Prospective Study on DEXTENZA® Safety And Efficacy Following Concomitant MIGS and Cataract Surgery
Phase: PHASE4
Conditions: Glaucoma, Cataract
Sponsor: The New York Eye Surgery Center

The SUSTAIN Study (V3) 
 
 
 
 
 
Compound: 
Sustained Release Dexamethasone, 
0.4 mg 
IND Number: 
146602 
NCT: 
               04200651 
 
Study Name: 
Prospective Study on DEXTENZA® 
Safety and Efficacy following 
concomitant MIGS and Cataract 
Surgery 
 
Clinical Phase: 
Phase IV open label prospective 
 
Date of Issue: 
10/18/2020 
 
Primary Investigator: 
Nathan M. Radcliffe, MD 
 
 
Sub Investigator: 
Nicholas Tan 
 
Site Name & Location: 
New York Eye Surgery Center, 1101 
Pelham Pkwy N, The Bronx, NY 
10469 
Clinical Study Protocol 
ProSpective StUdy on DEXTENZA® SafeTy And EffIcacy following 
coNcomitant MIGS and Cataract Surgery 
The SUSTAIN Study 

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CLINICAL STUDY PROTOCOL SYNOPSIS 
 
TITLE 
Prospective Study on DEXTENZA® Safety and 
Efficacy following concomitant MIGS and Cataract 
Surgery 
 
SITE LOCATION(S) 
New York Eye Surgery Center, 1101 Pelham Pkwy N, 
The Bronx, NY 10469 
 
PRINCIPAL 
INVESTIGATOR 
Nathan M. Radcliffe, MD 
 
OBJECTIVE(S) 
To compare dexamethasone insert to topical 
corticosteroid use through 90 days in glaucomatous 
eyes undergoing MIGS and cataract surgery as 
measured by: visual acuity, IOP control, adverse 
events, control of inflammation, macular health, and 
patient comfort. 
STUDY DESIGN 
Prospective Fellow-Eye, Randomized Open-label 
Interventional Study 
 
STUDY DURATION 
Fourteen months, including enrollment period 
 
ESTIMATED STUDY 
COMPLETION DATE 
POPULATION 
February 2022 
Sample Size: 
40 eyes 
Target Population: 
Patients with cataract and glaucoma 
 
TREATMENT(S) 
Study Drug 
Dose/Route/Schedule: 
 
 
 
ENDPOINT(S) 
Sustained Release Dexamethasone, 0.4 mg 
 
All study eyes will receive cataract extraction, IOL 
placement, minimally-invasive glaucoma surgery, and 
a postoperative topical antibiotic prescription. 20 eyes 
will be randomized to receive Sustained Released 
Dexamethasone, 0.4 mg. 20 eyes will be prescribed a 
prednisolone acetate 1% regimen. 
Primary: 
1. Reduction in IOP at 1 and 3 months 
2. BCVA at 1 and 3 months 
3. Difference in adverse events between groups 
4. Difference in # of glaucoma meds at 3 months 
Secondary: 
1. Number of patients requiring supplemental 
prednisolone acetate 1% eye drops 
2. Incidence of CME at 90 days as seen on OCT 
3. Difference in Ocular Comfort Index between 
groups at 1 month and 3 months 
4. Difference in % of patients with absence of 

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anterior chamber cells at 30 days between groups 
 
 
TABLE OF CONTENTS 
Clinical Study Protocol Synopsis ......................................................................... 2 
List of Tables ........................................................................................................... 4 
1. 
Introduction ..................................................................................................... 5 
1.1 
Type of study ................................................................................................ 5 
1.2 
Introduction .................................................................................................. 5 
1.3 
Rationale....................................................................................................... 5 
1.4 
Purpose ......................................................................................................... 6 
1.5 
Rationale for Study Design .......................................................................... 6 
2. 
Study Objectives .............................................................................................. 7 
2.1 
Primary Objective ......................................................................................... 7 
2.2 
Secondary Objectives ................................................................................... 8 
3. 
Study Design .................................................................................................... 8 
3.1 
Study Description and Duration ................................................................. 8 
4. 
Selection, Withdrawal, and Replacement of Patients................................. 8 
4.1 
Study Population ......................................................................................... 8 
4.1.1 
Inclusion Criteria .............................................................................. 8 
4.1.2 
Exclusion Criteria ............................................................................. 9 
4.2 
Treatment Logistics and Accountability ................................................... 9 
4.2.1 
Packaging, Labeling, and Storage ................................................... 9 
4.2.2 
Supply and Disposition of Treatments ......................................... 10 
4.2.3 
Treatment Accountability .............................................................. 10 
4.3 
Concomitant Medications and Procedures .............................................. 10 
5. 
Study Schedule of Events and Visit Descriptions ..................................... 10 
5.1 
Schedule of Events ..................................................................................... 10 
5.2 
Study Visit Descriptions ........................................................................... 12 
5.2.1 
Study Procedures ............................................................................ 12 
5.2.2 
Unscheduled Visits ......................................................................... 13 
5.2.3 
Adverse Event Information Collection ......................................... 14 
5.3 
Rescue Criteria........................................................................................... 14 

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6. 
Risk/Benefit Assessment .............................................................................. 14 
6.1 
Risks ............................................................................................................ 14 
6.2 
Prevention of Risks ................................................................................... 14 
6.3 
Benefits ....................................................................................................... 14 
6.4 
Alternative Treatments .............................................................................. 15 
7. 
Safety Definitions, Reporting, and Monitoring ............................................ 15 
7.1 
Definitions .................................................................................................. 15 
7.1.1 
Adverse Event ................................................................................. 15 
7.1.2 
Serious Adverse Event ................................................................... 15 
7.2 
Recording and Reporting Adverse Events .............................................. 16 
8. 
Study Variables .............................................................................................. 16 
8.1 
Demographic and Baseline Characteristics ............................................. 16 
8.2 
Primary and Secondary Endpoints ........................................................... 16 
9. 
Statistical Plan .............................................................................................. 17 
10. 
Ethical and Regulatory Considerations ................................................. 17 
10.1 Good Clinical Practice Statement ............................................................ 17 
10.2 Recruiting ................................................................................................... 17 
10.3 Informed Consent ...................................................................................... 17 
10.4 Storage of Data .......................................................................................... 18 
10.5 Confidentiality of Data.............................................................................. 18 
10.6 Participant Comprehension and Capacity ............................................... 19 
10.7 Costs to Participants .......................................................................... 19 
10.8 Compensation to Participants ................................................................... 19 
10.9 Institutional Review Board ....................................................................... 19 
LIST OF TABLES 
Table 1 
Schedule of Events ............................................................................. 11 

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1. 
INTRODUCTION 
1.1 
Type of study 
This is a drug study. The IND number is: 146602. 
 
1.2 
Introduction 
 
Following cataract surgery, the standard of care for controlling ocular 
inflammation has historically been a topically applied anti-inflammatory eye 
drop regimen. Such drops utilize steroids or non-steroidal anti-inflammatory 
drugs, with steroid drops being more commonly prescribed (Juthani et al. 
2017). Sustained-release steroid inserts, such as the FDA-approved 
intracanicular dexamethasone insert DEXTENZA®, have provided a 
“dropless” alternative to steroid eye drop regimens. DEXTENZA® was shown 
to be safe and effective following cataract surgery, in terms of ocular pain and 
anterior chamber cell clearance, in a multi-center trial (Tyson et al. 2018). 
However, in prior studies of DEXTENZA®, none have specifically examined 
the safety and efficacy of the insert in a glaucoma patient population. 
Furthermore, none have examined the outcomes of the insertion of 
DEXTENZA® following both cataract surgery and a minimally invasive 
glaucoma surgery (MIGS). DEXTENZA® may be of utility to glaucoma 
patients because it can simplify one’s combined eye drops regimen. A 
complicated medication schedule is a significant risk factor for poor 
adherence to glaucoma medication instructions (Newman-Casey et al. 2015). 
Furthermore, given that steroid eye drops are already administered after 
concomitant cataract and MIGS surgery, it is highly plausible that 
DEXTENZA (which uses a steroid as its active ingredient) should be similar 
in safety. This prospective fellow-eye study will thus target glaucomatous 
eyes to explore the further applications of DEXTENZA®. 
 
1.3 
Rationale 
Glaucoma and cataract surgery patients face an outsize postoperative 
burden. In addition to taking frequent anti-inflammatory eye drops, they 
often continue their glaucoma medications. This can cause patient confusion 
and nonadherence, potentially leading to poor healing, slower recovery 
period, and/or cystoid macular edema. DEXTENZA®, as a sustained release 
anti-inflammatory insert, could help preclude adherence difficulties and 
increase comfort by reducing eye drop load. However, glaucoma surgeons may 
hesitate to adopt DEXTENZA® due to concerns regarding safety with respect 
to elevated intraocular pressure. This prospective study will address those 
concerns directly, providing timely and high-quality clinical evidence 
comparing DEXTENZA® to standard-of-care steroid eye drops. For 
physicians and patients, the results of this study will prove immediately 
useful for therapeutic decision-making. 

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1.4 
Purpose 
The purpose of this study is to compare the safety and efficacy of sustained- 
release dexamethasone insert (DEXTENZA®) to steroid eye drops after 
glaucoma and cataract surgery. 
1.5 
Rationale for Study Design 
This prospective study will enroll 40 eyes from a variable number of total patients. The 
total patient number may vary due to the enrollment of both eyes from some patients 
where possible. All eyes will receive concomitant cataract and MIGS surgery. Each eye 
will be randomized to receive either insertion at the end of the surgery or to a standard of 
care prednisolone acetate 1% eye drop regimen. All eyes will receive the standard of care 
topical ofloxacin antibiotic regimen. The experimental group will consist of the 20 eyes 
receiving DEXTENZA® insertion. The control group will consist of the 20 eyes placed 
on the prednisolone eye drop regimen.  
 
In terms of study procedures, the majority are among cataract and MIGS 
preoperative, perioperative, and postoperative standards of care. Such 
procedures include: pachymeter, indirect ophthalmoscope, slit lamp exam, 
BCVA, IOP, visual field, OCT RNFL, corneal endothelial microscopy and 
gonioscopy. The ocular response analyzer will record corneal hysteresis data. 
Corneal hysteresis, as a measure of  the  cornea’s  ability  to  dampen  in  
response  to  an  external  force,  has  been shown in multiple studies to serve as 
an independently valuable risk factor indicating glaucoma progression (Lam 
et al. 2010; Agarwal et al. 2012; Medeiros et al. 2013). To better inform the 
treatment of glaucoma patients during this study, the ocular response analyzer 
is a valid and useful tool. 
 
In terms of primary study endpoints, change in IOP values at 1 and 3 months 
are crucial for quantifying glaucoma outcome differences between groups. 
We will use three methods to comprehensively assess IOP changes, including 
Goldmann applanation tonometry, CATS tonometer prism, and the automatic 
IOP readings provided by the ocular response analyzer. Goldmann is the 
current standard of care, and thus will be the primary measure. However, 
CATS tonometry is a valuable supplement because it utilizes a modified 
prism that may better account for central corneal thickness and corneal 
hysteresis when providing IOP measurements (McCaffertey et al. 2019). 
Change in number of glaucoma medications from preop to 3 months postop 
will be serve as an additional metric to compare glaucoma outcomes. BCVA 
measurements using an ETDRS chart at 4 meters will indicate whether 
DEXTENZA® placement in this population affects the visual acuity 
improvement conferred by an IOL and MIGS. Recording adverse events is 
necessary not only for the integrity of the study, but also for evaluating the 
safety of the DEXTENZA® insert for this study population. 
 
In terms of secondary endpoints, the number of patients requiring 

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supplementary prednisolone acetate 1% eye drops will be recorded to 
compare ocular inflammation between groups. Checking for absence of 
anterior chamber cells at 30 days will provide another measure of control of 
inflammation. Incidence of cystoid macular edema at three months will be 
used to compare macular health between groups. 
 
In previous trials of sustained-release ocular therapeutics, authors have 
commented on the need to explore patient experience as an additional 
measure (Kindle et al. 2018). Two modalities will be used to evaluate patient 
experience between groups. The Ocular Comfort Index (OCI) will be used to 
quantify ocular comfort. The OCI is a 12-item Likert-style questionnaire 
designed to assess the severity of ocular surface irritation. Authors compared 
the OCI against  the Ocular Surface Disease Index and tear-break up time 
(TBUT) values, and also examined changes in OCI scores after application of 
lubricant to dry eyes (Johnson and Murphy 2007). Statistical analysis of those 
three constructs support the use of the OCI to help quantify dry eye disease  
severity. Although participants in this study will not represent a dry eye 
disease population, the OCI nevertheless provides quantifiable data on 
general discomfort in each eye. For sustained released dexamethasone 
specifically, some physicians may be wary that its location in the punctum 
may contribute to discomfort in a way that an intracameral or intravitreal 
steroid would not. The OCI would address such concerns directly. From a 
clinical utility standpoint,  the  OCI  is  favorable  due  to  the  questionnaire’s  
free  access,  an included Excel calculator for rudimentary data analysis, and 
the brevity of  the 12-item questionnaire. Administering the OCI at 1 month 
postop and 3 months postop will offer insight into both the immediate and 
delayed changes in ocular comfort for each group. 
 
2. 
STUDY OBJECTIVES 
2.1 
Primary Objective 
To determine the effect of dexamethasone insert through 90 days as 
measured by – 
• Visual acuity 
• IOP control 
• Adverse events 
2.2 
Secondary Objectives 
To determine the effect of dexamethasone insert through 90 days as 
measured by – 
• Control of inflammation 
• Macular health 
• Patient comfort 
 
3. 
STUDY DESIGN 
3.1 
Study Description and Duration 
This prospective, open-label, single-center, randomized, fellow-eye, 

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investigator-initiated clinical study seeks to investigate the safety and 
efficacy of the dexamethasone insert in glaucoma patients after concomitant 
MIGS and cataract surgery. After screening a given patient for inclusion 
and exclusion criteria, and gaining informed consent, the patient’s eligible 
eye will be randomized to either receive the dexamethasone insert after 
concomitant cataract-MIGS or to receive prednisolone acetate 1% eye 
drops after concomitant cataract-MIGS. For participants who enroll only a 
single eye, block randomization will be performed to ensure that the type 
of MIGS surgeries will be balanced between the two treatment groups. 
This stratification is necessary because it is possible that different MIGS 
devices can confound endpoint measurements, such as IOP control. A 
stratified block randomization schedule will be developed in advance by 
the sub-investigator through a computer program, and each assignment 
will be placed in opaque, sealed envelopes that will be labeled with the 
stratifying MIGS category. The primary investigator will only open an 
envelope after a patient is enrolled and the MIGS type that is suitable for 
the patient is determined. In the few cases where a patient enrolls both 
eyes, the same MIGS surgery will be performed for each eye. Under such 
a circumstance, simple randomization will be sufficient to determine 
whether the first or second eye operated on will receive the 
dexamethasone insert. The other eye will be placed in the prednisolone 
acetate 1% eye drops group.   
 
Per enrolled eye, the study period will last for approximately 90 days after 
surgery, consisting of four postop follow-up visits. At Day 1, Day 7, Day 
30, and Day 90, primary and secondary endpoints will be assessed 
alongside standard-of-care procedures. Adjusting for enrollment period, 
the study will last a total of approximately twelve months.  
 
4. 
SELECTION, WITHDRAWAL, AND REPLACEMENT OF PATIENTS 
4.1 
Study Population 
This study aims to enroll 40 eyes from patients with both cataract and glaucoma.   
 
 
4.1.1 
Inclusion Criteria 
A patient must meet the following criteria to be eligible for inclusion in the 
study: 
 
• At or over the age of 21 
• Cataract surgery candidate and glaucoma present in at least one eye 
• Minimally-invasive glaucoma surgery candidate in at least one eye. 
Defined by having ocular hypertension requiring a medication, OR 
as by having mild, moderate, or severe glaucoma that is sufficiently 
stable and appropriate for operation. 

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4.1.2 
Exclusion Criteria 
A patient who meets any of the following criteria will be excluded from the 
study: 
• Maintains regular use (daily or more) of systemic or ocular steroids at 
time of enrollment 
• Maintains regular use (daily or more) of systemic or ocular non- 
steroidal anti-inflammatory drugs at time of enrollment 
• Anterior chamber cells present at time of enrollment 
• Recent febrile illness that precludes or delays participation for 3 
months 
• Pregnancy or lactation 
• Known allergy to dexamethasone 
• Known allergy to prednisolone 
• Treatment with another investigational drug within the last 20 years 
• Current recreational drug use 
• Preexisting ocular pathology likely to confound the visual acuity 
or comfort endpoints including but not limited to: severe 
corneal scarring, ocular surface disease, diabetic retinopathy, or 
macular edema  
• Corneal or retinal procedures (laser or incisional) during the study 
period and 6 months prior in either eye 
 
4.2 
Treatment Logistics and Accountability 
4.2.1 Packaging, Labeling, and Storage 
Intracanalicular dexamethasone insert must be stored in a secure area 
accessible only to the Investigator and their designee(s) and refrigerated and 
stored between 2o C and 80 C. Intracanalicular dexamethasone insert 
contains 0.4 mg dexamethasone and is designed to provide a sustained and 
tapered release of therapeutic levels of dexamethasone to the ocular surface 
for up to 30 days for the reduction of post-surgical inflammation and pain 
associated with ocular surgery. Dexamethasone is an anti-inflammatory 9-
fluoro-glucocorticoid (also termed a glucocorticoid agonist) and is the active 
ingredient found in MAXIDEX® 0.1% (dexamethasone ophthalmic 
suspension), which contains approximately 50 µg of dexamethasone per drop. 
 
Study inserts will be supplied by Ocular Therapeutix in a sealed foil pouch 
containing one intracanalicular dexamethasone insert in a foam carrier. 
 
Study inserts will be shipped to the site via overnight shipping using cold 
packs to maintain a temperature of 2° to 8° C. The Investigator, or an 
approved representative (e.g. pharmacist), will ensure that all study drug 
inserts are stored in a secured area, under recommended storage conditions 
and in accordance with applicable regulatory requirements. The shipping box 
is to be opened and stored immediately at the site in a refrigerator intended 

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for investigational products at a temperature of 2° to 8°C. 
 
When the insert is removed from the refrigerator, it should be visually 
inspected. Exposure of the insert to temperatures outside these limits it not 
recommended. Records of actual storage conditions (i.e. temperature log) at 
the study site must be maintained; and must include a record of the dates, 
when the refrigerator was checked, the initials of person checking, and the 
temperature. 
 
4.2.2 Supply and Disposition of Treatments 
Study insert will be shipped at a temperature of 2° to 8°C to the investigator 
as needed during the study. 
 
4.2.3 Treatment Accountability 
All study insert accountability records will be kept current. 
 
The investigator will account for all opened and unopened packaging of study 
inserts. These records will contain the dates, quantity, and study medication 
• Inserted in each patient, 
• disposed of at the site or returned to Ocular Therapeutix 
All accountability records will be made available for inspection by regulatory 
agency inspectors. 
 
4.3 
Concomitant Medications and Procedures 
At the discretion of their physician, patients may continue to receive all 
medications and standard treatments administered for other conditions. 
 
5. 
STUDY SCHEDULE OF EVENTS AND VISIT DESCRIPTIONS 
5.1 
Schedule of Events 
Study assessments and procedures are presented by visit in Table 1. 

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Table 1 
Schedule of Events 
 
Study Procedure 
Screening/ 
Baseline 
Surgica 
l Visit 
Day 0 
Day 1 
Day 7 
Day 30 
3 MTH 
post-op 
Early 
Termi 
nation 
Visit 
VISIT 1 
VISIT 2 
VISIT 3 
VISIT 4 
VISIT 5 
VISIT 6 
Windows for Visits 
(Day -90 to - 
1) 
(+/- 2 
days) 
(+/- 2 
days) 
(+/- 7 
days) 
(+/- 14 
days) 
Inclusion/Exclusion 
X 
Informed Consent 
X 
Demographics 
X 
Medical History and Concurrent 
Illnesses 
X 
Concomitant Medications (inc. 
glaucoma meds and supp. 
prednisolone) 
X 
X 
X 
X 
X 
BCVA (ETDRS at 4m) 
X 
X 
X 
X 
X 
Visual field mean deviation 
X 
X 
Ophthalmic Examination (dilated 
fundus exam) 
X 
X 
X 
X 
X 
Cataract density grade (scale 1 to 
4) and type 
X 
Glaucoma type and severity 
X 
OCT RNFL & Macula 
X 
X 
Intraocular Pressure (Goldmann 
and CATS) 
X 
X 
X 
X 
X 
Corneal Endothelial Specular 
Microscopy 
X 
 
 
 
X 
Gonioscopy 
X 
X 
Ocular Response Analyzer 
X 
X 
Pachymeter 
X 
Indirect Ophthalmoscope 
X 
X 
Indicate the incision type, 
location, and size (mm) 
X 
Type of IOL (e.g. monofocal, toric, 
multifocal, etc.) and lens power 
X 
X 
Type of MIGS device 
X 
X 
Record any surgical complications 
X 
X 
Subject reported AEs prior to or 
after surgery 
X 
X 
X 
X 
X 
X 
Intracanalicular dexamethasone 
insert 
X 
Ocular Comfort Index 
 
X 
X 
Anterior chamber cell count 
X 
X 
X 
X 
Anterior chamber cell flare 
X 
X 
X 
X 
Insert Visualization 
X 
X 
X 
X 
Prescribe post-operative topical 
therapy regimen 
X 

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5.2 
Study Visit Descriptions 
5.2.1 Study Procedures 
Screening/Baseline (Day -90 to -1) 
After the patient has provided informed consent, the following information 
will be collected: 
1. Inclusion/exclusion 
2. Demographics 
3. Medical history and concurrent illnesses 
4. Concomitant medications 
5. Best-corrected visual acuity as measured by ETDRS chart at 4m 
6. Visual field mean deviation 
7. Ophthalmic examination 
8. Grade cataract density and identify type 
9. Glaucoma type and severity 
10. OCT RNFL & Macula 
11. Goldmann Intraocular pressure and CATS intraocular pressure 
12. Corneal endothelial specular microscopy 
13. Gonioscopy 
14. Ocular Response Analyzer 
15. Pachymeter 
16. Indirect ophthalmoscope 
17. Type of IOL 
18. Type of MIGS device (Hydrus, iStent, canaloplasty, or Kahook Dual-Blade) 
19. Subject reported AEs prior to surgery 
 
Surgical visit/Day 0 
1. Indicate the incision type, location, and size 
2. Type of IOL 
3. Type of MIGS device (Hydrus, iStent, canaloplasty, or Kahook 
Dual-Blade) 
4. Record any surgical complications 
5. Intracanicular dexamethasone insert 
 
Day 1 postop (+/- 2 days) 
1. Concomitant medications 
2. Best-corrected visual acuity as measured by ETDRS chart at 4m 
3. Ophthalmic examination 
4. Goldmann Intraocular pressure and CATS intraocular pressure 
5. Subject reported AEs after surgery 
6. Anterior chamber cell count 
7. Anterior chamber cell flare 
8. Insert Visualization 
9. Prescribe post-operative topical therapy regimen 
 
Day 7 postop (+/- 2 days) 

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1. Concomitant medications 

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2. Best-corrected visual acuity as measured by ETDRS chart at 4m 
3. Ophthalmic examination 
4. Goldmann Intraocular pressure and CATS intraocular pressure 
5. Subject reported AEs after surgery 
6. Anterior chamber cell count 
7. Anterior chamber cell flare 
8. Insert Visualization 
 
Day 30 postop (+/- 7 days) 
1. Concomitant medications 
2. Best-corrected visual acuity as measured by ETDRS chart at 4m 
3. Ophthalmic examination 
4. Goldmann Intraocular pressure and CATS intraocular pressure 
5. Subject reported AEs after surgery 
6. Anterior chamber cell count 
7. Anterior chamber cell flare 
8. Insert Visualization 
9. Ocular Comfort Index 
 
3 month postop (+/- 14 days) 
1. Concomitant medications 
2. Best-corrected visual acuity as measured by ETDRS chart at 4m 
3. Ophthalmic examination 
4. Goldmann Intraocular pressure and CATS intraocular pressure 
5. Corneal endothelial specular microscopy 
6. Subject reported AEs after surgery 
7. Anterior chamber cell count 
8. Anterior chamber cell flare 
9. Insert Visualization 
10. OCT RNFL & Macula 
11. Visual field mean deviation 
12. Gonioscopy 
13. Ocular Response Analyzer 
14. Ocular Comfort Index 
15. Indirect ophthalmoscope 
 
 
5.2.2 Unscheduled Visits 
All attempts should be made to keep patients on the study schedule. 
Unscheduled visits may be necessary to repeat testing following abnormal 
laboratory results, for follow-up of AEs, or for any other reason, as warranted. 

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5.2.3 Adverse Event Information Collection 
The investigator (or designee) will record all AEs that occur during the study 
The definition of an AE and SAE, and information on the determination of 
severity and relationship to treatment are provided in Section 7. 
 
5.3 
Rescue Criteria 
Rescue criteria include any of the following: moderate to severe photophobia, 
moderate to severe ciliary or conjunctival injection, or excessive anterior 
chamber cells or flare. 
 
Rescue treatment would include supplementary prednisolone acetate 1% 
drops and/or topical NSAIDs, at the discretion of the study doctor. 
 
6. 
RISK/BENENFIT ASSESSMENT 
6.1 
Risks 
Use of corticosteroids on the eye, whether they are steroid drops or sustained- 
release inserts like DEXTENZA®, can worsen glaucoma with damage to the 
optic nerve by increasing intraocular pressure. Corticosteroids may suppress 
the host immune system and increase risk for bacterial infection, fungal 
infection, and viral infection. The use of steroids after eye surgery may delay 
healing and increase the incidence of bleb formation. DEXTENZA® may be 
ineffective. DEXTENZA® may cause discomfort in the eye. DEXTENZA® 
may involve unforeseeable risks. DEXTENZA® may involve additional risks 
that are currently unknown. Because DEXTENZA® is FDA approved for the 
treatment of postoperative ocular inflammation and pain, minimal overall  
risk to patients is anticipated. 
6.2 
Prevention of Risks 
At each follow-up visit, risks will be monitored through conversations with 
the participant regarding their postoperative issues and visualized thorough  
all components of the ophthalmic exam (please see Table 1). Rescue 
treatment will be administered as per the criteria of section 5.3. 
6.3 
Benefits 
For the eye receiving DEXTENZA®, a potential benefit is that the participant 
will not have to take steroid eye drops in that eye after surgery. 
DEXTENZA® may potentially be more comfortable and/or convenient than 
steroid eye drops. The results of this study will benefit future patients by 
providing clinical evidence comparing the safety and efficacy of DEXTENZA® 
to steroid eye drops in eyes with glaucoma and a cataract. 

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6.4 
Alternative Treatments 
Steroid eye drops are the standard-of-care alternative to DEXTENZA®. Also, 
DEXYCU® is another type of sustained-release dexamethasone drug that is 
currently FDA-approved for the same indication as DEXTENZA®. 
DEXYCU® is injected inside the eye, behind the iris of the eye. No currently 
published study has compared DEXTENZA® to DEXYCU®, so the relative 
advantages and disadvantages are not clearly known. 
 
 
7. 
SAFETY DEFINITIONS, REPORTING, AND MONITORING 
7.1 
Definitions 
7.1.1 Adverse Event 
An AE is any untoward medical occurrence in a patient administered a study 
drug which may or may not have a causal relationship with the study drug. 
Therefore, an AE is any unfavorable and unintended sign (including 
abnormal laboratory finding), symptom, or disease which is temporally 
associated with the use of a study drug, whether or not considered related to 
the study drug. 
 
An AE also includes any worsening (i.e. any clinically significant change in 
frequency and/or intensity) of a pre-existing condition that is temporally 
associated with the use of the study drug. 
 
7.1.2 Serious Adverse Event 
A SAE is any untoward medical occurrence that at any dose: 
• Results in death – includes all deaths, even those that appear to be 
completely unrelated to study drug (e.g. a car accident in which a patient 
is a passenger). 
• Is life-threatening – in the view of the investigator, the patient is at 
immediate risk of death at the time of the event. This does not include an 
AE that had it occurred in a more severe form, might have caused death. 
• Requires in-patient hospitalization or prolongation of existing 
hospitalization. In-patient hospitalization is defined as admission to a 
hospital or an emergency room for longer than 24 hours. Prolongation of 
existing hospitalization is defined as a hospital stay that is longer than 
was originally anticipated for the event, or is prolonged due to the 
development of a new AE as determined by the investigator or treating 
physician. 
• Results in persistent or significant disability/incapacity (substantial 
disruption of one’s ability to conduct normal life functions). 
• Is a congenital anomaly/birth defect 
• Is an important medical event – Important medical events may not be 
immediately life-threatening or result in death or hospitalization, but may 

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jeopardize the patient or may require intervention to prevent 1 of the  
other serious outcomes listed above (e.g., intensive treatment in an 
emergency room or at home for allergic bronchospasm; blood dyscrasias or 
convulsions that do not result in hospitalization; or development of drug 
dependency or drug abuse). Any malignancy (other than basal cell skin 
cancers) would be considered a medically important event. 
 
7.2 
Recording and Reporting Adverse Events 
All AEs and SAEs will be recorded only if they are medically relevant. 
 
All SAEs, regardless of assessment of causal relationship to study insert will 
be reported to Ocular Therapeutix. 
To report an SAE, Ocular Therapeutix will be contacted at the 
following: 
ocutx.pharmacovigilance@propharmagroup.com 
SAE hotline: 844-668-3948 
 
The investigator will promptly report to the IRB all unanticipated problems 
involving risks to patients. This includes death from any cause and all SAEs 
related to the use of the study insert. All SAEs will be reported to the IRB, 
regardless of assessed causality. 
 
8. 
STUDY VARIABLES 
8.1 
Demographic and Baseline Characteristics 
Baseline characteristics will include standard demography (e.g. age, race, 
weight, height, etc.), disease characteristics including medical history, and 
medication history for each patient. 
 
8.2 
Primary and Secondary Endpoints 
Primary Endpoints 
Effect of dexamethasone insert through Day 90 as measured by – 
1. Mean Reduction in IOP at 1 and 3 months as measured by Goldmann 
Applanation Tonometer and comparison between groups 
2. Mean change in ETDRS BCVA at 1 and 3 months and comparison 
between groups 
3. Difference in adverse events between the two groups 
4. Difference in number of glaucoma medications between the wo groups at 3 
months 
Secondary Endpoints 
Through Day 90 as measured by – 
1. Number of patients requiring supplemental prednisolone acetate 1% eye 
drops 
2. Incidence of CME at 90 days as seen on OCT 

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3. Difference in Ocular Comfort Index between the two groups at 1 month 
and 3 months 
4. Difference in percentage of patients with absence of anterior chamber cells 
at 30 days between groups 
 
9. 
STATISTICAL PLAN 
Primary endpoints and secondary endpoints will be analyzed through 
statistical hypothesis testing. Demographic and baseline characteristics will 
be summarized descriptively. Continuous variables will be summarized with 
mean, median, and standard deviation. Categorical variables will be 
summarized with frequency and percentage. 
 
10. 
ETHICAL AND REGULATORY CONSIDERATIONS 
10.1 Good Clinical Practice Statement 
It is the responsibility of the investigator(s) to ensure that this clinical study 
will be conducted in accordance with the ethical principles that have their 
origin in the Declaration of Helsinki, and that are consistent with the ICH 
guidelines for Good Clinical Practice (GCP) and applicable regulatory 
requirements. 
 
10.2 Recruiting 
Participants will be recruited from the New York Eye Surgery Center in the 
Bronx, NY. Potential participants will be identified based on information in 
their medical records and most recent exam findings. The investigator will 
discuss the study with potential participants at their check-up appointment. 
The potential participant will be provided with information on the study 
device, the study protocol, risks and benefits, patient data security, 
procedures if an adverse event occurs, travel compensation, and the informed 
consent form. The investigator will present reasonable alternatives to the 
study device. The investigator will emphasize that participation is entirely 
voluntary,  and  that  neither  the  patient’s  relationship  with  the  investigator 
nor his/her quality of care will be impacted by the decision to or to not 
participate. The investigator will encourage the potential participant to ask 
questions, and will respond to whatever questions arise. 
 
10.3 Informed Consent 
The principles of informed consent are described in ICH Guidelines for GCP. 
 
Ocular Therapeutix will have the right to review and comment on the 
informed consent form. 

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It is the responsibility of the investigator or designee (if acceptable by local 
regulations) to obtain written informed consent from each patient prior to 
his/her participation in the study and after the aims, methods, objectives, and 
potential hazards of the study have been explained to the patient in language 
that he/she can understand. The ICF will be signed and dated by the patient 
and by the investigator or authorized designee who reviewed the ICF with  
the patient. 
 
Patients who can write but cannot read will have the ICF read to them before 
signing and dating the ICF. 
Patients who can understand but who can neither write nor read will have 
the ICF read to them in presence of an impartial witness, who will sign and 
date the ICF to confirm that informed consent was given. 
 
The original ICF will be retained by the investigator as part of the patient’s 
study record, and a copy of the signed ICF will be given to the patient. 
 
If new safety information results in significant changes in the risk/benefit 
assessment, the ICF will be reviewed and updated appropriately. All study 
patients will be informed of the new information and provide their written 
consent if they wish to continue in the study. The original signed revised ICF 
will be maintained in the patient’s study record and a copy will be given to the 
patient. 
 
10.4 
Storage of Data 
Data from the study will be stored in paper files and electronically. The 
investigator, sub-investigator, study staff, and Ocular Therapeutix will have 
access to the data purely for research purposes. Microsoft Excel and the 
Medflow electronic medical record system will be used to manage and extract 
patient data. 
 
10.5 
Confidentiality of Data 
The investigator will take all appropriate measures to ensure that the 
anonymity of each study patient will be maintained. 
 
The patient’s and investigator’s personal data will be treated in compliance 
with all applicable laws and regulations. 
 
Paper files will be secured in a locked drawer accessible only to the 
investigator, the research assistant, and study staff. Medflow data will be 
stored under password protection in the servers of the New York Eye Surgery 

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CONFIDENTIAL 
 
 
Center. Excel spreadsheet data will be stored locally in the sub-investigator’s 
password-protected and antivirus-secured Macbook laptop. Participant  names 
will be coded by randomized numbers. 
10.6 
Participant Comprehension and Capacity 
To assess comprehension, the potential participant will be asked to “teach 
back” to the principal investigator what he/she learned about the study from 
the informed consent form. At minimum, they will be quizzed on: 1) What 
DEXTENZA® does; 2) Risks to participating; 3) How many follow-up visits 
they  are  expected   to  attend;  4)  How   late  the  participant’s   second   eye’s 
surgery can be scheduled after the first eye surgery; and 5) What happens in 
the event of a complication. Potential participants will also be asked to voice 
any questions they have to the principal investigator. 
 
10.7 
Costs to Participants 
The study doctor, Dr. Radcliffe, will be covering the costs of all procedures 
and necessary follow-ups associated with the study. 
10.8 
Compensation to Participants 
Participants will receive $10 at each post-surgical follow up visit, per eye, in order to 
cover the costs of travel. If a participant completes all four post-surgical follow-up visits 
in one eye, the participant will have received $40 in total. If a participant enrolls two eyes 
and completes a total of eight post-surgical follow-up visits, he or she will have received 
$80 in total. 
 
10.9 Institutional Review Board 
An appropriately constituted IRB, as described in ICH Guidelines for GCP, 
will review and approve: 
• The protocol, ICF, and any other materials to be provided to the patients 
(e.g. advertising) before any patient may be enrolled in the study 
• Any amendment or modification to the study protocol or ICF before 
implementation, unless the change is necessary to eliminate an 
immediate hazard to the patients, in which case the IRB will be informed 
as soon as possible 
 
Ongoing studies will be reviewed by the IRB/EC on an annual basis or at 
intervals appropriate to the degree of risk. 
 
In addition, the IRB will be informed of any event likely to affect the safety of 
patients or the continued conduct of the clinical study. 
 
A copy of the IRB approval letter will be sent to Ocular Therapeutix prior to 
shipment of drug insert supplies to the investigator. The approval letter will 
include the study title, the documents reviewed, and the date of the review. 

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Records of the IRB review and approval of all study documents (including 
approval of ongoing studies) will be kept on file by the investigator. 

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