Ahmed Versus Baerveldt Comparison Study

Background and Significance

Aqueous shunt devices have traditionally been reserved for treatment of only the most
refractory glaucomas. However, more recent studies have reported favorable results in
comparison with trabeculectomy in medically uncontrolled glaucomas at lower risk of
filtration failure. Consequently, aqueous shunt devices have been used increasingly in
glaucoma drainage surgery.

There are two principal designs of implant in common use, the Ahmed glaucoma valve implant
(New World Medical, Los Ranchos, CA, USA and the Baerveldt implant (Advanced Medical Optics,
Santa Ana, CA, USA).

Having both evolved from the Molteno, the Ahmed and Baerveldt devices have in common a tube
portion that drains aqueous humor from the anterior chamber to a plate that is implanted on
the equatorial sclera. The size of plate determines the surface area of the drainage bleb.

The Ahmed and Baerveldt implants differ in two major respects. Firstly, the plate surface
area of the Baerveldt 350 implant is almost double that of the Ahmed (185 mm2). Secondly,
the Ahmed has a flow-restrictor that limits early hypotony without the need for additional
external ligation.

We propose a randomized prospective clinical trial comparing the long-term safety and
efficacy of the Ahmed glaucoma valve implant (FP-7) with the 350-mm2 Baerveldt implant
(101-350) for surgical control of secondary glaucoma and primary glaucoma in eyes that have
undergone previous ocular surgery.

Objective

The objective of this study is to compare the long-term safety and efficacy of the Ahmed
FP-7 implant and the 350-mm2 Baerveldt implant in patients who are undergoing aqueous shunt
implant surgery. Patients who qualify for the study are randomized to receive either an
Ahmed FP-7 or Baerveldt BG-101-350 implant. Only one eye of a patient may be enrolled in the
study.

Outcome discrimination between the two treatment groups will be made using typical measures
of visual function (visual acuity and visual field), intraocular pressure, number of
glaucoma medications, and glaucoma reoperations. Emphasis will also be placed on
complication rates, including suprachoroidal hemorrhage, endophthalmitis, choroidal
effusion, diplopia, corneal edema, and shunt/tube erosion.

Assignment

Since the purpose of this study is to compare the safety and efficacy of two surgical
procedures used in the management of glaucoma, randomization techniques are used to assure
an unbiased treatment assignment to patients.

Stratification:

Patients will be stratified by clinical center. At each Clinical Center, half of the
patients will receive an Ahmed and half will receive a Baerveldt implant. Randomization
takes place at the time the patient is enrolled in the study after informed consent is
obtained.

Randomization:

A permuted variable block randomization scheme stratified by clinical center and type of
glaucoma will be performed.

The following scenarios will constitute a failure in the ABC Study for the purposes of
survival analysis:

- IOP > 21mmHG or < 6mmHg on 2 consecutive study visits at visits > 3 months

- IOP reduced by < 20% on 2 consecutive study visits at visits > 3 months

- Reoperation for glaucoma

- Loss of light perception vision

- Removal of implant for any reason

Clinical Procedures

Visual Acuity

Visual acuity is an important outcome variable in the ABC Study. Visual acuity is measured
before pupil dilation, tonometry, gonioscopy, or any other technique that could affect
vision. 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.

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.

Slit Lamp Biomicroscopy Conjunctiva examination Cornea examination An assessment is made of
the position and length of the tube in the eye. Anterior Chamber examination Iris
examination Lens examination 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 The Tono-Pen (Mentor) is used in
cases of corneal edema, corneal scarring, or irregular corneal astigmatism.

Central corneal thickness will be measured in each eye, by ultrasound pachymetry. A minimum
of 5 measurements will be taken and the lowest recorded.

Motility Evaluation Gonioscopy Ophthalmoscopy Perimetry Visual field assessment is an
important outcome measure in the ABC 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 ABC 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.

Surgical Procedures

The type of anesthesia is at the surgeon's discretion.

Conjunctival Flap:

An Ahmed FP-7 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. Sufficient exposure is obtained in the superotemporal quadrant to
permit placement of the Ahmed plate. A corneal traction suture or episcleral traction suture
may be used to rotate the globe inferonasally to improve exposure.

Priming the Implant

A 28- or 30- gauge cannula is used to prime the Ahmed valve. Occlusion of the tube with a
ligature is not permitted.

Attachment of Episcleral Plate:

The Ahmed plate is sutured to the sclera at a measured distance of 8 - 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.

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 Ahmed 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.

Coverage of Tube:

A donor patch graft composed of donor sclera, donor cornea, 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.

At the surgeons discretion, a viscoelastic of his or her choice may be inserted into the
anterior chamber, especially if the anterior chamber shallows after balanced salt solution
is inserted.

The use of intraoperative medications is at the surgeon's discretionBaerveldt Implantation
The type of anesthesia is at the surgeon's discretion.

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 8 - 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.

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.

The use of intraoperative medications is at the surgeon's discretion.

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)

Inclusion Criteria:

- Age 18 to 85 years, inclusive.

- Glaucoma that is inadequately controlled on tolerated medical therapy with
intraocular pressure greater than or equal to 18 mm Hg.

- Glaucoma drainage implant as planned surgical procedure.

- POAG with previous failed trabeculectomy or other intraocular surgery.

- Secondary glaucoma with or without previous intraocular surgery

Exclusion Criteria:

- Unwilling or unable to give consent or unwilling to accept randomization.

- Patient out of area and potentially unavailable for follow-up visits

- No light perception.

- Uveitis secondary to Juvenile Idiopathic Arthritis

- Previous cyclodestructive procedure or previous aqueous shunt device implanted in the
same eye.

- Supero-temporal buckling or other external impediment to supero-temporal aqueous
shunt implantation.

- Silicone oil-filled eyes or sufficient residual intraocular silicone oil to preclude
supero-temporal aqueous shunt implantation.

- Vitreous sufficient to require a vitrectomy present in the anterior chamber at the
time of surgery.