Clinical trial NCT00666237
Conditions: Glaucoma
Keywords: Tube shunt surgery Trabeculectomy
Sponsor: University of Miami
Start date: 2008-04-01; Completion date: 2021-04-01
Enrollment: 242 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of the Primary Tube Versus Trabeculectomy (PTVT) Study is to compare the long-term safety and efficacy of nonvalved tube shunt surgery to trabeculectomy with mitomycin C in eyes that have not had previous ocular surgery.

Detailed description:

Arms: arm 1: Participants in this group will receive a tube shunt surgery (Baerveldt Glaucoma implant). arm 2: Participants in this group will receive a Trabeculectomy surgery with Mitomycin C
Interventions: intervention 1: Tube shunt surgery intervention 2: Trabeculectomy intervention 3: Mitomycin C
Intervention descriptions: intervention 1: The procedure involves implantation of a Baerveldt consisting of a tube that is connected to an end plate. The tube is inserted into the anterior chamber and shunts aqueous humor to the end plate located in the equatorial region of the eye. The aqueous humor is then absorbed by the tissues around the eye. intervention 2: The procedure involves removal of a small portion of trabecular meshwork and adjacent tissue under a partial thickness scleral flap. Aqueous humor drains into the subconjunctival space producing a filtering bleb. The aqueous humor then diffuse out of the bleb. intervention 3: A fluid retaining sponge soaked in 0.4 mg/ml Mitomycin C will be applied in the region of Trabeculectomy site for about 2 minutes

Protocol documents:
Prot_SAP_ICF_000.pdf: 
PRIMARY TUBE VERSUS 
TRABECULECTOMY 
(PTVT) STUDY 
Manual of Procedures 
Version 7.0 
5/3/2010 
NCT#: NCT00666237 


 
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Table of Contents 
 
 
1. 
Introduction 
1.1 
Background and Significance 
1.2 
Objective 
1.3 
References 
 
2. 
Study Design 
2.1 
Inclusion Criteria 
2.2 
Exclusion Criteria 
2.3 
Sample Size Calculations 
2.4 
Randomization 
2.5 
Masking 
2.6 
Failure Criteria 
2.7 
Timetable for the Study 
 
3. 
Clinical Procedures 
3.1 
Visual Acuity 
3.2 
Slit Lamp Biomicroscopy 
3.3 
Seidel Testing 
3.4 
Tonometry 
3.5 
Pachymetry 
3.6 
Motility Evaluation 
3.7 
Gonioscopy 
3.8 
Ophthalmoscopy 
3.9 
Perimetry 
 
4. 
Surgical Procedures 
4.1 
Trabeculectomy with Mitomycin C 
4.2 
Baerveldt Implantation 
 
5. 
Study Organization 
5.1 
Introduction 
5.2 
Clinical Centers 
5.3 
Statistical Coordinating Center 
5.4 
Safety and Data Monitoring Committee 
5.5 
Steering Committee 
 
6. 
Policy Matters 
6.1 
Institutional Review Board Approval and Ethical Conduct 
6.2 
Publication and Presentation Policy 
6.3 
Ancillary Studies Policy 


 
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6.4 
Policy of Confidentiality 
6.5 
Authorship Policy 
7. 
Clinical Centers Procedures 
7.1 
Qualifying Assessment 
7.2 
Assignment of Patient Identification Number 
7.3 
Randomization Procedure 
7.4 
Schedule of Visits 
 
8. 
Statistical Coordinating Center Procedures 
8.1 
Data Management 
8.2 
Data Security 
8.3 
Data Forms 
 
9. 
Corneal Endothelial Changes Ancillary Study 
9.1 
Background 
9.2 
Clinical Procedures 
9.3 
Main Outcome Measures 
9.4 
Statistical Analysis 
9.5 
Sample Size 


 
4 
1. 
Introduction 
 
 
1.1 
Background and Significance 
 
1.2 
Objective 
 
1.3 
References 
 


 
5 
1.1 
Background and Significance 
 
 
Glaucoma surgery is indicated when further intraocular pressure (IOP) reduction 
is needed despite the use of maximum tolerated medical therapy and appropriate 
laser treatment.  Trabeculectomy (or guarded filtration procedure) is the most 
frequently performed glaucoma operation.  Eyes with previous ocular surgery 
and certain secondary glaucomas, such as neovascular glaucoma and uveitic 
glaucoma, are at great risk of trabeculectomy failure.  Wound healing modulation 
with antifibrotic agents, like mitomycin C (MMC) and 5-fluorouracil (5-FU), has 
been shown to increase the success of glaucoma filtering surgery in high risk 
eyes.1-3  The use of MMC and 5-FU in glaucoma surgery has become 
widespread in clinical practice.  The improved efficacy of trabeculectomy with an 
adjunctive antifibrotic agent in high risk eyes has prompted their use in eyes 
considered to be at low risk for failure.  A randomized clinical trial found similar 
IOP reduction and surgical complications with the intraoperative application of 
MMC and 5-FU in eyes undergoing primary trabeculectomy.4 
 
Although antifibrotic agents have increased the likelihood of IOP control following 
glaucoma filtering surgery, they have also increased the risk of complications.1-3  
The prevalence of bleb-related infections, bleb leaks, and bleb dysesthesia 
associated with a perilimbal filtering bleb suggests the need to consider 
alternative surgical approaches.  Favorable results have been reported with tube 
shunts (or glaucoma drainage implants),5-13 and these devices have been 
growing in popularity.14,15  In particular, the large surface of the Baerveldt 
glaucoma implant (Advance Medical Optics, Santa Ana, California) combined 
with its ease of insertion in a single quadrant offers an advantage over other tube 
shunts.  Similar surgical results have been reported with tube shunts and 
trabeculectomy with MMC or 5-FU when studied separately in similar patient 
groups.5-13,16-24  A comparable rate of serious complications has also been 
reported for the Baeveldt implant and trabeculectomy with an antifibrotic agent in 
a retrospective study.25 
 
The Tube Versus Trabeculectomy (TVT) Study is a multicenter randomized 
clinical trial comparing the safety and efficacy of tube shunt surgery using the 
Baerveldt implant and trabeculectomy with MMC in 212 patients with previous 
ocular surgery.26  Tube shunt surgery was more likely to maintain IOP control 
and avoid persistent hypotony or reoperation for glaucoma than trabeculectomy 
with MMC during the first year of follow-up in the TVT Study.27  Tube shunt 
surgery and trabeculectomy with MMC produced similar IOP reduction at 1 year, 
but there was less need for supplemental medical therapy following 
trabeculectomy.  There were a large number of surgical complications during the 
first year of follow-up in the TVT Study, but most were transient and self-limited.28  
The incidence of postoperative complications was higher following 
trabeculectomy with MMC than tube shunt surgery.  However, severe 
complications resulting in reoperation and/or vision loss occurred with similar 


 
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frequency with both surgical procedures.  Vision loss occurred at a similar rate 
following tube shunt surgery and trabeculectomy with MMC.  Patients who 
experienced surgical complications had greater vision loss than patients without 
complications. 
 
A randomized clinical trial by Wilson and colleagues compared the Ahmed 
glaucoma valve implant (New World Medical, Inc., Rancho Cucamonga, 
California) and trabeculectomy with and without and adjunctive antifibrotic agent 
in 117 patients.29  Lower mean IOP was observed in the trabeculectomy group 
after a mean follow-up of 9.7 months, and the Ahmed group had a greater 
adjunctive medication requirement.  The cumulative probability of success was 
similar between the two treatment groups.  This study was performed in Saudi 
Arabia and Sri Lanka, and it included patients with all glaucoma types and some 
eyes that had undergone previous ocular surgery.  A follow-up study continued 
enrollment in Sri Lanka to a total of 123 patients with primary open-angle 
glaucoma and primary angle-closure glaucoma without previous ocular surgery.30  
Lower mean IOP was noted in the trabeculectomy group than the Ahmed group 
during the first year of the study.  However, the IOPs were similar between 
treatment groups with longer follow-up, and there was no difference in the 
cumulative probability of success. 
 
 
1.2 
Objective 
 
 
The objective of this study is to compare the long-term safety and efficacy of 
placement of a 350-mm2 Baerveldt glaucoma implant and trabeculectomy with 
mitomycin C in patients who have not had previous ocular surgery.  Outcome 
discrimination between the two treatment groups will be made using typical 
measures of visual function (visual acuity and visual field), IOP, need for 
supplemental medical therapy, surgical complications, and reoperation for 
glaucoma or complications. 
 
 
1.3 
References 
 
 
1. 
The Fluorouracil Filtering Surgery Study Group.  Fluorouracil Filtering 
Surgery Study one-year follow-up.  Am J Ophthalmol 1989;108:625-635. 
 
2. 
The Fluorouracil Filtering Surgery Study Group.  Fluorouracil Filtering 
Surgery Study three-year follow-up.  Am J Ophthalmol 1993;115:82-92. 
 
3. 
The Fluorouracil Filtering Surgery Study Group.  Five-year follow-up of the 
fluorouracil filtering surgery study.  Am J Ophthalmol 1996;121:349-366. 


 
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4. 
Singh K, Mehta K, Shaikh NM, et al.  Trabeculectomy with intraoperative 
mitomycin C versus 5-fluorouracil: Prospective randomized clinical trial.  
Ophthalmology 2000;107:2305-2309.  
 
5. 
Minckler DS, Heuer DK, Hasty B, et al.  Clinical experience with the 
single-plate Molteno implant in complicated glaucomas.  Ophthalmology 
1988;95:1181-1188. 
 
6. 
Freedman J, Rubin B.  Molteno implants as a treatment for refractory 
glaucoma in black patients.  Arch Ophthalmol 1991;109:1417-1420. 
 
7. 
Lloyd MA, Sedlak T, Heuer DK, et al.  Clinical experience with the single 
plate Molteno implant in complicated glaucomas.  Update of a pilot study.  
Ophthalmology 1992;99:679-687. 
 
8. 
Heuer DK, Lloyd MA, Abrams DA, et al.  Which is better?  One or two?  A 
randomized clinical trial of single-plate versus double-plate Molteno 
implantation for glaucomas in aphakia and pseudphakia.  Ophthalmology 
1992;99:1512-1519. 
 
9. 
Hodkin MJ, Goldblatt WS, Burgoyne CF, et al.  Early clinical experience 
with the Baerveldt implant in complicated glaucomas.  Am J Ophthalmol 
1995;120:32-40. 
 
10. 
Mills RP, Reynolds A, Emond MJ, et al.  Long-term survival of Molteno 
glaucoma drainage devices.  Ophthalmology 1996;103:299-305. 
 
11. 
Huang MC, Netland PA, Coleman AL, et al.  Intermediate-term clinical 
experience with the Ahmed glaucoma valve implant.  Am J Ophthalmol  
1999;127:27-33. 
 
12. 
Broadway DC, Iester M, Schulzer M, Douglas GR.  Survival analysis for 
success for Molteno tube implants.  Br J Ophthalmol 2001;85:689-695. 
 
13. 
Roy S, Ravinet E, Mermoud A.  Baerveldt implant in refractory glaucoma: 
Long-term results and factors influencing outcomes.  Int Ophthalmol 
2001;24:93-100. 
 
14. 
Chen PP, Yamamoto T, Sawada A, et al.  Use of antifibrosis agents and 
glaucoma drainage devices in the American and Japanese Glaucoma 
Societies.  J Glaucoma 1997;6:192-196. 
 
15. 
Joshi AB, Parrish RK, Feuer WF.  2002 Survey of the American Glaucoma 
Society. Practice preferences for glaucoma surgery and antifibrotic use.  J 
Glaucoma 2005;14:172-174. 
 


 
8 
16. 
Heuer DK, Parrish RK, Gressel MG, et al.  5-fluorouracil and glaucoma 
filtering surgery:  II.  A pilot study.  Ophthalmology 1984;91:384-394. 
 
17. 
Heuer DK, Parrish RK, Gressel MG, et al.  5-fluorouracil and glaucoma 
filtering surgery:  III.  Intermediate follow-up of a pilot study.  
Ophthalmology 1986;93:1537-1546. 
 
18. 
Weinreb RN.  Adjusting the dose of 5-fluorouracil after filtration surgery to 
minimize side effects.  Ophthalmology 1987;94:564-570. 
 
19. 
Palmer SS.  Mitomycin as adjunct chemotherapy with trabeculectomy.  
Ophthalmology 1991;98:317-321. 
 
20. 
Prata JA, Minckler DS, Baerveldt G, et al.  Trabeculectomy in 
pseudophakic patients:  postoperative 5-fluorouracil versus intraoperative 
mitomycin C antiproliferative therapy.  Ophthalmic Surg 1995;26:73-77. 
 
21. 
Chen CW, Huang HT, Bair JS, Lee CC.  Trabeculectomy with 
simultaneous topical application of mitomycin-C in refractory glaucoma.  J 
Ocular Pharmacol 1990;6:175-182. 
 
22. 
Singh J, O’Brien C, Chawla HB.  Success rate and complications of 
intraoperative 0.2 mg/ml mitomycin C in trabeculectomy surgery.  Eye 
1995;9:460-466. 
 
23. 
Andreanos D, Georgopoulos GT, Vergados J, et al.  Clinical evaluation of 
the effect of mitomycin-C in re-operation for primary open angle glaucoma.  
Eur J Ophthalmol 1997;7:49-54. 
 
24. 
You YA, Gu YS, Fang CT, Ma XQ.  Long-term effects of simultaneous and 
subscleral mitomycin C application in repeat trabeculectomy.  J Glaucoma 
2002;110-118. 
 
25. 
Nguyen QH, Budenz DL, Parrish RK.  Complications of Baerveldt 
glaucoma drainage implants.  Arch Ophthalmol 1998;116:571-575. 
 
26. 
Gedde SJ, Schiffman JC, Feuer WJ, et al.  The Tube Versus 
Trabeculectomy Study: Design and baseline characteristics of study 
patients.  Am J Ophthalmol 2005;140:275-287. 
 
27. 
Gedde SJ, Schiffman JC, Feuer WJ, et al.  Treatment outcomes in the 
Tube Versus Trabeculectomy (TVT) Study after one year of follow-up.  Am 
J Ophthalmol 2007;143:9-22. 
 
 
 


 
9 
28. 
Gedde SJ, Herndon LW, Brandt JD, et al.  Surgical complications in the 
Tube Versus Trabeculectomy (TVT) Study during the first year of follow-
up.  Am J Ophthalmol 2007;143:23-31. 
 
29. 
Wilson MR, Mendis U, Smith SD, Paliwal A.  Ahmed glaucoma valve 
implant vs. trabeculectomy in the surgical treatment of glaucoma: A 
randomized clinical trial.  Am J Ophthalmol 2000;130:267-273. 
 
30. 
Wilson MR, Mendis U, Paliwal A, Haynatzka V.  Long-term follow-up of 
primary glaucoma surgery with Ahmed glaucoma valve implant versus 
trabeculectomy.  Am J Ophthalmol 2003;136:464-470. 


 
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2. 
Study Design 
 
 
2.1 
Inclusion Criteria 
 
2.2 
Exclusion Criteria 
 
2.3 
Sample Size Calculations 
 
2.4 
Randomization 
 
2.5 
Masking 
 
2.6 
Failure Criteria 
 
2.7 
Timetable for the Study 
 


 
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2.1 
Inclusion Criteria 
 
 
All of the criteria listed below must be present in the study eye in order for the 
patient to be eligible for enrollment in the study. 
 
a. 
Age 18 to 85 years, inclusive. 
 
b. 
Glaucoma that is inadequately controlled on tolerated medical therapy 
with intraocular pressure greater than or equal to 18 mm Hg and less than 
or equal to 40 mm Hg. 
 
c. 
No previous incisional ocular surgery (including keratorefractive surgery). 
 
 
2.2 
Exclusion Criteria 
 
 
If any of the following exclusion criteria are present in the study eye, the patient 
may not be entered into the study. 
 
a. 
Unwilling or unable to give consent, unwilling to accept randomization, or 
unable to return for scheduled protocol visits. 
 
b. 
Pregnant or nursing women. 
 
c. 
No light perception vision. 
 
d. 
Narrow anterior chamber angle. 
 
e. 
Iris neovascularization or proliferative retinopathy. 
 
f. 
Iridocorneal endothelial syndrome. 
 
g. 
Epithelial or fibrous downgrowth. 
 
h. 
Chronic or recurrent uveitis. 
 
i. 
Steroid-induced glaucoma. 
 
j. 
Severe posterior blepharitis. 
 
k. 
Unwilling to discontinue contact lens use after surgery. 
 
l. 
Previous cyclodestructive procedure. 


 
12 
 
m. 
Conjunctival scarring from prior ocular trauma or cicatrizing disease (e.g. 
Stevens Johnson syndrome, ocular pemphigoid) precluding a superior 
trabeculectomy. 
 
n. 
Functionally significant cataract. 
 
o. 
Need for glaucoma surgery combined with other ocular procedures (i.e. 
cataract surgery, penetrating keratoplasty, or retinal surgery) or 
anticipated need for additional ocular surgery. 
 
 
2.3 
Sample Size Calculations 
 
 
Sample size calculations were determined based on projected rates of 
complications and surgical success in each treatment group.  The results are 
shown in Table 1.  Enrollment of 88 patients in each treatment group, or a total of 
176 patients, is expected to generate statistically valid conclusions for the study.  
An attrition rate of 6% per year is anticipated.  Therefore, enrollment in the study 
will be offered to a total of 242 patients, including 121 patients in each treatment 
group. 
 
 
2.4 
Randomization 
 
 
Since the purpose of this study is to compare the safety and efficacy of two 
surgical procedures used in the management of glaucoma, a trabeculectomy with 
mitomycin C and Baerveldt glaucoma implant, randomization techniques are 
used to assure an unbiased treatment assignment to patients. 
 
Stratification: 
 
Previous studies have suggested that younger patients and those of African 
American ethnicity are at greater risk of failure with standard filtering surgery.  It 
also seems logical to assume that a patient who has failed glaucoma filtering 
surgery in one eye would be at greater risk for surgical failure in the fellow eye.  
Therefore, patients will be stratified based upon the following prognostic factors: 
 
1. 
Age (< 50 years or > 50 years) 
 
2. 
Ethnicity (African American or other) 
 


 
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3. 
Previous failed filtering surgery in the nonstudy eye (present or 
absent) 
 
Randomization: 
 
A procedure is used to randomly assign patients to treatment with either a 
Baerveldt glaucoma implant or trabeculectomy with mitomycin C.  At each 
Clinical Center, half of the patients in each stratum will receive a Baerveldt 
glaucoma implant and half will receive a trabeculectomy with mitomycin C.  
Randomization takes place at the time the patient is enrolled in the study.  
 
 
2.5 
Masking 
 
 
Neither the investigator nor the patient is masked as to which treatment the 
patient receives. 
 
 
2.6 
Failure Criteria 
 
 
Failure in the PTVT Study is defined by following criteria: 
 
• IOP > 21 mm Hg or not reduced by 20% below baseline on two 
consecutive follow-up visits after 3 months 
 
• IOP < 5 mm Hg on two consecutive visits after 3 months 
 
• Additional glaucoma surgery 
 
• Loss of light perception vision 
 
Eyes that have not failed and are not on supplemental medical therapy are 
considered complete successes.  Eyes that have not failed but require 
supplemental medical therapy are defined as qualified successes. 
 
 
 
 
 
 
 
 
 


 
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2.7 
Timetable for the Study 
 
 
April 2007 to October 2007: 
 
• Prepare Reseach Protocol for the University of Miami Institutional 
Review Board including a Patient Consent Form. 
 
• Write the Manual of Procedures (Version 1.0). 
• Produce data collection forms. 
 
November 2007 to April 2008: 
 
• Meet with potential investigators from selected Clinical Centers and 
potential members of the Safety and Data Monitoring Committee at the 
annual AAO Meeting. 
 
• Certify participating Clinical Centers by: 
a. 
Documenting number of patients who should be eligible. 
b. 
Identifying physicians at the Clinical Center who have 
performed requisite number of surgeries using both study 
treatments. 
c. 
Documenting IRB approval. 
 
• Produce randomization schedules. 
 
May 2008 to May 2012: 
 
• Recruit and randomize patients. 
 
• Produce follow-up schedule for each randomized patient. 
 
• Monitor submission of forms from Clinical Centers and perform data 
entry. 
 
• Monitor adverse events by treatment group. 
 
• Perform analyses to monitor for treatment differences and success 
rates on a routine basis. 
 
May 2012 to May 2013: 
 
• Continue to monitor data for adverse events and differences in 
success rates between treatment groups. 
 


 
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• Continue to collect follow-up data. 
 
• Perform data analyses on data on the one year outcomes from all 
patients, and prepare a manuscript. 
 


 
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Table 1.  Sample Size Calculations 
 
 
Complication 
 Rate 
Required Sample Size 
 
 
Trab 
Tube 
     in Each Group 
 
Bleb-related infection 
5.1% 
0.05% 
191 
(cumulative rate after 3 years)1 
 
Bleb leaks 
 
7.0% 
0.05% 
137 
(cumulative rate after 3 years)2 
 
Diplopia 
 
0.05% 
5.0% 
195 
 
Any postoperative complication3 
57% 
34% 
121 
(proportion after 1 year) 
 
Failure4 
13.5% 
3.9% 
154 
(rate after 1 year) 
 
Failure* 
3.0 
1 
194 
(relative risk at 1 year) 
 
Failure* 
2.0 
1 
370 
(relative risk at 1 year) 
 
Failure* 
3.0 
1 
44 
(relative risk at 5 years) 
 
Failure* 
2.0 
1 
88 
(relative risk at 5 years) 
 
 
 
 
 
 
*Power = 80%; alpha = 0.05; median control failure = 60 months 
 
1Wolner B, Liebmann JM, Sassani JW, et al.  Late bleb-associated endophthalmitis after trabeculectomy 
with adjunctive 5-fluorouracil.  Ophthalmology 1991;98:1053-1060. 
 
2The Fluorouracil Filtering Surgery Study Group.  Three-year follow-up of the Fluorouracil Filtering Surgery 
Study.  Am J Ophthalmol 1993;115:82-92. 
 
3Gedde SJ, Herndon LW, Brandt JD, et al.  Surgical complications in the Tube Versus Trabeculectomy 
(TVT) Study during the first year of follow-up.  Am J Ophthalmol 2007;143:23-31. 
 
4Gedde SJ, Schiffman JC, Feuer WJ, et al.  Treatment outcomes in the Tube Versus Trabeculectomy (TVT) 
Study after one year of follow-up.  Am J Ophthalmol 2007;143:9-22. 


 
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3. 
Clinical Procedures 
 
 
3.1 
Visual Acuity 
 
3.2 
Slit Lamp Biomicroscopy 
 
3.3 
Seidel Testing 
 
3.4 
Tonometry 
 
3.5 
Pachymetry 
 
3.6 
Motility Evaluation 
 
3.7 
Gonioscopy 
 
3.8 
Ophthalmoscopy 
 
3.9 
Perimetry 


 
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3.1 
Visual Acuity  
 
 
Visual acuity is an important outcome variable in the PTVT Study.  Visual acuity 
is measured before pupil dilation, tonometry, gonioscopy, or any other technique 
that could affect vision.  Two different techniques are used to measure visual 
acuity, including Snellen and ETDRS visual acuity testing.  Refraction is 
performed prior to formal measurement of visual acuity by either technique at the 
Qualifying Assessment and at the annual follow-up visits.  Snellen visual acuity is 
measured at the Qualifying Assessment and at every follow-up visit.  ETDRS 
visual acuity is tested at the Qualifying Assessment and at the 1 year, 3 year, 
and 5 year follow-up visits. 
 
Subjective Refraction: 
 
Subjective refraction must be performed at the Qualifying Assessment and at the 
annual follow-up visits in order to determine best-corrected visual acuity.  It is 
permissible to use a phoropter or trial frame to determine best-corrected Snellen 
visual acuity.  The left eye is occluded first.  An approximate beginning refraction 
may be determined by retinoscopy, automated refraction, or a subjective 
refraction from a prior visit.  The sphere is refined first.  The cylinder is then 
refined, first the axis followed by the power.  Finally, the sphere is rechecked.  
The right eye is then occluded, and the procedure is repeated for the left eye. 
 
If the patient wears contact lenses and has glasses also, he or she is instructed 
not to wear the contact lenses on the day of the Qualifying Assessment.  Patients 
unwilling to discontinue contact lens use after surgery will be excluded from the 
study.  In the event that the patient either has no glasses or has forgotten the 
instructions and reported for the Qualifying Assessment wearing contact lenses, 
the contact lenses are removed and at least thirty minutes allowed to elapse 
before subjective refraction and visual acuity testing is performed. 
 
ETDRS Visual Acuity: 
 
The logmar visual acuity testing for the PTVT Study has been adapted from the 
Early Treatment of Diabetic Retinopathy (ETDRS).  The logmar visual acuity 
scale facilitates statistical analysis and simplifies quantification of acuity at 
various distances.  The right eye is tested with ETDRS logmar chart 1, then the 
left eye is tested with ETDRS logmar chart 2.  Each chart is hidden from view 
until the eye being examined is ready for testing.  ETDRS visual acuity is 
measured after standardized refraction only during the Qualifying Assessment 
and at the 1 year, 3 year, and 5 year follow-up examinations. 
 
The room illumination should be at a level of 50 to 100 foot candles, and between 
50 and 125 foot candles should illuminate the ETDRS visual acuity chart.  The 
distance from the patient’s eye to the visual acuity chart is exactly 4.0 meters.  


 
19 
The patient may sit or stand, but he or she is not allowed to lean forward or 
backward so a constant testing distance is maintained.  After proper instruction, 
refraction, and placement of the appropriate lenses in a trial frame, the left eye is 
occluded and testing is begun with the right eye.  The patient is instructed that 
the chart has letters only and no numbers.  If the patient forgets this information 
and reads a number, he or she is reminded that the chart contains only letters 
and the examiner requests a letter in lieu of the number.  Each letter that is 
identified correctly is circled on the ETDRS Visual Acuity Worksheet.  The patient 
is advised to read slowly, so as to achieve the best identification of each letter.  
When the patient says he or she cannot read a letter, he or she is encouraged to 
guess.  The patient should be encouraged to fix eccentrically if this improves the 
visual acuity, but care must be taken to ensure that the fellow eye remains 
covered. 
 
Eyes reading fewer than 20 letters correctly at a test distance of 4.0 meters are 
tested at 1.0 meter.  Before testing at 1.0 meter, +0.75 sphere is added to the 4.0 
meter correction already in the trial frame to compensate for the closer testing 
distance.  The patient is asked to read only the first six lines at 1.0 meter, so the 
maximum score attainable at that distance is 30.  Correctly identified letters are 
circled on the ETDRS Visual Acuity Worksheet.  If the patient’s visual acuity is so 
poor that he or she cannot read the largest letter at 1.0 meter, assess his or her 
ability to count fingers.  After testing of the right eye is completed, chart 1 is 
replaced by chart 2 and the procedure is repeated for the left eye. 
 
Each letter read correctly and circled on the ETDRS Visual Acuity Worksheet is 
scored as one point.  The score for each line (which is zero if no letters were 
read correctly) and the total score is recorded after testing is completed.  If 
testing at 1.0 meter is not required (ie 20 or more letters were seen with testing at 
4.0 meters), 30 points are automatically scored for the 1.0 meter test.  The total 
score, equaling the sum of the 4.0 meter and 1.0 meter scores, is recorded on 
the data form.  The ETDRS Visual Acuity Worksheet is for clinic use only and 
should not be sent to the Statistical Coordinating Center. 
 
Snellen Visual Acuity: 
 
Snellen visual acuity may be measured using any standard visual acuity chart.  
The same type of chart must be used throughout the duration of the study.  
Snellen visual acuity is measured during the Qualifying Assessment and at all 
follow-up visits.  Standardized refraction is performed prior to Snellen visual 
acuity testing at the Qualifying Assessment and annual follow-up examinations. 
 
The patient is not allowed to lean forward or backward so that a constant testing 
distance is maintained.  After proper instruction and refraction, the left eye is 
occluded and testing is begun with the right eye.  Progressively smaller lines are 
presented to the patient until he or she makes two or more errors in a line.  When 
a patient states he or she is unable to read a letter, he or she is encouraged to 


 
20 
guess.  If a patient misses only two letters on a line, a second chance is provided 
by asking the patient to read the line backwards.  The patient is encouraged to fix 
eccentrically if this improves the visual acuity, but care must be taken to ensure 
that the fellow eye remains covered.  The Snellen visual acuity is recorded as the 
smallest line in which the patient misses one or fewer optotypes.  If the patient’s 
visual acuity is so poor that he or she cannot read the 20/400 line, assess his or 
her ability to count fingers.  After testing of the right eye is completed, the 
procedure is repeated for the left eye. 
 
Testing for Finger Counting: 
 
After proper instruction and refraction, the examiner’s hand is viewed at a 
distance of two feet from the patient’s eye.  The fellow eye is closed and 
completely occluded by the palm of the patient’s or assistant’s hand.  The 
examiner presents a random number of fingers to the patient.  The patient is 
asked to indicate the number of fingers seen.  If the number of fingers shown are 
correctly identified on four or more of five presentations, vision is recorded as 
count fingers. If the number of fingers presented cannot be identified on four or 
more of five presentations, test for hand motions. 
 
Testing for Hand Motions: 
 
In testing for hand motion, the examiner’s hand is viewed with all fingers 
extended and separated at a distance of two feet from the patient’s eye.  The 
fellow eye is closed and completely occluded by the palm of the patient’s or 
assistant’s hand.  The patient’s glasses are not be worn.  The examiner’s hand is 
presented in a random order under three conditions:  stationary, moving back 
and forth horizontally, and moving up and down vertically.  The speed of 
movement is approximately one complete cycle of movement (up and down or 
back and forth) per second.  The patient is instructed that the examiner’s hand 
will be presented in one of these conditions.  He or she is asked to respond to 
the question, “what is my hand doing now?” with either, “still”, “back and forth”, or 
“up and down”.  The process is repeated five times.  It is considered a correct 
response if the patient states the hand is still or he or she cannot see it while it is 
stationary, and he or she is able to recognize movement and identify its direction.  
If hand motions are correctly identified on four or more of five presentations, 
vision is recorded as hand motions.  If hand motions cannot be identified on four 
or more of five presentations, test for light perception. 
 
Testing for Light Perception: 
 
Light perception is tested using the same complete occlusion of the fellow eye 
with no other bright lights visible from the patient’s position.  The patient’s 
glasses are not worn.  The light of an indirect ophthalmoscope is directed into the 
eye from a distance of 2 feet for one or two seconds, then turned away.  The 
patient is asked to report “on” when he or she sees the light, and “off” when it 


 
21 
disappears.  The process is repeated five times in a nonrhythmic fashion.  The 
visual acuity is recorded as light perception if the patient responds correctly four 
or more out of five times. 
 
Testing Visual Acuity in Illiterate Patients: 
 
Patients who are illiterate and cannot read standard letter charts have visual 
acuity tested using either a number chart, an illiterate E chart, a Landolt ring 
chart, or picture chart.  The type of chart must be identified so that it can be used 
throughout the duration of the study.  The smallest line in which one or fewer 
optotypes are missed is recorded as the Snellen visual acuity, and a notation is 
made that testing was performed in an illiterate patient. 
 
 
3.2 
Slit Lamp Biomicroscopy 
 
 
Examination of the anterior segment using slit lamp biomicroscopy is performed 
at the Qualifying Assessment to document the preoperative status of the eye, 
and at all follow-up examinations to detect any changes in ocular status during 
the course of the study which may be attributable to the disease or treatment.  
Slit lamp biomicroscopy may be performed with any commercially available 
instrument, and it is used in a standard fashion starting anteriorly and working 
posteriorly.  Standardizing subjective grading of bleb leaks and lenticular 
opacities is difficult, if not impossible.  However, it is expected that subjective 
grading by each investigator is relatively reproducible.  Attempts will be made to 
compare subjective gradings between investigators. 
 
Lids: 
 
The lids are examined for signs of blepharitis, including scales and crusting of the 
lashes, inspissated Meibomian glands, and erythema of the lid margin.  Eyes 
with severe posterior blepharitis are excluded from the study. 
 
Conjunctiva: 
 
The conjunctiva is examined for scarring from prior trauma or cicatrizing disease 
(e.g. Stevens Johnson syndrome, ocular pemphigoid).  The presence and extent 
of conjunctival scarring may be evaluated using a cotton tipped applicator to test 
the mobility of the conjuctiva.  Eyes with conjunctival scarring that precludes a 
superior trabeculectomy are ineligible for the study. 
 
Eyes must undergo Seidel testing at all postoperative follow-up examinations to 
detect conjunctival wound leaks and bleb leaks.  Eyes that have undergone 
Baerveldt implantation are examined carefully for tube or shunt erosion.  The 
presence of an infiltrate or exudate in the bleb of eyes that have undergone a 


 
22 
trabeculectomy with mitomycin C suggests the presence of a bleb-related 
infection. 
 
Cornea: 
 
The cornea is examined at high magnification to evaluate the epithelium, stroma, 
and endothelium.  The techniques of diffuse illumination, scleral scatter, and 
retroillumination may be used.  Findings consistent with a diagnosis of the 
iridocorneal endothelial (ICE) syndrome, epithelial downgrowth, or fibrous 
downgrowth make the eye ineligible for the study.  The presence of corneal 
epithelial or stromal edema is noted.  Eyes that have undergone Baerveldt 
implantation are examined for the presence of tube-cornea touch. 
 
Anterior Chamber: 
 
Before fluorescein instillation or pupillary dilation, the degree of anterior chamber 
cell and flare is determined.  Eyes with chronic or recurrent uveitis are excluded 
from the study.  Careful assessment of the anterior chamber depth is made 
postoperatively.  If the anterior chamber is shallow, the central anterior chamber 
depth is measured relative to the corneal thickness.  The appropriate gradation of 
> 3 CT, > 2 CT, > 1 CT, < 1 CT, or lens-cornea touch is documented.  In eyes 
treated with tube shunt surgery, the position of the tube in the anterior chamber is 
assessed and its length measured with a slit beam. 
 
Iris: 
 
Before pupillary dilation, the pupillary iris is examined at high magnification for 
the presence of neovascularization.  If rubeosis iridis is present, the eye is 
ineligible for the study. 
 
Lens: 
 
After pupillary dilation, the investigator assesses the lens and grades any 
cataract present as mild, moderate, or severe. 
 
 
3.3 
Seidel Testing 
 
 
Seidel testing must be performed at each postoperative follow-up examination.  
The Seidel test is performed using a fluorescein strip moistened with one or two 
drops of 0.5% proparacaine which is then applied to the conjuctiva.  Alternatively, 
one drop of premixed fluorescein and anesthetic may be instilled.  The area is 
closely observed using high magnification and a broad slit beam with maximal 
intensity illumination using a cobalt blue filter.  Aqueous leakage is apparent as a 
light yellow stream and interrupts a dark green background of undiluted 


 
23 
fluorescein.  If the Seidel test is positive, the leak is graded as an ooze, frank 
leak, or brisk leak. 
 
 
3.4 
Tonometry 
 
 
Goldmann applanation tonometry is used to measure the intraocular pressure, 
except when irregular corneal astigmatism, corneal scarring, or corneal edema 
precludes accurate readings.  In these cases, the Tono-Pen (Mentor) is used.  
The intraocular pressure is measured prior to pupillary dilation.  Whenever 
possible, the intraocular pressure should be checked at the same time of the day 
as the Qualifying Assessment to minimize the effect of diurnal fluctuation of 
intraocular pressure. 
 
Goldmann Applanation Tonometry: 
 
The calibration of the Goldmann applanation tonometer is checked every 3 
months, as described in the Haag-Streit Goldmann Applanation Tonometer 
Operator’s Manual.  Clean the prism according to your institutional infection 
control policy.  The right eye is always tested first.  Following instillation of a drop 
of 0.5% proparacaine, a fluorescein strip is placed near the lateral canthus in the 
lower conjunctival sac.  Once the lacrimal fluid has been sufficiently colored, the 
fluorescein strip is removed.  Alternatively, one drop of premixed fluorescein and 
anesthetic may be instilled.  The patient’s head is properly positioned in the chin 
rest and against the forehead rest without leaning forward or straining.  Any tight-
fitting neckwear is loosened.  The patient is asked to look straight ahead at a 
distant object or fixation target.  If it is necessary to hold the eyelids open, the 
investigator holds the eyelids open against the orbital rim taking care not to apply 
any pressure on the globe.  The patient is instructed not to hold his or her breath.  
If corneal astigmatism is greater than 3.0 diopters, the prism is rotated so that the 
axis of the minus cylinder on the prism graduation corresponds to the red mark 
on the prism holder.  The investigator looks through the slit lamp and gently 
brings the tip of the prism in contact with the center of the cornea.  The mires 
should be well focused, centered horizontally, and positioned vertically so that 
they are of equal circumference above and below the horizontal dividing line.  If 
the mires are narrower than approximately one tenth their diameter, the 
investigator instills additional fluorescein.  The investigator adjusts the measuring 
drum until the inner borders of the two mires just touch each other.  If pulsation is 
present, the measuring drum is adjusted until the mires separate a given 
distance during systole and overlap the same distance during diastole.  The 
investigator removes the prism from the cornea and repeats the procedure in the 
right eye until two successive measurements are within 2 mm Hg.  The 
investigator records the last two successive measurements.  After testing of the 
right eye is complete, testing of the left eye follows the same technique. 
 


 
24 
Tono-Pen: 
 
The Tono-Pen (Mentor) is used in cases of corneal edema, corneal scarring, or 
irregular corneal astigmatism.  The Tono-Pen probe tip is covered with a new 
Ocu-Film Tip Cover.  The instrument is calibrated immediately prior to use, as 
described in the Mentor Tono-Pen Instruction Manual.  The right eye is always 
tested first.  A drop of 0.5% proparacaine is instilled.  The patient is positioned in 
the sitting position and instructed to fix on a distant object.  Tight-fitting neckwear 
is loosened, and the patient is instructed not to hold his or her breath.  The Tono-
Pen is activated by depressing the activation switch momentarily.  The Tono-Pen 
is brought in contact with the patient’s cornea lightly and briefly while holding the 
instrument perpendicular to the cornea.  A click will sound and a digital 
intraocular pressure measurement will be displayed each time a valid reading is 
obtained.  After four valid readings, a final beep sounds and the averaged 
measurement appears on the display, along with a single line denoting statistical 
reliability.  Measurements are repeated until two successive readings are 
obtained within 2 mm Hg and both have a statistical reliability of 5%, indicating 
that the standard deviation of the valid measurements is 5% or less of the 
number displayed.  The investigator records the last two successive 
measurements.  After testing of the right eye is complete, the same technique is 
applied to testing of the left eye. 
 
 
3.5 
Pachymetry 
 
 
Both surgical procedures under study, placement of a Baerveldt implant and 
trabeculectomy with MMC, can lead to progressive endothelial cell loss and 
corneal edema.  Central corneal thickness is measured with ultrasound 
pachymetry at the Qualifying Assessment and at the annual follow-up visits.  The 
right eye is tested first.  A drop of 0.5% proparacaine is instilled for anesthesia.  
The patient is asked to look straight ahead at a distant object or fixation target.  
The pachymeter probe is lined up with the center of the pupil and slowly 
advanced until it contacts the cornea.  The probe is withdrawn when an audible 
signal is made indicating that a measurement has been recorded.  The patient is 
instructed to blink.  The procedure is repeated to obtain three separate readings, 
and the investigator records the measurements.  After testing of the right eye is 
complete, the same technique is applied to testing of the left eye. 
 
 
3.6 
Motility Evaluation 
 
 
Diplopia is an important complication which may occur following Baerveldt  


 
25 
implantation.  The incidence of permanent restrictive strabismus associated with 
the Baerveldt implant is not precisely known, as this complication has not been 
studied prospectively.  In order to address this issue, a formal motility evaluation 
is performed in all patients preoperatively and in those patients with diplopia at 
the 6 month follow-up visit or beyond.  In addition, all patients will undergo a 
motility evaluation at the 1 year and 5 year follow-up visits.  Transient diplopia 
following Baerveldt implantation is not uncommon.  This study will focus on the 
incidence and nature of permanent restrictive strabismus associated with the 
Baerveldt implant. 
 
The cover-uncover and alternate cover tests are performed with the patient 
looking in primary gaze, as well as in upgaze, downgaze, left gaze, and right 
gaze.  Motility evaluation is performed with the patient looking in the distance and 
fixating at a near target.  Any heterophorias or heterotropias are identified, and 
the deviation is measured with hand-held prisms.  In patients who are unable to 
fixate for cover testing, the deviation may be measured by centering the corneal 
light reflexes with prism using the modified Krimsky method. 
 
 
3.7 
Gonioscopy 
 
 
Gonioscopy is performed with the patient sitting at the slit lamp using either a 
Zeiss type four-mirror gonioprism or Goldmann single- or three-mirror lens.  An 
examination of the anterior chamber angle for neovascularization is performed 
under high magnification for the purpose of excluding eyes with 
neovascularization from the study. 
 
 
3.8 
Ophthalmoscopy 
 
 
A dilated fundus examination is performed at the Qualifying Assessment to 
determine the preoperative status of the eye.  Ophthalmoscopy is done at the 1 
week, 1 month, 3 month, and annual follow-up examinations to detect any 
changes in ocular status produced by the disease or treatment.  Additionally, a 
dilated fundus examination is performed at any follow-up visit in which there is 
shallowing of the anterior chamber, intraocular pressure less than 6 mm Hg, or 
unexplained vision loss.  After pupil dilation with appropriate mydriatics, the optic 
nerve and posterior pole are examined at the slit lamp using a Hruby lens, fundus 
contact lens, or Volk 90 diopter, 78 diopter, or 60 diopter lens.  A head-mounted 
indirect ophthalmoscope and hand held condensing lens (20 diopter or 28 diopter 
Nikon aspheric lens) is used to evaluate the retinal periphery. 
 


 
26 
At the Qualifying Assessment, particular attention is paid for signs of proliferative 
retinopathy, including retinal neovascularization, neovascularization of the disc, 
vitreous hemorrhage, or preretinal hemorrhage.  Patients with active proliferative 
retinopathy are excluded from the study.  At postoperative follow-up visits, 
ophthalmoscopy is performed to evaluate for posterior segment complications, 
such as serous choroidal effusions, suprachoroidal hemorrhage, or hypotony 
maculopathy. 
 
 
3.9 
Perimetry 
 
 
Visual field assessment is an important outcome measure in the PTVT Study.  
Quantitative automated perimetry is performed using the Humphrey Field 
Analyzer.  Visual field testing is performed before tonometry, gonioscopy, or any 
other technique that could affect vision.  A visual field should be attempted in any 
eye that has sufficient vision to permit finger counting at two feet.  Eyes with poor 
central vision may have an intact, off-center island of vision which may be 
measured with perimetry. 
 
For the PTVT Study, a 24-2 threshold test is performed in all patients using a 
size III white stimulus.  Visual field testing may be performed with the Swedish 
Interactive Thresholding Algorithm (SITA) or full threshold strategy, but the same 
testing strategy must be used throughout the duration of the study.  The pupil 
diameter should be 3 mm or greater before visual field testing is undertaken, and 
this may require pharmacologic dilation.  Standardized refraction is performed to 
determine the patient’s distance refraction and best-corrected visual acuity prior 
to visual field testing.  The age appropriate plus lens is added to the distance 
refraction.  Patient education is provided, and the instrument is set up for the test.  
The technician should monitor the patient during testing.  Visual fields are 
performed preoperatively (within one month of enrollment in the study) and 
annually thereafter.  Copies of all visual fields are faxed to the Statistical 
Coordinating Center for evaluation. 


 
27 
4. 
Surgical Procedures 
 
 
4.1 
Trabeculectomy with Mitomycin C 
 
4.2 
Baerveldt Implantation 
 
 
 


 
28 
4.1 
Trabeculectomy with Mitomycin C 
 
 
Anethesia: 
 
The type of anesthesia is at the surgeon’s discretion. 
 
Conjunctival Flap: 
 
The trabeculectomy is performed in a superior quadrant.  A limbus-based or 
fornix-based conjunctival flap may be used depending on the surgeon’s 
preference.  Eyes with conjunctival scarring that precludes a superior 
trabeculectomy are excluded from the study.  A corneal traction suture or 
superior rectus traction suture may be used to rotate the globe inferiorly and 
improve exposure. 
 
Mitomycin C Application: 
 
A fluid retaining sponge soaked in mitomycin C (0.4 mg/ml) is applied to the 
sclera in the region of the trabeculectomy site for a period of exactly two minutes 
(120 seconds).  The mitomycin may be applied before or after scleral flap 
dissection, as determined by the surgeon.  This area is then copiously irrigated 
with balanced salt solution or Tis-U-Sol solution to remove any residual 
mitomycin C.  The type of sponge used for mitomycin C application is selected by 
the surgeon in keeping with his or her usual practice. 
 
Scleral Flap: 
 
A corneal-based scleral flap is dissected approximately one-half scleral 
thickness.  The shape and size of the scleral flap is determined by the surgeon in 
keeping with his or her usual practice. 
 
Paracentesis Tract: 
 
A peripheral clear cornea paracentesis tract is made. 
 
Excision of Limbal Tissue: 
 
A block of limbal tissue is excised from underneath the trabeculectomy flap using 
a sharp blade and Vannas scissors or a Kelly punch.  The amount of limbal 
tissue excised is at the surgeon’s discretion. 
 
Peripheral Iridectomy: 
 
A peripheral iridectomy is performed in all cases.  The sclerostomy opening is 
inspected for entrapped iris tissue, and a cellulose sponge is used to test for the 


 
29 
presence of vitreous.  Vitreous presenting to the surgical wound is excised.  The 
method used to remove vitreous present at the surgical site is at the surgeon’s 
discretion. 
 
Scleral Flap Closure: 
 
The scleral flap is reapproximated to the scleral bed with interrupted or 
releasable 10-0 nylon sutures.  The number and tension of scleral flap sutures is 
determined by the surgeon.  Following injection of balanced salt solution into the 
anterior chamber through the paracentesis tract, the anterior chamber should 
remain formed with a visible leak present around the scleral flap at equilibrium. 
 
Conjunctival Flap Closure: 
 
The type of suture material and needle used for the conjunctival flap closure is of 
the surgeon’s choice.  Either a double layered closure (conjunctiva and Tenon’s 
closed separately) or single layered closure (conjunctiva and Tenon’s together) 
may be performed. 
 
Reformation of the Anterior Chamber and Bleb Elevation: 
 
Balanced salt solution is injected through the paracentesis tract to deepen the 
anterior chamber and elevate the bleb.  A moistened fluorescein strip is used to 
check for a conjunctival leak or leakage from the paracentesis tract, which may 
be closed with additional sutures. 
 
Intraoperative Medications: 
 
The use of intraoperative medications is at the surgeon’s discretion.  
Subconjunctival antibiotics and corticosteroids may be injected, and a 
cycloplegic-mydriatic drop and steroid-antibiotic ointment may be instilled at the 
conclusion of the case, as determined by the surgeon in keeping with his or her 
usual practice. 
 
 
4.2 
Baerveldt Implantation 
 
 
Anesthesia: 
 
The type of anesthesia is at the surgeon’s discretion. 
 
 
 
 
 


 
30 
Conjunctival Flap: 
 
A 350-mm2 Baerveldt is used in all cases, and implantation is performed in the 
superotemporal quadrant.  A limbus-based or fornix-based conjunctival flap may 
be used depending on the surgeon’s preference. 
 
Scleral Exposure: 
 
Sufficient exposure is obtained in the superotemporal quadrant to permit 
placement of the Baerveldt plate.  A corneal traction suture or episcleral traction 
suture may be used to rotate the globe inferonasally and improve exposure. 
 
Insertion of Episcleral Plate: 
 
The 350-mm2 Baerveldt plate may be positioned under or over the superior 
rectus and lateral rectus muscles, depending on the surgeon’s usual practice.  
The implant is sutured to the sclera at a measured distance of 10 mm posterior to 
the limbus using the two fixation holes on the plate.  The type of nonabsorbable 
suture used is of the surgeon’s choice. 
 
Occlusion of Tube: 
 
The Baerveldt tube must be completely occluded in all cases in order to restrict 
aqueous flow to the plate until it becomes encapsulated.  This is done to 
minimize the incidence of postoperative hypotony.  The method of tube occlusion 
is left to the discretion of the surgeon.  Ligation of the tube with a polyglactin 
suture near the tube-plate junction, ligation with a polypropylene suture which is 
inserted into the anterior chamber with the tube, or internal occlusion of the tube 
using a “rip-cord” technique have all been used effectively.  A 30-gauge cannula 
is used to cannulate the end of the tube and confirm complete occlusion of the 
tube.  Following tube occlusion, the surgeon may fenestrate the tube if desired.  
The method of tube fenestration is left to the discretion of the surgeon. 
 
Preparation of Tube: 
 
The tube is trimmed bevel-up to extend 2 to 3 mm into the anterior chamber. 
 
Insertion of Tube into the Anterior Chamber: 
 
A 23-gauge needle is used to enter the anterior chamber at the posterior limbus 
parallel to the iris plane.  The Baerveldt tube is inserted through this entry 
incision and should be well positioned in the anterior chamber away from the 
corneal endothelium and just above the iris.  A 23-gauge needle produces an 
adequate entry incision for the tube without causing aqueous leakage around the 
tube. 
 


 
31 
Coverage of Tube: 
 
A donor patch graft composed of donor sclera, dura mater, or pericardium is 
used to cover the limbal portion of the tube.  The suture selected to fixate the 
patch graft is of the surgeon’s choice. 
 
Conjunctival Closure: 
 
Tenon’s and conjunctiva are reapproximated to the limbus.  The suture used for 
the conjunctival closure is determined by the surgeon in keeping with his or her 
usual practice. 
 
Intraoperative Medications: 
 
The use of intraoperative medications is at the surgeon’s discretion.  
Subconjunctival antibiotics and corticosteroids may be injected, and a 
cycloplegic-mydriatic drop and steroid-antibiotic ointment may be instilled at the 
conclusion of the case, as determined by the surgeon in keeping with his or her 
usual practice. 


 
32 
5. 
Study Organization 
 
5.1 
Introduction 
 
5.2 
Clinical Centers 
 
5.3 
Statistical Coordinating Center 
 
5.4 
Safety and Data Monitoring Committee 
 
5.5 
Steering Committee 
 


 
33 
5.1 
Introduction 
 
 
Multicenter clinical trials require an organizational structure that provides efficient 
operations and facilitates communication.  The following resource centers work 
together in this study: 
 
• Clinical Centers (CC) 
 
• Statistical Coordinating Center (SCC) 
 
• Safety and Data Monitoring Committee (SDMC) 
 
• Steering Committee (SC) 
 
 
5.2 
Clinical Centers: 
 
 
Each CC is responsible for screening potential study patients, enrolling an 
adequate number of eligible patients, and following the patients according to the 
protocol until the termination of the study.  Each CC has one principal 
investigator.  The responsibilities of the CC are as follows: 
 
• To assess the eligibility of patients for the PTVT Study. 
 
• To enroll an adequate number of patients in the study through 
informed consent. 
 
• To manage each patient in accordance with the randomized 
assignment provided by the SCC. 
 
• To examine patients using the techniques and schedules established 
for the study. 
 
• To complete the proper forms and obtain visual fields and quality of life 
assessments at the appropriate follow-up visits. 
 
• To respond promptly to requests made by the SCC. 
 
• To maintain patient records for the PTVT Study in an easily accessible 
and confidential manner. 
 


 
34 
• To obtain approval for the study and consent form from the local 
Institutional Review Board. 
 
• To provide annual reports to the local IRB while the study is collecting 
follow-up data. 
 
• To promote patient satisfaction and commitment to the trial. 
 
• To provide representation at all meetings of the SC. 
 
 
5.3 
Statistical Coordinating Center 
 
 
The SCC is located at the Department of Biostatistics at the Bascom Palmer Eye 
Institute.  The SCC receives, edits, processes, analyzes, and stores all study 
data.  The SCC coordinates the activities at the CC and monitors adherence to 
the study protocol.  The responsibilities of the SCC are listed below: 
 
• To provide guidance in the development and implementation of the 
design of the primary study and ancillary studies. 
 
• To confirm local IRB approval of the study and consent form before 
initiating participation of a CC. 
 
• To verify eligibility of the patient and completion of the consent form 
prior to randomization. 
 
• To randomize study patients. 
 
• To review data received, process, and store all study data. 
 
• To produce extensive monitoring reports for the SC and SDMC every 
six months and upon request. 
 
• To assist in the preparation of manuscripts. 
 
 
5.4 
Safety and Data Monitoring Committee 
 
 
The SDMC is responsible for the ethical conduct of the study.  This committee 
oversees the informed consent process and major changes in the protocol.  The 
SDMC reviews the accumulating data for evidence of adverse and beneficial 


 
35 
treatment effects.  This committee meets twice each year for the duration of the 
study.  Telephone conferences will occur as needed.  The responsibilities of the 
SDMC are as follows: 
 
• To review the study design and study documents before the start of 
the study to identify any problems that may affect future data analysis 
or patient safety. 
 
• To monitor adherence to the study protocol at each CC. 
 
• To review treatment reports prepared by the SCC for evidence of 
adverse and beneficial treatment effects. 
 
• To terminate the study if treatment benefits or treatment risks are so 
high for one treatment group that continuation of the trial is deemed 
unethical. 
 
• To advise the SC on interpretation of study data. 
 
• To recommend to the SC changes in study protocol based on periodic 
data analysis. 
 
• To review and approve all publications and presentations. 
 
• To determine when data collected in the study should be released to 
study investigators, study patients, the medical community, and the 
public. 
 
 
5.5 
Steering Committee 
 
 
The SC is composed of the principal investigator from each CC and the Study 
Chairmen.  The SC provides leadership for the trial.  This committee has overall 
responsibility for directing activities and formulating policy for the study.  This 
committee meets twice each year for the duration of the study.  Telephone 
conferences will occur as needed.  The specific functions of the SC are as 
follows: 
 
• To evaluate and approve operational procedures in the study, including 
the Manual of Procedures and data forms. 
 
• To change procedures and resolve technical issues during the course 
of the trial. 


 
36 
• To review study progress and take steps to correct deficiencies, such 
as patient recruitment, adherence to protocol, or data collection 
procedures. 
 
• To appoint and disband subcommittees needed for execution of the 
study. 
 
• To review and approve ancillary studies. 
 
• To collaborate in preparing manuscripts of study findings for 
publication.


 
37 
Policy Matters 
 
 
6.1 
Patient Consent 
 
6.2 
Publication and Presentation Policy 
 
6.3 
Ancillary Studies Policy 
 
6.4 
Policy of Confidentiality 
 
6.5 
Authorship Policy 
 


 
38 
6.1 
Institutional Review Board Approval and Ethical Conduct 
 
 
The Primary Tube Versus Trabeculectomy (PTVT) Study will be conducted in 
accordance with the ethical principles that have their origin in the Declaration of 
Helsinki and that are consistent with Good Clinical Practice and applicable 
regulatory requirements.  The principal investigator of each Clinical Center is 
responsible for obtaining approval for the study protocol and consent form from 
the local Institutional Review Board (IRB).  A copy of each Clinical Center’s 
approved consent and documentation of IRB approval must be submitted to the 
Statistical Coordinating Center prior to beginning patient enrollment in the study.  
A copy of the consent form prepared for the Institutional Review Board for the 
University of Miami, Miller School of Medicine is provided at the end of this 
section. 
 
The PTVT Study requires that written consent be obtained from each patient 
enrolled in the study.  It is the responsibility of the investigator to provide each 
subject with full and adequate verbal and written information using the IRB 
approved consent form document, including the objective and procedures of the 
study and the possible risks involved in inclusion in the study.  The signed 
consent form is kept with the study records at the Clinical Center.  A copy of the 
signed consent is given to the patient, and a second copy is sent to the Statistical 
Coordinating Center. 
 
 
6.2 
Publication and Presentation Policy 
 
 
A PTVT Study publication is one which contains details of the design, methods, 
or results of the PTVT Study, and is written by investigators from the PTVT 
Study.  Any paper classified as a PTVT Study publication must be approved by 
the Safety and Data Monitoring Committee prior to submission for publication.  
Similarly, any presentation made on behalf of the PTVT Study must be approved 
by the Safety and Data Monitoring Committee.  All papers of the PTVT Study will 
be published under conventional author format with acknowledgement of the 
PTVT Study Group. 
 
 
6.3 
Ancillary Studies Policy 
_______________________________________________________ 
 
A PTVT ancillary study is defined as any investigation which is carried out at one 
or more, but not all, of the participating PTVT Study Clinical Centers and which 
utilizes the resources of the PTVT Study.  The resources may involve the 
participants themselves (through collection of added items of data for special 


 
39 
analyses) or the PTVT Study database of one or more of the Clinical Centers.  All 
PTVT ancillary studies require review and approval from the Steering Committee 
and Safety and Data Monitoring Committee before they are implemented.  No 
PTVT ancillary study will be approved which interferes with the data collection, 
treatment, or recruitment process of the study.  Papers arising from ancillary 
studies will, as a rule, be published under the name of the investigator(s) 
responsible for the work, with or without the acknowledgement of the PTVT 
Study, depending on dictates of the Steering Committee.  Provisions for access 
to the main study file for the purpose of linking data from the ancillary study with 
the main study file must be discussed and approved by the Clinical Center and 
the Statistical Coordinating Center during approval of the project. 
 
 
6.4 
Policy of Confidentiality 
 
 
Materials distributed for Steering Committee and Safety and Data Monitoring 
Committee meetings are confidential.  Minutes from all study meetings are 
confidential.  Access to a participant’s record by any unauthorized individual is 
prohibited.  Tabulations or listings which reveal the identity of individual study 
participants are confidential. 
 
 
6.5 
Authorship Policy 
 
 
Mainline Papers:  Original papers detailing design, methods, or results of the 
TVT Study. 
 
• The individual who writes the paper is listed as first author. 
 
• Conventional author format. 
 
• Acknowledgement of the PTVT Study Group. 
 
• Full credit roster, indicating participating centers and associated 
personell, as well as a listing of all standing committees and their 
members. 
 
• Only investigators who have enrolled patients will be included in 
publications. 
 
Ancillary Papers:  Original papers dealing with a secondary aim of the study or 
dealing with a question developed and pursued by PTVT Study investigators 
using PTVT Study data. 


 
40 
• Conventional author format. 
 
• Full acknowledgement of the PTVT Research Group, if the Steering 
Committee so dictates. 
 
Presentations:  Any paper presented on behalf of the PTVT Study by one or 
more PTVT Study investigators. 
 
• Abstract and program listing indicate presentation is made on behalf of 
the PTVT Study Group. 
 
• Name of presenter is listed in abstract and program. 


 
41 
INFORMED CONSENT FORM 
 
PRIMARY TUBE VERSUS TRABECULECTOMY (PTVT) STUDY 
 
 
PURPOSE:   
Your doctor feels that you should have surgery as treatment for your glaucoma.  A 
trabeculectomy with mitomycin C or Baerveldt glaucoma implant are the two most 
common types of glaucoma operations performed.  Both procedures work by providing a 
route by which aqueous fluid can drain out of the eye to lower the intraocular pressure.  
The Baerveldt implant does so by placing a tube into the eye which shunts aqueous fluid 
to a silicone plate which is attached to the sclera (white portion of the eye).  A 
trabeculectomy allows aqueous fluid to drain through a trap door-like incision in the 
sclera, and mitomycin C is applied to this region to reduce the likelihood that the trap 
door will scar closed.  Comparable success rates and complication rates have been 
observed separately for the Baerveldt implant and trabeculectomy with mitomycin C.  
While both procedures have been shown to be safe and effective, it is unclear if one is 
superior to the other.  The purpose of this study is to determine if one type of surgery 
works better with fewer complications.  This form documents a request for your 
participation in this study. 
 
PROCEDURE:   
If you agree to participate in this study, you will be assigned by chance (like a flip of a 
coin) to undergo either a trabeculectomy with mitomycin C or Baerveldt implant.  Your 
doctor will perform the normal postoperative examinations at 1 day, 1 week, 1 month, 3 
months, 6 months, 12 months, 18 months, 2 years, 3 years, 4 years, and 5 years after 
surgery, in addition to any other visits he or she feels are necessary.  Information 
collected at these visits will be analyzed for this study.   
 
RISKS:   
The surgical risks are similar for the Baerveldt implant and a trabeculectomy with 
mitomycin C.  They include a risk of bleeding, infection, too low an intraocular pressure 
after surgery, failure of the operation to control the intraocular pressure, cataract, retinal 
swelling, and corneal swelling.  In addition, there is a risk of tube erosion and double 
vision associated with the Baerveldt implant, and a risk of leakage from the bleb and eye 
discomfort produced by the bleb with a trabeculectomy with mitomycin C.  There 
appears to be a higher risk of serious infection associated with a mitomycin 
trabeculectomy compared with a Baerveldt implant.  You would experience these 
surgical risks whether you participate in the study or not.  This study will not produce any 
change in the typical care you would receive following your surgery, so there are no 
additional risks to you for participating in the study. 
 
BENEFITS:   
No direct benefit can be promised to you for your participation in this study. 
 
ALTERNATIVES:   
You have the alternative not to participate in this study, and receive either a 
trabeculectomy with mitomycin C or Baerveldt implant as determined by your doctor. 
 
 
 


 
42 
COSTS:   
You or your insurance company will be responsible for medical costs of participating in 
this study.  If you have insurance, your insurance company may or may not pay for these 
costs.  If you do not have insurance, or if your insurance company refuses to pay, you 
will be expected to pay.  You will not incur any added costs by participating in the study. 
 
COMPENSATION FOR INJURY:   
You may be exposed to risk of injury from participation in this study.  If injury occurs, 
treatment will in most cases be available.  If you have insurance, your insurance 
company may or may not pay for these costs.  If you do not have insurance, or if your 
insurance company refuses to pay, you will be expected to pay.  Funds to compensate 
for pain, expenses, lost wages and other damages caused by injury are not routinely 
available. 
 
CONFIDENTIALITY:   
By signing this consent, you authorize the Investigator(s) and his/her/their staff to access 
your medical records and associated information as may be necessary for purposes of 
this study.  Your records and results will not be identified as pertaining to you in any 
publication without your expressed permission.  The investigator and his/her 
collaborators will consider your records confidential to the extent permitted by law.  The 
Food and Drug Administration (FDA) and Department of Health and Human Services 
(DHHS) may review these research records.  Your records may also be reviewed for 
audit purposes by authorized University of Miami employees or other agents who will be 
bound by the same provisions of confidentiality. 
 
RIGHT TO REFUSE OR WITHDRAW:   
Your participation in this study is voluntary.  You are free to refuse to participate in the 
study or withdraw your consent at any time during the study.  Your withdrawal or lack of 
participation will not prejudice further/additional medical treatment.  The investigator 
reserves the right to remove you from the study without your consent at such time that 
they feel it is in the best interest for you medically or for administrative reasons.  You 
may ask and will receive answers to any questions during the course of the study.  If you 
have any questions about this study, please contact Dr. Steven Gedde at 305-326-6435 
(daytime) or 305-867-9029 (nighttime).  If you have questions about your rights as a 
research participant, you may contact The Human Subjects Research Office at 305-243-
3195. 
 
 
____________________________________ 
 
_____________________ 
Signature of Subject  
 
 
 
 
Date 
 
____________________________________ 
 
_____________________ 
Signature of Witness  
 
 
 
 
Date 
 
____________________________________ 
 
_____________________ 
Signature of Person Obtaining Consent 
 
 
Date 
 
Principal Investigator’s Name:  Steven J. Gedde, M.D. 
Day Phone:  (305) 326-6435 
Night Phone:  (305) 867-9029 


 
43 
7. 
Clinical Center Procedures 
 
 
7.1 
Qualifying Assessment 
 
7.2 
Assignment of Patient Identification Number 
 
7.3 
Randomization Procedure 
 
7.4 
Schedule of Visits 
 


 
44 
7.1 
Qualifying Assessment 
 
 
The Qualifying Assessment establishes whether the patient satisfies PTVT Study 
eligibility criteria.  If the patient appears to be eligible for the study, the Clinical 
Center (CC) completes the Qualifying Assessment Form and Preoperative Form.  
Both forms are faxed to the Statistical Coordinating Center (SCC), along with a 
copy of the consent form.  Informed consent is an eligibility criterion because it is 
an agreement by the patient to be randomized and complete follow-up in their 
treatment group.  The SCC reviews each of the inclusion and exclusion criteria to 
ensure that the patient is eligible.  It is vital to the scientific validity of the 
study that every eligible patient be offered enrollment. 
 
 
7.2 
Assignment of Patient Identification Number 
 
 
Any patient who is confirmed by the SCC to meet the eligibility criteria and is 
enrolled in the study is assigned a patient identification number.  The SCC 
provides a list of patient identification numbers to each CC.  The patient 
identification number is a six digit, three letter code which is unique for each 
patient.  The first two digits refer to the CC.  The third digit refers to the patient’s 
stratum.  The fourth, fifth, and six digits are a sequential number for each patient 
within a stratum.  The final three letters are selected from the patient’s name by 
any system chosen by the CC.  For example, an identification number 03-1-003-
AZE refers to the third patient in stratum 1 enrolled at CC 3. 
 
 
7.3 
Randomization Procedure 
 
 
Randomization takes place at the time the patient is enrolled in the study.  After 
patient eligibility is confirmed and a patient identification number is provided, the 
SCC assigns treatment by saying, “trabeculectomy with mitomycin C” or 
“Baerveldt implant”.  The CC then repeats the assigned treatment.  The surgery 
date is the study entry date, and the dates for all postoperative follow-up visits 
are computed from this date. 
 
The randomization schedule is constructed using a computer pseudo-random 
number generator.  The allocation ratio is equal between the two treatment 
groups.  The randomization is blocked by clinic and study stratum using a 
scheme with small variable blocks.  This procedure ensures that there is an 
equal number of patients in each treatment group even early in the trial, and that 
the CC is not able to predict the next treatment assignment. 


 
45 
7.4 
Schedule of Visits 
 
 
All study investigators must be familiar with the schedule of visits to ensure that 
required data is collected and that future visits are scheduled within the 
appropriate time windows.  The need for continued follow-up and timely visits 
should be stressed to the patient during the informed consent process and 
throughout the study.  An appointment schedule is generated for each patient by 
the SCC and sent to the patient’s CC.  Time windows for follow-up visits are 
shown in Table 2.  Table 3 summarizes the required data at each of the 
scheduled visits. 
 


 
46 
Table 2.  Time Windows for Follow-Up Visits 
 
 
 
Number of Days After Surgery 
 
Follow-Up Visit 
Ideal Time 
Preferred Time 
Acceptable Time 
 
 
     
    Window 
      Window 
 
1 Day 
1 day  
1 day 
1–3 days 
 
1 Week 
7 days 
6–8 days 
4–14 days 
 
1 Month 
30 days 
23–37 days 
15–59 days 
 
3 Month 
90 days 
76–104 days 
60–120 days 
 
6 Month 
182 days 
161–203 days 
121–270 days 
 
12 Month 
365 days 
305–425 days 
271–455 days 
 
18 Month 
547 days 
487–607 days 
456–637 days 
 
2 Year 
730 days 
670–790 days 
638–912 days 
 
3 Year 
1095 days 
1005–1185 days 
913–1277 days 
 
4 Year 
1460 days 
1370–1550 days 
1278–1642 days  
 
5 Year 
1825 days 
1735–1915 days 
1643–2007 days


 
47 
Table 3.  Schedule of Visits 
 
 
 
Preoperative 
1 Day 
1 Week 
1 Month 
3 Month 
6 Month 
 
Refraction 
X 
 
 
 
 
 
Snellen VA 
X 
X 
X 
X 
X 
X 
 
ETDRS VA 
X 
 
Slit Lamp Biomicroscopy 
X 
X 
X 
X 
X 
X 
 
Seidel Testing 
 
X 
X 
X 
X 
X 
 
Tonometry 
X 
X 
X 
X 
X 
X 
 
Pachymetry 
X 
 
Motility Evaluation 
X 
 
 
 
 
# 
 
Gonioscopy 
X 
 
Ophthalmoscopy 
X 
$ 
X 
X 
X 
$ 
 
Humphrey 24-2 
X 
 
 
 
Informed Consent 
X 
 


 
48 
Table 3.  Schedule of Visits (continued) 
 
 
 
12 Month 
18 Month 
2 Year 
3 Year 
4 Year 
5 Year 
 
Refraction 
X 
 
X 
X 
X 
X  
 
 
 
 
Snellen VA 
X 
X 
X 
X 
X 
X 
 
ETDRS VA 
X 
 
 
X 
 
X 
 
Slit Lamp Biomicroscopy 
X 
X 
X 
X 
X 
X 
 
Seidel Testing 
X 
X 
X 
X 
X 
X 
 
Tonometry 
X 
X 
X 
X 
X 
X 
 
Pachymetry 
X 
 
X 
X 
X 
X 
 
Motility Evaluation 
       X 
# 
# 
# 
# 
       X 
 
Gonioscopy 
 
 
Ophthalmoscopy 
X 
$ 
X 
X 
X 
X 
 
Humphrey 24-2 
X 
 
X 
X 
X 
X 
 
 
# = if diplopia 
$ = if shallowing of the anterior chamber, IOP < 6 mm Hg, or unexplained vision loss 


 
49 
8. 
Statistical Coordinating Center Procedures 
 
 
8.1 
Data Management 
 
8.2 
Data Security 
 
8.3 
Data Forms 
 


 
50 
8.1 
Data Management 
 
 
A master log is kept of each patient randomized in the PTVT Study.  An 
appointment schedule is made for each patient and sent to the patient’s Clinical 
Center.  When a data form is received at the Statistical Coordinating Center, it is 
processed for filing and data entry.  Each form is data entered by a data entry 
clerk and then verified by double entry by the SCC Research Coordinator.  Edit 
checks, such as missing data and out-of-range values, will be clarified within the 
Clinical Center. 
 
The statistical package SPSS is used for data entry, management, and analysis.  
Each of the study’s two statisticians has a personal computer and one more is 
dedicated to data entry.  The Research Coordinator also has a personal 
computer to use for data management, study correspondence, reports, and 
manuscripts.  Each computer, except the one dedicated to data entry, has 
access to the University of Miami’s network for e-mail, Internet access, and data 
file transfer. 
 
 
8.2 
Data Security 
 
 
The paper data forms for the PTVT Study are kept in file cabinets in the 
Biostatistics facility in the Clinical Research Building.  The building is locked and 
access is by card key entry.  A security guard is present during working hours.  
The computer files for the study are kept on computers in the same location.  
These rooms are kept locked when not in use, and the study computer files are 
password-protected.  The data is backed up weekly, and monthly backups are 
stored at a remote facility.  Computer data files used for publication are saved 
and stored as separate files. 
 
 
8.3 
Data Forms 
 
 
The data forms were designed to be self-explanatory.  Their completion should 
not require reference to separate information manuals.  The data forms contain 
information to be collected at a given point in time during the study.  Information 
collected at another date is incorporated into a separate form.  Data forms are 
faxed to the Statistical Coordinating Center for data entry.  Forms will be 
reviewed periodically and revised as dictated by protocol changes.  The various 
data forms are provided at the end of this section. 


 
51 
8.4 
Data Management 
 
 
A master log is kept of each patient randomized in the PTVT Study.  An 
appointment schedule is made for each patient and sent to the patient’s Clinical 
Center.  When a data form is received at the Statistical Coordinating Center, it is 
processed for filing and data entry.  Each form is data entered by a data entry 
clerk and then verified by double entry by the SCC Research Coordinator.  Edit 
checks, such as missing data and out-of-range values, will be clarified within the 
Clinical Center. 


 
52 
9. 
Corneal Endothelial Change Ancillary Study 
 
 
9.1 
Background 
 
9.2 
Clinical Procedures 
 
9.3 
Main Outcome Measures 
 
9.4 
Statistical Analysis 
 
9.5 
Sample Size 


 
53 
9.1 
Background 
 
 
Historically, there has been widespread concern that tube shunts placed in the 
anterior chamber angle may mechanically damage peripheral corneal endothelial 
cells and result in long-term endothelial failure in susceptible eyes.  In eyes with 
glaucoma that require tube shunts, there are often a number of confounding 
influences including the severity and duration of intraocular pressure elevation, 
the number of previous intraocular surgical procedures, and the presence of co-
existing corneal disease.  In the types of glaucoma for which shunts were 
traditionally indicated, the small risk of corneal endothelial failure was considered 
a low risk relative to the high risk of blindness from progressive glaucoma. In 
such eyes, there was usually no effective alternative to tube shunt implantation.  
However, if tube shunt surgery is to receive widespread acceptance as a primary 
surgical option for primary open angle glaucoma, it will be important to test the 
hypothesis that shunts implanted in the anterior chamber angle can be positioned 
so that they are not associated with long-term progressive loss of corneal 
endothelial function in excess of the rate of loss that would have otherwise 
occurred.  This ancillary study to the PTVT Study is designed to compare long-
term corneal endothelial changes following tube shunt surgery and 
trabeculectomy with mitomycin C. 
 
 
9.2 
Clinical Procedures 
 
 
It is expected that Clinical Centers with the equipment for obtaining corneal 
endothelial cell counts will participate in this ancillary study.  PTVT patients 
undergo specular microscopy in both eyes at the Qualifying Assessment and at 1 
year, 3 year, and 5 year follow-up visits.  Additionally, patients in the tube group 
have the entry site of the tube assessed with gonioscopy at the 1 year, 3 year, 
and 5 year study visits. 
 
Specular Microscopy: 
 
Specular microscopy is performed at the Qualifying Assessment, and 
measurements are repeated at the 1 year, 3 year, and 5 year follow-up visits 
using the same instrument.  Central corneal endothelial cell counts are obtained 
in both eyes while in primary gaze.  The coefficient of variation of cell size and 
percentage hexagonality is used to indicate the degree of polymorphism and 
pleomorphism, respectively.  Three images are acquired and the best image 
selected for morphological analyses.  A frame area that contains 75 cells or more 
is used to reduce sampling errors, and only whole cells with continuous cell 
borders are accepted for the planimetric endothelial cell analysis.  In corneas in 
which obtaining good quality specular images proves difficult, the corneal 


 
54 
endothelial cell density is estimated by averaging the density from 3 best images 
taken. 
 
Gonioscopy: 
 
In patients randomized to the tube group, gonioscopy is used to identify the 
position of the tube entry site in the angle relative to a fixed landmark at the 1 
year, 3 year, and 5 year follow-up visits.  Schwalbe’s line serves as this 
landmark, and it is the peripheral limit of the corneal endothelium.  The tube entry 
is graded as all of tube posterior to Schwalbe’s line, some of the tube but less 
than 50% anterior to Schwalbe’s line, more than 50% and less than 100% of tube 
Anterior to Schwalbe’s line, and all of tube anterior to Schwalbe’s line. 
 
 
9.3 
Main Outcome Measures 
 
 
Central corneal endothelial cell density and central corneal thickness are the 
main outcome measures in this study.  Data are analyzed to explore the 
relationships between these outcome measures and tube entry site position, 
position of tube tip, postoperative intraocular pressure levels, complications, 
patient demographics, and time from glaucoma surgery. 
 
 
9.4 
Statistical Analysis 
 
 
The principal aim of this ancillary study is to compare the rates of loss of 
endothelial cells in the two randomized groups of the PTVT Study.  These rates 
are quantified as the difference in counts between baseline and follow-up 
measurements.  The largest differences are expected at the 5 year follow-up 
visit.  However, comparisons are made at 1 and 3 years postoperatively as there 
may be substantial loss to follow-up of study patients by 5 years. The 
significance of the difference between loss rates in the two treatment groups are 
assessed with analysis of covariance.  Covariates include baseline counts and 
classification of the tube site by gonioscopy in patients randomized to the tube 
group.  Baseline patient demographic variables are included in exploratory 
analyses.  Other analyses focus on coefficient of variation and percentage 
hexagonality measurements.  Another secondary analysis involves endothelial 
cell count loss rates in the study eye compared to the non-study eye.  The 
longitudinal measurements of count data are used to examine the characteristics 
of loss with time. 
 
 
 


 
55 
9.5 
Sample Size 
 
 
The PTVT Study has a fixed sample size.  This ancillary study is performed on all 
enrolled patients at Clinical Centers that are able to measure corneal endothelial 
density.