The AGS Second Aqueous Shunt Implant vs. Transscleral Cyclophotocoagulation Treatment Study
Phase: NA
Conditions: Glaucoma
Sponsor: Robert Feldman

IRB NUMBER: HSC-MS-15-1053 
IRB APPROVAL DATE: 08/20/2020 
2/16/2018 
Amendment 2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
The AGS Second Aqueous Shunt Implant vs. TransScleral 
Cyclophotocoagulation Treatment Study 
 
NCT02691455 
 
Version Date: 08/20/2020 
 
 

IRB NUMBER: HSC-MS-15-1053 
IRB APPROVAL DATE: 08/20/2020 
2/16/2018 
Amendment 2 
 
Short Title 
 
 
Long Title 
 
The AGS Second Aqueous Shunt Implant vs. 
TransScleral Cyclophotocoagulation Treatment 
Study 
 
 
 
1. TITLE PAGE 
 
 
Protocol Number: 
RCEC-2015-STSCPC 
 
Protocol Version: 
Amendment 2 
 
 
Treatment Arms: 
1. Second Aqueous Shunt 
2. Transscleral Diode Laser Cyclophotocoagulation 
 
 
Coordinating Investigator: 
Robert M. Feldman, M.D. 
6400 Fannin Street, Suite 1800 
Houston, TX 77030 
USA 
Telephone: (713) 559-5200 
Email: ASSISTS@cizikeye.org 
 
UTHealth Site Principal Investigator: Robert M. Feldman, MD 
 
 
 
Investigator Name: 
  
 
Address: 
  
 
 
Telephone: 
  
 

IRB NUMBER: HSC-MS-15-1053 
IRB APPROVAL DATE: 08/20/2020 
2/16/2018 
Amendment 2 
 
Protocol Signature Page 
 
 
The signature below constitutes my review and approval of Protocol RCEC-2015-STSCPC titled 
"The AGS Second Aqueous Shunt Implant vs. TransScleral Cyclophotocoagulation Treatment 
Study" and attachments and provides the necessary assurances that this trial 
will be conducted according to all stipulations, including all statements regarding 
confidentiality and according to local legal and regulatory requirements and 
applicable U.S. FDA regulations and ICH guidelines. 
 
 
Investigator Signature:   
 
 
 
Date:   
 

IRB NUMBER: HSC-MS-15-1053 
IRB APPROVAL DATE: 08/20/2020 
2/16/2018 
Amendment 2 
 
Table of Contents 
1. TITLE PAGE ......................................................................................................................... 1 
2. SUMMARY ........................................................................................................................... 6 
3. BACKGROUND INFORMATION ........................................................................................... 7 
4. TRIAL OBJECTIVES ............................................................................................................. 8 
4.1. Primary Aim ..................................................................................................................... 8 
4.2. Secondary Aims .............................................................................................................. 8 
5. TRIAL DESIGN ..................................................................................................................... 9 
6. PARTICIPANTS .................................................................................................................... 9 
6.1. Inclusion Criteria .............................................................................................................. 9 
6.2. Exclusion Criteria ............................................................................................................. 9 
6.3. Eye .................................................................................................................................10 
7. STUDY DESIGN CONSIDERATIONS .................................................................................10 
7.1. Stratification ....................................................................................................................10 
7.2. Randomization Scheme ..................................................................................................10 
7.3. Masking ..........................................................................................................................10 
7.4. Sample Size Calculations ...............................................................................................11 
7.5. Recruitment period .........................................................................................................11 
7.6. Investigator/Site Selection .............................................................................................. 11 
8. RECRUITMENT PROCEDURE ...........................................................................................11 
8.1. Randomization Procedure ..............................................................................................11 
9. SURGICAL PROCEDURES .................................................................................................12 
9.1. Second Aqueous Shunt (SAS) ........................................................................................12 
9.1.1. Anesthesia ...............................................................................................................12 
9.1.2. Placement of Aqueous Shunt ...................................................................................12 
9.1.3. Occlusion of Tube (Baerveldt only) ...........................................................................12 
9.1.4. Tube Coverage ........................................................................................................12 
9.1.5. Intraoperative Medications .......................................................................................12 
9.1.6. Concurrent Procedures ............................................................................................13 
9.1.7. Postoperative Medications .......................................................................................13 
9.2. Transscleral Diode Laser Cyclophotocoagulation (TLC) .................................................13 
9.2.1. Anesthesia ...............................................................................................................13 
9.2.2. Laser Settings ..........................................................................................................13 
9.2.3. Laser Procedure .......................................................................................................13 
9.2.4. Concurrent Procedures ............................................................................................13 
9.2.5. Postoperative Medications .......................................................................................13 

IRB NUMBER: HSC-MS-15-1053 
IRB APPROVAL DATE: 08/20/2020 
2/16/2018 
Amendment 2 
 
9.3. Enhancement Procedure ................................................................................................13 
9.3.1. Second Aqueous Shunt ............................................................................................14 
9.3.2. Transscleral Diode Cyclophotocoagulation ...............................................................14 
10. SCHEDULED STUDY VISITS and ASSESSMENTS ..........................................................14 
10.1. Study Visit Schedule .....................................................................................................14 
10.1.1. Screening/Baseline Visit ........................................................................................ 14 
10.1.2. Scheduled Follow-up Visits ....................................................................................14 
10.1.3. Post-Enhancement Scheduled Follow-up Visits......................................................15 
10.1.4. IOP Confirmation Visit ............................................................................................15 
10.2. Scheduled Assessments ...............................................................................................15 
10.3. Assessments ................................................................................................................17 
10.3.1. Ocular Medications .................................................................................................17 
10.3.2. Visual Acuity ..........................................................................................................17 
10.3.3. Binocular Diplopia ................................................................................................. 18 
10.3.4. External Ocular Examination (Exophthalmometry)..................................................18 
10.3.5. Specular Microscopy ..............................................................................................18 
10.3.6. Biomicroscopy ........................................................................................................18 
10.3.7. Intraocular Pressure ...............................................................................................19 
10.3.8. Ultrasonic Pachymetry .......................................................................................... 20 
10.3.9. Ophthalmoscopy ....................................................................................................20 
10.3.10. Optical Coherence Tomography (OCT) ................................................................20 
10.3.11. Universal Pain Scale ............................................................................................20 
10.3.12. Visual Function Questionnaire (VFQ-25) ..............................................................20 
11. PROTOCOL DEVIATIONS ................................................................................................ 20 
12. ADVERSE EVENTS ...........................................................................................................21 
12.1. Serious Adverse Events ................................................................................................21 
12.2. Recording Instructions ..................................................................................................22 
12.3. Follow-up of Adverse Events ........................................................................................22 
13. MONITORING ................................................................................................................... 22 
14. DATA AND SAFETY MONITORING BOARD .....................................................................22 
15. WITHDRAWAL OF A STUDY PARTICIPANT ....................................................................23 
16. DATA ANALYSIS .............................................................................................................. 23 
16.1. Interim Analysis/Safety Monitoring ................................................................................23 
16.2. Primary Analysis ...........................................................................................................23 
16.3. Secondary Analysis ..................................................................................................... 24 
16.3.1. To compare changes in vision related to quality of life from baseline to 1-, 3-, and 5- 
year visits between SAS and TLC groups, measured by NEI VFQ-25 ............................... 24 

IRB NUMBER: HSC-MS-15-1053 
IRB APPROVAL DATE: 08/20/2020 
2/16/2018 
Amendment 2 
 
16.3.2. To compare cumulative incidence of vision-threatening complications at 1, 3, and 5 
years post-treatment between groups ................................................................................ 24 
16.3.3. To compare BCVA at visits after the 6-month postoperative visit ............................ 24 
16.3.4. To compare incidence and severity of pain between groups at the initial 1-week and 
1-month postoperative visits. ............................................................................................. 24 
16.3.5. To compare the total number of visits during the first three months, during the first 
year, and during all five years of the study between groups ................................................25 
Appendix 1 ............................................................................................................................... 27 

IRB NUMBER: HSC-MS-15-1053 
IRB APPROVAL DATE: 08/20/2020 
2/16/2018 
Amendment 2 
 
2. SUMMARY 
 
Study Objective 
To compare the 1-, 3-, and 5-year outcomes of a second aqueous shunt 
(SAS) to Transscleral Diode Laser Cyclophotocoagulation (TLC) in eyes 
with uncontrolled glaucoma with a single existing aqueous tube shunt 
implant. 
Study Endpoint 
(Failure) 
1. 
Intraocular pressure (IOP) 
a. > 18 mmHg on maximum tolerated topical IOP-lowering 
medications, or 
b. reduced by < 20% on maximum tolerated topical IOP- 
lowering medications from medicated preoperative IOP, or 
c. 
≤ 5 mmHg without glaucoma medications 
on IOP confirmation visit(s), 6 months after initial study intervention; 
or 
2. Additional reoperation for glaucoma (enhancement procedures 
allowed in the first 4 months); or 
3. Addition of an oral carbonic anhydrase inhibitor (CAI) for the study eye 
on or after the 6-month visit; or 
4. No light perception (NLP) 
Study 
Population 
18 to 85 years of age with uncontrolled glaucoma on maximum tolerated 
topical therapy with a single existing tube shunt implant 
Study Design 
Prospective, multicenter, randomized, masked, parallel group 
Treatment 
Groups 
1. Second Aqueous Shunt Implant (SAS) 
2. Transscleral Diode Laser Cyclophotocoagulation (TLC) 
Duration of 
Participant 
Participation 
5 Years 
Number of 
Study Visits 
10 – 13 visits 
# of Evaluable 
Participants 
91 in each group (182 total) 
Anticipated 
Maximum # of 
Participants 
280, allowing for a 35% dropout 
Recruitment 
Period 
1 year 
Study Centers 
Up to 70 centers 
Site Funding 
Available 
No 
IRB Submission Site’s responsibility (submission, questions, fees) 

IRB NUMBER: HSC-MS-15-1053 
IRB APPROVAL DATE: 08/20/2020 
2/16/2018 
Amendment 2 
 
3. BACKGROUND INFORMATION 
 
Aqueous shunts (AS) are commonly used to treat eyes with glaucoma refractory to medical 
therapy or eyes that have failed or are at high risk of failing a filtering procedure. The Tube 
Versus Trabeculectomy (TVT) Study demonstrated that AS were more effective in the long term 
(5 years) than trabeculectomy in eyes with prior incisional surgery and uncontrolled glaucoma.2 
Largely due to the results of TVT, the frequency of AS implantation has increased 410% 
between 1994 and 2012.1 Additionally, it led to the question being evaluated in the Primary 
Tube Versus Trabeculectomy (PTVT) Study whether primary AS surgery may be appropriate in 
treating uncontrolled primary open-angle glaucoma, which may further increase the rates of 
implantation. Despite the favorable results compared to trabeculectomy, approximately 30-50% 
of AS fail within the first 5 years of implantation.2, 3 
For eyes where an initial AS fails to control IOP and medical therapy is ineffective, two 
surgical techniques are often used -- implantation of a second AS or cyclodestruction. 
Regrettably, there is very little clinical evidence to direct care in cases of initial AS failure. 
Published studies investigating these two approaches separately conclude that both of these 
procedures are valid options for eyes with failed initial AS,4-11 in that they are successful in 
lowering IOP. However, these studies are small and retrospective, with the exception of one 
small, non-comparative, prospective case series.12 
Two retrospective studies published compared second AS with cyclodestruction after a 
failed initial AS: one with 17 eyes (8 AS, 9 cyclodestruction) in pediatric patients,13 and the 
other with 47 eyes (15 AS, 32 cyclodestruction) predominantly in adults.14 Both studies reported 
reduction of IOP and number of IOP-lowering medications in both treatment groups. The latter 
study showed that eyes treated with cyclodestruction had a higher early failure rate (mean 13.5 
months), while the second AS group had few early failures, but a higher rate of long-term 
failures and complications (mean = 6.1 years).14 While these studies provide the best current 
clinical guidance for eyes that have failed an initial AS, there is no prospective, randomized, 
controlled clinical trial evaluating the efficacy or safety of these two treatment options, nor are 
there any data on the effects of these interventions in this setting on quality of life. 
The goal of this study is to provide high-level evidence to guide clinical decision-making in 
the management of this increasing population of patients given the increasing rates of AS 
implantation. 

IRB NUMBER: HSC-MS-15-1053 
IRB APPROVAL DATE: 08/20/2020 
2/16/2018 
Amendment 2 
 
4. TRIAL OBJECTIVES 
 
4.1. Primary Aim: 
 
The primary aim is to compare short- (1 year), mid- (3 years), and long-term (5 years) 
cumulative incidences of failures in participants who undergo a second aqueous shunt (SAS) to 
those cumulative incidences of failures in participants who undergo transscleral diode laser 
cyclophotocoagulation (TLC) for eyes with uncontrolled glaucoma with a single existing aqueous 
tube shunt implant. 
The primary outcome variable is success or failure of treatment at 1, 3, and 5 years, 
where treatment failure is defined as meeting one or more of the following 4 criteria: 
1. Intraocular pressure (IOP) 
a) >18 mm Hg on maximum tolerated topical IOP-lowering medications, or 
b) Reduction of < 20% IOP on maximum tolerated topical IOP-lowering 
medications from medicated preoperative IOP, or 
c) ≤ 5 mm Hg without IOP-lowering medications 
on IOP confirmation visit, 6 months after initial study intervention; or 
2. Reoperation for glaucoma; or 
3. Addition of an oral CAI for the study eye on or after the 6-Month Study Visit; or 
4. Loss of light perception vision (NLP). 
 
4.2. Secondary Aims 
 
The secondary aims are to compare safety (i.e. complications, loss of best-corrected visual 
acuity [BCVA], and pain) and vision-related quality of life between the two treatments, including: 
1. Cumulative incidence of vision-threatening complications at 1, 3, and 5 years after initial 
study intervention; 
2. BCVA at scheduled visits after the 6-month postoperative visit. Changes of BCVA from 
baseline and the incidence of eyes that have lost more than 2 lines of BCVA will be 
compared between groups at each visit. 
3. Incidence and severity of pain at the 1-week and 1-month postoperative visits. 
4. Total number of visits during the first 3 months, first year, and over 5 years. 
5. Changes in vision-related quality of life from baseline to 1-, 3-, and 5-year visits, 
assessed by the NEI VFQ-25. 

IRB NUMBER: HSC-MS-15-1053 
IRB APPROVAL DATE: 08/20/2020 
2/16/2018 
Amendment 2 
 
5. TRIAL DESIGN 
 
This proposed study is a prospective, randomized, multicenter, masked, parallel group study. 
Sites will be selected based on surgeon’s surgical qualifications and experience with the two 
study interventions, as well as on sufficient staffing and facility resources for conducting the 
study examinations. The participants will be randomly assigned to receive a SAS or undergo 
TLC. The cumulative incidences of treatment failure at 1, 3 and 5 years will be compared 
between groups. 
 
 
6. PARTICIPANTS 
 
All patients who meet the following eligibility criteria may be enrolled. 
 
6.1. Inclusion Criteria 
 
Patients who meet the following inclusion criteria may be enrolled: 
1. Women and men 18 to 85 years of age 
2. Glaucoma not adequately controlled (IOP > 18 mmHg on maximum tolerated topical 
therapy) with a single existing aqueous tube shunt (AS). If the participant is taking oral 
carbonic anhydrase inhibitors (CAI) at the time of screening, the IOP prior to initiation of 
an oral CAI may be used 
3. Best-corrected visual acuity (BCVA) of hand motion (HM) or better in the study eye 
 
6.2. Exclusion Criteria 
 
Patients who meet the following exclusion criteria may NOT be enrolled: 
1. Monocular 
2. Presence of more than one AS in the study eye 
3. Previous cyclodestruction in the study eye 
4. Presence of active iris neovascularization in the study eye 
5. Binocular diplopia 
6. Presence of scleral buckle in the study eye 
7. History of scleritis in either eye 
8. History of scleromalacia in the study eye 
9. Insufficient conjunctiva to cover AS in the study eye 
10. IOP cannot be accurately measured with Goldmann applanation, Pneumotonometer, or 
Tono-Pen in the study eye (e.g. keratoprosthesis) 

IRB NUMBER: HSC-MS-15-1053 
IRB APPROVAL DATE: 08/20/2020 
2/16/2018 
Amendment 2 
 
11. Presence of silicone oil in the study eye 
12. Presence of retinal detachment in the study eye 
13. Presence of intraocular or orbital tumor affecting the study eye 
14. Need for cataract extraction or concurrent procedure at the time of study treatment, 
except tectonic aqueous shunt revisions for both groups is allowed 
15. In the opinion of the investigator, should not be enrolled in this study (e.g. uncontrolled 
systemic diseases, altered mental status, etc.) 
16. Unwilling or unable to give consent and satisfy requirements of the study (e.g. accept 
randomization, follow-up for 5 years, etc.) 
6.3. Eye 
 
If both eyes of a participant are eligible and the investigator plans to perform either of the study 
procedures in both eyes within three months of screening, the first eye to be treated will be the 
study eye. 
 
 
7. STUDY DESIGN CONSIDERATIONS 
 
7.1. Stratification 
 
Eyes will be classified into neovascular glaucoma (NVG) or non-NVG group based on glaucoma 
diagnosis for the purposes of generalizability. 
7.2. Randomization Scheme 
An adaptive block randomization scheme will be implemented with a block size of 4 and 
balancing between NVG and non-NVG strata within each site. 
Upon completion of the Screening/Baseline visit, the study eye will be randomly assigned to 
one of the 2 treatment groups: SAS or TLC within each stratum (NVG vs non-NVG) and each 
site based on the computer generated assignment. 
7.3. Masking 
 
Since intraocular pressure (IOP) is one of the most important measurements for determining 
treatment success or failure, every effort will be made to obtain unbiased measurements 
through a masking procedure. IOP will be performed by two study personnel, an operator and a 
masked reader. Masking procedures are detailed in section 10.3.7. 

IRB NUMBER: HSC-MS-15-1053 
IRB APPROVAL DATE: 08/20/2020 
2/16/2018 
Amendment 2 
 
7.4. Sample Size Calculations 
 
The definition of success/failure in this study is similar to the Ahmed versus Baerveldt 
Comparison (ABC) study.3 In the ABC study, the 1- and 5-year failure rate for the primary 
Baerveldt tube shunt group was 14% and 34%, respectively. Anticipated failure rate for the SAS 
group is 50% more than the primary tube shunt (~21%=14% x1.5 for 1 year, and 50% = 
34%x1.5 for 5 years). Setting the power at 80% and alpha at 5%, a sample size of 91 
participants in each group (182 total) would allow us to detect a difference of 20% or more 
reduction in cumulative incidence of failures in the TLC group from an anticipated 50% failure at 
5 years in the SAS group (i.e. <30% in TLC vs 50% in SAS). 
The retention rate in the ABC study was 65% at the 5-year visit. A total of 280 participants 
would allow for a 35% dropout rate (or deaths) during the 5-year study period. 
7.5. Recruitment period 
 
The intent of this study is to answer a question that is desperately needed within the glaucoma 
community. In order to have the question answered in a timely manner, the study plans to 
involve as many sites as possible from the AGS membership and thereby shorten the 
recruitment period to one year. 
7.6. Investigator/Site Selection 
 
Study investigator/site selection will be based on the cumulative number of at least 10 TLCs 
and 20 ASs (at least 5 of which being inferonasal tube shunts) implanted by an investigator. 
Additionally, sites must have the necessary staffing and resources to conduct this study. 
 
 
8. RECRUITMENT PROCEDURE 
 
Recruitment is open for competitive enrollment. The Investigators and/or study staff will enroll 
qualified participants into the study. After reviewing and signing the informed consent form, a 
study number will be assigned to the participant in a sequential manner by site identification 
(assigned by REDCap) followed by participant number. All potential participants will undergo an 
initial screening examination (Table 2) in order to determine study eligibility. 
8.1. Randomization Procedure 
 
Upon completion of the Screening/Baseline visit, sites will enter the Screening/Baseline visit 
data into the research electronic data capture (REDCap) system to confirm eligibility. Once 
eligibility of the participant is confirmed, the REDCap system will provide the participant 

IRB NUMBER: HSC-MS-15-1053 
IRB APPROVAL DATE: 08/20/2020 
2/16/2018 
Amendment 2 
 
randomization assignment, SAS or TLC. The participant should be treated within 45 days of the 
Screening/Baseline visit or the Screening/Baseline visit must be performed again. 
 
 
9. SURGICAL PROCEDURES 
 
9.1. Second Aqueous Shunt (SAS) 
 
9.1.1. Anesthesia 
 
Anesthesia is at the discretion of the surgeon. The site will record accordingly. 
 
9.1.2. Placement of Aqueous Shunt 
 
Either a Baerveldt Glaucoma Implant 350-mm2 BG101-350 or an Ahmed Model FP7 Flexible 
Plate must be used for all participants unless there is insufficient space, in which case a 
Baerveldt Glaucoma Implant 250-mm2 BG103-250 may be used. The implant’s preferred 
location is approximately 180 degrees from the existing initial plate. Tube insertion through the 
anterior chamber, sulcus, or pars plana is acceptable and will be documented. The site will 
record the model selected, the quadrant in which it was implanted, the clock hour in which the 
tube was inserted, and complications, if any. 
Implants may not be modified in anyway (e.g. trimming the plate). 
 
9.1.3. Occlusion of Tube (Baerveldt only) 
 
The Baerveldt Glaucoma Implant must be completely occluded in all cases. The method of 
occlusion is left to the discretion of the surgeon. Occlusion must be tested ensuring there is no 
flow through the tube or around the sclerostomy. Fenestration of the tube or wick placement is 
allowed. The site will document the occlusion method used by the surgeon in each case. 
9.1.4. Tube Coverage 
 
The type and use of patch graft used to cover the tube is at the discretion of the surgeon. The 
site will record if a graft is used and the type in each case. 
9.1.5. Intraoperative Medications 
 
The use of mitomycin-C, 5-fluorouracil or anti-vascular endothelial growth factor (VEGF) agents 
are not allowed at the time of aqueous shunt implantation. Other intraocular medications are 
allowed. 

IRB NUMBER: HSC-MS-15-1053 
IRB APPROVAL DATE: 08/20/2020 
2/16/2018 
Amendment 2 
 
9.1.6. Concurrent Procedures 
 
Except for tectonic aqueous shunt revisions, concurrent procedures are not allowed at the time 
of aqueous shunt implantation. 
9.1.7. Postoperative Medications 
 
Postoperative medication regimen is at the surgeon’s discretion. The site will record 
accordingly. 
9.2. Transscleral Diode Laser Cyclophotocoagulation (TLC) 
 
9.2.1. Anesthesia 
 
Anesthesia is at the discretion of the surgeon. The site will record accordingly. 
 
9.2.2. Laser Settings 
 
Recommended settings are 2000 mW for 2 seconds, 1850 mW for 3 seconds, or 1750 mW for 4 
seconds duration, titrating the energy up or down just below where a pop is heard. The site will 
record starting energy, duration, end energy, and total energy used. 
9.2.3. Laser Procedure 
 
Four to eight spots should be used per quadrant for a total of up to 16 spots per 180 degrees (or 
2 quadrants). Up to 180 degrees (or 2 quadrants) should be lasered during the initial treatment 
session. Selection of quadrants to be treated is at the investigator’s discretion. The site will 
record the total number of treatment spots performed. If available, the site will record, the 
number of prior uses of the G probe. 
9.2.4. Concurrent Procedures 
 
Except for tectonic aqueous shunt revisions, concurrent procedures are not allowed at the time 
of TLC. 
9.2.5. Postoperative Medications 
 
Type of postoperative medications is at the surgeon’s discretion. The site will record 
accordingly. 
9.3. Enhancement Procedure 
 
The following qualified enhancement procedure must be completed within 4 months of the 
“initial study treatment visit/Day 0)”. 

IRB NUMBER: HSC-MS-15-1053 
IRB APPROVAL DATE: 08/20/2020 
2/16/2018 
Amendment 2 
 
9.3.1. Second Aqueous Shunt 
 
Needling of the bleb over the tube shunt plate is allowed within the first 4 months following the 
initial study treatment. Manual or laser opening of the ligature or obturator removal is not 
considered an enhancement. 
9.3.2. Transscleral Diode Cyclophotocoagulation 
 
One additional TLC session (up to 2 additional quadrants, not to retreat previously treated 
quadrants) may be performed in the first 4 months following the initial study treatment. 
 
 
10. SCHEDULED STUDY VISITS AND ASSESSMENTS 
 
10.1. Study Visit Schedule 
 
10.1.1. Screening/Baseline Visit 
 
After reviewing and signing the informed consent form, all potential participants will undergo a 
screening examination in order to determine study eligibility, establish baseline ocular 
characteristics, and assignment to SAS or TLC based on the computer-generated assignment. 
If available, the mean deviation (MD) from the most recent visual field, prior to or during the 
Screening/Baseline visit will be collected to further characterize the stage of disease within the 
study population. 
10.1.2. Scheduled Follow-up Visits 
 
Every attempt should be made to conduct each follow-up evaluation within the visit windows 
(Table 1): Week 1 (-3 days to +14 days), Month 1 (-8 days to +29 days), Month 3 (±1 month), 
Month 6 (-2 to +3 months), Month 12 (-3 to +6 months), Year 2 (±6 months), Year 3 (-6 months 
to +1 year), and Year 5 (-1 year to +6 months). Evaluations conducted outside the visit window 
will be considered protocol deviations. 

IRB NUMBER: HSC-MS-15-1053 
IRB APPROVAL DATE: 08/20/2020 
2/16/2018 
Amendment 2 
 
Table 1. Time Windows for Scheduled Follow-Up Visits (number of days after initial study 
surgery) 
Follow-Up 
Visit 
Ideal Time 
Preferred Time 
Window 
Acceptable Time 
Window 
Week 1 
7 days 
6-8 days 
4-21 days 
Month 1 
30 days 
23-37 days 
22-59 days 
Month 3 
90 days 
76-104 days 
60-120 days 
Month 6 
182 days 
161-203 days 
121-273 days 
Month 12 
365 days 
305-425 days 
274-547 days 
Year 2 
730 days 
670-790 days 
548-912 days 
Year 3 
1095 days 
1005-1185 days 
913-1460 days 
Year 5 
1825 days 
1735-1915 days 
1461-2007 days 
 
10.1.3. Post-Enhancement Scheduled Follow-up Visits 
 
If an enhancement is performed after the Month 3 Study visit, the participant should be 
scheduled to return for a follow-up visit 1 month from the enhancement and then resume the 
normal study schedule. If an enhancement occurs prior to the Month 3 Study visit, the 
Enhancement 1 Month Study Visit is not required. 
10.1.4. IOP Confirmation Visit 
 
If a participant’s study eye meets the IOP failure criteria, either at a study visit or a nonstudy 
visit, a confirmation visit will be scheduled at approximately the same time of day within six 
weeks during the first year postoperatively and within 3 months after 1 year postoperative visits. 
Unless an emergent intervention is required, confirmation visits should occur when: 
1. IOP is >18 mm Hg on maximum tolerated topical IOP-lowering medications 6 months 
after initial study intervention, or 
2. IOP reduction is < 20% on maximum tolerated topical IOP-lowering medications from 
medicated preoperative IOP 6 months after initial study procedure, or 
3. IOP is ≤ 5 mm Hg without IOP-lowering medications 6 months after initial study 
procedure 
10.2. Scheduled Assessments 
Table 2 outlines the schedule of assessments at each visit throughout the study period. Data 
from the study visits must be entered into the REDCap system within 5 business days of the 
exam. 

IRB NUMBER: HSC-MS-15-1053 
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Amendment 2 
 
Table 2: Schedule of Assessments 
Assessment 
Screening 
/ Baseline 
Surgery – Day 0 
Week 1 
Month 1 
Month 3 
Enhancement 
Procedure 
Enhancement 
Month 1 
Month 6 
Month 12 
Year 2 
Year 3 
Year 5 / Exit 
Confirmation 
Visit*** 
Informed Consent 
X 
Demographics 
X 
Medical / Ophthalmic 
History 
X 
Historical VF MD* 
SE 
Concomitant 
Medications 
OU 
OU 
OU 
OU 
OU 
OU 
OU 
OU 
OU 
OU 
OU 
OU 
Inclusion/Exclusion 
Criteria 
X 
Visual Acuity 
OU 
SE 
SE 
SE 
SE 
SE 
SE 
SE 
SE 
SE 
Binocular Diplopia 
X 
X 
X 
X 
X 
X 
X 
External Ocular 
Examination 
OU 
OU 
OU 
OU 
Specular Microscopy 
(CCT and CD)** 
SE 
SE 
SE 
Biomicroscopy 
SE 
SE 
SE 
SE 
SE 
SE 
SE 
SE 
SE 
SE 
Intraocular Pressure 
OU 
SE 
SE 
SE 
SE 
SE 
SE 
SE 
SE 
SE 
SE 
Ultrasonic 
Pachymetry 
OU 
SE 
SE 
Ophthalmoscopy 
SE 
SE 
SE 
OCT (macula) 
SE 
SE 
Procedure 
SE 
SE 
VFQ-25 
X 
X 
X 
X 
Randomization 
X 
Pain Scale 
X 
X 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Perform assessment, not eye specific (X), study eye only (SE), both eyes (OU) 
* The mean deviation from the participants last visual field (if available) prior to enrollment will be recorded to further describe the 
stage of disease in the study population. 
**Specular microscopy (SM) will be performed at sites where SM is available 
***Confirmation visits will occur prior to the conduct of any surgical intervention in the study eye when IOP is believed to have met 
endpoint (failure). 

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10.3. Assessments 
 
The same examiner should perform the same assessments for each participant whenever 
feasible throughout the study. 
10.3.1. Ocular Medications 
 
All IOP-lowering medications that the participant is taking at the time of the Screening/Baseline 
visit and for the duration of the study will be recorded. Concomitant medications will be 
captured by class of medication. 
No investigational drugs may be used during the study and participants may not 
participate in any other medical or device study during the course of this investigation. 
10.3.2. Visual Acuity 
 
Visual Acuity testing should precede IOP measurement, the administration of eye drops to 
dilate or anesthetize the eye, or any examination requiring contact with the eye. A decrease in 
visual acuity of more than two lines should be reported as an adverse event (or the cause of the 
decrease in visual acuity). 
Manifest refraction must be performed prior to Best-Corrected Visual Acuity (BCVA) at all 
visits assessing vision except Week 1. Pinhole visual acuity may be used for the Week 1 
postoperative visit. 
The Snellen visual acuity chart should be used to measure BCVA. The participant’s 
visual acuity will be recorded as the last line read on which two or fewer letters were missed. If 
the participant cannot read the largest letter on the chart, the examiner should perform the 
following tests: 
Count Fingers: The examiner should hold his/her fingers in front of the participant’s eye 
in good light and the vision is recorded as the furthest distance that the fingers can be 
counted, CF (feet). 
Hand Motion: If the participant cannot see or count fingers, the examiner should wave a 
hand in front of the eye at a distance of two feet. If movements of the hand are seen by 
the participant, then the vision is recorded as HM. 
Light Perception: If visual acuity is so poor that the participant cannot read any of the 
letters and fails counting fingers and hand motion test, light perception needs to be 
tested with the indirect ophthalmoscope as the light source. Room lighting should remain 
at the level of normal visual acuity testing. The participant should close the opposite eye 
and cover it with the palm of their hand. The indirect ophthalmoscope light should be in 

IRB NUMBER: HSC-MS-15-1053 
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Amendment 2 
 
focus at 1 meter (3 feet) with the rheostat set at maximum voltage. From a distance of 3 
feet, the beam should be directed in and out of the eye at least 4 times, and the 
participant should be asked to respond when he or she sees the light. If the examiner is 
convinced that the participant sees the light, vision should be recorded as LP. If the 
examiner is convinced that the participant does not see the light, vision should be 
recorded as NLP. 
10.3.3. Binocular Diplopia 
All participants will be assessed for presence of binocular diplopia with correction at 
Screening/Baseline and all visits on and after the 3-months postoperatively (except 
Enhancement Month 1 and IOP confirmation). It will be documented as “present” or “absent”. 
10.3.4. External Ocular Examination (Exophthalmometry) 
Participants will be assessed for proptosis at the Screening/Baseline, Month 1, Month 3 and 
Month 12 Visits. If proptosis is grossly present, a Hertel exophthalmometer should be used to 
measure the amount of proptosis. 
10.3.5. Specular Microscopy 
 
Three quality central corneal images of the study eye should be taken by Specular Microscopy 
at Screening/Baseline, Year-1, and Year-5 visits prior to any administration of drops or contact 
with the eyes. Central corneal thickness (CCT) and cell density (CD) will be obtained and the 
values will be recorded from each image. The average will be calculated for each variable. 
10.3.6. Biomicroscopy 
 
A slit lamp examination will be performed on the lids, conjunctiva, cornea, anterior chamber, iris, 
and lens at each visit (except surgery, enhancement, and IOP confirmation visits). Any 
abnormalities will be graded as clinically significant or not and severity graded as mild (=1), 
moderate (=2), or severe (=3). Cells will be graded as trace (1-5 cells), mild (6-15 cells), or 
moderate/severe (> 15 cells / High Powered Field). The study tube position will be examined in 
two places: (1) tube measured approximately 1mm in from the limbus, and (2) the tube tip in the 
anterior chamber (AC), and will be assessed as: 
(a) Touching cornea 
 
(b) Close to cornea 
 
(c) Mid-AC 
 
(d) Close to iris, or 

IRB NUMBER: HSC-MS-15-1053 
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(e) Touching iris. 
 
If the study tube is present and visible in the AC, the length of the tube will be measured with 
the slit beam in millimeters. If the tube is behind the iris, document whether the tube is tenting 
the iris. The initial AS tube will be measured in the same fashion as the study tube at the 
Screening/Baseline, Year-1, Year-3, and Year-5 Visits. 
If there is no view beyond the cornea, “inadequate view” will be marked on the data 
collection form. 
10.3.7. Intraocular Pressure 
 
IOP measurements should be performed at all study visits at approximately the same time of 
day from the Screening/Baseline visit. 
All IOP checks must be performed prior to dilation. 
Two individuals (an operator and a masked reader) must perform the IOP measurements. 
The operator will be responsible for operating the instrument while the masked reader will read 
and record the results. In order to minimize the measurement variation, all IOP measurements 
for any individual participant should preferably be performed by the same operator with the 
same tonometer. 
Starting with the right eye, alternating between the two eyes, two IOP measurements should 
be performed on each eye. The mean of the two measurements will be used for analysis. If the 
difference between the two measurements for an eye is greater than 2 mm Hg, a third 
measurement must be taken. The median of the three measurements will be used for analysis. 
Three instruments for measuring IOP are allowed and will be chosen based on the 
participant’s cornea status. The same type of instrument should be used for the duration of the 
study unless new pathology has developed that prevents accurate usage of the initial method. 
Goldmann Applanation Tonometry: Following instillation of a drop of fluorescein and 
anesthetic, ensure the participants head is properly positioned in the chin rest and against 
the forehead rest; encourage the participant to continue breathing normally. The operator 
will look through the slit-lamp and adjust the dial while the masked reader records the IOP 
measurement. The reader will be masked to the participant’s treatment. 
Pneumotonometry: A pneumotonometer will be used in cases of corneal edema, corneal 
scarring, or irregular corneal astigmatism. The technique described in the user’s manual 
should be performed. The operator will turn the display facing away from himself/herself 
while the masked reader records the measurements. 
Tono-Pen: The Tono-Pen will be used in cases of corneal edema, corneal scarring, or 
irregular corneal astigmatism at sites where a pneumotonometer is not available. The 

IRB NUMBER: HSC-MS-15-1053 
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technique described in the user’s manual should be performed. The operator will hold the 
display out to the reader for the IOP and reliability to be recorded. 
 
 
10.3.8. Ultrasonic Pachymetry 
 
CCT measurements will be obtained by Ultrasonic Pachymetry 5 times for each eye. The 
median of the 5 measurements will be used as the CCT. 
10.3.9. Ophthalmoscopy 
 
Any vitreous or retinal abnormalities will be noted and graded as clinically significant or not 
clinically significant. A vertical cup-to-disc ratio will be measured with a slit lamp lens. 
If a dilated exam has been performed within 1 month prior to Screening/Baseline visit, the 
information collected from that visit may be used for the study. 
If there is no view of the posterior chamber, “inadequate view” will be marked on the 
data collection form. 
10.3.10. Optical Coherence Tomography (OCT) 
 
OCT of the macula should be performed at the Screening/Baseline and Month 12 visits to 
assess for presence or absence of macular edema. Sites will be asked for the central macular 
thickness at Screening/Baseline and future visits requiring OCT if a participant presents with a 
decrease in visual acuity of more than 2 lines and macular edema is suspected. Sites will 
provide a deidentified copy of the macular thickness map to the DCC when performed. 
10.3.11. Universal Pain Scale 
 
Following the initial study treatment, participant pain or discomfort will be assessed at Week 1 
and Month 1 visits with the Universal Pain Scale (Appendix 1). 
10.3.12. Visual Function Questionnaire (VFQ-25) 
 
Participant-reported visual function will be assessed with the National Eye Institute (NEI) Visual 
Functioning Questionnaire 25 (VFQ-25, see Appendix 2) at Screening/Baseline, Year 1, Year 3, 
and Year 5 visits. The VFQ-25 will be administered by site study personnel. 
 
 
11. PROTOCOL DEVIATIONS 
 
Protocol deviations must be reported by the Study Site to the DCC within five business days. 
Sites will be notified of protocol deviations discovered during data monitoring and source 

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document verification. Study Sites must also submit protocol deviations to their IRB pursuant to 
their IRB policy. 
 
 
12. ADVERSE EVENTS 
 
An adverse event (AE) is any untoward medical occurrence in a participant who is administered 
a test article. The AE does not necessarily have a causal relationship with the treatment. An 
AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease temporally associated with study treatments. 
A nonserious AE is defined as a change in a participant’s ophthalmic and/or medical health 
that is not life-threatening, does not require hospitalization, does not prolong a current 
hospitalization and is not disabling. All AEs must be reported to the DCC using REDCap. All 
AEs must be reported whether they are considered study-related or not. 
12.1. Serious Adverse Events 
 
A serious adverse event is defined as any adverse experience occurring at any time during the 
study that results in: 
 
Death 
 
Life-threatening 
 
Inpatient hospitalization 
 
Prolongation of existing hospitalization 
 
Disability or permanent damage (including vision threatening complications) 
 
A congenital anomaly/birth defect 
 
Required intervention to prevent permanent impairment or damage and/or other 
serious important medical events 
 
SAEs will be documented the same as adverse events, but flagged as a SAE. All SAEs 
should be submitted in REDCap within five business days of the Investigator’s knowledge of the 
event. When new significant information is obtained as well as when the outcome of an event is 
known, the Investigator must provide updates in REDCap. If the participant is hospitalized, a 
deidentified copy of the discharge summary must be uploaded into the REDCap system as 
soon as it becomes available.  All SAEs must be submitted to the sites IRB pursuant to their 
IRB policy. 

IRB NUMBER: HSC-MS-15-1053 
IRB APPROVAL DATE: 08/20/2020 
2/16/2018 
Amendment 2 
 
12.2. Recording Instructions 
 
Mild, moderate, or severe should be used to describe the maximum intensity of the event. 
 
Mild – Does not interfere with the participant’s usual functions 
 
Moderate – Interferes to some extent with the participant’s usual functions 
 
Severe – Interferes significantly with the participant’s usual functions 
It should be noted that a severe intensity does not necessarily mean it is an SAE. 
The investigator will also be asked to determine the likelihood of the relationship between 
the study intervention and the AE. 
12.3. Follow-up of Adverse Events 
 
For participants who have ongoing ocular adverse events at the time of their exit visit, it is 
recommended that the Investigator schedule a follow-up visit to determine the outcome of the 
event. 
 
 
13. MONITORING 
 
Complete source documents will be monitored for the first participant enrolled in the study at 
each site and randomly thereafter. A deidentified copy of the source document will be 
submitted to DCC for source verification. Random monitoring of 10% of study visits will be 
performed; monitoring of additional study visits will be undertaken based on performance and 
queries. 
Deidentified source documents must be provided upon DCC request. Onsite 
monitoring visits may be required if Study Sites are unresponsive to DCC requests or excessive 
discrepancies are found. 
 
 
14. DATA AND SAFETY MONITORING BOARD 
 
Throughout the course of the study, all adverse events will be monitored and reported on an 
adverse event case report form, including seriousness, action taken and relationship to study 
treatment. A Data and Safety Monitoring Board (DSMB), independent from the study, will 
review all serious adverse events (SAE). The committee members will be selected for this 
study by the Chair, Dale Heuer, based on their experience and qualifications. If adverse events 
occur, the first concern will be the safety of the study participant. For additional details of the 
conduct and procedures for the DSMB please see the DSMB charter. 

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15. WITHDRAWAL OF STUDY PARTICIPANT 
 
If a participant wishes to withdraw from the study, the reason for withdrawal should be 
documented in the source document and REDCap. An exit visit should be performed if 
possible. If a participant does not return for a scheduled visit, every effort should be made to 
contact the participant and document the participant’s outcome. 
Relevant tests and assessments should be performed according to the schedule for Year 
5/Exit visit if withdrawal occurs between surgery and Year 5 visits. 
 
 
16. DATA ANALYSIS 
 
16.1. Interim Analysis/Safety Monitoring 
A number of interim analyses will be performed. The purpose of these analyses will be: 
a. 
To monitor recruitment targets in subgroups of interest (NVG vs non-NVG) and to 
monitor balance between treatment groups with regard to prognostic factors. 
b. 
To provide a regular mechanism for evaluating data quality, protocol adherence, and 
side-effect patterns including adverse reactions. 
c. 
To determine whether the study should be terminated early. Negative results could 
suggest that there is no possibility of ever establishing significance between-group 
differences. 
d. 
To assess the possibility that a positive but nonsignificant trend might require an 
increase in the originally projected sample size or an increase in the study duration. 
 
Interim analyses will be performed every 3 months for the first year of enrollment and every 
6 months thereafter. Interim analyses may also be performed at any time upon the request of 
the DSMB. The DCC will provide the results to the DSMB for making all decisions regarding the 
future conduct of the study. All investigators will be masked as to the results of interim analyses. 
16.2. Primary Analysis 
 
In the primary analysis, the null hypothesis is that there is no difference in one-year cumulative 
failure rates between the SAS group and the TLC group. The cumulative failure rates will be 
compared with Fisher exact test with one degree of freedom. The survival time from the 
treatment to failure will be estimated by Kaplan-Meier survival curve for each group and 
compared between the two treatment groups with the log-rank test. The potential effect of 
covariates will be assessed with the Cox proportional hazards models. 

IRB NUMBER: HSC-MS-15-1053 
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16.3. Secondary Analysis 
 
16.3.1. To compare changes in vision related to quality of life from baseline to 1-, 
3-, and 5-year visits between SAS and TLC groups, measured by NEI VFQ-25 
Differences between study groups in NEI-Visual Function Questionnaire (NEI-VFQ-25) and its 
subscales will be analyzed both cross-sectionally and longitudinally. Either a Student’s t-test or 
a nonparametric Wilcoxon rank sum test will be used for the cross-sectional comparison 
between groups and a mixed-effect model with repeated measurements will be used to 
compare two groups over the study period. 
16.3.2. To compare cumulative incidence of vision-threatening complications at 1, 
3, and 5 years post-treatment between groups 
Vision-threatening complications will be defined by the DSMB. The safety effect of treatment will 
be assessed by comparing the cumulative proportions of vision-threatening complications or the 
event rates per person-year from the time of randomization with asymptotic X2 test with one 
degree of freedom. The survival curve from the time of randomization to the first occurrence of 
vision-threatening events will be compared between the two randomization groups with the log- 
rank test. The potential effect of covariates will be assessed with the Cox proportional hazards 
models. 
16.3.3. To compare BCVA at visits after the 6-month postoperative visit 
 
Snellen BCVA will be converted to line scale by logMAR. Differences between study groups will 
be analyzed both cross-sectionally and longitudinally. Either a Student’s t-test or a 
nonparametric Wilcoxon rank sum test will be used for the cross-sectional comparison between 
groups and a mixed-effect model with repeated measurements will be used to compare two 
groups over the study period. 
The incidence of loss more than 2 lines from baseline to each follow-up visit will be 
compared with a Fisher exact test. 
16.3.4. To compare incidence and severity of pain between groups at the initial 1- 
week and 1-month postoperative visits. 
The incidence and severity of pain at the 1-week and 1-month follow-up visits will be compared 
with a Fisher exact test and a Student t test (or a Wilcoxon rank sum test), respectively. 

IRB NUMBER: HSC-MS-15-1053 
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Amendment 2 
 
16.3.5. To compare the total number of visits during the first three months, during 
the first year, and during all five years of the study between groups. 
Differences between study groups in total number of visits during the first three months, during 
the first year, and during all five years of the study will be compared between study groups on 
the distributions with either a Student’s t-test or a Wilcoxon rank sum test. 
The large number of measures used to assess safety and the frequency of interim 
analyses to monitor safety introduce the problem of multiple comparisons, i.e. some 
comparisons are statistically significant because of the large number of statistical tests 
conducted. Analyses that adjust for multiple comparisons will be conducted and both adjusted 
and unadjusted multiple comparisons will be reported to the Data and Safety Monitoring 
Committee. 

IRB NUMBER: HSC-MS-15-1053 
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2/16/2018 
Amendment 2 
 
 
REFERENCES 
1. 
Arora KS, Robin AL, Corcoran KJ, Corcoran SL, Ramulu PY. Use of Various Glaucoma 
Surgeries and Procedures in Medicare Beneficiaries from 1994 to 2012. Ophthalmology. 
2015;122(8):1615-1624. 
2. 
Gedde SJ, Schiffman JC, Feuer WJ, et al. Treatment outcomes in the Tube Versus 
Trabeculectomy (TVT) study after five years of follow-up. Am J Ophthalmol. 
2012;153(5):789-803 e782. 
3. 
Budenz DL, Barton K, Gedde SJ, et al. Five-year treatment outcomes in the Ahmed 
Baerveldt comparison study. Ophthalmology. 2015;122(2):308-316. 
4. 
Anand A, Tello C, Sidoti PA, Ritch R, Liebmann JM. Sequential glaucoma implants in 
refractory glaucoma. Am J Ophthalmol. 2010;149(1):95-101. 
5. 
Burgoyne JK, WuDunn D, Lakhani V, Cantor LB. Outcomes of sequential tube shunts in 
complicated glaucoma. Ophthalmology. 2000;107(2):309-314. 
6. 
Ness PJ, Khaimi MA, Feldman RM, et al. Intermediate term safety and efficacy of 
transscleral cyclophotocoagulation after tube shunt failure. J Glaucoma. 2012;21(2):83- 
88. 
7. 
Jimenez-Roman J, Gil-Carrasco F, Costa VP, et al. Intraocular pressure control after the 
implantation of a second Ahmed glaucoma valve. Int Ophthalmol. 2015. 
8. 
Semchyshyn TM, Tsai JC, Joos KM. Supplemental transscleral diode laser 
cyclophotocoagulation after aqueous shunt placement in refractory glaucoma. 
Ophthalmology. 2002;109(6):1078-1084. 
9. 
Smith M, Buys YM, Trope GE. Second Ahmed valve insertion in the same eye. J 
Glaucoma. 2009;18(4):336-340. 
10. 
Godfrey DG, Krishna R, Greenfield DS, Budenz DL, Gedde SJ, Scott IU. Implantation of 
second glaucoma drainage devices after failure of primary devices. Ophthalmic Surg 
Lasers. 2002;33(1):37-43. 
11. 
Ko SJ, Hwang YH, Ahn SI, Kim HK. Surgical Outcomes of Additional Ahmed Glaucoma 
Valve Implantation in Refractory Glaucoma. J Glaucoma. 2015. 
12. 
Francis BA, Kawji AS, Vo NT, Dustin L, Chopra V. Endoscopic cyclophotocoagulation 
(ECP) in the management of uncontrolled glaucoma with prior aqueous tube shunt. J 
Glaucoma. 2011;20(8):523-527. 
13. 
Sood S, Beck AD. Cyclophotocoagulation versus sequential tube shunt as a secondary 
intervention following primary tube shunt failure in pediatric glaucoma. J AAPOS. 
2009;13(4):379-383. 
14. 
Schaefer JL, Levine MA, Martorana G, Koenigsman H, Smith MF, Sherwood MB. Failed 
glaucoma drainage implant: long-term outcomes of a second glaucoma drainage device 
versus cyclophotocoagulation. Br J Ophthalmol. 2015. 
15. 
Gabelt BT, Kaufman PL. Changes in aqueous humor dynamics with age and glaucoma. 
Prog Retin Eye Res. 2005;24(5):612-637. 

IRB NUMBER: HSC-MS-15-1053 
IRB APPROVAL DATE: 08/20/2020 
2/16/2018 
Amendment 2 
 
APPENDIX 1. 
 
 
 
 
APPENDIX 2. 
National Eye Institute Visual Functioning Questionnaire – 25 (VFQ-25) version 2000 
(INTERVIEWER FORMAT) 

PB/IA 
 
National Eye Institute 
Visual Functioning Questionnaire - 25 
(VFQ-25) 
version 2000 
 
 
 
(INTERVIEWER ADMINISTERED FORMAT) 
 
 
 
January 2000 
 
 
 
 
 
 
 
 
RAND hereby grants permission to use the "National Eye Institute Visual Functioning Questionnaire 25 (VFQ-25) 
July 1996, in accordance with the following conditions which shall be assumed by all to have been agreed to as a 
consequence of accepting and using this document: 
 
1. Changes to the NEI VFQ-25 - July 1996 may be made without the written permission of RAND. However, all such 
changes shall be clearly identified as having been made by the recipient. 
 
2. The user of this NEI VFQ-25 - July 1996 accepts full responsibility, and agrees to hold RAND harmless, for the 
accuracy of any translations of the NEI VFQ-25 Test Version - July 1996 into another language and for any errors, 
omissions, misinterpretations, or consequences thereof. 
 
3. The user of this NEI VFQ-25 - July 1996 accepts full responsibility, and agrees to hold RAND harmless, for any 
consequences resulting from the use of the NEI VFQ-25. 
 
4. The user of the NEI VFQ-25 - July 1996 will provide a credit line when printing and distributing this document or 
in publications of results or analyses based on this instrument acknowledging that it was developed at RAND under 
the sponsorship of the National Eye Institute. 
 
5. No further written permission is needed for use of this NEI VFQ-25 - July 1996. 
 
7/29/96 
 
© R 1996 
 
 
 
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IRB NUMBER: HSC-MS-15-1053 
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© R1996 
 
- 1 - 
version 2000 
 
Instructions: 
 
I’m going to read you some statements about problems which involve your vision 
or feelings that you have about your vision condition. After each question I will 
read you a list of possible answers. Please choose the response that best 
describes your situation. 
 
Please answer all the questions as if you were wearing your glasses or contact 
lenses (if any). 
 
Please take as much time as you need to answer each question. All your 
answers are confidential. In order for this survey to improve our knowledge 
about vision problems and how they affect your quality of life, your answers must 
be as accurate as possible. Remember, if you wear glasses or contact lenses for 
a particular activity, please answer all of the following questions as though you 
were wearing them. 

IRB NUMBER: HSC-MS-15-1053 
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© R1996 
 
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version 2000 
 
 
 
 
Visual Functioning Questionnaire - 25 
 
 
PART 1 - GENERAL HEALTH AND VISION 
 
 
1. 
In general, would you say your overall health is*: 
(Circle One) 
 
READ CATEGORIES: 
Excellent .............................. 1 
Very Good ............................ 2 
Good .................................... 3 
Fair ....................................... 4 
Poor ....................................... 5 
 
 
 
2. 
At the present time, would you say your eyesight using both eyes (with 
glasses or contact lenses, if you wear them) is excellent, good, fair, 
poor, or very poor or are you completely blind? 
(Circle One) 
READ CATEGORIES: 
Excellent .............................. 1 
Good .................................... 2 
Fair ....................................... 3 
Poor ....................................... 4 
Very Poor ............................. 5 
Completely Blind ................. 6 
* Skip Question 1 when the VFQ-25 is administered at the same time as the SF-36 or RAND 
36-Item Health Survey 1.0 

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version 2000 
 
 
3. 
How much of the time do you worry about your eyesight? 
(Circle One) 
 
READ CATEGORIES: 
None of the time ............................. 1 
A little of the time ........................... 2 
Some of the time ............................ 3 
Most of the time ............................. 4 
All of the time? ............................... 5 
 
4. 
How much pain or discomfort have you had in and around your eyes 
(for example, burning, itching, or aching)? Would you say it is: 
(Circle One) 
READ CATEGORIES: 
None ..................................... 1 
Mild ....................................... 2 
Moderate .............................. 3 
Severe, or............................. 4 
Very severe? ........................ 5 
 
 
 
PART 2 - DIFFICULTY WITH ACTIVITIES 
 
The next questions are about how much difficulty, if any, you have doing 
certain activities wearing your glasses or contact lenses if you use them 
for that activity. 
 
5. 
How much difficulty do you have reading ordinary print in 
newspapers? Would you say you have: 
(READ CATEGORIES AS NEEDED) 
 
(Circle One) 
No difficulty at all ...................................................... 1 
A little difficulty ......................................................... 2 
Moderate difficulty .................................................... 3 
Extreme difficulty ..................................................... 4 
Stopped doing this because of your eyesight ....... 5 
Stopped doing this for other reasons or not 
interested in doing this ...................................... 6 

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6. 
How much difficulty do you have doing work or hobbies that require 
you to see well up close, such as cooking, sewing, fixing things 
around the house, or using hand tools? Would you say: 
(READ CATEGORIES AS NEEDED) 
(Circle One) 
No difficulty at all ...................................................... 1 
A little difficulty ......................................................... 2 
Moderate difficulty .................................................... 3 
Extreme difficulty ..................................................... 4 
Stopped doing this because of your eyesight ........ 5 
Stopped doing this for other reasons or not 
interested in doing this ...................................... 6 
7. 
Because of your eyesight, how much difficulty do you have finding 
something on a crowded shelf? 
(READ CATEGORIES AS NEEDED) 
(Circle One) 
No difficulty at all ...................................................... 1 
A little difficulty ......................................................... 2 
Moderate difficulty .................................................... 3 
Extreme difficulty ..................................................... 4 
Stopped doing this because of your eyesight ........ 5 
Stopped doing this for other reasons or not 
interested in doing this ...................................... 6 
 
 
8. 
How much difficulty do you have reading street signs or the names of 
stores? 
(READ CATEGORIES AS NEEDED) 
(Circle One) 
No difficulty at all ...................................................... 1 
A little difficulty ......................................................... 2 
Moderate difficulty .................................................... 3 
Extreme difficulty ..................................................... 4 
Stopped doing this because of your eyesight ........ 5 
Stopped doing this for other reasons or not 
interested in doing this ...................................... 6 
9. 
Because of your eyesight, how much difficulty do you have going 
down steps, stairs, or curbs in dim light or at night? 

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(READ CATEGORIES AS NEEDED) 
(Circle One) 
No difficulty at all ...................................................... 1 
A little difficulty ........................................................ 2 
Moderate difficulty .................................................... 3 
Extreme difficulty ..................................................... 4 
Stopped doing this because of your eyesight ........ 5 
Stopped doing this for other reasons or not 
interested in doing this ...................................... 6 
 
 
 
10. Because of your eyesight, how much difficulty do you have noticing 
objects off to the side while you are walking along? 
(READ CATEGORIES AS NEEDED) 
(Circle One) 
No difficulty at all ...................................................... 1 
A little difficulty ......................................................... 2 
Moderate difficulty .................................................... 3 
Extreme difficulty ..................................................... 4 
Stopped doing this because of your eyesight ........ 5 
Stopped doing this for other reasons or not 
interested in doing this ...................................... 6 
11. Because of your eyesight, how much difficulty do you have seeing 
how people react to things you say? 
(READ CATEGORIES AS NEEDED) 
(Circle One) 
No difficulty at all ...................................................... 1 
A little difficulty ......................................................... 2 
Moderate difficulty .................................................... 3 
Extreme difficulty ..................................................... 4 
Stopped doing this because of your eyesight ........ 5 
Stopped doing this for other reasons or not 
interested in doing this ...................................... 6 

IRB NUMBER: HSC-MS-15-1053 
IRB APPROVAL DATE: 087/2002/2020 
© R1996 
 
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12. Because of your eyesight, how much difficulty do you have picking out 
and matching your own clothes? 
(READ CATEGORIES AS NEEDED) 
(Circle One) 
No difficulty at all ...................................................... 1 
A little difficulty ......................................................... 2 
Moderate difficulty .................................................... 3 
Extreme difficulty ..................................................... 4 
Stopped doing this because of your eyesight ........ 5 
Stopped doing this for other reasons or not 
interested in doing this ...................................... 6 
13. Because of your eyesight, how much difficulty do you have visiting 
with people in their homes, at parties, or in restaurants ? 
(READ CATEGORIES AS NEEDED) 
(Circle One) 
No difficulty at all ...................................................... 1 
A little difficulty ......................................................... 2 
Moderate difficulty .................................................... 3 
Extreme difficulty ..................................................... 4 
Stopped doing this because of your eyesight ........ 5 
Stopped doing this for other reasons or not 
interested in doing this ...................................... 6 
 
 
 
14. Because of your eyesight, how much difficulty do you have going out 
to see movies, plays, or sports events? 
(READ CATEGORIES AS NEEDED) 
(Circle One) 
No difficulty at all ...................................................... 1 
A little difficulty ......................................................... 2 
Moderate difficulty .................................................... 3 
Extreme difficulty ..................................................... 4 
Stopped doing this because of your eyesight ........ 5 
Stopped doing this for other reasons or not 
interested in doing this .......................................6 

IRB NUMBER: HSC-MS-15-1053 
IRB APPROVAL DATE: 087/2002/2020 
© R1996 
 
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15. Now, I’d like to ask about driving a car. Are you currently driving, at 
least once in a while? 
(Circle One) 
 
Yes. ....................... 1 Skip To Q 15c 
 
No ......................... 2 
 
 
 
15a. IF NO, ASK: Have you never driven a car or have you given up 
driving? 
(Circle One) 
 
Never drove. ....... 1 Skip To Part 3, Q 17 
Gave up ............... 2 
 
 
 
15b. IF GAVE UP DRIVING: Was that mainly because of your 
eyesight, mainly for some other reason, or because of both your 
eyesight and other reasons? 
 
(Circle One) 
 
Mainly eyesight.....................................   1   Skip To Part 3, Q 17 
 
Mainly other reasons...........................   2   Skip To Part 3, Q 17 
Both eyesight and other reasons .... 3 Skip To Part 3, Q 17 
 
 
15c. IF CURRENTLY DRIVING: How much difficulty do you have 
driving during the daytime in familiar places? Would you say 
you have: 
 
(Circle One) 
No difficulty at all ................................ 1 
A little difficulty ................................... 2 
Moderate difficulty .............................. 3 
Extreme difficulty ................................ 4 

IRB NUMBER: HSC-MS-15-1053 
IRB APPROVAL DATE: 087/2002/2020 
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16. How much difficulty do you have driving at night? Would you say you 
have: (READ CATEGORIES AS NEEDED) 
 
(Circle One) 
No difficulty at all ...................................... 1 
A little difficulty ........................................ 2 
Moderate difficulty ................................... 3 
Extreme difficulty ..................................... 4 
Have you stopped doing this because 
of your eyesight ................................... 5 
Have you stopped doing this for other 
reasons or are you not interested in 
doing this ............................................. 6 
 
 
 
16a. How much difficulty do you have driving in difficult conditions, such 
as in bad weather, during rush hour, on the freeway, or in city traffic? 
Would you say you have: 
(READ CATEGORIES AS NEEDED) 
(Circle One) 
No difficulty at all ...................................... 1 
A little difficulty ........................................ 2 
Moderate difficulty ................................... 3 
Extreme difficulty ..................................... 4 
Have you stopped doing this because 
of your eyesight ................................... 5 
Have you stopped doing this for other 
reasons or are you not interested in 
doing this ............................................. 6 

IRB NUMBER: HSC-MS-15-1053 
IRB APPROVAL DATE: 087/2002/2020 
© R1996 
 
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PART 3: RESPONSES TO VISION PROBLEMS 
 
The next questions are about how things you do may be affected by your 
vision. For each one, I’d like you to tell me if this is true for you all, most, 
some, a little, or none of the time. 
(Circle One On Each Line) 
READ CATEGORIES: 
All of 
the 
time 
Most of 
the 
time 
Some 
of the 
time 
A little 
of the 
time 
None of 
the 
time 
 
 
 
17. Do you accomplish less 
than you would like 
because of your vision? 
1 
2 
3 
4 
5 
 
 
18. Are you limited in how 
long you can work or do 
other activities because of 
1 
2 
3 
4 
5 
your vision?....................... 
19. How much does pain or 
discomfort in or around 
your eyes, for example, 
burning, itching, or 
aching, keep you from 
doing what you’d like to 
be doing? Would you say: 
1 
2 
3 
4 
5 

IRB NUMBER: HSC-MS-15-1053 
IRB APPROVAL DATE: 087/2002/2020 
© R1996 
 
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For each of the following statements, please tell me if it is definitely true, 
mostly true, mostly false, or definitely false for you or you are not sure. 
(Circle One On Each Line) 
 
Definitely 
True 
20. I stay home most of the time 
Mostly 
True 
Not 
Sure 
Mostly 
False 
Definitely 
False 
because of my eyesight. ....... 1 
2 
3 
4 
5 
21. I feel frustrated a lot of the 
time because of my 
eyesight .................................. 1 
2 
3 
4 
5 
22. I have much less control 
over what I do, because of 
my eyesight. ........................... 1 
2 
3 
4 
5 
23. Because of my eyesight, I 
have to rely too much on 
what other people tell me... 
1 
2 
3 
4 
5 
24. I need a lot of help from 
others because of my 
eyesight. ................................. 1 
2 
3 
4 
5 
25. I worry about doing things 
that will embarrass myself 
or others, because of my 
eyesight. ................................. 1 
2 
3 
4 
5 
 
 
That’s the end of the interview. Thank you very much for your 
time and your help. 

IRB NUMBER: HSC-MS-15-1053 
IRB APPROVAL DATE: 087/2002/2020 
© R1996 
 
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Appendix of Optional Additional Questions 
 
SUBSCALE: GENERAL HEALTH 
 
A1. How would you rate your overall health, on a scale where zero is as 
bad as death and 10 is best possible health? 
 
(Circle One) 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Worst 
Best 
 
SUBSCALE: GENERAL VISION 
 
A2. How would you rate your eyesight now (with glasses or contact lens 
on, if you wear them), on a scale of from 0 to 10, where zero means the 
worst possible eyesight, as bad or worse than being blind, and 10 
means the best possible eyesight? 
 
(Circle One) 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Worst 
Best 
 
SUBSCALE: NEAR VISION 
 
A3. Wearing glasses, how much difficulty do you have reading the small 
print in a telephone book, on a medicine bottle, or on legal forms? 
Would you say: 
(READ CATEGORIES AS NEEDED) 
(Circle One) 
No difficulty at all ..................................................... 1 
A little difficulty ......................................................... 2 
Moderate difficulty .................................................... 3 
Extreme difficulty ..................................................... 4 
Stopped doing this because of your eyesight ........ 5 
Stopped doing this for other reasons or not 
interested in doing this ...................................... 6 

IRB NUMBER: HSC-MS-15-1053 
IRB APPROVAL DATE: 087/2002/2020 
© R1996 
 
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A4. Because of your eyesight, how much difficulty do you have figuring 
out whether bills you receive are accurate? 
(READ CATEGORIES AS NEEDED) 
(Circle One) 
No difficulty at all ...................................................... 1 
A little difficulty ......................................................... 2 
Moderate difficulty .................................................... 3 
Extreme difficulty ..................................................... 4 
Stopped doing this because of your eyesight ....... 5 
Stopped doing this for other reasons or not 
interested in doing this ...................................... 6 
A5. Because of your eyesight, how much difficulty do you have doing 
things like shaving, styling your hair, or putting on makeup? 
(READ CATEGORIES AS NEEDED) 
(Circle One) 
No difficulty at all ...................................................... 1 
A little difficulty ......................................................... 2 
Moderate difficulty .................................................... 3 
Extreme difficulty ..................................................... 4 
Stopped doing this because of your eyesight ........ 5 
Stopped doing this for other reasons or not 
interested in doing this ...................................... 6 
SUBSCALE: DISTANCE VISION 
 
A6. Because of your eyesight, how much difficulty do you have 
recognizing people you know from across a room? 
(READ CATEGORIES AS NEEDED) 
(Circle One) 
No difficulty at all ...................................................... 1 
A little difficulty ......................................................... 2 
Moderate difficulty .................................................... 3 
Extreme difficulty ..................................................... 4 
Stopped doing this because of your eyesight ........ 5 
Stopped doing this for other reasons or not 
interested in doing this ...................................... 6 

IRB NUMBER: HSC-MS-15-1053 
IRB APPROVAL DATE: 087/2002/2020 
© R1996 
 
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A7. Because of your eyesight, how much difficulty do you have taking part 
in active sports or other outdoor activities that you enjoy (like golf, 
bowling, jogging, or walking)? 
(READ CATEGORIES AS NEEDED) 
 
(Circle One) 
No difficulty at all ...................................................... 1 
A little difficulty ......................................................... 2 
Moderate difficulty .................................................... 3 
Extreme difficulty ..................................................... 4 
Stopped doing this because of your eyesight ....... 5 
Stopped doing this for other reasons or not 
interested in doing this ...................................... 6 
 
A8. Because of your eyesight, how much difficulty do you have seeing and 
enjoying programs on TV? 
(READ CATEGORIES AS NEEDED) 
(Circle One) 
No difficulty at all ...................................................... 1 
A little difficulty ......................................................... 2 
Moderate difficulty .................................................... 3 
Extreme difficulty ..................................................... 4 
Stopped doing this because of your eyesight ........ 5 
Stopped doing this for other reasons or not 
interested in doing this ...................................... 6 
 
 
SUBSCALE: SOCIAL FUNCTION 
 
A9. Because of your eyesight, how much difficulty do you have 
entertaining friends and family in your home? 
(READ CATEGORIES AS NEEDED) 
(Circle One) 
No difficulty at all ...................................................... 1 
A little difficulty ......................................................... 2 
Moderate difficulty .................................................... 3 
Extreme difficulty ..................................................... 4 
Stopped doing this because of your eyesight ....... 5 
Stopped doing this for other reasons or not 
interested in doing this ...................................... 6 

IRB NUMBER: HSC-MS-15-1053 
IRB APPROVAL DATE: 087/2002/2020 
© R1996 
 
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SUBSCALE: DRIVING 
 
A10.[This items, “driving in difficult conditions”, has been included as item 
16a as part of the base set of 25 vision-targeted items.] 
 
 
 
SUBSCALE: ROLE LIMITATIONS 
 
A11. The next questions are about things you may do because of your 
vision. For each item, I’d like you to tell me if this is true for you all, 
most, some, a little, or none of the time. 
(READ CATEGORIES AS NEEDED) 
(Circle One On Each Line) 
 
All of 
the 
time 
Most of 
the 
time 
Some 
of the 
time 
A little 
of the 
time 
None of 
the 
time 
 
 
a. 
Do you have more help 
from others because of 
your vision?....................... 
 
b. 
Are you limited in the 
kinds of things you can do 
because of your vision?. 
1 
2 
3 
4 
5 
1 
2 
3 
4 
5 

IRB NUMBER: HSC-MS-15-1053 
IRB APPROVAL DATE: 087/2002/2020 
© R1996 
 
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SUBSCALES: WELL-BEING/DISTRESS (#A12) and DEPENDENCY (#A13) 
 
The next questions are about how you deal with your vision. For each 
statement, please tell me if it is definitely true, mostly true, mostly false, or 
definitely false for you or you don’t know. 
 
(Circle One On Each Line) 
 
Definitely 
Mostly 
Not 
Mostly 
Definitely 
True 
True 
Sure 
False 
False 
 
A12. I am often irritable because 
of my eyesight....................... 
 
 
A13. I don’t go out of my home 
alone, because of my 
eyesight. ................................. 
1 
2 
3 
4 
5 
1 
2 
3 
4 
5