A Multi Center Study Comparing the Ex-PRESSTM Mini Glaucoma Shunt to Trabeculectomy in Subjects With Open Angle Glaucoma
Phase: NA
Conditions: Glaucoma
Sponsor: University of Virginia

A Multi-center Study Comparing the  
Ex-PRESSTM Mini Glaucoma Shunt to 
Trabeculectomy in Subjects with Open Angle 
Glaucoma  
 
XVT-01 
 
Revision D: September 5, 2011 

Protocol XVT-01                                                                                                                                 Amendment - 3 
Protocol Table of Changes 
 
Protocol Table of Changes 
 
 
Revision 
Date 
Description 
Paragraphs Changed 
 
05 July 2006 
Original 
NA 
B 
15 March 2007 See below section 
1.0 investigational plan 
9.1 Study synopsis – subject population 
9.2 Study Device 
9.3.3 Inclusion criteria 
9.3.4 Exclusion criteria 
12.0 Statistical analysis 
C 
19 March 2008 See below section 
1.0 investigational plan 
9.8 Subjects compensation 
14.0 Participating investigators (will be 
updated for each site under a current 
amendment version)  
 
D 
05 September 
2011 
See below section  
10.5 Record Retention 
14.0 Participating investigators 
 
 
Amendment 2 – Revision C from 19 March 2008  
Purpose / Justification: 
In order to enhance the recruitment rate, Dr. Edward Barnet and Carla Siegfried from Washington 
university in Missouri were added to the XVT study as investigators. In the future more sites will 
be added.  
 
Sites participating in the XVT study:  
Site Number Investigator 
Address 
1.  
Peter A. Netland, MD* 
University of Tennessee Memphis 
956 Court Ave. Memphis, TN 38163 
2.  
Iqbal K. Ahmed, MD 
3200 Erin Mills Pkwy. Unit 1 
Millway Plaza, Mississauga, ON. L5L 1W8. Canada 
3.  
Robert L. Stamper, MD 
University of California 
10 Koret Street. Box 0730. San Francisco,  
CA 94143-0730 
4.  
Marlene R. Moster, MD 
Wills Eye Hospital   
840 Walnut Street 11th floor. Philadelphia, PA 19107 
5.  
Mark B. Sherwood, MD 
University of Florida   
Box 100284, J.H.M.H.C. Gainesville, FL 32610 
6.  
Steve R. Sarkisian, MD 
Dean A. McGee Eye Institute 
608 Stanton L. Young Boulevard.  
Oklahoma City, OK  73104 
7.  
Edward Barnett 
Washington University 
660 South Euclid Ave., CB 8009. St. Louis, MO 63110 
 
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Protocol XVT-01                                                                                                                                 Amendment - 3 
Amendment 3 – Revision D from 05 September 2011  
Purpose / Justification: 
10.5 Record Retention: In accordance with the Coordinating Center’s interpretation of HIPAA, all 
investigators will retain any and all clinical trial material (documentation, photographs, etc) for a 
period of six (6) years following the completion of the study.   
 
14.0 Participating investigators: Dr. Netland is now Faculty at the University of Virginia and the 
University of Virginia is now the Study Coordinating Center.  Dr. Sarwat Salim is now the 
Investigator at the University of Tennessee, Memphis.   
 
Sites participating in the XVT study:  
Site Number Investigator 
Address 
1. 
Sarwat Salim, MD 
University of Tennessee Memphis 
956 Court Ave. Memphis, TN 38163 
2. 
Iqbal K. Ahmed, MD 
3200 Erin Mills Pkwy. Unit 1 
Millway Plaza, Mississauga, ON. L5L 1W8. Canada 
3. 
Robert L. Stamper, MD 
University of California 
10 Koret Street. Box 0730. San Francisco,  
CA 94143-0730 
4. 
Marlene R. Moster, MD 
Wills Eye Hospital   
840 Walnut Street 11th floor. Philadelphia, PA 19107 
5. 
Mark B. Sherwood, MD 
University of Florida   
Box 100284, J.H.M.H.C. Gainesville, FL 32610 
6. 
Steve R. Sarkisian, MD 
Dean A. McGee Eye Institute 
608 Stanton L. Young Boulevard.  
Oklahoma City, OK  73104 
7. 
Edward Barnett 
Washington University 
660 South Euclid Ave., CB 8009. St. Louis, MO 63110 
8. 
Garry Condon, MD 
Allegheny General Hospital 
East Wing Office Building 
420 East North Avenue, Suite 116 
Pittsburgh, PA 15212 
9.  
Peter A. Netland, MD, 
PhD*  
University of Virginia 
1300 Jefferson Park Ave. 
Charlottesville, VA 22903 
 
 
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Protocol XVT-01                                                                                                                                 Amendment - 3 
TABLE OF CONTENT 
1.0 
INVESTIGATIONAL PLAN  ................................................................................................... 6 
2.0 
STUDY PURPOSE  
................................................................................................... 6 
3.0 
RATIONALE FOR THE STUDY .............................................................................................. 6 
4.0 
POTENTIAL RISKS AND BENEFITS ....................................................................................... 6 
5.0 
BACKGROUND  
................................................................................................... 7 
 
5.1 
CLINICAL STUDIES ..................................................................... 7 
6.0 
DEVICE DESCRIPTION  
................................................................................................... 7 
7.0 
STUDY OBJECTIVE  
................................................................................................... 8 
 
7.1 
PRIMARY EFFECTIVENESS END POINTS ...................................... 8 
 
7.2 
SECONDARY EFFECTIVENESS END POINTS ................................. 8 
 
7.3 
PRIMARY SAFETY END POINTS .................................................. 8 
 
7.4 
SECONDARY SAFETY END POINTS ............................................. 8 
8.0 
STUDY CLAIM  
................................................................................................... 9 
9.0 
STUDY PROTOCOL 
................................................................................................... 9 
 
9.1 
STUDY SYNOPSIS........................................................................ 9 
 
9.2 
STUDY DEVICE ........................................................................... 9 
 
9.3 
STUDY POPULATION ................................................................ 10 
 
 
9.3.1  NUMBER OF SUBJECTS .................................................... 10 
 
 
9.3.2   STUDY POPULATION....................................................... 10 
 
 
9.3.3   INCLUSION CRITERIA ..................................................... 10 
 
 
9.3.4   EXCLUSION CRITERIA .................................................... 10 
 
9.4 
SUBJECT ENROLLMENT............................................................. 11 
 
 
9.4.1  INFORMED CONSENT AND ENROLLMENT ........................ 11 
 
 
9.4.2  BASELINE EVALUATION ................................................. 11 
 
9.5 
SURGICAL PROCEDURE ............................................................ 13 
 
 
9.5.1  MATERIALS AND EQUIPMENT.......................................... 13 
 
 
9.5.2  SURGICAL PROCEDURE.................................................... 13 
 
9.6 
FOLLOW UP .............................................................................. 14 
 
9.7 
STUDY WITHDRAWAL .............................................................. 15 
 
9.8 
SUBJECTS COMPENSATION ....................................................... 15 
10.0 
DATA HANDLING  
................................................................................................. 15 
 
10.1 
SUBJECT IDENTIFICATION ........................................................ 15 
 
10.2 
CONFIDENTIALITY ................................................................... 15 
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10.3 
CASE REPORT FORMS .............................................................. 16 
 
10.4 
ADMINISTRATIVE FORMS ......................................................... 16 
 
10.5 
RECORD RETENTION................................................................. 16 
11.0 
SAFETY  
................................................................................................. 16 
 
11.1 
ADVERSE EVENTS .................................................................... 16 
 
11.2 
REPORTING ADVERSE EVENTS ................................................. 17 
 
11.3 
TYPE AND DURATION OF FOLLOW-UP AFTER ADVERSE EVENTS 17 
12.0 
STATISTICAL ANALYSIS  ................................................................................................. 17 
13.0 
COMPLIANCE WITH PROTOCOL ......................................................................................... 17 
14.0 
PARTICIPATING INVESTIGATORS ....................................................................................... 18 
15.0 
REFERENCES  
................................................................................................. 19 
 
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Protocol XVT-01                                                                                                                                 Amendment - 3 
Protocol of Investigational Study 
Study XVT-01 
1.0 Investigational Plan 
A multicenter clinical research study will be conducted in the United States and Canada. A total 
of 120 subjects will be enrolled with 60 subjects in each arm to compare the safety and efficacy 
of the Ex-PRESS mini glaucoma shunt implantation versus trabeculectomy in patients suffering 
from glaucoma.  
2.0 Study Purpose 
The purpose of this study is to compare the safety and effectiveness of the Ex-PRESS mini 
glaucoma shunt to trabeculectomy in reducing the number of post operative complications, 
reducing intraocular pressure (IOP) and reducing the use of hypotensive medications in subjects 
with open-angle glaucoma or ocular hypertension.    
3.0 Rationale for the Study 
Trabeculectomy has been the surgical treatment of choice for primary open angle glaucoma since 
1970s (1), its success rates and complications however are less than ideal. Early hypotony and 
bleb infections are still of concern. 
The Ex-PRESS, a miniature stainless steel glaucoma device approved by FDA since March 
2002, is widely used worldwide for open angle glaucoma patients. This procedure is theoretically 
more reproducible and simple to perform as well as less traumatic to the ocular tissue than 
traditional filtering surgery. 
With regard to the inclusion of subjects diagnosed and being treated for ocular hypertension, 
several recently published studies demonstrate that in patients with elevated IOP, with or without 
the visual field loss or optic nerve damage of glaucoma, lowering IOP provides benefit in long-
term outcome of subsequent visual field loss (2-5).  In any case, all subjects enrolled in the study 
have the opportunity to be treated with ocular hypotensive medications during the follow-up 
period as judged appropriate by the investigator.  
4.0 Potential Risks and Benefits   
The potential risks with the use of the Ex-PRESS are the same, with the same probability of 
occurrence and of the same magnitude, as would be found with conventional glaucoma drainage 
surgery. They include a risk of bleeding, infection, too low an intraocular pressure after surgery, 
failure of the operation to control the intraocular pressure, corneal swelling, risk of implant 
erosion, and double vision.   
The following potential benefits have been identified:   
 If the implant is effective and reduces intraocular pressure, the subject may reduce or 
eliminate glaucoma medication therapy.  
 If the implant is effective and reduces intraocular pressure, the subject may not require 
additional glaucoma surgery.    
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 If the subject requires additional glaucoma surgery post Ex-PRESS implantation, this option 
requires a smaller conjunctival incision than trabeculectomy, therefore sparing more 
conjunctival tissue..  
 This procedure is less invasive than other conventional glaucoma surgeries, thus resulting in 
potentially fewer complications. 
 
5.0 Background 
 
Glaucoma filtering surgery is indicated when glaucomatous damage progresses despite the 
attempt to lower the intraocular pressure (IOP) obtained with pharmacological and/or laser 
treatment. In the past few years, filtering surgery has improved, with an increased likelihood of 
successfully lowering the IOP while minimizing complications. While full thickness filtration 
procedures considerably reduced the IOP, they were associated with early postoperative 
hypotony and related side effects and became progressively less popular. Trabeculectomy has 
been the surgical treatment of choice for open angle glaucoma (OAG) since the 1970s; its 
success rate and complication rate however are less than ideal. Early hypotony and bleb 
infections are still of concern. 
The Ex-PRESS is a miniature stainless steel glaucoma device, developed as an alternative to 
trabeculectomy and to the other types of glaucoma filtering surgery for patients with OAG. The 
Ex-PRESS mini glaucoma shunt is FDA approved since March 2002. This procedure is 
theoretically more reproducible and simple to perform as well as less traumatic to the ocular 
tissue than traditional filtering surgery.  
5.1 Clinical Studies 
Since the Ex-PRESS mini glaucoma shunt was FDA approved, post marketing studies were 
performed and presented in paper publications and meetings (1, 6-20). The Ex-PRESS was found 
to be safe and effective in the treatment of glaucoma subjects. A prospective randomized study 
comparing the Ex-PRESS to trabeculectomy in open angle glaucoma patients was performed in 
the Netherlands. A total of 40 subjects with primary open angle glaucoma were enrolled in each 
study arm and followed for 1 year. The Ex-PRESS implant under a scleral flap was found to 
have a more effective success rate, % IOP reduction and medication reduction compared to 
trabeculectomy (20). 
 
6.0 Device Description 
The Ex-PRESS is a miniature drainage device designed to regulate intraocular pressure in eyes 
suffering from glaucoma. The concept behind the Ex-PRESS is to divert aqueous humor through 
the implant from the anterior chamber to an intrascleral space - the bleb. The Ex-PRESS 
glaucoma implant is manufactured from implantable stainless steel. It consists of a 2-3 mm long 
and 0.4mm outer diameter and 50 micron inner diameter tube, which connects the anterior 
chamber to the intrascleral space. Despite its miniature size, the Ex-PRESS features several 
major structural elements (figure 1): 
1. 
A cannula for draining aqueous humor from the anterior chamber to the 
intrascleral space.  
2. 
A plate to prevent excessive penetration. 
3. 
A spur to prevent extrusion of the Ex-PRESSTM from the eye. 
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Protocol XVT-01                                                                                                                                 Amendment - 3 
4. 
Reserve orifices near the distal end, which constitute an alternative conduit for 
aqueous humor drainage in case of occlusion of the primary (axial) opening of 
the cannula by the iris. 
 
Figure 1: Ex-PRESS  
 
The Ex-PRESS is loaded on a specially designed disposable introducer. The introducer has a 
female Luer Lock base and mounted on a disposable 1 ml syringe. 
7.0 Study Objective 
The study objective is to compare the safety and effectiveness of Ex-PRESS implantation under 
a scleral flap versus trabeculectomy. 
7.1 Primary Effectiveness End Points 
The primary effectiveness measure will be qualified and complete success rate defined as 
IOP≤18mmHg with or without medications in the test group as compared to complete and 
qualified success rate in the concurrent control group at 12 months. 
   
7.2 Secondary Effectiveness End points 
The secondary effectiveness measure will be qualified and complete success rate defined as 
IOP≤18mmHg with or without medications in the test group as compared to qualified and 
complete success rate in the concurrent control group at 24 months. 
7.3 Primary Safety End Points 
Post operative safety profile defined as vitreous loss and hypotony (IOP≤5mmHg) and related 
complications (choroidal effusion, hyphema, shallow/flat AC, leaking bleb). 
 
7.4 Secondary Safety End Points 
Comparison of the incidence of all adverse events that occur during the intra-operative and 
postoperative periods between the two study arms. 
To evaluate and compare the incidence of elevated IOP (IOP spikes) in the immediate 
postoperative period in both study arms.  For this study, an IOP spike will be considered an 
increase of 10mmHg or more from baseline (21).   However, all measurements will be collected 
and analyzed. 
  
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Protocol XVT-01                                                                                                                                 Amendment - 3 
8.0 Study Claim 
The safety of the Ex-PRESS™ is superior and efficacy as good as trabeculectomy in open angle 
glaucoma patients. 
 
9.0 Study Protocol 
9.1 Study Synopsis 
Title: 
A prospective randomized multi-center study to compare the Ex-
PRESSTM  to trabeculectomy in patients with open angle glaucoma 
who failed medical treatment and for which filtering surgery is 
indicated 
Protocol Number: 
XVT-01 
Number of Sites: 
7 sites were approved.  
Study Period: 
2 year, 10 visits: 
Pre-operation, day of surgery, day 1, 1-2 Weeks, Months 1, 3, 6, 12, 
18 and 24 post operation. Additional visits will be performed and 
recorded as required for the optimal treatment and follow up of the 
patient. 
Additional visits are defined as visits that were not preplanned and 
considered emergent. 
Study design: 
A prospective, two arm, active control, unmasked, randomized 
study 
Objectives: 
A prospective randomized trial to compare the safety and efficacy 
of the Ex-PRESS to trabeculectomy in patients with open angle 
glaucoma who failed medical or are allergic to medical treatment 
and for which filtering surgery is indicated  
Control Arm 
Subjects undergoing trabeculectomy with the use of Mitomycin C 
Treatment Arm 
Subjects undergoing Ex-PRESS Under Scleral Flap implantation 
procedure with the use of Mitomycin C 
Subject Population: 
Open angle glaucoma patient's candidates for filtering surgery. 
The patients may have a history of cataract phacoemulsification 
surgery. 
Sample Size: 
Total of 120 subjects with 60 subjects in each arm. Each site can 
enroll a maximum of 30 subjects and a minimum of 5 subjects for 
each study arm. 
Follow-up duration: 
2 years 
Target enrollment period: 
Up to 1 year 
 
9.2 Study Device 
The Ex-PRESS R version miniature glaucoma shunt. 
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Protocol XVT-01                                                                                                                                 Amendment - 3 
9.3 Study Population 
9.3.1 Number of Subjects 
A total of 120 subjects will be enrolled into the study with 60 subjects in each arm. 
 
9.3.2 Study Population 
The study population will consist of subjects diagnosed with open-angle glaucoma (OAG) 
(which includes pseudoexfoliative and pigmentary glaucoma) and subjects diagnosed with ocular 
hypertension (OHT).   Subjects must be currently taking ocular hypotensive medications or 
found to be allergic to hypotensive medications.  Subjects may also have a history of cataract 
phacoemulsification surgery.    
  
All subjects will have IOP of 19mmHg or more.   For example, a subject who is currently taking 
two medications and has a pressure of 21mmHg with cataract phacoemulsification surgery 
performed 12 months before will qualify for enrollment in the study.  A complete listing of 
inclusion and exclusion criteria is presented in section 9.3.3 below.  
9.3.3 Inclusion Criteria 
 
Adult subject over the age of 18  
 
Subject diagnosed with open angle glaucoma (POAG, PXFG or PDSG) or ocular 
hypertension 
 
Subject is a candidate for filtering surgery with intra-operative anti-metabolites 
 
IOP > 18 mmHg on maximum tolerated medial therapy based on two measurements taken 
1 hour apart at the same visit. 
 
Subject willing to attend all follow-up evaluations 
 
Subject willing to sign informed consent. 
9.3.4 Exclusion Criteria 
 
Subject diagnosed with: PACG, NTG, secondary glaucoma, neovascular glaucoma  
 
Subject has history of glaucoma surgery (filtering, glaucoma drainage device, cyclo 
destructive procedures) 
 
Subject has history of penetrating keratoplasty (PKP) 
 
Subject underwent large incision extra capsular cataract extraction 
 
Subject underwent cataract phacoemulsification within the last month  
 
Subject has a visually significant cataract that is planned for extraction at the time of 
filtering surgery or within 12 months thereafter 
 
Any ocular disease or history in the operated eye other than glaucoma and cataract, such as 
uveitis, ocular infection, severe dry eye, severe blepharitis , active proliferative retinopathy, 
ICE syndrome, epithelial or fibrous down growth, aphakia, and ocular pathology that may 
interfere with accurate IOP measurements 
 
Subject has vitreous present in the anterior chamber for which vitrectomy is anticipated 
 
IOP of ≤18mmHg 
 
Subject participates in any other concurrent ocular investigation. 
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Protocol XVT-01                                                                                                                                 Amendment - 3 
9.4 Subject Enrollment 
9.4.1 Informed Consent and Enrollment 
The informed consent/patient information sheet written in the subject’s native language will be 
explained to each prospective subject by the investigator or a trained clinical professional.  The 
final informed consent form must be approved by the Institutional Review Board (IRB).  
Once the subject has been informed of all aspects of the study, the subject will then be given a 
choice to voluntarily confirm his or her participation in the study as documented by completion 
of the Informed Consent.  After signing the Informed Consent and the HIPAA (Health Insurance 
Portability and Accountability Act) authorization, the subject can then proceed with the 
screening evaluation.     
  
The subject has the right to withdraw from the study at any time without consequences, as 
indicated in the Patient Informed Consent documentation. 
9.4.2 Baseline Evaluation 
After obtaining an understanding of the purpose of this study, reviewing and signing the 
informed consent form, all potential subjects will undergo an examination in order to determine 
their eligibility for this study.    
  
The screening examination will consist of applanation tonometry to measure IOP, general slit-
lamp biomicroscopy to review the overall health of the eye, visual acuity (VA) measurements, 
and a review of current medications and prior surgeries.    All information should be compared to 
the specific inclusion and exclusion criteria in order to determine if the subject is eligible to 
participate in the study.   
The following criteria are provided below to assist with appropriate screening for all subjects in 
this study:  
  
 
Diagnosis  
Investigator is to provide the diagnosis in each eye, as either ocular hypertension (elevated IOP 
without evidence of visual field loss or cupping of the optic nerve head) or glaucoma (elevated 
IOP with either glaucomatous visual field loss, as judged by automated threshold visual field 
testing, or cupping of the optic nerve head.  
  
 
Measurement of intraocular pressure  
Each time IOP is measured, the surgeon or technician is to utilize a Goldmann tonometer, 
however, an independent observer should read the measurement and then record the 
measurement to minimize observer bias.   
Two measurements should be taken and the mean recorded on the case report form UNLESS 
they differ by more than 2 mmHg in which case a third measurement is taken and the median 
value is recorded.  
    
 
Visual Field Examination  
Visual fields must be automated threshold visual fields (e.g., 30-2 or 24-2 Humphrey).  SITA 
Standard visual fields are required.  Visual fields must be reliable, defined as less than 33% false 
positives, false negatives, and fixation losses.   
  
The visual field must be performed within three to six months of study entry and meet the 
aforementioned requirements.  Both the test eye and the fellow eye should have visual field data.  
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Visual fields are to be performed with a non-dilated pupil unless, in the opinion of the 
investigator, the pupil is so miotic that dilation is required (e.g., < 3 mm).  If dilation was 
performed at baseline, it should be performed at all subsequent visual field examinations.  
However, dilation should not be performed before the IOP measurement on the appropriate 
visits.  
  
For OAG subjects and in accordance with the American Academy of Ophthalmology (AAO) 
Preferred Practice Patterns, the severity of glaucoma damage can be assessed as follows: (1) 
Mild – characteristic optic nerve abnormalities are consistent with glaucoma, but there is a 
normal visual field and (2) Moderate – visual field abnormalities are in one hemifield and not 
within 5 degrees of fixation.  
  
For OHT subjects, qualifying visual fields must be normal and reliable in the study eye.   
 
 
Cup-to-Disc Ratio  
A numerical expression indicating the percentage of disc occupied by the optic cup.  A score 
from 0.1 to 0.9 (in 0.1 increments) should be indicated. 
 
 
Visual Acuity 
Best corrected visual acuity will be measured at baseline and at each follow-up visit. Visual 
acuity will be measured using Snellen line method. 
  
If a subject satisfies all inclusion and exclusion criteria the subject will be enrolled into the study. 
The subject is then randomized to participate in either Group A or Group B using the sealed 
envelope method of randomization. 
 
Group A  
Subjects will undergo implantation of the Ex-PRESS mini glaucoma shunt. 
Group B  
Subjects will undergo standard trabeculectomy.  
 
 
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9.5 Surgical Procedure 
9.5.1 Materials and Equipment 
A listing of general equipment and materials needed for the preoperative, operative, and 
postoperative steps of the investigational study is provided below.  
Goldmann Applanation Tonometer, Handheld direct ophthalmoscope, Viscoelastic Solution,    
Balanced Salt Solution, toothed forceps, tying forceps, non-toothed forceps, scissors, cautery, 
speculum, blades, punch, 25G or 23G needle and Ex-PRESS mini glaucoma shunt. 
 
9.5.2 Surgical procedure 
Ex-PRESS implantation procedure 
 
Local or topical anesthesia is administered and the eye is prepared and covered using 
conventional sterile procedures. Implantation is performed using a special introducer, 
conventional microsurgical instruments and a surgical microscope.  
The Ex-PRESS, mounted on its introducer is inserted into the anterior chamber at the limbus 
through the sclera under the scleral flap. 
The implantation procedure may be performed as follows: 
1. 
Creation of a fornix or limbal based conjunctival flap in the upper quadrants  
2. 
Creation of a limbal-based scleral flap extending into clear cornea  
3. 
Delicate application of MMC solution onto the sclerectomy bed. (MMC concentration 
0.4mg/ml for 1-3 minutes) 
4. 
Penetration into the anterior chamber using a 23-25G needle, halfway between the white 
sclera and the clear cornea (in the center of the grey zone), and creation of a track incision 
at the limbus  
5. 
Prior to implantation, a thorough mobility check should be performed 
6. 
Implantation of the Ex-PRESS implant loaded on its introducer, through that pre-incision  
7. 
Withdrawal of the introducer 
8. 
Tucking the plate under the scleral flap, and verification of its position  
9. 
Suturing the scleral flap with sutures  
After the implantation procedure, antibiotics and steroids are administered topically, the eye is 
covered with a pad and the patient is discharged.  
 
Standard trabeculectomy procedure 
 
1. 
Creation of a fornix or limbal based conjunctival flap in the upper quadrants  
2. 
Creation of a limbal-based scleral flap extending into clear cornea 
3. 
Delicate application of MMC solution onto the sclerectomy bed. (MMC 
concentration 0.4mg/ml for 1-3 minutes) 
4. 
Creation of fistula 1mm x 2mm in size 
5. 
Iridectomy 
6. 
Suturing the scleral flap 
7. 
Repositioning of the conjunctiva with sutures 
After the procedure, antibiotics and steroids are administered topically, the eye is covered with a 
pad and the patient is discharged. 
 
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9.6 Follow up 
All subjects will participate in defined follow-up visits for two years.  Follow up visits include 
day of surgery, day 1, 1-2 Weeks, Months 1, 3, 6, 12, 18 and 24 post surgery. Additional visits 
will be performed and recorded as required for the optimal treatment and follow up of the 
patient. Additional visits are defined as visits that were not preplanned and considered emergent. 
Table 1 presents the activities to be performed at each follow up visit. 
 
Table 1: Follow-up Activities 
Activity 
Screening Surgery 
1 
Day 
1-2 
Wk 
1 
Mo 
3 
Mo 
6 
Mo 
12 
Mo 
18 
Mo 
24 
Mo 
Ophthalmology 
Exam 
X 
 
 
 
 
 
 
 
 
 
Medical 
History 
X 
 
 
 
 
 
 
 
 
 
Medication 
Assessment 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Visual Field 
X 
 
 
 
 
 
 
X 
 
X 
CD ratio 
X 
 
 
 
 
 
 
X 
 
X 
Slit-lamp 
Exam 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Visual Acuity 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Fundus Exam 
X 
 
 
 
 
 
 
X 
 
X 
IOP 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Procedure 
 
X 
 
 
 
 
 
 
 
 
Adverse Event 
Assessment 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Protocol 
Deviation 
Assessment 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Intraocular pressure measurements during follow-up visits 
Each time IOP is measured, the surgeon or technician is to utilize a Goldmann tonometer, 
however, an independent observer should read the measurement and then record the 
measurement to minimize observer bias.   
Two measurements should be taken and the mean recorded on the case report form UNLESS 
they differ by more than 2 mmHg in which case a third measurement is taken and the median 
value is recorded. 
All attempts should be made to conduct each follow-up evaluation within the specified time 
intervals (Table 2). 
 
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Table 2: Follow up examination schedule 
Follow up visit 
Acceptable Time Interval (Days from 
Procedure) 
Day 1 pos-op 
Day 1 post op 
7-14 days post-op 
7-14 days post-op 
1 month post-op 
30 days ± 7 days 
3 months post-op 
90 days ± 14 days 
6 months post-op 
180 days ± 21 days 
12 months post-op 
360 days ± 30 days 
18 months post-op 
540 days ± 30 days 
24 months post-op 
720 days ± 30 days 
 
9.7 Study Withdrawal 
All subjects have the right to withdraw at any point during the treatment without prejudice.  The 
investigator can discontinue any subject at any time if medically necessary.  If a subject 
withdraws prematurely from the study, a genuine effort must be made to determine the reason(s) 
why the subject discontinued the study.  The reason must be recorded. 
 
9.8 Subjects Compensation 
Subjects will be compensated up to 100 USD for traveling and parking fee, against receipts. Half 
of the payment and up to 50 USD will be given at 12 months visit, and 50 USD at 24 months 
visit. The payment will be given by the study staff (e.g. site study coordinator/ clinical 
administrator/ investigator). 
  
10.0 Data Handling 
   
10.1 Subject Identification 
The subjects will be identified by a 2 digit sequential subject number.   The initials for each 
subject will also be included on CRFs.  In this way, information contained in the study records 
will be kept as confidential as possible. The allocation subject number will be as follows:  
XVT __ __ (Site number) - __ __ __ (subject enrollment number). Subject initials will include 
three letters, first letter of first name, middle name and last name. In cases where subject does not 
have a middle name a dash sign will be entered.   
10.2   Confidentiality 
All medical records associated with this clinical investigation will be made available for review 
by designated personel and governmental agencies involved.  The results of the study may be 
published in the future for scientific purposes, but the identity (name) of each subject will not be 
revealed.  All records will be stored in a secure area at the investigator’s facility 
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10.3 Case Report Forms 
The data from this study will be collected using the following forms: 
CRF 1 – Initial Data Sheet  
CRF 2 – Operative Form  
CRF 3 – Follow-Up Form (to be used for all follow-up visits)   
CRF 4 – Adverse Event Form  
CRF 5 – Protocol Deviation Form  
10.4 Administrative Forms 
The administrative forms include the Subject Log Form.  
10.5 Record Retention 
The investigator will retain any and all clinical trial material (documentation, photographs, etc.) 
for a period of six (6) years following the completion of the study.  
11.0 Safety 
At each visit, the ocular health of each subject will be assessed.  The cornea, anterior chamber, 
trabecular meshwork, and implant location (if applicable) will be examined.  If any abnormalities 
are observed, they are to be noted (type and location) within the case report forms. 
11.1 Adverse Events  
 Any ocular adverse events occurring during the trial whether they are considered to be device 
related or not must be documented in the subject’s records.  Date and time of the event, its 
severity, treatment (if any) and the assessed relationship of the event to the study will be 
recorded on CRF 4 Adverse Event Form.  Conditions which exist at the time the subject is 
enrolled do not need to be recorded on the Adverse Event Form as adverse events unless they 
increase in severity during the study.     
  
A brief overview of the differences between anticipated, unanticipated and serious adverse 
events is provided below:    
  
 
Anticipated Adverse Events  
Anticipated adverse events include those that might reasonably be expected to occur in this study 
because they are associated with glaucoma surgical procedures.    
  
 
Unanticipated Adverse Events  
  
Unanticipated adverse device effects (UADE) include any serious adverse effects on health or 
safety or any life-threatening problem or death caused by or likely directly related to the Ex-
PRESS mini shunt or the placement of the Ex-PRESS mini shunt within the eye that are not 
typically associated with glaucoma surgical procedures.  
 
 
Serious Adverse Events  
  
Serious adverse events include those events that require or prolong hospitalization, require 
surgical intervention, are sight or life-threatening or fatal, or result in significant disability or 
incapacity.    
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11.2   Reporting Adverse Events  
All serious adverse events (whether anticipated or unanticipated) must be reported to the 
reviewing IRB according to their guidelines given..  
All adverse events should be documented by completing CRF 4, Adverse Event Form and a 
specific IRB AE form (if applicable).  
  
Identification and collection of adverse event information will be the responsibility of the study 
investigator.  The investigator will follow the Declaration of Helsinki in order to ensure the 
safety of all subjects.  
 
11.3 Type and duration of follow-up after adverse events 
The investigator is responsible for recommending the type and duration of follow-up for each 
subject who experiences an adverse event.  All events must be followed until study completion, 
complete resolution or resolution with sequelae. All details must be documented on CRF 6, 
Adverse Event Form.    
12.0 Statistical Analysis 
The data provided from this randomized controlled study are intended to provide a reasonable 
assurance of safety and effectiveness for the Ex-PRESS mini shunt compared to standard 
trabeculectomy.    
   
The primary safety and effectiveness end points are provided in sections 7.1-7.4 of this protocol.   
The data will be analyzed using the Fishers exact test p-value and Student’s paired t test p-value 
comparison. Success rate will be analyzed using Kaplan-Meier survival analysis curves. Phakic 
and pseudophakic patients will be explored as a possible covariate in the efficacy and safety analysis. 
13.0 Compliance with Protocol 
The investigator shall conduct this investigation in accordance with the investigational plan, 
applicable FDA regulations, HIPAA Health Insurance and Accountability Act and any 
conditions of approval imposed by an IRB. 
 
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14.0 Participating Investigators 
The investigational sites recruited to participate in this multicenter study are listed below in 
Table 3: 
 
Table 3: Investigational sites for the XVT-01 study 
Site Number Investigator 
Address 
1.  
Sarwat Salim, MD 
University of Tennessee Memphis 
956 Court Ave 
Memphis, TN 38163 
2.  
Iqbal(Ike) K. Ahmed, 
MD 
3200 Erin Mills Pkwy. Unit 1 
Millway Plaza 
Mississauga, ON. L5L 1W8. 
Canada 
3.  
Robert L. Stamper, MD 
University of California 
Box 0730 
10 Koret Street 
San Francisco, CA 94143-0730 
4.  
Marlene R. Moster, MD 
Wills Eye Hospital   
840 Walnut Street 11th floor  
Philadelphia, PA 19107 
5.  
Mark B. Sherwood, MD 
University of Florida   
Box 100284, J.H.M.H.C.    
Gainesville, FL 32610 
6.  
Steve R. Sarkisian, MD 
Dean A. McGee Eye Institute 
608 Stanton L. Young Boulevard 
Oklahoma City, OK  73104 
7.  
Edward Barnett 
Washington University 
660 South Euclid Ave., CB 8009 
St. Louis, MO 63110 
8.  
Garry Condon, MD 
Allegheny General Hospital 
East Wing Office Building 
420 East North Avenue, Suite 116 
Pittsburgh, PA 15212 
9.  
Peter A. Netland, MD, 
PhD*  
University of Virginia 
1300 Jefferson Park Ave. 
Charlottesville, VA 22903 
 
* Principal Investigator  
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15.0 References  
1. 
C E Traverso, et al. Long term effect on IOP of a stainless steel glaucoma drainage 
implant (Ex-PRESS) in combined surgery with phacoemulsification. Br J Ophthalmol 
2005;89:425–429. 
2. 
Heijl A, Leski MC, Brentsson B, et al.  Reduction of intraocular pressure and glaucoma 
progression: results from the early manifest glaucoma trial.  Arch Ophthalmol 
2002;120:1268-79.  
3. 
Kass MA, Heuer DK, Higginbotham EJ, et al.  The ocular hypertension treatment 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.  
4. 
Lichter PR, Musch DC, Gillespie BW, et al.  Interim Clinical Outcomes in the 
Collaborative Initial Glaucoma Treatment Study Comparing Initial Treatment 
Randomized to Medications of Surgery.  Ophthalmology 2001; 108:1943-53.  
5. 
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. 
6. 
E Dahan, T R Carmichael. Implantation of a Miniature Glaucoma Device Under a Scleral 
Flap. J Glaucoma 2005;14:98–102  
7. 
A Mermoud. Ex-PRESS implant Fast, simple, safe, efficient?. Br J Ophthalmol 
2005;89:396–397.  
8. 
Verbraak FD, de Bruin DM, Sulak M, de Jong LA, Aalders M, Faber DJ, van Leeuwen 
TG. Optical coherence tomography of the Ex-PRESS miniature glaucoma implant. Lasers 
Med Sci. 2005;20(1):41-4.  
9. 
F.De Feo, M.Papadia, G.Bricola, C.E. Traverso. Long Term Efficacy and Safety of a 
Stainless Steel Glaucoma Drainage Implant (Ex-PRESS™). ARVO 2005  
10. 
P.J. Maris, M.E. Smith, P.A. Netland. Clinical Outcomes With the Ex-PRESS Miniature 
Glaucoma Implant. ARVO 2005  
11. 
J.F. Lopes, M.R. Moster, S.Wamsley, L.Haim, U.Altangerel, D.Lankaranian, 
J.Fontanarosa, W.C. Steinmann. ExPRESS Shunt Implantation With Scleral Flap 
Technique for Complicated Glaucoma. ARVO 2005  
12. 
C.H. Karabatsas, A.Katsanos, A.Polychronakos, M.Pefkianaki, D.Z. Chatzoulis. Ex-Press 
Mini Glaucoma Valve (Optonol) Provides Better Long Term Intraocular Pressure Control 
When Placed Under a Scleral Flap. ARVO 2005 
13. 
E.Dahan, T.R. Carmichael. The Surgical Treatment of Neovascular Glaucoma With a 200 
Micron Miniature Glaucoma Shunt. ARVO 2005  
14. 
P. J. Maris, K. Ishida, P.A. Netland. Clinical Outcomes of the Ex-PRESS Miniature 
Glaucoma Implant. AAO October 2005. 
15. 
E. Dahan, M. Ben-Hur. Performance of Two Different Versions of the Ex-PRESS Mini-
Shunt, Under a Scleral Flap in Open Angle Glaucoma Patients. ARVO May 2006. 
16. 
D. Johnson, C. Bair, J. Evangelista, R. Trespalacios, K. Mitchell, J. Frankel, R. Davis.  
Ex-PRESS Shunt Under a Scleral Flap as Primary Surgical Treatment for Open Angle 
Glaucomas. ARVO May 2006.  
17. 
J.A. Evangelista, D.L. Johnson, R. Trespalacios, J. Frankel. Ex-PRESS Shunt Under a 
Scleral Flap for Neovascular Glaucoma. ARVO May 2006.  
18. 
F.De Feo, A.Bagnis, G.Bricola, C.E. Traverso.  Efficacy and Safety of a Stainless Steel 
Glaucoma Drainage Device Implanted Under a Scleral Flap. ARVO May 2006.  
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19. 
R. Reis, D. Lankaranian, J.C. Ramos-Esteban, M.R. Moster, J.F. Lopes. Intermediate-
Term Results of Ex-PRESS Miniature Glaucoma Implant Under Scleral Flap. ARVO 
May 2006. 
20. 
L.A. De Jong Ex-PRESS Mini shunt Under Scleral Flap Compared to Standard 
Trabecelectomy. ARVO May 2006.  
21. 
Robin, AL.  The Effect of topical apraclonidine on the frequency of intraocular pressure 
elevations after combined extracapsular cataract extraction and trabeculectomy. 
Ophthalmology 1993;100:628-33