Randomized, Prospective Clinical Evaluation of the Safety and Effectiveness of Visco-Assisted CyPass® Implantation in Patients With Open Angle Glaucoma
Phase: NA
Conditions: Open Angle Glaucoma
Sponsor: Transcend Medical, Inc.

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PROTOCOL TMI-13-01 VERSION D 
Protocol TMI-13-01 
        Transcend Medical – Confidential 2014-10-07 
Version D 
PROTOCOL TMI-13-01  / NCT02448875
VERSION D 
RANDOMIZED PROSPECTIVE CLINICAL EVALUATION OF THE SAFETY 
AND EFFECTIVENESS OF VISCO-ASSISTED CYPASS IMPLANTATION IN 
PATIENTS WITH OPEN ANGLE GLAUCOMA  
SPONSOR: 
TRANSCEND MEDICAL, INC 
127 INDEPENDENCE DRIVE 
MENLO PARK, CA  94025 
USA 
PHONE:  650-223-6600 

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PROTOCOL TMI-13-01 
VERSION D 
 
RANDOMIZED PROSPECTIVE CLINICAL EVALUATION OF THE SAFETY 
AND EFFECTIVENESS OF VISCO-ASSISTED CYPASS IMPLANTATION IN 
PATIENTS WITH OPEN ANGLE GLAUCOMA  
 
SPONSOR: 
 
TRANSCEND MEDICAL, INC 
127 INDEPENDENCE DRIVE 
MENLO PARK, CA  94025 
USA 
PHONE:  650-223-6600 
 
 
 
 
 
 
 
I have read and agree to follow the study procedures as outlined in this protocol. 
 
 
 
____________________________________________________  
Investigator Name (Printed) 
 
____________________________________________________  
_______________________ 
Investigator Signature  
 
 
 
 
 
Date 
 
CONFIDENTIAL - DO NOT COPY 
This protocol contains confidential proprietary information with respect to Transcend Medical products and 
clinical trials. I agree to hold this information in confidence and not to disclose it to any third parties until this 
information becomes a matter of public knowledge or until a formal agreement for that purpose has been 
entered into by the parties. 
 
 
 

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TABLE OF CONTENTS 
1.	  
PERSONNEL AND FACILITIES .............................................................................................. 1	  
2.	  
STUDY SYNOPSIS .................................................................................................................... 2	  
3.	  
INTRODUCTION AND RATIONALE ..................................................................................... 4	  
3.1	  
Background ................................................................................................................................ 4	  
3.2	  
Rationale for the CyPass Micro-Stent ....................................................................................... 5	  
3.3	  
Rationale for Visco-Assisted CyPass Micro-Stent Implantation ............................................... 6	  
4.	  
CYPASS MICRO-STENT SYSTEM MODEL 231 ................................................................... 9	  
4.1	  
Device Description .................................................................................................................... 9	  
	  
 10	  
	  
 10	  
	  
 12	  
5.	  
STUDY DESIGN ...................................................................................................................... 13	  
5.1	  
Primary Endpoint ..................................................................................................................... 14	  
5.2	  
Secondary Endpoints ............................................................................................................... 14	  
6.	  
STUDY POPULATION ............................................................................................................ 15	  
6.1	  
Inclusion Criteria ..................................................................................................................... 15	  
6.2	  
Exclusion Criteria .................................................................................................................... 15	  
7.	  
STUDY PROCEDURES ........................................................................................................... 16	  
7.1	  
Subject Enrollment .................................................................................................................. 16	  
7.2	  
Subject Randomization ............................................................................................................ 17	  
7.3	  
Surgical Procedure ................................................................................................................... 18	  
7.4	  
Ocular Hypotensive Medication Re-Introduction ................................................................... 18	  
7.4.1	  
Medication Re-Introduction During 1st Postoperative Month ................................................. 19	  
7.4.2	  
Medication Re-Introduction After 1st Postoperative Month .................................................... 19	  
7.5	  
Study Visits .............................................................................................................................. 19	  
7.5.1	  
Unscheduled Visits .................................................................................................................. 20	  
7.6	  
Subject Disposition .................................................................................................................. 20	  
7.6.1	  
Terminated Subjects ................................................................................................................ 20	  
7.6.2	  
Completed Subjects ................................................................................................................. 20	  
8.	  
STATISTICAL METHODS ..................................................................................................... 21	  
8.1	  
Sample Size ............................................................................................................................. 21	  
	  
 21	  
8.3	  
Efficacy and Safety Analyses .................................................................................................. 21	  
9.	  
ADVERSE EVENTS, ADVERSE DEVICE EFFECTS AND DEVICE DEFICIENCIES ..... 22	  

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9.1	  
Intraoperative Adverse Events ................................................................................................. 23	  
9.2	  
Postoperative Adverse Events ................................................................................................. 23	  
9.3	  
Serious Adverse Events ........................................................................................................... 24	  
9.4	  
Serious Adverse Device Effects .............................................................................................. 24	  
9.5	  
Device Deficiencies ................................................................................................................. 25	  
10.	  
STUDY MONITORING PLAN ............................................................................................... 25	  
11.	  
DATA MANAGEMENT PLAN ............................................................................................... 25	  
12.	  
ETHICAL AND REGULATORY CONSIDERATIONS ........................................................ 25	  
12.1	  
Sponsor Responsibilities .......................................................................................................... 26	  
12.2	  
Investigator Responsibilities .................................................................................................... 26	  
12.3	  
Institutional Review ................................................................................................................. 26	  
12.4	  
Subject Informed Consent and Confidentiality ....................................................................... 27	  
12.5	  
Device Accountability ............................................................................................................. 27	  
13.	  
PUBLICATION POLICY ......................................................................................................... 27 
14.   
REFERENCES………………………………………………………………………………. 27 
  
 
 
 
 

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PROTOCOL TMI-13-01 
VERSION D 
 
RANDOMIZED PROSPECTIVE CLINICAL EVALUATION OF THE SAFETY 
AND EFFECTIVENESS OF VISCO-ASSISTED CYPASS IMPLANTATION IN 
PATIENTS WITH OPEN ANGLE GLAUCOMA  
 
 
1. PERSONNEL AND FACILITIES 
 
Study Sponsor: 
Transcend Medical, Inc. 
127 Independence Drive 
Menlo Park, CA  94025 
USA 
Phone:  650-223-6600 
 
 
 
 

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2.  STUDY SYNOPSIS 
 
2.1 
Objective 
The purpose of this research study is to assess the safety and effectiveness of visco-assisted CyPass 
Micro-Stent implantation for the lowering of intraocular pressure (IOP) in patients with open angle 
glaucoma (OAG). 
2.2 
Population 
Up to 150 eyes meeting subject eligibility criteria listed in Section 5 of the protocol will be randomized 
to study treatment at up to 5 investigational sites.  
2.3 
Design 
This is a prospective, randomized, controlled, multicenter, interventional study performed in two 
phases, as follows: 
 
Dose Selection Phase:  During this phase, the first cohort (Cohort 1) of 60 subjects will be randomized 
(1:1:1) to receive  either a CyPass Micro-Stent with 30 µl adjunct Healon 5 viscoelastic, a CyPass 
Micro-Stent with  60 µl of adjunct Healon 5 viscoelastic, or a CyPass Micro-Stent without adjunct 
viscoelastic.  After completion of at least 3 months follow-up on all subjects in this phase, an interim 
review of safety and efficacy data will be performed to determine the optimum dose of adjunct 
viscoelastic for the study expansion phase.  
 
Expansion Phase:  After the dose selection phase, the study will be expanded to include a second  
cohort (Cohort 2) of up to 90 additional subjects who will be randomized 1:1 to either the CyPass 
Micro-Stent without adjunct viscoelastic or to the CyPass Micro-Stent with 60 µl adjunct 
viscoelastic(the dose selected based on Dose Selection Phase results). 
 
2.4 
Primary Endpoint 
Proportion of eyes with ≥ 20% decrease in IOP from baseline up to 12 months post-operatively without 
use of IOP lowering medications. 
 
2.5 
Secondary Endpoints 
• 
Rate of intraoperative and post-operative device related ocular adverse events up to 12 months 
postoperatively 
• 
Mean change in medicated IOP from baseline to 12 months postoperatively  

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• 
Proportion of eyes using ocular hypotensive medications at 12 months postoperatively  
• 
Mean number of topical IOP lowering medications at 12 months postoperatively as compared with 
baseline. 
 
2.6 
Schedule of Visits and Examinations 
• 
Screening, Baseline, Operative, Day 1, Week 1, Months 1, Month 3, Month 6,Month 12 and Month 
12 Washout (if subject is using ocular hypotensive medication at the Month 12 visit) postoperative.  
(Parameters per Appendix 1 – Study Examinations and Procedures) 

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3. 
 INTRODUCTION AND RATIONALE 
3.1 
Background 
 
 
Glaucoma is one of the leading causes of blindness in the world.1   Findings of epidemiological 
investigations and risk factor analyses provide a framework for consideration of the cause and 
management of primary open angle glaucoma (POAG), which is as follows:  
• 
Elevated intraocular pressure (IOP)  
• 
Increased age  
• 
Family history of glaucoma  
• 
African or Hispanic/Latino descent  
• 
Reduced central corneal thickness2,3  
 
While the relationship between IOP and vision loss is fundamental to all current therapy for OAG, there 
are several other factors (e.g., blood supply to the optic nerve, substances toxic to the optic nerve or 
retina, axonal or ganglion cell metabolism, and the lamina cribosa extracellular matrix) that may play a 
role in the progressive loss of vision due to glaucoma.  When IOP is uncontrolled, permanent and 
irreversible loss of vision due to optic neuropathy can result.   
 
Because elevated IOP is treatable, one can expect to inhibit progression of glaucomatous optic 
neuropathy by lowering the IOP.  Results from randomized controlled trials and other studies reinforce 
this expectation and provide evidence that successful IOP lowering prevents or delays functional vision 
loss from glaucoma. 4-22     
 
In patients with glaucoma, it is generally assumed that the target IOP should be ≥ 20% lower than the 
pretreatment IOP.  Further reduction of the target IOP may be justified by the severity of existing optic 
nerve damage, the pretreatment IOP, the rapidity with which optic never damage has occurred and other 
risk factors. In general, the more advanced the optic nerve damage, the lower the target IOP should be.   
During 7 years of follow-up, patients from the Advanced Glaucoma Intervention Study whose IOP was 
consistently  < 18 mmHg had minimal visual field loss progression on average as compared with 
patients who had higher IOPs. 23 
 
 
Since IOP is homeostatically maintained by the balance of aqueous production with aqueous outflow, 
current medical therapies for IOP reduction work by either reducing aqueous production, or increasing 
aqueous outflow.   
 

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Surgical therapies for IOP reduction are almost exclusively intended to increase aqueous outflow by 
either creating an alternate or improved pathway to Schlemm’s canal, or by directing outflow to an 
alternative drainage site outside the intraocular environment. Trabeculectomy and implantable 
glaucoma shunts have been the mainstay of conventional glaucoma surgery for more than 20 years.  In 
most patients, the clinical effect of each procedure is relatively similar and results in significant IOP 
reduction, which is sustained for several years.  
 
Trabeculectomy and glaucoma shunts, however, are generally relegated to the end-stages of the 
glaucoma disease spectrum, largely due to the associated intraoperative and postoperative safety profile 
of the procedures.  Overall, the cumulative rate of significant ocular complications and adverse events 
may exceed 25 – 30% and, in many cases, these complications lead to visual deterioration, secondary 
surgical revision or rescue intervention.  Additionally, the median failure rate within the first year after 
surgery exceeds 20% at one year, with progressive attrition of effect in subsequent years. 24  
Such limitations of conventional filtering and glaucoma shunt surgery have led to new, less invasive 
surgical approaches for IOP reduction such as the implantation of the CyPass Micro-Stent.   
 
3.2 
Rationale for the CyPass Micro-Stent 
The CyPass Micro-Stent is a small tube made of polyimide, a material previously used in marketed 
ophthalmic implants.  The device, which is described in Section 4 of this protocol, functions by means 
of its through-lumen.  The principle behind device design is outlined in the following discussion of 
aqueous outflow physiology of the human eye.  
 
Aqueous fluid is produced at the rate of approximately 2-3 µl per minute by the secretory epithelium of 
the ciliary body, which extends circumferentially around the interior of the eye posterior to the iris and 
covers the ciliary processes.  Aqueous circulates anteriorly through the pupil and exits the eye by means 
of several independent pathways, including the trabecular, or canalicular, outflow pathway (the major 
outflow pathway that accounts for a very large percentage of aqueous outflow in the normal eye) and 
the uveoscleral outflow pathway.   
With the trabecular outflow pathway, aqueous passes through the trabecular meshwork into Schlemm’s 
canal, then into aqueous veins that drain into the episcleral venous plexus.  The pressure in these veins 
is generally around 10 mmHg.  This outflow pathway is known as “pressure dependent”.  
 

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The uveoscleral outflow pathway is “pressure independent”.  With uveoscleral outflow, aqueous moves 
from the anterior chamber through the intermuscular spaces of the ciliary muscle into the supraciliary 
and suprachoroidal spaces, then out of the eye through the substance of the sclera or the perivascular 
spaces of the emissarial channels (perforation in the sclera for the passage of nerves and blood vessels) 
at a rate of about 0.2 – 0.5 µl per minute.25  In monkeys, the posterior suprachoroidal pressure is 4 
mmHg lower than the anterior chamber pressure.  Aqueous flows from the anterior chamber into the 
supraciliary and suprachoroidal spaces because of this pressure gradient, which is due to the high 
oncotic absorptive potential of uveal vessels.26  
 
While in normal eyes the uveoscleral outflow may provide much less than 50% of total outflow, 
uveoscleral outflow may have a higher capacity for reduction of IOP in glaucomatous eyes.  Experience 
from glaucoma pharmacotherapy demonstrates that some of the most effective topical therapies for IOP 
reduction act primarily by increasing uveoscleral outflow.27  
 
The CyPass Micro-Stent is designed to facilitate aqueous flow from the anterior chamber into the 
supraciliary and suprachoroidal spaces of the eye by bypassing the ciliary body and creating a stented 
cyclodialysis into the supraciliary space.  Cyclodialysis clefts, whereby the ciliary body is separated 
from the scleral spur due to trauma, cataract surgery, or as an intentional surgical therapy for glaucoma 
have been studied previously.  Cyclodialysis creates an additional path between the anterior chamber 
and the supraciliary and suprachoroidal spaces, which markedly enhances outflow through the posterior 
portions of the uveoscleral pathway28 ; however, the creation of a cyclodialysis cleft for IOP reduction 
may result in surgical trauma, hypotony (IOP < 5 mmHg, which may be associated with ciliochoroidal 
detachment) and spontaneous cleft closure, which may lead to a sudden rise in IOP.    
 
The advantages of the CyPass Micro-Stent over simple surgical cyclodialysis reside in the device’s 
ability to predictably lower IOP to a safe level and to maintain a lower IOP over time. 
 
3.3 
 Rationale for Visco-Assisted CyPass Micro-Stent Implantation 
Clinical data from serial anatomic assessments of the supraciliary cleft post CyPass Micro-Stent 
implantation provide evidence regarding the benefit of structural stabilization of the ciliary space 
around the distal portion of the Micro-Stent.  Ahmed et al reported a statistically significant positive 
correlation between the size of the supraciliary cleft around and distal to the CyPass Micro-Stent and 
the IOP lowering effect.29   Patients who had larger space formation around the Micro-Stent (clinical 

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grade 3 – 4), as established via serial OCT imaging, had a more pronounced and sustained IOP effect 
than patients with a smaller space formation about the Micro-Stent  (clinical grade 0-2).  This finding is 
consistent with the physiologic rationale of supraciliary and suprachoroidal flow dynamics whereby 
aqueous outflow is related to the absorptive capacity of the surrounding supraciliary and suprachoroidal 
spaces.30  
 
As assessed by OCT, the size and nature of the supraciliary cleft around and distal to the CyPass Micro-
Stent appears to vary depending on the plasticity and compliance of the ciliary tissue and the surgical 
dissection forces at the time of Micro-Stent implantation.  It is believed that achievement of a more 
predictable, consistent and volumetrically discrete supraciliary cleft around and distal to the CyPass 
Micro-Stent may be facilitated via delivery of a standardized volume of ophthalmic viscoelastic to the 
supraciliary space immediately distal to the Micro-Stent at the time of device implantation.  This 
viscoelastic “spacer” may provide sustained anatomic stability of the area around the device to facilitate 
enhanced absorptive flow of aqueous. 
 
The use of viscoelastic as a “spacer” is supported by preclinical animal data in cyno models where 
Klemm et al reported on 12 eyes of 6 owl monkeys in which visco-assisted cyclodialysis was performed 
by injecting 50-80 µl of hyaluronic viscoelastic into the ciliary cleft.31   The procedure was safe, without 
any associated intraoperative or post-operative ocular adverse events.  The cleft opening was 
maintained through the maximum follow up of 140 days.  Another cyno study showed the safety and 
feasibility of visco-assisted cyclodialysis formation without any associated adverse effects 32  
 
Transcend Medical conducted a study in New Zealand white rabbits to characterize the safety of the 
visco-assisted CyPass Micro-Stent implantation.  In this study, 14 eyes of 7 rabbits were randomized to 
CyPass Micro-Stent implantation either with or without concurrent delivery of 50 µl of Healon® 5 
sodium hyaluronate ophthalmic viscoelastic through the Micro-Stent Applier guide wire posterior to the 
Micro-Stent’s distal end.  Ocular safety was assessed at multiple intervals up to 28 days postoperatively 
and a histologic evaluation was done at study completion.  The there were no device-related adverse 
events and the histological evaluation showed no adverse tissue reaction or morphologic changes 
related to the injection of viscoelastic.  
The visco-assisted CyPass Micro-Stent implantation system is designed to provide precision-guided, 
targeted delivery of Healon 5 viscoelastic to the space surrounding the distal end of the Micro-Stent via 
the modification to the Applier guide wire injection system.  The CyPass Micro-Stent, the Micro-Stent 

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Applier guide wire dimensions and flexibility, and Micro-Stent implantation technique are all 
unchanged.  Healon 5 is a highly purified, noninflammatory, high molecular weight fraction of sodium 
hyaluronate, which is commonly used in conjunction with intraocular surgery as an aid to maintain the 
anterior chamber or to gently separate, maneuver and hold tissue.33 
 
 

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4.  CYPASS MICRO-STENT SYSTEM MODEL 231 
4.1 
Device Description 
The CyPass System 231 consists of one (1) CyPass Micro-Stent (Model 2FX) contained in a loader and 
one (1) CyPass Applier (Model 231).    
 
The CyPass Micro-Stent (Figure 1) is an implantable polyimide tube with a through-lumen designed to 
provide a permanent conduit for aqueous outflow from the anterior chamber of the eye into the 
supraciliary and suprachoroidal spaces. 
 
 
Figure 1:  CyPass Micro-Stent, Model 2FX 
 
When implanted as directed in the product labeling, the CyPass Micro-Stent’s proximal end resides in 
the anterior chamber while the distal end rests against the sclera in the supraciliary space.  
 
The CyPass Micro-Stent Applier (Figure 2) consists of a medical-grade polymer hand piece containing 
an implant delivery guide wire. The guide wire is a pre-shaped nitinol wire with a blunt tip and curved 
radius at the distal end to facilitate locating and blunt-dissecting the tissue plane between the ciliary 
body and sclera. The guide wire is supported within a stainless steel guide wire tube. The CyPass 
Micro-Stent is loaded onto the extended guide wire prior to implantation, such that the Micro-stent’s 
proximal end rests against the guide wire tube.  
 
By connecting the male luer fitting of the Healon 5 viscoelastic syringe to the female luer fitting on the 
CyPass Applier, the Applier can be used to deliver the viscoelastic to the desired location in the eye. 
 
 

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Figure 2: CyPass Applier, Model 231, with guidewire extended  
 
 
 

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4.2.3 ViscoPass Study (Initial Phase) 
 
During the Dose Selection Phase of this study, 62 subjects were randomized using a 1:1:1 schedule to 
receive either CyPass Micro-Stent with 30 µl of adjunct Healon viscoelastic, CyPass Micro-Stent with 
60 µl of adjunct Healon viscoelastic, or the CyPass Micro-Stent with no adjunct Healon viscoelastic. 
 
With 6 months follow-up on all subjects, there was no difference in safety among the three arms, and 
the 60 µl arm had a comparable rate of AEs  to either the Cypass only arm or the 30 µl arm. Also, there 
were no unanticipated or vision-threatening adverse events in either group. Additionally, there was a 
trend towards higher efficacy with the 60 µl arm compared to the other two arms for the primary and 
secondary efficacy outcomes. 
 
Based on the results of the initial phase and considering the risk-benefit profile of each arm, the 60 µl 
arm was selected as the go-forward dose with recommended discontinuation of the 30 µl arm which had 
no appreciable benefit in either safety or efficacy. 
 
5. 
STUDY DESIGN 
 

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This is a prospective, randomized, multi-cohort and multi-center investigation in which up to 150 
subjects will be randomized to study treatment at up to 5 investigational sites.  After successful 
completion of baseline assessments, eligible subjects will receive the CyPass Micro-Stent either with or 
without visco-assisted implantation and be followed for 12 months postoperatively.  It is estimated that 
approximately 10% of those receiving the CyPass Micro-Stent may be lost to follow-up.   Enrollment 
will be implemented in two phases, as follows:  
 
Dose Selection Phase:  During this phase, the first dose-selection cohort of 60 subjects will be 
randomized (1:1:1) to receive one of the following treatments:   
o CyPass Micro-Stent with 30 µl adjunct Healon 5 viscoelastic, or 
o CyPass Micro-Stent with  60 µl of adjunct Healon 5 viscoelastic, or  
o CyPass Micro-Stent without adjunct viscoelastic.   
After completion of at least 3 months follow-up on all subjects in the dose selection phase, an interim 
review of safety and efficacy data was performed to determine the optimum dose of adjunct viscoelastic 
for the study expansion phase.  
 
Expansion Phase:  After the dose selection phase, the study will be expanded to include a second 
cohort  (Cohort 2) of up to 90 additional subjects who will be randomized 1:1 to either the CyPass 
Micro-Stent without adjunct viscoelastic or CyPass Micro-Stent with 60 µl of adjunct Healon 5 
viscoelastic.  This dose was selected based on previous phase results as discussed in Section 4.2.  
 
5.1 
Primary Endpoint  
• 
Proportion of eyes with ≥ 20% decrease in IOP from baseline up to 12 months post-operatively 
without IOP lowering medications.  
 
5.2 
Secondary Endpoints 
• 
Rate of intraoperative and post-operative device related ocular adverse events up to 12 months 
postoperatively 
• 
Mean change in medicated IOP from baseline to 12 months postoperatively  
• 
Proportion of eyes using ocular hypotensive medications at 12 months postoperatively  
• 
Mean number of topical IOP lowering medications at 12 months postoperatively as compared with 
baseline. 
 

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6. STUDY POPULATION    
 
6.1 
Inclusion Criteria 
 
Individuals will be assessed for study eligibility based on the criteria presented below. Unless specified 
otherwise, ocular criteria refer to the study eye only. 
 
1. 21 years of age or older, male or female. 
2. Able to understand study requirements, willing to follow study instructions, provide written 
informed consent, and comply with all study requirements, including required study follow-up 
visits. 
3. Diagnosis of OAG, including pseudoexfoliation glaucoma and pigmentary glaucoma, which  
meets diagnostic criteria defined below: 
• 
Vertical cup-to-disc ratio (C:D) on fundoscopic exam of at least 0.6, or 
• 
Heidelberg Retinal Tomograph (HRT) of good quality demonstrating a Moorfield 
Regression Analysis that is “outside normal limits”, or 
• 
Optical Coherence Tomography (OCT) demonstrating a thinness of the nerve fiber layer at 
the p < 5% level as defined by the instrument’s built-in age-adjusted normative database. 
• 
Glaucoma Visual Field (VF) with a Mean Deviation (MD)  < 0 dB 
4. Baseline unmedicated IOP of 21 mmHg – 36 mmHg.  Note:  Subjects who were using ocular 
hypotensive medication at the time of study enrollment must complete a required medication 
washout period prior to baseline IOP assessment as specified in Table 7. 
5. Gonioscopy confirming normal angle anatomy at site of implantation, and Shaffer grade of ≥ 
III in at least two quadrants, one of which must be the quadrant of the intended site of 
implantation. 
 
6.2 
Exclusion Criteria 
 
Individuals with the following characteristics noted at or before the baseline examination will be 
excluded from the study.  Unless specified otherwise, ocular criteria refer to the study eye only. 
 
1. Advanced glaucoma evidenced by a C:D ratio > .95, or encroachment of field loss within the 
central 5 degrees as indicated by > 2 depressed points of 0.5% probability on the  
24-2 SITA Standard Humphrey visual field or other standard automated perimetry test. 
2. Aphakia. 

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3. Clinically significant ocular pathology other than glaucoma. 
4. Any known ocular condition that may require intraocular intervention during the protocol-
required follow-up period. 
5. 
Diagnosis of acute angle closure, traumatic, congenital, malignant, uveitic or neovascular 
glaucoma. 
6. 
Prior incisional glaucoma surgery.  
7. 
Best corrected visual acuity (BCVA) of 20/200 (Snellen) or worse in the fellow eye. 
8. 
Clinically significant ocular inflammation or infection within 30 days prior to the Baseline 
Visit. 
9. 
Uncontrolled systemic disease that, in the opinion of the Investigator, would put the subject’s 
health at risk and/or prevent the subject from completing all study visits. 
10. Participation in any clinical trial within the past 30 calendar days prior to the Screening Visit. 
11. Pregnant or nursing females. 
 
Subjects who do not meet the inclusion/exclusion criteria specified will be exited from the study in 
accordance with Section 7.6 of the protocol.   
 
7.  STUDY PROCEDURES 
 
7.1 
Subject Enrollment 
 
The Investigator will discuss study participation requirements, risks and benefits with patients that may 
be eligible for the study.  The patient must sign a written Informed Consent Form (ICF) prior to the 
commencement of study-related procedures.  Once the subject signs the ICF, he/she is considered to be 
enrolled in the study.   One copy of the informed consent form will be retained with the subject’s 
medical records, and one copy will be provided to the subject.    
 
Only one eye per subject may be treated under the study protocol.  If both eyes qualify for the study, the 
study investigator will choose which eye will be the study eye.  
  
After the subject has successfully completed the preoperative screening exam, he/she will be instructed 
to discontinue use of ocular hypotensive medications in the study eye for the appropriate washout 
period listed in Table 7, prior to the Baseline Visit.  If the subject experiences an IOP spike of > 36 

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mmHg, or requires the reintroduction of hypotensive medications or a surgical intervention during this 
period, the subject will be exited from the study. 
 
Table 7   
Ocular Hypotensive Medication Washout Requirements 
Brand Name/Chemical Name 
Minimum Washout Period 
Carbonic Anhydrase Inhibitors  
5 days 
Alpha Adrenergic Agonists 
14 days 
Beta Blockers  
28 days 
Prostaglandin Analogs  
28 days 
Combined Medications 
28 days 
Other 
Contact Sponsor 
 
Subjects will be scheduled for a baseline examination within 45 days of screening, dependent on the 
required ocular hypotensive medication washout requirement after their screening examination.  
Subjects who are medication naïve at screening may have the screening and baseline testing performed 
on the same day.  At the baseline examination, subjects will undergo further evaluation of eligibility.  
After successful completion of the baseline examination, the subject will be scheduled for surgery to 
receive the CyPass Micro-Stent.   
It is recommended that the subject initiate the following perioperative medication regimen 2-3 days 
prior to the day of surgery: 
• 
Topical NSAID (e.g., ketorolac) QID  
• 
Topical antibiotic (4th generation quinolone, e.g., gatifloxacin) QID  
• 
Topical steroid (e.g., prednisolone acetate) QID  
The fellow eye will be followed according to the standard of care.  If a subject’s study eye fails to 
qualify for surgery, the fellow eye may be considered for study enrollment once IOP in the study eye is 
considered to be controlled.   
 
Ineligible subjects will be exited from the study and a study summary form completed.  Subjects who 
are exited from the study at either the screening or baseline assessments will be replaced. 
 
7.2 
Subject Randomization 
Subjects will be randomized to their assigned treatment group on the day of their surgical procedure.  
Randomization envelopes for each case will be provided for each study site.   
 

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During the Dose Selection Phase of the study, subjects will be randomized in Cohort 1 using a 1:1:1 
schedule to receive either CyPass Micro-Stent with 30 µl of adjunct Healon viscoelastic, CyPass Micro-
Stent with 60 µl of adjunct Healon viscoelastic, or the CyPass Micro-Stent with no adjunct Healon 
viscoelastic. 
 
During the Expansion Phase of the study, subjects will be randomized in Cohort 2 using a 1:1 schedule 
to receive either CyPass Micro-Stent without adjunct Healon viscoelastic or the CyPass Micro-Stent 
with 60 µl of adjunct Healon 5 viscoelastic . 
 
7.3 
Surgical Procedure   
The surgical procedure will be performed using intraocular microsurgical techniques and anesthesia per 
the investigator’s standard procedure. The CyPass Micro-Stent will be implanted according to the 
Instructions for Use (IFU) for CyPass System 231. 
 
Topical antibiotics and anti-inflammatory medication, as well as Apraclonidine, Brimonidine or other 
topical hypotensive agents may be administered at the conclusion of the procedure.   
The topical antibiotic/steroid/NSAID medication regimen described in Table 8 below is recommended 
during the initial postoperative month. 
 
Table 8 
Medication Regimen 
Time Period 
Antibiotic 
Steroid 
NSAID 
Surgery Day – Week 1 
4th generation 
fluoroquinolone (e.g., 
moxifloxacin) QID 
e.g., prednisolone 
acetate 1% QID 
e.g., ketorolac QID 
Week 2  
N/A 
e.g., prednisolone 
acetate 1% TID 
e.g., ketorolac QID 
Week 3 
N/A 
e.g., prednisolone 
acetate 1% BID 
e.g., ketorolac QID 
Week 4 
N/A 
e.g., prednisolone 
acetate 1% QD 
N/A 
 
Adjustments in the duration of postoperative medications may be necessary for subject safety.  
 
7.4 
Ocular Hypotensive Medication Re-Introduction 
 

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7.4.1 Medication Re-Introduction During 1st Postoperative Month 
Ocular hypotensive therapy may be initiated within the first postoperative week if the subject’s IOP > 
21 mmHg.  Additional IOP-lowering medication can be used with investigator discretion as necessary 
for IOP control. 
7.4.2 Medication Re-Introduction After 1st Postoperative Month 
Topical IOP lowering therapy may be initiated if the subject’s IOP > 21 mmHg.  Only 1 medication 
should be added at a visit.  The preferred order of medication reintroduction should be as follows: 
• 
Prostaglandin analogues 
• 
Beta blockers 
• 
Carbonic Anhydrase inhibitors 
• 
Alpha agonists  
Adjustments in IOP lowering therapy may be necessary for subject safety and should be based on 
investigator discretion.  
 
7.5 
 Study Visits  
Study subjects will participate in follow-up visits through 12 months postoperatively in accordance with 
Appendix 1 – Study Examinations and Procedures.  

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7.5.1 Unscheduled Visits 
An unscheduled visit is any visit to the clinical site (other than those specified in the protocol), during 
which the subject has a complaint regarding the study eye or study eye treatment is required.  No 
specific testing is required at unscheduled visits. 
     
7.6 
Subject Disposition 
 
7.6.1 Terminated Subjects 
Subjects may be terminated (exited) from the study early due to: 
• 
Screen failure 
• 
AE(s) 
• 
Administrative reasons (e.g., voluntary withdrawal, lost to follow-up) 
Subjects who are terminated prior to surgery will not be followed beyond the date of termination unless 
the reason for termination in an IOP-related adverse event (AE).  These subjects will be followed until 
resolution or stabilization of the AE.  Subjects who are terminated prior to surgery due to a non-IOP-
related AE will not be followed beyond the date of the AE report.  Subjects who undergo surgery but do 
not receive the CyPass due to a surgical AE will be followed until resolution or stabilization of the AE.  
Subjects who receive the CyPass Micro-Stent but are terminated from the study should be followed for 
safety until the end of study period.   
 
Study sites must make every attempt to follow-up on subjects who do not return for scheduled study 
examinations.  If a subject is non-responsive to these follow-up attempts, he/she will be considered to 
be lost to follow-up.  The sponsor should be notified promptly regarding subjects who are terminated 
prior to study completion.     
 
Subjects terminated after implantation of the CyPass Micro-Stent will not be replaced.   
 
7.6.2 Completed Subjects 
Completed subjects are those subjects who have not been terminated from the study prior to their 
completion of follow up. 
 
 

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8. 
 STATISTICAL METHODS 
 
8.1 
Sample Size  
The primary effectiveness endpoint is the outcome of ≥ 20% decrease in IOP from baseline without IOP 
lowering medications up to 12 months post-operatively (IOP response).  The proportion of eyes 
meeting the effectiveness outcome, IOP response rate, will be assessed at 12 months. A sample of at 
least 101 eyes will be enrolled across the two groups (CyPass only control and CyPass + Healon 5 dose 
selected) with an estimated 86 eyes completing their month 12 visit. Assuming a 30% success rate for 
the control eyes and a 60% success rate for the visco-assisted eyes, 80% power can be achieved with 43 
eyes per arm using a two-tailed alpha of 0.05. 
 
 
8.3 
Efficacy and Safety Analyses 
The primary effectiveness endpoint, the achievement of a 20% decrease in IOP relative to 
baseline in the absence of IOP lowering medications will be summarized at each postoperative 
visit by the number available for analysis (N), the proportion meeting success criteria, and the 
95% confidence interval (CI). 
 
Secondary endpoints describing proportions meeting given criteria will be summarized at each 
postoperative visit by N, percentage and 95% CI.  Continuous endpoints, IOP, mmHg decrease 

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in IOP and % decrease in IOP will be summarized by N, mean, standard deviation median, 
minimum and maximum.  For continuous change measures, the 95% CI of that change will 
also be provided.  
 
The safety profile of the CyPass device will be based on intraoperative and postoperative adverse event 
rates, slit lamp biomicroscopy and fundus examination.   All subjects who undergo CyPass implantation 
surgery will be included in the safety analysis.  The incidence of adverse events will be summarized by 
N, percentage, and CI.  
 
 
 
 
 
9. 
ADVERSE EVENTS, ADVERSE DEVICE EFFECTS AND DEVICE DEFICIENCIES    
 
An adverse event (AE) is any untoward medical occurrence, unintended disease or injury or any 
untoward clinical sign occurring in a study subject, whether or not related to the CyPass Micro-Stent.  
All AEs in the study eye must be reported on the appropriate CRF.  Each AE must be graded by degree 
of harm to the subject (note grading scale below), as well as by the relationship to study device or 
implantation procedure.   
AEs should be graded as follows: 
• 
Mild:  Discomfort noticed but no disruption of normal daily activity 
• 
Moderate:  Discomfort sufficient to reduce or affect normal daily activity 
• 
Severe:  Incapacitating with inability to work or perform normal daily activity 
 
Ocular conditions or diseases that are chronic but stable and do not render the subject ineligible for the 
study should be recorded under the subject’s ocular history.  Changes in the chronic condition or 
disease consistent with natural progression are not considered AEs. 
 
AEs associated with glaucoma surgical procedures that might reasonably be expected to occur in this 
study are listed below.  These anticipated AEs include, but are not limited to: 
 
 
 

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9.1 
Intraoperative Adverse Events 
• 
Lens touch 
• 
Choroidal detachment 
• 
Inadvertent perforation of sclera 
• 
Hyphema, which obscures surgeon’s view  
• 
Inadvertent loss of vitreous  
• 
Choroidal hemorrhage or effusion 
• 
Significant iris injury or trauma 
• 
Significant corneal damage 
• 
Zonular dialysis 
 
9.2 
Postoperative Adverse Events 
• 
Chronic pain in the study eye present at 3 months postoperatively or later 
• 
Flat anterior chamber with lens/cornea touch 
• 
Shallow chamber with peripheral iridocorneal apposition  
• 
BCVA loss of 3 Snellen  lines compared to baseline at 3 months postoperatively or later  
• 
Hypotony (defined as IOP < 6 mmHg) at 1 month postoperatively or later 
• 
Maculopathy  
• 
Hypotonic maculopathy 
• 
CyPass obstruction causing an untoward effect in the study eye  
• 
CyPass malposition  
• 
CyPass migration, causing an untoward effect in the study eye 
• 
Wound dehiscence 
• 
Persistent anterior chamber cell and flare requiring steroid treatment after 2 months 
postoperatively 
• 
Endophthalmitis 
• 
Cataract formation or progression outside of expected progression 
• 
Persistent hyphema present at 1 week postoperatively or later 
• 
Corneal opacification, or corneal decompensation 
• 
Significant corneal edema 
• 
Retinal complications (dialysis, flap tears, retinal detachment, or proliferative 
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• 
Choroidal hemorrhage or choroidal effusion, defined as a choroidal effusion or detachment 
with at least a partially hemorrhagic component that obstructs vision or causes pain 
(including both peripheral and “kissing” choroidal detachments) lasting longer than 1 
month  
• 
Significant elevation in IOP requiring non-medical intervention 
• 
Other events resulting in unplanned ocular surgical reintervention (other than paracentesis 
to relieve pressure prior to 1 week postoperative or Nd:YAG laser procedure for treatment 
of posterior capsular opacification)  
• 
Loss of eye  
• 
Significant ptosis 
• 
Atrophy/phthisis 
• 
Significant foreign body sensation at or after 3 months postoperative 
• 
Increase in C:D ratio of ≥ 0.3 units on slit lamp biomicroscopic examination 
• 
Confirmed increase in visual field loss outside of expected progression 
 
9.3 
Serious Adverse Events 
An AE should be classified as serious, regardless of relationship to the CyPass Micro-Stent if it: 
• 
Led to death 
• 
Led to a serious deterioration in health that: 
- Resulted in a life-threatening illness or injury, or 
- Resulted in a permanent impairment of a body structure or a body function, or 
- Required in-patient hospitalization or prolongation of existing hospitalization, or 
- Resulted in medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function 
• 
Led to fetal distress, fetal death or a congenital abnormality or birth defect 
 
Serious Adverse Events (SAE) must be reported to Transcend Medical within 1 week of learning 
of the event. 
 
9.4 
Serious Adverse Device Effects 
A serious adverse device effect (SADE) is an adverse event related to the use of the CyPass Micro-
Stent that resulted in any of the consequences characteristic of a SAE.  SADEs must be reported to 
Transcend Medical within 24 hours of learning of the event.     

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9.5 
Device Deficiencies 
 
A device deficiency is considered to be an inadequacy of the CyPass Micro-Stent System that is related 
to its identity, quality, durability, reliability, safety or performance (e.g., malfunction, misuse or user 
error, inadequate labeling).  Device deficiencies must be reported to Transcend Medical within 1 
week of learning of the deficiency.   
 
To report any SAE, SADE or device deficiency, please contact: 
 
Email:  
 
Phone:  
 
Fax: 
 
 
 
10.  STUDY MONITORING PLAN 
On-site monitoring visits will be performed periodically to assess the progress of the study and identify 
concerns related to adherence to the study protocol, EC review of the study and maintenance of study-
related records and reports. Remote monitoring will be conducted and subject eligibility will be 
approved by the Sponsor prior to randomization.a. 
 
11.  DATA MANAGEMENT PLAN 
Clinical study data will be documented on study-specific Case Report Forms (CRFs) and maintained in 
an electronic database, which has been established and validated for study use.  The Sponsor will 
confirm data entry accuracy and issue data queries as necessary.  Clinical study data will be maintained 
for the duration of the study until completion of the final clinical study report.  Thereafter, the data will 
be archived by Sponsor.  
    
12.  ETHICAL AND REGULATORY CONSIDERATIONS 
This protocol was designed and will be conducted, recorded, and reported in compliance with the 
principles of Good Clinical Practice (GCP).  These requirements are stated in global regulations as well 
as “Guidance for Good Clinical Practice”, International Conference on Harmonization (ICH).  
The study will be performed in accordance with the recommendations guiding physicians in biomedical 
research involving human subjects adopted by the 18th World Medical Assembly, Helsinki, Finland, 
1964 and later amendments. 
 

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12.1 Sponsor Responsibilities 
The Sponsor is responsible for the following activities with respect to this clinical investigation: 
• 
Clinical quality assurance and quality control 
• 
Clinical investigation planning and conduct, including:    Selection of clinical personnel, 
Preparation of clinical investigation documents and materials, Clinical investigation conduct, 
Clinical investigation monitoring, Safety evaluation and reporting and Clinical investigation 
close-out 
The Sponsor will maintain clinical study records throughout the study and for at least two years from 
the date on which the study was terminated or completed, and for providing access to these records for 
audit and inspection by regulatory authorities. 
 
Additionally, the Sponsor is responsible for providing reports on the study progress and performance in 
accordance with applicable regulatory requirements.   
 
12.2 Investigator Responsibilities 
The principal investigator at each site is responsible for implementation and management of the day-to-
day conduct of the clinical investigation as well as to confirm data integrity and the rights, safety and 
well-being of the subjects involved in the clinical investigation.    
 
The principal investigator must sign an Investigator Agreement acknowledging that he/she will comply 
with the protocol and other study obligations, including safety reporting.  No changes in this protocol 
can be made without the Sponsor’s written approval.   
 
All Investigators must participate in a protocol review conducted by the Sponsor or the Sponsor’s 
designated representative.   
 
Investigators are responsible for maintaining clinical study records throughout the study and for at least 
two years from the date on which the study was terminated or completed, and for providing access to 
these records for audit and inspection by regulatory authorities. 
 
12.3 Institutional Review 
Before enrollment of any study subjects, the protocol and the subject ICF must be reviewed and 
approved by an EC that is operating in accordance with local procedures and regulatory requirements.   

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It is the responsibility of the Investigator to obtain and maintain approval for the study protocol and 
ICF, and to keep the EC informed of the occurrence of serious adverse events.  It is also the 
Investigator’s responsibility to maintain a file of all correspondence with the EC and to forward copies 
of that correspondence to the Sponsor or Sponsor’s designated representative. 
 
12.4 Subject Informed Consent and Confidentiality 
Written informed consent is required prior to initiation of study-specific procedures or exams on study 
subjects.  It is the responsibility of the Investigator to complete the informed consent process and to 
provide each subject with a copy of the fully executed ICF.   The principal investigator and Sponsor (or 
designee) will use every effort will to ensure that subject names or other personal identifiers are not be 
used during the course of the study.  All subject data will be kept in a secure location. 
 
12.5 Device Accountability 
Study devices will be shipped to the site or hand carried to the site by the Sponsor or Sponsor’s 
designee.  Study device shipment records should be verified by comparing the shipping receipt 
confirmation to devices received at the site.  Study devices should be stored in a secure area to prevent 
unauthorized distribution. 
The Investigator will be responsible for keeping current and accurate records of devices dispensed and 
implanted.  After completion of study enrollment, all non-used study devices will be returned to the 
Sponsor or Sponsor’s representative.   
 
13.  PUBLICATION POLICY 
All publications and/or presentations concerning this study must be reviewed by the Sponsor prior to 
publication/presentation.    

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14.  REFERENCES 
1.  Am J Ophthalmol. 2012 Aug;154(2):315  
2. Ophthalmology. 2012 Nov;119(11):2245-53  
3. Invest Ophthalmol Vis Sci. 2012 Apr 24;53(4):219  
4. Javitt JC, Chiang YP. Preparing for managed competition. Utilization of ambulatory eye care visits 
to ophthalmologists. Arch Ophthalmol 1993;111:1034-5.  
5. Schappert S. Office visits for glaucoma: United States, 1991-92. Advance data from vital and health 
statistics. Vol. 262. Hyattsville, MD: National Center for Health Statistics, 1995.  
6. Congdon N, O'Colmain B, Klaver CC, et al. Causes and prevalence of visual impairment among 
adults in the United States. Arch Ophthalmol 2004;122:477-85.  
7. Sommer A, Tielsch JM, Katz J, et al. Racial differences in the cause-specific prevalence of 
blindness in east Baltimore. N Engl J Med 1991;325:1412-7.  
8. Primary Open Angle Glaucoma.  Preferred Practice Patterns, American Academy of 
Ophthalmology.http://one.aao.org/CE/PracticeGuidelines/PPP_Content.aspx?cid=a5a59e02-450b-
4d50-8091-b2dd21ef1ff2#references (Accessed 11-1-08). 
9. Jay JL, Allan D. The benefit of early trabeculectomy versus conventional management in primary 
open-angle glaucoma relative to severity of disease. Eye 1989;3:528-35.  
10. Migdal C, Gregory W, Hitchings R. Long term functional outcome after early surgery compared 
with laser and medicine in open-angle glaucoma. Ophthalmology 1994;101:1651-7.  
11. The Glaucoma Laser Trial (GLT). 2. Results of argon laser trabeculoplasty versus topical 
medicines. The Glaucoma Laser Trial Research Group. Ophthalmology 1990;97:1403-13.  
12. The Glaucoma Laser Trial (GLT) and Glaucoma Laser Trial Follow-up Study: 7. Results. Am J 
Ophthalmol 1995;120:718-31.  
13. Kass MA, Heuer DK, Higginbotham EJ, et al for the Ocular Hypertension Treatment Study Group. 
The Ocular HypertensionTreatment Study.  A randomized trial determines that topical ocular 
hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch 
Ophthalmol 2002;120:701-13.  
14. Gordon MO, Kass MA, for the Ocular Hypertension Treatment Study Group. The Ocular 
Hypertension Treatment Study. Design and baseline description of the participants. Arch 
Ophthalmol 1999:573-83.  
15. Collaborative Normal-Tension Study Group. Comparison of glaucomatous progression between 
untreated patients with normal-tension glaucoma and patients with therapeutically reduced 
intraocular pressures. Am J Ophthalmol 1998;126:487-97.  
16. Heijl A, Leske MC, Bengtsson B, et al for the Early Manifest Glaucoma Trial Group. Reduction of 
intraocular pressure and glaucoma progression.  Results from the Early Manifest Glaucoma Trial. 
Arch Ophthalmol 2002;120:1268-79.  
17. Leske MC, Heijl A, Hussein M, et al for the Early Manifest Glaucoma Trial Group. Factors for 
glaucoma progression and the effect of treatment.  The Early Manifest Glaucoma Trial. Arch 
Ophthalmol 2003;121:48-56.  

TRANSCEND CYPASS VX STUDY  
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18. Lichter PR, Musch DC, Gillespie BW, et al and the CIGTS Study Group. Interim clinical outcomes 
in the Collaborative Initial Glaucoma Treatment Study comparing initial treatment randomized to 
medications or surgery. Ophthalmology 2001;108:1943-53.  
19. The AGIS Investigators. The Advanced Glaucoma Intervention Study (AGIS): 7. The relationship 
between control of intraocular pressure and visual field deterioration. Am J Ophthalmol 
2000;130:429-40.  
20. The AGIS Investigators.  The Advanced Glaucoma Intervention Study (AGIS): 13. Comparison of 
treatment outcomes within race.  Ten-year results. Ophthalmology 2004;111:651-64.  
21. Miglior S, Pfeiffer N, Zeyen T et al for the European Glaucoma Prevention Study Group. Results of 
the European Glaucoma Prevention Study. Ophthalmology 2005;112:366-75.  
22. Miglior S, Zeyen T, Pfeiffer N, et al for the European Glaucoma Prevention Study Group. The 
European Glaucoma Prevention Study design and baseline description of the participants. 
Ophthalmology 2002;109:1612-21. 
23. The Advanced Glaucoma Intervention Study (AGIS): 7. The relationship between control of 
intraocular pressure and visual field deterioration.The AGIS Investigators. Am J Ophthalmol 
2000;130:429-40. 
24. Am J Ophthalmol. 2012 May;153(5):789-803.e2.  
25.  Ritch R, Shields MB, Krupin T.  The Glaucomas. St. Louis: Mosby, 1996; 337 – 343). 
26. Toris CB.  Extravascular albumin concentration of the uvea. Invest Ophthalmol Vis Sci  1987; 28: 
477. 
27. Curr Mol Med. 2010 Dec;10(9):824-40 
28. Suguruo K, Toris CB, Pederson JE.  Uveoscleral outflow following cyclodialysis in the monkey eye 
using a fluorescent tracer.  Invest Ophthalmol Vis Sci 1985: 26, 810.   
29. American Society of Cataract and Refractive Surgery 2012 
30. Invest Ophthalmol Vis Sci. 1985 Jun;26(6):810-3 
31. Graefes Arch Clin Exp Ophthalmol. 1995 Sep;233(9):592-7 
32. Fortschr Ophthalmol [Suppl] 88:234.89 
33. J Cataract Refract Surg. 2001 May;27(5):711-4 
34. ASCRS 2012 
35. AAO 2012

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