Comparative Study of the Safety and Effectiveness Between Off-Label Subconjunctival Bevacizumab and Mitomycin C in Glaucoma Filtering Surgery.

Glaucoma Filtration Surgery (GFS) remains the definitive surgical management for elevated IOL uncontrolled by medical management. Bleb failure is a major factor limiting the longterm success of trabeculectomy surgery. Bleb failure involves vascularization with fibroblast migration and eventual scarring of the fistula tract. Vascular Endothelial Growth Factor (VEGF) is a unique mitogen specific to vascular endothelial cells and the signal cascade leading to fibroblast migration and proliferation involves dynamic interaction between many proteins. Blocking the neovascular signal cascade with anti-VEGF molecules like Bevacizumab may lead to a decrease in fibroblast proliferation by decreasing the supply of mitogenic cytokines such as fibroblast growth factor (FGF) carried in by new vessel formation and decreasing the known synergism that exists between VEGF and fibroblast growth factor (FGF) The study is designed as an off-label, randomized, parallel, comparative study. Patients who meet the inclusion/exclusion criteria and sign the informed consent will be included. After enrollment, patients will be randomized into two groups: trabeculectomy with off-label subconjunctival bevacizumab or trabeculectomy with mitomycin-C.This study aims to compare the safety and effectiveness of off-label subconjunctival bevacizumab and subtenon Mitomycin C in glaucoma filtration surgery (GFS). The primary endpoint is to prove the effectiveness via the reduction of IOP and grading of bleb photographs according to the Moorfields Bleb Grading Protocol, and the secondary endpoint is to prove the safety via the incidence of complications and adverse events.

Procedure: Surgical technique Trabeculectomy will be performed after the administration of retrobulbar or peribulbar anesthesia with lidocaine. For the limbus-based procedure, a bridle suture (4-0 silk) will be placed under the superior rectus muscle tendon, and the conjunctiva and Tenon's capsule will be incised in the superior quadrant 8 to 10 mm posterior to the surgical limbus. The conjunctiva and Tenon's capsule will be dissected anterior to the limbus. Meticulous hemostasis will be achieved with bipolar cautery. In cases randomized to MMC usage, a cellulose sponge (approximately 6 × 12 mm × 1 mm) soaked with mitomycin C (0.2 mg/ml) will be applied over the intended site of the scleral flap for 1 to 3 minutes. The duration of mitomycin C application will be based on the preoperative evaluation of each patient's risk factors for failure. Copious irrigation with balanced salt solution will be performed to wash away residual MMC. A ½ to 2/3 thickness square scleral flap (approximately 3.5 × 3.5 mm) will be then dissected into the clear cornea. After resection of an anterior trabecular block (approximately 2.5 × 1 mm), an iridectomy will be performed. The scleral flap will be sutured with two or three 10-0 nylon sutures at its corners. The conjunctiva and Tenon's capsule will be closed in a single continuous layer with 8-0 Vicryl suture. In the subjects randomized to receive Injection Bevacizumab, 0.05 ml of reconstituted bevacizumab drug (1.25 mg) will be injected subconjunctivally adjacent to the bleb. Atropine eye ointment will be placed in the fornix and the eye will be patched. In the early postoperative period, all patients will be treated with topical corticosteroids (four times daily) for two weeks, which will be tapered-off slowly over six to eight weeks. Suture-lysis with argon laser will be performed under topical anesthesia when, in the opinion of the surgeon, filtration is judged to be too low and the IOP too high for the patient to meet the target pressure.

Preparation of the Drug:

Bevacizumab Avastin (Avastin) is available in a sterile vial (100 mg in 4 ml) preservative free and in order to ensure safety the vial injection will be administered within one day.

Subconjunctival Injections (1.25mg drug in 0.05ml) will be given at the end of the surgery adjacent to the bleb raised using a single-use 30-gauge needle and a tuberculin syringe.