XEN 45 Gel Stent: Long Term Performance and Safety Assessment (XEN LT)
Conditions: Glaucoma
Sponsor: Allergan

NCT03868254 
 
Study ID: CMO‐MA‐EYE‐0590 
 
 
Title:  XEN 45 Gel Stent: Long Term Performance and Safety Assessment (XEN LT) 
 
Protocol Date:17Sept2018 
 
 
 

CONFIDENTIAL - Allergan 
 
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Retrospective Observational Study Protocol 
Study No 
CMO-MA-EYE-0590 
ClinicalTrial.gov Registration Number 
Not yet registered 
Product 
XEN® 45 Gel Stent 
Product reference 
 
Study Title 
XEN 45 Gel Stent: Long Term Performance and 
Safety Assessment (XEN LT) 
Clinical Phase 
Post-market clinical follow-up study 
Study Sponsor 
Allergan Pharmaceuticals International Limited 
Clonshaugh Industrial Estate, 
Coolock, 
Dublin D17 E400, Ireland 
Date of Protocol 
17 Sep 2018 
Amendment 
Not Applicable 
Version History 
Protocol V1.0  
17 Sep 2018 
Confidentiality: This protocol is the property of Allergan and may not – in full or in part – be transferred, 
reproduced, published, or otherwise used without the express permission of Allegan. 

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Table of contents 
Table of contents .............................................................................................................. 2 
List of Tables .................................................................................................................... 5 
List of Figures .................................................................................................................. 5 
1 
SYNOPSIS ................................................................................................................... 6 
2 
LIST OF ABBREVIATIONS ......................................................................................... 11 
3 
Study Milestones and Timelines ................................................................................ 12 
4 
Amendments and Updates ........................................................................................ 13 
5 
INTRODUCTION ........................................................................................................ 13 
5.1 Background ...................................................................................................... 13 
5.2 Study Rationale ................................................................................................ 14 
6 
OBJECTIVES AND OUTCOME VARIABLES ................................................................... 15 
6.1 Objectives ........................................................................................................ 15 
6.1.1 
Primary objective .................................................................................... 15 
6.1.2 
Secondary objective ................................................................................ 15 
6.2 Key Variable Definitions ................................................................................... 15 
6.3 Outcome Variables ........................................................................................... 15 
7 
STUDY CONDUCT ...................................................................................................... 17 
7.1 Overall Design of the Study .............................................................................. 17 
7.2 Data Collection Periods .................................................................................... 18 
7.3 Patient Discontinuation, Site Termination or Study Termination ...................... 19 
7.3.1 
Withdrawal of Individual Patients Prior to Study Completion .......................... 19 
7.3.2 
Study or Study Site Termination ............................................................... 19 
8 
STUDY POPULATION ................................................................................................. 19 
8.1 Sites ................................................................................................................. 19 
8.2 Patients ............................................................................................................ 20 
8.2.1 
Inclusion Criteria .................................................................................... 20 
8.2.2 
Exclusion Criteria .................................................................................... 20 
8.2.3 
Minimum Required Dataset ...................................................................... 20 
9 
STUDY PROCEDURES ................................................................................................ 21 
9.1 Site Selection, Enrollment and Training ............................................................ 21 
9.1.1 
Sampling ............................................................................................... 21 
9.1.2 
Site Initiation ......................................................................................... 21 

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9.1.3 
Site Monitoring ....................................................................................... 21 
9.2 Patient Identification and Selection Procedures ............................................... 22 
10 STUDY ASSESSMENTS ............................................................................................... 23 
10.1 Data Collected in the Screening Log ................................................................. 23 
10.2 Demographics .................................................................................................. 23 
10.3 Ocular and Glaucoma Medical History ............................................................... 23 
10.4 Surgery-Related Data ....................................................................................... 23 
10.5 Intraocular Pressure Data ................................................................................ 24 
10.6 Eye Assessments .............................................................................................. 24 
10.6.1 Visual Field Exam ................................................................................... 24 
10.6.2 Best Corrected Visual Acuity ..................................................................... 24 
10.7 Needling Procedures ........................................................................................ 24 
10.8 Secondary Surgical Intervention ...................................................................... 24 
10.9 Safety Assessments .......................................................................................... 24 
10.9.1 Definitions ............................................................................................. 24 
10.9.2 Collection and reporting of Safety Events by Investigators ............................ 25 
10.9.3 Case Processing and Submission to Competent Authorities ........................... 26 
11 DATA SOURCES ......................................................................................................... 26 
12 DATA MANAGEMENT ................................................................................................. 27 
13 QUALITY CONTROL ................................................................................................... 27 
14 STATISTICAL METHODS ............................................................................................ 28 
14.1 Sample Size ...................................................................................................... 28 
14.2 Study Populations and Analyses ....................................................................... 28 
14.2.1 Study Populations and Analysis Methods .................................................... 28 
14.2.2 Disposition and Patients' characteristics ..................................................... 29 
14.2.3 Disease Progression ................................................................................ 29 
14.2.4 Primary Objective ................................................................................... 29 
14.2.5 Secondary Objectives .............................................................................. 29 
14.2.5.1 Change in IOP and Number of Topical IOP-Lowering Medications 4 
Years after XEN 45 Gel Stent Implantation ................................... 29 
14.2.5.2 Success over the Long Term of following implantation of the XEN 45 
Gel Stent ................................................................................ 29 
14.2.5.3 Safety over the long term following implantation of the XEN 45 Gel 
Stent ...................................................................................... 29 

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14.3 Bias and Limitations of the Study ..................................................................... 30 
14.3.1 Sites ..................................................................................................... 30 
14.3.2 Patients ................................................................................................. 30 
14.3.3 Information Bias ..................................................................................... 30 
15 ETHICAL CONDUCT OF THE STUDY ............................................................................ 31 
15.1 Ethics Statement .............................................................................................. 31 
15.2 Informed Consent ............................................................................................ 31 
15.3 Institutional Review Board / Independent Ethics Committee Approval ............ 31 
15.4 Adherence to the Protocol ................................................................................ 31 
15.5 Protocol Amendment ........................................................................................ 31 
15.6 Retention of Patient Records ............................................................................ 32 
15.7 Confidentiality .................................................................................................. 32 
16 Plans for dissemintating and communicating study report ....................................... 32 
17 REFERENCES ............................................................................................................. 33 
APPENDICES .................................................................................................................. 35 
 
 

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List of Tables 
Table 1 
Study Milestones and Timelines ............................................................................ 12 
Table 2 
Schedule of Data Collection ................................................................................. 19 
Table 3 
Data Collected in Screening Logs .......................................................................... 23 
Table 4 Result from the MS-001 Study ................................................................................ 28 
 
List of Figures 
Figure 1 Examples of Data Extraction Period for Eligible Eyes ................................................. 18 
 

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1 
SYNOPSIS 
Title 
XEN 45 Gel Stent: Long Term Performance and Safety Assessment 
(XEN LT) 
Protocol number 
CMO-MA-EYE-0590 
Clinical trials.gov 
Registration Number 
Not yet registered 
Planned study dates 
Data extraction is planned to be conducted between fourth quarter 2018 
and second quarter 2019. 
Objectives 
Primary objective: 
 
The primary objective of this study is to assess the performance of 
XEN 45 Gel Stent over the long term as assessed by the change in 
intraocular pressure (IOP) compared to medicated IOP at baseline 
and the change in the number of topical IOP-lowering medications 
compared to baseline, 3 years after implantation. 
Secondary objectives: 
 
Assess the performance of XEN 45 Gel Stent over the long term as 
assessed by the change in IOP compared to medicated IOP at 
baseline and the change in the number of topical IOP-lowering 
medications compared to baseline, 4 years after implantation. 
 
Assess success over the long term following implantation of the XEN 
45 Gel Stent[a]. 
 
Assess safety over the long term following implantation of the XEN 
45 Gel Stent 
[a] Qualified success of implantation of the XEN 45 Gel Stent will be defined 
as ≥20% reduction from medicated baseline with no secondary surgical 
intervention (SSI) for glaucoma and no clinical hypotony (as defined in 
synopsis section “Data Collection and Procedures”) while staying on same or 
fewer topical IOP-lowering medications than at baseline.  
Complete success of implantation of the XEN 45 Gel Stent will be defined as 
≥20% reduction from medicated baseline with no SSI for glaucoma and no 
clinical hypotony while taking no topical IOP-lowering medications. 
Study Design 
This is a retrospective, non-interventional, observational, multi-center, chart 
review study to be conducted in patients who underwent placement of the 
XEN 45 Gel Stent as a standalone procedure or in combination with 
phacoemulsification from 1 January 2014 to 1 October 2015.  
Rationale 
XEN 45 Gel Stent performance and safety have been previously 
demonstrated in clinical trials designed for regulatory approval. However, 
studies conducted to date only provide data up to 2 years. This study will 
allow an assessment of the long-term performance and safety of the XEN 45 
Gel Stent surgeries performed in Europe in typical clinical settings. 

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Duration of study 
Data extraction will cover the period from 1 January 2014 up to 1 October 
2018. 
For each eye selected, retrospective data available from baseline (i.e., day 
when decision was made to implant XEN 45 Gel Stent) until Last Visit (i.e., 
date of the last follow-up visit available prior to 1 October 2018 or date on 
which the patient had a SSI for glaucoma, whichever occurs first), will be 
extracted from existing medical records. 
Patient Population and 
Key Selection Criteria 
The study population will include eyes treated with XEN 45 Gel Stent for 
open angle glaucoma as a standalone procedure or in combination with 
phacoemulsification between 1 January 2014 and 1 October 2015; and with 
documented post-operative follow-up available in the medical charts. For 
patients implanted bilaterally both eyes can be entered into the study 
database if they both meet eligibility criteria. 
Sample Size 
This chart review study plans to accrue a minimum of 60 study eyes that 
have had at least 3 years of follow-up data after the initial implant with XEN 
45 Gel Stent without a SSI for glaucoma. Based on data from the MS-001 
trial, it has been assumed that mean IOP reduction at 3 years will be -5.6 
(±6.32) mmHg. The 95% confidence interval (CI) of the projected mean 
reduction afforded by a sample of 60 study eyes is -7.2 to -4.0 mmHg. That 
is, the half-length of the interval is 1.6 mmHg, which provides a reasonable 
precision for the estimate of the projected mean reduction in IOP. 
Data collection for a study eye will stop at the Last Visit. While a precise 
sample size cannot be calculated, it has been assumed based on the 2-year 
outcomes from the MS-001 trial that selecting at least 150 eyes into the 
study will ensure that this chart review study will accrue a minimum of 60 
study eyes with at least 3 years of follow-up data after the initial implant 
with XEN 45 Gel Stent. 
Outcome Variables and 
Assessments 
Performance 
 
Change in IOP from medicated baseline to 3 years after XEN 45 Gel 
Stent implantation 
 
Change in IOP from medicated baseline to 4 years after XEN 45 Gel 
Stent implantation 
 
Study pre-defined IOP outcomes achieved while staying on the 
same number or fewer IOP-lowering medications and without 
clinical hypotony: 20% reduction from medicated baseline, IOP 
below 12 mmHg, below 13 mmHg, …, up to IOP below 18 mmHg 
 
Change in the number of topical IOP-lowering medications from 
medicated baseline to 3 years after XEN 45 Gel Stent implantation 
 
Change in the number of topical IOP-lowering medications from 
medicated baseline to 4 years after XEN 45 Gel Stent implantation 
 
Qualified or complete success 3 years after XEN 45 Gel Stent 
implantation  
 
Qualified or complete success 4 years after XEN 45 Gel Stent 
implantation 

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Safety 
 
Adverse events of special interest (AESIs) as defined below in the 
Section “Data Collection Procedures” 
Study Procedures 
Patients' medical charts will be extracted until the study target population 
has been reached. Site personnel will be required to complete a screening 
log for patients treated with XEN 45 Gel Stent on or after 1 January 2014 
until 31 December 2014 to identify eligible patients. End date can be up to 1 
October 2015 if the target number of eyes for the primary analysis has not 
been reached. For each eye selected, retrospective data will be extracted 
from existing medical records from XEN 45 Gel Stent implantation until 1 
October 2018 or until the date on which the patient received a SSI for 
glaucoma, whichever occurs first. The study will not impose any separate 
patient visits at the site. In case key data are not available within the charts 
at the site, site personnel will be asked to liaise with the patients’ treating 
ophthalmologist to request data to be made available for investigators for 
data entry. 
When both eyes from the same patient meet eligibility criteria, each eye will 
be included in the study database with a unique identifier, and eyes will be 
paired in the electronic data capture system. 
Data Collection 
Procedures 
Screening Log 
The following data concerning eyes treated at the site with XEN 45 Gel Stent 
during the period of interest will be extracted in anonymous screening logs. 
If both eyes of a patient had undergone XEN 45 Gel Stent implantation, one 
line should be completed in the screening log per treated eye. 
 Eye in which XEN 45 Gel Sent was implanted (Oculus Dexter vs. Oculus 
Sinister) 
 Indication for XEN 45 Gel Stent implantation 
 Date (MM YYYY) of XEN 45 Gel Stent implantation 
 Date (MM YYYY) of Last Visit 
 
Reason why the patient has not been selected for the study, if applicable 
 
Case Report Form 
The following data concerning eye treatment and clinical condition will be 
collected chronologically for eligible eyes at the indicated time points. 
Baseline is defined as the day when the decision was made to implant XEN 
45 Gel Stent. For each selected eye, all retrospective data available from 
baseline until Last Visit, will be extracted from existing medical records. 
 
Demographics at baseline (age, race and gender) 
 
Ocular and glaucoma medical history: glaucoma diagnosis and 
stage, previous ocular and glaucoma procedures, previous ocular 
medications (including whether or not eye is treated with Diamox on 

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the day when decision was taken to implant XEN 45 Gel Stent) and 
ocular pathologies observed at baseline. 
 
Surgery data: anti-metabolite and/or anti-fibrotic used prior to XEN 45 
Gel Stent implantation, procedure performed (i.e., XEN 45 Gel Stent 
implantation alone or phacoemulsification + XEN 45 Gel Stent 
implantation), XEN 45 Gel Stent and cataract-related complications, and 
if available surgical notes 
 
IOP data: IOP and number of IOP-lowering medications at baseline and 
at all data collection points defined for the study period. 
 
Eye assessment: visual field exam and best corrected visual acuity at all 
data collection points defined for the study period. 
 
Dates of needling procedures 
 
SSI for glaucoma: nature and date 
 
AESIs: 
o Anterior chamber defects (shallow with peripheral iridocorneal touch; 
flat with irido-corneal touch extending to the pupil); 
o Bleb leak; 
o Blebitis; 
o Choroidal effusion, hemorrhage or mixed effusion hemorrhage 
(extending posterior to the equator, with or without blood; obscuring 
disc or macula, with or without blood; with choroids touching in the 
center of the eye, with or without blood); 
o Corneal decompensation (transient i.e. <30 days or persistent i.e. 
>30days);  
o Endophthalmitis; 
o Hyphema (≥ 2 mm in height (layered) at any time; present or arising 
> 30 days postoperatively); 
o Persistent Hypotony (IOP < 6 mmHg, present at two consecutive 
visits postoperatively > 30 days apart); 
o Clinical Hypotony (vision reduction (2 lines or more) related to 
macular changes consistent with hypotony maculopathy (macular 
folds), optic disc edema, and/or serious choroidal detachments 
because of low IOP 
o Implant blockage; 
o Implant exposure or extrusion / conjunctival erosion; 
o Implant migration; 
o Implant repositioning requiring surgical intervention; 
o Implant touching iris or cornea; 
o Iritis (requiring treatment after the postoperative medication taper); 
o Macular edema; 
o Retinal detachment; 
o Suture abscess or other local infection;  
o Vitreous hemorrhage; 

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o And any other adverse event that leads to permanent visual 
impairment or requires surgical or medical intervention to prevent 
permanent visual impairment 
Statistical Methods 
Analysis Populations 
Data will be presented for all eyes selected and meeting the selection 
criteria, i.e. Analysis Population. Additional groups may be also examined, 
as deemed appropriate (e.g. eyes that did or did not undergo 
phacoemulsification). 
Primary Objective 
Change in IOP from medicated baseline and change in the number of topical 
IOP-lowering medications compared to baseline will be summarized 
descriptively at Year 3 after XEN 45 Gel Stent implantation in eyes from the 
Analysis Population with at least 3 years of follow-up data and were not 
treated with Diamox on the day when decision was taken to implant XEN 45 
Gel Stent. 
Secondary Objectives 
Change in IOP and Number of Topical IOP-Lowering Medications at 4 Years 
after XEN 45 Gel Stent Implantation 
Change in IOP from medicated baseline and change in the number of topical 
IOP-lowering medications compared to baseline will be summarized 
descriptively at Year 4 after XEN 45 Gel Stent implantation in eyes from the 
Analysis Population with at least 4 years of follow-up data and were not 
treated with Diamox on the day when decision was taken to implant XEN 45 
Gel Stent. 
Success over the Long Term of Implantation of the XEN 45 Gel Stent 
Number and proportion of eyes achieving a 20% reduction in IOP from 
medicated baseline, and number and proportion of eyes with an IOP <18 
mmHg, IOP <17 mmHg, …, down to IOP<12 mmHg will be described at all 
data collection time-points in eyes from the Analysis Population that did not 
underwent SSI for glaucoma, did not have clinical hypotony, and were not 
treated with Diamox on the day when decision was taken to implant XEN 45 
Gel Stent. 
The number and proportion of eyes achieving “success" at 3 and 4 years 
after XEN 45 Gel Stent implantation will be summarized descriptively. 
Analyses will be conducted in the Analysis Population. Kaplan-Meier 
analyses will be conducted to analyze time from initial procedure to SSI for 
glaucoma. 
Safety over the Long Term of Implantation of the XEN 45 Gel Stent 
Surgical complications and post-operative AESIs will be summarized 
descriptively using frequencies and percentages. Analyses will be performed 
in the Analysis Population. 
The study shall be conducted in compliance with the ethical principles arising from the Declaration of Helsinki revised in 2013, ISO-14155-
2011, European and National laws in terms of data protection, and the Guidelines on Medical Devices: Post Market Follow-Up Studies- a Guide 
for Manufacturers and Notified Bodies (MEDDEV 2.12/2 rev 2). 

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2 
LIST OF ABBREVIATIONS 
Abbreviation Definition 
AE 
Adverse event 
AESI 
Adverse event(s) of special interest 
BCVA 
Best corrected visual acuity 
CI 
Confidence interval  
CRA 
Clinical research associate(s) 
CRO 
Contract research organization 
EC 
Exclusion criteria 
eCRF 
Electronic case report form 
EDC 
Electronic data capture 
EDTRS 
Early Treatment Diabetic Retinopathy Study 
IC 
Inclusion criteria 
IEC 
Independent ethics committee 
IOP 
Intra-ocular pressure 
ISO 
International Organization for Standardization 
LogMAR 
Logarithm of Minimum Angle of Resolution 
MEDDEV 
European Medical Device Vigilance System 
MedDRA 
Medical dictionary for regulatory activities 
MIGS 
Minimally invasive glaucoma surgery 
OD 
Oculus dexter 
OS 
Oculus sinister 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SD 
Standard deviation 
SSI 
Secondary surgical intervention 
WHO 
World Health Organization 
 

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3 
STUDY MILESTONES AND TIMELINES 
The planned study milestones and timelines are described in Table 1 below. 
Table 1 
Study Milestones and Timelines 
Milestone 
Estimated Date 
Ethics submission 
Third quarter 2018 
Start of data collection 
Fourth quarter 2018 
End of data collection 
Second quarter 2019 
Final Report of study results 
Third quarter 2019 
 
 

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4 
AMENDMENTS AND UPDATES 
This section is not applicable (original protocol). 
5 
INTRODUCTION 
5.1 
Background 
The term “glaucoma” refers to a group of diseases that have in common a characteristic damage to 
the optic nerve with associated visual field loss. Glaucoma is the second leading cause of blindness 
worldwide; blindness from glaucoma is irreversible. Glaucoma can occur in all age groups including 
infants, but it is most common in elderly people (Glaucoma Panel, 2016). Other risk factors include 
race with estimated prevalence being six times higher for certain age groups in black American 
populations, a steepest increase in open-angle glaucoma with age in white populations compared 
to black American populations, and a higher incidence of primary angle-closure glaucoma in Asian 
populations compared to white patients (McMonnies, 2016). There are two major types of 
glaucoma, primary open-angle glaucoma and primary angle-closure glaucoma. 
The goal in the treatment of glaucoma is to prevent further loss of functional vision and to avoid an 
adverse impact on the patient’s quality of life (Glaucoma Panel, 2016). Glaucoma is a chronic 
progressive disease that requires continuous long-term cooperation of the patient with the 
glaucoma management proposed by the doctor. Currently, the only approach proven to be efficient 
in preserving visual function is lowering intra-ocular pressure (IOP) (Heijl et al., 2002) as elevated 
IOP is recognized as the primary risk-factor for glaucoma. IOP is lowered using medications, laser 
therapy or incisional surgery. Medical treatment is usually initiated as a first step in most cases. 
However, non-adherence to treatments dosed daily is common in glaucoma and has been linked to 
poor outcomes in vision-related quality of life (Thompson et al., 2018). Laser therapy is generally 
efficient in the first few months after treatment initiation, but has been shown to lose efficiency in 
the long term (Wienreb et al., 1995). Incisional surgeries can be defined as an attempt to lower 
IOP by the surgical formation of an artificial drainage pathway from the anterior chamber to the 
subconjunctival space (Lewis et al., 2014). Although several techniques have been developed to 
provide subconjunctival drainage, too many short- and long-term complications are still associated 
with this surgery, as over-filtration results in hypotony and under-filtration due to scarring in 
surgical failure (Watson et al. 1990). 
More recently, several medical devices have been developed to treat glaucoma. The term 
“Minimally invasive glaucoma surgery” (MIGS), defined in a joint meeting of the American 
Glaucoma Society and US Food and Drug Administration (Caprioli et al., 2015), refers to a group of 
devices that are significantly less invasive and offers a new perspective of IOP reduction with less 
risk, short operating times and rapid recovery. The three main approaches of IOP reduction by 
MIGS devices include increasing trabecular–Schlemm’s canal outflow (iStent, Hydrus Microstent), 
increasing uveoscleral outflow via uprachoroidal pathways (CyPass Micro-Stent), or creating a 
subconjunctival drainage pathway (XEN 45 Gel Stent) (Richter et al., 2016).  
XEN 45 Gel Stent (Allergan Inc.) is an ab interno gelatin stent implanted via a clear corneal incision 
without conjunctival incision and is the only available filtering micro-invasive glaucoma surgery 
device that allows the subconjunctival filtration. The stent is intended to be implanted in the angle 
and through the sclera, connecting the anterior chamber to the subconjunctival space. It is a tube 
with an inside diameter of approximately 45 µm, its outside diameter is approximately 150 µm, 

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and it is approximately 6 mm long in its dry state. The gelatin imparts hydrophilic properties that 
allow the tube to expand when hydrated by contact with aqueous fluid. This expansion of the outer 
diameter of the tube aids in keeping the gelatin stent in its intended location after surgical 
implantation. The implant is housed in a disposable preloaded handheld inserter designed 
specifically for surgical implantation. The XEN 45 Gel Stent is intended to reduce intraocular 
pressure in patients with primary open angle glaucoma where previous medical treatments have 
failed (XEN 45 Gel Stent direction for use). The performance and safety of XEN 45 Gel Stent has 
been previously demonstrated in a few clinical trials. IOP reduction one year after XEN 45 Gel Stent 
has been shown to vary between 23% and 41% (Galal et al., 2017; De Gregorio et al., 2017; 
Mansouri et al., 2018, Perez-torregrosa et al. 2016, Stalmans and Vera, 2017). In a larger 
retrospective study including 242 eyes, decrease in IOP one year after XEN 45 Gel Stent 
implantation reached 54.1% (Hengerer et al., 2017) with a reduction in the number of IOP 
medication from approximately 3 before XEN 45 implantation to 0.3 one year after stent 
implantation. One prospective, multi-center, open-label trial, the MS-001 Trial, collected data over 
the 2 years following XEN 45 Gel Stent implantation (data not yet available). Overall, these studies 
demonstrated a good safety profile of XEN 45 Gel Stent with a relatively low number of events. 
Most common complications that may occur in conjunction with the use of XEN 45 Gel Stent 
include, but are not limited to, choroidal effusion, hyphema, hypotony, implant migration, implant 
exposure, wound leak, need for secondary surgical intervention (SSI) and other known 
complications of intraocular surgeries (e.g. flat or shallow chamber, corneal edema, 
endophthalmitis) (XEN 45 Gel Stent label). 
 
5.2 
Study Rationale 
XEN 45 Gel Stent performance and safety have been previously demonstrated in clinical trials 
designed for regulatory approval. However, studies conducted to date only provide data up to 2 
years. This study will allow an assessment of the long-term performance and safety of the XEN 45 
Gel Stent surgeries performed in Europe in typical clinical settings. 

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6 
OBJECTIVES AND OUTCOME VARIABLES 
6.1 
Objectives 
6.1.1 Primary objective 
The primary objective of this study is to assess the performance of XEN 45 Gel Stent over the long 
term as assessed by the change in IOP compared to medicated IOP at baseline and the change in 
the number of topical IOP-lowering medications compared to baseline, 3 years after implantation. 
6.1.2 Secondary objective 
The secondary objectives of this study are to: 
 
Assess the performance of XEN 45 Gel Stent over the long term as assessed by the change 
in IOP compared to medicated IOP at baseline and the change in the number of topical IOP-
lowering medications compared to baseline, 4 years after implantation. 
 
Assess success over the long term following implantation of the XEN 45 Gel Stent as 
defined in Section 6.2. 
 
Assess safety over the long term following implantation of the XEN 45 Gel Stent. 
6.2 
Key Variable Definitions 
Qualified success of implantation of the XEN 45 Gel Stent will be defined as ≥20% reduction from 
medicated baseline with no SSI for glaucoma and no clinical hypotony while staying on the same 
number or fewer topical IOP-lowering medications than at baseline. 
Complete success of implantation of the XEN 45 Gel Stent will be defined as ≥20% reduction from 
medicated baseline with no SSI for glaucoma and no clinical hypotony while taking no topical IOP-
lowering medications. 
6.3 
Outcome Variables 
Performance outcomes: 
o 
Change in IOP from medicated baseline to 3 years after XEN 45 Gel Stent 
implantation 
o 
Change in IOP from medicated baseline to 4 years after XEN 45 Gel Stent 
implantation 
o 
Study pre-defined IOP outcomes achieved while staying on the same number or 
fewer topical IOP-lowering medications and without clinical hypotony: 20% reduction 
from medicated baseline, IOP below 12 mmHg, IOP below 13 mmHg, …, up to IOP 
below 18 mmHg 
o 
Change in the number of topical IOP-lowering medications from medicated baseline 
to 3 years after XEN 45 Gel Stent implantation 
o 
Change in the number of topical IOP-lowering medications from medicated baseline 
to 4 years after XEN 45 Gel Stent implantation 
o 
Qualified or complete success 3 years after XEN 45 Gel Stent implantation 

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o 
Qualified or complete success 4 years after XEN 45 Gel Stent implantation 
 
Safety outcomes: 
o 
Adverse events of special interest (AESIs), as defined in Section 10.9.2. 

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7 
STUDY CONDUCT 
7.1 
Overall Design of the Study 
This is a retrospective, non-interventional, observational, multi-center, chart review study to be 
conducted in patients who underwent placement of the XEN 45 Gel Stent as a standalone 
procedure or in combination with phacoemulsification from 1 January 2014 to 1 October 2015. For 
patients implanted bilaterally, both eyes can be entered into the study database if they both meet 
eligibility criteria. Data from approximately 150 eyes will be collected by retrospective review of 
medical charts in 5 European countries. Countries considered at time of protocol development are: 
Austria, Belgium, Germany, Spain and the United Kingdom. Sites will be centers with certified XEN 
45 Gel Stent surgeons known to have implanted XEN 45 Gel Stent in the time period being studied. 
Patients' medical charts will be extracted until the target number of eyes for the primary analysis 
has been reached. Site personnel will be required to complete a screening log for patients treated 
with XEN 45 Gel Stent on or after 1 January 2014 to identify eligible patients (see Section 9.2). For 
each eye selected, all retrospective data available from baseline (i.e. day when decision was made 
to implant XEN 45 Gel Stent) until Last Visit (i.e. date of the last follow-up visit available prior to 1 
October 2018 or date on which the patient had a SSI for glaucoma, whichever occurs first) will be 
extracted from existing medical records. The study will not impose any separate patient visits to 
the site. In case key data are not available within the charts at the site, site personnel will be 
asked to liaise with the patients’ treating ophthalmologist to request data to be made available for 
investigators for data entry. 
A feasibility assessment will be conducted prior to the study conduct in the considered countries to 
assess whether targeted sites have access to complete patient records including patient’s follow up 
after implantation of XEN 45 Gel Stent, to assess the number of eligible eyes, and to assess sites 
willingness to participate in the study. 
If both eyes from the same patient meet eligibility criteria, each eye will be included in the study 
database with a unique identifier and eyes will be paired in the electronic data capture system 
(EDC). Study procedures, and evaluations are described in detail in Sections 9 and 10 and data to 
be collected are summarized in Table 2: surgery data (procedure performed, XEN 45 Gel Stent and 
cataract related complication, anti-metabolite and/or antifibrotic therapy used), IOP level, number 
of topical IOP-lowering medications taken, eye examination (visual field exam, best corrected 
visual acuity…), interventions performed on the study eyes, IOP lowering medications, and AESIs. 
Safety events to be collected are described in Section 10.9. 
Data extraction may begin as soon as sites are initiated. This study will collect anonymized data 
(i.e. no list of identifier will be kept by the sites and once data are entered in the system, 
investigators, study personnel and sponsor will not be able to identify patients), therefore no 
informed consent will be requested from patients. 

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7.2 
Data Collection Periods 
Figure 1 provides examples of data extraction periods for eligible eyes, depending on when 
baseline and Last Visit occurred during the study period. 
Figure 1 Examples of Data Extraction Period for Eligible Eyes 
 
 
 
 
 
 
 
 
 
 
 
In a) and b) eye did not have a secondary surgical intervention (SSI) for glaucoma and all data available between the day 
when decision was taken to implant XEN 45 Gel Stent and data cut-off, i.e. 1 October 2018, will be extracted. In c) and d), 
eyes had a SSI for glaucoma and data are extracted from the day when decision was taken to implant XEN 45 Gel Stent 
until the SSI. 
Some data such as IOP and eye assessments (see Section 10.5 and 10.6 for additional details) will 
be collected if they are within time windows defined around data collections points of interest. All 
data available within these time windows have to be collected. 
 
Month 12: data between Month 9 and Month 15 after XEN 45 Gel Stent implantation  
 
Month 24: data between Month 21 and Month 27 after XEN 45 Gel Stent implantation 
 
Month 36: data between Month 33 and Month 39 after XEN 45 Gel Stent implantation 
 
Month 48: data between Month 45 and Month 51 after XEN 45 Gel Stent implantation 
 
Study Period 
1 January 2014 
1 October 2018 
a) 
b) 
c) 
Data extraction period 
XEN 45 Gel Stent Implantation 
Last Visit = Secondary surgical intervention 
Day when decision was taken to implant XEN 45 Gel Stent 
d) 
Last Visit = last follow-up visit available before 1 October 2018 

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Table 2 displays the time frame during which study variables will be collected. 
Table 2 
Schedule of Data Collection 
Data Collected 
Baseline[a] 
XEN 45 Gel 
Stent 
Implantation 
Study Period[b] 
Eligibility Assessment 
X 
 
 
Demography 
X 
 
 
Ocular and Glaucoma Medical History 
X 
 
 
Surgery-related data 
 
X 
 
Number of IOP-lowering medications 
X 
 
X 
Visual field exam[c] 
X 
 
X 
Intraocular pressure 
X 
 
X 
Best corrected visual acuity 
X 
 
X 
Needling procedures 
 
 
X 
Secondary surgical intervention for glaucoma 
 
 
X 
Adverse events of special interest 
 
 
X 
IOP=intra-ocular pressure. 
[a] Baseline is defined as the day when the decision was made to implant XEN 45 Gel Stent. 
[b] The study period is defined as the period between XEN 45 Gel Stent implantation and 1 October 2018. For each eye 
selected, all retrospective data available from baseline until 1 October 2018 or until the date on which the patient received a 
SSI for glaucoma, whichever occurs first, will be extracted from existing medical records. 
[c] If no visual field exam is available at baseline, a value measured up to 12 months prior to baseline is acceptable. In the 
event that more than one value is available in this 12-month period, the value closest to the baseline date will be used. 
 
7.3 
Patient Discontinuation, Site Termination or Study 
Termination 
7.3.1 Withdrawal of Individual Patients Prior to Study Completion 
Considering the retrospective study design, no withdrawal of individual patients prior to study end 
is expected. 
7.3.2 Study or Study Site Termination 
The Sponsor reserves the right, at any time, to discontinue selection of additional patients into the 
study, at any site; or to discontinue the study for administrative reasons. 
8 
STUDY POPULATION 
8.1 
Sites 
Site selection will aim to recruit sites where investigators are certified XEN 45 Gel Stent surgeons 
and are known to have implanted XEN 45 Gel Stent in the time period being studied. A sample of 
ophthalmologists working in experienced glaucoma centers will thereby be selected. 

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8.2 
Patients 
The study population will include patients with one or both eyes with open angle glaucoma that 
underwent XEN 45 Gel Stent implantation. 
8.2.1 Inclusion Criteria 
A patient’s eye must meet all of the following criteria to be eligible for participation in the study. 
1. 
Eye treated with XEN 45 Gel Stent for open angle glaucoma as a standalone procedure 
or in combination with phacoemulsification 
2. 
XEN 45 Gel Stent was implanted between 1 January 2014 and 1 October 2015 
8.2.2 Exclusion Criteria 
None 
8.2.3 
Minimum Required Dataset 
Medical charts that do not include the following data will not be selected for the study. Therefore, if 
no data is available within the charts at the study site, before selecting the chart for inclusion in the 
study it must be established that certain key data from other locations will be made available for 
investigators for data entry. 
Patient characteristics 
• 
Age 
• 
Gender 
Intraocular Pressure 
 
IOP at baseline (i.e. medicated IOP) and until last visit (1 October 2018 or until the date on 
which the patient received a SSI for glaucoma, whichever occurs first) 
 
Number of topical IOP-lowering medication prescribed for the study eye at baseline and until 
last visit (1 October 2018 or until the date on which the patient received a SSI for 
glaucoma, whichever occurs first)  
Secondary surgical intervention 
 
Date of the SSI for glaucoma, if any 
 

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9 
STUDY PROCEDURES 
9.1 
Site Selection, Enrollment and Training 
9.1.1 Sampling 
Sites will be identified using Allergan field-based knowledge among sites where investigators are 
certified XEN 45 Gel Stent surgeons and are known to have implanted XEN 45 Gel Stent in the time 
period being studied. All sites identified by Allergan will be approached for participation in the study 
in the following countries of interest: Austria, Belgium, Germany, Spain and the United Kingdom. 
A recruitment mail containing the study summary, the site qualification questionnaire and a reply 
coupon will be sent to all sites. If the return rate is insufficient, non-responders will be contacted by 
telephone to fill out the site qualification questionnaire. 
Allergan or designee will qualify sites with sufficient resources (time, personnel, and facilities) to 
participate in the study. Sites will be required to obtain approval from the appropriate Independent 
Ethics Committee (IEC) as appropriate according to local laws, and will be responsible for 
maintaining all related documents, before enrollment of any patient into the study. 
Recruitment will end once approximately 15 qualified sites have agreed to participate in the study. 
9.1.2 Site Initiation 
Sites will receive a study kit once all the necessary administrative procedures have been completed 
(confidentiality agreement, research contract agreement, curriculum vitae… where applicable). 
The study kit contains the following: 
 
Study protocol 
 
Screening Log 
 
Electronic case report form (eCRF) user manual. 
An initiation telephone call will be organized by Clinical Research Associates (CRA) to explain the 
protocol, data collection, and the practical aspects of the study. 
In addition, designated study personnel will participate in a training program that will encourage 
consistency of processes and procedures at the investigative sites and ensure collection of high-
quality data for this study. All sites will be trained on the protocol, study logistics, and the EDC 
system. Retraining will be conducted as needed. 
9.1.3 Site Monitoring 
During the data-extraction period, sites will be contacted by telephone by CRAs to follow the site 
identification of patients, the eCRF completion and to answer any questions sites may have 
concerning data to be collected and the logistics of the study. Frequency of telephone calls will be 
site dependent and based on identified needs for each site. A close out call will be performed by 
CRAs at the end of the study. Site monitoring processes will be further detailed in the Site 
Management and Monitoring Plan. 

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9.2 
Patient Identification and Selection Procedures 
Medical charts will be screened by the investigative site personnel to identify eyes who satisfy all 
the inclusion and none of the exclusion criteria. The number of eyes selected at each site will be 
chosen based on the results of the feasibility assessment and consultations with the Sponsor. Eye 
selection will not be competitive and will stop when the target number of eligible eyes has been 
reached. 
Once a site has been initiated, site personnel will be invited to complete a screening log with all 
patients’ eyes that underwent XEN 45 Gel Stent implantation from 1 January 2014 until 31 
December 2014. Data collected in the screening log, listed in Section 10.1, will help site personnel 
identify eligible eyes. Upon screening log completion, the sites will proceed through the patients’ 
eyes listed in the screening log and extract data from eyes who meet all the inclusion criteria and 
none of the exclusion criteria. Consent from patients will not be requested; as the study is 
retrospective and fully anonymized, a waiver of consent will be requested from the IECs. Sites will 
proceed chronologically for entry of eligible eyes data in the EDC system, starting with the eligible 
eyes that underwent XEN 45 Gel Stent implantation the closest to 1 January 2014. Exceptions will 
be made when sites encounter an eye from a patient with both eyes meeting selection criteria. 
Once data from the first eye have been extracted, sites will extract data from the second eye, 
regardless of its XEN 45 Gel Stent implantation date, so that eyes can be paired in the EDC.  
Once the charts of all eligible eyes listed in the screening log have been extracted for entry on the 
eCRF, and if the target number of eyes for the primary analysis has not been reached, site 
personnel will be invited to complete a new screening log with charts of patients’ eyes that 
underwent XEN 45 Gel Stent implantation in the following 3 months (i.e. between 1 January 2015 
and 31 March 2015). This process will be repeated periodically thereafter as applicable until the 
target number of eyes has been reached. 
Sites will make sure that after data have been entered in the study database, there will be no 
possibility to link the data collected in the screening log or eCRF to a patient name. 

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10 
STUDY ASSESSMENTS 
10.1 
Data Collected in the Screening Log 
Once a site has been initiated, site personnel will be required to complete an anonymized screening 
log with all patients’ eyes that underwent XEN 45 Gel Stent implantation as described in Section 
9.2. If both eyes of a patient had undergone XEN 45 Gel Stent implantation, one line should be 
completed in the screening log per treated eye. For all screened patients’ eyes, the data listed in 
Table 3 will be collected to help site personnel identify eligible eyes. 
Table 3 
Data Collected in Screening Logs 
Data Collected 
Selection 
Criteria  
 
Eye in which XEN 45 Gel Sent was implanted (OD vs. OS)  
N/A 
 
Indication for XEN 45 Gel Stent implantation 
IC1 
 
Date (MM YYYY) of XEN 45 Gel Stent implantation 
IC2 
 
Date (MM YYYY) of Last Visit[a,b] 
IC2 
 
Reason why the patient has not been selected for the study (did not meet selection 
criteria, lack of time, quotas were met, insufficient access to complete medical 
records, etc.) 
N/A 
IC=Inclusion criteria; N/A=not applicable; OD=oculus dexter; OS=oculus sinister 
[a]. Last Visit is defined as the date of the last follow-up visit available prior to 1 October 2018 or date on which the 
patient had a SSI for glaucoma, whichever occurs first. 
[b] Automated calculation will be implemented in the screening log to verify whether Last Visit occurred at least 3 years 
after XEN 45 Gel Stent implantation 
10.2 
Demographics 
Patients' age at implantation of XEN 45 Gel Stent, gender and race will be recorded in the eCRF. 
Selected eye characteristics (OD vs. OS), along with information about whether patient’s other eye 
was also selected will be collected. 
10.3 
Ocular and Glaucoma Medical History 
Ocular history of the selected eye will be collected, such as glaucoma diagnosis, previous ocular 
and glaucoma procedures, previous ocular medications (including whether or not eye is treated 
with Diamox on the day when decision was taken to implant XEN 45 Gel Stent) and ocular 
pathologies observed at baseline. Glaucoma stage at baseline will be determined by investigators 
based on visual field assessment. 
10.4 
Surgery-Related Data 
Use of anti-metabolite and/or anti-fibrotic, procedure performed (i.e., XEN 45 Gel Stent 
implantation alone or phacoemulsification + XEN 45 Gel Stent implantation), XEN 45 Gel Stent and 
cataract-related complications, and, if available surgical, notes will be collected.  

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10.5 
Intraocular Pressure Data 
IOP-related data, i.e. IOP and number of IOP-lowering medications, will be collected at the visit 
when the decision was made to implant XEN 45 Gel Stent, and not the day of implantation. IOP-
related data will also be collected for all data collection points defined for the study period. 
10.6 
Eye Assessments 
10.6.1 Visual Field Exam 
Mean deviation expressed in decibels will be collected at baseline and at all data collection points 
defined for the study.  
Note: If no visual field exam is available at baseline, a value measured up to 12 months prior to 
baseline is acceptable. In the event that more than one value is available in this 12-month period, 
the value closest to the baseline date will be used. 
10.6.2 Best Corrected Visual Acuity 
BCVA in the study eye will be collected at baseline and at all data collection points defined for the 
study. Values will be recorded in the eCRF according to local practice (Snellen, LogMAR, EDTRS, 
etc.) along with scale name or method used to assess BCVA. 
10.7 
Needling Procedures 
Date of needling procedures performed on the bleb after XEN 45 Gel Stent implantation will be 
collected throughout the study period. 
10.8 
Secondary Surgical Intervention 
If a SSI for glaucoma was performed on the study eye during the study period, the nature and date 
of the SSI will be collected. SSIs for glaucoma include but are not limited to trabeculectomy, table 
shunt, second gel stent, i-Stent, GATT, ABiC, and transscleral cycloablative procedures. 
10.9 
Safety Assessments 
10.9.1 Definitions 
The investigators will classify the adverse event based on the following definitions according to ISO 
14155 (2011). 
Adverse Event (AE) 
Any untoward medical occurrence, unintended disease or injury, or untoward clinical signs 
(including abnormal laboratory findings) in subjects, users or other persons, whether or not related 
to the investigational medical device. 
Serious Adverse Event (SAE) 
An adverse event that: 
a) led to death, 
b) led to serious deterioration in the health of the subject, that either resulted in 
1) a life-threatening illness or injury, or 

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2) a permanent impairment of a body structure or a body function, or 
3) in-patient or prolonged hospitalization, or 
4) medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function, 
c) led to fetal distress, fetal death or a congenital abnormality or birth defect 
Note: Planned hospitalization for a pre-existing condition, or a procedure required by the clinical 
investigation plan, without serious deterioration in health, is not considered a serious adverse 
event. 
Device Malfunction/Failure – Device Specific Events 
A device specific event is any malfunction of the device, related or not to the device, resulting or 
not in the patient undergoing undesirable or harmful experience, that occurs in relation with the 
conduct of the study. 
Device malfunction means the failure of a device to meet its performance specifications or 
otherwise perform as intended. Performance specifications include all claims made in the labeling 
for the device. The intended performance of a device refers to the intended use for which the 
device is labeled or marketed. 
Device malfunction may or may not result in the subject experiencing a harmful effect. 
All AEs/SAEs associated with a device failure are by definition device related. 
10.9.2 Collection and reporting of Safety Events by Investigators 
Considering that study aims to explore occurrence over the long term of adverse events identified 
during clinical studies, this study will collect only the following AESIs: 
 
Anterior chamber defects: 
o 
Shallow with peripheral iridocorneal touch 
o 
Flat with irido-corneal touch extending to the pupil 
 
Bleb leak 
 
Blebitis 
 
Choroidal effusion, hemorrhage or mixed effusion hemorrhage recorded as follows: 
o 
Extending posterior to the equator, without blood 
o 
Extending posterior to the equator, with blood 
o 
Obscuring disc or macula, without blood 
o 
Obscuring disc or macula, with blood 
o 
With choroids touching in the center of the eye, without blood 
o 
With choroids touching in the center of the eye, with blood 
 
Corneal decompensation (transient i.e. <30 days or persistent i.e. >30days) 
 
Endophthalmitis 
 
Hyphema  

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o 
≥ 2 mm in height (layered) at any time 
o 
Present or arising > 30 days postoperatively 
 
Persistent hypotony: IOP < 6 mmHg, present at two consecutive visits postoperatively > 30 
days apart 
 
Clinical hypotony: vision reduction (2 lines or more) related to macular changes consistent 
with hypotony maculopathy (macular folds), optic disc edema, and/or serious choroidal 
detachments because of low IOP 
 
Implant blockage 
 
Implant exposure or extrusion / conjunctival erosion 
 
Implant migration 
 
Implant repositioning requiring surgical intervention 
 
Implant touching iris or cornea 
 
Iritis (requiring treatment after the postoperative medication taper) 
 
Macular edema 
 
 
 
Retinal detachment 
 
Suture abscess or other local infection 
 
Vitreous hemorrhage 
 
Any other adverse event that leads to permanent visual impairment or requires surgical or 
medical intervention to prevent permanent visual impairment 
Due to the retrospective design of the study, the reporting of safety events to the sponsor is not 
solicited for this study. AEs occurring outside of the data collection period 01 January 2014 to 01 
October 2018 are not within the scope of this study and will not be collected. However, should any 
AEs occur that are outside of this range, Investigators are reminded of the requirement for 
unsolicited AE reports to be submitted directly to Allergan’s Product Surveillance. 
10.9.3 Case Processing and Submission to Competent Authorities 
As the study is retrospective, all AEs collected during the study should have been reported to the 
competent authorities at time of occurrence. AEs collected during this study will not be submitted 
to the competent authorities as this would result in double reporting. However, all AESIs collected 
for the study will be recorded in the study database and summarized in the study report. 
The investigators are responsible for maintaining compliance with any applicable site-specific 
requirements related to the reporting of SAEs or other safety information to the local IEC that 
approved the study. 
11 
DATA SOURCES 
This is a retrospective, observational study, and patient data collected from the sites will be 
extracted from medical charts. 

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12 
DATA MANAGEMENT 
Electronic data collection will be performed using eCRFs. Site personnel will enter data into the EDC 
system according to the schedule of assessments and according to instructions from the Sponsor 
and/or designee. Only authorized personnel will have access to the EDC system. Selected eyes will 
be identified by an identification number assigned when they are selected for the study. For 
patients implanted bilaterally, both eyes can be entered into the study database if they both eyes 
meet eligibility criteria. In that case, each eye will be included in the study database with a unique 
identifier, and eyes will be paired in the EDC. Data will be anonymized and once entered in the 
system, investigators and study personnel will not be able to identify patients. 
Each investigator is responsible for ensuring that accurate data are entered into the EDC system in 
a timely manner. Specific processes used to manage the data throughout the study will be 
documented in the Data Management Plan. Briefly, on-line logic checks will be built into the 
system, so that missing or illogical data are not submitted. In the event that inconsistent data 
persist, no queries will be issued as investigators will not be able to connect the patient with 
his/her eye identification number. Consequently, all data entered into the eCRF should be reviewed 
by the principal investigator. The principal investigator will be responsible for endorsing data within 
the eCRF. This approval method will include applying an electronic signature, a uniquely assigned 
user name, and a password that together will represent a traditional handwritten signature. 
Medical history and AEs will be coded using Medical Dictionary for Regulatory Activities (MedDRA, 
the most recent version); coding will be done at the Lower Level Term. IOP lowering medications 
will be coded with the WHO Drug Dictionary. 
A final validation of the database will be performed, and the database will be locked, before the 
statistical analysis is conducted. 
13 
QUALITY CONTROL 
Designated study personnel will participate in a training program that will encourage consistency of 
process and procedures at the investigative site and ensure collection of high-quality data for this 
study. All sites will be trained on the protocol, study logistics, and the EDC. Retraining will be 
conducted as needed. Investigators will be reminded of the processes and importance of reporting 
AESI, SAEs, and other information. 
Quality controls performed during statistical analyses will be described in the statistical analysis 
plan (SAP). 
Secure electronic archive will be maintained and will include but will not be limited to: final raw 
data, analysis datasets, programs and associated documentation. Access to the archive will be 
controlled and limited to authorized personnel only. 

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14 
STATISTICAL METHODS 
14.1 
Sample Size 
To answer study primary objective, this chart review study plans to accrue a minimum of 60 study 
eyes that have had at least 3 years of follow-up data without a SSI for glaucoma after the initial 
implant with XEN 45 Gel Stent. 
Data from the Allergan study MS-001 demonstrated that the mean IOP reduction from baseline 
differed slightly among the 7 visits (see below) in the 24-month post-implant period. The absence 
of a clear waning-out trend suggests that the effect of XEN 45 Gel Stent implantation on IOP 
reduction may last to Month 36 and beyond. The minimum mean reduction (negative sign stands 
for reduction) in IOP among the visits was -5.6 (±6.32) mmHg, which was observed at Month 3. 
This value was then taken as an initial estimate for the mean reduction projected for Month 36. The 
95% confidence interval (CI) of the projected mean reduction afforded by a sample of 60 study 
eyes is -7.2 to -4.0 mmHg. That is, the half-length of the interval is 1.6 mmHg, which provides a 
reasonable precision for the estimate of the projected mean reduction in IOP. 
Table 4 Result from the MS-001 Study 
Visit 
Number of study eyes 
Mean (SD) change in IOP from 
medicated baseline (mmHg) 
Month 1 
167 
-6.3 (6.41) 
Month 3 
167 
-5.6 (6.32) 
Month 6 
168 
-6.4 (4.92) 
Month 9 
134 
-6.1 (5.68) 
Month 12 
161 
-6.7 (5.41) 
Month 18 
149 
-7.1 (5.10) 
Month 24 
149 
-6.2 (4.94) 
The MS-001 study enrolled 199 patients (218 study eyes). In this study, patients’ discontinuation 
rate tended to be linear over the 2-year follow-up period, with an overall study discontinuation rate 
of approximately 20%. Using data from the MS-001 study, it could be assumed that 30% of the 
eyes selected for this study have less than 3 years of follow-up data. Taking into consideration that 
MS-001 study was a clinical trial and that patient retention rate is expected to be lower in a real-
world setting, the study will aim to select 150 eyes to ensure obtaining a minimum of 60 eyes with 
at least 3 years of follow-up data. 
14.2 
Study Populations and Analyses 
A formal SAP that will provide details of all analyses and presentation of study data will be 
approved prior to data analysis. Statistical analysis will be carried out using SAS software version 
9.2 or later. 
14.2.1 
Study Populations and Analysis Methods 
• 
Analysis Population: all eyes selected and meeting the selection criteria. 
• 
Subgroups analyses will be conducted in eyes that did or did not undergo 
phacoemulsification. Additional subgroups may be further considered in the SAP. 
Continuous variables will be described by their mean, standard deviation, median, upper and lower 
quartiles, extreme values (minimum and maximum) and the number of missing data. 

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Categorical variables will be described by the number and percentage of each response and the 
number of missing data. 
Figures will be generated, when appropriate, to describe change in parameters over time. 
Some of the data will only be collected if they occurred within study-defined time windows (see 
Section 7.2). Since all data within the defined time windows will be collected, more than one value 
could be available per time window for a given parameter. Rules to determine which value will be 
used for the analysis will be defined in the SAP. 
14.2.2 Disposition and Patients' characteristics 
Number and percentage of eyes in the Analysis Population and in subgroups will be described. 
Demographic characteristics will be summarized descriptively at a patient level. 
14.2.3 Disease Progression 
Ocular medical history, IOP lowering medications and needling procedures will be summarized 
descriptively. Visual field exam and BCVA will be summarized descriptively at baseline and for all 
time points of interest. 
14.2.4 Primary Objective 
Change in IOP from medicated baseline and change in the number of topical IOP-lowering 
medications compared to baseline will be summarized descriptively at Year 3 after XEN 45 Gel 
Stent implantation in eyes from the Analysis Population with at least 3 years of follow-up data and 
were not treated with Diamox on the day when decision was taken to implant XEN 45 Gel Stent. 
14.2.5 
Secondary Objectives 
14.2.5.1 Change in IOP and Number of Topical IOP-Lowering Medications 4 Years after 
XEN 45 Gel Stent Implantation 
Change in IOP from medicated baseline and change in the number of topical IOP-lowering 
medications compared to baseline will be summarized descriptively at Year 4 after XEN 45 Gel 
Stent implantation in eyes from the Analysis Population with at least 4 years of follow-up data and 
were not treated with Diamox on the day when decision was taken to implant XEN 45 Gel Stent. 
14.2.5.2 Success over the Long Term of following implantation of the XEN 45 Gel Stent 
Number and proportion of eyes achieving a 20% reduction in IOP from medicated baseline, and 
number and proportion of eyes with an IOP <18 mmHg, IOP <17 mmHg, …, down to IOP<12 
mmHg will be described at all time-points of interest in eyes from the Analysis Population that did 
not underwent SSI for glaucoma, did not have clinical hypotony, and were not treated with Diamox 
on the day when decision was taken to implant XEN 45 Gel Stent. 
The number and proportion of eyes achieving qualified or complete success at 3 and 4 years after 
XEN 45 Gel Stent implantation will be summarized descriptively. Analyses will be conducted in the 
Analysis Population. Kaplan-Meier analyses will be conducted to analyze time from initial procedure 
to SSI for glaucoma.  
14.2.5.3 Safety over the long term following implantation of the XEN 45 Gel Stent 
Surgical complications and post-operative AESIs will be summarized descriptively using frequencies 
and percentages. Analyses will be performed in the Analysis Population. 

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14.3 
Bias and Limitations of the Study 
14.3.1 Sites 
Sites will be selected to be representative of sites experienced with glaucoma management. 
Because the participating sites comprise a population of volunteers, a non-response selection bias 
is possible. 
14.3.2 Patients 
In order to limit bias in the selection of patients’ eyes, each site will be asked to select in a 
chronological order all eyes that meet the selection criteria, regardless of demography or other 
considerations, based on date of XEN 45 Gel Stent implantation (see Section 9.2). Exception to the 
selection in a chronological order will be made for patients with both eyes meeting the selection 
criteria with both eyes included at the same time. All patients’ eyes that had XEN 45 Gel Stent 
implanted and meeting the selection criteria, regardless of whether or not they will be selected for 
the study, will be recorded in an anonymized screening log collecting minimum non-identifying 
patient information (see Section 10.1). Characteristics of selected and non-selected patients’ eyes 
will be compared to assess selection bias and reason for not being selected will be described (eye 
did not meet selection criteria, lack of time, quotas were met, site was unable to retrieve data 
missing from the chart from other locations etc.). 
14.3.3 Information Bias 
As the study is retrospective, the study will rely on data collected for another purpose (e.g. patient 
care). As a result, not all data to be collected in this study may be recorded in the medical charts, 
leading to a potential bias due to missing data. 
Moreover, as data are anonymized, no queries will be issued to the sites in case of missing or 
incoherent data. 
Finally, as this is a multicenter study conducted in different countries, the quality and quantity of 
medical information available from medical records will be variable. Medical records from some 
providers may not contain information for all encounters with the ophthalmologist. To limit this 
bias, it will be verified during the feasibility assessment that targeted sites have access to complete 
patient records, including patients’ follow up after implantation. In case key data are missing from 
the charts at the site, site personnel will be asked to liaise with the patients’ treating 
ophthalmologist to request data to be made available for investigators for data entry. Finally the 
methods used to estimate the data variables collected (e.g. visual field, best corrected visual 
acuity…) during the chart review process may be heterogeneous across sites. This could potentially 
result in greater variability in the study result. 
Information bias can be minimized by the use of electronic data capture technology. In addition to 
minimize the burden on the investigators and the sites, electronic data capture technology will 
maximize the quality and relevance of the data using automated online controls (e.g., automated 
controls on value ranges, units, internal consistency, and missing key data). 

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15 
ETHICAL CONDUCT OF THE STUDY 
15.1 
Ethics Statement 
To ensure the quality and integrity of research, the study shall be conducted in compliance with the 
ethical principles arising from the Declaration of Helsinki revised in 2013 (World Medical 
Association, 2013), ISO-14155-2011 (ISO, 2011), the MEDDEV 2.12/2 rev2 (MEDDEV, 2012), 
European and National laws in terms of data protection and all current local regulations (2016/679, 
2016). 
15.2 
Informed Consent 
Due to the retrospective and anonymous nature of data collection for this study, signature of 
informed consent by patients is not required to extract data from the patient's chart. A waiver of 
consent will be requested from IECs. 
15.3 
Institutional Review Board / Independent Ethics Committee 
Approval 
This study is non-interventional. As the study is based on a secondary use of data, it does not 
come under applicable laws and regulation on clinical trials 
Submissions and/or notification to the appropriate IEC will be performed as required by local 
legislation in each country for this type of study. 
Patients' personal data and investigator's personal data shall be treated in compliance with the 
European Regulation (EU 2016/679) on the protection of individuals with regard to the processing 
of personal data and all local applicable laws and regulations. 
Data about investigators will be declared to applicable data protection authority and the 
investigators will be informed – within the framework of the site qualification questionnaire – of 
their right to access to, rectify or erase data, or their right to restrict or object to processing of the 
data, as well as the right to data portability. 
Patient data will be anonymized, i.e. investigators will not be able to connect the patient with 
his/her identification number. The sponsor will be blinded to the patient information. 
Submission(s) to competent data protection authorities will be performed as appropriate. 
15.4 
Adherence to the Protocol 
The study must be conducted as described in the approved protocol. Any significant deviation from 
the protocol (i.e. jeopardizing patient safety) must be reported immediately to the Sponsor and 
IEC. 
15.5 
Protocol Amendment 
Any amendment to the protocol will be created by the Sponsor, and subsequently submitted by the 
site to the IEC and appropriate regulatory authority for approval.  

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15.6 
Retention of Patient Records 
When the study is completed, the investigators must retain the essential documents for as long as 
needed to comply with regulatory guidelines and Sponsor requirements. The investigators will 
notify the Sponsor prior to moving or destroying any of the study documents. 
The Sponsor will maintain the data collected (study database) for at least 5 years. 
15.7 
Confidentiality 
The information in this and related documents from the Study Sponsor includes trade secrets and 
commercial information that are confidential and may not be disclosed, unless such disclosure is 
required by federal or other laws or regulations. In any event, persons to whom the information is 
disclosed must be informed that the information is confidential and may not be further disclosed by 
them. 
Individual patient medical information obtained as a result of this study is considered confidential, 
and disclosure to third parties, other than those noted below, is prohibited. Such medical 
information may be given to the patient's personal physician or to other appropriate medical 
personnel responsible for the patient's welfare. 
Data generated as a result of this study are to be available for inspection on request of the 
Sponsor's representative, the IEC, or local regulatory agency. 
16 
PLANS FOR DISSEMINTATING AND COMMUNICATING 
STUDY REPORT 
The Sponsor and/or designee will develop a final study report after the end of the study. Results 
will be posted on Clinical Trials.gov. 
This study is intended for publication, even if terminated prematurely. Publication may include any 
or all of the following: posting of a synopsis online, abstract and/or presentation at a scientific 
conference, or publication of a full manuscript. . Authorship credit will follow the guidelines 
established by the International Committee of Medical Journals Editors (ICMJE, 2016) and, as such, 
should be based on the following criteria 1) substantial contributions to the conception or design of 
the work; or the acquisition, analysis, or interpretation of data for the work; 2) drafting the work or 
revising it critically for important intellectual content; 3) final approval of the version to be 
published and 4) agreement to be accountable for all aspects of the work in ensuring that 
questions related to the accuracy or integrity of any part of the work are appropriately investigated 
and resolved. All authors must meet all above criteria. Although publication planning may begin 
before conducting the study, final decisions on authorship and the order of authors’ names will be 
made based on participation and actual contributions to the study and writing, as discussed above. 

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17 
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Stalmans I. A minimally invasive approach to sub-conjunctival outflow: 1 year results of an ab-
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specialty/en/products/pms/xen-45-dfu-english-3037-004-rev-a.pdf  

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APPENDICES 
None