Comparison of Silicone and Porous Plate Ahmed Glaucoma Valves
Phase: NA
Conditions: Glaucoma
Sponsor: Peter Netland, MD

Comparison of Silicone and Porous Plate Ahmed Glaucoma Valves        
CONFIDENTIAL                    
Version: March 25, 2015  
 
 
 
 
 
Comparison of Silicone and Porous Plate Ahmed Glaucoma Valves 
 
Protocol Version Date: March 25, 2015  
 
 
 
Sponsor: 
 
University of Virginia 
 
 
 
 
Department of Ophthalmology 
 
 
 
P.O. Box 800715 
 
 
 
Charlottesville, VA  22908-0715 
 
 
 
Tel: (434) 243-2852 
 
 
 
Fax: (434) 243-4393 
 
 
Correspondence: 
Peter A. Netland, M.D, Ph.D. 
 
 
 
Department of Ophthalmology 
 
 
 
University of Virginia 
 
 
 
 
 
 
1300 Jefferson Park Ave, Room 2815B / P.O. Box 800715 
 
 
 
Charlottesville, VA USA 22903 
 
 
 
Tel: (434) 982-1086 
 
 
 
Fax: (434) 924-5180 
 
 
Medical Monitor: Peter A. Netland, M.D., Ph.D. 
 
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TABLE OF CONTENTS 
 
1. Introduction and Background  
 
2. Device Description 
 
3. Study Objective 
 
4. Study Hypothesis 
 
5. Study Endpoints 
5.1 Primary Endpoint 
5.2 Secondary Endpoints  
 
6. Study Synopsis 
 
7. Study Population 
7.1 Study Inclusion Criteria 
7.2 Study Exclusion Criteria 
 
8. Study Design 
8.1 Screening Visit / Baseline Evaluation  
8.2 Surgical Procedure 
8.3 Post-Operative Follow-Up Visits 
8.4 Unscheduled Visits 
8.5 Early Withdrawal  
8.6 Schedule of Visit Tests and Procedures 
 
9. Concomitant Medications and Procedures 
9.1 Prohibited Concomitant Medications 
9.2 Glaucoma Medication Management 
9.3 Post-Operative Medications 
9.4 Device Explant, Repositioning, or Replacement 
 
10.  Safety 
10.1 Anticipated Adverse Events 
10.2 Unanticipated Adverse Events 
10.3 Serious Adverse Events 
10.4 Assessment of Adverse Event Severity 
10.5 Reporting Adverse Events 
10.6 Follow-up of Adverse Events 
10.7 Aggregate Review of Adverse Events  
 
11. Statistical Considerations 
11.1 Determination of Sample Size 
11.2 Assessment of Primary Endpoint 
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11.3 Assessment of Secondary Endpoints 
11.4 Accrual 
11.5 Plans for Interim Analysis 
11.6 Plans for Final Analysis  
11.7 Rules for Termination of Study  
 
12. Recruitment 
 
13. Good Clinical Practice 
 
14. Retention of Records 
 
15. References  
 
 
 
 
 
 
 
 
 
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1. Introduction and Background  
Glaucoma with optic nerve damage is usually associated with abnormal elevation 
of intraocular pressure (IOP) in the eye.  Uncontrolled intraocular pressure may 
result in progressive and painless blindness from optic neuropathy.  This damage 
to the optic nerve is permanent and irreversible.  To prevent damage to the optic 
nerve and subsequent visual field loss, the intraocular pressure in the eye may 
be lowered using medical and/or surgical intervention.   
 
Glaucoma drainage devices are helpful in the management of intractable 
glaucoma, which does not respond well to conventional medical and surgical 
therapies.  The Ahmed Glaucoma Valve is a glaucoma drainage device that has 
a flow-resistive valve mechanism.1-3 This valve is helpful in minimizing 
postoperative hypotony and complications associated with hypotony, including 
flat anterior chamber, choroidal effusions, and suprachoroidal hemorrhage.4,5 
 
After Ahmed Glaucoma Valve implantation, patients may require adjunctive anti-
glaucoma medications for adequate control of intraocular pressure.4-6  With 
smaller glaucoma valve implants, such as the Molteno implant, increasing the 
device surface area may lead to lower mean intraocular pressure and fewer 
adjunctive glaucoma medications.7,8   However, additional surface area does not 
dramatically improve the results with larger implants, such as the Ahmed Valve 
and the Baerveldt implant.9-12   In contrast with trabeculectomy, use of adjunctive 
mitomycin C does not appear to improve the results with the Ahmed Glaucoma 
Valve.13 
 
In experimental studies, different glaucoma drainage implant plate materials may 
influence capsule formation and influence the results of glaucoma drainage 
implants.14,15   In clinical comparisons, different plate materials have been 
associated with significant difference of mean postoperative intraocular pressure 
in some16-18  but not in all studies.19,20   In a randomized prospective trial, 
transient elevation of intraocular pressure during the early postoperative period, 
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known as a "hypertensive phase," was less frequent after silicone plate 
compared with polypropylene plate Ahmed Glaucoma Valve implantation.16   In 
addition to implant plate size and material, other variables influencing success of 
glaucoma drainage implant surgery have been identified, including race, 
treatment with silicone oil endotamponade, and neovascular glaucoma.21   
 
A silicone plate Ahmed Glaucoma Valve has demonstrated efficacy and safety in 
clinical studies.16-20 An Ahmed Glaucoma Valve plate constructed with porous 
material, which is Food and Drug Administration (FDA) approved, but has not 
been studied in clinical trials, may offer advantages in reducing encapsulation of 
the implant, thereby potentially improving postoperative intraocular pressure 
control.   
 
2.  Device Description 
Glaucoma drainage implants used in this study are the Ahmed Glaucoma Valve 
(New World Medical, Inc., Rancho Cucamonga, CA)  Model FP7 (silicone plate, 
184 mm2 surface area) and Model M4 (porous polyethylene plate, 191 mm2 
surface area).  Both the Model FP7 and Model M4 are Food and Drug 
Administration-approved for implantation in humans with intractable glaucoma.  
Both of these valves will be supplied free of charge by New World Medical Inc for 
use in this study.  Each participating site will be responsible for obtaining FP7 
and M4 valves from New World Medical.  The valves will not be shipped to UVA 
and then distributed to participating sites.   
 
The Model M4 plate is approximately the same size as the Model FP7 plate (191 
mm2 and 184 mm2 surface area, respectively).  However, the theoretical surface 
area of the M4 is much higher because of the porous nature of the material.  The 
porous polyethylene material is formed by a proprietary process (Porex 
Corporation, Fairburn, GA).  The porous plate material is high density 
polyethylene with a long history of use in surgical implants (MEDPOR Biomaterial 
implants).   Average pore sizes are greater than 100 micro-meters and pore 
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volume is in the 50 percent range, with an interconnecting open pore structure 
that allows for tissue ingrowth.   
 
3. Study Objective 
To evaluate and compare the clinical outcomes after implantation of the porous 
plate (polyethylene) Ahmed Glaucoma Valve with the silicone plate Ahmed 
Glaucoma Valve in subjects with intractable glaucoma. 
 
4. Study Hypothesis 
Eyes undergoing implantation with the porous plate Ahmed Glaucoma Valve are 
less likely to develop an elevation of intraocular pressure during the post-
operative period and subsequently will have lower intraocular pressure and 
possibly require fewer glaucoma medications as compared with the silicone plate 
Ahmed Glaucoma Valve. 
 
5. Study Endpoints 
All study endpoints refer to the selected study eye only and are measured from 
Baseline to 12 months post-operative in the porous plate Ahmed Glaucoma 
Valve group as compared to the silicone plate Ahmed Glaucoma Valve group.   
 
5.1 Primary Endpoint 
The primary endpoint is the mean intraocular pressure in the porous plate 
group as compared to the silicone plate group at 12 months. 
 
5.2 Secondary Endpoints  
(a) The mean number of anti-glaucoma medications in the porous plate 
group as compared to the silicone plate group at 12 months. 
(b) Surgical success in the porous plate group as compared to the silicone 
plate group at 12 months.  Surgical success is defined as:   
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Unqualified surgical success: 5 mmHg < intraocular pressure < 22  
  
mmHg with no loss of light perception and no additional glaucoma  
  
procedures or glaucoma medications.   
  
Qualified surgical success: 5 mmHg < intraocular pressure < 22  
  
mmHg with no loss of light perception and no additional glaucoma  
  
procedures, but with the adjunctive use of glaucoma medications.   
   
6. Study Synopsis 
Title: 
Comparison of Silicone and Porous Plate Ahmed 
Glaucoma Valves 
Study Period: 
12 months, 9 visits: Screening/Baseline; Day of 
Surgery; Post-Operative Days 1 and 7; and Post-
Operative Months 1, 3, 6, 9, and 12.  Unscheduled 
visits will be performed and recorded as required for 
the optimal treatment and follow up of the subject. 
Study design: 
A prospective, two-arm, unmasked, randomized, 
controlled study. 
Objectives: 
A prospective, randomized trial to evaluate and 
compare the clinical outcomes after implantation of the 
porous plate (polyethylene) with the silicone plate 
Ahmed Glaucoma Valve in subjects with intractable 
glaucoma. 
Control Arm: 
Subjects undergoing surgery with the silicone plate 
Ahmed Glaucoma Valve (Model FP7) 
Treatment Arm: 
Subjects undergoing surgery with the porous plate 
Ahmed Glaucoma Valve (Model M4) 
Subject 
Population: 
Patients with intractable glaucoma who are candidates 
for valve surgery.   
Sample Size: 
Total of 88 subjects with a planned 40 subjects in each 
arm. Each site can enroll a maximum of 40 subjects. 
Follow-up 
duration: 
12 months. 
 
7.  Study Population 
This is a prospective, two-arm, unmasked, randomized, controlled study of 80 
enrolled subjects with intractable glaucoma that have not responded to 
conventional medical and surgical therapy.  The study will accrue up to 88 
subjects to allow for a dropout rate of 10 %. 
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7.1  Inclusion Criteria 
• Male or female of any race ≥18 years ≤ 80 years of age. 
• Diagnosis of intractable glaucoma in the study eye, with the exception of 
silicone oil endotamponade induced glaucoma, which has not responded 
to conventional medical and surgical therapy.   
• Elevated intraocular pressure > 21 mmHg in the study eye. Two 
consecutive measurements using Goldmann Applanation Tonometry will 
be obtained and the mean of those two measurements will be considered 
the subject’s baseline intraocular pressure.  
• Subject is a candidate for surgery in the study eye with a glaucoma 
drainage device. 
• Subject is willing and able to sign the informed consent. 
 
7.2 Exclusion Criteria 
• Diagnosis of silicone oil endotamponade induced glaucoma in the study 
eye. 
• History of prior drainage implant surgery in the study eye. 
• History of cyclophotocoagulation of the study eye.   
• Pregnancy. 
• Prisoner.   
 
Eligible subjects may have significant conjunctival scarring, precluding 
trabeculectomy in the study eye.  Presence of diabetes mellitus, prior ocular 
surgery (with the exception of prior drainage implant surgery) or laser treatment 
for glaucoma, and use of glaucoma medications in the study eye will be noted, 
but are not exclusion criteria for determining eligibility.   
 
8. Study Design 
 
8.1   Screening Visit / Baseline Evaluation  (Days -60 to -1) 
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After obtaining informed consent in the patient’s, all potential subjects will 
undergo a baseline examination to determine study eligibility.  Standard-of-
care evaluations for glaucoma patients that are documented by the 
investigator may be utilized as the baseline evaluation to determine subject 
eligibility, provided the evaluations occur within 60 days prior to the planned 
surgical intervention, even if these evaluations occur prior to the subject 
consenting to participate in the study.  This avoids the potentially 
unnecessary repetition of screening evaluations that are a part of the 
standard-of-care for glaucoma patients.   
 
The following examinations, tests, and procedures are required as part of the 
baseline evaluation to determine subject eligibility and must be conducted 
within 60 days of the planned surgical intervention: 
• Signing of the informed consent 
• Review of Inclusion / Exclusion Criteria 
• Demographic Information (Date of Birth, Sex, Self-Identified Ethnicity) 
• Type of Glaucoma (Diagnosis) 
• Review of Medical and Ocular Surgical History 
• Review of Concomitant Systemic Medications 
• Review of Concomitant Glaucoma Medications 
• Review of History of Previous Glaucoma Treatments (laser and surgery) 
• Review of Other Concomitant Ocular Medications 
• Manifest Refraction and Snellen Visual Acuity  
• Intraocular Pressure 
• 
Intraocular Pressure will be measured utilizing Goldmann 
applanation tonometry.  Two consecutive measurements will be obtained 
and the mean of those two measurements will be considered the subject’s 
baseline intraocular pressure. The intraocular pressure should be 
performed at the same time of day at all visits, when possible. 
• Slit Lamp Examination 
• Gonioscopy  
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• Funduscopic Examination  
• 30-2 or 24-2 SITA Standard Humphrey Visual Field (if available, and may 
be used if obtained within 12 months of the planned surgical intervention) 
• Determination of the study eye and subject eligibility (if both eyes qualify, 
the study eye will be the eye with the highest baseline intraocular 
pressure, then worst baseline visual acuity, then the right eye; unless in 
the investigator’s best judgment the other eye should be selected) 
• Urine or Serum Pregnancy Test for women of child-bearing potential (to 
be conducted as part of the site’s standard pre-operative testing).  The 
test must be negative to be eligible to participate.  
 
All ophthalmic tests and examinations are for the selected study eye only.   
If the subject satisfies all inclusion and exclusion criteria, the subject will be 
enrolled into the study.   
 
8.2   Surgical Procedure (Day 0)  
The surgical procedure must be performed within 60 days of the completion 
of the screening evaluation.  The subject will be randomized to undergo 
surgical intervention with either the Model FP7, Silicone Plate Ahmed 
Glaucoma Valve (Group A) or the Model M4, Porous Plate Ahmed Glaucoma 
Valve (Group B), using the sealed envelope method of randomization.  
Randomization will take place on the day of surgery.   
 
The following steps are considered guidelines for implantation of both the 
Model FP7 and Model M4.  However, the use of any specific surgical 
technique or maneuver is at the sole discretion of the surgeon.   
 
1. The implant should be examined and primed prior to implantation.  
Priming is accomplished by injecting 1cc balanced salt solution or 
sterile water through the drainage tube and valve, using a blunt 
26 gauge cannula. 
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2. A fornix-based incision is made through the conjunctiva and 
Tenon’s capsule.  A pocket is formed at the superior quadrant 
between the medial or lateral rectus muscles by blunt dissection 
of Tenon’s capsule from the episclera.   
3. The valve body is inserted into the pocket between the rectus 
muscles and sutured to the episclera.  The leading edge of the 
device should be at least 8-10mm from the limbus.   
4. The drainage tube is trimmed to permit 2-3mm insertion of the 
tube into the anterior chamber.  The tube should be bevel out to 
an anterior angle of 30° to facilitate insertion. 
5. A paracentesis is performed and the anterior chamber is entered 
at the limbus with a sharp 23 gauge needle, parallel to the iris.  
Caution: Care must be taken to ensure that the drainage tube 
does not contact the iris or corneal endothelium after insertion. 
6. The drainage tube is inserted into the anterior chamber 
approximately 2-3mm, through the needle track and parallel to the 
iris.  The leading edge of the device should be 8-10mm from the 
limbus. 
7. The exposed drainage tube is covered with a small piece of 
preserved, donor sclera or pericardium, which is sutured into 
place and the conjunctiva is closed.  Note:  As an alternative, a 
2/3 thickness limbal-based scleral flap may be made.  The tube is 
inserted into the anterior chamber through a 23 gauge needle 
puncture made under the flap.  The flap is sutured closed.   
 
8.3   Post-Operative Follow-Up Visits (1 Day; 7 Day; 1, 3, 6, 9, 12 months) 
Follow-up visits will be conducted at the following post-operative time points: 
• 1 Day Post-Operative (1 Day + 1 day)  
• 7 Day Post-Operative (7 Days +/- 4 days) 
• 1 Month Post-Operative (30 Days +/- 7 days) 
• 3 Months Post-Operative (90 Days +/- 14 days) 
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• 6 Months Post-Operative (180 Days +/- 14 days) 
• 9 Months Post-Operative (270 Days +/- 14 days) 
• 12 Months Post-Operative (360 Days +/- 28 days) 
 
The following examinations, tests, and procedures are required at each post-
operative follow-up visit:  
• Review of Adverse Events and Assessment of Device Complications 
• Review of Concomitant Systemic Medications 
• Review of Concomitant Glaucoma Medications 
• Review of Other Concomitant Ocular Medications 
• Snellen Visual Acuity and Manifest Refraction (per clarification in 
Administrative Letter #2 dated Oct 3, 2013, Manifest Refraction is 
optional). 
• Intraocular Pressure 
• 
Intraocular Pressure will be measured utilizing Goldmann 
applanation tonometry.  Two consecutive measurements will be obtained.  
The intraocular pressure should be performed at the same time of day at 
all visits, when possible. 
• Slit Lamp Examination 
• Gonioscopy (at Months 3, 6, 9, and 12 only)  
• Funduscopic Examination  
• Ultrasound biomicroscopy or Anterior Segment Optical Coherence 
Tomography to measure the capsule thickness around the plates (Months 
6 and 12 only) (optional) 
 
Post-Operative Follow-Up Visits (1 Day; 7 Day; 1, 3, 6, 9, 12 months) 
All ophthalmic tests and examinations are for the selected study eye only.   
 
 
8.4   Unscheduled Visits 
Additional (unscheduled) visits will be performed and recorded as required for 
the optimal treatment and follow-up of the subject.  The tests, exams, and 
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procedures required at the unscheduled visit are dependent upon the reason 
for the unscheduled visit and will be performed at the investigator’s discretion.  
The following tests, exams, and procedures may be conducted at the 
unscheduled visit: 
• Review of Adverse Events and Assessment of Device Complications 
• Review of Concomitant Systemic Medications 
• Review of Concomitant Glaucoma Medications 
• Review of Other Concomitant Ocular Medications 
• Manifest Refraction and Snellen Visual Acuity  
• Intraocular Pressure 
• 
Intraocular Pressure will be measured utilizing Goldmann 
applanation tonometry.  Two consecutive measurements will be obtained. 
The intraocular pressure should be performed at the same time of day at 
all visits, when possible. 
• Slit Lamp Examination 
• Gonioscopy  
• Funduscopic Examination  
• Ultrasound biomicroscopy or Anterior Segment Optical Coherence 
Tomography to measure the capsule thickness around the plates (Months 
6 and 12 only) 
 
8.5   Early Withdrawal 
All subjects have the right to withdraw from the study at any point.  The site 
investigator or the Medical Monitor may discontinue a subject from the study 
for any of the following reasons: 
 
a.   
Noncompliance with the study requirements 
b. 
At the discretion of the Investigator or Medical Monitor, due to 
 
subject safety concerns.   
If a subject withdraws prematurely from the study, a genuine effort must be 
made to determine the reason(s) for the subject’s early discontinuation and 
the subject should complete an Early Withdrawal visit, which includes the 
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same tests, exams, and procedures required at the Month 12 Post-Operative 
Visit.  
 
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8.6   Schedule of Visit Tests and Procedures  
 
 
SCR² 
Day 
0 
POD 
1 
POD 
7 
Mo 
1 
Mo 
3 
Mo 
6 
Mo 
9 
Mo 
12/ 
Early 
Term 
Un-
sched 
Visit 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
Inclusion/ Exclusion 
Criteria Review 
X 
 
 
 
 
 
 
 
 
 
Demographic 
Information 
X 
 
 
 
 
 
 
 
 
 
Glaucoma Diagnosis 
X 
 
 
 
 
 
 
 
 
 
Review of Medical & 
Ocular Surgical History 
X 
 
 
 
 
 
 
 
 
 
Review of Concomitant 
Systemic Medications 
X 
 
 
 
 
 
 
 
 
 
Review of Concomitant 
Glaucoma Medications 
X 
 
 
 
 
 
 
 
 
 
Review of History of 
Previous Glaucoma 
Surgeries 
X 
 
 
 
 
 
 
 
 
 
Review of Other 
Concomitant Ocular 
Medications 
X 
 
 
 
 
 
 
 
 
 
Manifest Refraction & 
Snellen Visual Acuity 
X 
 
X 
X 
X 
X 
X 
X 
X 
X³ 
Intraocular Pressure 
X 
 
X 
X 
X 
X 
X 
X 
X 
X³ 
Slit Lamp Examination 
X 
 
X 
X 
X 
X 
X 
X 
X 
X³ 
Gonioscopy 
X 
 
 
 
 
X 
X 
X 
X 
X³ 
Funduscopic 
Examination 
X 
 
X 
X 
X 
X 
X 
X 
X 
X³ 
Visual Field Test 
X 
 
 
 
 
 
 
 
 
 
Study Eye Determination 
X 
 
 
 
 
 
 
 
 
 
Pre-operative tests 
(labwork, EKG, physical 
exam) ¹ 
X 
 
 
 
 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
 
 
 
Surgical Intervention 
 
X 
 
 
 
 
 
 
 
 
Concomitant Medication 
Review 
 
 
X 
X 
X 
X 
X 
X 
X 
X³ 
Adverse Event Review 
 
 
X 
X 
X 
X 
X 
X 
X 
X³ 
Ultrasound 
Biomicroscopy or 
Anterior Segment OCT³ 
 
 
 
 
 
 
X 
X 
X 
X³ 
1. A serum or urine pregnancy test is required for women of child-bearing potential only, 
prior to randomization.   
2. All Screening Exams must be completed within 60 days of the planned Surgical 
Intervention, except the visual field test which must be completed within 12 months of the 
planned Surgical Intervention.   
3. Optional.  
 
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9. Concomitant Medications and Procedures 
 
9.1 Prohibited Concomitant Medications 
There are no prohibited concomitant ocular or non-ocular medications during 
participation in this study. 
 
9.2 Glaucoma Medication Management 
Use of topical or systemic glaucoma medications will be documented at 
baseline and throughout the post-operative follow-up period for the study eye.  
Glaucoma medications for the study eye should be suspended only on the 
day of surgery and reinstituted, if indicated, with necessary adjustments after 
surgery to manage any elevated intraocular pressure in the study eye.  The 
decision to re-institute glaucoma medications in the study eye will be made at 
the discretion of the investigator.  
 
9.3 Post-operative Medications  
Selection, dosage, and frequency of the study eye post-operative topical 
antibiotic agent and post-operative anti-inflammatory agent will be made at 
the discretion of the investigator.  All prescribed post-operative ocular 
medications must be recorded in the study records. 
 
9.4 Device Explant, Repositioning, or Replacement 
The device may be revised, repositioned, removed, or replaced by the same 
kind of device or another marked drainage device if the original device was 
damaged or determined to be not functioning. If surgical intervention for 
repositioning or replacement is required, the subject will be required at a 
minimum to complete all of the protocol required post-operative visits.  If 
sequalae persist, the subject should be followed until all sequalae are 
considered to be stabilized or resolved.  
 
 
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10. Safety 
 
At each visit, the ocular health of the subject will be assessed.   The cornea, 
anterior chamber, trabecular meshwork, device implant location (if available), and 
fundus will be examined.  Any ocular unanticipated adverse events occurring 
during the study whether they are considered to be device related or not, must be 
documented on the Adverse Event Case Report Form.  Date and time of the 
event, event severity, treatment (if any), and the assessed relationship of the 
event to the study devices will be recorded on the Adverse Event Case Report 
Form.  Conditions that exist at the time the subject is enrolled in the study do not 
need to be recorded on the Adverse Event Form as adverse events, unless they 
increase in severity during the study and constitute an unanticipated adverse 
event..   
 
The collection and recording of unanticipated adverse events will begin at the 
start of the surgical intervention and will end at the subject’s Month 12 or Early 
Termination Visit.  Unanticpated adverse events must be followed until the 
adverse event has recovered or recovered with ongoing sequelae that will likely 
not change in the view of the investigator.  This period may extend beyond study 
termination.  
 
A brief overview of the differences between anticipated, unanticipated and 
serious adverse events is provided. 
 
10.1 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.   Anticipated adverse events for both the porous plate and 
silicone plate glaucoma valves include: 
 
* Wound Leak 
 
* Shallow Anterior Chamber 
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* Flat Anterior Chamber 
 
* Choroidal effusion 
 
* Exposure of Tube, Patch Graft, Plate 
 
* Severe Inflammation 
 
* Tube and/or Flow Obstruction 
 
* Corneal Edema 
 
* Motility Disturbance (i.e. Diplopia) 
 
* Suprachoroidal hemorrhage 
 
* Hypotony (≤ 5 mmHg) 
 
* Elevated intraocular pressure 
 
* Retinal Detachment 
 
  
 
10.2 Unanticipated Adverse Events  
Unanticipated adverse events include any serious adverse effects on health 
or safety or any life-threatening problem or death caused by or likely directly 
related to the Ahmed Glaucoma Valve (M4 or FP7) or the placement of the 
Ahmed Glaucoma Valve (M4 or FP7) within the eye that are not typically 
associated with glaucoma surgical procedures.   
 
10.3 Serious Adverse Events   
Serious adverse events include those events that require (≥ 24 hours) or 
prolong hospitalization, require surgical intervention, are sight or life-
threatening or fatal, or result in significant disability or incapacity.    
 
10.4 Assessment of Adverse Event Severity 
The investigator will make an assessment of event severity for each 
unanticipated adverse event and serious adverse event reported during the 
study according to the following definitions: 
 
Mild: An event that is easily tolerated by the subject, causing minimal 
 
discomfort and not interfering with everyday activities. 
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Moderate: An event that is sufficiently discomforting to interfere with 
 
the subject’s normal everyday activities.  
 
Severe: An event that prevents the subject’s normal everyday activities.   
 
10.5 Reporting Adverse Events   
Identification and collection of anticipated and unanticipated adverse event 
information is the responsibility of the study investigator.  All unanticipated 
adverse events should be documented by completing the Adverse Event 
Case Report Form.  and submitted to the study coordinating site per study 
Manual of Procedures.    All adverse events (whether anticipated or 
unanticipated) should be reported to the Institutional Review Board according to site 
guidelines. 
 
The identification and collection of serious adverse events is the responsibility 
of the study investigator.  All serious adverse events should be documented 
by completion of the Serious Adverse Event Case Report Form.  All Serious 
Adverse events should be reported to the Medical Monitor within 24 hours of 
the site’s notification of the event and to the Institutional Review Board 
according to site guidelines.   
  
10.6 Follow-up of Adverse Events 
The investigator is responsible for recommending the type and duration of 
follow-up for each subject who experiences an adverse event.  All 
unanticipated events must be followed until study completion or adverse 
event resolution or stabilization of adverse event sequelae if the unanticipated 
adverse event(s) persists post study completion.  All follow-up must be 
documented and submitted to the study coordinating site via   the Adverse 
Event Case Report Form within the appropriate time frames per the study 
Manual of Operations.    
 
 
10.7 Aggregate Review of Adverse Events 
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The Medical Monitor will be responsible for the continuous review of 
unanticipated adverse events.   
 
11.  Statistical Considerations 
This prospective, two-arm, unmasked, randomized, controlled trial will evaluate 
and compare the clinical outcomes after implantation of the porous plate 
(polyethylene) Ahmed Glaucoma Valve (M4) with the silicone plate Ahmed 
Glaucoma Valve (FP7) in patients with intractable glaucoma.  Subjects will be 
randomized in a 1:1 ratio to one of two surgical intervention arms - surgical 
intervention with the Model FP7, Silicone Plate Ahmed Glaucoma Valve (Group 
A) or the Model M4, Porous Plate Ahmed Glaucoma Valve (Group B).  The 
computer-generated randomization scheme (using varying block sizes of 2 to 4) 
will be completed by a staff member of the University of Virginia, Department of 
Ophthalmology, whose sole role in this study is to generate the randomization 
scheme.  The subject surgical intervention arm assignment will be placed in a 
sealed envelope, securely delivered to the sites, and will be accessed by the site 
study staff in the site Surgical Admission Suite immediately prior to local 
anesthesia injection for the surgical procedure.  Post-randomization, the 
assigned surgical intervention arm will be unmasked to the subject.    
 
11.1 Sample Size Considerations  
With a sample size of 40 in each group, the power of the study will be 0.8 
(80%) to detect a 1.5 mmHg difference in intraocular pressure with a 
standard deviation of 3 mmHg.  Investigators will screen and treat patients 
.until the study is fully enrolled or the study is terminated.  All subjects 
undergoing surgical intervention will be entered in the statistical analysis. 
Based on prior studies, failure to complete the 12 month post-operative 
period is not likely to exceed 10% of randomized subjects. 
 
11.2 Assessment of the Primary Endpoint   
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The primary efficacy endpoint is the mean intraocular pressure in the 
porous plate group as compared to the silicone plate group at 12 months 
The analysis will compare the changes of intraocular pressure after the 
surgical intervention in the porous plate group as compared to the silicone 
plate group.  Baselines will be compared to check for statistically significant 
differences and, if needed, a change from baseline analysis will be 
performed.  The statistical significance of the differences in intraocular 
pressure will be determined using two-tailed paired t-tests. 
 
11.3 Assessment of the Secondary Endpoints  
Thesecondary endpoint is the mean number of anti-glaucoma medications 
and surgical success in the porous plate group as compared to the silicone 
plate group at 12 months.  The baseline number of medications will be 
compared to check for statistically significant differences and, if needed, a 
change from baseline analysis will be performed.  The statistical 
significance of the differences in the number of medications will be 
determined using two-tailed paired t-tests.  The mean number of 
medications at individual time points will be compared in the two groups.  
Kaplan-Meier survival analysis will be performed for statistical analysis of 
success rates, with comparisons of groups using the log rank test.  
Complications will be compared using comparison of proportions (z) test. 
 
11.4 Accrual  
Maximum study accrual is estimated to be 88 subjects to accrue the 
targeted 80 subjects required to meet the study objectives.  Maximum 
accrual allows for a 5% ineligibility rate and a 5% rate of coming off study 
before the planned surgical intervention.  Once target accrual is reached, 
the study allows those within the screening process to be enrolled.  As this 
allowance is not to exceed 4 patients, up to 84 patients may be treated with 
Ahmed Glaucoma Valves.  Based upon accrual rates to prior drainage 
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implant studies, accrual is estimated at 15 per month; thus, accrual to the 
study should be completed in less than 6 months. 
 
11.5 Plans for Interim Analysis 
There will be no formal interim analysis.  However, for purposes of safety 
and surgical failures only, unanticipated adverse events will be reviewed 
periodically by the Medical Monitor to detect a statistically significant 
increase 
of 
vision-threatening 
complications 
(e.g., 
suprachoroidal 
hemorrhage, endophthalmitis, and surgical failures.  If vision-threatening 
complications and surgical failures exceed a threshold of 30% during the 
study, consideration will be given by the Medical Monitor to terminate the 
study early.   
   
11.6 Plans for Final Analysis  
Subjects will be monitored until they complete the study period.  Primary 
analysis will include all subjects undergoing the study surgical intervention.  
All subjects who receive any study intervention will be monitored for 
adverse events.  Adverse event information will be tabulated by type and 
severity of adverse events.  If the subject is determined to be a treatment 
failure (e.g., increased intraocular pressure, hypotony, loss of light 
perception vision, or additional glaucoma surgery), this will be documented 
in the study database. 
 
11.7 Rules for Termination of Study 
The Medical Monitor will conduct periodic reviews of unanticipated adverse 
events and will terminate the study as necessary.  
 
12.  Recruitment 
To allow the coordinating site to monitor accrual, all study sites must email 
the coordinating site prior to the randomization of each subject.  No other 
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study documentation needs to be sent to the coordinating site at this time 
point.   
13. Good Clinical Practice (GCP) Compliance 
This study will be conducted in accordance with Good Clinical Practice (GCP) 
using the guidance documents and practices offered by the International 
Conference on Harmonization (ICH) and United States Food and Drug 
Administration (FDA), and in accordance with site local regulations.  
 
14. Retention of Records 
The site investigator is responsible for maintaining intact study records for a 
period of at least 6 years following the completion of the study.  Study 
records may be retained for a longer period if specified by local policies. 
 
 
15. References 
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glaucoma implant devices.  Ophthalmic Surg Lasers 1999; 30: 662-667. 
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drainage implants during dynamic and steady-state flow conditions.  
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characteristics of glaucoma drainage implants.  Ophthalmology 1995; 102: 
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7. Heuer DK, Lloyd MA, Abrams DA, Baerveldt G, Minckler DS, Lee MB, 
Martone JF.  Which is better?  One or two?  A randomized clinical trial of 
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17. Hinkle DM, Zurakowski D, Ayyala RS. A comparison of the polypropylene 
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