Multi-Center Prospective Randomized Controlled Study of the Safety and Effectiveness of the Sight Sciences VISCO™360 System in Canaloplasty vs Selective Laser Trabeculoplasty in the Reduction of IOP in Primary Open Angle Glaucoma
Phase: NA
Conditions: Open-Angle Glaucoma
Sponsor: Sight Sciences, Inc.

PROTOCOL: SIGHTVISCO-001 
 
 
CONFIDENTIAL 
 
  
 
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Multi-Center, Prospective, Randomized, Controlled Clinical 
Evaluation of the Safety and Effectiveness of the Sight 
Sciences VISCO™360 Viscosurgical System in Canaloplasty 
versus Selective Laser Trabeculoplasty in the Reduction of IOP 
in Primary Open Angle Glaucoma 
 
 
Protocol SIGHTVISCO-001 
 
 
February 1, 2017 
 
COMPANY NAME AND ADDRESS 
 
Sight Sciences, Inc. 
3000 Sand Hill Road 
Bldg. 3, Suite 105 
Menlo Park, CA 94025 
 

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I have read and agree to follow the procedures as outlined in this protocol. 
 
 
 
 
____________________________________ 
____________________ 
Signature of Investigator 
Date 
 
 
CONFIDENTIALITY AGREEMENT 
 
This protocol contains confidential proprietary information with respect to Sight Sciences, Inc. 
products and clinical trials.  I agree to hold this information in confidence and not to disclose it 
to any third parties for a period of three (3) years after the completion of the study, or until said 
information shall become a matter of public knowledge or until a formal written agreement for 
that purpose has been entered into by the parties. 
 
____________________________________ 
Print Name of Investigator 
 
____________________________________ 
_______________________ 
Signature of Investigator 
 Date 
 
 

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TABLE OF CONTENTS 
1.0 
STUDY OBJECTIVE ............................................................................................................................ 15 
2.0 
STUDY DESIGN ................................................................................................................................... 15 
3.0 
INTRODUCTION AND BACKGROUND ........................................................................................... 16 
3.1 
Aqueous Humor Outflow Pathway .................................................................................................... 16 
3.2 
Trabeculocanalicular Outflow Pathway Physiology and Resistance ............................................... 17 
3.3 
Outflow Resistance .............................................................................................................................. 18 
3.4 
Selective Laser Trabeculoplasty ......................................................................................................... 19 
3.5 
Rationale for the Study ........................................................................................................................ 19 
4.0 
DEVICE DESCRIPTION ...................................................................................................................... 22 
5.0 
PRIOR PRE-CLINICAL AND CLINICAL TESTING ........................................................................ 24 
5.1 
Viscocanalostomy ................................................................................................................................. 24 
5.2 
Canaloplasty ......................................................................................................................................... 26 
6.0 
STUDY ENDPOINTS ............................................................................................................................ 29 
6.1 
Effectiveness Endpoints ....................................................................................................................... 29 
6.2 
Safety Endpoints .................................................................................................................................. 30 
6.3 
Exploratory Analyses .......................................................................................................................... 30 
7.0 
STUDY POPULATION ......................................................................................................................... 32 
7.1 
Inclusion Criteria ................................................................................................................................. 32 
7.2 
Exclusion Criteria ................................................................................................................................ 33 
8.0 
STUDY PROCEDURES ........................................................................................................................ 35 
8.1 
Informed Consent ................................................................................................................................ 35 
8.2 
Screening and Baseline Evaluation .................................................................................................... 36 
8.2.1 
Randomization ..................................................................................................................................... 36 
8.3 
Training ................................................................................................................................................ 36 
8.4 
Material and Equipment ..................................................................................................................... 37 
8.5 
VISCO™ 360 Viscosurgical System Procedure ................................................................................ 38 
8.5.1 
Pre-Operative Instructions .................................................................................................................... 38 
8.5.2 
Surgical Instructions .............................................................................................................................. 38 
8.5.3 
VISCO360 Postoperative Instructions ................................................................................................... 45 
8.6 
SLT Procedure ..................................................................................................................................... 46 
8.7 
Washout ................................................................................................................................................ 46 
8.8 
Management of IOP After Surgery/SLT Procedure ......................................................................... 48 
8.9 
Follow-Up ............................................................................................................................................. 50 
8.10 
Withdrawal Criteria ............................................................................................................................ 53 
8.11 
Lost to Follow-Up Subjects ................................................................................................................. 53 
8.12 
Device Return ....................................................................................................................................... 53 
8.13 
Protocol Modification and Deviations ................................................................................................ 53 
9.0 
DATA HANDLING AND RECORDKEEPING ................................................................................... 54 

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9.1 
Subject Identification .......................................................................................................................... 54 
9.2 
Subject Accountability ........................................................................................................................ 54 
9.3 
Confidentiality ...................................................................................................................................... 54 
9.4 
Source Data and Case Report Forms ................................................................................................. 54 
9.5 
Device Accountability .......................................................................................................................... 55 
9.6 
Record Retention ................................................................................................................................. 55 
9.7 
Database Management ........................................................................................................................ 56 
10.0 
ADVERSE EVENTS ............................................................................................................................. 56 
10.1 
Anticipated Adverse Events ................................................................................................................ 56 
10.2 
Unanticipated Adverse Device Effect ................................................................................................. 58 
10.3 
Reporting Adverse Events and Unanticipated Adverse Device Effects .......................................... 58 
10.4 
Type and Duration of Follow-Up after Adverse Events ................................................................... 58 
11.0 
MONITORING PLAN .......................................................................................................................... 59 
12.0 
STATISTICAL PLAN ........................................................................................................................... 59 
13.0 
MEDICAL MONITOR ......................................................................................................................... 60 
14.0 
COMPLIANCE WITH PROTOCOL ................................................................................................... 60 
15.0 
BIBLIOGRAPHY .................................................................................................................................. 61 
APPENDIX 1: EXAMINATION PROCEDURES, TESTS, EQUIPMENT AND TECHNIQUES .................. 65 
A. 
MEASUREMENT OF INTRAOCULAR PRESSURE ............................................................................................................. 65 
B. 
VISUAL FIELD EXAMINATION .................................................................................................................................. 68 
C. 
PACHYMETRY ...................................................................................................................................................... 68 
D. 
REFRACTION AND VISUAL ACUITY ...................................................................................................................... 69 
E. 
DILATED FUNDUS EXAMINATION ............................................................................................................................. 70 
F. 
SLIT LAMP EXAMINATION ...................................................................................................................................... 71 
G. 
GONIOSCOPY ...................................................................................................................................................... 74 
H. 
OCULAR HYPOTENSIVE MEDICATIONS ..................................................................................................................... 74 
I. 
PREGNANCY TESTING, NURSING AND CONTRACEPTIVES ............................................................................... 74 
J. 
PATIENT QUESTIONNAIRE (PRO) ............................................................................................................................ 74 
APPENDIX 3: INVESTIGATOR’S AGREEMENT AND OBLIGATIONS .................................................... 77 
APPENDIX 4: DECLARATION OF HELSINKI ............................................................................................. 79 
 
 
 

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TABLES 
TABLE 1:  OCULAR HYPOTENSIVE MEDICATION WASHOUT PERIODS ........................................................................................... 47 
TABLE 2:  SCHEDULE OF VISITS AND STUDY PROCEDURES ......................................................................................................... 51 
 
FIGURES 
FIGURE 1: THE SIGHT SCIENCES VISCOTM360 VISCOSURGICAL SYSTEM ........................................................................................ 23 
FIGURE 2:  RED RETAINER FOR VISCO™ 360 SYSTEM ............................................................................................................. 39 
FIGURE 3:  PRIMING OF THE VISCO™ 360 SYSTEM ................................................................................................................ 40 
FIGURE 4:  VISCO™360 SYSTEM READY FOR USE IN THE HUMAN EYE ....................................................................................... 41 
FIGURE 5:  180-DEGREE MICROCATHETER ADVANCEMENT ......................................................................................... 42 
FIGURE 6:  180-DEGREE MICROCATHETER RETRACTION .............................................................................................. 43 
 
 
 

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SIGHT SCIENCES, INC. 
PROTOCOL SIGHTVISCO-001 
 
A MULTI-CENTER, PROSPECTIVE, RANDOMIZED, CONTROLLED CLINICAL EVALUATION OF 
THE SAFETY AND EFFECTIVENESS OF THE SIGHT SCIENCES VISCO™360 VISCOSURGICAL 
SYSTEM IN CANALOPLASTY VERSUS SELECTIVE LASER TRABECULOPLASTY IN THE 
REDUCTION OF IOP IN PRIMARY OPEN ANGLE GLAUCOMA 
 
 
MEDICAL 
MONITOR 
 
 
 
  
 
 
 
 
STUDY SYNOPSIS 
 
STUDY TITLE 
A Multi-Center, Prospective, Randomized, Controlled Clinical Evaluation of 
the Safety and Effectiveness of the Sight Sciences VISCO™360 Viscosurgical 
System in Canaloplasty versus Selective Laser Trabeculoplasty in the 
Reduction of IOP in Primary Open Angle Glaucoma 
INVESTIGATIONAL 
DEVICE 
Sight Sciences VISCO™360 Viscosurgical System 
CONTROL DEVICE 
Selective Laser Trabeculoplasty (SLT) 
STUDY OBJECTIVE 
To establish the safety and effectiveness of the Sight Sciences VISCO™360 
Viscosurgical System in support of the proposed Indications for Use Statement. 
INDICATIONS FOR 
USE 
The Sight Sciences VISCO™360 Viscosurgical System is a manually operated 
device for delivery of small amounts of viscoelastic fluid, for example 
Healon™ or HealonGV™ from Abbott Medical Optics (AMO), Amvisc™ 
from Bausch & Lomb, or PROVISC™ from Alcon, during ophthalmic surgery. 
The VISCO™360 Viscosurgical System is indicated for catheterization and 
transluminal viscodilation of Schlemm's canal (i.e. canaloplasty) to reduce 
intraocular pressure in adult, pseudophakic patients with open angle glaucoma. 

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STUDY DESIGN 
 
This is a multicenter, prospective, single-masked, randomized, controlled trial.  
Two study groups will be included in the study.  The treatment group consists 
of subjects who undergo canaloplasty with the VISCO™ 360 Viscosurgical 
System.   The control group consists of subjects who undergo Selective Laser 
Trabeculoplasty (SLT).  The clinical examinations and study visit schedules are 
included in Appendix 1. 
A total of approximately 298 subjects will be enrolled and randomized in a 1:1 
ratio at up to 30 clinical sites.  Only one eye from each eligible subject will be 
enrolled in the study.  
 
 
• 
VISCO 360 Arm: 149 enrolled subjects 
• 
Control Arm: 149 enrolled subjects 
The study will consist of two phases.  In the initial phase, 30 subjects will be 
enrolled and randomized at up to 5 of the 30 investigational sites.  When the 
first 30 subjects randomized complete the 1-month follow-up examination, 
safety data will be submitted to the FDA to request approval for expansion to 
the full population in order to have 298 enrolled and treated subjects. 
 
 
CLINICAL SITES 
A maximum of 30 clinical sites will be selected.  A minimum enrollment of ten 
investigational device subjects per investigator should be sought. No 
investigator should enroll more than 25% of the total number of investigational 
device or control subjects. For centers with more than one investigator, the 
center's total enrollment (investigational or control arm) should not exceed 33% 
of the total. 
Investigational sites for the clinical study will be selected with the goal of 
obtaining an appropriate balance of gender, minority, and age during the study. 
ELIGIBILITY 
CRITERIA 
Inclusion Criteria  
(only one eye of each subject is eligible and all criteria apply to study eye only 
unless otherwise indicated): 
 
1. 
Male or female subjects, 22 years or older. 
2. 
Pseudophakic with Posterior Chamber IOL (PCIOL) 
3. 
Subjects diagnosed with mild to moderate primary open angle glaucoma 
(POAG). The diagnosis of POAG must include evidence of: 
o Glaucomatous optic nerve damage as evidenced by any of the 
following optic disc or retinal nerve fiber layer structural 
abnormalities documented with stereo disc photos: 
 
Diffuse thinning, focal narrowing, or notching of the optic 
disc rim, especially at the inferior or superior poles 
 
Localized abnormalities of the peripapillary retinal nerve 
fiber layer, especially at the inferior or superior poles 
 
Optic disc neural rim asymmetry of the two eyes consistent 
with loss of neural tissue 
 
Disc rim or peripapillary retinal nerve fiber layer 
hemorrhages  

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And/Or 
 
o Visual field defect consistent with glaucomatous optic nerve 
damage (substantiated with the Humphrey automated perimeter 
using the SITA Standard 24-2 testing algorithm). Mean deviation 
(MD) score must be between -3dB and -12dB corresponding to 
Mild/Moderate disease (Mills RP, Budenz DL, Lee PP, et al.  
Categorizing the stage of glaucoma from pre-diagnosis to end-stage 
disease.  Am J Ophthalmol 2006; 141:24-30.) At least one of the 
following two findings: 
 
(1) On pattern deviation (PD), there exists a cluster of 3 or more 
points in an expected location of the visual field depressed 
below the 5% level, at least 1 of which is depressed below the 
1% level; 
(2) Glaucoma hemi-field test “outside normal limits.” 
 
4. 
Intraocular pressure ≥ 18.0 mmHg and ≤30.0 mmHg and not at the 
patient’s target pressure while on 1-3 topical ocular medications or while 
not on topical ocular medication due to intolerance of medication or 
history of poor compliance (Screening Visit). Combination glaucoma 
medications that consist of two or more glaucoma drugs will have each 
glaucoma drug component counted as a separate drug. 
5. 
At the Baseline Visit, an unmedicated IOP ≥ 21.0 mmHg and  
≤ 36.0 mmHg and ≥ 3.0 mmHg higher than the medicated IOP measured 
at the Screening Visit 
6. 
Shaffer grade of ≥ III in all four quadrants 
7. 
Subjects able and willing to comply with the protocol, including 
randomization assignment and all follow-up visits through 24 months. 
8. 
Subject understands and signs the informed consent. 
 
Exclusion Criteria  
(All criteria apply to the study eye unless otherwise noted and both eyes of a 
single subject need not be eligible): 
1. 
Phakia or aphakia 
2. 
Posterior Capsular Opacification graded as moderate or severe using the 
sample images provided in Appendix 1. In this case, a laser capsulotomy 
can be performed and the subject screened again a minimum of two weeks 
following the capsulotomy. 
3. 
Presence of Anterior Chamber IOL (ACIOL) 
4. 
History of complicated cataract surgery (e.g. vitreous loss, sutured IOL, 
decentered IOL, etc.) 
5. 
Pre-existing IOL instability 
6. 
Diagnosis of acute angle closure, traumatic, congenital, malignant, uveitic, 
pseudoexfoliative, pigmentary or neovascular glaucoma  
7. 
Inability to properly visualize angle (due to corneal scar, edema, etc.) 
8. 
Abnormal angle anatomy as determined by gonioscopy (e.g. peripheral 
anterior synechiae, rubeosis or other angle abnormalities) 

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9. 
Conditions associated with elevated episcleral venous pressure such as 
active thyroid orbitopathy, cavernous sinus fistula, Sturge-Weber 
syndrome, orbital tumors, orbital congestive disease. 
10. The subject would be at significant risk by washout of ocular hypotensive 
medication including any of the following: 
o Unmedicated IOP after washout period is expected to exceed upper 
limit of 36.0 mmHg at Baseline visit  
o Presence of afferent pupillary defect in either eye 
o C:D ratio ≥ 0.9 in either eye 
o Requiring oral medications (e.g., acetazolamide) for IOP control in 
either eye 
o Evidence of advanced glaucoma in either eye by 24-2 SITA 
Standard Humphrey visual field defined as mean deviation (MD) 
of -12.00 or worse and at least one of the following: (a) On PD 
plot, greater than or equal to 75% of points depressed below the 
5% level and greater than or equal to 50% of points depressed 
below 1% level; or  (b) At least 50% of points (i.e., 2 or more) 
within central 5 degrees with sensitivity of < 0dB on the dB plot; or 
(c) Points within the central 5 degrees of fixation with sensitivity  
< 15dB in both hemifields on the dB plot.  
o Visual field defects threatening fixation in either eye defined as any 
(1 or more) point(s) within the central 5° depressed below the 5th 
percentile on PD plot unless this/these points are >25 dB on 
Threshold Values (decibel) plot. 
11. Subjects with Snellen best-corrected visual acuity worse than 20/80 in 
either eye.  
12. At Baseline visit, subject has not completed appropriate medication 
washout, if applicable 
13. Inability to complete a reliable 24-2 SITA Standard Humphrey visual field 
at screening (fixation losses, false positive errors and false negative errors 
should not be greater than 33%).  A visual field done within 90 days prior 
to the subject informed consent date and in accordance with the 24-2 SITA 
Standard requirements can be used for the screening evaluation.   
14. Use of more than 3 ocular hypotensive medications (combination 
medications count as 2 medications) 
15. Use of oral hypotensive medication treatment for glaucoma  
16. Previous glaucoma procedure with or without an implantable glaucoma 
device (including incisional surgery, ALT, iridectomy/iridotomy, etc.). 
Subjects with one prior 180 degree SLT application or one prior 360 
degree SLT application (>3 months prior to screening) or prior ECP 
(performed > 12 months prior to screening) can be enrolled. 
17. Clinically significant sequelae from trauma (e.g., chemical burns, blunt 
trauma, etc.) 
18. History of elevated IOP due to steroid response 
19. Use of systemic medications (either current, within 30 calendar days of 
screening exam, or anticipated) that may cause an increase in IOP, (e.g., 
systemic steroids including inhaled steroids used on a regular basis) 
20. Ocular pathology or medical condition for which, in the investigator's 
judgment, the following factors would either place the subject at increased 
risk of complications or contraindicate surgery or interfere with 

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compliance to elements of the study protocol (e.g., ophthalmic 
examinations, follow-up visits): 
a) 
inability to reliably complete visual field testing over the course of 
the study, 
b) 
uncontrolled systemic disease (e.g. diabetes, hypertension) that 
could compromise their participation in the study, 
c) 
disorders that pose a fall risk, as well as compromise ability to take a 
visual field exam and take glaucoma medications (e.g., Parkinson's 
disease), 
d) 
inability to discontinue use of blood thinners in accordance with 
surgeon’s standard pre-operative and postoperative instructions, 
e) 
immunodeficiency concerns, 
f) 
other clinically significant ocular pathology other than glaucoma.  
21. Proliferative diabetic retinopathy  
22. Previous surgery for retinal detachment  
23. Central corneal thickness that is less than 450 microns or greater than 620 
microns. 
24. Clinically significant corneal dystrophy (e.g., bullous keratopathy, guttata, 
etc.) 
25. Previous corneal surgery  
26. Wet age-related macular degeneration  
27. Clinically significant ocular inflammation or infection ≤ 30 days prior to 
screening. 
28. Participation in any clinical trial ≤ 30 days prior to screening. 
29. Women of childbearing potential if they are currently pregnant or intend to 
become pregnant during the study period; are breast-feeding; or are not in 
agreement to use adequate birth control methods to prevent pregnancy 
throughout the study. (A negative serum pregnancy test must be verified for 
females of child bearing potential). All women are considered to be of 
childbearing potential unless: 
A. Postmenopausal for at least 1 year   
OR 
B. Surgically sterile 
 
STUDY DURATION 
The primary safety and effectiveness endpoints will be evaluated when each 
study subject has a minimum of 12 months of post- follow-up data.  All 
subjects will be followed through the 24-month time point. 
SCHEDULE OF 
VISITS 
1 day, 1 week, and 1, 3, 6, 12, 18, and 24 months 

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1.0 
STUDY OBJECTIVE 
To establish the safety and effectiveness of the Sight Sciences VISCO™360 Viscosurgical 
System in support of the proposed Indications for Use Statement. 
 
2.0 
STUDY DESIGN 
This is a multi-center, prospective, single-masked, randomized, and controlled study. Subjects 
who meet the study enrollment criteria will be randomized to viscocanaloplasty with the 
VISCO™360 Viscosurgical System or Selective Laser Trabeculoplasty (SLT). 
A total of approximately 298 subjects will be enrolled and randomized in a 1:1 ratio at up to  
30 clinical sites.  Only one eye from each eligible subject will be enrolled in the study. If both 
eyes are eligible, the right eye will be selected for the study. 
• 
VISCO 360 Arm: 149 enrolled subjects 
• 
Control Arm: 149 enrolled subjects 
Anticipating a 40% screening failure rate (including baseline IOP failure), up to 497 subjects will 
undergo screening and baseline exams in order to have at least 298 randomized subjects, and 
have at least 134 randomized subjects per study group reach the 12-month visit, assuming an 
annual drop-out rate of 10%.  In order to minimize the number of subjects with out-of-window 
visits at 12 months and to perform the specified washout of any ocular hypotensive medications 
for subjects, the investigational sites will be reminded of subjects with upcoming 12-month 
visits. 
 
See separate Statistical Analysis Plan for more information related to sample size calculation. 
A washout of ocular hypotensive medications, if necessary, will be performed at baseline and at 
12 months. The primary effectiveness endpoints will be evaluated at 12 months and all study 
subjects will be followed for 24 months. 
A minimum enrollment of ten investigational device subjects per investigator should be sought. 
No investigator should enroll more than 25% of the total number of investigational device or 
control subjects. For centers with more than one investigator, the center's total enrollment 
(investigational or control arm) should not exceed 33% of the total. 
Investigational sites for the clinical study will be selected with the goal of obtaining an 
appropriate balance of gender, minority, and age during the study. 
 
The study will consist of two phases.  In the initial phase, 30 subjects will be enrolled and 
randomized at up to 5 of the 30 investigational sites.  When the first 30 subjects randomized 
complete the 1-month follow-up examination, safety data will be submitted to the FDA to 
request approval for expansion to the full study population in order to have 298 enrolled and 
randomized subjects. 
 
 

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3.0 
INTRODUCTION AND BACKGROUND  
Glaucoma is a term describing a group of ocular disorders with multi-factorial etiology united by 
a clinically characteristic intraocular pressure-associated optic neuropathy. Glaucomatous optic 
neuropathy can lead to irreversible, progressive visual field loss often resulting in blindness. It is 
often associated with increased intraocular pressure in the eye where there is decreased facility of 
outflow of the fluid in the eye (aqueous humor). Glaucoma has been called the "silent thief of 
sight" because the loss of vision often occurs gradually, painlessly, and asymptomatically over a 
long period of time, and symptoms become manifest only when the disease is quite advanced. 
Once lost, vision cannot be recovered, so treatment is aimed at preventing further loss. 
Worldwide, glaucoma is the second-leading cause of blindness after cataracts and it is the 
number one cause of irreversible blindness. It is also a particularly severe cause of blindness 
among those of African extraction. Glaucoma affects one in 200 people aged fifty and younger 
and one in 10 over the age of eighty. The disease affects 60-80 Million people worldwide. If the 
condition is detected early enough, it is often possible to arrest the development or slow the 
progression with medical and surgical means. 
Optic nerve damage in glaucoma involves loss of retinal ganglion cells in a characteristic pattern. 
The many different subtypes of glaucoma can all be considered to be a type of optic neuropathy. 
Raised intraocular pressure (typically above 21 mmHg) is the most important and only currently 
known modifiable risk factor for glaucoma. However, some may have high eye pressure for 
years and never develop damage, while others can develop nerve damage at a relatively low 
pressure. Untreated glaucoma can lead to permanent damage of the optic nerve and resultant 
visual field loss, which over time can progress to blindness. 
Glaucoma can generally be divided into two broad categories, "open-angle" and "closed-angle" 
(or "angle closure") glaucoma. The anterior chamber angle refers to the angle formed between 
the anterior surface of the iris and posterior surface of the cornea. At the vertex of this angle 
resides the trabecular meshwork through which fluid must flow to escape the eye and ultimately 
enter the systemic venous circulation. Closed-angle glaucoma can appear suddenly and is often 
painful; visual loss can progress quickly, but the discomfort often leads patients to seek medical 
attention to expedite treatment. Chronic, open-angle glaucoma tends to progress at a slower rate 
and patients may not notice they have lost vision until the disease has progressed significantly. 
 
3.1 
AQUEOUS HUMOR OUTFLOW PATHWAY 
Aqueous humor circulation through the anterior segment of the eye represents one of the many 
cardiac circulatory loops that also include the various arteriovenous, lymphatic, and 
cerebrospinal fluid circulations. Each of these circulatory loops is driven down a continuous 
pressure gradient initially set up by the heart. Aqueous humor is formed by the ciliary processes, 
passes from the posterior chamber to the anterior chamber through the pupil, and exits the eye at 
the anterior chamber angle. 
 
 

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Aqueous returns to the venous system primarily by means of the conventional or 
trabeculocanalicular pathway (83-96% of flow). The pathway is through the trabecular 
meshwork into Schlemm's canal (hence the “trabeculocanalicular” pathway). Aqueous collector 
channels connect the lumen of Schlemm’s canal to the episcleral veins, completing the 
circulatory pathway for aqueous return to the heart. 
Aqueous humor also returns to the heart by a secondary pathway known as the uveoscleral or 
unconventional route. The uveoscleral route accounts for from 5 to 15% of flow. 
Extracanalicular aqueous flow is through the anterior ciliary muscle and iris stroma to reach the 
supraciliary and suprachoroidal spaces. From these spaces the fluid passes through the sclera and 
the loose connective tissue around the penetrating nerves and vessels. 
3.2 
TRABECULOCANALICULAR OUTFLOW PATHWAY PHYSIOLOGY AND RESISTANCE 
The trabecular meshwork is an area of tissue in the eye located around the base of the cornea, 
near the ciliary body, and allows for drainage of the aqueous humor from the anterior chamber of 
the eye (the fluid filled space bound anteriorly by the corneal endothelium and posteriorly by the 
iris plane). The meshwork tissue is spongy, porous, and lined by trabeculocytes; it allows fluid to 
drain into a modified vascular sinus called Schlemm’s canal that then drains into collector 
channels which themselves drain into the systemic circulation. 
 
The meshwork is divided up into three parts, with characteristically different ultrastructures: 
1. Inner uveal meshwork – Closest to the anterior chamber angle, contains thin cord-like 
trabeculae, orientated predominantly in a radial fashion, enclosing trabeculae spaces larger 
than the corneoscleral meshwork. 
2. Corneoscleral meshwork – Contains a large amount of elastin,  arranged as a series of thin, 
flat, perforated sheets arranged in a laminar pattern; considered the ciliary muscle tendon. 
3. Juxtacanalicular tissue – Lies immediately adjacent to Schlemm’s canal, composed of 
connective tissue ground substance full of glycoaminoglycans and glycoproteins. This thin 
strip of tissue is covered by a monolayer of endothelial cells. 
Schlemm’s canal is a modified wall of a vessel. In other vessels such as arteries, pressure 
gradients are higher in the vessel lumen. With the canal, in contrast, pressures are higher external 
to the lumen of Schlemm’s canal. Intravascular fluid moves from the higher pressure in the 
lumen of vessels across vessel walls to the lower pressure in adjacent tissues as a response to the 
hydrostatic pressure gradient. Again, in contrast, aqueous humor flows from the anterior 
chamber, across the modified vascular wall represented by the trabecular meshwork, into the 
lower pressure vascular lumen of Schlemm’s canal. A series of adaptations is required as a result 
of the pressure gradient and fluid flow reversals. These adaptations are reflected in the unique 
tissue anatomy, geometry and responses to pressure in the wall of Schlemm’s canal that differ 
from those of the walls of other vessels. 
 
 
 

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Schlemm’s canal is a vascular sinus with a lumen that is circumferential around the entire 
anterior chamber angle. The lumen has a flattened elliptical cross-section with a circumference 
of approximately 36 mm. As the lining wall of a vessel, Schlemm’s canal endothelium has 
properties of a vascular endothelium. The canal is surrounded by sclera, trabecular meshwork, 
and the scleral spur. Generally, Schlemm’s canal has a lumen that is 190-370 microns in length 
in the radial plane. In hypotony, the shape varies, but when Schlemm’s canal shape is triangular, 
the lumen typically measures approximately 50 microns at its posterior base and narrows to 
about 5-10 microns at its apex. However, the diameter of the canal lumen is IOP dependent and 
the space can be absent at high pressures or very large at low pressures. Contrary to popular 
thought, the canal may sometimes be compartmentalized with septae or walls that may limit 
continuous circumferential flow. 
Schlemm’s canal is drained by a series of collector channels that in turn drain into a complex 
system of intrascleral, episcleral, and subconjunctival venous plexus. The collector channels 
arise from the outer wall of Schlemm’s canal at irregular intervals (0.3- 2.8 mm) that average  
1.2 per mm creating a total of 20-30 collector channels. At the origin of some collector channels, 
openings are observed that are associated with septa. Septa at collector channel ostia limit or 
prevent trabecular tissue from completely occluding the opening. A few (4-6) direct collector 
channels (approximately 70 micron diameter) proceed directly from Schlemm’s canal through 
the sclera thus communicating directly with aqueous veins on the surface of the eye. Indirect 
collector channels are smaller (approximately 50 micron diameter), more numerous (15-20) and 
enter into the intrascleral drainage network. A few (4-6) intermediate types are present.  
 
3.3 
OUTFLOW RESISTANCE 
Raised intraocular pressure (IOP) can theoretically result from three causes: increased aqueous 
production, elevated systemic venous pressure, or increased aqueous outflow resistance (reduced 
aqueous outflow). There is a great deal of experimental evidence suggesting that in a majority of 
patients, raised IOP results from an abnormality of the resistance characteristics of the outflow 
system. Investigators have proposed two different leading models of the exact resistance location 
and mechanism, but both are located within the overall trabeculocanalicular tissue.  
The first model envisions the main resistance localized to the juxtacanalicular space. The 
juxtacanalicular space acts as a syncytium of extracellular matrix material and elastic-like fiber 
network that attaches to Schlemm’s canal endothelium. The syncytium must provide a 
sufficiently stable geometry so that the extracellular matrix material can act as a passive filter 
regulating resistance. After passing through the juxtacanalicular resistance, aqueous passes 
through low-resistance pores in Schlemm’s canal endothelium.  
The second model places the initial resistance to IOP-generated forces at Schlemm’s canal 
endothelium. The model necessitates redistribution of IOP-induced resistive forces at Schlemm’s 
canal endothelium to structural elements throughout a tensionally integrated trabecular 
meshwork. The force redistribution takes place via cytoplasmic process attachments to 
Schlemm’s canal endothelium. A second component of the Schlemm’s canal 
endothelium/trabecular meshwork resistance model is pressure-induced distention of Schlemm’s 

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The Sight Sciences VISCO™360 is used for delivery of small amounts of viscoelastic fluid into 
the eye including the anterior segment.  The VISCOTM360 components responsible for the fluid 
dispensing are the following: 
 
o The reservoir within the handle is analogous to a syringe plunger.  Prior to use, the 
viscoelastic fluid is loaded into the reservoir. 
 
o The plunger tube is connected to the injection tube and it communicates with the 
reservoir. During use the plunger tube acts like the graduated cylinder. 
 
o The injection tube, initially located within the cannula, advances and retracts from the 
device to dispense fluid.  The injection tube is analogous to a syringe dispensing-tip. 
 
o The user interfaces with the device by using the finger wheels. This action is 
analogous to moving the dispensing tip to the desired location and depressing the 
plunger handle, see Figure 1. 
 
 
FIGURE 1: THE SIGHT SCIENCES VISCOTM360 VISCOSURGICAL SYSTEM 
 
 
 
 
 

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To operate the device and dispense fluid, first the entire device including the reservoir, plunger 
tube and injection tube are flushed with viscoelastic fluid until fluid is visualized at the cannula 
tip.  Next, the device is placed within the eye and using the finger wheel, the injection tube is 
advanced from the cannula to the desired location for fluid dispensing. Advancing the injection 
tube also moves the reservoir and plunger tube forward or distal within the handle.  Finally, the 
injection tube is retracted into the cannula and fluid is dispensed.  Retracting the injection tube 
displaces the plunger tube into the reservoir to exchange volume and dispense fluid.  Since the 
injection tube and plunger tube are connected, the fluid flows from the reservoir through the 
plunger tube and out of the injection tube.  
 
5.0 
PRIOR PRE-CLINICAL AND CLINICAL TESTING 
The VISCO360 injector has been subjected to a comprehensive battery of nonclinical laboratory 
studies reviewed by FDA to support 510(k) clearance: 
 
• Biocompatibility 
• Sterilization 
• Shelf-Life 
• Packaging Integrity 
• Mechanical testing 
Additionally, a review of the clinical literature was performed which described the outcomes 
following ab externo viscocanalostomy and ab externo canaloplasty for the reduction of IOP. 
Viscocanalostomy involves the viscodilation of only 60-90 degrees of Schlemm’s canal using a 
rigid, stainless steel injection needle.   Canaloplasty, used to dilate all 360 degrees of Schlemm’s 
Canal, is the evolution of viscocanalostomy using catheters which are flexible and are able to 
transluminally circumnavigate and viscodilate up to all 360 degrees of Schlemm’s canal. These 
surgical approaches have been performed over the past two decades and found to have a good 
safety and effectiveness profile.  The clinical experience with both procedures is described 
below. 
 
5.1 
VISCOCANALOSTOMY 
Ab externo viscocanalostomy unroofs and dilates Schlemm’s canal without penetrating the 
trabecular meshwork or anterior chamber. It was pioneered by Dr. Robert Stegmann in the 
1990’s. In this procedure, a high-viscosity viscoelastic solution (sodium hyaluronate) is used to 
dilate a 60-90 degree section of Schlemm’s canal and the trabecular meshwork.  
Viscocanalostomy is effective at lowering IOP and it avoids bleb-related complications. Like 
other ab externo approaches, however, it does not spare conjunctiva, sclera, or limbus. 
 

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Recently, the iTrack™ microcatheter is being used for ab interno canaloplasty to spare the sclera 
and conjunctiva.   Like ab externo canaloplasty, ab interno canaloplasty addresses the trabecular 
meshwork, Schlemm canal, and collector channels. It follows the same dilation principles of ab 
externo canaloplasty, where the controlled delivery of viscoelastic during withdrawal of the 
iTrack microcatheter creates microperforations in the trabecular meshwork and separation of the 
compressed tissue planes within Schlemm’s canal. The procedure pulls any herniated inner wall 
and juxtacanalicular tissue out of the collector channels.  It should be noted that ab interno 
canaloplasty is expected to provide equivalent or better IOP reduction as compared to an ab 
externo approach while avoiding some of the complications observed in the aforementioned 
studies including inadvertent bleb and suture extrusion through the TM. As mentioned, an ab 
interno approach has the benefit of sparing the conjunctiva, sclera, or limbus for additional 
surgery (including trabeculectomy or an implantable glaucoma shunt). Therefore, as is the case 
with laser trabeculoplasty which also spares the conjunctiva, more invasive surgeries for further 
IOP reduction are available to the patient, if indicated. 
6.0 
STUDY ENDPOINTS 
6.1 
EFFECTIVENESS ENDPOINTS 
The primary effectiveness endpoint is change in mean diurnal IOP from baseline at 12 months 
compared between the VISCO360 group and the control group. 
Criteria for Failure to Respond 
The mean diurnal IOP at 12 months will be imputed for subjects who meet the following 
criteria: 
• IOP persistently below 6mmHg (defined as an intraocular pressure below 6mm that is 
present on two consecutive follow-up visits after the three-month visit)  
• underwent secondary IOP lowering interventions to control IOP (e.g., laser 
trabeculoplasty, trabeculectomy, shunt or valve placement, iridotomy/iridectomy) prior to 
the 12-month visit, 
• post-operative introduction of an oral carbonic anhydrase inhibitor,ii  
• no diurnal IOP data collected from the available Month 12 visit, 
• underwent other secondary surgical interventions that could affect IOP,  
• use of ocular hypotensive medication within 4 weeks of the Month 12 washout visit iii 
For subjects who meet any of the criteria above, the mean washout diurnal IOP at baseline will 
be imputed as the mean washout diurnal IOP at 12 months.  
 
 
 
 
 
ii Does not include use in the perioperative period 
iii If the study subject fails to remember not to use ocular hypotensive medication for the study eye per the 
required washout period prior to this visit, they can be reinstructed to washout and return for a 12 month 
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4. 
Intraocular pressure ≥ 18.0 mmHg and ≤30.0 mmHg and not at the patient’s target pressure 
while on 1-3 topical ocular medications or while not on topical ocular medication due to 
intolerance of medication or history of poor compliance (Screening Visit). Combination 
glaucoma medications that consist of two or more glaucoma drugs will have each glaucoma 
drug component counted as a separate drug. 
5. 
At the Baseline Visit, an unmedicated IOP ≥ 21.0 mmHg and ≤ 36.0 mmHg and ≥ 3.0 
mmHg higher than the medicated IOP measured at the Screening Visit 
6. 
Shaffer grade of ≥ III in all four quadrants 
7. 
Subjects able and willing to comply with the protocol, including randomization assignment 
and all follow-up visits through 24 months. 
8. 
Subject understands and signs the informed consent. 
 
7.2 
EXCLUSION CRITERIA 
All criteria apply to the study eye unless otherwise noted and both eyes of a single subject need 
not be eligible): 
1. Phakia or aphakia 
2. Posterior Capsular Opacification graded as moderate or severe using the sample images 
provided in Appendix 1. In this case, a laser capsulotomy can be performed and the subject 
screened again a minimum of two weeks following the capsulotomy. 
3. Presence of Anterior Chamber IOL (ACIOL) 
4. History of complicated cataract surgery (e.g. vitreous loss, sutured IOL, decentered IOL, etc.) 
5. Pre-existing IOL instability 
6. Diagnosis of acute angle closure, traumatic, congenital, malignant, uveitic, 
pseudoexfoliative, pigmentary or neovascular glaucoma  
7. Inability to properly visualize angle (due to corneal scar, edema, etc.) 
8. Abnormal angle anatomy as determined by gonioscopy (e.g. peripheral anterior synechiae, 
rubeosis or other angle abnormalities) 
9. Conditions associated with elevated episcleral venous pressure such as active thyroid 
orbitopathy, cavernous sinus fistula, Sturge-Weber syndrome, orbital tumors, orbital 
congestive disease. 
10. The subject would be at significant risk by washout of ocular hypotensive medication 
including any of the following: 
o Unmedicated IOP after washout period is expected to exceed upper limit of 
36.0 mmHg at Baseline visit  
o Presence of afferent pupillary defect in either eye 
o C:D ratio ≥ 0.9 in either eye 
o Requiring oral medications (e.g., acetazolamide) for IOP control in either eye 

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d) inability to discontinue use of blood thinners in accordance with surgeon’s 
standard pre-operative and postoperative instructions, 
e) immunodeficiency concerns, 
f) other clinically significant ocular pathology other than glaucoma.  
21. Proliferative diabetic retinopathy  
22. Previous surgery for retinal detachment  
23. Central corneal thickness that is less than 450 microns or greater than 620 microns. 
24. Clinically significant corneal dystrophy (e.g., bullous keratopathy, guttata, etc.) 
25. Previous corneal surgery  
26. Wet age-related macular degeneration  
27. Clinically significant ocular inflammation or infection ≤ 30 days prior to screening. 
28. Participation in any clinical trial ≤ 30 days prior to screening. 
29. Women of childbearing potential if they are currently pregnant or intend to become pregnant 
during the study period; are breast-feeding; or are not in agreement to use adequate birth 
control methods to prevent pregnancy throughout the study. (A negative serum pregnancy 
test must be verified for females of child bearing potential). All women are considered to be 
of childbearing potential unless: 
• Postmenopausal for at least 1 year   
o OR 
• Surgically sterile 
 
8.0 
STUDY PROCEDURES 
8.1 
INFORMED CONSENT 
The informed consent will be presented and explained to each prospective subject by the 
investigator or a trained clinical professional.  The final Informed Consent Document (ICD) must 
be approved by the Institutional Review Board (IRB) and Sight Sciences, Inc. 
 
Once the subject has been informed of all aspects of the study, the subject will be given a choice 
to voluntarily confirm his or her participation in the study as documented by completion of the 
Informed Consent.  After signing the Informed Consent, the HIPAA (Health Insurance 
Portability and Accountability Act) authorization, and other applicable local documentation (e.g., 
California Bill of Rights), the subject can then proceed with the screening evaluation.  The 
subject has the right to withdraw from the study at any time without consequences, as indicated 
in the Informed Consent Document. 
 
The subject’s signed and dated informed consent must be obtained before conducting any 
procedure specifically for the study.  Subjects are enrolled upon signing the ICD even if they 
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8.6 
SLT PROCEDURE 
The type of anesthesia will be at the surgeon’s discretion. 
 
For patients assigned to the SLT treatment arm, a single application of pilocarpine and 
apraclonidine (1 %) or brimonidine (0.2 % or 0.15 %) will be instilled into the operative eye 
prior to the laser treatment. A frequency doubled, q-switched Nd:YAG laser emitting at 532 nm 
with a pulse duration of 3 ns, a spot size of 400 μm, and pulse energies ranging from 0.6 to 1.6 
mJ, coupled to a slit lamp delivery system with a helium-neon laser aiming system will be used 
in all cases. Any mirrored gonioscopic lens that does not magnify is acceptable for use during the 
procedure. The laser will be focused on the trabecular meshwork using the HeNe aiming beams 
and a single laser pulse will be delivered at the 3 o’clock position. The laser energy will be 
increased or reduced by 0.1-mJ increments until fine ‘champagne’ bubbles are generated. During 
laser application, bubble formation will be monitored with each pulse to avoid excessive bubble 
formation and to avoid no observed response. 
 
Additional details are included in the SLT laser manufacturer’s approved instructions for 
performing SLT. 
 
180° treatments of approximately 50 applications should be applied first inferiorly and then 
superiorly with the goal of 360° treatment.  If necessary, the superior 180° SLT treatment can be 
performed in a separate session within 1 week of the first SLT session and the reason for deferral 
should be recorded.  The total number of pulses delivered, the number of clock hours treated, and 
the total amount of energy delivered will be recorded following each treatment. 
 
One drop of apraclonidine (1 %) or brimonidine (0.2 % or 0.15 %) should be applied 
immediately after the SLT procedure and an NSAID (e.g. Ketorolac 0.4%) 1 drop 4 times per 
day for 4 days should be prescribed following SLT. 
 
The IOP should be checked and recorded within 1 hour of the laser procedure. An IOP increase ≥ 
10 mmHg should be recorded as an AE. 
 
8.7 
WASHOUT 
Subjects who meet all screening eligibility criteria will be instructed to discontinue their ocular 
hypotensive medication regimen in the study eye only, and to return for a baseline visit after 
completing the appropriate washout period.  Glaucoma medication discontinuation can be staged 
so that the pressure increase duration is minimized to the greatest possible extent during the 
washout period. 
If the subject does not currently take any glaucoma medication, the Baseline Exam can be 
scheduled as soon as two (2) days after completing the Screening Exam. 
 
 

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8.8 
MANAGEMENT OF IOP AFTER SURGERY/SLT PROCEDURE 
Both groups (treatment and control) should be treated consistently. In general, the primary 
consideration for management of IOP is the preservation of the retinal nerve fiber layer, optic 
nerve and visual field.  
 
Ocular hypotensive medication “rescue therapy” will be introduced 1 month postoperatively or 
later to any subject if his/her IOP increases ≥ 21 mmHg and is ≤ 20% below their preoperative 
medicated IOP (at two consecutive visits within a two week period).  
 
For subject safety, a change in medical therapy may be implemented or additional surgical 
measures may be performed at any time during the study at the Investigator’s discretion in the 
event it is required. The primary concern of the Investigator, Medical Monitor and Sponsor at all 
times is the health and safety of the subjects.  
 
Administration of glaucoma medication in subjects with IOP < 21 mmHg will be considered on a 
case-by-case basis by the study investigator and the Medical Monitor. In these cases, the Medical 
Monitor will consult with the physician to understand the rationale for the intervention and it will 
be documented by the investigator on the follow-up form in the field identified as “Investigator 
rationale for intervention”.  For the intervention, the reason for the decision will be noted on the 
case report form as one or more of the following:  “IOP> target IOP”, “visual field change”, and 
“optic nerve change”.   A field for “Other” will be used to document any other reason for the 
intervention. 
 
Re-introduction of hypotensive medications will be standardized as follows: 
 
• The same medication class(es) as used preoperatively will be re-introduced. Dependent 
on preoperative IOP medication use, the reintroduction/addition of IOP medications 
postoperatively should follow the order below: 
 
1. Prostaglandin Analogues 
2. Alpha Agonists 
3. Beta Blockers 
4. Carbonic Anhydrase Inhibitors (CAIs). 
 
• No more than one ocular hypotensive agent should be added at a single visit or within a 
2-week period, without approval of the Medical Monitor.  Approval of the Medical 
Monitor must be obtained prior to or promptly after the subject’s visit (e.g. within 3 
working days). 
 
In the event of a steroid response (IOP increase), the usual guidelines requiring a reproducible 
increase in IOP should be followed; however, topical hypotensive medications should be 
discontinued once the topical steroid has been discontinued. 
 
Use of glaucoma medications in the first month after surgery/SLT will be allowed at the 
discretion of the study investigator. This short-term use of glaucoma medications in the 

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immediate postoperative period will not be considered "rescue therapy" and will not be 
considered in the effectiveness analyses for the study.  
 
If a pressure rise is observed, a paracentesis may be performed as necessary by either the 
principal investigator or the sub-investigator. If a paracentesis is performed and there is no 
protocol-defined adverse event, the paracentesis will be documented in the subject’s medical 
record, the applicable visit CRF and the Ocular Procedures log. If, however, the paracentesis is 
performed in conjunction with an AE, then the AE is recorded as such, and the paracentesis is 
also recorded on the AE CRF as a treatment for the protocol-defined AE (as well as the other 
CRFs mentioned above). 
Usage of hypotensive medications specifically indicated for prevention of IOP increases 
following Nd:YAG capsulotomy and administered for up to 72 hours after Nd:YAG 
capsulotomy, will not be considered rescue therapy. 
Medications which have been re-started by the investigator may be discontinued if the 
investigator’s judgment is that the target intraocular pressure has been reached and the continued 
use of some or all of the therapy may not be required. Discontinuation of medications after re-
introduction is recommended to be in the reverse order of re-introduction.  The rationale for 
discontinuation will also be documented on the follow-up form by the investigator and the 
Medical Monitor will follow up with the investigator as needed to assure consistency within the 
study parameters.  For medication discontinuation, the reason for the decision will be noted on 
the case report form as “IOP controlled” or “allergy to medication”.  A field for “Other” will be 
used to document any other reason for glaucoma medication discontinuation. 
A record of all ocular hypotensive medications added, discontinued or changed will be 
documented on the appropriate Case Report Form for each scheduled visit or on a Case Report 
Form for an Unscheduled Visit, if necessary. 
Another potential reason for intervention is hypotony.  Intervention should only be considered if 
the hypotony has caused or is likely to cause sequelae such as a flat chamber. No intervention is 
indicated when the vision is unchanged from screening, there is no persistent choroidal 
detachment, the anterior chamber is not flat with lens corneal touch, or the patient is 
asymptomatic.  No intervention should be undertaken for hypotony which is not causing, or 
threatening to cause, a reduction in vision. 
If another glaucoma procedure occurs, the event will result in the subject being followed 
according to standard of care until the adverse event resolves and the follow-up visits over the 
two years period under the protocol schedule will be part of the safety analyses.  Any extra visits 
to evaluate the patient due to the secondary procedure will be considered “Unscheduled Visits” if 
performed outside of the standard visit windows in the protocol and the Unscheduled Visit form 
will be used to document the visit. 
For any surgery or interventions not directly related to the subject’s glaucoma that occur during 
the study, the standard of care for the particular type of intervention will be followed until the 
subject has recovered.  Unless a visit coincides with the standard protocol follow-up visit, the 

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visits will be handled as “Unscheduled Visits” and the Unscheduled Visit form will be used to 
document the visit. 
 
8.9 
FOLLOW-UP 
All subjects will participate in defined follow-up visits throughout two years as follows: 
 
o Screening (Day -45 TO -2) 
 
o Baseline (Day -15 TO 0 after completion of medication washout) 
 
o Surgery/SLT Procedure (Day 0) 
 If necessary, the second 180° SLT treatment can be performed in a separate 
session within 1 week of the first SLT session and the schedule of visits will not be 
altered (the Unscheduled Visit CRF will be used for this visit) 
 
o 1 Day Postop (Day 1)  
 
o 1 Week Postop (Day 5-9)  
o 1 Month Postop (Day 21-35) 
o 3 Months Postop (Day 70-98) 
 
o 6 Months Postop (Day 150 –210)  
o 12 Months Postop (Day 330 – 420) 
 At the 12 M Postoperative Visit, only subjects who are ocular hypotensive 
medication-free will have Diurnal IOP measurements performed.  Subjects using 
ocular hypotensive medications at this visit will undergo medication washout and 
return for the 12 M Postoperative Washout Visit for Diurnal IOP measurements.   
 
o 12 Month Washout (Day 330 – 420, after completion of medication washout) 
o 18 Months Postop (Day 510 – 600) 
o 24 Months Postop (Day 690 – 780) 
 
A follow-up case report form shall be completed from source data gathered at the time the 
subject is examined.  Unscheduled visits should also be recorded using the appropriate forms.  
Table 2 provides an overview of all activities to be conducted during the clinical study.   
 
All attempts should be made to conduct each follow-up evaluation within the specified time 
intervals shown in Table 2.  Evaluations conducted outside the prescribed time period will be 
considered protocol deviations.  Visits conducted outside scheduled timeframes will be 
considered an additional visit and must be documented using the Unscheduled Visit form.

 
 
 
 
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8.10 
WITHDRAWAL CRITERIA 
All subjects have the right to withdraw at any point during the treatment without prejudice.  The 
investigator can discontinue any subject at any time if continued participation in the study would 
result in harm to the subject.  All efforts should be made by the investigator to retain the patient 
in the study.  If a subject withdraws prematurely from the study, a genuine effort must be made 
to determine the reason(s) the subject discontinued the study.  The reason must be recorded in 
the subject’s file and on the End of Study Form and faxed to Sight Sciences, Inc. and the CRO 
(Sierra Clinical Services). 
 
8.11 
LOST TO FOLLOW-UP SUBJECTS 
Subjects who do not show up for a follow-up must be contacted to attempt to have them come 
for the follow-up.  For those subjects who cannot be reached, at least 3 phone call attempts 
should be made and documented.  If still no response, a registered letter shall be sent to the 
address on file for the subject in an attempt to make contact.  If there is still no response, the 
subject will be considered lost-to-follow-up unless there is a further communication by the 
subject. 
 
8.12 
DEVICE RETURN 
If a Sight Sciences device needs to be returned, the Device Return Form must be completed and 
returned with the product as instructed by the Device Return Procedure (located in the 
Regulatory Binder).  Reasons for return could include any of the following: 
1. Device has exceeded the labeled expiration date. 
2. Device was not present or damaged in packaging. 
3. Device was damaged or contaminated before or during surgical procedure. 
4. Device could not be inserted during surgical procedure. 
5. Unused inventory upon completion of the study or site exiting from the study. 
 
For any device to be returned that has been exposed to blood or tissue, a special package will be 
provided by Sight Sciences, Inc. for return of the device. 
 
8.13 
PROTOCOL MODIFICATION AND DEVIATIONS 
Protocol modifications may occur during the study.   Each will be approved by the sponsor 
before implementation. Each will undergo Institutional Review Board (IRB) review and approval 
as necessary. 
 
Any deviations from this protocol intended to protect the life or physical well-being of a subject 
in an emergency are to be reported to Sight Sciences, Inc. as well as the IRB as soon as possible, 
and no later than 5 working days after the emergency occurred. 
 
All protocol deviations will be documented using Protocol Deviation form. 
 
 
 
 

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9.0 
DATA HANDLING AND RECORDKEEPING 
9.1 
SUBJECT IDENTIFICATION 
The subjects will be identified by a seven digit subject number composed of a one-digit study 
identification number, a three digit center identification number followed by a three digit 
sequential subject number.  The subject identification will be assigned when ICD is obtained.  
The initials for each subject will also be included on CRFs.  In this way, information contained 
in the study records will be kept as confidential as possible. 
 
9.2 
SUBJECT ACCOUNTABILITY 
All subjects randomized in this clinical investigation shall be monitored for the duration of the 
investigation. The clinical investigation shall be considered completed when all subjects that 
have been enrolled in the investigation, excluding subjects who were withdrawn, have reached 
the final reporting period.   
 
9.3 
CONFIDENTIALITY 
All medical records associated with the clinical investigation will be made available for review 
by Sight Sciences personnel, its contract research organization (CRO) and 
governmental/regulatory agencies involved.  The results of the study may be published in the 
future for scientific and marketing purposes, but the identity (name) of each subject will not be 
revealed.  All records will be stored in a secure area at the investigator’s facility, the CRO, and at 
Sight Sciences, Inc. 
 
9.4 
SOURCE DATA AND CASE REPORT FORMS 
The following forms will be utilized to collect source data during this clinical investigation.  
Source Data Form Completion Guidelines will be provided at the investigational sites.  These 
guidelines provide added instructions for the completion of all forms.  These guidelines will be 
updated as needed throughout the trial to provide continuing clarification as required. 
 
Source data forms are to be maintained at the site in the subject records.  All entries must be 
made in black or blue ink and changes must be made by strike-through only with date and initials 
or signature.  All source documents must be completed and signed by the authorized study 
personnel (e.g., study coordinator).    No “white-out” is to be used on the source documents. 
 
 
 
 

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The source data will be entered into a validated electronic system at each site by trained 
personnel in accordance with 21CFR Part 11 requirements.   
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
9.5 
DEVICE ACCOUNTABILITY 
With each shipment of investigational devices, Sight Sciences will include a Packing List that 
will give the amount shipped and the lot numbers. This packing list must be reconciled by the 
investigational site with the contents of the shipment and then complete the Inventory Logs for 
the VISCO™360 Viscosurgical System (these logs are contained within the regulatory binder at 
the site).  All investigational products at the site must be stored in a secured/locked area.  Device 
reconciliation activities will also be conducted periodically in conjunction with site monitoring 
visits. 
 
The investigator must maintain accurate records of the receipt of all devices shipped by Sight 
Sciences, including the date and lot numbers received with the use of the device inventory 
tracking log. The use of devices will also be recorded.  An extra label provided with the device 
may be placed in the patient records. 
 
9.6 
RECORD RETENTION 
Clinical sites are to retain any and all clinical trial material (documentation, photographs, etc.) 
for a period of two years from the date the marketing application is approved or two years after 
the investigation has been discontinued and the FDA notified, or as directed by their institutional 
document retention requirements, whichever is the longest.  After that time, the items must be 
returned to Sight Sciences for archiving.  Unused medical devices are to be returned to the 
sponsor at the conclusion of the enrollment period. 
 

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11.0 
MONITORING PLAN 
Sight Sciences or CRO personnel will monitor the study in a manner consistent with applicable 
health authority regulations and the clinical research standards adopted by Sight Sciences.  Study 
monitoring will involve the following elements: 
 
• Sight Sciences or CRO personnel meet with investigators and clinical study staff prior 
to the initiation of the study in order to review the adequacy of the subject population, 
facilities, and equipment with respect to the needs of the study, and to familiarize the 
investigator with the study protocol. 
• Sight Sciences or CRO personnel meet with the investigator(s) and clinical study staff 
at the time the site begins to enroll in order to ensure that subjects are being properly 
selected and that study data are being correctly recorded. 
• Sight Sciences or CRO personnel visit the clinical site at any time during the study to 
review and/or collect the Case Report Forms. 
• Interim monitoring visits and telephone consultation will occur as necessary during the 
course of the study to ensure the proper progress and documentation of the study 
findings. 
 
12.0 
STATISTICAL PLAN 
 
The Statistical Analysis Plan for the SightVisco-001 clinical study has been detailed in a separate 
document. The sample size for the primary effectiveness endpoint and the corresponding 
statistical hypotheses is based on the following assumptions and criteria. 
 
• The standard deviation of change in mean diurnal IOP from baseline at 12 months is 
assumed to be 5.0 mmHg.  Per Seymenoglu1, the mean and standard deviation (SD) of 
the change in IOP from baseline to 12 months was 5.5 mmHg ± 3.8 mmHg for the 
pseudophakic eyes with SLT, without additional medications, without SLT 
retreatments, and without any glaucoma-related secondary surgical intervention.  Since 
the study will study the change in the mean diurnal IOP from baseline after washout to 
12 months after washout, the SD of the endpoint is expected to be larger than the 
published SD of 3.8 mmHg.   It is assumed an SD of 5 mmHg for the study. 
• Significance level is 0.025 (one-sided) and statistical power is 90% at a true mean 
difference of 2 mmHg. 
• Two-sample t-test will be used. 
• A yearly dropout rate of 10% is considered. 
• The randomization ratio for the study is 1:1. 
Based on the criteria above, the 12-month sample size for the primary effectiveness endpoint and 
corresponding statistical hypotheses are 133 VISCO 360 and 133 control subjects at 12 months.  
With the yearly dropout rate of 10%, approximately 296 subjects (148 VISCO 360 and  
148 controls) should be randomized. 
 
 

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The sample size calculation for the secondary effectiveness endpoint and the corresponding 
statistical hypotheses described is based on the following assumptions and criteria: 
 
• The 12-month IOP response rates for the control group (pc) are estimated to be 0.5. Per 
Seymenoglu, the 12-month IOP response rate was 0.62 for the pseudophakic eyes with 
SLT, without additional medications, without SLT retreatments, and without any 
glaucoma-related secondary surgical intervention.  Due to the requirement of 
medication washout in this study, it is expected that the 12-month response rate for the 
control group of this study is lower than the published 0.62.  Therefore, a 12-month 
response rate of 0.50 is assumed for the control group. 
• Significance level is 0.025 (one-sided) and statistical power is 90% at a difference in 
the responder rate of 0.2.  In other words, the power is 90% if the true pv (the 12-
month response rate of the VISCO 360 group) is 0.2 and the true pc is 0.5. 
• Fisher’s exact test will be used. 
• A yearly dropout rate of 10% is considered. 
• The randomization ratio for the study is 1:1. 
Based on the criteria above, the 12-month sample size for the secondary effectiveness endpoint 
and corresponding statistical hypotheses are 134 VISCO 360 and 134 control subjects at 12 
months.   With the yearly dropout rate of 10%, approximately 298 subjects (149 VISCO360 and 
149 controls) should be randomized. 
 
Since the sample size for the secondary effectiveness endpoint is larger than that for the primary 
effectiveness endpoint, approximately 298 randomized subjects will be required for this study.  
If a 40% screening failure is considered, approximately 497 subjects should be enrolled and 
screened. 
 
13.0 
MEDICAL MONITOR 
An independent Medical Monitor will be used in the study.  The Medical Monitor will not be an 
investigator in the study.  The Medical Monitor will be a certified ophthalmologist with 
glaucoma specialization.  The Medical Monitor will review adverse events and determine if the 
appropriate action have or are being taken.  If a subject cannot be washed out of their ocular 
hypotensive medications, the medical monitor will review the subject records and the decision in 
a masked fashion. 
 
14.0 
COMPLIANCE WITH PROTOCOL 
An investigator shall conduct this investigation in accordance with the signed agreement with the 
sponsor, the investigational plan, the IDE regulation and other applicable FDA regulations, and 
any conditions of approval imposed by an IRB or FDA. 
 
 

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Flare 
0 = None 
1+ = Faint 
2+ = Moderate (iris and lens details clear)  
3+ = Marked (iris and lens details hazy) 
4+ = Intense (fibrin or plastic aqueous) 
 
The presence of hypopyon is recorded separately.  The presence of “microhyphema” or “layered 
hyphema” in the anterior chamber should also be recorded. Layered hyphema will be graded 
using the following scale (If Grade 1, also record size in mm on the CRF).49 
 
 
 
 
 
 
 
                                                          
49 http://www.aao.org/image/hyphema-grading-system-2 

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Posterior Capsule Opacification 
As a routine part of the slit lamp examination, posterior capsule opacification (PCO) will be 
evaluated using the following scale: 
 
 
 
If a subject with PCO is scheduled for a YAG laser capsulotomy, the subject’s best-corrected 
visual acuity (BCVA) must be measured prior to the YAG procedure and at a subsequent interim 
visit following the YAG procedure.  Additionally, all information related to hypotensive 
medications prescribed to a subject before or after a YAG procedure must be collected.  This 
information must be captured on the appropriate source document and study case report form. 
 
Other Slit Lamp Findings (complete for each finding) 
• 
Trace 
• 
Mild 
• 
Moderate 
• 
Severe 
 
 
NONE 
Minimal (Top left image) 
Mild (Top right image) 
Moderate (bottom left 
image) 
Severe (bottom right image) 

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APPENDIX 2: SPONSOR’S OBLIGATIONS 
 
GENERAL RESPONSIBILITIES OF SPONSORS  
Sponsors are responsible for selecting qualified Investigators and providing them with the 
information they need to conduct the investigation properly, ensuring proper monitoring of the 
investigation, and ensuring that each local investigator has obtained IRB review and approval.  
 
SPECIFIC RESPONSIBILITY OF SPONSORS 
1. Selecting Investigators - A Sponsor shall select Investigators qualified by training and 
experience to investigate the device. 
2. Obtaining Agreements - A Sponsor shall obtain from each participating Investigator a signed 
agreement that includes: 
a) 
The Investigator’s curriculum vitae. 
b) Where applicable, a statement of the Investigator’s relevant experience, including the 
dates, location, extent, and type of experience. 
c) 
A statement of the Investigator’s commitment to: 
(1) Conduct the investigation in accordance with the agreement, the investigational 
plan, and conditions of approval imposed by the reviewing IRB; 
(2) Supervise all testing of the device involving human subjects; and  
(3) Ensure that the requirements for obtaining informed consent are met  
(21CFR Part 50). 
 
SPONSOR RECORDS 
A Sponsor shall maintain the following accurate, complete, and current records relating to 
an investigation for a period of 3 years after completion of the study: 
1. All correspondence with a monitor, an Investigator, an IRB, including required reports. 
2. Records of shipment. Records of shipment shall include the name and address of the 
consignee, type and quantity of device, date of shipment, and serial number.  
3. Signed Investigator agreements. 
4. Records concerning adverse device effects (whether anticipated or unanticipated) and 
complaints.  
 

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SPONSOR REPORTS 
A Sponsor shall prepare and submit the following complete, accurate, and timely reports: 
 
1. 
Unanticipated Adverse Device Effects - A Sponsor who conducts an evaluation of an 
unanticipated adverse device effect shall report the results of such evaluation to the 
reviewing IRB and participating Investigator within 10 working days after the Sponsor first 
receives notice of the effect. 
2. 
Withdrawal of IRB Approval - A Sponsor shall notify the reviewing IRB and participating 
Investigator of any withdrawal of approval of an investigation or a part of an investigation 
by a reviewing IRB within 5 working days after receipt of the withdrawal of approval. 
3. 
Withdrawal of FDA Approval - A Sponsor shall notify the reviewing IRB and participating 
Investigator of any withdrawal of FDA approval of the investigation, and shall do so within 
5 working days after receipt of notice of the withdrawal of approval. 
4. 
Progress Reports - At regular intervals, and at least yearly, a Sponsor shall submit progress 
reports to all reviewing IRBs. 
 
 
 
 

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APPENDIX 3: INVESTIGATOR’S AGREEMENT AND OBLIGATIONS 
 
GENERAL RESPONSIBILITIES OF INVESTIGATORS 
An Investigator is responsible for ensuring that an investigation is conducted according to the 
signed agreement, the investigational plan and applicable FDA regulations, for protecting the 
rights, safety, and welfare of subjects under the Investigator’s care, and for the control of devices 
under investigation. An Investigator also is responsible for ensuring that informed consent is 
obtained in accordance with 21 CFR part 50. 
 
SPECIFIC RESPONSIBILITIES OF INVESTIGATORS 
1. 
Awaiting approval - An Investigator may determine whether potential subjects would be 
interested in participating in an investigation, but shall not request the written informed 
consent of any subject to participate, and shall not allow any subject to participate before 
obtaining IRB approval. 
2. 
Subject Qualification -The Investigator is responsible for ensuring that all subjects entering 
the study conform to the patient selection criteria. 
3. 
Compliance - An Investigator shall conduct an investigation in accordance with the signed 
agreement with the Sponsor, the investigational plan, all applicable FDA regulations, and 
any conditions of approval imposed by an IRB or FDA. 
 
INVESTIGATOR RECORDS 
A participating Investigator shall maintain the following accurate, complete, and current records 
relating to the Investigator’s participation in an investigation for a period of 3 years after 
completion of the study:  
1. 
All correspondence with another Investigator, an IRB, the Sponsor, a monitor, or FDA, 
including required reports. 
2. 
Records of each subject’s case history and exposure to the device. Case histories include 
the study CRF’s/worksheets and supporting data including, for example, signed and dated 
consent forms and medical records.  Such records shall include: 
a) 
Documents evidencing informed consent. 
b) All relevant observations, including records concerning adverse device effects 
(whether anticipated or unanticipated), information and data on the condition of each 
subject upon entering, and during the course of, the investigation, including 
information about relevant previous medical history and the results of all diagnostic 
tests. 
3. 
The protocol, with documents showing the dates and reasons for each deviation from the 
protocol. 
4. 
Any other records that FDA requires to be maintained by regulation or by specific 
requirement for a category of investigations or a particular investigation. 
 

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INVESTIGATOR REPORTS 
An Investigator shall prepare and submit the following complete, accurate, and timely reports: 
1. 
Unanticipated Adverse Device Effects - An Investigator shall submit to the Sponsor and to 
the reviewing IRB a report of any unanticipated adverse device effect occurring during an 
investigation as soon as possible, but in no event later than 10 working days after the 
Investigator first learns of the effect. 
2. 
Withdrawal of IRB Approval - An Investigator shall report to the Sponsor, within 5 
working days, a withdrawal of approval by the reviewing IRB of the Investigator’s part of 
an investigation. 
3. 
Progress - An Investigator shall submit progress reports on the investigation to the Sponsor, 
the monitor, and the reviewing IRB at regular intervals, but in no event less often than 
yearly. 
4. 
Deviations from the Investigational Plan - An Investigator shall document and report to the 
Sponsor any deviation from the investigational plan.  
5. 
Informed Consent - If an Investigator enrolls a subject without obtaining informed consent, 
the Investigator shall report such use to the Sponsor and the reviewing IRB within 5 
working days after the use occurs. 
6. 
Final Report - An Investigator shall, within 3 months after termination or completion of the 
investigation or the Investigator’s part of the investigation, submit a final report to the 
Sponsor and the reviewing IRB. 
7. 
Other - An Investigator shall, upon request by a reviewing IRB or FDA, provide accurate, 
complete, and current information about any aspect of the investigation. 
 
 
 

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APPENDIX 4: DECLARATION OF HELSINKI 
 
I. 
PREAMBLE 
 
1. 
The World Medical Association (WMA) has developed the Declaration of Helsinki as a 
statement of ethical principles for medical research involving human subjects, including 
research on identifiable human material and data. 
 
The Declaration is intended to be read as a whole and each of its constituent paragraphs 
should be applied with consideration of all other relevant paragraphs. 
 
2. 
Consistent with the mandate of the WMA, the Declaration is addressed primarily to 
physicians. The WMA encourages others who are involved in medical research 
involving human subjects to adopt these principles. 
 
 
II. 
GENERAL PRINCIPLES 
 
1. 
The Declaration of Geneva of the WMA binds the physician with the words, “The 
health of my patient will be my first consideration,” and the International Code of 
Medical Ethics declares that, “A physician shall act in the patient's best interest when 
providing medical care.” 
 
2. 
It is the duty of the physician to promote and safeguard the health, well-being and 
rights of patients, including those who are involved in medical research. The 
physician's knowledge and conscience are dedicated to the fulfilment of this duty. 
 
3. 
Medical progress is based on research that ultimately must include studies involving 
human subjects. 
 
4. 
The primary purpose of medical research involving human subjects is to understand the 
causes, development and effects of diseases and improve preventive, diagnostic and 
therapeutic interventions (methods, procedures and treatments). Even the best proven 
interventions must be evaluated continually through research for their safety, 
effectiveness, efficiency, accessibility and quality. 
 
5. 
Medical research is subject to ethical standards that promote and ensure respect for all 
human subjects and protect their health and rights. 
 
6. 
While the primary purpose of medical research is to generate new knowledge, this goal 
can never take precedence over the rights and interests of individual research subjects. 
 
 

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7. 
It is the duty of physicians who are involved in medical research to protect the life, 
health, dignity, integrity, right to self-determination, privacy, and confidentiality of 
personal information of research subjects. The responsibility for the protection of 
research subjects must always rest with the physician or other health care professionals 
and never with the research subjects, even though they have given consent. 
 
8. 
Physicians must consider the ethical, legal and regulatory norms and standards for 
research involving human subjects in their own countries as well as applicable 
international norms and standards. No national or international ethical, legal or 
regulatory requirement should reduce or eliminate any of the protections for research 
subjects set forth in this Declaration. 
 
9. 
Medical research should be conducted in a manner that minimizes possible harm to the 
environment. 
 
10. Medical research involving human subjects must be conducted only by individuals with 
the appropriate ethics and scientific education, training and qualifications. Research on 
patients or healthy volunteers requires the supervision of a competent and appropriately 
qualified physician or other health care professional. 
 
11. Groups that are underrepresented in medical research should be provided appropriate 
access to participation in research. 
 
12. Physicians who combine medical research with medical care should involve their 
patients in research only to the extent that this is justified by its potential preventive, 
diagnostic or therapeutic value and if the physician has good reason to believe that 
participation in the research study will not adversely affect the health of the patients 
who serve as research subjects. 
 
13. Appropriate compensation and treatment for subjects who are harmed as a result of 
participating in research must be ensured. 
 
 
III. RISKS, BURDENS AND BENEFITS 
 
• 
In medical practice and in medical research, most interventions involve risks and 
burdens. 
 
Medical research involving human subjects may only be conducted if the importance of 
the objective outweighs the risks and burdens to the research subjects. 
 
• 
All medical research involving human subjects must be preceded by careful assessment 
of predictable risks and burdens to the individuals and groups involved in the research 
in comparison with foreseeable benefits to them and to other individuals or groups 
affected by the condition under investigation. 
 

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Measures to minimize the risks must be implemented. The risks must be continuously 
monitored, assessed and documented by the researcher. 
 
• 
Physicians may not be involved in a research study involving human subjects unless 
they are confident that the risks have been adequately assessed and can be satisfactorily 
managed. 
 
When the risks are found to outweigh the potential benefits or when there is conclusive 
proof of definitive outcomes, physicians must assess whether to continue, modify or 
immediately stop the study. 
 
 
IV. VULNERABLE GROUPS AND INDIVIDUALS 
 
• 
Some groups and individuals are particularly vulnerable and may have an increased 
likelihood of being wronged or of incurring additional harm. 
 
All vulnerable groups and individuals should receive specifically considered protection. 
 
• 
Medical research with a vulnerable group is only justified if the research is responsive 
to the health needs or priorities of this group and the research cannot be carried out in a 
non-vulnerable group. In addition, this group should stand to benefit from the 
knowledge, practices or interventions that result from the research. 
 
 
V. 
SCIENTIFIC REQUIREMENTS AND RESEARCH PROTOCOLS 
 
• 
Medical research involving human subjects must conform to generally accepted 
scientific principles, be based on a thorough knowledge of the scientific literature, other 
relevant sources of information, and adequate laboratory and, as appropriate, animal 
experimentation. The welfare of animals used for research must be respected. 
 
• 
The design and performance of each research study involving human subjects must be 
clearly described and justified in a research protocol. 
 
The protocol should contain a statement of the ethical considerations involved and 
should indicate how the principles in this Declaration have been addressed. The 
protocol should include information regarding funding, sponsors, institutional 
affiliations, potential conflicts of interest, incentives for subjects and information 
regarding provisions for treating and/or compensating subjects who are harmed as a 
consequence of participation in the research study. 
 
In clinical trials, the protocol must also describe appropriate arrangements for post-trial 
provisions. 
 
 

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VI. RESEARCH ETHICS COMMITTEES 
 
• 
The research protocol must be submitted for consideration, comment, guidance and 
approval to the concerned research ethics committee before the study begins. This 
committee must be transparent in its functioning, must be independent of the 
researcher, the sponsor and any other undue influence and must be duly qualified. It 
must take into consideration the laws and regulations of the country or countries in 
which the research is to be performed as well as applicable international norms and 
standards but these must not be allowed to reduce or eliminate any of the protections 
for research subjects set forth in this Declaration. 
 
The committee must have the right to monitor ongoing studies. The researcher must 
provide monitoring information to the committee, especially information about any 
serious adverse events. No amendment to the protocol may be made without 
consideration and approval by the committee. After the end of the study, the researchers 
must submit a final report to the committee containing a summary of the study’s 
findings and conclusions. 
 
 
VII. PRIVACY AND CONFIDENTIALITY 
 
• 
Every precaution must be taken to protect the privacy of research subjects and the 
confidentiality of their personal information. 
 
 
VIII. INFORMED CONSENT 
 
• 
Participation by individuals capable of giving informed consent as subjects in medical 
research must be voluntary. Although it may be appropriate to consult family members 
or community leaders, no individual capable of giving informed consent may be 
enrolled in a research study unless he or she freely agrees. 
 
• 
In medical research involving human subjects capable of giving informed consent, each 
potential subject must be adequately informed of the aims, methods, sources of funding, 
any possible conflicts of interest, institutional affiliations of the researcher, the 
anticipated benefits and potential risks of the study and the discomfort it may entail, 
post-study provisions and any other relevant aspects of the study. The potential subject 
must be informed of the right to refuse to participate in the study or to withdraw 
consent to participate at any time without reprisal. Special attention should be given to 
the specific information needs of individual potential subjects as well as to the methods 
used to deliver the information. 
 
After ensuring that the potential subject has understood the information, the physician 
or another appropriately qualified individual must then seek the potential subject’s 
freely-given informed consent, preferably in writing. If the consent cannot be expressed 
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All medical research subjects should be given the option of being informed about the 
general outcome and results of the study. 
 
• 
When seeking informed consent for participation in a research study the physician must 
be particularly cautious if the potential subject is in a dependent relationship with the 
physician or may consent under duress. In such situations the informed consent must be 
sought by an appropriately qualified individual who is completely independent of this 
relationship. 
 
• 
For a potential research subject who is incapable of giving informed consent, the 
physician must seek informed consent from the legally authorized representative. These 
individuals must not be included in a research study that has no likelihood of benefit for 
them unless it is intended to promote the health of the group represented by the 
potential subject, the research cannot instead be performed with persons capable of 
providing informed consent, and the research entails only minimal risk and minimal 
burden. 
 
• 
When a potential research subject who is deemed incapable of giving informed consent 
is able to give assent to decisions about participation in research, the physician must 
seek that assent in addition to the consent of the legally authorized representative. The 
potential subject’s dissent should be respected. 
 
• 
Research involving subjects who are physically or mentally incapable of giving 
consent, for example, unconscious patients, may be done only if the physical or mental 
condition that prevents giving informed consent is a necessary characteristic of the 
research group. In such circumstances the physician must seek informed consent from 
the legally authorized representative. If no such representative is available and if the 
research cannot be delayed, the study may proceed without informed consent provided 
that the specific reasons for involving subjects with a condition that renders them 
unable to give informed consent have been stated in the research protocol and the study 
has been approved by a research ethics committee. Consent to remain in the research 
must be obtained as soon as possible from the subject or a legally authorized 
representative. 
 
• 
The physician must fully inform the patient which aspects of their care are related to the 
research. The refusal of a patient to participate in a study or the patient’s decision to 
withdraw from the study must never adversely affect the patient-physician relationship. 
 
• 
For medical research using identifiable human material or data, such as research on 
material or data contained in biobanks or similar repositories, physicians must seek 
informed consent for its collection, storage and/or reuse. There may be exceptional 
situations where consent would be impossible or impracticable to obtain for such 
research. In such situations the research may be done only after consideration and 
approval of a research ethics committee. 
 

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IX. USE OF PLACEBO 
 
• 
The benefits, risks, burdens and effectiveness of a new intervention must be tested 
against those of the best proven intervention(s), except in the following circumstances: 
 
Where no proven intervention exists, the use of placebo, or no intervention, is 
acceptable; or 
 
Where for compelling and scientifically sound methodological reasons the use of any 
intervention less effective than the best proven one, the use of placebo, or no 
intervention is necessary to determine the efficacy or safety of an intervention 
 
and the patients who receive any intervention less effective than the best proven one, 
placebo, or no intervention will not be subject to additional risks of serious or 
irreversible harm as a result of not receiving the best proven intervention. 
 
Extreme care must be taken to avoid abuse of this option. 
 
 
X. 
POST-TRIAL PROVISIONS 
 
• 
In advance of a clinical trial, sponsors, researchers and host country governments 
should make provisions for post-trial access for all participants who still need an 
intervention identified as beneficial in the trial. This information must also be disclosed 
to participants during the informed consent process. 
 
 
XI. RESEARCH REGISTRATION AND PUBLICATION AND DISSEMINATION OF 
RESULTS 
 
• 
Every research study involving human subjects must be registered in a publicly 
accessible database before recruitment of the first subject. 
 
• 
Researchers, authors, sponsors, editors and publishers all have ethical obligations with 
regard to the publication and dissemination of the results of research. Researchers have 
a duty to make publicly available the results of their research on human subjects and are 
accountable for the completeness and accuracy of their reports. All parties should 
adhere to accepted guidelines for ethical reporting. Negative and inconclusive as well 
as positive results must be published or otherwise made publicly available. Sources of 
funding, institutional affiliations and conflicts of interest must be declared in the 
publication. Reports of research not in accordance with the principles of this 
Declaration should not be accepted for publication. 
 
 
 
 

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XII. UNPROVEN INTERVENTIONS IN CLINICAL PRACTICE 
 
• 
In the treatment of an individual patient, where proven interventions do not exist or 
other known interventions have been ineffective, the physician, after seeking expert 
advice, with informed consent from the patient or a legally authorized representative, 
may use an unproven intervention if in the physician's judgment it offers hope of saving 
life, re-establishing health or alleviating suffering. This intervention should 
subsequently be made the object of research, designed to evaluate its safety and 
efficacy. In all cases, new information must be recorded and, where appropriate, made 
publicly available.