A Prospective, Open-label, Single Arm, Multicenter Clinical Investigation to Assess the Safety and Performance of the ARGOS-SC Suprachoroidal Pressure Sensor System in Patients With Glaucoma Undergoing Non-penetrating Glaucoma Surgery
Phase: NA
Conditions: Glaucoma, Open Angle Glaucoma
Sponsor: Implandata Ophthalmic Products GmbH

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CONFIDENTIALITY NOTE 
The content of this document is confidential and proprietary to  
Implandata Ophthalmic Products GmbH 
Unauthorized use, disclosure or reproduction is strictly prohibited. 
CLINICAL INVESTIGATION PLAN 
A first in man, prospective, open-label, single arm, multicenter clinical 
investigation to assess the safety and performance of the ARGOS-SC 
suprachoroidal pressure sensor system in patients with glaucoma 
undergoing non-penetrating glaucoma surgery 
Reference Number: ARGOS-SC01 
Revision: 
Release Date: 
Sponsor: 
Rev. G 
June 25, 2019 
Implandata Ophthalmic Products GmbH 
Kokensstrasse 5 
30159 Hannover 
Germany 

 
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Investigator Signature Page 
ARGOS-SC01 
A first in man, prospective, open-label, single arm, multicenter clinical investigation to assess the safety 
and performance of the ARGOS-SC suprachoroidal pressure sensor system in patients with glaucoma 
undergoing non-penetrating glaucoma surgery 
 
Investigator Statement 
I have read this protocol and agree to conduct this study in accordance with all stipulations of the 
Clinical Investigation Plan, any applicable standards for the conduct of clinical investigations with 
human patients, any requirements imposed by the responsible competent authority/ethics 
committee, any other applicable local, institutional or legal requirements and in accordance with the 
principles outlined in the Declaration of Helsinki. 
 
 
 
 
 
 
Name 
 
Signature  
 
Date 
 
 
 
 
Institution 
 
 
 
 
Institution address / stamp 
 
 
 
 

 
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Responsibilities and Contact Information 
Sponsor 
Implandata Ophthalmic Products GmbH 
Kokensstrasse 5 
30159 Hannover, Germany 
Phone: +49 (0) 511 2204 2580 
Fax: +49 (0) 511 2204 2589 
 
Max Ostermeier, Managing Director 
mostermeier@implandata.com 
 
Stefan Meyer, Chief Technology Officer 
smeyer@implandata.com 
Coordinating Investigator 
Prof. Dr. med. Peter Szurman 
Knappschaftsklinikum Saar GmbH 
Augenklinik Sulzbach 
An der Klinik 10 
66280 Sulzbach, Germany 
Phone: +49 (0) 6897 574 1119 
Email: Peter.Szurman@kksaar.de 
 
Investigational Sites 
A list of investigational sites is filed separately in 
the TMF. A final list will be shown in the clinical 
investigation Report 
Data Safety Monitoring Board 
Prof. em. Dr. med. Günther K. Krieglstein, 
Cologne 
(E-Mail: gkkrieglstein@googlemail.com) 
Dr. Jose Maria Martinez de la Casa, Clínica de 
oftalmológíca Martinez de la Casa Matilla 
Madrid 
(E-Mail: jmmartinezcasa@gmail.com) 
Prof. Dr. med. Norbert Körber, Augencentrum 
Köln 
(E-Mail: N.Koerber@gmx.de) 
Data Management and Study Monitoring 
CRO Dr. med. Kottmann GmbH & Co. KG 
Beverstraße 64 
59077 Hamm 
Phone: +49 (0) 2381 97 20 99 
Fax: +49 (0) 2381 902 43 45 
Email:kontakt@cro-kottmann.de 
 
 

 
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SYNOPSIS 
Title 
A first in man, prospective, open-label, single arm, multicenter clinical 
investigation to assess the safety and performance of the ARGOS-SC 
suprachoroidal pressure sensor system in patients with glaucoma undergoing 
non-penetrating glaucoma surgery 
Study Number 
ARGOS-SC01 
Sponsor 
Implandata Ophthalmic Products GmbH 
Name of IMD 
ARGOS-SC System 
The ARGOS-SC system is a non-CE marked investigational medical device 
composed of the implant and its accessories: 
Implant: ARGOS-SC pressure sensor implant for suprachoroidal placement 
Accessories: MESOGRAPH reading device, telemetric Multiline Connector 
Intended use 
The sensor device is intended to be permanently implanted in the human eye 
and used in conjunction with the hand-held MESOGRAPH reading device to 
telemetrically measure the intraocular pressure (IOP) of the implanted eye. 
Indication for 
use 
Patients with glaucoma and scheduled for non-penetrating glaucoma surgery 
Study Purpose 
The purpose of this study is to evaluate both the safety and feasibility of the 
surgical implantation of the ARGOS-SC implant during non-penetrating glaucoma 
surgery and the safety and usability of the ARGOS-SC implant and system in the 
year following the implantation. 
Study Design 
This study is designed as a prospective, open-label, multicenter, single-arm 
clinical investigation. Subjects will be followed up at regular intervals for one year 
following implantation to collect safety and performance information. 
Enrollment will be halted at every serious adverse device event (SADE).  
Sample Size 
Considerations 
The sample size calculation was based on the study’s dual purpose of establishing safety 
and comparability of IOP measurements with the ARGOS-SC system to those made with 
GAT and DCT. IOP measurements will be made with all devices at various time points, 
resulting in a within individual control for IOP variables. Based on these calculations 
(performance, safety) and considering possible drop-outs, the exploratory investigation 
will enroll 24 patients. The minimum number of measurements required to hold the 
performance claim is approx. 120. With multiple (>8) measurements with either method 
(ARGOS, GAT) per patient, a sufficient number of paired measurements (in total >>120 
measurement pairs) will be available to show equivalence of the methods (primary 
objective)[2]. 

 
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Subject  
Population 
Patients with glaucoma who are scheduled to undergo non-penetrating 
glaucoma surgery.  
Study 
Objectives 
Primary Objective 
Performance 
To evaluate the limits of agreement between measurements with Goldmann 
Applanation Tonometry (GAT), Pascal Dynamic Contour Tonometry (DCT) and 
the ARGOS-SC system in the 12 months following implantation 
Secondary Objectives 
Safety 
To evaluate the safety and tolerability the ARGOS-SC pressure during 
implantation and throughout a 12 months follow-up period. 
Performance 
To evaluate the performance of the ARGOS-SC system up to 12 months after 
implantation 
Patient 
Selection 
Inclusion Criteria 
Eligible subjects must meet all the following inclusion criteria: 
1. Subjects able to understand the informed consent and willing to 
participate as evidenced by providing informed consent. 
2. Patients aged ≥ 18 on the day screening 
Female subjects of childbearing potential (not surgically sterilized or more than 
one year post-menopausal) must have a negative pregnancy test (urine beta-
hCG) within 24 hours prior to ARGOS-SC pressure sensor implantation. 
3. Diagnosis of open angle glaucoma requiring a non-penetrating glaucoma 
surgery (NPGS). The medical indication for a non-penetrating glaucoma 
surgery must be given irrespective of the study participation. Potential 
study patients will be solicited for participation in the clinical trial only 
after the patient has given consent to the non-penetrating glaucoma 
operation. 
4. Subjects able and willing to attend all scheduled visits and comply with 
all study procedures. 
 
Exclusion Criteria 
Eligible subjects must not meet any of the following exclusion criteria prior to 
implantation: 
1. Contraindications for a non-penetrating glaucoma surgery 

 
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• 
Neovascular glaucoma, primary and secondary angle closure 
glaucoma 
• 
Condition after previous glaucoma incisional surgery 
• 
IOP > 40 mmHg 
2. Myopia (> -6 dpt) or hypermetropia (> +4 dpt) 
3. Axis length < 22 mm or > 26 mm 
4. Patient with single eye vision (monovision) 
5. Exudative 
age-related 
macular 
degeneration, 
instable 
macular 
degeneration 30 days prior to inclusion, or macular edema 
6. Acute retinal detachment 
7. Uncontrolled Diabetes Mellitus (DM) with manifestation of moderate to 
severe non-proliferative diabetic Retinopathy (DR) or proliferative DR.  
8. History or evidence of severe active inflammatory eye diseases (i.e. 
uveitis, retinitis, scleritis) in one or both eyes within 6 months prior to 
ARGOS-SC implantation 
9. Ocular surgery procedure(s) (excluding selective laser trabeculoplasty 
and peripheral iridotomy) within 6 months (cataract surgery within 3 
months) prior to ARGOS-SC implantation in the study eye that can affect 
the assessment of IOP by Goldmann Applanation tonometry 
10. Ocular disease other than glaucoma that may affect assessment of visual 
acuity and/or IOP by Goldmann Applanation tonometry/Pascal Dynamic 
Contour Tonometry (e.g. choroidal hemorrhage or detachment, lens 
subluxation, thyroid ophthalmopathy) 
11. Existence of other active medical eye implant and/or other active 
medical implants in the head/neck region 
12. Difficulties or complications during NPGS procedure or implantation of 
ARGOS-SC sensor, as assessed by surgeon (e.g. perforation of trabeculo-
descement’s membrane; excessive aqueous filtration through TDM 
leading to shallow anterior chamber; excessive bleeding; choroidal 
detachment) 
13. Severe generalized disease resulting in a life expectancy shorter than a 
year 
14. Currently pregnant or breastfeeding 
15. Participation in any study involving an investigational drug or device 
within the past 30 days or ongoing participation in a study with an 
investigational drug or device 
16. Patients who are not suitable for the study based on the surgeon’s 
evaluation (e.g. patients affected by Parkinson’s disease or essential 
tremor) 
17. Patients unable or unwilling to understand or comply with required 
study procedures 
18. Patients with psychiatric disorders influencing their judgement or 
autonomy 

 
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19. Subject and/or an immediate family member is an employee of the 
investigational site directly affiliated with this study, the sponsor or the 
contract research organization. 
20. Enrollment of the fellow eye in this clinical study 
 
Study 
Procedures 
Screening (SC) 
Consecutive potential subjects will undergo informed consent process up to 28 
days prior to surgery. Consenting subjects will be screened. Screening visit will 
include: 
• 
Demographics 
• 
Medical history  
• 
Pregnancy tests for females of child-bearing potential 
General 
• 
Vision-related Quality of Life (VQoL) questionnaire 
• 
Visual acuity (ETDRS) 
• 
Perimetry 
• 
Concomitant medication 
• 
External eye photography 
Anterior segment  
• 
Optical coherence tomography (OCT) of cornea and anterior chamber 
• 
Slit lamp biomicroscopy 
• 
Gonioscopy 
Posterior segment  
• 
Slit lamp biomicroscopy 
• 
Optical coherence tomography (OCT) of macula and optic nerve 
• 
Fundus photography 
IOP measurements  
• 
Goldmann Applanation tonometry (GAT) 
• 
Pascal Dynamic Contour Tonometry (DCT) (if available) 
 
Surgery (V01) 
On day of surgery or one day prior to surgery, subjects will again be assessed for 
eligibility requirements including pregnancy testing for females of childbearing 
potential. Subjects who continue to meet eligibility requirements will undergo 
non-penetrating glaucoma surgery with ARGOS-SC pressure sensor implantation 

 
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and standard clinical procedures. If it becomes apparent during the surgery that 
the subject is not a suitable candidate for the ARGOS-SC pressure sensor implant, 
the subject will be removed from the study and returned to standard of care. 
At Visit 01, data will be collected regarding: 
General 
• 
Implantation procedure questionnaire (surgeon) 
• 
AE/ADE/SAE/SADE/UADE 
• 
Concomitant medication 
• 
Device deficiency 
 
Follow-up (V02 to V09) 
The follow-up period after surgery will consist of 8 visits (Day 1 until Day 360). 
The examinations performed at each visit are listed without mentioning the 
single visit in parentheses. Examinations that are carried out only at distinct visits 
are indicated in parentheses. The follow-up visits will include:  
General 
• 
VQoL questionnaire (V06, V07, V09) 
• 
Visual acuity (EDTRS) 
• 
Perimetry (V06, V07, V09) 
• 
External Eye Photography (V04-V09) 
• 
Heidelberg Engineering ANTERION® (location of ARGOS-SC)(V04-V09), if 
available 
• 
User acceptance questionnaire (investigator) (V09) 
• 
User acceptance questionnaire (patient) (V09) 
• 
AE/ADE/SAE/SADE/UADE  
• 
Concomitant medication 
• 
Device deficiency 
Anterior Segment 
• 
Slit-lamp biomicroscopy  
• 
Optical coherence tomography (OCT) of cornea and anterior chamber 
(V04-V06) 
• 
Gonioscopy (V06, V07, V09) 
Posterior segment 
• 
Slit lamp biomicroscopy  

 
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• 
Optical coherence tomography (OCT) of macula and optic nerve (V06, 
V07, V09) 
• 
Fundus photography (V06, V07, V09) 
 
IOP measurements 
• 
GAT 
• 
Pascal DCT (V05-V09) (if available) 
• 
ARGOS-SC system measurements 
• 
Optional: 24-hours measurements inpatient with ARGOS-SC and GAT 
(V06, V07, V09) 
• 
ARGOS-SC system self-measurement at home 
Data Analysis 
and Statistics 
Primary Endpoint 
Performance 
- 
Level of Agreement between measurements made using GAT, Pascal DCT 
and the ARGOS-SC system from V02 (day 1) through V09 (day 360).  
 
Secondary Endpoints 
Safety 
- 
Number of patients experiencing a device-related SAE (SADE) at any time 
during implantation and in the first 12 months (Day 0 to Day 360) following 
it 
- 
Incidence, nature, severity and seriousness of observed adverse events and 
adverse device events at any time during implantation and in the 12 months 
following it 
Performance 
- 
Repeatability of the ARGOS-SC measurement 
- 
Incidence, nature and seriousness of observed device malfunctions during 
implantation and in throughout a 12 months follow-up period. 
Utility 
- 
User acceptance of the ARGOS-SC implantation procedure by means of 
evaluation of implantation procedure questionnaires (investigators) 
- 
User acceptance of the ARGOS-SC system at the investigational site by 
means of evaluation of patient acceptance questionnaires (by investigators) 
- 
User acceptance of the ARGOS-SC system at home by means of evaluation 
of patient acceptance questionnaires (patients) 

 
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- 
Daily IOP self-measurement profiles (patients) 
 
Definition of the analysis populations 
The safety population comprises all subjects for whom ARGOS-SC pressure 
sensor implantation was attempted, whether or not the implantation was 
successful. The Per Protocol Set (PPS) will comprise all subjects in whom an 
ARGOS-SC pressure sensor was successfully implanted and for whom the full 
data set including IOP measurements made in the clinic and safety data 
according to protocol are available until 3 months (Visit 6) after surgery. 
 
Statistical analysis 
Safety analysis 
AEs, SAEs, ADEs and SADEs will be listed and analyzed by descriptive and 
explorative statistical methods.  
Performance analysis 
The probability distribution of the difference of the paired measurements 
grouped within 1 mmHg will be compared to the primary objective of the 
accepted 70% of the measurements to agree between +/- 5 mmHg. 
Interim analysis 
An interim analysis will be conducted to assess safety and performance after the 
last patient has completed the 6 months follow up visit. 
Safety 
Monitoring 
A Data Safety Monitoring Board (DSMB) will be established prior to enrollment 
of the first patient. The DSMB will review the safety data, including SAEs/SADEs, 
on a regular basis and will advise on any changes required in the conduct of this 
clinical investigation. 
Data Collection 
Data will be collected using a Case Report Form (CRF).  
Study Duration 
The overall study duration for each individual subject is up to 13 months. 
Subjects will undergo screening a maximum of 28 days prior to surgery and will 
be followed for 12 months afterwards.  
The overall recruitment period is expected to last a maximum of 12 months. 
At the start of the study, all patients enrolled in Switzerland will be requested to 
sign up for an additional follow-up of 2 years. These patients will automatically 
transition to the ARGOS-SC_Follow-up.  
The estimated total duration of the study from first patient screened to last 
patient last visit is 25 months. 

 
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TABLE OF CONTENTS 
RESPONSIBILITIES AND CONTACT INFORMATION ............................................................ 5 
SYNOPSIS ...................................................................................................................... 6 
TABLE OF CONTENTS ................................................................................................... 13 
LISTINGS OF FIGURES AND TABLES ............................................................................... 19 
2. 
ABBREVIATIONS AND DEFINITIONS .................................................................... 20 
3. 
BACKGROUND INFORMATION ........................................................................... 22 
3.1 
Nature and Incidence of Glaucoma......................................................................................... 22 
3.2 
Treatment Options .................................................................................................................... 22 
3.3 
Advantages of Experimental Treatment ................................................................................. 24 
4. 
IDENTIFICATION AND DESCRIPTION OF THE INVESTIGATIONAL DEVICE ................ 25 
4.1 
Summary description of the investigational device and its intended purpose .................. 25 
4.2 
Description of the investigational device including any materials that will be in contact 
with tissues or body fluids .................................................................................................... 26 
4.3 
Details about the manufacturer of the investigational device.............................................. 28 
4.4 
Device and accessories identification .................................................................................... 28 
4.5 
Device accountability and storage ......................................................................................... 28 
4.6 
Necessary training and experience requirements ................................................................ 29 
4.7 
Description of any specific medical or surgical procedures involved in the use of the 
investigational device. ........................................................................................................... 30 
4.8 
Pre-clinical testing/assessment .............................................................................................. 31 
4.8.1 
In vitro/Bench/Lab testing .................................................................................................... 31 
4.8.1.1 First study in human cadaver eyes ......................................................................................... 31 
4.8.1.2 Functional Testing in Porcine Eyes ......................................................................................... 31 
4.8.1.3 Validation of implantation method/approach and validation of approach for surgical removal of 
implant in human cadaver eyes ............................................................................................ 32 

 
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4.8.1.4 Functional Testing ............................................................................................................... 32 
4.8.1.5 Biocompatibility and Cytotoxicity .......................................................................................... 33 
4.8.1.6 Exclusion of possible adverse effects ..................................................................................... 34 
4.8.1.7 MRI Compatibility, Compatibility with other Implantable/Wearable medical devices ................ 34 
4.8.1.8 Packaging, Cleaning, Sterilization .......................................................................................... 35 
4.8.2 
In vivo Studies ..................................................................................................................... 35 
4.8.2.1 Animal Studies .................................................................................................................... 35 
4.8.2.2 Human cadaver eye study .................................................................................................... 38 
4.9 
Clinical experience with similar devices ................................................................................ 39 
4.9.1 
Method validation: Clinical experience with EYEMATE-IO .................................................. 39 
4.9.2 
Experience with Ologen and Esnoper V-2000 implant ........................................................ 40 
5. 
JUSTIFICATION FOR THE DESIGN OF THE CLINICAL INVESTIGATION ...................... 40 
6. 
RISK EVALUATION ............................................................................................. 41 
6.1 
Anticipated clinical benefits .................................................................................................... 41 
6.2 
Risk Management Process ...................................................................................................... 42 
6.3 
Possible complications and adverse events ......................................................................... 43 
6.4 
Risks and Benefits associated with the participation in the clinical investigation ............ 44 
6.5 
Possible Interactions with Concomitant Medical Treatments .............................................. 45 
6.6 
Possible Alternative Treatments ............................................................................................. 47 
6.7 
Risk/Benefit Assessment ......................................................................................................... 47 
7. 
OBJECTIVES AND HYPOTHESES OF THE CLINICAL INVESTIGATION ........................ 48 
7.1 
Objectives ................................................................................................................................. 48 
7.1.1 
Primary Objectives .............................................................................................................. 48 
7.1.2 
Secondary Objectives .......................................................................................................... 48 
7.2 
Claims and intended performance of the IMD to be verified ................................................ 48 
7.3 
Risks and anticipated adverse device effects to be assessed ............................................ 48 
8. 
DESIGN OF THE CLINICAL INVESTIGATION .......................................................... 50 
8.1 
General Aspects ....................................................................................................................... 50 
8.1.1 
Description of the type of clinical investigation .................................................................... 50 
8.1.2 
Description of the measures to be taken to minimize or avoid bias .................................... 50 
8.1.3 
Primary and secondary endpoints ....................................................................................... 51 
8.1.3.1 Primary endpoints ............................................................................................................... 51 
8.1.3.2 Secondary endpoints ........................................................................................................... 51 
8.1.4 
Equipment to be used to assess the clinical investigation variables and arrangements for 
monitoring maintenance and calibration .............................................................................. 51 
8.1.5 
Any procedures for the replacement of subjects ................................................................. 52 

 
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8.2 
Investigational device(s) and comparator(s) ......................................................................... 52 
8.2.1 
Description of the exposure to the investigational device(s) or comparators, if used .......... 52 
8.2.2 
Justification of the choice of comparator ............................................................................. 52 
8.2.3 
Other medical devices or medication to be used ................................................................. 52 
8.2.4 
Number of investigational devices to be used ..................................................................... 53 
8.3 
Subjects ..................................................................................................................................... 53 
8.3.1 
Inclusion Criteria .................................................................................................................. 53 
8.3.2 
Exclusion Criteria ................................................................................................................. 53 
8.3.3 
Discontinuation or Withdrawal Criteria ................................................................................ 54 
8.3.3.1 Study stopping rules ............................................................................................................ 54 
8.3.3.2 Screen Failures .................................................................................................................... 55 
8.3.3.3 Premature subject withdrawal .............................................................................................. 55 
8.3.3.4 Completed Subjects ............................................................................................................. 56 
8.3.3.5 Subjects lost to follow-up ..................................................................................................... 56 
8.3.3.6 Pregnancy ........................................................................................................................... 57 
8.3.4 
Point of enrollment ............................................................................................................... 57 
8.3.5 
Total expected duration of the clinical investigation ............................................................ 57 
8.3.6 
Expected duration of each subject’s participation ............................................................... 57 
8.3.7 
Number of subjects required ............................................................................................... 57 
8.3.8 
Informed Consent ................................................................................................................ 58 
8.3.9 
Allocation of Patient Number ............................................................................................... 58 
8.3.10 
Methods and timing for assessing, recording, and analyzing parameters ........................... 58 
8.3.11 
Safety .................................................................................................................................. 58 
8.3.12 
Performance ........................................................................................................................ 59 
8.3.13 
Assessments ....................................................................................................................... 59 
8.3.13.1 Patient demographics/other baseline characteristics .............................................................. 59 
8.3.13.2 Medical history .................................................................................................................... 60 
8.3.13.3 Concomitant medication, treatments and devices .................................................................. 60 
8.3.13.4 AEs/ADEs/SAEs/SADEs ......................................................................................................... 61 
8.3.13.5 Device Deficiencies .............................................................................................................. 61 
8.3.13.6 Acceptance Questionnaires ARGOS-SC .................................................................................. 61 
8.3.13.7 National Eye Institute – Vision related Quality of Life Questionnaire-25 (VFQ-25) ..................... 62 
8.3.13.8 Visual Acuity (VA) ................................................................................................................ 62 
8.3.13.9 Visual Field (Perimetry) ........................................................................................................ 62 
8.3.13.10 External Eye Photography ................................................................................................... 62 
8.3.13.11 Heidelberg Engineering ANTERION® (if available) .................................................................. 62 
8.3.13.12 Anterior eye segment measurement .................................................................................... 63 
8.3.13.13 Posterior eye segment measurement ................................................................................... 63 
8.3.13.14 Intraocular pressure (IOP) measurement .............................................................................. 64 
8.3.14 
Surgery ................................................................................................................................ 66 
8.3.14.1 Non-penetrating glaucoma surgery and preparation for implantation ...................................... 66 
8.3.14.2 ARGOS-SC pressure sensor implantation ................................................................................ 66 
8.3.14.3 ARGOS-SC pressure sensor explantation, if medically necessitated .......................................... 66 
8.3.15 
Study Visits .......................................................................................................................... 67 
8.3.16 
Visit SC - Screening (Day -28 to 0) ..................................................................................... 70 
8.3.17 
Surgery, Visit 01 (Day 0) ..................................................................................................... 70 
8.3.18 
Follow-up visits (V02 to V09) ............................................................................................... 71 
9. 
STATISTICS ....................................................................................................... 72 
9.1 
Statistical design, method and analytical procedures .......................................................... 72 
9.1.1 
Demographic and baseline characteristics .......................................................................... 72 
9.1.2 
Subject Disposition .............................................................................................................. 72 

 
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9.1.3 
Safety Analysis .................................................................................................................... 73 
9.1.4 
Performance Analysis .......................................................................................................... 73 
9.2 
Sample Size Calculation .......................................................................................................... 73 
9.3 
Level of significance and the power of the clinical investigation ........................................ 74 
9.4 
Expected drop-out rates .......................................................................................................... 74 
9.5 
Pass/fail criteria to be applied to the results of the clinical investigation .......................... 74 
9.6 
Interim analysis ........................................................................................................................ 74 
9.7 
Criteria for termination of the clinical investigation .............................................................. 74 
9.8 
Procedures for reporting of deviations from the original statistical plan ........................... 75 
9.9 
Specification of Subgroups for Analysis ............................................................................... 75 
9.10 Treatment of missing, unused and spurious data, including drop-outs and withdrawals 75 
9.11 Datasets to be analyzed ........................................................................................................... 76 
9.11.1 
Safety set ............................................................................................................................. 76 
9.11.2 
Per protocol set ................................................................................................................... 76 
9.12 Number of subjects at each site ............................................................................................. 76 
10. 
DATA MANAGEMENT ........................................................................................ 76 
10.1 Site Monitoring .......................................................................................................................... 76 
10.2 Data collection .......................................................................................................................... 77 
10.3 Database Management and Quality Control .......................................................................... 77 
10.4 Verification, validation and security of electronic data system ........................................... 78 
10.5 Data retention and Retention period ....................................................................................... 78 
10.5.1 
Investigator Records Retention ........................................................................................... 78 
10.5.2 
Sponsor Records Retention ................................................................................................ 78 
11. 
ADVERSE EVENTS, ADVERSE DEVICE EFFECTS AND DEVICE DEFICIENCIES .............. 80 
11.1 Definitions ................................................................................................................................. 80 
11.2 Adverse Event (AE) .................................................................................................................. 80 
11.2.1 
Adverse Device Effect (ADE) .............................................................................................. 80 
11.2.2 
Serious Adverse Events (SAE) ............................................................................................ 80 
11.2.3 
Serious Adverse Device Effect (SADE) ............................................................................... 81 
11.2.4 
Anticipated Serious Adverse Device Effect (ASADE) .......................................................... 81 
11.2.5 
Unanticipated Serious Adverse Device Effect (USADE) ..................................................... 81 
11.2.6 
Device Deficiency ................................................................................................................ 81 
11.3 Recording of Adverse Events (AEs) ....................................................................................... 82 

 
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11.3.1 
Seriousness ......................................................................................................................... 82 
11.3.2 
Intensity/Severity ................................................................................................................. 82 
11.3.3 
Relationship to study device ................................................................................................ 82 
11.3.4 
Action taken ......................................................................................................................... 83 
11.3.5 
Outcome .............................................................................................................................. 84 
11.4 Reporting of Serious Adverse Events (SAEs) ....................................................................... 84 
11.5 Recording and Reporting of Device Deficiencies.................................................................. 86 
11.6 Medical Care ............................................................................................................................. 86 
11.7 Safety Monitoring ..................................................................................................................... 87 
11.8 Sponsor Responsibilities ......................................................................................................... 87 
12. 
ADMINSTRATIVE PROCEDURES AND RESPONSIBILITIES ....................................... 88 
12.1 Informed Consent ..................................................................................................................... 88 
12.2 Vulnerable Subjects ................................................................................................................. 89 
12.3 Regulatory and Ethical Compliance ....................................................................................... 90 
12.4 Approval from Ethics Committee or Regulatory Authority .................................................. 90 
12.5 Investigator Responsibilities for Ethics Committees and Regulatory Authorities ............ 90 
12.6 Reporting responsibilities ....................................................................................................... 91 
12.6.1 
Investigator Reporting Responsibilities ............................................................................... 91 
12.6.2 
Sponsor Reporting Responsibilities ..................................................................................... 91 
12.7 Insurance ................................................................................................................................... 91 
12.8 Amendments to the CIP ........................................................................................................... 91 
12.9 Recording, Reporting and Analysis of CIP Deviations ......................................................... 92 
12.10 Corrective and preventive action and principal investigator disqualification criteria ....... 92 
12.11 Suspension or Premature Termination .................................................................................. 92 
12.12 Criteria for access to a breaking/masking code in the case of suspension or premature 
termination of the clinical investigation, if applicable ........................................................ 93 
12.13 Subject follow-up requirements .............................................................................................. 93 
12.14 Investigator and Site Selection ............................................................................................... 93 
13. 
PUBLICATION POLICY ........................................................................................ 94 
13.1 Study Report and Publication ................................................................................................. 94 
13.2 Publication of Study Results ................................................................................................... 94 

 
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13.3 Registration in a Clinical Trial Database ................................................................................ 94 
14. 
REFERENCES ..................................................................................................... 95 
 
 
 

 
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LISTINGS OF FIGURES AND TABLES 
 
Table 1. Assessment Schedule ARGOS-SC01 ......................................................................................... 68 
Table 2. SAE reporting requirements .................................................................................................... 86 
Table 3. Sponsor Reporting Responsibilities ......................................................................................... 88 
 
 
Figure 1. Antenna coils of the EYEMATE-IO / ARGOS-SC pressure sensor ............................................ 33 
 
 
 

 
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2. 
ABBREVIATIONS AND DEFINITIONS 
Abbreviation 
Definition 
α 
Type I error 
ADE 
Adverse Device Effect 
AE 
Adverse Event 
AS 
Anterior Segment 
ASADE 
Anticipated serious adverse device effect 
ASIC 
Application specific integrated circuit  
BfArM 
Bundesinstitut für Arzneimittel und Medizinprodukte 
BMO-MRW 
Minimum rim width at Bruch membrane opening 
CIP 
Clinical Investigation Plan 
D 
Day 
dB 
Decibel 
DCT 
Dynamic contour tonometry 
DSMB 
Data Safety Monitoring Board 
EC 
Ethics Committee 
eCRF 
Electronic Case Report Form 
EEPROM 
Electrically erasable programmable read-only memory 
ETDRS 
Early Treatment Diabetic Retinopathy Study 
EtO 
Ethylene oxide 
FAS 
Full-analysis-set 
GAT 
Goldmann Applanation Tonometry 
GCP 
Good Clinical Practice 
GDD 
Glaucoma Drainage Device 
GSM 
Global System for Mobile Communications 
IB 
Investigator’s Brochure 
ICD 
Implantable Cardioverter Defibrillator 
ICH 
International Conference on Harmonisation 
IFU 
Instruction for Use 
IO 
Intraocular 
IOL 
Intraocular lens 
IOP 
Intraocular Pressure 
ISF 
Investigator Site File 
ISO 
International Organization for Standardization 
LAL 
Limulus amebocyte lysate 
MHz 
Megahertz 

 
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Mm 
Millimeter 
mmHg 
millimeter(s) of mercury (a unit of pressure equal to the pressure that can 
support a column of mercury 1 millimeter high) 
MPG 
Medizinproduktegesetz 
MRI 
Magnetic resonance imaging 
N 
Sample number 
NCT 
Non-contact tonometry 
ND:YAG 
Neodymium doped yttrium aluminum garnet 
NPGS 
Non-penetrating glaucoma surgery 
OCT 
Optical coherence tomography 
OU 
Oculus uterque 
P 
Pressure or statistical significance 
PIC 
Patient informed consent 
PS 
Posterior Segment 
RA 
Regulatory Authority 
Rev. 
Revision 
RNFL 
Retinal Nerve Fiber Layer Thickness 
SADE 
Serious Adverse Device Effect 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SC 
Suprachoroidal 
SDV  
Source Data Verification 
T 
Tesla 
TDM 
Trabeculo-descement’s membrane 
TMF 
Trial Master File 
V 
Visit 
VQoL 
Vision-related quality of life 
USADE 
Unanticipated serious adverse device effect 
 
 

 
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3. 
BACKGROUND INFORMATION 
3.1 
Nature and Incidence of Glaucoma 
An estimated 1 in 40 adults over the age of 40 has glaucoma, a group of conditions characterized by a 
progressive thinning of the retinal nerve fiber layer of the optic nerve head and the neuroretinal rim 
that appears as a central depression in the optic disc. Glaucoma leads to loss of visual field and if not 
controlled in end-stage disease, also to blindness, of which it is the second most common cause 
worldwide [4–6]. In open angle glaucoma (OAG), which accounts for approximately 70% of the 
glaucoma cases seen, aqueous outflow from the eye is restricted, most likely due to increased 
resistance in the trabecular meshwork.  
3.2 
Treatment Options 
Glaucoma treatment 
Glaucoma often remains asymptomatic until late in the disease, when irreversible vision problems and 
vision field restriction become evident. Although it may be present with normal intraocular pressure 
(IOP), the higher the IOP, the more rapidly the damage progresses [4]. Reduction of IOP is the only 
known treatment to prevent visual disability in the patient’s lifetime [6]. Lowering the IOP of patients 
with OAG by 20 to 40% can halve the rate of progressive nerve fibres damage [4]. However, the chronic 
nature of OAG necessitates a lifelong treatment. 
 
Governed by the ultimate treatment objectives of maintaining quality of live and quality of vision while 
containing costs, treatment guidelines recommend a progression from single topically administered 
medications 
(prostaglandin 
analogues, 
beta 
blockers, 
carbonic 
anhydrase 
inhibitors, 
sympathomimetics and/or miotics) to combinations thereof, to laser therapy with or without 
medications to surgery, again with or without medications, to reduce IOP to an acceptable target range 
[7].  
 
Surgical treatments expand the natural outflow pathway or create alternative routes for aqueous 
humor to drain from the anterior chamber. In deep sclerectomy, an intrascleral space is created by 
removing a lamellar band of the sclera, to expose the trabeculo-Descemet’s membrane. The 
intrascleral space acts as an aqueous reservoir and as a filtration site. In viscocanalostomy, a high-
viscosity sodium hyaluronate is additional injected left and right to the surgical incision in the 

 
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Schlemm’s canal to improve the aqueous drainage by this route whereas in canaloplasty, a recent and 
more reproducible variation viscocanalostomy, the Schlemm's canal is dilated along its entire length 
utilizing a flexible microcatheter, and additionally tensioned by suture material [8]. 
 
If surgery alone is not sufficiently effective, use of IOP lowering medications is generally resumed and 
doses increased as needed to attain target IOP. However, these medications frequently cause systemic 
side effects that may be severe and can have a greater immediate impact on patients’ quality of life 
than OAG itself (NICE). Consequently, there is a need to reduce medication use to the minimum 
needed to maintain the target IOP.  
IOP measurement 
Ensuring maintenance of target IOP is adequate requires frequent monitoring using a tonometric 
device. There are a number of tonometric devices on the market, of which the Goldmann Applanation 
Tonometer (GAT), which was first described in the 1950’s, is considered to be the gold standard to 
which all others are compared.  
 
The accuracy of most of these devices is limited to the degree that the secondary biometric parameters 
they measure, principally the force needed to applanate a section of the cornea or sclera, are affected 
by factors other than IOP, such as corneal thickness [9]. The majority of the direct tonometers require 
use of corneal anesthetics. The greatest limitation however is that almost all of the devices are 
cumbersome and require skill and training to use, in effect limiting their use to the clinic /office setting. 
 
The cost and inconvenience of the required office visits result in treatment decisions that are made 
based on only a few IOP measurements taken months apart. However, fluctuations in IOP due to 
patient activity and circadian rhythm are normal. The level of imprecision in repeated IOP 
measurements has been estimated at +/- 5 mmHg, meaning that to be 95% certain there is any 
treatment effect, a difference greater than 7 mmHg must be seen between single pre- and post- 
treatment IOP levels [10]. When 24-hour IOP profiles are taken, which require patients be admitted to 
the clinic, peak values – thought to be the most relevant for patient outcome in the long term – are 
seen outside of normal office hours in 80% of the cases, resulting in changes to treatment [5, 11]. 
 

 
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For these reasons, alternative methods are being sought that would allow more frequent IOP 
assessments in the home setting. 
3.3 
Advantages of Experimental Treatment 
The ARGOS-SC system that is the subject of this investigation is anticipated to provide a feasible 
solution to these problems. It is a multicomponent system consisting of the ARGOS-SC device, an 
intraocular pressure sensor that is intended to be permanently implanted in the patient’s 
suprachoroidal space during the non-penetrating glaucoma surgery, and the MESOGRAPH, an external 
handheld reader that powers and interrogates the ARGOS-SC implant telemetrically. Because the 
sensor itself is in direct contact with the choroid, it measures IOP directly from the vitreous throw the 
force on the choroid, without interference from either the cornea and sclera, or physical contact with 
the external eye. The device is easy to use, permitting patients or their immediate caregivers to 
measure IOP themselves in the home setting several times per day. The IOP measurements so obtained 
are stored in the Mesograph memory and can be accessed by the treating ophthalmologist, either 
directly from the Mesograph during patient visits or between visits when uploaded by the patient using 
the accessory Multiline Connector to a central database. The implantation itself, as a part of the non-
penetrating glaucoma surgeries, doesn’t elongate or complicate the surgery itself, as many other 
implantation procedures for IOP sensors do. Therefore, the sensor gives extra benefit with multiple 
feasible IOP-measurements without creating and extra risk for the patient by extended operating times 
and special implantation entrance or manipulation. 
 
The related EYEMATE-IO system, which is implanted in the sulcus and received CE-mark approval in 
2017, has been shown to effectively measure IOP in glaucoma patients who underwent cataract 
surgery [12], with an accuracy comparable to that of GAT. 
 
Although developed using the same materials and technology as the EYEMATE-IO, the form and 
location of placement of the ARGOS-SC differ sufficiently to require independent clinical investigation. 
The present investigation, which is the first-in-human, will test its use in patients with glaucoma 
undergoing concurrent indicated NPGS. If shown to be safe and accurate, it is anticipated that the 
ARGOS-SC system will permit a detailed tracking of IOP levels in this patient population, thereby 
facilitating timely adjustments medication while at the same time, ultimately reducing the number of 
control visits required of patients.  
 

 
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The purpose of this clinical investigation, which will follow up all patients who receive an ARGOS-SC 
device for 12 months after implantation, is to determine the safety of implantation of the ARGOS-
SC in conjunction with a non-penetrating glaucoma surgery, as well as to explore the agreement of 
the IOP measured with ARGOS-SC system and GAT and DCT (dynamic contour tonometry). 
4. 
IDENTIFICATION AND DESCRIPTION OF THE INVESTIGATIONAL DEVICE 
4.1 
Summary description of the investigational device and its intended purpose 
The ARGOS-SC system was developed for the wireless, contactless measurement of the hydrostatic 
pressure of the aqueous humor of the human eye (IOP, intraocular pressure). It is made up of two 
components: the ARGOS-SC implant and the external hand-held Mesograph reading device (with the 
later one already carrying CE mark as an accessory for the EYEMATE-IO posterior chamber IOP sensor 
implant). An additional component, the Multiline connector, can be used by the subjects between 
study visits to upload recorded measurement data from the Mesograph reading device to a secure 
centralized database that can be accessed by the investigator. 
 
The ARGOS-SC implant is comprised of a micro-electromechanical system (MEMS) application specific 
integrated circuit (ASIC) bonded to a micro-wire wound coil of gold and encapsulated in a special 
silicone-rubber material that has been extensively proven to be well tolerated by the eye when silicone 
intraocular lenses (IOL) were still popular. It is intended to be implanted during otherwise required 
ocular surgery and to remain in place indefinitely. In the ARGOS-SC01 study, the implant will be 
introduced into suprachoroidal space of the eye during non-penetrating Glaucoma surgery, using the 
associated surgical access.  
 
Activation of the Mesograph reading device in the near vicinity of the eye establishes an inductive link 
between the reader and the micro-coil. This induces a slight current in the otherwise electrically 
passive implant, supplying it with power and permitting data transmission. Pressure-sensor cells and 
an A/D converter incorporated in the ASIC measure IOP and the digitized data is then transmitted to 
the reader. Data is stored in non-volatile memory inside the reader device, preventing data loss in case 
of an error, and can be uploaded to a computer, or to an internet-based database through the Multiline 
connector. 
 

 
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Because the ARGOS-SC pressure sensor is implanted such that its pressure sensitive membranes are in 
unobstructed hydraulic contact with the interior of the eye, it measures IOP directly, without 
interference from corneal properties or examiner skill. This enables numerous IOP measurements 
daily, providing a complete IOP profile for the entire interval between office visits, and allowing timely 
detection of both peaks due to patient activities and circadian rhythms and trends due to disease 
progression. This will provide an accurate, reproducible method of measuring IOP in Glaucoma 
patients that can be performed frequently without requiring more frequent clinic visits.  
4.2 
Description of the investigational device including any materials that will be in 
contact with tissues or body fluids 
The ASIC and micro-wire wound coil components of the implant are hermetically encapsulated in a 
biocompatible silicone-rubber material (Nusil MED-6820) that has been extensively proven to be well 
tolerated by the eye when silicone intraocular lenses (IOL) were still popular, and with the EYEMATE-
IO family of implants that received CE mark approval in May 2017. This layer of material: 
• 
Forms a biocompatible, soft and atraumatic surface of the implant in order to avoid trauma to 
the tissues surrounding the implant 
• 
Prevents and protects the patient from substances being washed out from the electronic 
module and leaking into the aqueous humor 
• 
Provides a hermetic leak-proof seal around the electronic module, protecting it from the 
electrolytes and water contained in aqueous humor. 
 
The ASIC itself contains silicon, silicon dioxide, silicon nitride, gold, and traces of aluminum, titanium, 
phosphorus, arsenic, borium, polyimide and tungsten-titanium, all of which have been previously used 
in ocular implants. Detailed risk assessments commissioned by the sponsor determined that, even in 
the event of a breach of the silicone barrier, none of the materials comprising the implant pose any 
risk of an adverse biological effect to the patient [13]. Cytotoxicity and chemical analyses of extracts 
obtained from final sensors detected no organic or inorganic leachables above the lower limit of 
quantification 
and 
no 
evidence 
that 
the 
sensors 
contained 
or 
would 
release 
any 
residues/contaminants in toxicologically relevant concentrations during clinical application [14]. Above 
described testing has been performed using EYEMATE-IO devices, which are technically equivalent to 
ARGOS-SC, with the exception of the telemetry coil being integrated within the electronic module (not 
patient contacting), which is a three-dimensional micro-wire wound coil instead of a galvanically 

 
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etched planar microcoil. The micro-wire has been tested to be non-cytotoxic according to EN ISO 
10993-5. See the Investigator’s Brochure for more information. 
 
The implant is designed to be seated firmly within a surgically created artificial cyst between the inner 
layers of the sclera and the choroid. After healing, the cyst is tightly enveloping the implant, being no 
larger than necessary. Relative to the eyeball, the implant will be situated between the limbus and the 
equator of the eye, in a 12 o`clock position, hidden under the upper eyelid.  
 
For non-penetrating Glaucoma surgery, a scleral flap and a smaller “scleral lake” are prepared down 
to or almost down to the choroid. A hyaluronic acid-based viscoelastic (e.g. Healon OVD, Abbott 
Medical Optics Inc.) will be injected using an atraumatic cannula, to separate the sclera from the 
choroid, which additionally serves as a safeguard against injuries of the surrounding tissue. The 
viscoelastic will be resorbed within a few days or weeks after surgery. A special designed implantation 
forceps padded with silicone coatings (Implandata Ophthalmic Products GmbH, Germany) facilitates 
the implantation and protects the ARGOS-SC implant from damage through mechanical irritation. The 
device will be implanted into the suprachoroidal space by pushing it gently through the scleral opening 
into the suprachoroidal space/the volume of viscoelastic material. 
 
The back side of the implant that is interfacing with the innermost layer of the sclera has a spherical 
shape with a dihedral angle matching the average eye, which will ensure, together with the intraocular 
pressure acting onto the uveal layer, a firm seat of the implant within the newly created suprachoroidal 
space. The profile and thickness of the implant are minimized and its edges tapered and rounded to 
avoid causing trauma or damage to surrounding tissue even with direct long-term contact, and to 
minimize open space for deposition of fibrous material. The choroidal interface of the implant, which 
contains planar pressure sensor cells, is planar and slightly indenting the uveal layers, minimizing the 
risk of choroidal detachment. The indentation is necessary to remove all mechanical stress from the 
area covering and surrounding the pressure sensor cells, in order to facilitate the unobstructed 
translation of the mechanical force components induced by and directly proportional to the intraocular 
pressure. 
 
Manufacturing, testing, cleaning, packaging and labelling process are carried out under monitored 
clean room conditions following international standards by ISO 13485 Implandata Opthalmic Products 

 
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GmbH itself or a certified contract manufacturer. Each implant is packaged in multiple protective 
layers: the implant is first wrapped in sturdy Tyvek and placed in a small plastic box, and then packaged 
in two SteriClin sterilization bags, in conformance with EN ISO 11607-1:2006. Labels identifying each 
individual implant are located on the inner SteriClin bag as well as on the outer layer. Following 
packaging, the implant are sent to another contract manufacturer where they are sterilized with 
ethylene oxide using processes validated according to AAMI TIR 28:2009 and ISO 11135-1:2014. Prior 
to release, samples from each batch undergo testing Limulus Amebocyte Lysate (LAL) testing using the 
gel clot method (United States Pharmcopeial Convention Procedure UPS 85) to detect any residual 
bioburden or endotoxins [15]. 
4.3 
Details about the manufacturer of the investigational device 
The sponsor Implandata Ophthalmic Products GmbH is the manufacturer of the implant and the 
Mesograph reading device.  
4.4 
Device and accessories identification 
Each ARGOS-SC pressure sensor implant will be identified by a unique 32-bit hexadecimal serial 
number stored in non-volatile memory on the ASIC. The reading device can be identified by a unique 
seven-digit serial number. 
4.5 
Device accountability and storage 
The investigational team at each site is responsible for ensuring investigational device accountability 
throughout the course of the study in accordance with regulatory requirements. Upon receipt of the 
devices, the investigator or designee will check for accurate delivery and acknowledge receipt by 
signing and dating the documentation provided by the sponsor. A copy of the receipt will be retained 
in the Investigator Site File. 
 
Site staff will carefully record the serial number of each implant and reading device, as well as the 
ID number of the patient for which they were used, on the device accountability forms provided by 
the Sponsor. An accurate documentation of device accountability will be available for verification by 
the monitor at each monitoring visit. In addition, each patient will be given an implant pass identifying 
his/her device with type and serial number and listing further information including implantation date, 
sponsor contact information, implanting clinic and surgeon and warnings relevant to interactions with 
other medical procedures and devices as well as with metal detectors.  

 
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Investigational device accountability records will include: 
• Confirmation of device delivery to the study site 
• Device inventory at the site 
• Device allocation to subjects, including date of device implantation, patient number and 
device identification number (serial number). 
 
The sponsor’s monitoring staff will verify that the study site’s device accountability records match the 
records of used devices recorded in the CRFs. 
 
The device must not be used for any purpose other than the present study. Unused devices will be 
returned to the sponsor at the end of the study period in accordance with the sponsor’s instructions. 
 
The investigator or authorized designee will alert the responsible monitor as soon as possible of any 
expected or potential shortage of devices during the study, so that the sponsor can organize the 
shipment of extra devices. Some extra devices will be provided in case any devices cannot be used. 
 
The investigational devices must be kept in a secure place with restricted access. The shelf life of the 
device is 1 year under temperature conditions ranging from +5° C to +25° C. 
4.6 
Necessary training and experience requirements 
It is assured that ophthalmic surgeons performing the surgery will be adequately trained on the 
ARGOS-SC pressure sensor implantation. Site personnel responsible for device handling including 
accountability, storage and shipment procedures will be trained during the initiation visit. If new site 
personnel are assigned during the study, they will be trained by the principal investigator or the 
monitor. 
Surgical implantation 
• 
The ARGOS-SC device will only be implanted by ophthalmic surgeons who are experienced in 
performing the non-penetrating glaucoma surgery and who have been familiarized with the 
handling and implantation of the sensor either through instruction by Sponsor representatives 
or by intensive consultation of the Implant Instruction for Use (IFU) [16]. 

 
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Intraocular pressure measurement using the Mesograph Reading Device 
• 
Intraocular pressure (IOP) measurement with the ARGOS-SC system may be carried out by any 
trained individual, including patients and care givers. Health care professionals will be trained 
by sponsor representatives or their delegates. Prior to hospital discharge following surgery, 
trial staff will instruct subjects on the use of the reading device for IOP self-measurement. 
Subjects will also be given separate written handling instructions provided by the Sponsor.  
Setup of Mesograph and downloading of measurement data 
• 
Only specially trained personnel may set up the Mesograph reading device or download data 
from it. Special attention must be paid to maintaining data protection in this when handling 
patient data. Training will be provided by Sponsor representatives. 
Evaluation of data  
• 
The data obtained by the ARGOS-SC system measurement will only be used for the evaluation 
of the trial outcome. Diagnosis, therapeutic assessments and decisions about additional 
medical treatments will be based primarily on IOP measurements made with the tonometry 
method(s) conventionally used by the investigator in this patient population. However, 
because study patients will perform regular self-monitoring of IOP, which is not currently 
possible, it is conceivable that detection of elevated IOP levels by the patients may lead to 
more frequent unscheduled visits. 
4.7 
Description of any specific medical or surgical procedures involved in the use of 
the investigational device. 
Detailed implantation instructions are presented in the Instructions for Use (IFU) [16] and the 
Investigator’s Brochure (IB) [17] and in Section 8.3.14 Surgery of this CIP. 
 
Following completion of the IOP lowering portion of the non-penetrating glaucoma surgery, hyaluronic 
acid-based viscoelastics such as Healon OVD (Abbott Medical Optics Inc.) are used to separate the 
sclera from the choroid. The scleral flap is enlarged or an additional small incision made next to it to 
ensure a final flap width of at least 3.2 mm to 3.5 mm. The ARGOS-SC sensor is then gently pushed 
through the opening into the suprachoroidal space with the “pressure sensing side” of the ASIC facing 
the eye.   

 
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4.8 
Pre-clinical testing/assessment 
4.8.1 
In vitro/Bench/Lab testing 
4.8.1.1 
First study in human cadaver eyes 
On July 18, 2013, Prof. Szurman implanted 3 early ARGOS-SC demonstrators into 2 adult human 
cadaver eyes, using different methods and orientations of the implant.  
 
As an initial effort to determine the required form factor for the implant, non-functional demonstrators 
were implanted into human cadaver eyes by Prof. Dr. med. Peter Szurman at Knappschaftsklinik 
Sulzbach [18]. The size of the demonstrators was about 7.5mm x 3.5mm x 1mm, and Prof. Szurman 
used a surgical approach where he opened the conjunctiva with a small incision in an oblique quadrant, 
and then prepared a laminated scleral incision with a width of about 4mm, about 2mm posterior of 
the limbus. All implants were easily inserted radially; one implant was turned 90° for a horizontal 
position parallel to the limbus. Eyes were sectioned in half, and the position of the implants 
underneath the choroid was inspected. All implants were securely positioned, without any sign of 
tissue damage, with a position starting from about 1mm anterior of the ora serata. In posterior 
direction, none of the implants reached the equator of the eye. Prof. Szurman determined that a 
pressurized vitreous body would secure the implant in place, securely preventing implant migration.  
 
The bulbi were fixated in formalin, and sent for histology preparation in a special cutting-grinding 
technique to preserve the structure of the implanted structure. Macroscopic findings and histology 
results were assessed [19] and did not reveal any compromise to the eye’s integrity, with the sclera 
(apart from the surgical wound) and especially the choroid being fully intact. 
4.8.1.2 
Functional Testing in Porcine Eyes 
On April 26, 2013, a fully functional ARGOS-SC demonstrator was implanted in the suprachoroidal 
location as proposed by Prof. Szurman. Measurements showed very good concordance compared to 
water column and an electronic pressure gauge (both connected to anterior chamber using a 20G 
Lewicky anterior chamber maintainer through a tightly sealed off paracentesis), with an R2 of 0.99 or 
better. Results have been documented in [20]. 

 
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4.8.1.3 
Validation of implantation method/approach and validation of approach for 
surgical removal of implant in human cadaver eyes 
On August 21, 2017, in an effort to develop/validate the surgical approaches for implantation, and, if 
necessary, explantation, have been performed by Prof. Peter Szurman and Dr. Sigfried Mariacher at 
Knappschaftsklinik Sulzbach in human cadaver eyes came from local eye bank. As in all prior 
experiments, it was easily possible to insert the implant through a full thickness scleral cut of about 
4.5mm width, after preparing the surgical site in the same was as done throughout the pre-clinical 
studies; in a second approach, the implant was placed as it will be during non-penetrating glaucoma 
surgery. A superficial scleral flap was created measuring about 5.5 mm (lateral) by 5 mm (anterior-
posterior). Due to the missing corneoscleral button (eyebank eyes), the anterior flap ended at the rim 
of the front hole of the globe. A 3 mm (wide, lateral) by 2 mm (anterior-posterior) deep scleral lake 
was then created within the borders of the superficial flap, dissecting down to the choroid. Hyaluronic 
acid was injected to form a cavity between the sclera and the choroid (towards the equator of the 
eye). The implant was easily inserted into its in-situ position, through the deep scleral lake, without 
any widening if the incision. The rounded sclera facing side of the implants fits the inner shape of the 
bulbus well. 
4.8.1.4 
Functional Testing 
Accuracy, precision and long-term stability of measurement are being tested using the same processes 
that have been implemented for the CE marked EYEMATE-IO system. As ARGOS-SC is based on the 
exact same technology as EYEMATE-IO, it can be expected that the long-term measurement stability 
data derived with EYEMATE-IO is also applicable for ARGOS-SC. We have validated this assumption by 
comparing the accuracy and precision data of ARGOS-SC with that of EYEMATE-IO. 
 
Both systems have a specified 3-sigma accuracy of 2 mmHg, and an annual drift rate not to exceed 2.5 
mmHg. The output value of both systems is a pressure reading in mmHg. ISO 8612:2009 -- Ophthalmic 
instruments – Tonometers, the international standard that is specifying the requirements for 
conventional tonometers measuring intraocular pressures, is specifying a tolerance of +/- 5 mmHg. 

 
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(Concordance with Goldmann Applanation Tonometry and with DCT Pascal Tonometer in human eyes 
is one of the objectives of this clinical investigation.) 
 
In several test cycles, it has been shown that EYEMATE-IO devices exceed above mentioned 
specifications, especially long-term drift, where values below 1 mmHg/a over a time span of >10 years 
were accomplished in all tests that has been conducted to date.  
4.8.1.5 
Biocompatibility and Cytotoxicity 
The outer layer composition of CE-certified EYEMATE-IO is exactly the same as for the experimental 
ARGOS-SC, with the exact same processing methods. The electronic modules of both devices are 
similar, with the exception that ARGOS-SC uses a gold wire wound antenna coil, with Polyimide as 
isolator, where EYEMATE-IO uses a planar, photogalvanically manufactured gold coil on a Polyimide 
substrate (Figure 1). From a material composition point of view, the only additional material in ARGOS-
SC is a very thin layer of Polyvinylbutyral to stabilize the wire wound coil. However, the cytotoxicity 
profile of both electronic module variants does not differ. 
Figure 1: Antenna coils of the EYEMATE-IO / ARGOS-SC pressure sensor 
 
Top: Antenna coil EYEMATE-IO. Bottom: Antenna coil ARGOS-SC 
 

 
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4.8.1.6 
Exclusion of possible adverse effects 
Temperature Elevation (worst case estimation) 
The theoretical temperature elevation of surrounding tissues due to the malfunction of the EYEMATE-
IO implant was estimated for the worst-case scenario and found to be well below the acceptable limit 
defined in EN ISO 45502-1 and EN ISO 14708-1:2014 (section 17.1) [21]. Since the electronic modules 
of both devices are similar and share the same principle of power supply (and data transfer), the worst-
case estimation also applies for the ARGOS-SC device. 
Hazards due to RF Field Exposure during IOP Measurements with ARGOS-SC device 
The risks associated with exposure of the patient to intended and unintended radio frequency fields 
and of the risk of interaction of the ARGOS/EYEMATE-IO, which also applies to the technical similar 
ARGOS-SC device, with other AIMDs were estimated based on available literature. It was concluded 
that: 
• 
The risks due to exposure to heating effects and RF fields under normal use are negligible. 
• 
Exposure of pacemakers or ICDs to the activated MESOGRAPH could interact with pacemakers 
and ICDs when in close proximity. The MESOGRAPH must not be activated closer than 22 cm from 
such devices.  
• 
It is not known how the ARGOS-SC system will interact with cochlear implants, implantable 
hearing aids or implanted neurostimulators in the head/neck region. Use of the ARGOS-SC implant 
is contraindicated in these patients. 
• 
The Mesograph was tested according to EN ISO 60601-1-2 and ETSI standards and should not 
interact with other medical devices. 
• 
Foreign magnetic fields do not pose a risk of harm to the patient. 
4.8.1.7 
MRI Compatibility, Compatibility with other Implantable/Wearable medical devices 
Non-clinical testing in accordance with the relevant standards (ASTM F 2052 (Displacement), F 2182 
(Heating), F2119-07 (Artifacts)) by means of magnetic resonance tomography (MRT) devices on the 
technically similar EYEMATE-IO device demonstrated that ARGOS-SC device is “MRI conditional” (safe, 
but imaging artifacts likely) with a magnetic field strength up to 3 T [22]. It is unlikely that there is a 
danger in MRT devices with higher field strengths; the manufacturer is to be contacted if an 
examination in such a device should be necessary. 

 
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4.8.1.8 
Packaging, Cleaning, Sterilization 
The packaging system used for ARGOS-SC is the same that is used for CE certified EYEMATE-IO. All 
packing related validation is adopted from EYEMATE-IO. 
• 
Packaging Validation 
• 
Cleaning Process 
• 
Sterilization 
• 
Manufacturing 
 
4.8.2 
In vivo Studies 
4.8.2.1 
Animal Studies 
Prove-of-concept study: “Tübingen I” 
Six ARGOS-SC telemetric pressure transducers were implanted into the suprachoroidal space of 6 eyes 
from 6 New Zealand White rabbits. Functionality of each device was verified 1, 4, 8, 12 and 30 weeks 
after implantation on May 23 and May 24, 2014. After cannulation of the anterior chamber different 
intracameral pressure levels were generated using a height adjustable water column. Telemetric 
assessed IOP and intracameral pressure were analyzed using scatter plots and Bland-Altman analysis 
(95% CI). Mean bias (limits of agreement) 1, 4, 8, 12 and 30 weeks after implantation was 0.14 mmHg 
(-2.04 to 2.31 mmHg), 0.01 mmHg (-2.83 to 2.86 mmHg), 0.62 mmHg (-2.08 to 3.32 mmHg), 0.47 mmHg 
(-3.04 to 3.98 mmHg) and 0.33 mmHg (-2.75 to 3.42 mmHg) respectively. A slight variability of offset 
and proportional bias was explained with the mechanical stress that was exerted onto the implants 
due to the fact that the posterior chamber of the rabbit’s eye differs significantly from the larger 
structures of the human eyes. In rabbit eyes the anterior segment is proportional larger and the 
posterior segment smaller than in human eyes [23], so mechanical stress and dislocation of the implant 
due to altered conditions is more likely in rabbit eyes. 
 
Ophthalmological examinations showed no signs of conjunctival, scleral, choroidal or retinal lesions. 
Histological analyses revealed a small band of fibrosis next to the implantation site but showed no 
signs of inflammation, necrosis or other pathologies. Implantable telemetric suprachoroidal pressure 
sensors provided promising concordance between telemetric and intracameral IOP values. Clinical and 
histological examinations revealed good biocompatibility 30 weeks after implantation. 
 

 
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Devices used for this exploratory study were technology demonstrators which outer shape was not 
100% identical with the final design. The purpose of this study was to prove the long term feasibility 
of suprachoroidal measurement of intraocular pressure. Technically, from a sensor and material point 
of view, devices were identical to the final devices. The devices were of rectangular shape (Dimensions: 
x mm x y mm x z mm), and encapsulated in PDMS silicone polymer with rounded edges. 
 
Devices tended to slightly extrude out of the suprachoroidal cavity towards the incision, which was 
addresses in a follow-up study (see below). 
Biocompatibility study: “Tübingen II” 
A second implantation study with 8 ARGOS-SC devices in the final design was performed at the 
University of Tübingen, Germany. The sensor device, ARGOS-SC was tested on local tolerance in a 6 
months study in New Zealand White (NZW) rabbits. The objective of this implantation study was to 
evaluate possible adverse effects of ARGOS-SC device. The report [24] deals with the results of the 
pathology evaluation. 
 
Testing has been carried out in lieu of DIN EN ISO 10993-6:2017-09: Although the rabbit eye is different 
from the human eye in many aspects, it is still the model of choice for pre-clinical testing of intraocular 
implants. Due to the smaller size of the rabbit eye, the implants are oversized relative to the structures 
of the posterior chamber. However, apart from intensified mechanical stress level between the tissue 
surrounding the implant and the implant itself, histology findings were assessed to be representative 
for implantations in humans. In our view, this test strategy if far more meaningful and significant than 
implanting the device into muscular tissue for a max. 12 weeks. The material the outer surface of the 
device consists of (Nusil MED 6820) is a well-known material for long term implantation in numerous 
regions of the body, including the eye. Such testing would not reveal specific issues that may be existing 
in direct contact with the delicate structures of the eye wall.  
 
Purpose of this test was to assess the biocompatibility of the final design, as well as the tendency of 
the devices to migrate out of the suprachoroidal cavity. 
Histology Findings 
Images of the in-situ situation and during explantation were taken by digital microscopy (Keyence 
2000). The implantation sites did not reveal any gross lesion. The implants were visible through the 

 
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overlaying tissue. In two samples (sample no. 2.2 and 4.2, right), there was distinct bubbles noted in 
the retina. Furthermore, on the inner eye surface, a striated tissue overlaying the implant was recorded 
in these samples. Histologically, these regions correlate to a partial replacement of a cyst-forming 
fibrotic reaction. They are deemed to represent remainders of a traumatic insult during surgery. 
 
The histology examiner found the implant pouch (if visible on the section) to be located in all samples 
between choroidea and sclera. Further analysis did not reveal any indication of pathological changes 
in all samples. The implant was tolerated by the tissue fully. In some sample, even a fibrotic reaction 
was not traceable. In other samples, the fibrotic reaction consisted of an extremely thin rim of 
connective fibers. Only in two eyes, a few macrophages attached to the inner capsule surface were 
found. No other inflammatory reactions could be noted. 
 
In three eyes, focally limited degeneration of the retina consisting of a partial replacement by a cyst-
forming fibrotic reaction was noted by the histology examiner. By digital microscopy, it correlated to 
small bubbles and striations in the retina overlaying the implant. These findings were also assessed by 
the surgical team.  
 
The surgeon performing all implantations reported difficulties forming a suprachoroidal cavity in 
rabbits, compared to the same task when performed in human eyes (surgeon has extensive experience 
in suprachoroidal implantation of Ologen implants of similar size). He presumed there are tissue 
adhesions between the rabbit sclera and choroidal, which he never experienced in human eyes. This 
is one likely explanation for the additional mechanical insult that have been reported by the 
histological examiner. Implantation in human eyes should be easier to perform, with significantly 
reduced mechanical irritation. 
 
The reported retinal lesions may also have been caused by a reduced nourishment of retinal tissues. 
Similar effects can be found in cases of retinal detachment. However, since in human eyes, a large 
portion of the implant will be located in the pars plana region (a region without retinal coverage), and 
the remainder will be covered by the very peripheral retina (that portion of the retina does not 
contribute to the central vision of the eye). 
 

 
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A third factor may be the, compared to human eyes, the additional mechanical effect of the implant 
due to the strong curvature of rabbit eye, and the resulting short axial length: The relative size of the 
implant is larger compared to the rabbit eye than to the human eye. 
 
All in all, both the implanting surgeon (Professor Dr. Peter Szurman, Chefarzt, ehemaliger Leiter der 
Sektion “Experimentelle Ophthalmichirurgie”Univ. Tübingen) and the histological examiner view the 
findings to be uncritical and most likely to be less prevalent in human eyes. 
Implant integrity after explantation 
Surface roughness measurements was performed on the explanted devices. No cell adhesion was 
observed on the implants. Overall the implants can be considered clean with minor adhesion of 
particles, likely fibrin. Overall the data shows very homogenous surfaces both between the defined 
areas within an implant as well as between different implants.  
Implant migration 
In one of the animals, the implant was dislocated into the vitreous cavity. Comparing the lesion of the 
retina from this eye, and in the absence of any further inflammatory or degenerative lesion, it is 
concluded that the migration took place during the necropsy/collection phase, but not during the in-
life phase. The main supporting factor is the formation of a focally limited retinal alteration. In case of 
an in-vivo phase migration, a multifocal retinal lesion should be expected. Furthermore, the fibrotic 
reaction seen in both other animals are indicative for traumatic trauma (pressure). Since the lesion in 
the eye with migrated implant was qualitatively of a same character, there is no question on another 
cause than a focal traumatic insult (pressure). 
4.8.2.2 
Human cadaver eye study 
Furthermore, two ARGOS-SC devices were implanted in a human donor eye by means of non-
penetrating glaucoma surgery. One ARGOS-SC device was implanted at 12 o’clock and the other one 
at the opposite side. The eye was subsequently fixated and preserved in Formalin [25].  
 
The eye was then examined by means of high resolution ANTERION® (Heidelberg Engineering) and 7T-
MRT scan (Hannover Medical School). The ANTERION®®, a new development within the field of OCT 
imaging, works on a different wavelength compared to the commercially broad distributed OCT 
imagers, thus allows for a deeper visual scan of the eye structures, in particular within the area of the 

 
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sclera. With this novel imaging technique, the position of the implant within the suprachoroidal space 
as well as the state of the eye tissues can be assessed.  
 
Neither the ANTERION® scans, nor the 7T-MRT scans revealed any damage to the eye tissue layers, i.e. 
choroid, and eye structures. The position of the implant was as expected. Furthermore, the back 
(convex) plane of the ARGOS-SC device is supported by the sclera as intended [17]. 
4.9 
Clinical experience with similar devices 
4.9.1 
Method validation: Clinical experience with EYEMATE-IO 
In the ARGOS-02 clinical trial, which involved the EYEMATE-IO device, surgical complications were 
reported in 7 of 23 patients. In five of those seven patients, complications occurred during the 
implantation of the EYEMATE-IO device. The complications most often (five times each) were 
Irisprolapse/floppy iris and pigment dispersion. Flat anterior chamber and “vis a tergo” (“pressure from 
behind”) were reported twice each.  
Serious adverse events which were considered to be at least possibly related to either the implant or 
the implantation procedure were: 
- 
Fibrin reaction in the anterior chamber (postoperative event which was resolved by 
medication)  
- 
Increased intraocular pressure (was most likely caused by pigment dispersion)  
- 
Corneal decompensation (was most likely caused by excessive surgical manipulation) 
 
These complications are connected with the cataract surgical procedure and are possibly related to 
the implants position but not to the functional principle of the implant, and as such not associated 
with the ARGOS-SC device. 
 
The EYEMATE-IO IOP measurement method showed an excellent level of concordance to the 
conventional GAT IOP measurement though a dependence of the differences between GAT IOP and 
EYEMATE-IO IOP on the respective IOP level was observed. In the range of physiological IOP (≤ 21 
mmHg), the differences between both methods are in the range of the physiological variety of IOP. In 
IOPs considered to be higher as normal (> 21 mmHg) the differences between the two methods were 
higher than the average variety of IOP in human eyes. The higher the IOP the larger the difference 
between the methods, as also observed by other groups [26, 27]. 

 
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4.9.2 
Experience with Ologen and Esnoper V-2000 implant 
Over the last decades, a large variety of implants were introduced in the market to facilitate the non-
penetrating glaucoma surgery concept. The majority of the implants, which are implanted in the 
conjunction with the intervention, aim to maintain the intrascleral space and upkeep the aqueous 
outflow. The Ologen implant, a biodegradable collagen-glycosaminoglycan copolymer matrix implant, 
is unique in this sense. This implant - and most recently the Esnoper V-2000 - is, within the non-
penetrating glaucoma surgery procedure, fully implanted into the suprachoroidal space to upkeep the 
aqueous humor outflow from the suprachoroidal space via the uveoscleral pathway across the sclera 
to the orbital vessels as well as via the uveovortex pathway across the choroid to the vortex veins [28]. 
With exception of the common surgery based (i.e. hyphema) and drainage based (i.e. transient 
hypotony) complications, no position based (suprachoroidal space) complications were observed with 
these implants. 
5. 
JUSTIFICATION FOR THE DESIGN OF THE CLINICAL INVESTIGATION 
The suprachoroidal approach for placing an intraocular pressure sensor implant was developed in 
parallel with the EYEMATE-IO, which received CE-mark approval in 2017, for placement into the 
posterior chamber/ciliary sulcus placement. This parallel approach was chosen for several reasons: 
• 
Access to the suprachoroidal space is part of or can be easily combined with surgery to lower 
intraocular pressure, either penetrating or non-penetrating surgery techniques. While high 
volume Cataract surgeon may be reluctant to operate in the posterior segment, Glaucoma 
surgeons routinely access this area. 
• 
EYEMATE-IO requires crystalline lens removal. While Cataract and Glaucoma often coincide in 
the relevant age group, many patients will not be eligible for EYEMATE-IO implantation, or will, 
at younger age, not be willing to have their crystalline lens removed prior to end stage 
presbyopia. A major advantage of the suprachoroidal approach is that the anterior chamber 
stays unaffected during implantation. Therefore, the procedure can be performed regardless 
of the lens status and any anterior chamber pathologies. 
 
EYEMATE-IO has been lauded to measure the actual intraocular pressure, b/c it is located within the 
anterior segment, immersed in aqueous humor. A concern was that the slightly indirect measurement 
of the pressure within the vitreous cavity with ARGOS-SC is not representative of the actual intraocular 

 
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pressure. However, in vitro and in vivo testing has shown that the pressure level set within the anterior 
chamber (via water column connected through cannula penetrating the cornea) is comparable to the 
pressure measured with ARGOS-SC. 
 
Functionality of the ARGOS-SC device is independent of Glaucoma surgery, and could well be 
implanted in a standalone procedure. However, in order to mitigate initial risk, surgical consultants 
recommended to, in a first step, combine the implantation with non-penetrating Glaucoma surgery. 
If it is demonstrated to be safe and reliable in humans, the ARGOS-SC system will provide in all 
postoperative phases an accurate method of measuring intraocular pressure that:  
• 
Is not influenced by the condition of the cornea or the presence of sutures  
• 
Is not limited to the use for pseudophakic patients, as EYEMATE-IO is 
• 
Can be conducted frequently and conveniently in a non-clinic setting, by patients themselves 
or any assisting personnel. 
 
The ARGOS-SC will thereby permit rapid detection of postoperative IOP changes and patterns between 
clinic visits, providing a complete and accurate IOP profile that allows treatment to be titrated up or 
down according to each patient’s individual condition. 
 
At this point in time, all technical risk factors, and risk factors that can be evaluated in bench testing or 
animal models have been assessed. A study in patients undergoing non-penetrating glaucoma surgery 
is needed to determine if concomitant implantation of an ARGOS-SC device is also safe in this 
population. Comparison of the IOP measurements obtained with the ARGOS-SC device to those 
obtained using methods standard in this population at various time points, resulting in a within 
individual control of IOP variables, will also allow initial conclusions to be made regarding the 
usefulness of the device. 
6. 
RISK EVALUATION 
6.1 
Anticipated clinical benefits 
Intraocular pressure (IOP) is one of the most important determinants of disease progression in 
glaucoma as IOP reduction remains, to date, the only proven therapeutic intervention for disease 
control and prevention [29, 30]. Despite the emergence of newer technology [31, 32], the Goldmann 

 
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Applanation Tonometry (GAT) is currently the most common method to routinely measure IOP [29]. 
The accuracy of Goldmann Applanation Tonometry is dependent on corneal biomechanics, curvature, 
and thickness [33, 34]. In some situations, Applanation Tonometry is not possible such as in eyes 
implanted with keratoprosthesis [35]. 
 
Current methods of IOP measurement do not permit frequent, round-the-clock, or continuous 
recording, or self-measurement of IOP by the patient in his home environment. Such measurements 
may be critical in understanding the progression of glaucomatous visual loss especially in normotensive 
or low-tension glaucoma [36–38]. 
 
Due to these facts, the treating Ophthalmologist is missing important information regarding the short- 
and long-term fluctuation of IOP. In clinical routine, IOP is measured once every 3 months. This is not 
sufficient to reach a good judgment regarding patients’ therapy, or success of therapy, or to adequately 
adjust therapy. A further advantage of the non-invasive IOP measurement will be the possibility to 
acquire continuous IOP data in the patient’s normal living environment. 
 
An intraocular pressure sensor, which is delivering objective data with regard to the actual situation of 
the pressure within the eye will give the Ophthalmologist important information about the influencing 
factors of elevate IOP and Glaucoma. 
 
Providing an easy-to-use way of self-measuring IOP will provide patients with a feedback about their 
therapy, which is especially important in Glaucoma, a disease with a very slow progression. The 
motivation for the patients to apply their eye drops according to the treatment plan is likely to be 
significantly improved by that fact (similar to e.g. self-measurement of blood pressure in hypertensive 
patients). To date, the patient compliance, which means the patients willingness to adhere to the 
treatment plan with eye drops and other medications is not optimal, which can jeopardize success of 
therapy [39, 40]. 
 
6.2 
Risk Management Process  
Potential risks related to the intended use and foreseeable misuse of the ARGOS-SC system were 
identified and mitigated on an ongoing basis according to the risk management analysis prescribed by 
ISO 14971:2013 and detailed in the document Risk Management Report [41].  

 
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Risk control measures were undertaken to reduce the probability of unacceptable and borderline 
acceptable risks. Where ever possible, priority was given to eliminating the risk first through design 
changes to eliminate it and if this was not feasible, mitigating it by integrating protective measures in 
the medical device itself or in the manufacturing process to minimize the risk. Risks due to human 
factors that could not be eliminated or checked in advance, such as mistakes in the implant or explant 
procedures were mitigated by including clear warnings and cautions in the literature and packaging 
accompanying the device and by limiting implantation use to experience ophthalmic surgeons. The 
resulting measures were finally reassessed to ensure that no new risks had been introduced during the 
mitigation process. 
6.3 
Possible complications and adverse events 
Complications may occur due to additional surgical manipulation of the eye while implanting the 
ARGOS-SC device. While it is possible to implant the device in a standalone procedure, for a first-in-
human trial, implantation will be combined with non-penetrating glaucoma surgery (NPGS). The 
complications which might occur during the implantation may also be associated with the standard 
non-penetrating glaucoma surgery. However, implantation of the additional device may increase their 
likelihood and/or severity. Nevertheless, it is assumed that these adverse events could be minimized 
or eliminated by surgeon training as well as following all of the instructions regarding implant handling 
and surgical procedure. Possible adverse events might be: 
• 
Perforation/Rupture of the trabeculo-descement‘s membrane (TDM) 
• 
Anterior chamber inflammation 
• 
Hypotony 
• 
Shallow anterior chamber  
• 
Suprachoroidal hemorrhage 
• 
Choroidal detachment 
• 
Retinal detachment  
• 
Hyphema 
• 
Blebitis 
• 
Iris incarceration in TDM 
• 
Temporary visual impairment as a secondary effect caused by the adverse events described 
above. 

 
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It is assumed that in most cases, the complications that may arise following NPGS with combined 
ARGOS-SC implantation are expected to be temporary and manageable by medication. 
 
For the clinical evaluation process, IOP management therapy and assessment of therapy success will 
be based solely on IOP values measured with Goldmann Tonometry and, when available, Dynamic 
Contour Tonometry. IOP values derived from the ARGOS-SC implant will in no case be used for 
therapy decisions as long as not validated.  
6.4 
Risks and Benefits associated with the participation in the clinical investigation 
• 
ARGOS-SC system associated risks – As described in Section 6.2, a full risk analysis was performed 
during the development of the ARGOS-SC system to anticipate and eliminate or at least minimize 
all foreseeable ARGOS-SC system-related risks. However - as with any new device - it is possible 
that unknown risks remain that will only become apparent as more experience is gained with the 
device. The safety of the study patients is of paramount importance and will be monitored 
throughout the study at all times. If at any time a safety issue arises that is thought to be related 
to the ARGOS-SC implant, to the specific procedures necessary to implant it, or to its use to 
measure IOP, appropriate measures will be initiated immediately to minimize risk to current and 
future study patients. All investigators will be kept informed of such issues. The ARGOS-SC was 
designed to be able to remain in the eye even in the event of failure. If it must be removed, for 
example due to adverse effects, the risks of removal correspond to those associated with 
implantation. 
• 
Data Privacy Risks – Health data about study patients will be collected and transferred to an 
electronic database. Although all currently required methods will be used to protect patients’ 
privacy, the security of such databases can never be completely ensured. For this reason, no 
information that can identify study patients other than the pseudonymising Subject ID will be used 
on the database or on any study documentation other than the patient log, which will remain at 
the site. Potential patients will be informed of the data privacy policy during the informed consent 
process. 
• 
Because of patients’ vulnerable nature, there is a risk that they may either feel obligated to 
participate in the study or that their knowledge of the study may influence their decision whether 

 
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or not to undergo NPGS at this time. To mitigate these risks, only patients who have already 
consented to NPGS will be informed of the study and all potential study patients will be told 
explicitly that they are free to choose not to participate, and that refusing will not affect their 
treatment except in regards to the ARGOS-SC system. 
• 
Patients will be requested to attend visits on a regular basis. It is possible that this will be 
uncomfortable or inconvenient for them. Patients will be reminded that the information they 
provide is confidential, that it will be used to better the care they and fellow patients receive, and 
that their continued participation is voluntary. 
6.5 
Possible Interactions with Concomitant Medical Treatments 
Interaction of the ARGOS-SC implant with other medical treatments and devices is possible both during 
the implantation, which is intended to occur concomitantly with non-penetrating glaucoma surgery, 
and indefinitely following implantation due to the intended permanence of the implantation and the 
continuing use of the external reader. 
 
Possible interactions of the ARGOS-SC implant with other devices and/or substances used in 
treatments of the eye:  
• 
Instrumentation and substances used during the implantation procedure:  
o 
Padded forceps for manipulation of the implant 
o 
Other instruments commonly used for the non-penetrating glaucoma surgery: to 
prevent damage to the surface of the implant, it is important to avoid contact of the 
implant with sharp or pointed instruments such as toothed forceps. No instrument of 
any kind should come into contact with sensor at the ASIC. 
o 
Viscoelastic surgical devices 
• 
High energy ultrasound: Do not use high energy ultrasound in the vicinity of the implant 
• 
Diathermy: Do not use diathermy in the vicinity of the implant 
• 
Therapeutic ionizing radiation: Do not use therapeutic ionizing radiation in the vicinity of the 
implant 
• 
Laser: Do not expose the implant to direct laser energy impact to avoid damage to the 
implant’s electronic components. However, because laser beams can be precisely guided and 

 
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controlled, pointing the laser beam at the contact would be likely only result from a grave 
treatment error. 
• 
Interaction of the device with topically applied ophthalmic medications: Although the device 
could theoretically affect effectiveness of the medication, thereby compromising therapeutic 
success of medication could interfere with functionality of the device, these risks are 
considered very unlikely. No drug-device interaction was observed either during pre-clinical 
studies in rabbits [42] or during the ARGOS-02 study with the technical similar EYEMATE-IO 
device. 
 
Interactions with other general medical procedures: 
• 
Magnetic Resonance Imaging (MRI): it is safe to use MRI with the ARGOS-SC implant for MRI 
field strength of up to 3T (please refer to section 9 in the Implant IFU for details), however 
imaging artifacts are likely to be seen in the proximity of the implant. 
• 
X-ray: medical X-rays are unlikely to cause deletion of the EEPROM from the ASIC. Gamma 
radiation must not be used on the ARGOS-SC implant because it will very likely erase the 
EEPROM. 
• 
Other devices generating high-frequency electromagnetic fields: although it is conceivable 
that the device could be influenced by exposure to high-frequency electromagnetic energy, 
because it operates only on a narrow band length (13.56 MHz) the likelihood of this occurring 
is small. However, interaction with oncological therapy or other hypothermia devices having 
high performance levels cannot be ruled out. 
 
Interactions with other active implanted medical devices: 
• 
Pacemakers: the ARGOS-SC reader must not be activated in direct proximity to a pacemaker 
generator 
• 
Implantable cardioverter defibrillator (ICD): the ARGOS-SC reader device must not be 
activated in direct proximity to an ICD generator. 
• 
Cochlear Implants: the ARGOS-SC is contraindicated in patients with cochlear implants 
• 
Other (head and neck region) nerve stimulators: the ARGOS-SC is contraindicated in patients 
with other nerve stimulators 

 
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6.6 
Possible Alternative Treatments 
Only patients who require and have already consented to non-penetrating glaucoma surgery will be 
contacted regarding participation in this study. They will undergo the same non-penetrating glaucoma 
surgery regardless of whether they participate in the study or not. The only differences in their 
treatment will be any adaptations to the surgery required by the ARGOS-SC implant related 
procedures, such as placement of the ARGOS-SC implant, access to the suprachoroidal space and a 
slightly longer surgery time.  
 
Treatment decisions during the follow-up period will be based primarily on IOP measurements 
obtained using conventional tonometry. Abnormalities in IOP detected through measurements 
obtained with the ARGOS-SC device may however result in additional clinic visits for further diagnosis. 
If potential subjects choose not to participate in the study, their IOP levels will be monitored using 
their physician’s preferred method. 
6.7 
Risk/Benefit Assessment 
Based on the risk management effort, and the resulting design implementation and user information, 
the Implandata management team concludes that the benefits for a patient from the implantation of 
an ARGOS-SC implant device outweighs the residual risks as described above. Predicate implantable 
ophthalmic medical devices and procedures, show that there is also residual risk with regard to the 
surgical procedure in general. The surgical placement method of the ARGOS-SC implant slightly differs 
from non-penetrating glaucoma surgery, but there is no significant difference in the risk profile for the 
patient. The medical benefit of the implantation of the device, and resulting possibility of direct IOP 
measurement and frequent self-tonometry by the patients at home clearly outweighs the identified 
residual risks of the device. The residual risks and their probability of occurrence are within the 
acceptable range, compared to similar marketed devices in the ophthalmic field. 
 
Being able to monitor IOP quasi-continuously over extended periods of time will give the treating 
ophthalmologists valuable information about the individual disease of a patient and the effectiveness 
of the medication regimen. The ARGOS-SC system will help the patients to actively monitor their 
condition, which will in turn improve their motivation and ultimately compliance. This is particularly 
important in a disease where the loss of vision normally occurs gradually over long periods of time and 
is often only recognized in advanced cases. 

 
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7. 
OBJECTIVES AND HYPOTHESES OF THE CLINICAL INVESTIGATION 
7.1 
Objectives 
The purpose of this study is to evaluate the safety and performance of the ARGOS-SC suprachoroidal 
pressure sensor in patients with glaucoma undergoing non-penetrating glaucoma surgery.  
7.1.1 
Primary Objectives 
Performance 
• 
To evaluate the limits of agreement between measurements with the Goldmann Applanation 
tonometry (GAT), Pascal Dynamic Contour Tonometry (DCT) and the ARGOS-SC system in the 12 
months following implantation. 
7.1.2 
Secondary Objectives 
Safety 
• 
To evaluate the safety and tolerability of the ARGOS-SC pressure sensor during the implantation 
and throughout a 12 months follow-up period. 
Performance 
• 
To evaluate the performance of the ARGOS-SC system up to 12 months after implantation 
7.2 
Claims and intended performance of the IMD to be verified 
This study is designed to show agreement between IOP measurements obtained with the ARGOS-SC 
device, GAT and DCT at the same time point. Furthermore, it will allow initial assessment of the safety 
of implanting the ARGOS-SC sensor during non-penetrating glaucoma surgery.  
7.3 
Risks and anticipated adverse device effects to be assessed 
Information will be collected on all AEs and ADEs to allow assessment of the safety of implantation and 
use of the ARGOS-SC sensor in humans undergoing non-penetrating glaucoma surgery. Particular 
attention will be paid to ophthalmic AEs, for which increased risks are considered possible. However, 
because these AEs are common in this patient population, an independent assessment of their 
relationship to the ARGOS-SC sensor implant will not be possible. Possible adverse device effects will 
be subject to evaluations of the DSMB. Incidence, nature and severity will be compared to literature 
of standalone NPGS. AEs of particular interest include: 
• 
Perforation/Rupture of the trabeculo-descement’s membrane (TDM) 

 
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• 
Anterior chamber inflammation 
• 
Hypotony (IOP < 5 mmHg for more than one month or hypotony maculopathy (e.g. with 
signs of maculopathy)) 
• 
Shallow anterior chamber 
• 
Suprachoroidal hemorrhage 
• 
Choroidal detachment 
• 
Retinal detachment 
• 
Hyphema 
• 
Iris incarceration in TDM 
• 
Temporary visual impairment as a secondary effect caused by the adverse events described 
above 
Procedures that are anticipated in the general patient population in the follow-up period include: 
• 
360°-suture removal after canaloplasty 
• 
Nd:YAG membranectomy 
• 
Nd:YAG goniopuncture 
• 
Nd:YAG iridotomy 
• 
Retinal detachment repair 
• 
Transcleral cyclophotocoagulation 
• 
Vitrectomy with epiretinal membrane peeling 
• 
Choroidal drainage 
• 
Anterior chamber infusion with or without recombinant tissue plasminogen activator 
• 
Re-suturing of the scleral flap 
• 
Subconjunctival injection of dexamethasone 
• 
Inserting a therapeutic soft contact-lens 

 
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8. 
DESIGN OF THE CLINICAL INVESTIGATION 
8.1 
General Aspects 
8.1.1 
Description of the type of clinical investigation 
This prospective, open-label, single-arm multicenter clinical investigation will enroll only adult patients 
who are planning to undergo indicated non-penetrating glaucoma surgery for the treatment of 
glaucoma. 
Prospective patients will undergo informed consent and screening up to 28 days prior to the planned 
surgery. Following surgery, all patients who receive an ARGOS-SC implant will attend additional 8 
scheduled follow-up visits during the 12-month post-surgical period (days 1, 3, 10, 30, 90, 180, 270 and 
360).  
 
To investigate the performance of the device and detect possible safety issues, patients will undergo 
ophthalmic examinations and be questioned regarding their health by the investigator at every visit.  
 
Additional visits may be held as deemed appropriate by the investigator. The content and reasons for 
visits will be documented on a separate unscheduled visit CRF.  
8.1.2 
Description of the measures to be taken to minimize or avoid bias 
No randomization or blinding/masking procedures will be used in this study. To avoid bias resulting 
from patient selection, all consecutive patients who potentially meet the eligibility requirements will 
be informed of the study and asked to participate. Those agreeing will undergo the informed consent 
procedure and if they consent, will be screened. All eligible patients will be enrolled.  
 
There will be no control group for safety events. Incidence, nature and severity will be compared to 
literature of standalone NPGS. To allow assessment of performance, measurements of IOP with the 
ARGOS-SC sensor will be compared to those obtained with the standard GAT method and Pascal DCT 
at the same time point. To prevent possible influence of prior knowledge of the IOP value obtained 
with the ARGOS-SC, which is objectively displayed, measurements will always be made first with 
GAT/DCT.  Data on all device deficiencies will be recorded. 

 
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8.1.3 
Primary and secondary endpoints 
8.1.3.1 
Primary endpoints 
Performance 
• 
Level of Agreement between measurements made using GAT and the ARGOS-SC system from V02 
(day 1) through V04 (day 10) and with GAT, Pascal DCT and the ARGOS-SC system from V05 (day 
30) through V09 (day 360).  
 
8.1.3.2 
Secondary endpoints 
Safety 
• 
Number of patients experiencing a device-related SAE (SADE) at any time during implantation and 
in the first 12 months (Day 0 to Day 360) following it.  
• 
Incidence, nature, severity and seriousness of observed adverse events and adverse device events 
at any time during implantation and 12 months following it. 
 
Performance 
• 
Repeatability of the ARGOS-SC measurement 
• 
Incidence, nature and seriousness of observed device malfunctions during implantation and in 
the 12 months follow-up 
 
Utility 
• 
User acceptance of the ARGOS-SC implantation procedure by means of evaluation of implantation 
procedure questionnaires (investigators) 
• 
User acceptance of the ARGOS-SC system at the investigational site by means of evaluation of 
patient acceptance questionnaires (by investigators) 
• 
User acceptance of the ARGOS-SC system at home by means of evaluation of patient acceptance 
questionnaires (patients) 
• 
Daily IOP self-measurement profiles (patients) 
8.1.4 
Equipment to be used to assess the clinical investigation variables and arrangements 
for monitoring maintenance and calibration 
Sites will use their own diagnostic devices. The study monitor will verify that the sites maintain and 
calibrate these devices on a regular basis. 

 
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8.1.5 
Any procedures for the replacement of subjects 
Screen failures (i.e. consented patients withdrawn for any reason up to implant of the ARGOS-SC 
device) will be replaced. Subjects who withdraw their consent after implantation will not be replaced. 
8.2 
Investigational device(s) and comparator(s) 
8.2.1 
Description of the exposure to the investigational device(s) or comparators, if used 
The ARGOS-SC pressure sensor is intended to be permanently implanted in the subject’s 
suprachoroidal space concomitantly with a non-penetrating glaucoma surgery of the same eye. 
Subjects will be exposed to transient (2 seconds) low-levels of electromagnetic energy (0.25 W) 
emitted by the MESOGRAPH reading device during the reading sessions, at which time their skin may 
also be exposed to the MESOGRAPH outer surface. 
IOP measurements will be made with the ARGOS-SC system at every follow-up visit. The values 
obtained at Visits 02 through 04 will be compared to those obtained using GAT and at Visits 05 through 
09 with GAT and if available Pascal DCT. Patients will also be requested to make daily measurements 
with the ARGOS-SC system in the out-patient setting.  
8.2.2 
Justification of the choice of comparator 
GAT, considered by the medical community to be the gold standard method of IOP measurement, will 
be used as comparator. However, GAT actually estimates IOP based on a measurement of the force 
needed to applanate a predetermined area of the cornea while the ARGOS-SC sensor will be in direct 
contact with the aqueous humor and measure IOP directly. Consequently, differences are anticipated 
between the IOP values obtained with the two devices. However, trends in IOP are expected to remain 
the same regardless of the method used. Therefore, to assess the accuracy of the ARGOS-SC system, 
IOP profiles obtained with ARGOS will be compared to those obtained with GAT.  
 
Pascal DCT is designed to eliminate some of the measurement errors in GAT that come from variations 
in corneal thickness and rigidity. It is believed to be closer to true IOP, especially at higher IOPs. It is 
also less prone to “user error”. 
8.2.3 
Other medical devices or medication to be used 
The ARGOS-SC system is the only investigational medical device that will be used during this study. No 
other devices or medications will be used specifically for this clinical investigation. Standard devices 
will be used as required for ophthalmic diagnostics and treatment procedures, including if needed 
glaucoma treatment.  

 
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8.2.4 
Number of investigational devices to be used 
ARGOS-SC pressure sensor will be implanted in a maximum of 24 patients undergoing non-penetrating 
glaucoma surgery. Sites will be provided with implants at surgery. Approximately 48 devices including 
replacement devices, will be required for this study. 
8.3 
Subjects 
8.3.1 
Inclusion Criteria 
In order to ensure that the study population is representative of the eligible patient population, the 
Investigator must ensure that all patients who meet the following inclusion criteria are offered 
enrollment in the study. The investigator may not apply any additional eligibility criteria.  
 
Eligible subjects must meet all the following inclusion criteria: 
1. Subjects able to understand the informed consent and willing to participate as evidenced by 
providing informed consent. 
2. Patients aged ≥ 18 years on the day of screening 
Female subjects of childbearing potential (not surgically sterilized or more than one year post-
menopausal) must have a negative pregnancy test (urine beta-hCG) within 24 hours prior to ARGOS-SC 
pressure sensor implantation. 
3. Diagnosis of open angle glaucoma requiring a non-penetrating glaucoma surgery (NPGS). The 
medical indication for a non-penetrating glaucoma surgery must be given irrespective of the 
study participation. Potential study patients will be solicited for participation in the clinical trial 
only after the patient has given consent to the non-penetrating glaucoma operation. 
4. Subjects able and willing to attend all scheduled visits and comply with all study procedures 
8.3.2 
Exclusion Criteria 
Eligible subjects must not meet any of the following exclusion criteria: 
1. Contraindications for a non-penetrating glaucoma surgery 
Ø Neovascular glaucoma, primary and secondary angle closure glaucoma 
Ø Condition after previous glaucoma surgery 
Ø IOP > 40 mmHg 
2. Myopia (> -6 dpt) or hypermetropia (> +4 dpt) 
3. Axis length < 22 mm or > 26 mm 
4. Patient with single eye vision (monovision) 
5. Exudative age-related macular degeneration, instable macular degeneration 30 days prior to 
inclusion, or macular edema 
6. Acute retinal detachment 

 
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7. Uncontrolled Diabetes Mellitus (DM) with manifestation of moderate to severe non-
proliferative diabetic Retinopathy (DR) or proliferative DR.  
8. History or evidence of severe active inflammatory eye diseases (i.e. uveitis, retinitis, scleritis) 
in one or both eyes within 6 months prior to ARGOS-SC implantation 
9. Ocular surgery procedure(s) (excluding selective laser trabeculoplasty and peripheral 
iridotomy) within 6 months (cataract surgery within 3 months) prior to ARGOS-SC implantation 
in the study eye that can affect the assessment of IOP by Goldmann Applanation 
tonometry/Pascal Dynamic Contour Tonometry  
10. Ocular disease other than glaucoma that may affect assessment of visual acuity and/or IOP by 
Goldmann Applanation tonometry (e.g. choroidal hemorrhage or detachment, lens 
subluxation, thyroid ophthalmopathy) 
11. Existence of other active medical eye implant and/or other active medical implants in the 
head/neck region 
12. Difficulties or complications during NPGS procedure or implantation of ARGOS-SC sensor, as 
assessed by surgeon (e.g. perforation of trabeculo-descement’s membrane, excessive aqueous 
filtration through TDM leading to shallow anterior chamber, excessive bleeding, choroidal 
detachment). 
13. Severe generalized disease resulting in a life expectancy shorter than a year 
14. Currently pregnant or breastfeeding 
15. Participation in any study involving an investigational drug or device within the past 30 days 
or ongoing participation in a study with an investigational drug or device 
16. Patients who are not suitable for the study based on the surgeon’s evaluation (e.g. Persons 
affected by Parkinson’s disease or essential tremor) 
17. Patients unable or unwilling to understand or comply with required study procedures  
18. Patients with psychiatric disorders influencing their judgement or autonomy 
19. Subject and/or an immediate family member is an employee of the investigational site directly 
affiliated with this study, the sponsor or the contract research organization. 
20. Enrollment of the fellow eye in this clinical study 
 
8.3.3 
Discontinuation or Withdrawal Criteria 
8.3.3.1 
Study stopping rules 
The study may be discontinued at any time for administrative reasons; if new negative data about the 
investigational device resulting from this or any other study becomes available; and/or on the 
recommendation of the sponsor, the investigators, and/or the EC or regulatory authorities.  

 
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If the study is prematurely terminated or suspended, the sponsor will promptly inform the 
investigators, the Regulatory Authorities and the ECs of termination or suspension and the reason 
behind it. If the study is prematurely terminated for any reason, the investigator should promptly 
inform the site’s study subjects and assure they receive appropriate therapy and/or follow-up. 
 
The study can be terminated at any time for any reason by the sponsor. 
8.3.3.2 
Screen Failures 
Screen failures are subjects who have signed the informed consent form and either fail to meet 
eligibility criteria for enrollment e.g. they do not meet one or more of the inclusion criteria or do meet 
one or more of the exclusion criteria, and subjects who revoke their consent and agreement 
preoperatively. Such subjects will return to standard treatment. 
 
The only data collected on subjects who fail to meet eligibility criteria prior to surgery will be the date 
of their screening visit, the date they gave informed consent and reason they are a screen failure. This 
data will be entered on the screening summary page in the CRF.   
8.3.3.3 
Premature subject withdrawal 
Subjects will be informed that they have the right to withdraw from the study at any time. The 
investigator must determine whether voluntary withdrawal is due to a cause that could raise safety 
concerns. 
 
All subjects who withdraw from the study after implantation and before completing the follow-up visits 
per protocol will be considered to be drop-outs. Subjects who drop-out or are withdrawn after 
implantation will not be replaced. Unless the patient revokes his/her permission to use it, any data 
collected up to the point of the patient’s withdrawal will be included in the analysis. The data of all 
subjects who undergo implantation of the ARGOS-SC pressure sensor will be included in the efficacy 
analysis under the Full Analysis Set. 
 
A subject will be withdrawn for any of the following reasons: 
• 
The subject withdraws informed consent. 

 
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• 
It is determined during NPGS surgery that the subject is not feasible for ARGOS-SC pressure 
sensor implantation. Subjects withdrawn before implantation of the sensor will be replaced. 
For subjects determined to be ineligible during NPGS surgery, additional information will be 
collected about the procedure up to that point.  
• 
The ARGOS-SC pressure sensor must be removed for any reason. 
If the subject permits, all end-of-study assessments indicated in the visit schedule will be performed 
for implanted early discontinuing subjects. 
Any subject who has been discontinued from the study because of an AE related to a study device or 
procedure will be followed as deemed appropriate by the investigator until resolution or stabilization 
of the event. This will be documented in the medical chart and in the CRF. Any subject who has been 
discontinued from the study because of an AE not related to a study device or procedure will be 
followed as deemed appropriate by the investigator. 
The investigator will classify the termination reason of each subject at the end of the study in the 
termination page of the CRF according to the following:  
• 
AE  
• 
Non-compliance with clinical investigation plan (CIP) 
 
• 
Lost to follow up  
• 
Voluntary withdrawal not for AE  
• 
Other reason 
The choice of keeping the implant or letting the implant be retrieved will be offered to the participating 
patients. 
8.3.3.4 
Completed Subjects 
A completed subject is considered to be a subject that completed all procedures as defined by the 
clinical investigation plan. 
8.3.3.5 
Subjects lost to follow-up 
If a subject fails to appear for a follow-up examination, reasonable effort should be made to locate or 
contact them to at least to determine their health status while fully respecting the subject’s right, 
followed by mandatory contacts with the patient’s treating doctor for exchange information on the 
patient’s health status. Reasonable effort consists of at least three attempts to contact the subject by 

 
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phone or post. These efforts should be documented in both the subject’s source documents and CRF. 
So that the monitor can verify if the study center’s attempted contacts with the patient and patient’s 
family doctor were adequate. 
8.3.3.6 
Pregnancy 
If a subject becomes pregnant between screening and surgery, she will be withdrawn from the study. 
If a subject becomes pregnant between surgery and the end of the study, she may remain in the study 
if she wishes. Her follow-up will be limited at the discretion of the Investigator until the end of the 
pregnancy as necessary to protect her health and that of the fetus/embryo. The pregnancy will be 
documented as an AE and as a protocol deviation. The pregnancy will be followed until the end to 
determine its outcome. 
8.3.4 
Point of enrollment 
A subject is considered as being enrolled into the clinical investigation when he/she gives written 
consent to participate in this investigation. 
8.3.5 
Total expected duration of the clinical investigation 
The estimated total duration of the study from first patient screened to last patient last visit is 
25 months. At the start of the study, all patients enrolled in Switzerland will be requested to sign up 
for an additional follow-up of 2 years. These patients will automatically transition to the ARGOS-
SC_Follow-up.  
8.3.6 
Expected duration of each subject’s participation 
The maximum duration of each subject’s participation in this clinical intervention is 13 months. The 
point of enrollment is considered to be the time point at which potentially eligible subjects sign the 
informed consent form. Surgery will be performed within 28 days of enrollment. The subject will be 
followed-up for 12 months post-surgery to obtain data on safety and performance. At the start of the 
study, all patients enrolled in Switzerland will be requested to sign up for an additional follow-up of 2 
years. These patients will automatically transition to the ARGOS-SC_Follow-up.  
8.3.7 
Number of subjects required 
This exploratory investigation will enroll 24 patients.  
The overall recruitment time is expected to last a maximum of 12 months. 

 
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8.3.8 
Informed Consent 
Eligible patients may only be included in the study after providing written informed consent as 
described in Section 12.1. Failure to obtain signed informed consent renders the patient ineligible for 
the study. 
8.3.9 
Allocation of Patient Number 
Each subject is uniquely identified in the study by a combination of his/her country identifier (e.g. DE 
for Germany and CH for Switzerland), site number and patient number. The number is assigned by the 
sponsor to the investigational site. Upon signing the Informed Consent Form, the subject is assigned a 
patient number by the investigator. The patient number will be composed of the abbreviation of 
suprachoroidal and 01 (SC01) (and a 3-digit string consisting of a 1-digit center identifier and a 2-digit 
patient identifier. This 2-digit patient identifier corresponds to the chronological order of enrollment 
in the center (e.g. the 3rd subject included in the study at site 1 in Germany will be patient DE-SC01-1-
03). Once the patient number has been assigned to a subject, a number will not be reused even if the 
subject is a screen failure. 
8.3.10 
Methods and timing for assessing, recording, and analyzing parameters 
During the study, subjects will attend 10 clinic visits, including 1 screening visit (up to 28 days prior to 
surgery), 1 surgery visit (day 0), and 8 follow-up visits (days 1, 3, 10, 30, 90, 180, 270 and 360). The 
assessment schedule in Table 1 summarizes all visits and the assessments to be performed at each. 
The visit window given in the table should be adhered to as closely as possible. 
At the start of the study, all patients enrolled in Switzerland will be requested to sign up for an 
additional follow-up of 2 years. These patients will automatically transition to the ARGOS-SC_Follow-
up (V10 –V13).  
8.3.11 
Safety 
At each follow-up visit, the Investigator will examine the subject and record information about any 
new or ongoing adverse events, adverse device events or clinically significant anomalies. In addition, 
the Investigator or designated site staff will ask the subject non-leading questions to ascertain if the 
subject experienced any adverse events or adverse device events between visits. 

 
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8.3.12 
Performance 
IOP level will be assessed at every follow-up visit in a series of 2 GAT standard measurements followed 
by 3 consecutive measurements with the ARGOS-SC system. From V05 (day 30) on, if available, 
additional 2 DCT measurements followed by 3 consecutive measurements with the ARGOS-SC system. 
Optional: At visits V06, V07 and V09, 24-hours measurements with GAT and ARGOS-SC will be done 
inpatient. 
Patients will be given a MESOGRAPH reading device at Visit 01 in order to measure the IOP daily at 
home. Measurements shall be taken at least 4 times per day (morning, noon, afternoon, evening). The 
MESOGRAPH reading device will be connected to an external GSM module, which will transfer the 
measured value directly to a secure database. Investigators can log into the database in order to track 
the pressure levels of their patients as required. At every follow-up visit, site staff will examine the 
subject’s hand-held reader device and download all readings recorded since the last visit. In addition, 
they will ask subjects non-leading questions to determine if any device deficiencies occurred since the 
last visit. All device deficiencies will be recorded on the device deficiency page of the CRF. 
 
To ensure accuracy and comparability of the recorded parameters, all responsible site personnel will 
be thoroughly instructed on the agreed measurement methods.  
 
To access the user acceptance of the implantation procedure and the general usability of the ARGOS-SC 
system, surgeons and personnel performing the ARGOS-SC system measurements will be asked to 
complete user acceptance questionnaires. The aim of these questionnaires is to gain more information 
about the level of user-acceptance of the ARGOS-SC system during implantation and during IOP 
measurement. The data collected with these questionnaires is only of exploratory nature and will not 
be included in the analysis. Results will provide the sponsor with data that could influence future device 
system improvements. 
8.3.13 
Assessments 
8.3.13.1 Patient demographics/other baseline characteristics 
Patient demographic and baseline characteristic data to be collected on all subjects include: year of 
birth, age, sex, race, pre-treatments and source of subject referral. This information will be collected 
at the Screening visit. 

 
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8.3.13.2 Medical history 
Relevant medical history/current medical condition data includes data regarding ongoing or significant 
previous ophthalmic and general medical conditions and procedures until start of ARGOS-SC pressure 
sensor implantation. Relevant medical history should be supplemented by review of the subject’s 
medical chart and/or by documented dialog with the subject’s referring physician. If possible, 
diagnoses and not symptoms are to be recorded. 
8.3.13.3 Concomitant medication, treatments and devices 
There are no restrictions for the use of concomitant medications required for ophthalmologic or 
systemic diseases during this clinical investigation. All medications including non-prescription 
medications used by the subject during the trial and medications in use at enrollment, will be 
documented in the subject’s file and in the CRF, as will all diagnostic procedures and medical 
interventions. There are following recommendations: 
 
30 days prior to surgery (advisable, but not mandatory) 
Modification of the glaucoma therapy:  
• 
If possible, stop prostaglandin drops  
 
On day of surgery 
Treatment in the ward: 
• 
1x antibiotic eye drops (e.g. Polyspectran©) 
• 
Topical Povidone-Iodine Solution  
• 
Pilocarpine (1-2%) eye drops as required 
Treatment in the Operation room 
• 
1x Local anesthetic eye drops (e.g. Oxybuprocaine) 
• 
Acetylcholine or Carbachol solution as needed 
Immediately postoperative: 
• 
Steroid-antibiotic combination ointment or drop (e.g. Isopto-Max© or Tobradex©) 
• 
Protective eyepatch 
 
Postoperative follow-up: 
Treatment after discharge: 

 
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• 
Avoid prostaglandin treatment until postoperative inflammation is resolved 
• 
Non-steroidal anti-inflammatory or corticosteroid (surgeon’s discretion) and antibiotic eye 
drops (e.g. Tobradex©)  
• 
Artificial tears as required 
 
Month 1 
- 
Protective eye-shield at night for one week (also daily, if necessary. In case of monocular vision: 
use transparent eye-shield) 
- 
Non-steroidal anti-inflammatory or corticosteroid (surgeon’s discretion) and antibiotic eye 
drops (e.g. Tobradex©) 6x daily, degressive reduction over 1 month or frequency at surgeon’s 
discretion 
- 
Artificial tears as required 
- 
Minimum 4 weeks non-steroidal anti-inflammatory or corticosteroid eye drops or ointment 
and minimum 2 weeks antibiotic eye drops or ointment 
 
Month 2 
- 
Non-steroidal anti-inflammatory drops (e.g. Acular© or Nevanac©), 4x daily or frequency at 
surgeon’s discretion 
 
8.3.13.4 AEs/ADEs/SAEs/SADEs 
All AEs/ADEs/SAEs/SADEs will be recorded starting with the implantation of the ARGOS-SC pressure 
sensor. 
8.3.13.5 Device Deficiencies 
A device deficiency form will be completed and sent to the sponsor for all observed device 
malfunctions or deficiencies, including defects in devices that have not been implanted in a subject or 
used otherwise. Starting with the implantation of the ARGOS-SC implant, all relevant malfunctions will 
also be recorded in the subject’s chart and CRF. 
8.3.13.6 Acceptance Questionnaires ARGOS-SC 
In the study, three types of questionnaires will be used to assess potential strengths and weaknesses 
of the ARGOS-SC system. Surgeons are asked to complete an implantation procedure questionnaire 
after each implantation at V01 (D0). At V09 (D360), the investigator responsible for IOP measurement 

 
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as well as the patients will be asked to complete a user acceptance questionnaires for the MESOGRAPH 
reading device and the general measurement procedure.  
 
The aim of these questionnaires is to gain more information about the level of user-acceptance of the 
ARGOS-SC system during implantation and during IOP measurement. The data collected with these 
questionnaires is only of exploratory nature and will not be included in the analysis. Results will provide 
the sponsor with data that could influence future device system improvements. 
8.3.13.7 National Eye Institute – Vision related Quality of Life Questionnaire-25 (VFQ-25) 
The VFQ-25 is a standardized questionnaire about quality of life relating to the patient’s vision. It 
should be completed by the patient at V06, V07 and V09. 
8.3.13.8 Visual Acuity (VA) 
The best corrected visual acuity will be determined after objective and subjective determination of 
refraction with the ETDRS chart in accordance with the ETDRS protocol. The number of character 
read and the reading distance will be recorded. The standard testing distance is 4 meters. 
8.3.13.9 Visual Field (Perimetry) 
The purpose of visual field testing is to determine both the outer limits of visual perception by the 
peripheral retina and the varying qualities of vision within that area. Perimetry is performed to obtain 
an accurate examination of the peripheral extent of the visual field. Automated perimeters will be used 
either with standard glaucoma field, field 30-2 or equivalent. This should always be done on both eyes 
in order to compare study and fellow eye. 
 
A change of the perimeter during the study should be avoided. 
8.3.13.10 External Eye Photography 
External eye photography will be performed through a slit lamp camera or equivalent in order to 
document potential changes to the outer eye at Screening and V04 through V09. 
8.3.13.11 Heidelberg Engineering ANTERION® (if available) 
The ANTERION® from Heidelberg Engineering will be used for determination of the ARGOS-SC 
location at V04 through V09 (only at sites where it is available). 

 
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8.3.13.12 Anterior eye segment measurement 
Slit-lamp biomicroscopy (undilated, anterior segment) 
At every visit, the external ocular structures and the front of the eye will be assessed using the slit-lamp 
biomicroscopy according to standard site procedures. Particular attention will be paid to the ocular 
surface and possible effects of the ARGOS-SC. The following structures will be assessed: 
a) Lids 
b) Conjunctiva (irritation) 
c) Cornea 
d) Anterior chamber (cells/flares (SUN-Classification), fibrin, flattening) 
e) Iris 
f) Pupil 
g) Lens 
h) Anterior vitreous body (cells/haze (NIH-Grading)) 
 
Optical Coherence Tomography (OCT) 
Anterior Segment OCT will be used to evaluate effects on change in chamber angle and after non-
penetrating glaucoma surgery and to assess the central corneal thickness (Screening, V04 through 
V09). 
 
Gonioscopy 
Standard gonioscopy will be used to confirm glaucoma classification and to assess other problems 
within the anterior chamber, such as the presence of foreign bodies hidden in the recess of the angle. 
The gonioscopic grading system according to Shaffer is used in this study (Screening, V06, V07, V09).  
8.3.13.13 Posterior eye segment measurement 
Biomicroscopy (dilated, fundus)  
The posterior eye segment will be examined using a slit lamp in combination with a 90D or “Superfield” 
or comparable lenses. The following parameters will be assessed: 
a) Optic nerve lesions 
b) Other posterior pole lesions 
c) Vitreous opacities 
d) Optic nerve head 

 
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e) Fundus lesions 
f) Retinal arteries and veins (AV) 
g) Macular area 
h) Fundus periphery 
i) 
Normal and abnormal variations of the fundus. 
Optical coherence tomography (OCT) 
Posterior segment OCT will be used to assess both macular structures and the peripapillary nerve fiber 
layer (RNFL) at Screening, V06, V07 and V09. 
If available, the Heidelberg Engineering Spectralis Glaucoma-Module Premuim Edition (Minimum rim 
width at Bruch membrane opening ((BMO-MRW), RNFLT and macula) should be used. This should 
always be done on both eyes in order to compare study and fellow eye. 
Fundus photography 
Standard fundus photography will be performed at Screening and V06, V07, 08 and V09 to document 
potential changes to the interior surface of the eye, including the retina. Additionally, a photo of the 
optic nerve and nerve fiber layer will be performed in red-free illumination. 
8.3.13.14 Intraocular pressure (IOP) measurement 
Intraocular pressure will be measured using three techniques. Goldmann Applanation Tonometry 
(GAT) will be performed in the clinic at every visit and if available, Pascal Dynamic Contour Tonometry 
(DCT) at V05 through V09. ARGOS-SC measurements will be performed in the clinic at every visit and 
by the patient at home between the visits. Only GAT will be used to guide any treatment decisions. 
The GAT and DCT must be performed by as few dedicated investigators as possible at each site to 
reduce potential bias. 
 
IOP measurement in the clinic 
IOP measurement will be conducted at V02 through V09 as a series of 2x GAT (in case of a difference 
of more than 2mmHg, a third GAT-measurement is required) followed by 3x ARGOS-SC system. When 
series of measurements are made, GAT must always be used first to avoid potential operator bias. For 
the ARGOS-SC measurements the patient has to stay in the same position as for the GAT-
measurements (chin on chin rest, forehead installed). From V05 through V09 additionally (if available), 
a series of 2x DCT (in case of a difference of more than 2mmHg, a third DCT-measurement is required) 

 
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followed by 3x ARGOS-SC will be performed after the series of GAT and ARGOS-SC measurements. For 
the ARGOS-SCmeasurements, the patient has to stay in the same position as for the DCT-
measurements (chin on chin rest, forehead installed). 
 
Optional: At V06, V07 and V09, the patient will be hospitalized for 24-hours measurements with GAT 
and ARGOS-SC. IOP measurements with ARGOS-SC will be done automatically via an external antenna. 
IOP measurements with GAT will be done every three hours, if it is possible even at night. If night 
measurements are not possible every three hours at night, the last measurement should take place 
between 22 and 24 o’clock and the three-hours rhythm should be resumed between 5 and 7 o’clock 
on the next morning. 
 
 
ARGOS-SC system measurement by the subject at home 
Subjects will receive detailed instruction in the use of the MESOGRAPH reading device. At V02, they 
will receive an individual MESOGRAPH reading device, a copy of the instructions for use and the 
Multiline Connector to perform self-tonometry at home. Subjects will be requested to perform at least 
4 IOP measurements daily with the MESOGRAPH, one each in the morning after getting up, at noon, 
in the afternoon and in the evening before going to bed. 
 
No data will be recorded manually by the subject. The MESOGRAPH reading device, which is capable 
of storing up to 3,000 measurements, will be connected to an external GSM module, which will transfer 
the measured value directly to a secure database. Investigators can log into the database in order to 
track the pressure levels of their patients as required.  
 
The MESOGRAPH will also be brought to every visit, at which time site staff will assess its functionality 
and delete recorded IOP data from its memory.  

 
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8.3.14 
Surgery 
During the first implantations and if desired, a member of Implandata staff will be present at 
the surgery. 
8.3.14.1 Non-penetrating glaucoma surgery and preparation for implantation  
At the start of the procedure, the conjunctiva is excised over 2 clock hours around the limbus next to 
the proposed operation side after which the non-penetrating glaucoma surgery is performed using the 
surgeon’s normal preferred procedure. Because the ARGOS-SC sensor will be placed in the 
suprachoroidal space following completion of the IOP lowering portion of the non-penetrating 
glaucoma surgery, hyaluronic acid-based viscoelastics such as Healon OVD (Abbott Medical Optics Inc.) 
should be used to separate the sclera from the choroid. This additionally serves as a safeguard against 
injuries of the surrounding tissue. Viscoelastics based on hydroxpropyl methylcellulose (HMPC) or 
other synthetic or semi-synthetic alternatives to hyaluronic acids are to be avoided. 
8.3.14.2 ARGOS-SC pressure sensor implantation 
To ensure proper function of the sensor when implanted, it is critical to confirm before implantation 
that the ASIC is in the proper orientation.  Care must be taken throughout the process to avoid 
damaging the ASIC. The sensor may only be handled using the specially designed implantation forceps 
(Implandata Ophthalmic Products GmbH, Germany), the tips of which are padded with silicone to 
protect the microsensor from damage and facilitate its implantation.  
 
A scleral window of at least 3.2 to 3.5 mm (maximum 4x4 mm) is necessary for the implantation of the 
sensor. If a narrower scleral flap was used for the IOP lowering surgery, the width of the flap will be 
enlarged or an additional small incision made next to it to ensure a final width of at least 3.2 mm.  
 
Using the specially designed implantation forceps, the implant is pushed gently through the scleral 
opening into the suprachoroidal space with the “pressure sensing side” of the ASIC facing the eye. The 
sensor must not be forcibly inserted. 
 
For the detailed ARGOS-SC implantation process, please see “IFU ARGOS-SC Implant”. 
8.3.14.3 ARGOS-SC pressure sensor explantation, if medically necessitated 
In the event that the sensor must be explanted, a scleral incision of 4.5 to 5 mm is made above the 
pars plana at the short side of the sensor, preferably above it. The incision must be fully opened to 

 
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ensure a safe explantation procedure. A hyaluronic acid-based viscoelastic (see implantation) is then 
inserted in the suprachoroidal space to ensure complete separation of the sclera and the choroid. 
Following explantation, the scleral incision should be sealed using at least one suture.  
The explanted device is to be returned to Implandata Ophthalmic Products GmbH for analysis. 
For the detailed ARGOS-SC explantation, please see “IFU ARGOS-SC Implant). 
8.3.15 
Study Visits  
Assessments and procedures to be performed at each visit are indicated with an X in the assessment 
schedule in Table 1 (see also Section 8.3.13 Assessments). The visits should be arranged as closely as 
possible to the specified visit day, accepted tolerances are set up for every visit (see Table 1). 

 
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Table 1: Assessment Schedule ARGOS-SC01 
Visit 
SC 
V01 
V02 
V03 
V04 
V05 
V06 
V07 
V08 
V09 
Indicative Days (D) 
Visit window 
Up to 
28 days 
before 
surgery 
D0 
D1 
D3 
- 1/+ 2 
Days 
D10 
+/- 1 
Day 
D30 
+/- 5 
Days 
D90  
+/- 10 
Days 
D180  
+/- 15 
Days 
D270  
+/- 15 
Days 
D360  
+/- 15 
Days 
GENERAL 
Informed consent signed 
X 
 
 
 
 
 
 
 
 
 
Allocation of subject 
number 
X 
 
 
 
 
 
 
 
 
 
Inclusion & exclusion criteria 
X 
X1 
 
 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
 
 
 
Past and current significant 
medical history  
X 
 
 
 
 
 
 
 
 
 
Pregnancy test (urine beta-
hCG) 
X 
X2 
 
 
 
 
 
 
 
 
Non-penetrating glaucoma 
surgery and ARGOS-SC 
pressure sensor 
implantation 
 
X 
 
 
 
 
 
 
 
 
Vision related Quality of Life 
(VQoL) questionnaire 
X 
 
 
 
 
 
X 
X 
 
X 
Visual acuity (ETDRS)3 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Perimetry4 (OU) 
X 
 
 
 
 
 
X 
X 
 
X 
Heidelberg Engineering  
ANTERION® 
 
 
 
 
X 
X 
X 
X 
X 
X 
External eye photography5 
X 
 
 
 
X 
X 
X 
X 
X 
X 
Implantation procedure 
questionnaire (surgeon) 
 
X 
 
 
 
 
 
 
 
 
User acceptance 
questionnaire (patient) 
 
 
 
 
 
 
 
 
 
X 
User acceptance 
questionnaire (investigator) 
 
 
 
 
 
 
 
 
 
X 
Concomitant medication 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
AE/ADE/SAE/SADE 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Device malfunction 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ANTERIOR SEGMENT 
Optical Coherence 
Tomography6 
X 
 
 
 
X 
X 
X 
X 
X 
X 
Slit-lamp biomicroscopy7 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Gonioscopy8 
X 
 
 
 
 
 
X 
X 
 
X 
POSTERIOR SEGMENT 
Slit-lamp biomicroscopy9 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Optical coherence 
tomography (OCT)10 (OU) 
X 
 
 
 
 
 
X 
X 
 
X 
Fundus photography11 
X 
 
 
 
 
 
X 
X 
 
X 

 
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1 Eligibility must be reassessed at V01 prior to surgery. 
2 For females of childbearing potential, a pregnancy test performed within 24 hours preceding surgery must be negative to confirm 
eligibility. 
3 The best corrected visual acuity will be determined after objective and subjective determination of refraction with the ETDRS chart in 
accordance with the ETDRS protocol. 
4 Perimetry is performed to obtain an accurate examination of the peripheral extent of the visual field. Automated perimeters will be 
used either with standard glaucoma field, field 30-2 or equivalent. 
5 External eye photography is performed through a slit lamp camera or equivalent. The outer eye shall be photographed in order to 
document potential changes to the iris or pupil structure. 
6 Anterior segment OCT is performed to evaluate effects on change in chamber angle after non-penetrating glaucoma surgery and to 
assess corneal thickness. 
7 Slit-lamp biomicroscopy is performed through an undilated pupil to assess the following anatomic parameters of the anterior segment: 
lids, conjunctiva, cornea, anterior chamber, iris, pupil, lens and anterior vitreous body. 
8 Standard gonioscopy is used to confirm glaucoma classification and to evaluate the presence of iris tumors, foreign bodies, anterior 
synechiae and to predict the anterior chamber angle. The gonioscopic grading system according to Shaffer is used in this clinical 
investigation. 
9 Posterior segment biomicroscopy is performed by means of indirect ophthalmoscopy on a slit lamp with the aid of a 90D or “Superfield” 
or comparable lenses. For this examination the pupil needs to be dilated by the use of mydriatic agents. This method is used to evaluate 
the following parameters: optic nerve lesions, other posterior pole lesions, vitreous opacities, optic nerve head, fundus lesions, retinal 
arteries and veins (AV), macular area, fundus periphery, normal and abnormal variations of the fundus. 
10 Posterior segment OCT is used to assess macular structures and the peripapillary nerve fiber layer thickness (RNFLT) and if possible 
Minimum rim width at Bruch membrane opening (BMO-MRW). 
11 The fundus should be photographed in order to document potential changes to the optic nerve (cup/disc ratio) and nerve fiber layer 
(red-free illumination). 
12 V02 to V09 IOP measurements will be made in series of 2 GAT measurements (in case of a difference of more than 2 mmHg, a third 
GAT measurement is required) followed by 3 directly consecutive ARGOS-SC system measurements; if DCT is available: V05 to V09 
additionally followed by 2 Pascal DCT measurements (in case of a difference difference of more than 2 mmHg, a third Pascal DCT 
measurement is required) and 3 directly consecutive ARGOS-SC system measurements. 
13 Optional: Patient’s admission at the site for a 24h series of measurements with GAT and ARGOS-SC sensor. Measurements with 
EYEMATE-SC sensor will be done automatically via an externa antenna. GAT will be done every three hours, if it is possible even at 
night. If night measurements are not possible every three hours at night, the last measurement should take place between 22 and 24 
o’clock and the three-hours rhythm should be resumed between 5 and 7 o’clock on the next morning. 
14 All patients will receive a MESOGRAPH reading device after implantation in order to measure the IOP daily at home. Measurements 
will be taken at least 4 times per day (morning, noon, afternoon, evening). The MESOGRAPH reading device will be connected to an 
external GSM module, which will transfer the measured value directly to a secure database. Investigators can log into the database in 
order to track the pressure levels of their patients as required. 
 
Visit 
SC 
V01 
V02 
V03 
V04 
V05 
V06 
V07 
V08 
V09 
Indicative Days (D) 
Up to 
28 days 
before 
surgery 
D0 
D1 
D3 
- 1/+ 2 
Days 
D10 
+/- 1 
Day 
D30 
+/- 5 
Days 
D90  
+/- 10 
Days 
D180  
+/- 15 
Days 
D270  
+/- 15 
Days 
D360  
+/- 15 
Days 
IOP Measurement 
Goldmann Applanation 
Tonometry12 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Pascal Dynamic Contour 
Tonometry12 
X 
 
 
 
 
X 
X 
X 
X 
X 
ARGOS-SC pressure sensor 
measurement12 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
Optional:  
24-hours measurements 
inpatient with GAT and 
ARGOS-SC over 24h13  
 
 
 
 
 
 
X 
X 
 
X 
ARGOS-SC pressure sensor 
self-measurement14 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 

 
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8.3.16 
Visit SC – Screening (Day -28 to 0) 
Only patients who have already agreed to undergo non-penetrating glaucoma surgery will be 
approached by the trial team about participation in the study.  
 
At the screening visit (SC), the Investigator will conduct the informed consent process (Section 12.1), 
ensuring that the subject has signed and received a copy of the patient informed consent (PIC) form 
before any study specific procedures are conducted. Once the PIC is signed, the subject will be assigned 
a patient number (Section 8.3.9) and the Investigator will determine if the subject meets the eligibility 
criteria, surgery (V01) will be scheduled and the sponsor will be informed.  
 
In addition, the following procedures will be performed at the screening visit: 
• 
Collection of background information about the subject including: demographics, medical 
history with prior treatments and current medications and indication for non-penetrating 
glaucoma surgery. 
• 
Pregnancy test, when applicable 
• 
Vision-related Quality of Life (VqoL) questionnaire 
• 
Visual acuity (ETDRS) 
• 
External eye photography 
• 
Anterior Segment assessments (slit-lamp biomicroscopy, AS-OCT, gonioscopy) 
• 
Posterior Segment assessments (biomicroscopy, PS-OCT and fundus photography) 
• 
IOP measurement with GAT and if available DCT 
• 
Instruct subjects on the need to report as soon as possible any SAEs occurring at any time 
throughout the study (starting from Visit 02 surgery) 
• 
Complete the CRF.  
 
8.3.17 
Surgery, Visit 01 (Day 0) 
The following procedures may be carried out up to one day before surgery (in subjects already 
hospitalized for the surgery) or prior to surgery on the day of surgery: 
• 
Verify that the subject continues to meet eligibility criteria 

 
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• 
For female subjects of childbearing potential: collect urine for pregnancy test. A test done 
within 24 hours prior to surgery must be negative 
• 
Perform external eye photography 
 
The following procedures are to be performed on the day of the surgery: 
• 
Updating medical history (up to start of ARGOS-SC implantation)  
• 
Recording of concomitant medications, device deficiencies or malfunctions (including those 
detected during device preparation) and any Aes (starting from the point of inclusion/signing 
of the informed consent) 
• 
Non-penetrating glaucoma surgery and ARGOS-SC pressure sensor implantation (described in 
Section 8.3.12) 
• 
Completion of the implantation procedure questionnaire (surgeon) and the CRF  
• 
Complete the patient inclusion form and fax it to the sponsor 
• 
Instruct subjects on the need to immediately report any SAE that may occur at any time during 
the study. 
• 
Schedule Visit 2 (V02). 
 
The duration of the subject’s hospitalization following surgery is at the discretion of the Investigator. 
Durations of up to 6 days will not be considered to be SAEs.  
 
8.3.18 
Follow-up visits (V02 to V09) 
Procedures to be conducted at the early post-surgical visits include: 
• Recording of Aes/SAEs/ADEs/SADEs, concomitant medications and device malfunctions 
• VqoL questionnaire (V06, V07, V09) 
• User acceptance questionnaire (investigator) (V09) 
• User acceptance questionnaire (patient) (V09) 
• Visual acuity (ETDRS) 
• External eye photography (V04-V09) 
• Heidelberg Engineering ANTERION® (optional V04-V09) 
• Perimetry (V06, V07, V09) 

 
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• Anterior Segment assessments: slit-lamp biomicroscopy, AS-OCT (V04-V06), gonioscopy (V06, 
V07, V09)  
• Posterior Segment assessments: biomicroscopy, PS-OCT (V06, V07, V09), fundus photography 
(V06, V07, V09) 
• IOP Measurement: GAT and ARGOS-SC. Optional, if available V05 –V09 Pascal DCT;  
Optional: 24-hour measurements inpatient with ARGOS-SC and GAT (V06, V07, V09) 
• Instruction of subjects on the use of the MESOGRAPH and Multiline Connector 
• At V02, provide the patient with a MESOGRAPH and Multiline Connector for home-use for the 
rest of the study. Patient should bring both devices to all subsequent visits.  
• Remind subjects to promptly report any SAE that may occur at any time during the study. 
• Complete the CRF and arrange the next visit.  
 
Visit 09 is the study discharge/end of study visit. At this visit, subjects will be informed about the 
planned surveillance registry and asked if they wish to participate (ARGOS-SC01_Follow-up) or they 
will return to standard of care. At the start of the study, all patients enrolled in Switzerland will be 
requested to sign up for an additional follow-up of 2 years. These patients will automatically transition 
to the ARGOS-SC_Follow-up.  
 
9. 
STATISTICS 
9.1 
Statistical design, method and analytical procedures 
The primary purpose of this investigation is to assess the performance of the investigational device.  
9.1.1 
Demographic and baseline characteristics 
Demographic characteristics (age, sex, educational level), lens status, anti-glaucoma medication, and 
other previous and concurrent treatments will be tabulated for the safety set.  
9.1.2 
Subject Disposition 
The number and percentage of screened, enrolled and implanted subjects, as well as those who 
complete the follow-up will be tabulated for the safety set. The number and percentage of screen 
failures and early withdrawals will also be tabulated, along with the reason for the screen failure or 
drop-out. 

 
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9.1.3 
Safety Analysis 
The incidence and nature of adverse events observed within the safety population will be analyzed by 
descriptive and explorative statistical methods. 
Safety will be described in detail by frequency, seriousness, severity, nature and duration of events.  
 Number of adverse events as well as the number and relative frequency of patients reporting adverse 
events will be tabulated by system organ class and preferred terms. The same table will be prepared 
for serious adverse events. In addition, the number and relative frequency of patients reporting 
adverse events will be tabulated by system organ class and preferred terms in dependence on the 
worst severity and worst causal relationship. Furthermore, number of adverse device effects as well 
as the number and frequency of patients reporting adverse device effects will be tabulated by system 
organ class and preferred terms and not by event description as stated in the protocol. 
 
9.1.4 
Performance Analysis 
The probability distribution of the difference of the paired measurements grouped within 1 mmHg will 
be compared to the primary objective of the accepted 70% of the measurements to agree between 
+/- 5 mmHg. 
 
9.2 
Sample Size Calculation 
The sample size calculation was based on the study’s dual purpose of establishing safety and 
comparability of IOP measurements with the ARGOS-SC system to those made with GAT and DCT. IOP 
measurements will be made with all devices at various time points, resulting in a within individual 
control for IOP variables. Based on these calculations (performance, safety) and considering possible 
drop-outs, the exploratory investigation will enroll 24 patients. The minimum number of 
measurements required to hold the performance claim is approx. 120. With multiple (>8) 
measurements with either method (ARGOS, GAT) per patient, a sufficient number of paired 
measurements (in total >>120 measurement pairs) will be available to show equivalence of the 
methods (primary objective)[2]. 
 
 

 
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9.3 
Level of significance and the power of the clinical investigation 
Significance level is set to 0.10, Power to 80%. 
9.4 
Expected drop-out rates 
The drop-out rate for this study following implantation is expected to be low. The ARGOS-SC is 
intended to remain in situ and the patient population generally requires close follow-up care by the 
ophthalmologist. Subjects who do not undergo implantation of an ARGOS-SC will be replaced. 
9.5 
Pass/fail criteria to be applied to the results of the clinical investigation 
This investigation will be considered a success if no more than one of the 24 patients experiencing 
SADEs during the follow-up period (SADEs evaluated by DSMB) and if 70% of the measurements agree 
between +/- 5 mmHg (limits of agreement from GAT and ARGOS-SC measurements are between +/- 5 
mmHg). 
9.6 
Interim analysis 
One interim analysis is planned for this study. It will take place when all patients have completed the 
first 6 months of the follow-up period.  
9.7 
Criteria for termination of the clinical investigation  
The participation of an individual site in the study will be discontinued if the sponsor, the investigator 
or the responsible ethics committee deems it necessary for any reason. 
 
The complete study will be discontinued: 
• 
If the sponsor and/or any responsible regulatory authority or ethic committee judges it 
necessary for any reason. See also Section 8.3.3 Discontinuation or Withdrawal Criteria Early 
Patient Withdrawal and Section 12.11 Criteria for Suspension and Premature Termination of 
Study 
• 
If, throughout the course of the study, the DSMB comes to the conclusion that further 
implantation of the ARGOS-SC pressure sensor would subject study patients to undue risk 
 
Patients who already have an ARGOS-SC pressure sensor implanted by the time of premature 
termination will continue to be followed up.  If the study is discontinued for safety reasons it will be 

 
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proven whether explantation of all ARGOS-SC sensors deems necessary or follow-up of patients is 
sufficient. 
9.8 
Procedures for reporting of deviations from the original statistical plan 
Significant deviations from the original statistical analysis plan will be listed and clarified in the final 
clinical investigation report. 
9.9 
Specification of Subgroups for Analysis 
In order to permit investigation of their impact on performance and safety, information will be 
collected prospectively on the following variables: 
• 
Gender 
• 
Post-surgical complications 
• 
Successful implantation 
• 
Age groups  
• 
Country of investigational site 
• 
Educational level 
• 
Medical 
History 
(primary 
underlying 
ophthalmic illness or injury necessitating 
the non-penetrating glaucoma surgery) 
• 
Pre-treatment  
• 
Concomitant medications 
 
Which subgroup analyses are actually performed will be decided at a final data review meeting 
preceding the statistical analysis, based on the actual distribution of subjects in the study population. 
9.10 
Treatment of missing, unused and spurious data, including drop-outs and 
withdrawals 
All data of the patients will be used as available. All analyses will be performed on observed cases only. 
Missing data will not be replaced. Implausible values will be only excluded from the analysis if 
reasonable. The reason for exclusion will be given in the footer of the table or description of the figure. 
Patients terminating the trial prematurely due to whatever reason will be evaluated like any patient 
completing the trial as per protocol, within the analysis sets they qualify for. 
Subjects who dropped out during a scheduled visit will be counted for that visit. 

 
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9.11 
Datasets to be analyzed 
9.11.1 
Safety set 
The safety population comprises all subjects for whom ARGOS-SC pressure sensor implantation was 
attempted, defined as introduction of the ARGOS-SC pressure sensor into the eye, whether or not the 
implantation was successful. 
9.11.2 
Per protocol set 
The Per Protocol Set (PPS) will comprise all subjects in whom an ARGOS-SC pressure sensor was 
successfully implanted and for whom the full data set including IOP measurements made in the clinic 
and safety data according to protocol are available until 3 months (V06) after surgery. Because IOP 
measurements conducted outside the clinic will be made at varying times under varying conditions, 
they are not anticipated to be comparable to those made in the clinic and will not be included in the 
Per-Protocol evaluation of agreement. 
 
Additional information about the drop-outs: all subjects who revoke their consent and agreement 
preoperatively will be regarded as screen failures and will not be included in the statistical evaluation. 
All subjects who revoke their consent and agreement postoperatively will be considered withdrawals. 
Unless the subject also withdrew consent to use their data, they will be evaluated in the safety analysis. 
9.12 
Number of subjects at each site 
It is planned to enroll an approximately equal number of subjects at each site. Due to the small sample 
size a stratified design / analysis will not have the power to detect center specific treatment effects.  
10. 
DATA MANAGEMENT 
10.1 
Site Monitoring 
The study will be monitored in compliance with the Declaration of Helsinki, ISO 14155, the Clinical 
Investigation Plan (CIP) and all applicable national and local regulations. All monitoring activities will 
be conducted by trained and qualified monitors, who will document each individual monitoring visit. 
In general, during monitoring visits the monitor will ensure that the study is being conducted according 
to the CIP, ISO 14155, ICH GCP (International Conference on Harmonisation Good Clinical Practice) and 
other applicable regulations, and will compare the CRF entries to original source data. He/she will also 

 
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make sure the informed consent procedure has been appropriately carried out and will ensure that all 
SAEs have been reported within applicable timeframes. He/she will also ensure that investigational 
device accountability has been maintained and will, after completion of the study, perform final 
accountability and arrange return or destruction of investigational products. For each patient lost to 
follow-up, the monitor will verify if the study center’s attempted contacts with the patient, followed 
by contacts with the patient’s family doctor, were adequate. 
Detailed monitoring procedures will be described in a separate monitoring plan. 
10.2 
Data collection 
Data will be collected through a Case Report Form (CRF) provided by the sponsor or its designee to the 
centers prior to study start. Designated site staff will enter study data in the CRF during or as soon as 
possible after the visit (within 3 days at the latest).  
10.3 
Database Management and Quality Control 
The investigator is responsible for maintaining accurate, complete, and up-to-date records for each 
subject. This includes maintaining any source documentation related to the study. The privacy of 
participating subjects must be maintained. The sites will maintain a list of the subjects´ names and the 
Patient ID assigned to each individual subject. Subjects will not be identified except by Patient ID on 
any document submitted to the sponsor. All documents that could identify the subject beyond the 
Patient ID (e.g. the signed informed consent document) must be maintained in strict confidence by the 
investigator, except to the extent necessary to allow inspections by the regulatory authorities and 
audits by the study monitor or sponsor representatives. 
 
The investigator must review the completed CRFs for each subject and must confirm the accuracy of 
all data entered with his/her signature at the end of each documented subject’s visit in the CRF within 
3 days. Any corrections made to data entries will be GCP conform. 
 
During data review, data management will generate queries for any missing, out of range or 
questionable data and send those to the investigator for resolution. The physician will answer the 
query and this answer will be documented. All queries must be answered and the database locked 
before any (interim) analysis of the data may begin. 

 
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10.4 
Verification, validation and security of electronic data system 
The sponsor will verify that only validated and secure electronic data systems will be used in this clinical 
investigation. Electronic data systems include the clinical data management database and the 
ARGOS-SC system measurement database. Database validation and security follow the respective 
national and international requirements. 
10.5 
Data retention and Retention period 
10.5.1 
Investigator Records Retention 
All study documents must be retained by the investigator for a period of at least 15 years after 
completion of the study. The investigator at each investigational site must maintain adequate records 
of the clinical study, including: 
• Completed case report forms 
• Medical records 
• Signed informed consent forms 
• Product accountability 
• Shipment and receipt records  
• Adverse Events reports  
• All correspondence between the Investigator and the Ethics Committee, Regulatory 
Authorities, the sponsor and the CRO  
• Any other pertinent data relevant to the study 
 
The investigator must obtain written permission from the sponsor before destroying any study specific 
documentation. Hospital records will be archived according to local regulations. 
10.5.2 
Sponsor Records Retention 
The sponsor will maintain the following records for at least 15 years after the last device has been 
manufactured or until the company ceases to exist: 
• All correspondence pertaining to the investigation 
• Signed and dated Investigator Agreements and signed and dated investigator curriculum vitae 
that were current at the time of the study 
• Copies of all EC approval letters, the EC review and approval procedures, and relevant EC 
correspondence  

 
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• Names and addresses of the institutions where the clinical investigation was conducted, as 
well as records of approval from site administration 
• Correspondence with authorities as required by national legislation 
• Insurance certificates 
• Adverse Events report forms 
• Names/contact addresses of monitors 
• Statistical analyses and underlying supporting data 
• Final and all interim reports of the clinical investigation 
• Study training records for site personnel and sponsor/CRO personnel. 
• Quality assurance 
 
To assure accurate, complete and reliable data, the sponsor or its representatives will do the following: 
• Provide instructional material to the investigational sites as appropriate 
• Perform a detailed initiation visit to instruct and train the investigational site personnel 
concerning the investigational device and all relevant study procedures 
• Perform regular monitoring visits at the investigational sites 
• Be available for consultation and stay in contact with study site personnel by mail telephone 
and fax 
• Review and evaluate CRF data on a regular basis 
• Conduct assessment of the site’s electronic patient database. 
 
In addition, the sponsor or its representatives may periodically check a sample of subject data recorded 
against source documents at the study site. 
To ensure the safety of study subjects, and to ensure accurate, complete, and reliable data, the 
investigator will keep records of clinical notes and subject medical records in the patient files as original 
source documents for the study. If requested, the investigator will provide the sponsor, applicable 
regulatory agencies, and applicable ethical committees with direct access to original source 
documents. 
 
The study may be audited by the sponsor or its representatives at any time. Such an audit will be 
conducted according to a specific audit plan. Investigators will be given notice before an audit occurs. 

 
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The regulatory authorities, both national and foreign, may inspect the study site at any time. The 
investigator is responsible for notifying the sponsor of such an inspection immediately upon gaining 
knowledge of it. During the audit or inspection, the investigator/institution will permit the auditor, and 
regulatory inspector(s) direct access to all relevant medical records and other source data, study 
related files and CRFs. 
11. 
ADVERSE 
EVENTS, 
ADVERSE 
DEVICE 
EFFECTS 
AND 
DEVICE 
DEFICIENCIES  
11.1 
Definitions 
The following definitions are taken from Global Harmonization Task Force Document GHTF/SG5/N5, 
and are based on ISO 14155 and MEDDEV 2.7/3. 
11.2 
Adverse Event (AE) 
An Adverse Event (AE) is defined as any untoward medical occurrence, unintended disease or injury, 
or untoward clinical signs (including abnormal laboratory findings) in a subject, whether or not related 
to the investigational medical device 
NOTE 1: This definition includes events related to the investigational medical device. 
NOTE 2: This definition includes events related to the procedures involved. 
NOTE 3: For users or other persons, this definition is restricted to events related to investigational 
medical devices. 
11.2.1 
Adverse Device Effect (ADE) 
Any Adverse Event (AE) that is related to the use of the investigational medical device is defined as 
Adverse Device Effect (ADE). 
NOTE 1: This definition includes adverse events resulting from insufficient or inadequate instructions 
for use, deployment, implantation, installation, or operation, or any malfunction of the 
investigational medical device. 
NOTE 2: This definition includes any event resulting from use error or from intentional misuse of the 
investigational medical device. 
11.2.2 
Serious Adverse Events (SAE) 
A Serious Adverse Event (SAE) is defined as any Adverse Event that: 

 
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1. Led to death 
2. Led to a serious deterioration in the health of a subject that: 
a) Resulted in a life-threatening illness or injury 
b) Resulted in a permanent impairment of a body structure or body function 
c) Required in-patient hospitalization or prolongation of existing hospitalization 
d) Required medical or surgical intervention to prevent permanent impairment to body 
structure or a body function 
3. Led to fetal distress, fetal death or a congenital abnormality or birth defect  
NOTE: An Adverse Event is considered ‘Serious’ if any one of the conditions 1, 2, or 3 applies in 
combination with serious deterioration in health (e.g. a pre-planned hospitalization for a 
pre-existing condition, without a serious deterioration in health, is not considered to be a SAE). 
NOTE for Germany: In Germany the term SAE is defined according to §2 Section 5 MPSV [Medical 
Devices Safety Plan Ordinance]: For the purposes of this Regulation, 'serious adverse event' 
means any unintended event occurring in a clinical trial which has led, may have led or may 
lead, directly or indirectly, to the death or serious deterioration in the state of health of a 
subject, user or other person, without taking into account whether the event was caused by 
the medical device. 
11.2.3 
Serious Adverse Device Effect (SADE) 
An Adverse Device Effect that has resulted in any of the consequences characteristic of a SAE. 
11.2.4 
Anticipated Serious Adverse Device Effect (ASADE) 
A Serious Adverse Device Effect (SADE) which by its nature, incidence, severity or outcome has been 
identified in the risk analysis report is defined as an Anticipated Serious Adverse Device Effect (ASADE).  
11.2.5 
Unanticipated Serious Adverse Device Effect (USADE) 
A Serious Adverse Device Effect (SADE) which by its nature, incidence, severity or outcome has not 
been identified in the current version of the risk analysis report is defined as an Unanticipated Serious 
Adverse Device Effect (USADE). 
11.2.6 
Device Deficiency 
An inadequacy of a medical device with respect to its identity, quality, durability, reliability, safety or 
performance is defined as a Device Deficiency. 
NOTE: Device Deficiencies include malfunctions, use errors, and inadequate labeling. 

 
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11.3 
Recording of Adverse Events (AEs) 
All AEs will be documented throughout the clinical trial as per ISO 14155, chap. 6.4.1, meaning from 
the point of inclusion/signing of the informed consent, until resolution or stabilization, or for a 
maximum of 7 days after the last subject has been discharged from the study.  
 
All AEs will be reported on an Adverse Event Form, one for each Adverse Event, which is part of the 
CRF.  
AEs will be collected with a non-leading question at each visit: “Have you had any new or worsening 
health problems since the last visit?” as well as by reporting those events directly observed and 
spontaneously reported by the subject. Clearly related signs, symptoms and abnormal diagnostic 
procedures should preferably be grouped together and recorded as a single diagnosis or syndrome 
whenever possible. Seriousness, severity (mild, moderate or severe), outcome and relationship to 
investigational device as well as expectedness and action taken will be recorded in the AE page of the 
CRF. Start and end date and time of the event will also be recorded. SAEs will be followed until 
resolution or stabilization. AEs will be followed until resolution or stabilization, or for a maximum of 7 
days after the last subject has been discharged from the study. 
11.3.1 
Seriousness 
Seriousness will be recorded as described in Section 11.2.2. 
11.3.2 
Intensity/Severity 
Severity of AEs will be assessed according to the following definitions: 
• Mild: sign or symptom of the AE is apparent but is easily tolerated by the subject 
• Moderate: the AE interferes somewhat with the subject’s usual activities (disturbing)  
• Severe: the AE prevents the subject from working or performing his/her usual activities 
(unacceptable).  
Note: Severity is not seriousness. An AE may be severe but not serious, as in a severe headache, while 
an SAE may be mild, as in a mild myocardial infarct. 
11.3.3 
Relationship to study device 
Assessment of causality is based on the following considerations: associative connections (time and/or 
place), pharmacological or physical explanations, previous knowledge of the device, presence of 

 
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characteristic clinical or pathological phenomena, exclusion of other causes, and/or absence of 
alternative explanations. 
 
The investigator will assess causal relationship to the investigational device according to following 
classifications: 
• None: The time course between use of the device and occurrence or worsening of the AE rules 
out causal relationship; and/or another cause is confirmed and no indication for involvement 
of the study device in the occurrence/worsening of the AE exists 
• Unlikely: The time course between use of the device and occurrence/worsening of the AE 
makes causal relationship unlikely; and/or the known effects of the device provides no 
indication for involvement of the study device in the occurrence/worsening of the AE; and/or 
although it is conceivable based on previous knowledge that study device may have causal 
relationship to occurrence/worsening of the AE, another cause is much more probable; and/or 
another cause is confirmed and involvement of the study device in the occurrence/worsening 
of the AE is unlikely 
• Possible: It is conceivable based on previous knowledge that study device may have causal 
relationship to the occurrence/worsening of the AE but other factors exist that are equally 
likely to be causative factors; or although the previous knowledge on study device does not 
provide any support for causal relationship, no other possible causative factors exist. 
• Probable: Time relationship exists and previous knowledge about the study device supports a 
causal relationship although another cause cannot be ruled out. 
• Definite: The criteria for probable relationship are fulfilled and no other possible causative 
factors exist. 
11.3.4 
Action taken 
The investigator will document the action taken in relation to the investigational device and to other 
treatments. The categories in relation to the investigational device are: 
• No action taken 
• Device removed 
• Subject withdrawn from the study 
• Other, specify 

 
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The categories in relation to other treatments are: 
• No action 
• Medication given (must be specified in the concomitant medication page) 
• Non-medication treatment given (must be specified) 
• Hospitalization 
• Other, specify 
 
11.3.5 
Outcome  
The investigator will document the outcome by choosing one of the following alternatives: 
• Recovered 
• Recovered with sequelae 
• Recovering 
• Death 
• Unknown. 
 
11.4 
Reporting of Serious Adverse Events (SAEs)  
The site must report the following events to the sponsor immediately after becoming aware of them:   
1. Any SAE affecting a subject, regardless of its relationship to the device or the study-procedures 
(beginning with the implantation of the ARGOS-SC sensor) 
2. A SADE affecting a user or third party (all) 
3. A device deficiency that might have led to an SAE involving a subject, user or third party if 
suitable action or intervention had not been taken or if circumstances had been less fortunate 
(all) 
If the site is uncertain as to whether an event is an SAE, they should report it to the sponsor as if it 
were. 
 
The sponsor will report SAEs to the Competent Authority in accordance with ISO 14155, Annex X of 
Directive 93/42/EEC, its amendment Directive 2007/47/EC, Annex 7 of Directive 90/385/EEC, MEDDEV 
2.7/3, the German Ordinance on Medical Device Vigilance (MPSV) and applicable local laws and 

 
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regulations. Reporting modalities defined in the MPSV and MEDDEV 2.7.3 will be followed. All SAEs 
will be documented completely. SAEs for which a relationship to the study device or diagnostic or 
therapeutic procedures performed as part of the clinical trial or other conditions of the trial cannot be 
excluded will be reported to BfArM immediately using the SAE report form found on the BfArM 
website.  A summary report for all other SAEs will be submitted to BfArM every three months or as 
requested by BfArM using the SAE summary table from MEDDEV 2.7.3. 
 
Information reported on the SAE shall include: 
• 
The date the event was reported to the sponsor 
• 
The country  
• 
Site and Patient ID  
• 
The date the subject underwent implantation with the study device 
• 
The date of event onset  
• 
The affected organ system 
• 
A description of the event 
• 
Actions, treatments and patient outcome as a result of the event  
• 
The date the event was first noticed by or reported to the investigator 
• 
An assessment of the relatedness of the event to the procedure  
• 
An assessment of the relatedness of the event to the device  
• 
The expectedness of a SADE  
• 
The event status  
• 
The date of event resolution 
 
Initial SAE reporting may be done by telephone or email, followed by the completed SAE form. Contact 
information is given on each SAE form and is available in the Investigator Site File. 
 
All Adverse Events will be documented in the source documents and reported on the Adverse Event 
form in the CRF in a timely manner after the investigator first learns of the event. 
 

 
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Regulatory authority and ECs will be informed about SAEs according to local regulations as described 
in Table 2. 
 
Table 2: SAE reporting requirements 
Reporting 
Party 
Reports to 
Causal Relationship to 
Study Devices or 
Procedures 
Reporting Timeline 
Reporting Method 
Investigator 
Sponsor 
All SAEs, regardless of 
relationship 
Immediately upon 
learning of the event 
SAE Report Form 
Sponsor 
 BfArM 
Relatedness cannot be 
excluded 
Immediately upon 
learning of the event 
Submission of  
SAE report form for 
single events  
(BfArM website) 
Relatedness can be 
excluded 
Summary report 
every 3 months or as 
otherwise requested 
by BfArM 
Submission of 
MEDDEV 2.7.3 Summary 
Table 
 
11.5 
Recording and Reporting of Device Deficiencies  
The investigator will record all observed device deficiencies by completing a Device Deficiency Form. 
The reporting modalities are defined in ISO 14155 and MEDDEV 2.7/3 in line with the requirements of 
Annex X of Directive 93/42/EEC and its amendment Directive 2007/47/EC, Annex 7 of 90/385/EEC and 
local laws and regulations. 
All device deficiencies must be reported to the sponsor as soon as possible. Any Investigational Medical 
Device Deficiency that might have led to a SAE if a) suitable action had not been taken or b) 
intervention had not been made or c) if circumstances had been less fortunate must be reported as 
described in Table 2 following the SAE reporting modalities. 
 
Any adverse device effect causing injury with the nature of a SADE to a person other than a study 
subject must be reported to the sponsor in accordance with the SAE reporting procedure.  
11.6 
Medical Care 
The medical care of the subject is at the discretion of the investigator at all times. Following the study, 
the subjects will return for standard control visits as needed. 

 
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11.7 
Safety Monitoring 
A Data Safety Monitoring Board (DSMB) will be established prior to enrollment of the first patient. The 
DSMB will review the safety data on a regular basis and will advise on any changes required in the 
conduct of this clinical investigation. The DSMB will consist of 2-4 independent clinicians with expertise 
in the treatment of glaucoma who are not otherwise involved in the study and will be designated to 
review safety related issues including reported SAEs/SADEs on a frequent basis and advise the sponsor 
on any changes required to the conduct of the study. It is anticipated that these clinicians may come 
to one of three types of binding recommendations, namely: 
1. 
Continue the study as planned --No safety issues exist and it is ethical and feasible to continue 
the study as planned. 
2. 
Continue the study with protocol amendments – Ethical to continue the study but recommend 
an amendment to the protocol (e.g. incorporate additional or more frequent safety 
examinations). 
3. 
Stop enrollment and treatment -- Sufficient evidence for a serious safety concern exists, 
making further implantation of ARGOS-SC pressure sensors in subjects unethical. 
11.8 
Sponsor Responsibilities 
The Sponsor is responsible for reporting Serious Adverse Events, interim or annual safety reports, 
premature termination or suspension of the clinical investigation, and the final Study Report to 
Regulatory Authorities, the ECs and investigators. Refer to Table 2 and Table 3 for details.  

 
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Table 3: Sponsor Reporting Responsibilities 
Reporting Responsibility 
Reports to 
Description 
Serious Adverse Events 
(SAEs) 
Regulatory Authorities, 
ECs 
See Section 11.2.2 for details 
Interim or annual safety 
reporting 
ECs and/or CA per local 
regulations 
An interim or annual safety report may be required 
by country regulations, or may be specifically 
requested by the EC/CA 
Premature termination or 
suspension of the clinical 
investigation 
Investigators, ECs, 
relevant Regulatory 
Authorities 
Provide prompt notification of termination or 
suspension and reasons.  
GERMANY: According to MPG §23a, Abs. 1, the 
Sponsor is required to notify BfArM of the completion 
of the clinical investigation within 90 days after close-
out. 
GERMANY: According to MPG §23a, Abs. 2, the 
Sponsor is required to notify BfArM of the premature 
termination of the clinical investigation within 15 
days after termination. 
Final Study Report 
Investigators, ECs, 
relevant Regulatory 
Authorities 
The sponsor will notify the investigators of the 
completion or termination of the study. A Final Study 
Report will be submitted to the investigators and the 
ECs following local regulations. Germany: According 
to MPG §23a, a CIR has to be submitted to BfArM 
within 12 months completion or premature 
termination of the clinical investigation. 
12. 
ADMINSTRATIVE PROCEDURES AND RESPONSIBILITIES 
12.1 
Informed Consent 
Eligible patients may only be included in the study after providing written informed consent as 
approved by the responsible ethic committee. The Patient Informed Consent (PIC) form must be fully 
signed and dated prior to any study related activities required by the CIP (including any diagnostic 

 
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testing, questionnaires, or other study-related procedures). Failure to obtain signed informed consent 
renders the patient ineligible for the study. 
 
A proposed PIC that complies with the ISO 14155 standard and is considered appropriate for this study 
will be submitted to the Ethics Committees. The PIC will be translated into the local language of each 
country in which the study will be conducted and will contain language that is non-technical and 
understandable to the patient. Any changes to the PIC suggested by the investigator must be agreed 
to by Implandata Ophthalmic Products GmbH before submission to the EC and a copy of the EC 
approved version must be provided to the monitor after EC approval. 
 
The Investigator or designated sub-investigator must explain the study to the patient in detail, talking 
through all points described in the PIC. The patient must be given the opportunity to ask questions and 
ample time to consider his/her participation. The patient will also be informed of his/her right to 
withdraw from the study at any time without giving a reason. If the patient is willing to participate in 
the study, he/she must sign and date two copies of the PIC, which must also be signed and dated at 
the same time by the investigator or designated sub-investigator who explained the study.  
 
One copy of the PIC will be given to the patient and the other will be retained in the Investigator Site 
File (ISF). 
 
Subject information and the PIC will be revised if new information becomes available or a CIP 
amendment is issued regarding patient safety, study procedures or any aspects of the study that could 
potentially influence a subject’s willingness to continue in the study. After the new subject information 
documents have been approval by EC and regulatory authorities, the subject will be informed of the 
changes and will be asked to sign the new consent form to confirm his/her continuation in the study. 
The investigator is to ensure that the subject is informed in a timely manner about any new safety-
relevant information that could affect the subject’s willingness to continue in the study and agrees to 
request the subject’s consent again, if necessary. 
12.2 
Vulnerable Subjects 
Only mentally competent subjects will be enrolled in this study.  

 
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12.3 
Regulatory and Ethical Compliance 
This clinical study was designed and shall be implemented and reported in accordance with ISO 
14155:2011, with applicable local laws and regulations, and with the ethical principles laid down in the 
Declaration of Helsinki and described in the ICH-GCP guidelines. 
12.4 
Approval from Ethics Committee or Regulatory Authority 
The Clinical Investigation Plan (CIP) and the proposed PIC must be reviewed and approved by a properly 
constituted Ethics Committee (EC) before the start of the investigation. A signed and dated statement 
from the EC that the CIP and PIC have been approved by the EC must be given to Implandata 
Ophthalmic Products GmbH before study initiation. 
 
The study must be reviewed and approved by the responsible Regulatory Authorities (RA) before study 
initiation, according to local and national regulations, if required. When an approval process is not 
required by the Regulatory Authority at least a notification shall be performed. Any additional 
requirements imposed by the EC or Regulatory Authority will be followed. 
 
If any alterations, other than changes of an administrative nature only, are made to the study CIP, a 
formal CIP amendment will be issued and submitted to the relevant EC and RA for approval. The 
amendment will not be implemented until EC and RA approval, except in cases where immediate 
implementation is necessary to eliminate or prevent imminent hazard to the subjects. 
12.5 
Investigator Responsibilities for Ethics Committees and Regulatory Authorities 
Prior to study start, the investigator is required to sign a CIP signature page confirming his or her 
agreement to conduct the investigation in accordance with all of the instructions and procedures 
found in this CIP and associated documents and to give access to all relevant data and records to 
Implandata Ophthalmic Products GmbH, monitors, auditors, Quality Assurance representatives, 
designees, Ethics Committees, and regulatory authorities as required. If an inspection of the 
investigational site is requested by a regulatory authority, the investigator must immediately inform 
Implandata Ophthalmic Products GmbH that this request has been made. 

 
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12.6 
Reporting responsibilities 
12.6.1 
Investigator Reporting Responsibilities 
The investigator or designee is responsible for completing (including review and signature) and 
submitting to the sponsor all case report forms, as well as reports of any AEs (according to country-
specific collection requirements), deaths or deviations from the clinical investigation plan. If any action 
is taken by the EC with respect to the investigation, the investigator will forward the information to 
the sponsor as soon as possible. Reports are subject to inspection and to the retention requirements 
as described in Section 11.3. Refer to Tables Table 2 and Table 3 for SAE reporting responsibilities. 
12.6.2 
Sponsor Reporting Responsibilities 
The sponsor is responsible for reporting SAEs, interim or annual safety reports, premature termination 
or suspension of the clinical investigation, and the Final Study Report. Refer to Table 3 for details. 
12.7 
Insurance  
The sponsor will maintain appropriate clinical trial liability insurance coverage as required under 
applicable laws and regulations and will comply with applicable local law and custom concerning 
specific insurance coverage. If required, proof of the clinical trial insurance policy will be provided to 
the Ethics Committee. If required by national regulations, indemnification will be provided. 
12.8 
Amendments to the CIP 
The sponsor will inform the investigator about any relevant changes to the CIP. Changes will be 
documented as an amendment to the CIP that will be signed by each investigator. Unless required to 
prevent harm to a subject, no changes to the CIP may be implemented by the investigator before a 
fully approved amendment is available. If applicable due to the nature of the amendment and in 
accordance with local regulations, EC and RA notification and/or approval is also required before the 
amendment is implemented.  
 
The investigator is expected to take any immediate action required to ensure the safety of any subject 
included in this study, regardless of any need for approval of formal CIP amendments, even if this 
action represents a deviation from the CIP. In such cases, the sponsor should be notified of this action 
promptly and the Ethics Committee responsible for the study site should be informed. 

 
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12.9 
Recording, Reporting and Analysis of CIP Deviations  
Deviations will be documented in writing and maintained in the Investigator Site File (ISF) and Trial 
Master File (TMF). The site will report all deviations, regardless of whether medically justifiable or 
taken to protect the subject in an emergency, to the sponsor in a timely manner on a protocol deviation 
form. In addition, the investigator is required to adhere to the Ethics Committee procedures for 
reporting deviations.  
 
Deviations include, but are not limited to the following list: 
• 
Failure to obtain informed consent prior to conducting study specific activities  
• 
Incorrect version of the PIC used 
• 
Subject did not attend treatment visit, or visit was outside the required timeframe 
• 
CIP-required testing and/or measurements were not done or were done incorrectly  
• 
SAEs or SADEs were not reported by investigators within the required timeframe as specified 
in the CIP 
• 
Source data permanently lost 
• 
Pregnancy of a subject 
 
A sponsor representative or monitor will review site compliance with regard to deviations at each 
monitoring visit. The monitor will discuss any deviations that occurred at the investigational site 
directly with the investigator and will summarize the findings in a follow-up letter to the site. In 
addition, all deviations from the CIP will be documented in the final study report. 
12.10 
Corrective and preventive action and principal investigator disqualification criteria 
See section 12.9 Recording, Reporting and Analysis of CIP Deviation. After analyzing and taking 
corrective actions, site personnel will be retrained by the sponsor or its representatives on the relevant 
study procedures. All necessary measurements will be taken to prevent re-occurrence of the protocol 
deviation. If an investigational site continues to deviate from the CIP despite retraining, the site will be 
discontinued from the study. 
12.11 
Suspension or Premature Termination 
The sponsor may temporarily or permanently discontinue the study at a single site or at all sites for 
safety, ethical, compliance or other reasons. If it is necessary to discontinue the study, the sponsor will 

 
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endeavor to provide advance notification to the site. If the study is suspended or discontinued, the 
investigator or the sponsor will be responsible for promptly informing the ethics committee. The 
monitor will visit the site to conduct a study site closure visit. 
12.12 
Criteria for access to a breaking/masking code in the case of suspension or 
premature termination of the clinical investigation, if applicable 
This is an open-label study and will not be masked. 
12.13 
Subject follow-up requirements 
All pregnancies will be followed up to birth. All on-going AEs will be followed-up until resolution or 
until 7 days after the last subject has been discharged from the study. All SAEs will be followed-up until 
resolution or stabilization. 
12.14 
Investigator and Site Selection 
Site selection will be based on the site’s experience with and access to patients requiring non-
penetrating glaucoma surgery. Sites need to meet the following criteria: 
• Compliance: 
§ Willing to comply with the Clinical Investigation Plan (CIP), all required procedures, the 
Declaration of Helsinki, ISO 14155 and national and local regulations 
• Expertise  
§ Investigator experienced in performing non-penetrating glaucoma surgery and in the 
care of glaucoma patients 
§ Access to the patient population  
• Patient recruitment potential 
§ Potential of 2 - 8 subjects in the given timeline 
§ Patient enrollment and site commitment not expected to be impacted by any competing 
studies 
• Clinical support staff  
§ Study nurse/assistant/coordinator or equivalent with adequate training and time to 
perform study administration including data entry 
• Time investment 
§ Sufficient availability of the investigator to fulfill the study requirements, including 
reporting and attendance at the study meetings. 

 
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• Equipment / Procedures 
§ Separate rooms to perform study procedures 
§ Sufficient, lockable storage capacities for study materials 
13. 
PUBLICATION POLICY 
13.1 
Study Report and Publication 
The sponsor is responsible for generating a Clinical Investigation Report (CIR) for the study after the 
study is completed. This report, or parts of it, will be submitted to the relevant authorities as 
applicable. 
 
A CIR will be submitted to BfArM within 12 months after completion or premature termination of the 
clinical investigation in accordance with the German MPG §23a.  See Table 3 in section 11.8 for further 
details. 
13.2 
Publication of Study Results 
The publication of study results will be agreed between the sponsor and the investigator(s). The 
sponsor is interested in publishing the results of the study, but to prevent publication of any 
confidential information, the sponsor retains the right to review all publications and presentations 
before they are made public. 
13.3 
Registration in a Clinical Trial Database 
The investigation will be registered in a clinical trial database such as clinicaltrials.gov prior to the 
start of enrollment. Following finalization of the final report, a summary of the investigation results 
will also be publicized on the database. 
 
 

 
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