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

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to compare the safety and efficacy of the Ahmed valve and the Baerveldt implant in treating refractory glaucoma. Eligible patients will be recruited from multiple study centers and randomized to a glaucoma drainage device for implantation. They will be followed long-term based upon outcome measures including intraocular pressure, glaucoma medication use, visual acuity, complications of the surgery and further treatments required.

Detailed Description
-----------------
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: Investigator Committee (IC): Composed of study investigators and under the leadership of the Study Chair. The IC's responsibilities are defined below: Designing the study protocol to ensure valid scientific method and proper ethical conduct. Overseeing clinical centers to ensure that the protocol and ethical standards of the study are being upheld. 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. Drafting and editing study documents critically for intellectual content and ethical considerations. Clinical Centers (CC): Composed of study sites led by a Site Primary Investigator, whose responsibilities are defined below: Enrolling patients in the study after determining eligibility and providing patient education. Informed consent must be written. Ensuring that the study protocol and ethical standards of the study are upheld. Ensuring that the study adheres to the policies set forth by the local Institutional/Ethical Review Board. Acquiring study data and making it available to the Data Monitoring & Statistics Committee. Data Acquisition & Statistical Center (DASC): Composed of Study Director and Study Statistician, with the following responsibilities: Acquiring study data from each Clinical Center using the online study database (http://www.avsbstudy.com) 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: Intraocular pressure (IOP) by Goldmann Applanation Tonometry Visual Acuity (VA) using a Snellen Chart or Low Vision Chart Glaucoma Medication Use Slit Lamp Biomicroscopy & Ophthalmoscopy Complications of Surgery 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) IOP: 5 mmHg <= IOP <= 18 mmHg with a reduction in IOP of 20% or greater from baseline at every visit after 3 months. Medications: No anti-glaucoma medications are required. Complications: No vision threatening complications related to the implant/surgery. Interventions: No additional glaucoma surgery or laser procedures are allowed. 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) 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. Medications: Anti-glaucoma medications may be used. Surgery/Complications: No vision threatening complications or surgery occurred after implantation of the GDD. Interventions: Surgical and laser interventions to correct non-vision threatening complications of implant/surgery are allowed, but no additional glaucoma procedures are allowed. Vision: No progression to no light perception. Failure: (if any of the following criteria are met) IOP: IOP <5 mmHg or >18 mmHg or reduction <20% from pre-operative IOP in two consecutive visits after 3 months. 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. Interventions: An additional glaucoma procedure is required (e.g. cyclodestruction, gold shunt implantation). Vision: Progression to no light perception.

Official Title
-----------------
The Ahmed Versus Baerveldt (AVB) Study: Prospective, Multicenter Trial Comparing the Ahmed-FP7 Valve With the Baerveldt-350 Implant in Treating Refractory Glaucoma

Conditions
-----------------
Glaucoma

Intervention / Treatment
-----------------
* Device: Ahmed FP7 Valve
* Device: Baerveldt-350 Tube


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ahmed FP7 Valve<br>Ahmed valve glaucoma drainage device implant for treatment of refractory glaucoma. | Device: Ahmed FP7 Valve<br>* Implantation of Ahmed FP7 Valve to lower intraocular pressure in refractory glaucoma.<br>* Other names: AGV FP7;|
| Active Comparator: Baerveldt-350 Tube<br>Baerveldt tube glaucoma drainage device implant for treatment of refractory glaucoma. | Device: Baerveldt-350 Tube<br>* Implantation of Baerveldt-350 Tube to lower intraocular pressure in refractory glaucoma.<br>* Other names: BG 101-350;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Surgical Failure (Composite Measure) | IOP out of target range (5-18 mmHg inclusive) or <20% reduction from baseline for 2 consecutive visits after 3 months. De novo glaucoma surgery required (e.g., cyclodestructive procedure, additional tube shunt). Removal of the implant. Severe vision loss related to the surgery (endophthalmitis, suprachoroidal hemorrhage with vision loss, enucleation, evisceration, or phthisis bulbi) or progression to no light perception for any reason. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intraocular Pressure (IOP) |  | 5 years | 
| Anti-glaucoma Medications |  | 5 years | 
| LogMAR Snellen Visual Acuity | Visual acuity (VA) was tested monocularly (one eye at a time) using the manifest refraction adjusted for optical infinity using a standard Snellen Visual Acuity chart at 20 feet. Normal vision, or 20/20 vision, means that the participant can see at 20 feet what a healthy control can also see at 20 feet. Legal blindness, or 20/200 vision, means the participant can see at 20 feet what a healthy control can see at 200 feet. Hence, an increasing denominator implies visual impairment. Counting fingers was designated as 20/2000 vision, hand motions was 20/16000, light perception was 20/32000 and no light perception was 20/64000. To allow for appropriate statistical analysis, logMAR Snellen Visual Acuity was calculated using the formula: -logMAR (Snellen Acuity). This means that normal vision (20/20) would correspond to a value of 0, legal blindness (20/200) would correspond to a value of 1, and no light perception (20/64000) would correspond to 3.5. | 5 years | 
| Number of Participants With Complications During or After Surgery |  | 5 years | 
| Number of Participants With Interventions After Surgery |  | 5 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Glaucoma Drainage Device, Aqueous Shunt Implant, Ahmed Valve, Baerveldt Tube, Refractory Glaucoma