the ICH 
Guidelines for Good Clinical Practices, the Declaration of Helsinki and the 
United States Code of Federal Regulations. 
16.2 
Ethics Committee/Institutional Review Board 
It is the Investigators’ responsibility to obtain and maintain written approval 
of the final study protocol, including the Informed Consent, from the 
appropriate Institutional Review Board/Ethics Committee.  It is also the 
Investigators’ responsibility to notify that body about any amendments to 
these documents.  A copy of the written approval and the approved versions 
of the documents and a list of the Institutional Review Board/Ethics 
Committee members, their titles and occupations must be forwarded to the 
responsible study personnel at Second Sight Medical Products prior to first 
device shipment.  The written approval must identify the study and 
document the date of review. 
The Investigators must file all correspondence with the Institutional Review 
Board/Ethics Committee and forward copies of such correspondence to 
Sponsor. 
16.3 
Emergency Actions 
Second Sight Medical Products accepts the right of the Investigator to 
deviate from the protocol in an emergency when necessary to safeguard the 
life or the physical well being of a study subject.  The Investigator must give 
notice of any emergency deviations and justification for the deviation to the 
study personnel responsible at Sponsor and the Institutional Review 
Board/Ethics Committee as quickly as possible after the episode, in any 
event no later than 24 hours after the emergency. 
16.4 
Informed Consent Form 
It is the responsibility of the Investigator to give each subject before 
inclusion in the study, full and adequate verbal and written information 
about the objectives and the procedures of the study and the possible risks 
involved.  The subjects must be informed about their right to withdraw from 
the study at any time and for any reason without sanction, penalty, or loss 

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of benefits to which they are otherwise entitled and that withdrawal from the 
study will not jeopardize their future medical care.  It is the responsibility of 
the Investigator to obtain a signed Informed Consent form from each subject 
prior to performing any investigational procedures. 
The Informed Consent must be updated or amended whenever new 
information becomes available that may be relevant to the subject.  
Modifications to these documents must be approved by Second Sight Medical 
Products. 
16.5 
Amending the Protocol 
This protocol is to be followed exactly.  Only Second Sight Medical Products 
is permitted to write amendments in order to alter the protocol.  All protocol 
amendments must be approved following applicable FDA and Institutional 
Review Board/Ethics Committee procedures before implementation.  
Following approval, the protocol amendment(s) will be distributed to all 
protocol recipients with instructions to append them to the protocol. 
17 Study Administration 
17.1 
Study Timelines for the Post-Approval Phase of the 
Study 
Expected date of study initiation:  The post-approval phase of this study 
will begin in May 2013, following FDA approval of Second Sight’s 
Humanitarian Device Exemption (HDE) application for the Argus II Retinal 
Prosthesis System and IRB approval of the protocol at the participating sites. 
Expected monthly number of study sites with IRB approvals:  Second 
Sight anticipates that all sites who enrolled subjects in the investigational 
phase of the study will continue to participate in the post-approval phase of 
the study. 
Expected number of subjects enrolled per month:  Enrollment in the 
study is complete.  All subjects have been enrolled in the study during the 
investigational phase of the study.   
Expected date of study follow up completion: Study follow-up will be 
completed by October 2019 (taking into account the allowable follow-up 
window). 
Expected date for Final Report submission:  Assuming all follow-up has 
been completed by October 2019, the final report will be submitted to the 
FDA by January 2020.   

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17.2 
Study Reporting Schedule 
Data collected in this study prior to Humanitarian Device Exemption (HDE) 
approval have been reported to the FDA in the HDE application.  Data 
reported after the FDA has approved the HDE application will be reported to 
the FDA as part of the post-approval reporting process.   
In the post-approval phase of the study, the study sponsor will prepare the 
following reports for the FDA.  Copies of the final clinical report will be 
provided to all principal investigators for submission to their reviewing 
Institutional Review Boards.  Copies of the routine progress reports will be 
provided to principal investigators upon their request.  
• Routine Progress Reports:  Progress reports, which report the number 
of sites participating in the study, the number of subjects still enrolled 
in the study, and the rates of adverse events will be provided at the 
following intervals from the date of HDE approval: 
o 6 Months 
o 1 Year 
o 1.5 Years 
o 2 Years 
o Annually thereafter until the study is complete 
 
• Final Clinical Report:  A final clinical report, reporting all safety and 
benefit data, will be prepared once all subjects have completed 10 
years follow-up. 
17.3 
Record Retention 
In order to constitute evidence with respect to product safety or regulatory 
or legal compliance, the Investigator agrees to retain study-related 
documents in a location that is secure and to which access can be gained if 
required.  The following documents must be archived: the Investigator’s File 
containing all required Good Clinical Practice documents, including signed 
Informed Consent forms and subject-related materials, Case Report Forms 
and electronic records.   
In general, documents related to the clinical trial must be retained for at 
least 2 years (USA) after its completion or regulatory approval.  Refer to the 
Clinical Trial Agreement for the record retention period for your site.  
17.4 
Criteria for Terminating the Entire Study 
Sponsor reserves the right to terminate the study but intends only to 
exercise this right for valid scientific or administrative reasons and reasons 

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related to protection of subjects.  Investigators and associated Institutional 
Review Boards will be notified in writing in the event of termination. 
Possible reasons for study termination include: 
• 
The discovery of an unexpected, significant, or unacceptable risk to the 
subjects enrolled in the study. 
• 
A decision on the part of Sponsor to suspend or discontinue development 
of the device. 
17.5 
Criteria for Terminating the Study at an 
Investigational Site 
The Sponsor reserves the right to stop the inclusion of subjects at a study 
center at any time after the study initiation visit if no subjects have been 
enrolled.  In addition, the Sponsor may elect to terminate the study at an 
investigational site if the site has severe protocol violations without any 
justification or adequate corrective action or if the center fails to adequately 
staff the study.   
Likewise, a principal investigator may terminate the study at his/her 
institution.  This decision must be followed by written notification to the 
Sponsor within five working days, stating the reasons for termination. 
 
17.6 
Sponsor Responsibilities and Commitments 
Second Sight Medical Products is responsible for complying with the 
Declaration of Helsinki and all applicable health authority regulations 
governing the conduct of clinical research studies. These responsibilities and 
commitments are listed in Appendix A. 
 
17.7 
Investigator Qualifications/Responsibilities 
Each Investigator must be qualified to participate in the study and agree to 
meet the responsibilities detailed in the Investigator Agreement (CP-003-
008). 
18 Publication Policy 
Refer the Procedures and Operations Manual for the complete publication 
policy. 

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Appendix A - Sponsor Responsibilities 
1. Protecting the rights, health, safety and welfare of study subjects. 
2. Informing the clinical investigators of any new information about the 
study which may affect the health, safety or welfare of the subjects, or 
may influence their decision to continue participation in the study. 
3. Providing the clinical investigators with the study protocol and a full 
set of Case Report Forms on which to document the study evaluation 
variables for each subject entered into the study. 
4. Providing the statistical analysis and resources necessary to complete 
reporting of the study results. 
5. Ensuring equity of consideration among all investigators in multi-
center studies in all matters of publications, meeting presentations, 
etc. 
6. Certifying that Institutional Review Board/Ethics Committee approval 
of the protocol and Investigators Agreement will be completed prior to 
treatment at an investigational site. 

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Appendix B - Clinical Risk/Benefit Assessment 
 
1. Surgical Risks 
The subjects’ risks may involve standard surgical risks resulting from the use 
of general anesthesia, steroids and antibiotics, use of conscious sedation, 
surgical related equipment and device implant.  The common surgical risks 
for vitreo-retinal procedures have been evaluated and are shown below:37 
 
Complication 
Incidence (95% CI) 
Chest Pain 
0.48 (0.06 – 1.72) 
Urinary Retention 
0.96 (0.26 – 2.43) 
Myocardial Infarction 
0.24 (0.01 – 1.33) 
Pulmonary Embolism 
0.48 (0.06 – 1.72) 
Deep vein 
Thrombosis 
0.48 (0.06 – 1.72) 
Other risks associated with general surgery include: 
• Respiratory failure  
• Blood loss greater than anticipated 
• Infection of operative site 
• Systemic infection 
• Hospitalization longer than seven days 
• Allergic reaction to anesthesia 
Some subjects may require clear corneal phacoemulsification at the start of 
the implant procedure to remove the lens.  The incidence of adverse events 
associated with clear corneal phacoemulsification is very low, and a high 
volume cataract surgeon typically observes a rate of adverse events of 
approximately 0.1% for this procedure. The adverse events can range from 
posterior capsular tear to cortical drop in vitreous, or vitreous prolapse. All 
these adverse events can be successfully managed in the operative setting, 
since associated vitrectomy is being performed at the same time.  
If a subject has a small eye, a canthotomy may be performed to help fit the 
implant in the orbit.  A careful canthotomy, followed by layered suturing 
usually does not lead to any adverse effects.  Possible side effects of 
canthotomy include improper apposition of the eyelids, tearing, and chronic 
irritation at the lid margin. 

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If a subject has an epiretinal membrane present at the time of implant 
surgery, this membrane may be gently peeled off the surface of the retina, 
usually with forceps.  Possible adverse events associated with this procedure 
include accidental tearing of the retina, improper removal of the membrane 
causing re-proliferation of the membrane, and macular hole if the membrane 
covers the macular area. 
During the clinical feasibility study of the Argus 16, there were no surgery-
related adverse events in the six subjects implanted.38  The implantation 
surgery for the Argus II is anticipated to be approximately three hours (five 
hours shorter than the Argus 16) and should present a lower risk for the 
surgical procedure.  In addition, the Argus II does not require implantation 
in the skull, again reducing the risks for the implantation procedure. 
2. Study Procedure Risks 
2.1. Retinal Photography and Optical Coherence Tomography 
Retinal photography and optical coherence tomography (OCT) are standard 
non-invasive diagnostic tests used routinely.  Possible adverse reactions may 
arise from the pupil dilation and include blood pressure changes and other 
cardiovascular reactions particularly in elderly subjects.39,40  
As the subjects enrolled in this study have end-stage retinitis pigmentosa, 
they will have undergone multiple eye examinations using such pupil dilation 
and thus the risk of a reaction during the study is remote. 
2.2. Electrically Evoked Response  
To determine optic nerve function in subjects with no light perception an 
electrically evoked response will be performed.  In this test, a low current 
stimulus is applied via a standard ERG corneal electrode and the subject is 
asked if they perceive the stimulus as a light. Additional risks include pain 
and muscle stimulation.  In a study of 17 subjects, Dorfman, et. al. reported 
no adverse events beyond muscular twitch in the stimulated eye.41 
2.3. Fluorescein Angiogram  
Fluorescein angiography, a routine ophthalmic test, requires the injection of 
a fluorescent dye into the bloodstream followed by retina photography.  
Allergic response including nausea and occasional vomiting are the most 
likely adverse reactions to the dye, occurring in five to ten percent of 
subjects.42  In rare cases (<0.1%), anaphylactic shock may occur.43,44,45  
As the subjects enrolled in this study have retinitis pigmentosa, they will 
have undergone multiple eye examinations using such dyes and thus the risk 
of a reaction during the study is remote. 

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2.4. CT Scan 
This will be performed once only to document the surgical placement of the 
device.  No contrast media is required for this scan hence risks associated 
with allergic responses to such media are not applicable.  As the effect of the 
scan on the functioning of the system is unknown, all CT scans will be 
performed with the system off. 
2.5. Orientation and Mobility Testing 
During Orientation and Mobility (O&M) testing, subjects will be asked to walk 
a simple course without any obstacles in their way while closely supervised.  
During this testing the subjects may become disoriented with an elevated 
risk of bumping against walls and falling. 
3. Device-Related Risks 
Adverse events specifically associated with the use of the Argus II System 
may occur. These may include transient electric shock, facial nerve 
stimulation and/or pain.  In addition, excessive heating of the external 
equipment may cause burn to the user.   
The Argus II Retinal Implant System may unexpectedly stop functioning. 
The cause of failure may include electrical shorts, and/or interconnect 
failure.  As a result of such a failure, explant may be required. 
3.1. Related to Sterility 
The surgical procedure and/or the Argus II implant may introduce sources of 
infection into the operative region.  To minimize the risk of infection, the 
Argus II implant is sterilized to a sterility assurance level (SAL) of 10-6 and 
the surgical procedure will be performed using sterile technique.  In addition, 
subjects will be provided the standard pre- and post-operative antibiotic 
regimen of the hospital.  Sustained infection may result in explant of the 
Argus II implant, removal of the eye, sepsis or death. 
The Argus II implant is sterilized using ethylene oxide (EtO).  High levels of 
EtO residuals are known to be toxic in the eye.  Testing has been performed 
to demonstrate that the ethylene oxide (EtO) residuals present on the device 
after sterilization are below acceptable safety limits for this type of device.   

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3.2. Related to Materials 
The Argus II implant is manufactured with known biocompatible materials.  
A risk remains, however, that a subject may have a foreign body reaction to 
the implant.  If this type of reaction were to occur, it would be treated 
medically.  A sustained reaction may require explant of the Argus II implant. 
3.3. Related to Cleanliness 
The Argus II implant may carry pyrogens and other contaminants, which 
may result in fibrin proliferation within the eye, fever and corneal opacity. 
The Argus II is periodically tested to assure that bioburden is within required 
levels. 
3.4. Related to Sclerotomy and Vitrectomy 
Preparation of the eye to receive the Argus II implant requires multiple 
sclerotomy sites followed by pars plana vitrectomy.  The surgical removal of 
the vitreous has a risk of retinal detachment of approximately 4%, 46,47,48,49 
endophthalmitis of 0.05% and a risk of sympathetic ophthalmia of 0.1%.50   
In addition, vitrectomy may result in hyphema/vitreous hemorrhage, 
suprachoroidal hemorrhage, cystoid macular edema, or changes to 
intraocular pressure.  
3.5. Related to the Extra-ocular Case and Scleral Band 
Implantation of the Argus II requires the placement of a scleral band upon 
which the case and internal coil ride.  Potential complications following band 
placement include band infection, endophthalmitis, scleral erosion and band 
extrusion.  In a series of 19 subjects with primary scleral band placement, 
Arroyo, et al. found no occurrence of band infection, endophthalmitis, scleral 
erosion or band extrusion.51 
In two histopathologically examined cases, D’Hermies, et al. found the 
scleral bands well encapsulated with changes to the scleral curvature and 
thickness, with implant durations of 60 and 161 months.52  The changes 
noted did not result in band infection, endophthalmitis or band extrusion. 
Additional potential risks of the scleral band and case are increased intra-
ocular pressure, scleral perforation, eye-movement disruption and ptosis, 
ocular pain and discomfort, conjunctival or scleral erosion, retinal tear and 
disrupted ocular lubrication resulting in dryness and corneal erosion or 
vascularization. 

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3.6. Related to the Retinal Tack 
In the Argus II System, the retinal tack fixes the array to the vitreal surface 
of the retina.  Retina tacks of different materials have been used for many 
years to repair retinal tears and detachments.  The tack penetrates the eye 
wall, thereby holding together the layers of the eye.  A dislodged tack may 
damage intraocular structures.  In particular it may cause a retinal break or 
detachment through contact with the lower retinal surface, through allowing 
the array edge to contact the retina, or through the extrusion process.  A 
dislodged tack will require the subject to have a procedure to re-tack the 
implant to the retina.   
As with any surgical implant, the retina tack is subject to fibrovascular 
proliferation and scar formation.  The proliferative growth around the tack 
could cause epiretinal membranes or fibrin strands to grow within the 
vitreous, potentially leading to proliferative retinopathy (PVR). 
Studies as short a two months and as long as 2.5 years have shown this 
phenomenon, 53,54,55 although Gerding, et.al. 56 showed that for tack 
implantation post-vitrectomy, no fibrous strand or PVR occurred.  Ohira, et 
al. also studied chronic implantation and found that after 2.5 years of 
implant, that all tacks were intact and that retinal tissue was normal within 
one millimeter of the tacks.57 
In clinical practice, Abrams, et al 58 reported 50/53 (94%) of tacks 
implanted remained stable over 5 months and in a ten year follow-up of one 
subject, Puustäjrvi 59 reported that 12/13 (92%) tacks were in place after 
120 months. 
Based on the above, the risk of tack dislodgement and proliferation leading 
to detachment is small.   
3.7. Electrode Array/Cable/Electronics Package 
The electrode array is connected to the extra-ocular case via a polyimide 
cable, passing through a sclerotomy.  The retinal tack holds the array in 
place.   
There is a risk of a comparatively long recovery period from the original 
sclerotomy procedure and of conjunctival erosion in the area over the 
electronics package.  In the Argus 16 clinical study, only two subjects (2/6, 
33%) had conjunctival erosion requiring surgical intervention.38  The smaller 
size and increased flexibility of the cable for the Argus II will reduce the risk 
of conjunctival erosion.  However, the presence of the transcleral cable may 
predispose subjects to a leak at this sclerotomy site which could cause low 
intraocular pressure. 

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Placement of the array may result in retinal touching, leading to retinal 
damage, break, or detachment.  In addition, the retinal structure under the 
array may be damaged during the implant procedure, by long-term pressure 
exerted by the array on the retina or by migration/twisting of array across 
the retina.  Such damage may result in retinal break and/or detachment.  In 
the Argus 16 clinical study, no subjects have had the implant removed due 
to movement of the array. 
We do not believe that pressure damage associated with the array will 
prevent the perception of phosphenes based on the reported experience with 
cochlear implants.  Linthicum, et.al. 60 performed a post-mortem 
histopathological analysis of 22 temporal bones and one brain stem from 13 
cochlear implant subjects and reported, “Results of analysis suggested that 
ganglion cells were the responding elements to this implant and that useful 
auditory sensation could result from as few as 10 percent of the normal 
number of ganglion cells.” 
In addition, the subjects for this feasibility study are the most advanced in 
the disease.  Edwards, et.al. and Gartner, et.al. indicate that advanced 
retinitis pigmentosa provides a protective effect against possible retinal 
detachment.61,62 
3.8. Related to the Heating by the Implant 
The Argus II implant is an electronic implant which converts energy from 
incoming radiofrequency electromagnetic waves to electrical current to 
stimulate the retina and power the electronics in the case.  The process of 
energy conversion and the operation of the implanted electronics generate 
heat.  This heat is mostly concentrated on and near the extra-ocular case.  
The most sensitive tissues within the eye are those contained within the 
retina.  These tissues are also the most critical to the continued operation of 
the Argus II.  Excessive heating of biological tissues denatures proteins 
within the cellular structure and kills living cells.  Piyathaisere, et al. showed 
that no retinal tissue damage occurred when the temperature of the vitreous 
increased by 5 °C, with 2 °C at the retina, using direct heating with 
500mW.63 
In vitro testing of the Argus II has shown an extra-ocular temperature rise 
of less than 2 °C.  This small temperature increase indicates that heating 
damage to ocular structures is unlikely to occur with the current design 
which limits transmitted power to a nominal value of 100mW. 
In the unlikely event of heating damage, potential adverse events are 
cellular death, retinal detachment and loss of ability to elicit percepts. 

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3.9. Related to the Explant Procedure 
The explant procedure has the same risks as the implant procedure, array 
placement and retinal tacking.  In addition, the removal of scleral bands has 
an 8.3% risk of retinal damage. 64 
3.10. Related to Revision Surgery 
Revision surgery is expected to have the same surgical risks as the implant 
procedure, array placement and retinal tacking. It is possible for the revision 
surgery to be more extensive than the initial implant if the device requires 
significant repositioning or replacement.  In such cases it is important to 
evaluate the potential benefits of revision surgery against the risks of 
prolonged general anesthesia and significant manipulation of the ocular 
structures.  These decisions will be based on clinical grounds on a per 
subject basis.  
It is possible that the revision surgery may not achieve the desired 
improvement or may worsen the system performance.  In addition, it is 
possible that the implant may become damaged during the revision surgery, 
requiring further surgical intervention to remove or repair it. Guidance for 
avoiding damage to the device during revision surgery is provided in the 
Clinician’s Manual. 
3.11.  Long-Term Radiofrequency Transmission Risks 
With radio-frequency transmitter coils, there is a concern about the risk to 
the subject related to their long-term use.  The FDA has approved, as safe 
and effective, a number of implanted nerve stimulators that are powered by 
radio-frequency coils.  There is a substantial history dating back to the 
1960s of using radio-frequency to power various implanted nerve 
stimulators.  Such power transmission obviates the need for implanting 
bulky batteries (and the need for surgery to replace batteries).  The history 
of these devices in subjects, which includes cochlear implants and a class of 
spinal cord stimulators, demonstrates uniform safety and reliability of the 
radio-frequency links. 
Furthermore, the radio-frequency transmission in the megahertz frequency 
range would be too rapid to effect any nerve stimulation; the only 
established effect would be tissue heating when very high powers are 
applied.  With this in mind, several organizations have established standards 
for safe levels of energy deposition.  The specific absorption rate (SAR) is a 
measure of the rate of energy absorbed by (dissipated in) an incremental 
mass contained in a volume element of dielectric materials such as biological 
tissues.  The table below lists several organizations that have established a 
recommended SAR level for this type of device.   

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3.11.1. Radiofrequency Transmission Standards 
Organization 
SAR Level 
Federal Communications Commission 
(FCC) Office of Engineering and 
Technology (OET) 65  
<8 W/kg (during occupational or 
controlled partial-body exposure) 
Institute of Electrical and Electronics 
Engineers (IEEE) 66  
<8 W/kg (during occupational or 
controlled partial-body exposure) 
<1.6 W/kg (in uncontrolled 
environments) 
International Commission on Non-
Ionizing Radiation Protection (ICNIRP) 
67  
<10 W/kg (during occupational or 
controlled localized head or trunk 
exposure) 
 
Lazzi et.al. have modeled the thermal elevation due to induced electric and 
magnetic fields and have found that power dissipation under worst case 
conditions for a retinal implant are 0.6C in the eye and 0.2C in the retina.68 
The maximum SAR for the radio-frequency coil used in this study has been 
calculated to be well below each of the levels recommended by the 
organizations listed above.  Based on these data, the radio-frequency energy 
transmitted by the coil does not pose a risk to the subject. 
3.12. Risks of Stimulation 
Stimulation of the retina may result in muscle stimulation, pain and 
disorientation.  Stimulation waveforms with anodic and cathodic phases that 
do not contain the same amount of total charge may result in damage to the 
retina and the implanted device.  Both the implant and VPU have automatic 
safety checks to ensure that all delivered stimulation is charge balanced. 
3.12.1. Risks of High Stimulation 
One of the risks of electrical stimulation is that high levels of stimulation for 
prolonged periods of time can result in damage to the electrodes, to the 
tissue being stimulated and/or to the retina.  To protect against this, the 
Argus 60 System incorporates a preset limit and other safety checks to limit 
the maximum stimulation that can be delivered to the subject.  The 
maximum allowable chronic stimulation charge is 350 μC/cm2.   
The Argus II implant has been tested to demonstrate that the electrodes can 
withstand this maximum stimulation level for the duration of use anticipated 
in this study. 
McCreery, et al. studied the risk of neural damage related to peripheral 
neural stimulation.69  In their study, they found that at lower frequencies 

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(<50Hz), continuous stimulation at up to 1600 μc/cm2 induced little or no 
neural injury using electrodes of a similar size to that of the Argus II.  In 
addition, they concluded that even when nerves must be stimulated at 
higher frequency it should be possible to safely stimulate the nerve 
continuously at an amplitude that fully recruits all the motor-neuron axons in 
the nerve (i.e. it is possible to activate the nerve and reach therapeutic 
effect before causing damage).   
Weiland, et al.70  showed no histopathological changes with up to 120 days 
of stimulation in the canine model at current levels of 180 µA and 90 µA and 
Rizzo, et al.71 found no clinical or histological damage using charge densities 
of up to 1000 μC/cm2 acutely in humans. 
In the event that physiologic responses cannot be achieved at 350 μC/cm2, 
it may be necessary to temporarily exceed the safe chronic limit (i.e. 
stimulate up to 1000 μC/cm2).  If it is necessary to exceed the 350 μC/cm2 
limit, this would only occur for brief periods of time (i.e. not more than 4 
hours at any one time in the clinic).  The risk of increasing the charge 
density limit is that damage could occur to the electrodes or to the tissue.  
In physiologic saline, electrolysis of water and bubbling occurs (gassing 
limit) above 2000 μC/cm2 with platinum electrodes, therefore stimulation at 
1000 μC/cm2 should be well below the limit for the electrode material.  In 
addition to Rizzo’s results, experimental data from acute experiments 
performed at Johns Hopkins showed acute stimulation in patients with 
injected charge as high as 4900 μC/cm2/phase (with platinum electrodes) 
resulted in no adverse events and no histopathologic abnormalities. 
Based on these results, the potential for injury related to the maximum 
stimulation current allowable by the Argus II is remote.  
  
3.13. Risks of Device Degradation 
All implantable devices are susceptible to degradation over time due to the 
harsh environment of the body.  The Argus II implant has been tested to 
demonstrate that it can survive (i.e. maintain hermeticity and functionality) 
for the duration of this study.  In the remote event that the device did lose 
hermeticity or functionality, it may require explantation. 
 
3.14. Risks of System Use While Mobile 
Subjects are allowed to use the system while mobile as long as they do not 
use the system as their only mobility aid.  When using the system while 
mobile, they may become disoriented leading to an elevated risk of bumping 
against walls and falling.  A failure of the system while mobile could also 
cause these events.  In addition, subjects may become entangled in the 

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Glasses cable while walking.  The Glasses cable is designed to easily break 
away from VPU to reduce the likelihood of an injury occurring.  By requiring 
subjects to not use the system as their only mobility aid, the likelihood of 
these events occurring should be minimal. 
4. General Population Risks 
This section lists the general life-risks associated with our targeted 
population.  It is not anticipated that the Argus II System will increase the 
frequency of these risks. 
4.1. General Risks 
Neurologic 
• Depression 
• Degeneration or change in cognition 
• Vertigo 
Cardiovascular 
• Stroke/Transient Ischemic Attack 
• Cardiac arrhythmia 
• Cardiac arrest 
Musculo-Skeletal 
• Arthritis 
• Fracture 
• General musculo-skeletal degeneration 
Gastro-Intestinal 
• Ulcer 
• Mesenteric ischemia 
Systemic 
• Infection unrelated to the implant site. 
• Carcinoma 
 
4.2. Depression 
Depression is commonly associated with vision loss due to the loss of a 
sensory organ and the social isolation. 72,73  Functional ability is inversely 

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correlated with depression 74 and both optical and non-optical interventions 
has a positive effect on the incidence of depression.75  In the Argus II Study, 
subjects will have retinitis pigmentosa and therefore be at the highest risk 
for depression.  Literature would indicate, however, that the provision of 
percepts may reduce the incidence in this population. 
4.3. Falls and Minor Injuries 
Falls and minor injuries are a serious concern for aging subjects.  Nordell in 
a retrospective survey found that 30% of subjects over the age of 65 had 
suffered falls and that a contributor to the risk of falling was visual acuity. 76  
The potential for falls increases as the subject’s acuity decreases.  Tobis 
et.al. studied non-impaired, blind and deaf subjects for the propensity to 
fall.77  They found that the rate of falling in blind subjects (20/200 – no light 
perception) was twice that of non-impaired subjects (53.4% vs. 26.7%, p = 
0.003). 
5. Potential Benefits 
The potential benefits of the Argus II System are under study in the 
feasibility human trial stage and as such cannot be numerically evaluated.  
Evidence from the rate of increasing depression, isolation, falls and minor 
injuries in blind subjects would suggest that the use of the Argus II System 
might: 
• allow subjects to have an increased interaction with their 
surroundings, 
• reduce the risk of injury by providing visual cues for obstacles, and  
• increase the quality of life of subjects 
 
6. Risk/Benefit Analysis 
The implantation and use of the Argus II System has a small risk of serious 
injury and many of the anticipated adverse events can be treated either 
non-invasively with minimally invasive surgery, although unforeseen risks 
may be identified during the course of study.  In addition, this feasibility 
study will enroll only subjects with minimal or no vision, reducing the risk to 
residual vision and the potential for retinal detachment.  The potential 
benefits to the subjects overall life quality, with greater independence and 
mobility outweigh the relatively minor risks from implantation and use. 

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22 Freda R, Fujii G, Agrawal RJ, et.al. Epiretinal Prosthesis Implantation in 
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26 Humayun MS, Hopkins J, Greenwald SH, et.al.  Electrical effects and 
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32 Massof RW, Hsu CT, Baker FH, et.al.  Visual Disability Variables II: The 
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33 Geruschat DR, Turano KA, Stahl JW.  Traditional Measures of Mobility 
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34 Turano KA, Broman AT, Bandeen-Roche K, et al.  Association of Visual 
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