A Randomized, Controlled, Masked (Reading Center) Prospective Study of the Effectiveness and Safety of the Ocular Therapeutix Dextenza 0.4 mg for the Treatment of Post-op. Inflammation and Pain in PRK
Phase: PHASE4
Conditions: Refractive Surgery
Sponsor: Vance Thompson Vision

The RESTORE Study (V1) 
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CONFIDENTIAL 
 
 
Investigator-Initiated Study Protocol 
 
 
A Randomized, Controlled, Masked (Reading Center) Prospective Study of 
the Effectiveness and Safety of the Ocular Therapeutix Dextenza 
(dexamethasone Ophthalmic insert) 0.4 mg for the treatment of post-
operative inflammation and pain in patients who have undergone 
PhotoREfractive Keratectomy (PRK) 
 
The RESTORE Study 
 
 
 
Compound: 
DEXTENZA (dexamethasone 
ophthalmic insert) 0.4 mg for 
intracanalicular use 
 
 
Study Name: 
A Randomized, Controlled, Masked 
(Reading Center) Prospective Study 
of the Effectiveness and Safety of the 
Ocular Therapeutix Dextenza 
(dexamethasone ophthalmic insert) 
0.4 mg for the treatment of post-
operative inflammation and pain in 
patients who have undergone 
Photorefractive Keratectomy (PRK)- 
The RESTORE Study 
 
 
Clinical Phase: 
Prospective, Randomized, Controlled, 
Masked Investigator-Initiated Trial 
 
 
Date of Issue: 
December 17, 2019 
 
 
Primary Investigator: 
John Berdahl, MD 
 
 
Sub Investigator: 
Mitch Ibach, OD 
 
Site Name & Location: 
Vance Thompson Vision Center 
3101 West 57th Street 
Sioux Falls, South Dakota 
57108 
 
 
 
 

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CONFIDENTIAL 
CLINICAL STUDY PROTOCOL SYNOPSIS 
TITLE 
A Randomized, Controlled, Masked (Reading 
Center) Prospective Study of the Effectiveness and 
Safety of the Ocular Therapeutix Dextenza 
(dexamethasone ophthalmic insert) 0.4 mg for the 
treatment of post-operative inflammation and pain 
in patients who have undergone Photorefractive 
Keratectomy (PRK) 
SITE LOCATION(S) 
 
Vance Thompson Vision Center 
3101 West 57th Street 
Sioux Falls, South Dakota 
57108 
PRINCIPAL 
INVESTIGATOR 
John Berdahl, MD 
OBJECTIVE(S) 
To determine patient preference and treatment 
outcomes with an intracanalicular dexamethasone 
(0.4mg) insert compared to standard steroid drop 
regimen in the contralateral eye following bilateral 
PRK surgery. 
STUDY DESIGN 
Prospective Open-label Interventional Study 
Randomized, self-controlled design in which one 
eye (Group A) receives Dextenza and the second 
eye (Group B) receives prednisolone acetate 1% 
QID 1 week, BID 1 week following bilateral PRK 
surgery. All eyes will receive topical moxifloxacin 
QID for one week. Moxifloxacin in used post-op 
regardless of the research.  Post-operative 
evaluations to be performed on Day 3 and Day 4, 
Month 1, and Month 3. Phone call survey to be 
performed on Week 2.  
STUDY DURATION 
3 months 
ESTIMATED STUDY 
COMPLETION DATE 
January 2021 
POPULATION 
 
Sample Size: 
N=20 (40 eyes) 
Target Population: 
Patients planning to undergo bilateral 
Photorefractive Keratectomy (PRK) surgery. 
TREATMENT(S) 
 

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Study Drug 
 
 
 
Dose/Route/Schedule: 
DEXTENZA (dexamethasone ophthalmic insert) 
0.4 mg for intracanalicular use  
 
All patients will be enrolled for bilateral PRK 
surgery. The first eye will be randomized to Group 
A or B; the second eye will be selected for the 
opposite group. Group A will receive Dextenza at 
the time of PRK surgery while Group B will receive 
prednisolone acetate 1% QID 1 week, BID 1 week 
following bilateral PRK surgery. All eyes will 
receive topical moxifloxacin QID for 1 week. 
Moxifloxacin is used post-op regardless of the 
research.  
 
ENDPOINT(S) 
 
Primary: 
Adapted COMTOL Survey 
 
 
Secondary: 
 
 
 
 
 
 
 
 
Safety: 
Percentage of eyes epithelialized at POD 4 
Corneal Staining 
Corneal haze 
Ocular Pain Assessment 
Uncorrected distance visual acuity  
Corrected distance visual acuity 
Manifest refraction spherical equivalent 
Modified SPEED questionnaire  
 
IOP spikes (increase of 10 mm Hg or greater than 
baseline) 
Adverse events 
 

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TABLE OF CONTENTS 
Clinical Study Protocol Synopsis ................................................................................ 2 
List of Tables ................................................................................................................... 5 
1. 
Introduction and Rationale .................................................................................. 6 
1.1 
Introduction ......................................................................................................... 6 
1.2 
Rationale ............................................................................................................... 6 
1.2.1 
Rationale for Study Design .................................................................. 7 
2. 
Study endpoints ...................................................................................................... 7 
2.1 
Primary Endpoint ............................................................................................... 7 
2.2 
Secondary Endpoints ......................................................................................... 7 
2.3 
Safety Endpoints ................................................................................................. 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 ................................................................................. 11 
5.2.1 
Study Procedures .................................................................................. 11 
5.2.2 
Unscheduled Visits ............................................................................... 14 
5.2.3 
Adverse Event Information Collection............................................. 14 
5.3 
Rescue Criteria .................................................................................................. 15 
6. 
Safety Definitions, Reporting, and Monitoring .............................................. 15 
6.1 
Definitions .......................................................................................................... 15 
6.1.1 
Adverse Event ....................................................................................... 15 

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6.1.2 
Serious Adverse Event ........................................................................ 15 
6.2 
Recording and Reporting Adverse Events .................................................. 16 
7. 
Study Variables ..................................................................................................... 16 
7.1 
Demographic and Baseline Characteristics ............................................... 16 
8. 
Ethical and Regulatory Considerations........................................................... 16 
8.1 
Good Clinical Practice Statement ................................................................. 16 
8.2 
Informed Consent ............................................................................................. 16 
8.3 
Patient Confidentiality and Data Protection ............................................. 17 
8.4 
Institutional Review Board ............................................................................ 17 
 
LIST OF TABLES 
Table 1 
Schedule of Events ................................................................................... 11 
  
 

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1. 
INTRODUCTION AND RATIONALE 
1.1 
Introduction 
 
Photorefractive Keratectomy (PRK) is a well-studied, FDA approved, 
refractive surgery option for many patients. Post-operatively patients are 
commonly treated with antibiotic drops for infection prophylaxis, steroid drops 
for inflammation and corneal haze prevention, and finally NSAIDs (non-
steroidal anti-inflammatory drugs) for pain management. Although the types 
of medications are standardized, there are many different protocols that vary 
based on surgeon and practice preference.  
 
Post-operative drop regimens frequently induce both concerns and 
questions for patients undergoing ocular surgery. Poor compliance with post-
operative medications can lead to unexpected and or unsatisfactory outcomes.  
With refractive surgery visual outcomes and safety at such a high level, patient 
satisfaction and experience can be altered by post-operative convenience.  
 
Dextenza (dexamethasone 0.4mg ophthalmic insert) is a steroid eluting 
intracanalicular plug approved on-label for the treatment of pain and post-
operative inflammation in patients who’ve undergone ocular surgery. Utilizing 
Dextenza, in place of ophthalmic steroid drops, will provide patients with a 
lessened number of post-operative drops which decreases both contamination 
possibilities and improper drug installation. Dextenza’s hydrogel technology is 
proposed to offer patients a gradual sustained delivery of steroid to the ocular 
surface which may decrease subjective post-operative pain.  
 
The tear film is a key component in corneal epithelial healing as well as 
refractive outcomes in PRK. In many studies, inflammation and inflammation 
markers are a driver to decreasing tear film homeostasis. With an 
intracanalicular steroid plug there is potential benefit to restoring tear film 
homeostasis sooner, combined with increased tear volume, leading to improved 
epithelialization and refractive outcomes. Finally, intracanalicular steroid 
plugs offer patients a preservative free steroid option to further promote 
epithelial health by decreasing topical preservatives. 
 
1.2 
Rationale 
 
DEXTENZA (dexamethasone 0.4mg ophthalmic insert) has increasing 
research and evidence for post-cataract surgery patients, but a gap remains in 
many other ophthalmic surgeries. Refractive surgery, similar to cataract 
surgery, has post-operative visual acuity as a major determinant of surgery 
success. Dextenza’s ability to treat post-operative inflammation while also 
increasing remaining tear volume by punctal occlusion has potential to 
improve visual outcomes for patients while also decreasing post-operative drop 
inconvenience.  
 

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1.2.1 
Rationale for Study Design 
 
This prospective contralateral eye study will compare the outcomes of 
20 patients undergoing bilateral PRK. In one eye the patient will receive a 
topical steroid and the contralateral eye will receive a Dextenza ophthalmic 
insert. Both eyes will receive a topical antibiotic. 
The primary endpoint of patient preference and pain was chosen based 
on previous studies that have shown decreasing topical medications increases 
patient satisfaction. Secondary endpoints including SPEED survey and 
corneal staining were chosen to test the hypothesis of less ocular surface 
disease with Dextenza. Time to epithelialization will be studied to see the 
positive or neutral effects of steroid plus punctal occlusion on epithelialization. 
Finally, the other secondary endpoints are standard measures for PRK.  
The study inclusion and exclusion criteria were chosen based on patients 
who normally would be successful with laser refractive surgery. The study 
follow-up visits were based on the Vance Thompson Vision standard post-
operative follow-up protocols.  
 
2. 
STUDY ENDPOINTS 
2.1 
Primary Endpoint 
To determine at Month 1 (Day 28 +/-3 days):  
• Patient preference as measured by adapted COMTOL survey at Month 
1 following surgery. 
 
2.2 
Secondary Endpoints 
To determine at Post-Operative Day 3 and 4: 
• Percentage of eyes epithelialized at Day 3 and Day 4. 
To determine through Month 1 (Day 28 +/- 3 days): 
• Mean pain score per eye (Group A vs. Group B) as measured by the 
Numerical Rating Scale (NRS) at Day 3, Day 4, Week 2 (collected via 
telephone survey), and Month 1. 
• Patient preference as measured by a modified SPEED questionnaire at 
Pre-op Visit and Month 1. 
To determine through Month 3 (+/- 4 days): 
• Incidence and grade of post-operative corneal haze as measured by 
Heidelberg Anterior Segment OCT at Pre-op Visit, Month 1, and 
Month 3. 
• Post-operative corneal staining score as measured by the National Eye 
Institute (NEI) grading system at Day 3, Day 4, Month 1, and Month 3. 

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• Uncorrected visual acuity as measured by ETDRS chart at 4m at Month 
1 and Month 3. 
• Best-corrected visual acuity as measured by ETDRS chart at 4m at 
Month 1 and Month 3 
• Manifest Refraction Spherical Equivalent as measured by the 
Optometrist at Month 1 and Month 3.  
2.3 
Safety Endpoints 
To determine through Month 3 (+/- 4 days): 
• Incidence of increased IOP >10 mmHg above baseline at all timepoints 
• Occurrence of adverse events at all timepoints 
 
3. 
STUDY DESIGN 
3.1 
Study Description and Duration 
This 
prospective, 
open-label, 
single-center, 
randomized, 
investigator-
sponsored clinical study seeks to investigate the outcomes of patients 
undergoing bilateral PRK surgery with the treatment of a dexamethasone 
intracanalicular insert compared to topical standard of care steroid. All eyes 
will receive treatment. Additionally, all eyes will receive topical moxifloxacin 
QID for 1 week. Moxifloxacin is used post-op regardless of the research.  
 
Twenty patient eyes undergoing bilateral PRK surgery will be randomized to 
receive either Dextenza (Group A) OR standard of care prednisolone acetate 
1% QID for 1 week, BID for 1 week (Group B). The contralateral eye will receive 
treatment with either Dextenza or topical prednisolone as a comparator based 
on randomization of first eye to Group A or Group B. Post-operative 
evaluations to be performed on Day 3, Day 4, phone call survey at Week 2, 
Month 1, and Month 3. 
 
4. 
SELECTION, WITHDRAWAL, AND REPLACEMENT OF PATIENTS 
4.1 
Study Population 
The study aims to enroll 20 patients planning to undergo bilateral PRK 
surgery. 
 
4.1.1 
Inclusion Criteria 
A patient’s study eye must meet the following criteria to be eligible for 
inclusion in the study: 
• Any adult patient who is planned to undergo bilateral PRK surgery. 
• Willing and able to comply with clinic visits and study related 
procedures 
• Willing and able to sign the informed consent form 
 

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4.1.2 
Exclusion Criteria 
A patient who meets any of the following criteria will be excluded from the 
study: 
• Patients under the age of 18. 
• Patients who are pregnant (must be ruled out in women of child-
bearing age with pregnancy test). 
• Active infectious ocular or systemic disease. 
• Patients with active infectious ocular or extraocular disease. 
• Patients actively treated with local or systemic immunosuppression 
including systemic corticosteroids. 
• Patients with known hypersensitivity to Dexamethasone. 
• Patients with severe disease that warrants critical attention, deemed 
unsafe for the study by the investigator. 
• Patients with a history of ocular inflammation or macular edema. 
• Patients with allergy or inability to receive intracameral antibiotic. 
• Patients on systemic non-steroidal anti-inflammatory drugs (NSAID) 
greater than 1,200 mg/day 
• Patients with a corticosteroid implant (i.e. Ozurdex).  
• Patient with corneal pathology which pre-disposes them to 
unsatisfactory outcomes.  
• Patients who do not have 20/20 snellen visual acuity potential pre-
operatively.  
• MRSE greater than 6 diopters.  
• Greater than 2 diopters anisometropia. 
 
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 

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CONFIDENTIAL 
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 
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 
 
 
 
Surgical 
Visit  
Day 0 
 
 
 
 
 
Day 3 
 
 
 
 
 
 
Day 4 
 
 
 
 
 
 
Day 14 
 
 
 
 
 
Day 28 
 
 
 
3 MTH 
post-op  
 
 
 
Early 
Terminat
ion 
Visit 
VISIT 1 
VISIT 2 
VISIT 3 
VISIT 4 
Phone 
call 1 
VISIT 5 
VISIT 6 
 
Windows for Visits 
(Day -30 to 
-1) 
 
 
 
(+/- 2 
days) 
(+/- 3 
days) 
(+/- 3 
days) 
 
Inclusion/Exclusion 
X 
 
 
 
 
 
 
 
Informed Consent 
X 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
Medical History and 
Concurrent Illnesses 
X 
 
 
 
 
 
 
 
Concomitant Medications 
X 
X 
X 
X 
 
X 
X 
 
Randomization 
X 
 
 
 
 
 
 
 
Confirm Treatment Group 
 
X 
 
 
 
 
 
 
Uncorrected Distance VA 
testing 
X 
 
 
 
 
X 
X 
 
Manifest Refraction 
X 
 
 
 
 
X 
X 
 
BCVA (ETDRS at 4m) 
X 
 
 
 
 
X 
X 
 
Corneal Haze (via AS-OCT) 
X 
 
 
 
 
X 
X 
 
Intraocular Pressure 
X 
 
X 
X 
 
X 
X 
 
Corneal Staining 
X 
 
X 
X 
 
X 
X 
 
Slit Lamp Exam 
X 
 
X 
X 
 
X 
X 
 
Ophthalmic Examination 
(dilated fundus exam) 
X 
 
 
 
 
 
 
 
Ocular Pain Assessment 
X 
 
X 
X 
X 
X 
 
 
SPEED Questionnaire 
X 
 
 
 
 
X 
 
 
COMTOL Survey 
 
 
 
 
 
X 
 
 
Record any surgical 
complications 
 
 
X 
 
 
 
 
 
 
Subject reported AEs prior to 
or after surgery 
X 
X 
X 
X 
X 
X 
X 
 
Intracanalicular 
dexamethasone insert* 
 
 
X 
 
 
 
 
 
 
Prescribe post-operative 
topical therapy regimen** 
 
X 
 
 
 
 
 
 
Insert Visualization 
 
 
X 
X 
 
X 
X 
 
 
*Eye Randomized to Group A 
**Specific for each eye based on Group A or B 
5.2 
Study Visit Descriptions 
5.2.1 Study Procedures 
Visit 1: Screening/Baseline (Day -30 to -1) 
After the patient has provided informed consent, the following information will 
be collected: 
• Inclusion/exclusion 

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• Demographics 
• Medical History and Concurrent Illnesses 
• Concomitant Medications 
• Randomization 
• Uncorrected Distance visual acuity as measured by ETDRS chart at 
4m 
• Manifest Refraction 
• Best-corrected visual acuity as measured by ETDRS chart at 4m 
• Corneal haze (via AS-OCT) 
• Intraocular pressure 
• Corneal Staining 
• Slit Lamp Exam 
• Ophthalmic Examination (dilated fundus exam) 
• Subject reported AEs prior to or after surgery 
• Ocular pain assessment 
• Modified Speed questionnaire  
 
 
Visit 2: Surgical Day 0 
• Concomitant medications 
• Confirm treatment group 
• Record any surgical complications 
• Subject reported AEs prior to or after surgery  
• Intracanalicular dexamethasone insert 
• Prescribe post-operative topical therapy regimen 
 
 
Visit 3: Day 3 
• Concomitant medications 
• Intraocular pressure 
• Corneal staining 
• Slit lamp exam 
• Subject reported AEs prior to or after surgery  
• Insert visualization 
• Ocular pain assessment 
 
Visit 4: Day 4 
• Concomitant medications 
• Intraocular pressure 
• Corneal staining 
• Slit lamp exam 
• Subject reported AEs prior to or after surgery  
• Insert visualization 
• Ocular pain assessment 

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Phone Call 1: Day 14 (+/- 2 days) 
• Subject reported AEs prior to or after surgery  
• Ocular pain assessment 
 
Visit 5: Day 28 (+/- 3 days) 
• Concomitant medications 
• Uncorrected Distance visual acuity as measured by ETDRS chart at 
4m 
• Best-corrected visual acuity as measured by ETDRS chart at 4m 
• Manifest refraction 
• Corneal haze 
• Intraocular pressure 
• Corneal staining 
• Slit lamp exam 
• Subject reported AEs prior to or after surgery 
• Insert visualization 
• Ocular pain assessment 
• Modified Speed questionnaire  
• Adapted COMTOL Survey 
 
Visit 6: Month 3 (+/- 3 days) 
• Concomitant medications 
• Uncorrected Distance visual acuity as measured by ETDRS chart at 
4m 
• Best-corrected visual acuity as measured by ETDRS chart at 4m 
• Manifest refraction 
• Corneal haze 
• Intraocular pressure 
• Corneal staining 
• Slit lamp exam 
• Subject reported AEs prior to or after surgery 
• Insert visualization 
 
Medical and Ocular History obtained: The site will ask and document all past 
Ocular history, relevant medical history and surgical history. A list of current 
medications, dose, route, start date and indications will be obtained and 
documented for each subject. There will be a subsequent diagnosis and start 
date for each medication. 
BCDVA on ETDRS chart: (manifest refraction performed if vision is worse 
than 20/20 with current MRx). The BCDVA will be captured on an ETDRS 
worksheet and calculated  

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Slit Lamp Examination (SLE): Slit lamp examination will be performed on 
the study eye and fellow eye of each subject by a masked examiner, and will 
include assessment of the lids and lashes, conjunctiva, tear film, cornea, 
anterior chamber, iris, and lens. At the screening/Day 0 visit, and 30 day/exit 
visit SLE will be performed both prior to and following application of the 
ELM or Lipiflow.   
Corneal Staining: A drop of fluorescein will be instilled on the eye, then the 
masked examiner will use the cobalt blue filter on the slit-lamp to examine 
the cornea. A grading scale of 0 to 3 is used to evaluate each of the five areas 
on the cornea. 0 being no staining to 3 being severe staining. All areas are 
then added together for a maximum score of 15.  
 
National Eye Institute/Industry Grading System  
 
 
 
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. 
 
If patient presents on POD 4 and have not epithelialized, patient will be 
brought in on POD 5 to re-assess epithelialization and remove bandage contact 
lens (BCL). This will be collected as an unscheduled visit.  
 
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 6. 

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5.3 
Rescue Criteria 
If the investigator determines either eye requires additional post-operative 
treatment, topical prednisolone acetate 1% therapy may be added to the 
DEXTENZA eye or increased dosing frequency may be offered to eyes 
receiving topical prednisolone acetate 1%. The investigator may also 
prescribe either or both topical cyclosporine 0.05% or topical cyclosporine 
0.09%.  
6. 
SAFETY DEFINITIONS, REPORTING, AND MONITORING 
6.1 
Definitions 
6.1.1 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. 
 
6.1.2 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 
jeopardize the patient or may require intervention to prevent 1 of the 
other serious outcomes listed above (e.g., intensive treatment in an 

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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. 
 
6.2 
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. 
 
7. 
STUDY VARIABLES 
7.1 
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. 
ETHICAL AND REGULATORY CONSIDERATIONS 
8.1 
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. 
 
8.2 
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. 
 
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 

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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. 
 
8.3 
Patient Confidentiality and Data Protection 
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.   
 
8.4 
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. 
 

The RESTORE Study (V1) 
 
December 17, 2019 
 
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CONFIDENTIAL 
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. 
 
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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December 17, 2019 
 
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CONFIDENTIAL 
REFERENCES 
 
1. DEXTENZA [PACKAGE INSERT]. BEDFORD, MA: OCULAR THERAPEUTIX, 
INC; 2019.  
2. Walters TR, Bafna S, Vold S, et al. Efficacy and Safety of Sustained 
Release Dexamethasone for the Treatment of Ocular Pain and 
Inflammation after Cataract Surgery: Results from Two Phase 3 
Studies. J Clin Exp Ophthalmol. 2016;7(4):1-11.  
3. Tyson SL, Bafna S, Gira JP, et al. Multicenter randomized phase 3 
study of a sustained-release intracanalicular dexamethasone insert for 
treatment of ocular inflammation and pain after cataract surgery. 
[published correction appears in J Cataract Refract Surg. 
2019;45(6):895]. J Cataract Refract Surg. 2019;45(2):204-212.