The Tube Versus Trabeculectomy Study:
Design and Baseline Characteristics of Study
Patients
STEVEN J. GEDDE, MD, JOYCE C. SCHIFFMAN, MS, WILLIAM J. FEUER, MS,
RICHARD K. PARRISH II, MD, DALE K. HEUER, MD, JAMES D. BRANDT, MD, AND THE
TUBE VERSUS TRABECULECTOMY STUDY GROUP
● PURPOSE: The Tube Versus Trabeculectomy (TVT)
Study will compare the safety and efficacy of nonvalved
tube shunt surgery to trabeculectomy with mitomycin C
in patients with previous intraocular surgery.
● DESIGN: Multicenter randomized clinical trial.
● METHODS: SETTING: 17 Clinical Centers. STUDY POPU-
LATION: Patients 18 to 85 years of age who have under-
gone previous trabeculectomy, cataract extraction with
intraocular lens implantation, or both and have inade-
quately controlled glaucoma with intraocular pressure
(IOP) >18 mm Hg and <40 mm Hg on tolerated medical
therapy. INTERVENTIONS: Study patients were randomized
to undergo placement of a 350-mm2 Baerveldt glaucoma
implant or trabeculectomy with mitomycin C (0.4 mg/ml
for 4 minutes). MAIN OUTCOME MEASURES: IOP, complica-
tion rates, visual acuity, visual field, quality of life,
reoperations for glaucoma, and need for supplemental
medical therapy.
● RESULTS: A total of 212 patients were enrolled be-
tween October 1999 and April 2004. The age of the
study population was 71.0 ⴞ 10.4 years (mean ⴞ SD),
and 53% were women. The baseline IOP was 25.3 ⴞ 5.3
mm Hg (mean ⴞ SD). There were no significant differ-
ences in the demographic and ocular characteristics
between the 2 treatment groups.
● CONCLUSIONS: Practice patterns vary in the surgical
management of glaucoma, and there are differing opin-
Accepted for publication March 7, 2005.
From the Bascom Palmer Eye Institute, Miller School of Medicine,
University of Miami, Miami, Florida (S.J.G., J.C.S., W.J.F., R.K.P. II);
Department of Ophthalmology, Medical College of Wisconsin, Milwau-
kee, Wisconsin (D.K.H.); and Department of Ophthalmology, University
of California, Davis, Sacramento, California (J.D.B.).
Supported by a research grant from Pfizer, Inc, New York, New York,
by grant EY014801 from the National Eye Institute, National Institutes of
Health, Bethesda, Maryland, and by Research to Prevent Blindness, Inc,
New York, New York.
*A listing of additional investigators who participated in this study
appears in the Appendix.
Inquiries to Steven J. Gedde, MD, Bascom Palmer Eye Institute, 900
N.W. 17th Street, Miami, Florida 33136; fax: 305-326-6478; e-mail:
sgedde@med.miami.edu
0002-9394/05/$30.00 © 2005 BY ELSEVIER INC. ALL
doi:10.1016/j.ajo.2005.03.031
ions among glaucoma surgeons regarding the preferred
surgical approach in patients who have undergone previ-
ous cataract extraction and/or failed filtering surgery.
Forthcoming data from the TVT Study should provide
valuable information comparing two surgical procedures
commonly used in this patient population. (Am J Oph-
thalmol 2005;140:275–287. © 2005 by Elsevier Inc. All
rights reserved.)
T
HE SURGICAL MANAGEMENT OF GLAUCOMA HAS
evolved over the past several decades. Trabeculectomy
(or guarded filtration surgery) replaced full thickness
procedures when it became clear that similar success rates
could be achieved with a lower rate of complications. Eyes
that had undergone previous ocular surgery, including cata-
ract extraction and/or failed glaucoma filtering surgery, were
found to be at higher risk for subsequent trabeculectomy
failure. Wound-healing modulation with antifibrotic agents,
such as 5-fluorouracil (5-FU) and mitomycin C (MMC), was
subsequently introduced and improved the success rate of
trabeculectomy.1–3 The use of 5-FU and MMC as adjuncts
with glaucoma filtering surgery has now become widespread
in clinical practice.4
Although wound-healing modulation has increased the
likelihood of intraocular pressure control (IOP) following
filtering surgery, there has been a growing concern within
the ophthalmic community about the complications asso-
ciated with the use of 5-FU and MMC. The prevalence of
bleb-related infections, bleb leaks, and bleb dysesthesia
associated with a perilimbal filtering bleb suggests the need
to consider alternatives. Glaucoma drainage implants (or
tube shunts) have been growing in popularity in recent
years, and these devices offer an alternative surgical ap-
proach to trabeculectomy to reduce IOP in glaucoma
patients. Favorable results have been reported with glau-
coma drainage implants (GDIs) in the treatment of
refractory glaucomas.5–15 Comparable rates of severe com-
plications have been observed with GDI surgery and
trabeculectomy with antifibrotic agents.16
RIGHTS RESERVED. 275.e1
 TABLE 1. Tube Versus Trabeculectomy Study Synopsis

Purpose To compare the safety and efficacy of nonvalved tube shunt surgery to trabeculectomy with mitomycin C

Treatment groups 350-mm2 Baerveldt glaucoma implant

Patient eligibility
Inclusion criteria
Exclusion criteria
Treatment assignment
Follow-up examinations
Outcome measures
Enrollment
Study centers and committees
Trabeculectomy with mitomycin C (0.4 mg/ml for 4 minutes)
Age 18 to 85 years
Inadequately controlled glaucoma with IOP ⱖ18 mm Hg and ⱕ40 mm Hg on tolerated medical
therapy
Previous trabeculectomy, cataract extraction with intraocular lens implantation, or both
Unwilling or unable to give consent, unwilling to accept randomization, or unable to return for
scheduled protocol visits
Pregnant or nursing women
No light perception vision
Active iris neovascularization or active proliferative retinopathy
Iridocorneal endothelial syndrome
Epithelial or fibrous downgrowth
Aphakia
Vitreous in the anterior chamber for which a vitrectomy is anticipated
Chronic or recurrent uveitis
Severe posterior blepharitis
Unwilling to discontinue contact lens use after surgery
Previous cyclodestructive procedure, scleral buckling procedure, or silicone oil present
Conjunctival scarring precluding a trabeculectomy superiorly
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
Random
Stratified by clinic and type of previous intraocular surgery
1 day, 1 week, 1 month, 3 months, 6 months, 12 months, 18 months, 1 year, 2 years, 3 years
4 years, 5 years
IOP
Complication rates
Visual acuity
Visual field
Quality of life
Reoperations for glaucoma
Need for supplemental medical therapy
212 patients
17 Clinical Centers
Safety and Data Monitoring Committee
Statistical Coordinating Center
Steering Committee

The Tube Versus Trabeculectomy (TVT) Study is a
multicenter randomized clinical trial comparing the safety
and efficacy of placement of a Baerveldt glaucoma implant
(Advanced Medical Optics, Irvine, California, USA) to
trabeculectomy with the adjunctive use of MMC in eyes
that have undergone previous filtering surgery, cataract
surgery with intraocular lens implantation, or both.
METHODS
A SYNOPSIS OF THE TVT STUDY DESIGN FEATURES IS PRO-
vided in Table 1. The Institutional Review Board at each
Clinical Center approved the study protocol before initi-
ating recruitment. An effort was made to recruit every
eligible patient into the study. Following a discussion of
the study, informed consent was obtained in accord with
Health Insurance Portability and Accountability Act
(HIPAA) regulations.
● STUDY ORGANIZATION: Multicenter clinical trials re-
quire an organizational structure that provides efficient
operations and facilitates communication. The Appendix
describes the study organization and lists the participating
centers and committees. Investigators at 17 Clinical Cen-
ters have been responsible for screening potential study
patients, enrolling eligible patients, and following the
patients according to the study protocol set forth in detail

275.e2 AMERICAN JOURNAL OF OPHTHALMOLOGY AUGUST 2005

in the Manual of Procedures. An independent Safety and
Data Monitoring Committee (SDMC) monitors all aspects
of the study. The SDMC reviews the accumulating data for
evidence of adverse and beneficial treatment effects. The
Statistical Coordinating Center (SCC) receives, edits,
processes, analyzes, and stores all study data. The SCC
coordinates activities at the Clinical Centers and monitors
adherence to the study protocol. The Steering Committee
(SC) is composed of the principal investigators from each
Clinical Center and the study chairmen. The SC provides
leadership for the study, and this committee has overall
responsibility for directing activities and formulating pol-
icy for the study.
● ELIGIBILITY CRITERIA: Patients had to meet specific
criteria to be eligible for the TVT Study. In patients with
two eligible eyes, only the first eye undergoing surgical
treatment was enrolled in the study.
Inclusion Criteria. All of the following criteria must
have been present in the study eye to be eligible for
enrollment in the study:
1. Age 18 to 85 years
2. Inadequately controlled glaucoma with IOP ⱖ18 mm
Hg and ⱕ40 mm Hg on tolerated medical therapy
3. Previous trabeculectomy, cataract extraction with
intraocular lens implantation, or both
Exclusion Criteria. The patient was not entered into the
study if any of the following exclusion criteria were
present, with ocular exclusion criteria applying only to the
study eye:
1. Unwilling or unable to give consent, unwilling to
accept randomization, or unable to return for sched-
uled protocol visits
2. Pregnant or nursing women
3. No light perception vision
4. Active iris neovascularization or active proliferative
retinopathy
5. Iridocorneal endothelial syndrome
6. Epithelial or fibrous downgrowth
7. Aphakia
8. Vitreous in the anterior chamber for which a
vitrectomy was anticipated
9. Chronic or recurrent uveitis
10. Severe posterior blepharitis
11. Unwilling to discontinue contact lens use after
surgery
12. Previous cyclodestructive procedure, scleral buck-
ling procedure, or silicone oil present
13. Conjunctival scarring precluding a trabeculectomy
superiorly
14. Need for glaucoma surgery combined with other
ocular procedures (that is, cataract surgery, pene-
trating keratoplasty, or retinal surgery) or antici-
pated need for additional ocular surgery
VOL. 140, NO. 2 TVT STUDY
● ENROLLMENT AND TREATMENT ASSIGNMENT: After
the SCC confirmed patient eligibility, a patient identifi-
cation number was provided. Randomization to placement
of a Baerveldt glaucoma implant or trabeculectomy with
MMC occurred at the time the patient was enrolled in the
study. Patients were stratified by Clinical Center into the
following 4 categories based on type of previous intraocular
surgery:
1. Previous cataract extraction only
2. Previous trabeculectomy or combined procedure
without an antifibrotic agent
3. Previous trabeculectomy with 5-FU or combined
procedure with 5-FU or MMC
4. Previous trabeculectomy with MMC
Patients were randomized with a randomly permuted
block scheme in which the block size varied between 2 and
6 with an equal number of patients randomized to each
treatment group at the end of each block at each Clinical
Center and within each stratum.
● SURGICAL PROCEDURES: The surgical procedures un-
der investigation in the TVT Study were standardized, but
allowed the surgeon some latitude to perform the opera-
tions in a manner with which he or she felt comfortable.
Baerveldt Implantation. A 350-mm2 Baerveldt glaucoma
implant was placed in the superotemporal quadrant in all
patients randomized to the tube group. A limbus-based or
fornix-based conjunctival flap was used, depending on the
surgeon’s preference. The Baerveldt plate was positioned
under or over the superior rectus and lateral rectus muscles,
according to the surgeon’s usual practice. Use of MMC was
not allowed in any implant surgery. The implant was
sutured to sclera with nonabsorbable suture at a measured
distance of 10 mm posterior to the limbus, using the two
fixation holes in the Baerveldt plate. The Baerveldt tube
was completely occluded to temporarily restrict aqueous
flow to the plate until it became encapsulated, to minimize
the risk of early postoperative hypotony. The method of
temporary tube occlusion was left to the discretion of the
surgeon. The surgeon was given the option of fenestrating
the tube for early IOP reduction. The Baerveldt tube was
trimmed bevel-up to extend 1 to 2 mm into the anterior
chamber. A 23-gauge needle was used to create a tight
entry incision into the anterior chamber at the posterior
limbus. The tube was inserted through this entry incision
and positioned away from the corneal endothelium, just
above the iris. A patch graft of sclera, dura mater, or
pericardium was used to cover the limbal portion of the
tube. The type of suture material used to fixate the patch
graft and close the conjunctiva, and the method of
conjunctival closure were determined by the surgeon. The
use of intraoperative and postoperative medications was at
the surgeon’s discretion.
275.e3
 TABLE 2. Study Measures at Scheduled Tube Versus Trabeculectomy Study Visits

Baseline 1 Day 1 Week 1 Month 3 Months 6 Months 1 Year 18 Months 2 Years 3 Years 4 Years 5 Years

Snellen visual acuity X X X X X X X X X X X X

ETDRS visual acuity X X X X X X
Slit-lamp biomicroscopy X X X X X X X X X X X X
Seidel testing X X X X X X X X X X X
Tonometry X X X X X X X X X X X X
Motility evaluation X If X If If If If X
diplopia diplopia diplopia diplopia diplopia
Gonioscopy X
Ophthalmoscopy X X X X X X X X X X X X
Perimetry X X X X X X
Quality of life assessment X X X X X X

ETDRS ⫽ Early Treatment Diabetic Retinopathy Study.

Trabeculectomy With Mitomycin C. All patients ran-
domized to the trabeculectomy group underwent a
trabeculectomy superiorly. A limbus-based or fornix-
based conjunctival flap was dissected, depending on the
surgeon’s preference. A fluid retaining sponge soaked in
MMC (0.4 mg/ml) was applied to the superior sclera for
4 minutes before or after scleral flap dissection, depend-
ing on the surgeon’s preference. This area was then
copiously irrigated with balanced saline solution (BSS).
A paracentesis tract was created in the peripheral
cornea, and a corneal-based scleral flap was dissected
approximately half scleral thickness. A block of limbal
tissue was excised underneath the trabeculectomy flap.
The scleral flap was reapproximated to the scleral bed
with interrupted or releasable 10-0 nylon suture. Fol-
lowing injection of BSS into the anterior chamber
through the paracentesis tract, the anterior chamber
remained formed with a visible leak present around the
scleral flap at equilibrium. The dimensions of the scleral
flap, the size of the inner block, and the number and
tension of the scleral flap sutures were at the surgeon’s
discretion. The type of suture material and method of
conjunctival closure (single-layered or double-layered
closure) were of the surgeon’s choice. BSS was injected
through the paracentesis tract to elevate the bleb at the
conclusion of the case. A moistened fluorescein strip
was used to check for a conjunctival leak or leakage
from the paracentesis tract, and additional sutures were
placed as needed. The use of intraoperative and postop-
erative medications was determined by the surgeon.
● STUDY MEASUREMENTS: A list of study measurements
for scheduled follow-up visits is presented in Table 2. An
appointment schedule was generated for each patient at
enrollment by the SCC and sent to the patient’s Clinical
Center. The date of surgery was the study entry date for
patients in the TVT Study, and all follow-up visits were
computed from this date. Enrolled patients complete fol-
low-up visits 1 day, 1 week, 1 month, 3 months, 6 months,
1 year, 18 months, 2 years, 3 years, 4 years, and 5 years
postoperatively.
Visual Acuity. Distance visual acuity is measured using 2
techniques, Snellen visual acuity and the standard proce-
dure developed for the Early Treatment Diabetic Retinop-
athy Study (ETDRS).17 Refraction is performed before
measurement of visual acuity by both techniques at the
baseline examination and annual follow-up visits. Snellen
visual acuity is measured at the baseline examination and
every follow-up visit. ETDRS visual acuity is tested at the
baseline examination and annual follow-up visits. The
examining clinician provides a reason for Snellen visual
acuity less than 20/30 at the baseline examination, or
reduction of visual acuity by 2 or more lines from baseline
at the 6-month follow-up visit or after.
Slit-lamp Biomicroscopy. Examination of the anterior
segment using slit-lamp biomicroscopy is performed at the
baseline examination to document the preoperative status
of the eye, and at all follow-up visits to detect any changes
in ocular status during the course of the study that may be
attributable to the disease or treatment.
Seidel Testing. Seidel testing is performed at each fol-
low-up visit. If the Seidel test is positive, the leak is graded
as an ooze, frank leak, or brisk leak.
Tonometry. Goldmann applanation tonometry is used
to measure IOP, except when irregular corneal astigma-
tism, corneal scarring, or corneal edema precludes accurate
readings. In these cases, the Tono-Pen (Mentor) is used.
IOP readings are repeated until 2 consecutive or noncon-
secutive measurements are obtained differing by 1 mm Hg
or less, and the average of the 2 readings serves as the IOP
measurement for the visit.

275.e4 AMERICAN JOURNAL OF OPHTHALMOLOGY AUGUST 2005

 TABLE 3. Demographic Characteristics of Tube Versus Trabeculectomy Study Patients

Overall Group Tube Group Trabeculectomy Group

(n ⫽ 212) (n ⫽ 107) (n ⫽ 105) P-Value

Age (years)
Mean ⫾ SD 71.0 ⫾ 10.4 70.9 ⫾ 11.0 71.1 ⫾ 9.9 .89*
Range 32–85 40–85 32–85
Gender, n (%)
Male 100 (47) 43 (40) 57 (54) .055†
Female 112 (53) 64 (60) 48 (46)
Race, n (%)
White 95 (45) 52 (49) 43 (41) .53‡
Black 82 (39) 40 (37) 42 (40)
Hispanic 30 (14) 12 (11) 18 (17)
Other 5 (2) 3 (3) 2 (2)
Hypertension, n (%) 124 (59) 61 (57) 63 (60) .76†
Diabetes mellitus, n (%) 67 (32) 31 (29) 36 (34) .49†

SD ⫽ standard deviation.
*Student t-test.
†
Chi-square test.
‡
Exact permutation chi-square test.

Motility Evaluation. Diplopia is a significant com-
plication that may occur following Baerveldt implantation.
The incidence of permanent restrictive strabismus associ-
ated with the Baerveldt glaucoma implant is not precisely
known, as this complication has not been studied prospec-
tively. To address this issue, a formal motility evaluation is
performed for all patients at baseline and at the 1-year and
5-year follow-up visits. Additionally, motility evaluation is
performed in those patients with diplopia at the 6-month
follow-up visit or after. 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 glaucoma im-
plant. 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 a hand-held prism. In patients who are unable to
fixate for cover testing, the deviation is measured by
centering the corneal light reflexes with a prism using the
modified Krimsky method.
Gonioscopy. Gonioscopy is performed at the baseline
examination. The anterior chamber angle is examined for
neovascularization under high magnification for the pur-
pose of excluding eyes with neovascularization from the
study.
Ophthalmoscopy. A dilated fundus examination is per-
formed at the baseline examination and all follow-up
visits. At the baseline examination, particular attention
is directed toward identifying signs of proliferative
retinopathy or a scleral buckling element. The presence
of either excludes the eye from the study. At all
follow-up visits, ophthalmoscopy is performed to evalu-
ate for posterior segment complications such as serous
choroidal effusions, suprachoroidal hemorrhage, or hy-
potonous maculopathy.
Perimetry. Quantitative automated perimetry is per-
formed within 1 month of enrollment and at annual
follow-up visits. The Humphrey Field Analyzer is used to
conduct a 24-2 threshold test with a size III white stimulus
in all patients.
Quality of Life Assessment. There has been a growing
interest within the medical community to determine the
impact of different medical interventions on a patient’s
functional status and quality of life. The 25-item National
Eye Institute-Visual Function Questionnaire (NEI VFQ-
25) is a quality of life instrument that was designed to
evaluate visual disability and its impact on daily function-
ing in ophthalmic patients.18 The SCC administers the
NEI VFQ-25 through telephone interview at the baseline
examination and follow-up visits. Patients at the Bascom
Palmer Eye Institute also have the option of completing
the questionnaire in the clinic at the time of their
follow-up visit.
● OUTCOME MEASURES: Because glaucoma surgeries are
intended to reduce IOP, IOP is a primary outcome measure
in the TVT Study. Concern about complications associ-
ated with both surgical procedures was a major stimulus for
the study, so the rate of complications is another primary

VOL. 140, NO. 2 TVT STUDY 275.e5

 TABLE 4. Baseline Ocular Characteristics of Tube Versus Trabeculectomy Study Patients

Overall Group (n ⫽ 212) Tube Group (n ⫽ 107) Trabeculectomy Group (n ⫽ 105) P-value

Study eye, n (%)

Right 100 (47) 51 (48) 49 (47) .99*
Left 112 (53) 56 (52) 56 (53)
IOP (mm Hg)
Mean ⫾ SD 25.3 ⫾ 5.3 25.1 ⫾ 5.3 25.6 ⫾ 5.3 .56†
Range 18–40 18–40 18–38
Glaucoma medications, n (%)
0 3 (1) 1 (1) 2 (2)
1 17 (8) 7 (7) 10 (10)
2 41 (19) 15 (14) 26 (25)
3 68 (32) 39 (36) 29 (28)
4 63 (30) 35 (33) 28 (27)
ⱖ5 20 (9) 10 (9) 10 (10)
Mean ⫾ SD 3.1 ⫾ 1.2 3.2 ⫾ 1.1 3.0 ⫾ 1.3 .13†
Previous laser therapy, n (%) 110 (52) 57 (53) 53 (50) .79*
Laser trabeculoplasty 73 (34) 42 (39) 31 (30)
Laser iridotomy 20 (9) 8 (7) 12 (11)
Other laser procedures 28 (13) 13 (12) 15 (14)
Previous intraocular surgery
Mean ⫾ SD 1.3 ⫾ 0.5 1.3 ⫾ 0.5 1.2 ⫾ 0.5 .35†
Range 1–4 1–3 1–4
Interval (months) ⫾ SD# 57 ⫾ 52 54 ⫾ 50 60 ⫾ 55 .42†
Diagnosis, n (%)
POAG 172 (81) 88 (82) 84 (80)
CACG 18 (8) 7 (7) 11 (10)
PXFG 8 (4) 7 (7) 1 (1)
PG 1 (1) 1 (1) 0
Other 13 (6) 4 (4) 9 (9) .057‡
Lens status, n (%)
Phakic 45 (21) 24 (22) 21 (20) .85‡
PCIOL 160 (75) 80 (75) 80 (76)
ACIOL 7 (3) 3 (3) 4 (4)
ETDRS VA score, mean ⫾ SD 63.6 ⫾ 21.9 62.7 ⫾ 24.1 64.4 ⫾ 19.6 .56†
Snellen VA
Median 20/35 20/30 20/40 .76§
Range 20/17–HM 20/17–HM 20/20–2/200
Reason for VA ⬍20/30, n (%)
Glaucoma 78 (37) 39 (36) 39 (37) 1.00*
Macular disease 17 (8) 6 (6) 11 (10) .29*
Cataract 10 (5) 0 (0) 10 (10) .001‡
Other 17 (8) 9 (8) 8 (8) 1.00*
Unknown 5 (2) 1 (1) 4 (4)
Humphrey visual fields储
MD, mean ⫾ SD ⫺15.9 ⫾ 9.9 ⫺16.0 ⫾ 10.2 ⫺15.8 ⫾ 9.6 .87†
PSD, mean ⫾ SD 7.0 ⫾ 3.5 7.1 ⫾ 3.5 6.9 ⫾ 3.5 .73†
NEI-VFQ score,¶ mean ⫾ SD 71.2 ⫾ 16.9 70.1 ⫾ 17.2 72.3 ⫾ 16.6 .37†
Diplopia, n (%) 7 (3) 2 (2) 5 (5) .28‡

ACIOL ⫽ anterior chamber intraocular lens; CACG ⫽ chronic angle-closure glaucoma; ETDRS ⫽ Early Treatment Diabetic Retinopathy
Study; IOP ⫽ intraocular pressure; MD ⫽ mean deviation; NEI-VFQ ⫽ National Eye Institute-Visual Function Questionnaire; PCIOL ⫽ posterior
chamber intraocular lens; PG ⫽ pigmentary glaucoma; POAG ⫽ primary open-angle glaucoma; PSD ⫽ pattern standard deviation; PXFG ⫽
pseudoexfoliative glaucoma; SD ⫽ standard deviation.
*Chi-square test.
†
Student t-test.
‡
Exact permutation chi-square test.
§
Mann-Whitney U test.
#
Interval between last intraocular surgery and surgical treatment in study.
储
34 patients did not receive a preoperative 24-2 Humphrey visual field.
¶
10 patients did not receive a preoperative NEI-VFQ.
 TABLE 5. Glaucoma Medications at Baseline in the Tube Versus Trabeculectomy Study

Overall Group Tube Group Trabeculectomy Group

(n ⫽ 212) (n ⫽ 107) (n ⫽ 105) P-value

Prostaglandin analogue, n (%) 181 (85) 90 (84) 91 (87) .74*

Beta blocker, n (%) 164 (77) 87 (81) 77 (73) .22*
Topical carbonic anhydrase inhibitor, n (%) 132 (62) 71 (66) 61 (58) .27*
Alpha2 agonist, n (%) 119 (56) 63 (59) 56 (53) .50*
Oral carbonic anhydrase inhibitor, n (%) 30 (14) 14 (13) 16 (15) .80*
Miotic, n (%) 27 (13) 18 (17) 9 (9) .11*
Epinephrine compound, n (%) 5 (2) 2 (2) 3 (3) .68†
None, n (%) 3 (1) 1 (1) 2 (2) .62†

*Chi-square test.
†
Exact permutation chi-square test.

outcome measure. A secondary outcome measure will be
failure, defined by the following criteria:
1. IOP ⬎21 mm Hg or not reduced by 20% below
baseline on two consecutive follow-up visits after 3
months
2. IOP ⱕ5 mm Hg on two consecutive follow-up visits
after 3 months
3. Additional glaucoma surgery
4. 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. Other outcome
measures include visual acuity, visual field, and quality of
life.
● SAMPLE SIZE AND POWER CALCULATIONS: Sample
size calculations were performed based on projected differ-
ences in complication rates and IOP levels between
treatment groups. In particular, the rate of late-onset
bleb-related infection was estimated to be 5.0%19 in the
trabeculectomy group and 0.05% in the tube group. The
incidence of persistent postoperative diplopia was assumed
to be 5.0% in the tube group and 0.05% in the trabecu-
lectomy group. The study was originally designed with a
sample size of 195 in each group to detect a difference of
5.0% versus 0.05% with a 2-sided significance level of 0.05
and a power of 0.80. The SDMC determined that a sample
size of 95 patients in each treatment group would provide
sufficiently narrow 95% confidence limits of 2% to 11%
around the expected 5.0% complication rates. This sample
size would detect a difference between 10.0% and 0.05%
with the original significance level and power.
With a 2-sided significance level of 0.05, a sample size of
95 patients in each group would be expected to detect a
difference in mean IOP of 2.5 mm Hg with 0.80 power. For
the secondary outcome of successful surgery, this sample
size would have a power of 0.80 to detect a treatment group
hazard ratio of ⬍0.63 and ⬎1.7. Additional patients were
recruited to allow for losses to follow-up, and recruitment
was terminated with 212 patients.
● QUALITY ASSURANCE: Data collection is standardized
through description of all study measures in a comprehensive
Manual of Procedures and the use of uniform data collection
forms. All personnel were certified before beginning data
collection for the study. Patient eligibility was independently
reviewed by the SCC before enrollment. All data forms are
received and secured at the SCC. Each form is data entered
by a data entry clerk and then verified by double entry by the
SCC Research Coordinator. Edit checks, including missing
and questionable data, are clarified with Clinical Centers.
The study is regularly reviewed by the SDMC. This
committee monitors adherence to the study protocol at
each Clinical Center, and it reviews treatment reports
prepared by the SCC for evidence of adverse or beneficial
treatment effects. The SDMC would have terminated the
study if treatment benefits or treatment risks were so great
for 1 treatment group that continuation of the trial was
deemed unethical.
● STATISTICAL ANALYSIS: The comparability of treat-
ment groups at baseline was evaluated using 2-sided
Student t test, Mann-Whitney U test, and ␹2 tests. Interim
analyses are regularly prepared by the SCC and reviewed
by the SDMC to assess treatment benefits and risks for
each group.
RESULTS
A TOTAL OF 212 PATIENTS WERE ENROLLED IN THE TVT
Study at 17 Clinical Centers between October 1999 and
April 2004. All patients received their assigned treatment.
Baerveldt implantation was performed in 107 patients, and
105 patients underwent trabeculectomy with MMC.
The demographic characteristics of the overall study group
and both treatment groups are presented in Table 3. The

VOL. 140, NO. 2 TVT STUDY 275.e7

 TABLE 6. Enrollment by Stratum in the Tube Versus Trabeculectomy Study

Overall Group Tube Group Trabeculectomy Group

(n ⫽ 212) (n ⫽ 107) (n ⫽ 105) P-value*

Stratum 1–Previous cataract extraction, n (%) 94 (44) 44 (41) 50 (48) .42†

PECE (clear cornea) 26 (28) 9 (20) 17 (34)
PECE (scleral tunnel) 31 (33) 17 (39) 14 (28)
ECCE 24 (26) 11 (25) 13 (26)
ICCE 1 (1) 0 (0) 1 (2)
Unknown type 12 (13) 7 (16) 5 (10)
Stratum 2–Previous trabeculectomy or combined
procedure without an antifibrotic agent, n (%) 49 (23) 26 (24) 23 (22) 1.00†
Trabeculectomy 29 (59) 15 (58) 14 (61)
Combined procedure 20 (41) 11 (42) 9 (39)
Stratum 3–Previous trabeculectomy with 5-FU or
combined procedure with 5-FU or MMC, n (%) 35 (17) 18 (17) 17 (16) .18†
Trabeculectomy with 5-FU 12 (34) 8 (44) 4 (24)
Combined procedure with 5-FU 2 (6) 2 (11) 0 (0)
Combined procedure with MMC 21 (60) 8 (44) 13 (76)
Stratum 4–Previous trabeculectomy with MMC, n (%) 34 (16) 19 (18) 15 (14)

5-FU ⫽ 5-fluorouracil; ECCE ⫽ extracapsular cataract extraction; ICCE ⫽ intracapsular cataract extraction; MMC ⫽ mitomycin C;
PECE ⫽ phacoemulsification cataract extraction.
*P-value ⫽ .79 comparing the difference in proportions of the four strata between the two treatment groups using the chi-square test.
†
Exact permutation chi-square test.

mean age of the overall group at enrollment was 71.0 ⫾ 10.4
years (mean ⫾ SD), and 112 patients (53%) were women.
There was a trend toward a difference in gender distribution
among treatment groups with 64 women (60%) in the tube
group and 57 men (54%) in the trabeculectomy group, but
this did not reach statistical significance (P ⫽ .055). By
self-attribution, 95 patients (45%) were white, 82 (39%) were
black, 30 (14%) were Hispanic, and 5 (2%) were other races.
Hypertension was present in 124 patients (59%), and 67
(32%) had diabetes mellitus. There were no significant
differences in the demographic characteristics between treat-
ment groups.
The ocular characteristics of the entire study group and
each treatment group are summarized in Table 4. No signif-
icant differences were detected in the ocular characteristics
between treatment groups. Of the 212 study eyes, 112 (53%)
were left eyes. The IOP at baseline for the overall study group
was 25.3 ⫾ 5.3 mm Hg (mean ⫾ SD). Corneal abnormalities
precluded reliable Goldmann applanation tonometry in two
patients, and the Tono-Pen (Mentor) was used to measure
IOP in these cases. The average number of glaucoma medi-
cations at the time of enrollment was 3.1 ⫾ 1.2 (mean ⫾
SD), and a majority of study eyes were receiving three or more
medications. Table 5 provides information on the types of
glaucoma medications that were used at baseline. Approxi-
mately half of the eyes (52%) had ocular laser therapy before
enrollment. Laser trabeculoplasty had been performed in 73
eyes (34%), and 20 (9%) had laser iridotomy. The mean
number of previous incisional surgeries was 1.3 for the overall
group. There was no significant difference between treatment
groups in the number of previous surgeries and the time
interval between the last intraocular surgery and surgical
treatment in the study.
The most common diagnosis was primary open-angle
glaucoma in 172 eyes (81%). Chronic angle-closure glau-
coma was present in 18 eyes (8%), pseudoexfoliative
glaucoma in 8 eyes (4%), pigmentary in 1 eye (1%), and
other glaucoma types were diagnosed in 13 eyes (6%).
Most eyes were pseudophakic with 160 (75%) containing
a posterior chamber intraocular lens and 7 eyes (3%) had
an anterior chamber intraocular lens (aphakic eyes were
excluded from the study); the remaining 45 eyes (21%)
were phakic. Eyes were stratified based on type of previous
intraocular surgery; Table 6 lists the enrollment numbers
by stratum.
The mean ETDRS visual acuity was 63.6 ⫾ 21.9 (mean ⫾
SD). The median Snellen visual acuity was 20/35. Reduced
visual acuity less than 20/30 was attributed to glaucoma in 78
eyes (37%), macular disease in 17 eyes (8%), and cataract
formation in 10 eyes (5%). The average mean deviation with
Humphrey visual field testing was ⫺15.9 ⫾ 9.9 dB (mean ⫾
SD), and the average pattern standard deviation was 7.0 ⫾
3.5 (mean ⫾ SD). Several patients had poor vision that
precluded meaningful automated perimetry, and 34 patients
did not receive a preoperative visual field. The mean score on
the NEI-VFQ was 71.2 ⫾ 16.9 (mean ⫾ SD). There were 10
patients who could not be contacted by telephone before
surgical treatment to administer the baseline quality of life
questionnaire. Diplopia was reported by seven patients (3%)
during the baseline examination.

275.e8 AMERICAN JOURNAL OF OPHTHALMOLOGY AUGUST 2005

 TABLE 7. Surgical Results in Aphakic/Pseudophakic Eyes

Follow-up (months)

Authors Procedure Eyes Success Rate IOP Success Criteria (mm Hg) Mean Range

Heuer et al.21 Trab with 5-FU A 79% (27/34) ⱕ21 with meds 7.0 3.0–15.6
ⱕ25 without meds
Heuer et al.22 Trab with 5-FU A 69% (33/48) ⱕ21 with meds 18.5 6–34
ⱕ25 without meds
Weinreb23 Trab with 5-FU A 86% (13/15) ⱕ21 with meds 12
ⱕ25 without meds
FFSS1 Trab with 5-FU A/P 72% (58/81) ⱕ21 12
FFSS2 48% (37/77) 36
Palmer24 Trab with MMC A/P 75% (6/8) ⱕpredetermined level 12.3 6–30
Prata et al.25 Trab with 5-FU P 75% (12/16) ⱕ21 13.4
Trab with MMC 70% (21/30) 10.4
Minckler et al.5 SP Molteno A/P 63% (26/41) ⱕ21 16.2 7–30
Freedman & Rubin6 SP Molteno A/P 83% (20/24) ⱕ21 22 8.1–53.3
Lloyd et al.7 SP/DP Molteno A/P 56% (28/50) ⱕ21 and ⬎5 48.6 7–78
Heuer et al.8 SP Molteno A/P 50% (25/50) ⱕ21 and ⬎6 14.9 6 –29
DP Molteno 75% (38/51) 16.4 7–30
Hodkin et al.9 Baerveldt A/P 74% (26/35) ⱕ21 16.3 6.1–26.1
Mills et al.10 SP/DP Molteno A/P 58% (14/24) ⱕ22 45 6–107
Huang et al.11 Ahmed A 88% (28/32) ⬍22 and ⬎5 13.4 4–44
P 88% (84/96)
Broadway et al.12 SP/DP Molteno A 70% (21/30) ⬍22 43
P 66% (23/35)
Roy et al.13 Baerveldt A 75% (6/8) ⱕ21 and ⬎6 37.6 12–68

A ⫽ aphakia; DP ⫽ double-plate; 5-FU ⫽ 5-fluorouracil; IOP ⫽ intraocular pressure; MMC ⫽ mitomycin C; P ⫽ pseudophakia; SP ⫽
single-plate.

DISCUSSION The lack of consensus among glaucoma surgeons regard-

PRACTICE PATTERNS VARY IN THE SURGICAL MANAGE-
ment of glaucoma. An anonymous survey of members of
the American Glaucoma Society (AGS) and Japanese
Glaucoma Society (JGS) by Chen and associates in 1996
presented ten clinical situations requiring glaucoma surgi-
cal intervention.4 The majority of respondents preferred
trabeculectomy with MMC for all clinical situations pro-
vided (51% to 87%), although many of those surveyed
elected to use a GDI, trabeculectomy with 5-FU, or
trabeculectomy without an antifibrotic agent. A follow-up
study by Joshi and associates in 2002 readministered the
same survey to members of the AGS. Respondents con-
tinued to report a preference for trabeculectomy with
MMC in the ten clinical situations, but the percentage
usage of GDIs had significantly increased.20 In particular,
selection of GDIs as the preferred surgical approach in eyes
with a previous trabeculectomy increased from 7% to 20%,
and in eyes with previous extracapsular or intracapsular
cataract surgery increased from 8% to 22%. The TVT
Study has enrolled patients who have undergone prior
cataract surgery or failed filtering surgery, the population
that has seen the greatest shift in glaucoma surgical
practice patterns in recent years.
ing use of a GDI or trabeculectomy with an antifibrotic
agent in eyes that have had previous cataract extraction or
failed filtering surgery likely relates to the fact that avail-
able clinical data has not shown one surgical procedure to
be superior to the other. Surgical results reported in case
series with GDIs and 5-FU and MMC trabeculecto-
mies in aphakic/pseudophakic eyes are summarized in
Table 7. Success rates ranged from 50% to 88% for
GDIs,5–15 and 48% to 86% for filtering surgery with an
antifibrotic agent1,2,21–25 in aphakic/pseudophakic eyes.
Table 8 lists the surgical results obtained in eyes with failed
filters. Success rates ranged from 44% to 88% for
GDIs,5,7,9,10,12,13 and 61% to 100% for 5-FU and MMC
trabeculectomies1,2,21–24,26 –29 in eyes with failed filters.
There are obvious difficulties in making comparisons
between case series, given differences in study populations,
follow-up periods, and criteria by which success is defined.
However, comparable success rates have been reported
with both GDIs and filtering surgery with an antifibrotic
agent in eyes that have undergone prior cataract surgery or
failed filtering surgery when each procedure has been
studied separately.
Retrospective studies have compared surgical results
with GDIs and filtering surgery in matched patient groups.

VOL. 140, NO. 2 TVT STUDY 275.e9

 TABLE 8. Surgical Results in Eyes With Failed Filters

Follow-up (months)

Authors Procedure Success Rate IOP Success Criteria (mm Hg) Mean Range

Heuer et al.21 Trab with 5-FU 89% (8/9) ⱕ21 with meds 7.8 4.5–13
ⱕ25 without meds
Heuer et al.22 Trab with 5-FU 81% (13/16) ⱕ21 with meds 18.5 9–27
ⱕ25 without meds
Weinreb23 Trab with 5-FU 86% (13/15) ⱕ21 with meds 12
ⱕ25 without meds
FFSS1 Trab with 5-FU 79% (19/24) ⱕ21 12
FFSS2 61% (14/23) 36
Chen et al.26 Trab with MMC 78% (35/45) ⬍21 36 12–96
Palmer24 Trab with MMC 100% (7/7) ⱕpredetermined level 21.7 6–42
Singh et al.25 Trab with MMC 83% (10/12) ⱕ21 12.8 4–24
Andreanos et al.28 Trab with MMC 83% (20/24) ⱕ20 18 11–34
You et al.29 Trab with MMC 89% (39/44) ⱕ21 38.2 6–53
Minckler et al.5 SP Molteno 70% (7/10) ⱕ21 12.3 6–25
Lloyd et al.7 SP/DP Molteno 75% (9/12) ⱕ21 and ⬎5 41.4 15–64
Hodkin et al.9 Baerveldt 75% (9/12) ⱕ21 16.1 7.1–26.1
Mills et al.10 SP/DP Molteno 44% (4/9) ⱕ22 42 8–78
Broadway et al.12 SP/DP Molteno 58% (34/59) ⬍22 43
Roy et al.13 Baerveldt 88% (15/17) ⱕ21 and ⬎6 37.6 12–68

DP ⫽ double-plate; 5-FU ⫽ 5-fluorouracil; IOP ⫽ intraocular pressure; MMC ⫽ mitomycin C; SP ⫽ single-plate.

Chihara and associates compared the effect of tube shunt
surgery using a White pump shunt in 16 eyes with that of
a trabeculectomy with 5-FU in 31 eyes with neovascular
glaucoma.14 The probability of success (IOP ⱕ26 mm Hg
and ⱖ5 mm Hg) was 53.0% in the implant group and
45.4% in the trabeculectomy group at 3 years with Kaplan-
Meier survival analysis. Bluestein and Stewart compared
the outcomes of 22 patients who underwent single-plate
Molteno implantation with those of a matched group who
had trabeculectomy with 5-FU.15 Similar mean IOP levels
of 15.4 ⫾ 8.0 mm Hg in the Molteno group and 16.1 ⫾ 5.6
mm Hg in the trabeculectomy group were observed after 6
months of follow-up.
In nonrandomized prospective studies and retrospective
case series, selection biases may produce treatment groups
with different underlying risk factors for failure. Results
reported in such studies must be interpreted with caution. A
randomized clinical trial aims to produce comparison groups
that differ only by the treatment that their subjects receive
and offers the best means for comparing treatments.
Wilson and associates performed a randomized clinical
trial comparing the Ahmed glaucoma valve implant to
trabeculectomy in 117 patients.30 The use of an adjunctive
antifibrotic agent in patients randomized to trabeculec-
tomy was not standardized and left to the discretion of the
surgeon. The cumulative probabilities of success (IOP ⬍21
mm Hg and at least 15% reduction in IOP from preoper-
ative levels) was 83.6% for trabeculectomy and 88.1% for
Ahmed implant. While there was no statistically signifi-
cant difference in success and complication rates between
the two treatment groups, the Ahmed implant group had a
greater adjunctive medication requirement. 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 intraocular surgery. A follow-up study
continued enrollment in Sri Lanka of 123 patients with
primary open-angle and angle-closure glaucoma without
prior intraocular surgery.31 Lower IOPs were noted for the
trabeculectomy group during the first year. However, the
IOPs and cumulative probabilities of success were compa-
rable between the two study groups with longer follow-up.
The TVT Study has restricted its study population to
patients who have undergone previous intraocular surgery.
A standard dosage of MMC was used as an adjunct in all
patients randomized to the trabeculectomy group. It has
become common practice for glaucoma specialists to use an
adjunctive antifibrotic agent when performing filtering
surgery in previously operated eyes.4 MMC is a more
potent inhibitor of fibroblast proliferation than 5-FU, and
studies have shown that trabeculectomy with the adjunc-
tive use of MMC yields lower IOPs than 5-FU.32,33
We decided to exclude several secondary glaucomas
from the TVT Study, including neovascular glaucoma,
uveitic glaucoma, and glaucoma associated with the
iridocorneal endothelial syndrome and epithelial or
fibrous downgrowth. It was the consensus of the inves-
tigators that use of a GDI is the preferred surgical
approach with these types of refractory glaucomas.
Severe posterior blepharitis and patient unwillingness to
discontinue contact lens use after surgery were exclusion

275.e10 AMERICAN JOURNAL OF OPHTHALMOLOGY AUGUST 2005

criteria because of concern about the increased risk of
infection, should these patients be randomized to the
trabeculectomy group. Conjunctival scarring precluding
a trabeculectomy superiorly is a clear indication for GDI
surgery, and these eyes were excluded from the study.
Eyes were excluded if other ocular procedures (that is,
cataract surgery, penetrating keratoplasty, or retinal
surgery) were needed in conjunction with glaucoma
surgery, or if there was an anticipated need for addi-
tional ocular surgery in the future. While there has been
limited experience with the effect of subsequent in-
traocular surgery on GDI function,34 there are numerous
studies demonstrating decreased trabeculectomy function
and increased IOP when various ocular procedures are
performed in eyes with a pre-existing filtering bleb.35– 47
The current study does not address the question of which
glaucoma surgical procedure is preferred when concurrent
or subsequent ocular surgery is planned.
Randomization has succeeded in creating two bal-
anced treatment groups. There were no significant
differences between groups with respect to baseline
demographic and ocular characteristics. Future publica-
tions will present forthcoming data from the study. We
expect that the TVT Study will provide information
that will be valuable for surgical decisions in similar
patient populations.
REFERENCES
1. The Fluorouracil Filtering Surgery Study Group. Fluorouracil
Filtering Surgery Study one-year follow-up. Am J Ophthal-
mol 1989;108:625– 635.
2. The Fluorouracil Filtering Surgery Study Group. Fluorouracil
Filtering Surgery Study three-year follow-up. Am J Ophthal-
mol 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.
4. 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.
5. Minckler DS, Heuer DK, Hasty B, et al. Clinical experience
with the single-plate Molteno implant in complicated glau-
comas. 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 glau-
comas. 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 pseudophakia. Ophthalmology 1992;99:1512–1519.
VOL. 140, NO. 2 TVT STUDY
9. Hodkin MJ, Goldblatt WS, Burgoyne CF, et al. Early clinical
experience with the Baerveldt implant in complicated glau-
comas. 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 Ophthal-
mol 2001;85:689 – 695.
13. Roy S, Ravinet E, Mermoud A. Baerveldt implant in refrac-
tory glaucoma: long-term results and factors influencing
outcomes. Int Ophthalmol 2001;24:93–100.
14. Chihara E, Kubota H, Takanashi T, Nao-i N. Outcome of
White pump shunt surgery for neovascular glaucoma in
Asians. Ophthalmic Surg 1992;23:666 – 671.
15. Bluestein EC, Stewart WC. Trabeculectomy with 5-fluoro-
uracil vs single plate Molteno implantation. Ophthalmic
Surg 1993;24:669 – 673.
16. Nguyen QH, Budenz DL, Parrish RK. Complications of
Baerveldt glaucoma drainage implants. Arch Ophthalmol
1998;116:571–575.
17. Ferris FL, Kassoff A, Bresnick GH, Bailey I. New visual
acuity charts for clinical research. Am J Ophthalmol 1982;
94:91–96.
18. Mangione CM, Lee PP, Gutierrez PR, et al. Development of
the 25-item National Eye Institute visual function question-
naire. Arch Ophthalmol 2001;119:1050 –1058.
19. Wolner B, Liebmann JM, Sassani JW, et al. Late bleb-related
endophthalmitis after trabeculectomy with adjunctive 5-flu-
orouracil. Ophthalmology 1991;98:1053–1060.
20. 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.
21. Heuer DK, Parrish RK, Gressel MG, et al. 5-fluorouracil and
glaucoma filtering surgery: II. A pilot study. Ophthalmology
1984;91:384 –394.
22. 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.
23. Weinreb RN. Adjusting the dose of 5-fluorouracil after
filtration surgery to minimize side effects. Ophthalmology
1987;94:564 –570.
24. Palmer SS. Mitomycin as adjunct chemotherapy with trab-
eculectomy. Ophthalmology 1991;98:317–321.
25. Prata JA, Minckler DS, Baerveldt G, et al. Trabeculectomy
in pseudophakic patients: postoperative 5-fluorouracil versus
intraoperative mitomycin C antiproliferative therapy. Oph-
thalmic Surg 1995;26:73–77.
26. 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.
27. Singh J, O’Brien C, Chawla HB. Success rate and complica-
tions of intraoperative 0.2 mg/ml mitomycin C in trabecu-
lectomy surgery. Eye 1995;9:460 – 466.
28. 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.
275.e11
29. You YA, Gu YS, Fang CT, Ma XQ. Long-term effects of
simultaneous and subscleral mitomycin C application in
repeat trabeculectomy. J Glaucoma 2002;11:110 –118.
30. 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.
31. Wilson MR, Mendis U, Paliwal A, Haynatzka V. Long-term
follow-up of primary glaucoma surgery with Ahmed glau-
coma valve implant versus trabeculectomy. Am J Ophthal-
mol 2003;136:464 – 470.
32. Kitazawa Y, Kawase K, Matsushita H, Minobe M. Trabecu-
lectomy with mitomycin: a comparative study with fluororu-
racil. Arch Ophthalmol 1991;109:1693–1698.
33. Skuta GL, Beeson CC, Higginbotham EL, et al. Intraop-
erative mitomycin versus postoperative 5-fluororuacil in
high risk glaucoma filtering surgery. Ophthalmology 1992;
99:438 – 444.
34. Bhattacharyya CA, WuDunn D, Lakhani V, et al. Cataract
surgery after tube shunts. J Glaucoma 2000;9:453– 457.
35. Thompson WS, Smiddy WE, Flynn HW, Rubsamen PE.
Outcome of functioning filtering blebs after pars plana
vitrectomy. Ophthalmic Surg Lasers 1996;27:367–373.
36. Kirkness CM, Steele AD, Ficker LA, Rice NS. Coexistent
corneal disease and glaucoma managed by either drainage
surgery and subsequent keratoplasty or combined drainage
surgery and penetrating keratoplasty. Br J Ophthalmol 1992;
76:146 –152.
37. Alpar JJ. Cataract extraction and lens implantation in eyes
with pre-existing filtering blebs. J Am Intraocular Implant
Soc 1979;5:33–35.
38. Binkhorst CD, Huber C. Cataract extraction and intraocular
lens implantation after fistulizing glaucoma surgery. J Am
Intraocular Implant Soc 1981;7:133–137.
39. Obstbaum SA. Glaucoma and intraocular lens implantation.
J Cataract Refract Surg 1986;12:257–261.
40. Antonios SR, Traverso CE, Tomey KF. Extracapsular cata-
ract extraction using a temporal limbal approach after
filtering operations. Arch Ophthalmol 1988;106:608 – 610.
41. Murchison JF, Shields MB. An evaluation of three surgical
approaches for coexisting cataract and glaucoma. Ophthal-
mic Surg 1989;20:393–398.
42. Brooks AMV, Gillies WE. The effect of cataract extraction
with implant in glaucomatous eyes. Aust N Z J Ophthalmol
1992;20:235–238.
43. Yamagami S, Araie M, Mori M, Mishima K. Posterior
chamber intraocular lens implantation in filtered or nonfil-
tered glaucoma eyes. Jpn J Ophthalmol 1994;38:71–79.
44. Dickens MA, Cashwell LF. Long-term effect of cataract
extraction on the function of an established filtering bleb.
Ophthalmic Surg Lasers 1996;27:9 –14.
45. Seah SKL, Jap A, Prata JA, et al. Cataract surgery after
trabeculectomy. Ophthalmic Surg Lasers 1996;27:587–594.
46. Chen PP, Weaver YK, Budenz DL, et al. Trabeculectomy
function after cataract extraction. Ophthalmology 1998;105:
1928 –1935.
47. Swamynathan K, Capistrano AP, Cantor LB, WuDunn D.
Effect of temporal corneal phacoemulsification on intraocu-
lar pressure in eyes with prior trabeculectomy with an
antimetabolite. Ophthalmology 2004;111:674 – 678.
275.e12 AMERICAN JOURNAL
APPENDIX
Participating Centers and Committees in the Tube Ver-
sus Trabeculectomy Study
● CLINICAL CENTERS:
Bascom Palmer Eye Institute, University of Miami (Miami,
Florida). Principal Investigator: Steven Gedde, MD; Coin-
vestigators: Douglas Anderson, MD, Donald Budenz, MD,
MPH, Madeline Del Calvo, David Greenfield, MD, Eliza-
beth Hodapp, MD, Alexia Marcellino, Paul Palmberg,
MD, PhD, Richard Parrish II, MD
Duke University (Durham, North Carolina). Principal
Investigator: Leon Herndon, MD; Coinvestigators: Pratap
Challa, MD, Cecile Santiago-Turla, MD
Indiana University (Indianapolis, Indiana). Principal In-
vestigator: Darrell WuDunn, MD, PhD
Loyola University (Maywood, Illinois). Principal Investi-
gator: Geoffrey Emerick, MD
Medical College of Wisconsin (Milwaukee, Wisconsin).
Principal Investigator: Dale Heuer, MD
Medical University of South Carolina (Charleston, South
Carolina). Principal Investigator: Alexander Kent, MD;
Coinvestigators: Carol Bradham, Lisa Langdale
Moorfields Eye Hospital (London, England). Principal
Investigator: Keith Barton, MD; Coinvestigator: Poornima
Rai, MD
New York Eye and Ear Infirmary (New York, New York).
Principal Investigator: Paul Sidoti, MD; Coinvestigators:
Amy Gedal, James Luayon
Scripps Clinic (La Jolla, California). Principal Investiga-
tor: Quang Nguyen, MD
St. Louis University (St. Louis, Missouri). Principal In-
vestigator: Steven Shields, MD; Coinvestigators: Kevin
Anderson, Frank Moya, MD
University of California Davis (Sacramento, California).
Principal Investigator: James Brandt, MD; Coinvestigator:
Michele Lim, MD, Marilyn Sponzo
University of Florida (Gainesville, Florida). Principal Investiga-
tor: Mark Sherwood, MD; Coinvestigator: Revonda Burke
University of Oklahoma (Oklahoma City, Oklahoma).
Principal Investigator: Gregory Skuta, MD; Coinvestiga-
tors: Jason Jobson, Lisa Ogilbee, Adam Reynolds, MD
University of Southern California (Los Angeles, California).
Principal Investigator: Rohit Varma, MD, MPH; Coinves-
tigators: Brian Francis, MD, Frances Walonker
University of Texas Houston (Houston, Texas). Principal
Investigator: Robert Feldman, MD; Coinvestigators: Laura
Baker, Nicholas Bell, Athena Espinoza
University of Virginia (Charlottesville, Virginia). Principal
Investigator: Bruce Prum, MD; Coinvestigator: Janis Beall
University of Wisconsin (Madison, Wisconsin). Principal
Investigator: Todd Perkins, MD; Coinvestigators: Paul
Kaufman, MD, Tracy Perkins, Barbara Soderling
OF OPHTHALMOLOGY AUGUST 2005
● STATISTICAL COORDINATING CENTER:
Bascom Palmer Eye Institute, University of Miami (Miami,
Florida). William Feuer, MS, Luz Londono, Joyce Schiff-
man, MS
● SAFETY AND DATA MONITORING COMMITTEE:
Philip Chen, MD, William Feuer, MS, Joyce Schiffman,
MS, Kuldev Singh, MD, MPH, George Spaeth, MD,
Martha Wright, MD
● STEERING COMMITTEE:
Keith Barton, MD, James Brandt, MD, Geoffrey Emer-
ick, MD, Robert Feldman, MD, Steven Gedde, MD, Leon
Herndon, MD, Dale Heuer, MD, Alexander Kent, MD,
Quang Nguyen, MD, Richard Parrish II, MD, Todd Per-
kins, MD, Bruce Prum, MD, Mark Sherwood, MD, Steven
Shields, MD, Paul Sidoti, MD, Gregory Skuta, MD, Rohit
Varma, MD, MPH, Darrell WuDunn, MD, PhD
● STUDY CHAIRMEN:
Steven Gedde, MD, Dale Heuer, MD, Richard Parrish
II, MD
● FINANCIAL DISCLOSURES:
The following investigators have disclosed a financial
interest in the previous and current manufacturer of the
Baerveldt glaucoma implant.
VOL. 140, NO. 2 TVT STUDY
James Brandt, MD: Pfizer, consultant, speakers bureau,
honoraria; Advanced Medical Optics, consultant. Donald
Budenz, MD, MPH: Pfizer, honoraria, speakers bureau. Philip
Chen, MD: Pfizer, honoraria. Geoffrey Emerick, MD: Pfizer,
honoraria, speakers bureau. Robert Feldman, MD: Pfizer,
consultant, grant support, honoraria, speakers bureau. Brian
Francis, MD: Pfizer, speakers bureau. Steven Gedde, MD:
Pfizer, honoraria, speakers bureau; Advanced Medical Optics,
honoraria. David Greenfield, MD: Pfizer, consultant, hono-
raria, speakers bureau. Leon Herndon, MD: Pfizer, honoraria,
speakers bureau. Dale Heuer, MD: Pfizer, honoraria, speakers
bureau. Paul Kaufman, MD: Pfizer, consultant, grant support,
honoraria, speakers bureau, travel expenses; Advanced Med-
ical Optics, consultant, grant support. Frank Moya, MD:
Pfizer, speakers bureau. Quang Nguyen, MD: Pfizer, consul-
tant, honoraria, speakers bureau. Paul Palmberg, MD, PhD:
Pfizer, consultant, speakers bureau, honoraria. Richard Parrish
II, MD: Pfizer, consultant, honoraria. Bruce Prum, MD: Pfizer,
grant support, speakers bureau. Adam Reynolds, MD: Pfizer,
honoraria. Steven Shields, MD: Pfizer, consultant. Kuldev
Singh, MD, MPH: Pfizer, consultant. Gregory Skuta, MD:
Pfizer, consultant, honoraria, speakers bureau. George Spaeth,
MD: Pfizer, grant support, honoraria. Rohit Varma, MD,
MPH: Pfizer, consultant, grant support, honoraria, speakers
bureau. Martha Wright, MD: Pfizer, speakers bureau. Darrell
WuDunn, MD, PhD: Pfizer, honoraria, speakers bureau.
275.e13
 Biosketch
Steven J. Gedde, MD, is an Associate Professor of Ophthalmology and Residency Program Director at the Bascom Palmer
Eye Institute. He is a study chairman in the Tube Versus Trabeculectomy Study. His research interests include glaucoma
drainage implants, complications of glaucoma surgery, quality of life, and resident education.

275.e14 AMERICAN JOURNAL OF OPHTHALMOLOGY AUGUST 2005