The Evaluation of the Safety and Efficacy of Sustained Release Dexamethasone Intracanalicular Insert (DEXTENZA) in Pediatric Patients Following Retinal Surgery or Laser Treatment Under Anesthesia (TENDER)
Phase: EARLY_PHASE1
Conditions: Vitreoretinopathy, Coats' Disease, Exudative Retinopathy, Lattice Degeneration, Retinal Hole, Sickler's Syndrome, Retinal Detachment Rhegmatogenous, Retinal Detachment Exudative, Retinal Detachment Traction
Sponsor: Lejla Vajzovic, MD, FASRS

The TENDER Study  
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CONFIDENTIAL 
 
 
 
EvaluaTion of the Safety and Efficacy of  SustaiNed Release 
Dexamethasone Intracanalicular Insert (DEXTENZA) in pEdiatric patients 
following Retinal surgery or laser treatment under anesthesia 
 
The TENDER Study 
 
 
 
Compound: 
DEXTENZA (dexamethasone 
ophthalmic insert) 0.4 mg, for 
intracanalicular use 
 
 
Study Name: 
The TENDER Study 
 
 
Clinical Phase: 
Investigator-Initiated Clinical Trial 
Protocol Version: 
2.0 
 
 
Date of Issue: 
9/12/2022 
 
 
Primary Investigator: 
Lejla Vajzovic, MD 
 
 
Sub Investigator: 
Xi Chen, MD 
 
Site Name & Location: 
Duke University Eye Center 
 
Durham, NC 
 
 
 
NCT05620901 

The Tender Study 
 
Lejla Vajzovic, MD 
 
 
Duke University 
 
 
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CONFIDENTIAL 
Clinical Study Protocol Synopsis 
Title 
The EvaluaTion of the Safety and Efficacy of  SustaiNed 
Release 
Dexamethasone 
Intracanalicular 
Insert 
(DEXTENZA) in pEdiatric patients following Retinal 
surgery or laser treatment under anesthesia 
 
Site Location(s) 
 
Duke University Eye Center 
Principal Investigator 
Lejla Vajzovic, MD 
Objective(s) 
To determine safety and efficacy of the dexamethasone 
ophthalmic insert in pediatric patients following retinal 
surgery or laser treatment under anesthesia 
Study Design 
Prospective Open-label Interventional Study 
Study Duration 
45 days postoperative 
Estimated 
Study 
Completion Date 
August 1, 2023 
Population 
 
Sample Size: 
30 
Target Population: 
Pediatric patients ages 3 to 17 undergoing routine 
retinal surgeries or laser treatment under anesthesia 
Study Drug 
 
 
Dose/Route/Schedule: 
DEXTENA (dexamethasone ophthalmic insert) 0.4 mg, 
for intracanalicular use  
 
All eyes will undergo routine retinal surgery or laser 
treatment under anesthesia.  
 
Patients in each treatment group (surgery or laser) will 
be randomized 2:1 at the time of surgery/laser to either: 
1)  Treatment Arm: Dextenza insert intraoperatively 
for perioperative ocular inflammation and pain. 
These patients will not be prescribed topical 

The Tender Study 
 
Lejla Vajzovic, MD 
 
 
Duke University 
 
 
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CONFIDENTIAL 
steroid drops post-operatively, or 
2) Control Arm: Prednisolone forte 1% steroid drop 
taper for 28 days post-operatively to treat 
perioperative ocular inflammation and pain; drops 
four times per day (QUID) on days 0-7, three 
times per day (TID) on days 7-14, twice per day 
(BID) on days 14-21 and once per day (QD) on 
days 21-28. 
Each treatment group (surgery or laser) will include 15 
patients total, 10 receiving Dextenza and 5 receiving the 
control drug. 
Drops for dilation and antibiotic coverage will be used as 
clinically indicated in all groups and arms. 
 
There will be a total of six visits for both treatment arms 
Screening/Baseline visit (day -30 to 0), Surgical Visit 
(day 0), and four post-operative follow up appointments 
occurring at post-op day 1, 7, 28/30 and 45 ( +/- three 
days for all post-operative timepoints). Exams to be 
performed on these days are outlined in section 5.1.. 
Treatment Arm Schedule of Events in Table 1. Control 
Arm Schedule of Events in Table 2 
 
Endpoint(s) 
                                                                                                 
Primary Endpoint: 
To evaluate if pediatric patients receiving retinal 
surgery or laser would benefit from DEXTENZA implant 
compared to topical ocular drop therapy to manage post-
operative pain (measured with the Face, Legs, Activity, 
Cry Consolability (FLACC) Behavioral Pain Rating 
Scale). Pain will be measured at each visit with final 
outcome determined by the FLACC  Pain Rating Scale 
score on day 45 (final visit). 
 
 Secondary Endpoints: 
• Incidence and severity of adverse events from 
baseline through post-op day 45 
• Degree of inflammation (AC cell count) 
• Resolution of inflammation as defined as either 0 

The Tender Study 
 
Lejla Vajzovic, MD 
 
 
Duke University 
 
 
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or 0.5 or less cell on follow up post op exams 
• Resolution of pain using the Face, Legs, Activity, 
Cry, Consolability (FLACC) Behavioral Pain 
rating Scale. Ratio of Intraocular pressure 
increase with insert 
• % of patients with rebound inflammation from 
baseline through post-op care 
• % of patients that were given supplementary 
prednisolone drops and the number of drops 
needed in these patients 
• Mean change in BCVA from baseline over time 
using either ETDRS or HOTV chart testing 
depending on age 
• Primary caregiver’s ability to adhere to treatment 
plan as prescribed and therapeutic preferences 
measured with primary caregiver satisfaction 
survey 
 
 
 

The Tender Study 
 
Lejla Vajzovic, MD 
 
 
Duke University 
 
 
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CONFIDENTIAL 
Table of Contents 
1. 
Introduction and Rationale ........................................................................................... 7 
2. 
Study Objectives............................................................................................................. 7 
2.1 
Primary Objective ................................................................................................ 7 
2.2 
Secondary Objectives........................................................................................... 7 
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 ............................................................ 10 
4.2.1 
Packaging, Labeling, and Storage .............................................. 10 
4.2.2 
Treatment Accountability ............................................................. 11 
4.3 
Concomitant Medications and Procedures......................................................... 11 
5. 
Study Schedule of Events and Visit Descriptions ..................................................... 12 
5.1 
Schedule of Events ............................................................................................. 12 
5.2 
Study Visit Descriptions for control and treatment groups ............................... 17 
5.2.1 
Study Procedures ............................................................................ 17 
5.2.2 
Unscheduled Visits ......................................................................... 18 
5.2.3 
Adverse Event Information Collection....................................... 18 
5.3 
Rescue Treatment............................................................................................... 18 
6. 
Safety Definitions, Reporting, and Monitoring ......................................................... 19 
6.1 
Definitions.......................................................................................................... 19 
6.1.1 
Adverse Event ..................................................................................... 19 
6.1.2 
Serious Adverse Event ........................................................................ 19 
6.1.3 
Events of Special Interest.................................................................... 20 
6.2 
Recording and Reporting Adverse Events ......................................................... 20 
7. 
Study Variables ............................................................................................................ 21 
7.1 
Demographic and Baseline Characteristics ....................................................... 21 
8. 
Statistical Considerations ............................................................................................ 21 
8.1 
Sample Size Considerations and Analysis Plan ................................................. 21 

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Duke University 
 
 
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8.1.1 
Participant Disposition and Study Drug Exposure ............................. 21 
8.1.2 
Safety .................................................................................................. 21 
9. 
Ethical and Regulatory Considerations ..................................................................... 22 
9.1 
Good Clinical Practice Statement ...................................................................... 22 
9.2 
Informed Consent............................................................................................... 22 
9.3 
Patient Confidentiality and Data Protection ...................................................... 23 
9.4 
Institutional Review Board ................................................................................ 23 
10. Appendices .................................................................................................................... 25 
10.1 
Primary caregiver satisfaction survey ................................................................ 25 
10.2 
HOTV Chart testing protocol and example (from Bernell Vision Therapy) 2 ... 27 
10.3 
FLACC Pain Rating Scale for measuring ocular pain3 ...................................... 28 
10.4 
Ocular Inflammation Grading (AC cell and flare) 4 .......................................... 29 
11. References ..................................................................................................................... 29 
 
 
 
Table of Tables 
Table 1 Treatment Group Schedule of Events (20 patients total) ....................... 13 
Table 2 Control Group Schedule of Events (10 patients total) ............................ 14 
 
 
 
 

The Tender Study 
 
Lejla Vajzovic, MD 
 
 
Duke University 
 
 
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CONFIDENTIAL 
1. 
INTRODUCTION AND RATIONALE 
Corticosteroids are routinely prescribed for the post-operative management of 
inflammation and pain following retinal surgery. Persistent ocular inflammation 
can increase the risk of ocular complications such as increased intraocular 
pressure (IOP), ocular pain, and reduced visual outcomes, where as untreated 
pain can affect overall patient satisfaction.1 Despite the widespread use of 
topical eyedrops, this means of treatment is often associated with poor patient 
compliance. This issue is further complicated in pediatric patients, who often 
dislike eye drops leading to difficulty with administration in the post-op period 
by parents. Largely across preparations, there is poor bioavailability from 
eyedrops with less that 5% of the applied dose of topical preparations predicated 
to reach the intraocular tissues.1 
To optimize the delivery of a corticosteroid after ocular surgery, a sustained-
release 
intracanalicular 
dexamethasone 
insert 
(DEXTENZA, 
Ocular 
Therapeutix, Inc) has been approved by the FDA to treat ocular pain and to 
control inflammation after ocular surgery.1 
 
2. 
STUDY OBJECTIVES 
2.1 
Primary Objective 
To determine if pediatric retinal patients would benefit from the placement of 
the 0.4 mg sustained release Dexamethasone intracanalicular insert 
(DEXTENZA) in the inferonasal lacrimal system during surgery in the 
surgical/treated eye compared to topical ocular drop therapy to manage post-
operative pain (measured with Face, Legs, Activity, Cry Consolability (FLACC) 
Behavioral Pain Rating Scale). Pain will be measured at each visit with final 
outcome determined by the FLACC Behavioral Pain Rating Scalescore on day 
45. 
 
 
2.2 
Secondary Objectives 
• Incidence and severity of adverse events from baseline through post-op 
day 45 
• Degree of inflammation (AC cell count) 
• Resolution of inflammation as defined as either 0 or 0.5 or less cell on 
follow up post op exams 
• Resolution of pain using the FLACC Behavioral Pain Rating Scale 
• Ratio of Intraocular pressure increase with insert 
• % of patients with rebound inflammation from baseline through post-op 
care 
• % of patients that were given supplementary prednisolone drops and the 
number of drops needed in these patients 

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Lejla Vajzovic, MD 
 
 
Duke University 
 
 
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CONFIDENTIAL 
• Mean change in BCVA from baseline over time using either ETDRS or 
HOTV chart testing depending on age 
• Primary caregiver’s ability to adhere to treatment plan as prescribed and 
therapeutic preferences measured with primary caregiver satisfaction 
survey 
 
 
3. 
STUDY DESIGN 
3.1 
Study Description and Duration 
This prospective, open-label, single-center, randomized, investigator-initiated 
clinical study seeks to investigate the safety and efficacy of the DEXTENZA 
insert in pediatric patients following retinal surgery or laser treatment under 
anesthesia. 
 
 
4. 
SELECTION, WITHDRAWAL, AND REPLACEMENT OF PATIENTS 
4.1 
Study Population 
The study aims to enroll 30 pediatric patients undergoing routine retinal 
surgery or laser treatment under anesthesia. Patients in each treatment group 
(surgery or laser) will be randomized 2:1  at the time of surgery/laser to receive 
either: 
3)  Treatment Arm: Dextenza insert intraoperatively for perioperative ocular 
inflammation and pain. These patients will not be prescribed topical 
steroid drops post-operatively, or 
4) Control Arm: Prednisolone forte 1% steroid drop taper for 28 days post-
operatively to treat perioperative ocular inflammation and pain; drops four 
times per day (QUID) on days 0-7, three times per day (TID) on days 7-14, twice per 
day (BID) on days 14-21 and once per day (QD) on days 21-28. 
Each treatment group (surgery or laser) will include 15 patients total, 10 
receiving Dextenza and 5 receiving the control drug. Drops for dilation and 
antibiotic coverage will be used as clinically indicated in all groups throughout 
the study period. Follow up will occur at post-op day 1, 7, 28/30 and 45 ( +/- three 
days for all post-operative timepoints). 
4.1.1 
Inclusion Criteria 
A patient’s study eye must meet the following criteria to be eligible for inclusion 
in the study: 

The Tender Study 
 
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Duke University 
 
 
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• 3 to <17 year old pediatric patients undergoing routine retinal surgery or 
laser treatment under anesthesia for a variety of visual conditions. These 
conditions and procedures include but are not limited to: 
 
o Conditions: 
 Familial Exudative Vitreoretinopathy 
 Coats’ Disease 
 Exudative Retinopathy 
 Lattice degeneration 
 Retinal holes 
 Sickler’s syndrome 
 Retinal detachment, rhegmatogenous 
 Retinal detachment, exudative 
 Retinal detachment, tractional 
 
o Procedures 
 Laser photocoagulation  
 Cryotherapy 
 Retinal detachment repair with scleral buckle and cryotherapy 
 Retinal detachment repair with vitrectomy 
 
 
• Written informed consent from parent/legal guardian 
 
 
4.1.2 
Exclusion Criteria 
A patient who meets any of the following criteria will be excluded from the 
study: 
Preprocedural 
• Subjects needing laser or ocular surgery in the fellow eye concurrently as 
the study eye.  
• Active or history of chronic or recurrent inflammatory eye disease in 
either eye 
• Any patient of reproductive potential that has a positive pregnancy test 
during pre-procedural testing 
• Active or history of increased ocular pressure 
• Patients with active corneal, conjunctival, and canalicular infections 
• Patients with punctal stenosis or other punctal anatomical abnormalities 
that would not be conducive with device insertion 
• Nasolacrimal duct obstruction 
• Laser or incisional ocular surgery during the study period and 3 months  
prior in the study eye 
• current use of systemic or topical steroids or NSAIDS on a regular basis 

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Duke University 
 
 
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• History of autoimmune disease that may interfere with 
treatment/outcomes 
• Ocular pain at the time of screening 
• Known malignancy 
• Current use of cyclosporin or a TNF blocker 
• Ocular hypertension IOP >25, actively taking medications for ocular 
hypertension, any history of IOP spikes in either including steroid 
associated IOP elevation 
• Congenital ocular lid and tear duct system abnormalities (e.g. congenital 
ectropion/entropion, trichiasis) 
• Evidence of acute external ocular infection of the study eye 
• Active or history of HSV 
• Previous trauma causing deformity 
• Previous enrollment or current enrollment with another clinical trial 
within the last 30 days that may interfere with treatment 
• Known allergies to product under investigation 
• Inability to engage in VA testing 
• Investigator determines that the candidate is not eligible for participation 
based on clinical or historical factors that would interfere with treatment 
or impact patient safety not specified above 
• Current artificial tear use >4x daily 
• Anyone who, in the opinion of the investigator, would not be a good 
candidate for the study. 
 
Intraoperatively 
• Multiple and/ or extensive procedures required at the surgeon’s discretion.  
• Complication occurs that surgeon determines makes the patient ineligible 
for study inclusion 
• Unsuccessful dilation of the punctum to 0.7mm when dilation attempted 
• During the exam under anesthesia, if it is decided that periocular Kenalog 
injection is indicated this patient fails screen and will no longer be eligible 
for the study 
 
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 

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Lejla Vajzovic, MD 
 
 
Duke University 
 
 
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CONFIDENTIAL 
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 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 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. 
Antibiotic regimen will not exceed 4x daily and will be the same in both 
treatment groups/arms. 
 
Removal of insertion should occur if based on examination it is determined that 
patient is having AE directly related to DEXTENZA implant. 

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Lejla Vajzovic, MD 
 
 
Duke University 
 
 
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CONFIDENTIAL 
 
 
 
5. 
STUDY SCHEDULE OF EVENTS AND VISIT DESCRIPTIONS 
5.1 
Schedule of Events 
Study assessments and procedures are presented by visit in Table 1 (treatment 
arm schedule of events) and Table 2 (control arm schedule of events). 
 
 

The Tender Study 
 
Lejla Vajzovic, MD 
 
 
Duke University 
 
 
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CONFIDENTIAL 
Table 1 Treatment Arm Schedule of Events  
Study Procedure 
Screening/ 
Baseline 
Surgical Visit 
Day 0 
Day 1 
Day 7 
Day 28 
Day 45 
Visit 
VISIT 1 
VISIT 2 
VISIT 3 
VISIT 4 
VISIT 5 
VISIT 6 
Windows for Visits 
(Day -30 to 0) 
 
+/- 3 days 
+/- 3 days 
+/- 3 days 
+/- 3 days 
Inclusion/Exclusion 
X 
 
 
 
 
 
Informed Consent 
X 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
Medical History and 
Concurrent Illnesses 
X 
 
 
 
 
 
Concomitant Medications 
X 
 
 
 
 
 
Pregnancy testing as 
indicated/appropriate 
 
X 
 
 
 
 
Subject reported AEs prior to 
or after surgery 
X 
X 
X 
X 
X 
X 
Randomization with 
subsequent  intracanalicular 
dexamethasone insert 
placement 
 
X 
 
 
 
 
Easy of insertion 
 
X 
 
 
 
 
If dilator was used 
 
X 
 
 
 
 
Document administration of 
prescribed medications 
 
 
X 
X 
X 
X 
Ocular Pain Assessment 
(FLACC) 
X 
 
X 
X 
X 
X 
Distance VA testing 
X 
 
X 
X 
X 
X 
BCVA (ETDRS at 4m) 
X 
 
X 
X 
X 
X 
Anterior chamber cell count 
X 
 
X 
X 
X 
X 

The Tender Study 
 
Lejla Vajzovic, MD 
 
 
Duke University 
 
 
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CONFIDENTIAL 
Study Procedure 
Screening/ 
Baseline 
Surgical Visit 
Day 0 
Day 1 
Day 7 
Day 28 
Day 45 
Visit 
VISIT 1 
VISIT 2 
VISIT 3 
VISIT 4 
VISIT 5 
VISIT 6 
Windows for Visits 
(Day -30 to 0) 
 
+/- 3 days 
+/- 3 days 
+/- 3 days 
+/- 3 days 
Anterior chamber cell flare 
X 
 
X 
X 
X 
X 
Punctum examination 
X 
X 
X 
X 
X 
X 
Insert Visualization and ease 
of visualization score 
 
 
X 
X 
X 
X 
Intraocular Pressure 
X 
 
X 
X 
X 
X 
Ophthalmic 
Examination 
(dilated fundus exam) 
X 
 
X 
X 
X 
X 
Satisfaction Survey 
 
 
 
 
 
X 
 
 
Table 2 Control Arm Schedule of Events  
Study Procedure 
Screening/ 
Baseline 
Surgical  Visit 
Day 0 
Day 1 
Day 7 
Day 28 
Day 45 

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Lejla Vajzovic, MD 
 
 
Duke University 
 
 
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CONFIDENTIAL 
Visit 
VISIT 1 
VISIT 2 
VISIT 3 
VISIT 4 
VISIT 5 
VISIT 6 
Windows for Visits 
(Day -30 to 0) 
 
+/- 3 days 
+/- 3 days 
+/- 3 days 
+/- 3 days 
Inclusion/Exclusion 
X 
 
 
 
 
 
Informed Consent 
X 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
Medical History and 
Concurrent Illnesses 
X 
 
 
 
 
 
Concomitant Medications 
X 
 
 
 
 
 
Pregnancy testing as 
indicated/appropriate 
 
X 
 
 
 
 
Subject reported AEs prior to 
or after surgery 
X 
X 
X 
X 
X 
X 
Randomization without 
intracanalicular 
dexamethasone insert 
placement 
 
X 
 
 
 
 
Document administration of 
prescribed medications 
 
 
X 
X 
X 
X 
Ocular Pain Assessment 
(FLACC) 
X 
 
X 
X 
X 
X 
Distance VA testing 
X 
 
X 
X 
X 
X 
BCVA (ETDRS at 4m) 
X 
 
X 
X 
X 
X 
Anterior chamber cell count 
X 
 
X 
X 
X 
X 
Anterior chamber cell flare 
X 
 
X 
X 
X 
X 
Punctum examination 
X 
X 
 
 
 
 
Intraocular Pressure 
X 
 
X 
X 
X 
X 

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Lejla Vajzovic, MD 
 
 
Duke University 
 
 
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CONFIDENTIAL 
Study Procedure 
Screening/ 
Baseline 
Surgical  Visit 
Day 0 
Day 1 
Day 7 
Day 28 
Day 45 
Visit 
VISIT 1 
VISIT 2 
VISIT 3 
VISIT 4 
VISIT 5 
VISIT 6 
Windows for Visits 
(Day -30 to 0) 
 
+/- 3 days 
+/- 3 days 
+/- 3 days 
+/- 3 days 
Ophthalmic 
Examination 
(dilated fundus exam) 
X 
 
X 
X 
X 
X 
Satisfaction Survey 
 
 
 
 
 
X 
 
 

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Duke University 
 
 
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5.2 
Study Visit Descriptions for control and treatment arms 
5.2.1 Study Procedures 
Visit 1 (Day -30 to 0) Screening/Baseline 
After the patient has provided informed consent, the following information will 
be collected: 
• Inclusion/exclusion 
• Demographics 
• Medical history and concurrent illnesses 
• Concomitant medications 
• Subject reported AE’s prior to surgery 
• Ocular Pain Assessment (FLACC) 
• Distance VA testing, when applicable 
• Best-corrected visual acuity as measured by ETDRS or HOTV chart at 4m 
based on patient age (HOTV for pre-literate patients) 
• Anterior chamber cell count 
• Anterior chamber cell flare 
• Punctum examination 
• Intraocular pressure 
• Ophthalmic Examination including dilated fundus exam 
 
 
Visit 2 Surgical Visit ( Day 0) 
• Subject reported AE’s prior to surgery 
• Indicate the incision type, location, and size (mm) 
• Punctum examination 
• If you are a patient who could possibly be pregnant (you have started menstruation), a 
urine pregnancy test will be performed, and it must be negative in order to continue in 
the study.  
• Randomization 
and 
potential 
placement 
of 
intracanalicular 
dexamethasone insert if assigned to treatment arm 
• Record any surgical complications 
 

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Lejla Vajzovic, MD 
 
 
Duke University 
 
 
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Visit 3 (Day 1 +/- 3 days) Visit 4  (Day 7 +/- 3 days) Visit 5 (Day 28 +/- 3 days) 
Visit 6 (Day 45 +/- 3 days) 
• Subject reported AE’s after surgery 
• Document administration of prescribed medication (if used and number of 
drops used) 
• Ocular Pain Assessment (FLACC) 
• Distance VA testing, when applicable 
• Best-corrected visual acuity as measured by ETDRS or HOTV chart at 4m 
based on patient age (HOTV for pre-literate patients) 
• Anterior chamber cell count 
• Anterior chamber cell flare 
• Punctum examination and ease of insert visualization (for patients 
receiving DEXTENZA insert only) 
• Intraocular pressure 
• Ophthalmic Examination including dilated fundus exam 
• Satisfaction Survey (at the end of visit 6 only) 
 
 
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. 
 
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. 
 
5.3 
Rescue Treatment 
Rescue treatment will be left to the discretion of the surgeon. Rescue treatment 
includes but is not limited to topical NSAID, oral and topical steroids.  Rescue 
treatment will be adequately documented to include the dosage needed.  
 
 
 

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Duke University 
 
 
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6. 
SAFETY DEFINITIONS, REPORTING, AND MONITORING 
Safety will be assessed from surgery through 45 days post surgery. Safety will be 
assessed only by frequency and incidence of events of special interest (ESI) and 
SAEs.  
Monitoring for ESIs and SAEs will occur from the initial study-specific 
procedure through 28 days post last study drug dose (including the weaning 
doses). 
 
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 

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Duke University 
 
 
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• 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 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. 
 
6.1.3 
Events of Special Interest 
The patients enrolled in this trial will have trauma to the eye as a direct result 
of surgery with known and previously reported potential significant eye-related 
events. The following events will not be included in the primary safety outcome, 
but they are clinical events of special interest (ESI) that may relate to safety and 
that will be tracked and reported in the trial results. These AEs are to be 
reported to study database, regardless of whether these events meet serious 
criteria or unexpectedness: 
 
• Elevated intraocular pressure 
• Eye pain and local erythema 
• Infection  
• Allergic reaction 
• Trauma to the punctum 
• Eyelid swelling 
• Hazy or cloudy vision 
• Feeling like something is in the eye 
• Increased sensitivity to light 
 
 
 
6.2 
Recording and Reporting Adverse Events 
All ESIs and SAEs will be recorded in the study database. 
 
All SAEs, regardless of assessment of causal relationship to study insert will be 
reported to the sponsor. The sponsor will provide these reports to Ocular 
Therapeutix. 
 
The investigator will promptly report to the IRB all unanticipated problems 
involving risks to patients.  This includes death from any cause and all SAEs 

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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. 
STATISTICAL CONSIDERATIONS 
8.1 
Sample Size Considerations and Analysis Plan 
This is a feasibility study and the sample size of 30 is not designed to provide 
power to determine any differences between arms.  
Analysis results will be presented by study drug vs. standard of care topical 
drops overall and by surgical procedure group.  
Descriptive statistics such as number of observations, mean, median, standard 
deviation, minimum and maximum will be presented by treatment arms for 
continuous variables (such as age, weight, etc.). Other descriptive statistics such 
as counts, proportions, and/or percentages will be presented by group to 
summarize discrete variables (such as race, sex, etc.). 
8.1.1 
Participant Disposition and Study Drug Exposure 
Study disposition, demographic and baseline characteristics, and study 
medication exposure will be summarized for study patients. Study drug 
administration will be summarized, number of days of dosing, and reasons for 
final discontinuation of study drug.  
Demographic and baseline characteristics will include race, age, sex, and 
selected clinical variables recorded prior to initiation of study drug.  
8.1.2 
Safety 
The safety reports will be summarized. 
Serious adverse events will be presented overall. Severity and relationship to 
study drug will be provided.  
Events of special interest will be presented overall and summarized by 
participant characteristics. 

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Duke University 
 
 
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Prior and concomitant medications will be summarized by World Health 
Organization (WHO) drug class.  
 
 
9. 
ETHICAL AND REGULATORY CONSIDERATIONS 
9.1 
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. 
The study will be conducted in accordance with US regulations (e.g. 45 CFR 46 
and 21 CFR 312), the International Council for Harmonisation guidelines for 
Good Clinical Practice (GCP) (ICH E6),. The US Code of Federal Regulations 
(CFR) include but are not limited to:  
o 45 CFR 46 (Human Subjects Protection)  
o 45 CFR 160 and 164 Subparts A and E (Health Insurance Portability 
and Accountability Act [HIPAA] Privacy Rule) 
o 21 CFR 312 (Investigational New Drug [IND] Application) as 
applicable 
o 21 CFR 50 (Protection of Human Subjects, including Subpart D - 
Additional Safeguards for Children in Clinical Investigations)  
o 21 CFR 56 (Institutional Review Boards [IRB]) 
 
9.2 
Informed Consent 
The principles of informed consent are described in 45 CFR 46 and 21 CFR 50. 
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 
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. 

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Duke University 
 
 
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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. 
 
9.3 
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.   
 
9.4 
Institutional Review Board  
An appropriately constituted IRB, as described in 21 CFR 56 and 45 CFR 46 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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Duke University 
 
 
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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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Duke University 
 
 
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CONFIDENTIAL 
10. 
APPENDICES 
10.1 
Primary caregiver satisfaction survey  
Administer this questionnaire to the primary caregiver in charge of the child’s 
post-operative eye drop administration at day 45 (+/- 3 days) follow-up (Visit 6): 
 
# 
 
 
Questions 
Strongly 
Disagree 
 
Disagree 
 
Not 
Sure 
 
Agree 
 
Strongly 
Agree 
 
1 
2 
3 
4 
5 
1. 
The instructions I was given on 
how to administer my child’s 
eye drop treatment were clear 
and easy to follow 
 
 
 
 
 
2. 
I did not have initial concerns 
regarding the administration 
instructions I was given on eye 
drop administration but some 
questions/issues arose for me 
after the dosing experience 
 
 
 
 
 
3. 
It was difficult to fill and pick-
up my child’s eye drop 
prescription 
 
 
 
 
 
4. 
My child’s eye drops were 
expensive to purchase 
 
 
 
 
 
5. 
My child cries or becomes upset 
when it is time to administer the 
eye drop treatment 
 
 
 
 
 
6. 
Eye drop treatment appears to 
cause my child distress; my baby 
acts to avoid therapy 
 
 
 
 
 
7. 
I sometimes forget to wash my 
hands prior to administering my 
child’s eye drop treatment 
 
 
 
 
 
8. 
It is difficult and/or frustrating to 
administer my child’s eye drop 
treatment 
 
 
 
 
 
9 
A second person is needed to 
help me administer my child’s 
eye drop treatment 
 
 
 
 
 
10. I worry my child is not receiving 
enough eye drop treatment when 
I administer it 
 
 
 
 
 
11. I worry I am incorrectly 
administering the eye drop 
treatment to my child 
 
 
 
 
 

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Lejla Vajzovic, MD 
 
 
Duke University 
 
 
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12. I worry I will injure my child or 
cause infection trying to 
administer the eye drop 
treatment 
 
 
 
 
 
 
 
# 
 
 
Questions 
Strongly 
Disagree 
 
Disagree 
 
Not 
Sure 
 
Agree 
 
Strongly 
Agree 
 
13. It takes me a while (several 
minutes or longer) to soothe my 
child or get them to settle down 
after administering eye drop 
treatment 
 
 
 
 
 
14. I sometimes forget to administer 
my child’s eye drop treatment 
 
 
 
 
 
15. Administering eye drops to my 
child causes me stress 
 
 
 
 
 
16. I am the only capable person that 
can administer my child’s eye 
drop treatment and I do not trust 
other caregivers to administer it, 
such as daycare personnel, the 
nanny/babysitter, grandparents, 
etc. 
 
 
 
 
 
17. I have to adjust my daily 
schedule in order to correctly 
follow my child’s eye drop 
schedule 
 
 
 
 
 
18. I would prefer a post-operative 
treatment regimen for my child 
that has fewer eye drops or none 
at all 
 
 
 
 
 
 
 
 
 

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Duke University 
 
 
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10.2 
HOTV Chart testing protocol and example (from Bernell Vision Therapy) 2 
 

The Tender Study 
 
Lejla Vajzovic, MD 
 
 
Duke University 
 
 
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10.3 
FLACC Pain Rating Scale for measuring ocular pain3  
 
The FLACC Scale will be used in the assessment of pain. BCVA and FLACC will 
occur prior to other visit assessments.  The FLACC assessment will be 
performed 
by 
masked 
site 
personnel. 
 
 
 
 

The Tender Study 
 
Lejla Vajzovic, MD 
 
 
Duke University 
 
 
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10.4 
Ocular Inflammation Grading (AC cell and flare) 4 
• Use high intensity 1mm x 1mm slit beam based on Standardization of 
Uveitis Nomenclature Working Group (SUN grading scheme) 
 
 
 
 
11. 
REFERENCES 
 
1. Dextenza (dexamethasone insert) Prescribing Information, Ocular 
Therapeutix, Inc. 2019 http://www.dextenza.com/wp-
content/uploads/2019/06/NDA-208742-S001-Dextenza-labeling-19Jun19.pdf 
 
2. Bernell Vision Training Products:  
http://www.bernell.com/downloads/GL600302-Instructions.pdf 
 
 
3. Cable, Melissa. (2012). Comparison of bromfenac 0.09% QD to 
nepafenac 0.1% TID after cataract surgery: Pilot evaluation of 
visual acuity, macular volume, and retinal thickness at a single 
site. Clinical ophthalmology (Auckland, N.Z.). 6. 997-1004. 
10.2147/OPTH.S32179.