The AVB Study: Prospective Study Comparing the Ahmed Valve and the Baerveldt Implant for Treating Refractory Glaucoma

Introduction:

The use of a glaucoma drainage device (GDD) is indicated in cases of refractory glaucoma not
responsive to conventional medication, laser and surgical therapy. Most of these patients are
at high risk for surgical failure, with serious concomitant ocular and systemic diseases.
GDD's are increasingly being used to obtain low target intraocular pressures (IOP) in
patients who have failed antimetabolite trabeculectomy or have active neovascular glaucoma.

Since Molteno's original design, several drainage devices have become commercially available
for implantation. Currently, the two most commonly used devices are the Ahmed Glaucoma Valve
(AGV) (New World Medical, Inc., Rancho Cucamonga, CA), and the Baerveldt Glaucoma Device
(BGD) (Advanced Medical Optics, Santa Ana, CA). The AGV, with a venture-based
flow-restrictive valve is helpful in minimizing postoperative hypotony and complications
associated with hypotony, including flat anterior chamber, choroidal effusions, and
suprachoroidal hemorrhage. However, there appears to be a high rate of encapsulation and
hypertension associated with this device, and increased requirement of postoperative glaucoma
medication use. The BGD, a non-valved device, requires early ligature of flow by the use of a
suture restriction to allow adequate time for bleb formation. Although this can result in an
initial post-operative hypertension phase, it results in less encapsulation and theoretically
fewer postoperative glaucoma medications and better IOP control. However, the lack of a
flow-restrictor and the large filtering surface area may result in a greater risk for
hypotony related complications.

Although several studies comparing the AGV and BGD have been reported, they have all been
retrospective, nonrandomized, small scale, and compare different patient populations. The
results have been inconclusive and conflicting in evaluating the relative efficacy and
characteristics of these two devices, and further research needs to be done in order to
answer these questions.

Objective:

The Ahmed vs. Baerveldt (AVB) Study is the first multicenter prospective randomized clinical
trial comparing the Ahmed FP7 valve and the Baerveldt-350 tube shunt glaucoma drainage
devices. Primary outcome is surgical failure, a composite criteria evaluating the intraocular
pressure lowering effect of the devices, complications of the surgery, treatments for
complications, glaucoma medication use, and the preservation of visual acuity. Secondary
outcomes will evaluate these variables individually, and any non-glaucoma related ocular
pathology and required interventions.

AVB Study Manual:

An AVB Study Manual including the study design and protocol, standardized surgical technique,
patient education and consent form, and data collection protocol was distributed to each
clinical site. The contents of the manual received ethics approval by the Institutional
Review Board (IRB) at the primary site.

Study Organization:

1. Investigator Committee (IC): Composed of study investigators and under the leadership of
the Study Chair. The IC's responsibilities are defined below:

1. Designing the study protocol to ensure valid scientific method and proper ethical
conduct.

2. Overseeing clinical centers to ensure that the protocol and ethical standards of
the study are being upheld.

3. Overseeing the Data Acquisition & Statistical Center to ensure that all practices
are in accordance with those outlined in the protocol, and meet the ethical
standards of the study.

4. Drafting and editing study documents critically for intellectual content and
ethical considerations.

2. Clinical Centers (CC): Composed of study sites led by a Site Primary Investigator, whose
responsibilities are defined below:

1. Enrolling patients in the study after determining eligibility and providing patient
education. Informed consent must be written.

2. Ensuring that the study protocol and ethical standards of the study are upheld.

3. Ensuring that the study adheres to the policies set forth by the local
Institutional/Ethical Review Board.

4. Acquiring study data and making it available to the Data Monitoring & Statistics
Committee.

3. Data Acquisition & Statistical Center (DASC): Composed of Study Director and Study
Statistician, with the following responsibilities:

1. Acquiring study data from each Clinical Center using the online study database
(http://www.avsbstudy.com)

2. Statistical analysis of the study data.

Methods:

Patient Enrollment and Treatment Assignment:

Patients were recruited from 7 study sites by 10 surgeons. After patient eligibility and
written informed consent was obtained by the Site PI, randomization to placement of an Ahmed
FP7 valve or a Baerveldt-350 tube shunt was made by coin toss.

Pre-operative data collection:

The following data was collected in the 3 months prior to surgery: date of birth, gender,
race, glaucoma diagnosis and etiology, past ocular history (diagnoses, surgical and laser
procedures), best corrected visual acuity, intraocular pressure, glaucoma medication use,
abnormal slit lamp findings, and abnormal fundus exam findings.

Surgical Procedure:

The surgical procedures used for the AVB Study are standardized, and any complications during
surgery will be noted and defined.

Ahmed FP7 valve implantation:

A superior or inferior corneal traction suture with 8-0 Vicryl was placed for globe fixation
as required. A 90-degree conjunctival peritomy was followed by blunt dissection to mobilize a
fornix or limbus-based conjunctival flap over the area of intended device implantation.
Non-preserved lidocaine 1% was injected under the conjunctival flap, posteriorly, and under
the extraocular muscle bellies with a blunt cannula. Gentle cautery was used to obtain
hemostasis.

The Ahmed Glaucoma Valve model FP-7 was primed with balanced salt solution, and placed in the
intended quadrant. The plate was sutured to sclera 8-10mm posterior to the limbus with two
8-0 or 10-0 Nylon sutures.

A paracentesis was made if required, and a viscoelastic agent used to form the anterior
chamber. A 22-gauge needle was used to create needle tract into the anterior chamber.

The tube was trimmed, and placed into the anterior chamber through the needle tract. The tube
was attached to the sclera using a 10-0 Nylon suture if required. A sclera or corneal graft
was placed over the tube and sutured to the sclera with 10-0 Nylon.

The conjunctival flap was closed with 8-0 or 10-0 Vicryl suture. At the conclusion of the
case, Maxitrol ointment was placed on the eye. No patients were patched, although shields
were given to patients. That day, patients were started on antibiotic and steroid eye drops.
A cycloplegic was used as indicated.

Baerveldt-350 tube shunt implantation:

A superior or inferior corneal traction suture with 8-0 Vicryl was placed for globe fixation.
A 90 to 120-degree conjunctival peritomy was followed by blunt dissection to mobilize a
fornix or limbus-based conjunctival flap over the area of intended device implantation.
Non-preserved lidocaine 1% was injected under the conjunctival flap, posteriorly, and under
the extraocular muscle bellies with a blunt cannula. Gentle cautery was used to obtain
hemostasis.

Both adjacent extraocular muscles were isolated using a muscle hook. 4-0 silk sutures were
used for fixation if necessary.

The Baerveldt drainage device model BG101-350 was checked with balanced salt solution, and a
4-0 Nylon releasable intraluminal suture was placed. A 7-0 or 8-0 Vicryl ligature suture was
placed around the tube. The plate was placed in the intended quadrant and under the muscle
bellies. The plate was sutured to the sclera 8-12mm posterior to the limbus with two 8-0 or
10-0 Nylon sutures.

A paracentesis was made if it was required, and a viscoelastic agent used to form the
anterior chamber. A 22-gauge needle was used to create needle tract into the anterior
chamber. The tube was trimmed, and placed into the anterior chamber through the needle tract.
The tube was attached to the sclera using a 10-0 Nylon suture if required. A sclera or
corneal graft was placed over the tube and sutured to the sclera.

The conjunctival flap was closed with an 8-0 or 10-0 Vicryl suture. At the conclusion of the
case, Atropine 1% drops and Maxitrol ointment was placed on the eye. No patients were
patched, although shields were given to patients. On the day of surgery, patients were
started on antibiotics and steroid eye drops. A cycloplegic agent was used as indicated.

Post-operative data collection:

Patients were seen post-operatively at a minimum of 1 day, 1 week, 2 weeks, 1 month, 2
months, 3 months, 6 months, 12 months, 18 months 2 years, 3 years, 4 years and 5 years.
Further visits were made as deemed necessary. At each visit, the following data was
collected:

1. Intraocular pressure (IOP) by Goldmann Applanation Tonometry

2. Visual Acuity (VA) using a Snellen Chart or Low Vision Chart

3. Glaucoma Medication Use

4. Slit Lamp Biomicroscopy & Ophthalmoscopy

5. Complications of Surgery

6. Interventions/Treatment of Complications

Outcome measures:

Based upon the pre-operative data and post-operative results, a study outcome will be
assigned to each patient, as defined below:

Complete Success: (requires all of the following criteria)

1. IOP: 5 mmHg <= IOP <= 18 mmHg with a reduction in IOP of 20% or greater from baseline at
every visit after 3 months.

2. Medications: No anti-glaucoma medications are required.

3. Complications: No vision threatening complications related to the implant/surgery.

4. Interventions: No additional glaucoma surgery or laser procedures are allowed.

5. Vision: No greater than a doubling of the mean angle of resolution (logMAR), which
corresponds to approximately 2 Snellen lines.

Qualified Success: (requires all of the following criteria)

1. IOP: 5 mmHg <= IOP <= 18 mmHg with a reduction in IOP of 20% or greater from baseline,
with no two consecutive visits after 3 months which do not meet this criterion.

2. Medications: Anti-glaucoma medications may be used.

3. Surgery/Complications: No vision threatening complications or surgery occurred after
implantation of the GDD.

4. Interventions: Surgical and laser interventions to correct non-vision threatening
complications of implant/surgery are allowed, but no additional glaucoma procedures are
allowed.

5. Vision: No progression to no light perception.

Failure: (if any of the following criteria are met)

1. IOP: IOP <5 mmHg or >18 mmHg or reduction <20% from pre-operative IOP in two consecutive
visits after 3 months.

2. Surgery/Complications: Vision threatening complications or surgery required that is
related to the implant. This includes severe choroidal effusions requiring drainage,
suprachoroidal hemorrhage, endophthalmitis or malignant glaucoma requiring surgery.

3. Interventions: An additional glaucoma procedure is required (e.g. cyclodestruction, gold
shunt implantation).

4. Vision: Progression to no light perception.

Inclusion Criteria:

- Age greater than or equal to 18.

- Inadequately controlled glaucoma determined as intraocular pressure (IOP) greater than
target, which has not responded to conventional medical and surgical therapy.

- Patients with significant conjunctival scarring or high-risk disease (active
neovascular glaucoma) precluding antimetabolite trabeculectomy will be included in the
study.

- Provide written informed consent to participate in the study.

Exclusion Criteria:

- Age less than 18.

- Patient will undergo an additional procedure at the time of glaucoma drainage device
implantation (i.e. lensectomy, penetrating keratoplasty)

- No light perception vision.

- Patient has already been enrolled in the study in the contralateral eye.

- Patient is unwilling or unable to provide informed consent to participate in the
study, or adhere to the study requirements including implant randomization and
required follow-up visits.