Safety and Efficacy of Using Off-label Bevacizumab Versus Mitomycin C to Prevent Bleb Failure in a Single-site Phacotrabeculectomy by a Randomized Controlled Clinical Trial Sabyasachi Sengupta, DO, DNB,*w Rengaraj Venkatesh, MD,*w and Ravilla D. Ravindran, MD*w Purpose: To analyze the safety and efficacy of bevacizumab (1.25 mg/0.05 mL) versus 0.03% mitomycin C (MMC) for prevent- ing bleb failure in patients undergoing single-site phacotrabecu- lectomy for primary open-angle glaucoma or chronic angle-closure glaucoma. Materials and Methods: Thirty-eight consecutive patients with visually significant cataract and coexistent primary open-angle glaucoma or chronic angle-closure glaucoma were randomized into 3 groups. One group received conventional 0.03% MMC (n=13); the second group received 3 subconjunctival injections of bevacizumab (1.25 mg in 0.05 mL) (n=13); and the third group received bevacizumab soaked in sponges (1.25 mg in 0.05 mL) (n=12) intraoperatively on the sclera. Patients were followed up for 6 months. The primary outcome measure was treatment success and bleb morphology in the study eye at 6-month follow-up. Results: All 3 groups showed significant reduction in mean intraocular pressure at 1 week after treatment, which was maintained at 6 months. However, the subconjunctival bevacizu- mab group had 90% patients with complete success as opposed to 60% in each of the other 2 groups (P=0.04). In both bevacizumab groups, bleb vascularity increased progressively over the 6-month follow-up. One patient in the subconjunctival bevacizumab group showed a local conjunctival necrosis. Conclusion: In this pilot study with a small number of subjects, short-term outcomes suggest that subconjunctival bevacizumab is equally effective in reducing intraocular pressure with a better safety profile compared with MMC in the dosing schedule studied. However, bevacizumab soaked in a sponge appears to have no advantages over MMC. Subconjunctival bevacizumab may be a useful agent for improving success and for limiting scar tissue after phacotrabeculectomy. Key Words: trabeculectomy, phacoemulsification, bevacizumab, mitomycin C (J Glaucoma 2012;21:450–459) T he main determinant of long-term intraocular pressure (IOP) control after glaucoma filtration surgery is the healing response. 1,2 Although antimetabolites have revolu- tionized glaucoma filtration surgery (GFS) (particularly in patient groups with a high risk of surgical failure because of scarring), the use of these agents is still associated with blinding complications. 3 Moreover, because surgery can fail despite the use of powerful antimetabolites, there is a need for better agents with improved risk-benefit ratios. Recent research has suggested that glaucomatous progression can be stopped in the majority of patients for more than a decade if pressure can be controlled in the 10 to 15 mm Hg range. 4 The conjunctiva occupies over 90% of the ocular surface and plays a significant role in the maintenance of bleb integrity after GFS. Hence, modulation of post- operative conjunctival wound-healing responses after trabeculectomy need careful understanding of the basic concepts involved in the complex, yet harmonious, process of wound healing. The pathogenesis of wound healing has been modified to prolong bleb lifespans in the past. Yet, an agent with a potentially better safety profile than those existent currently still eludes us. This study was a pilot trial to analyze the viability of augmenting single-site phaco- trabeculectomy with anti-vascular endothelial growth factor (VEGF) antibody, bevacizumab (Bevacizumab; Genentech, Inc., San Francisco, CA), with 6 months of follow-up and to analyze the bleb characteristics using the Indiana Bleb Appearance System (IBAS) in comparison with mitomycin C (MMC). 5 MATERIALS AND METHODS Patient Recruitment Thirty-eight eyes of 38 consecutive consenting patients (1 eye from each patient) who presented at our glaucoma specialty clinic within the study period were randomized for the study. All patients received a detailed explanation that included the study’s purpose and methods, expected out- comes and risks, and availability of other therapies. All patients choosing to participate in the study were required to provide an informed consent. The study was approved by the Institutional Review board and by the Ethical committee of the Aravind Eye Care Systems. Men and women >40 years of age requiring phacoemulsification combined with glaucoma surgery for the first time were enrolled if they satisfied the inclusion Copyright r 2012 by Lippincott Williams & Wilkins DOI:10.1097/IJG.0b013e31821826b2 Received for publication June 3, 2010; accepted February 28, 2011. From the *Glaucoma Services, Aravind Eye Hospital; and wPost Graduate Institute of Ophthalmology, Pondicherry, India. Disclosure: The authors declare no conflicting interests and no sources of support. The study has never been submitted to any journal in the past and has never been published. Reprints: Sabyasachi Sengupta, DO, DNB, Aravind Eye Hospital, Pondicherry 605007, India (e-mail: drsunny1980@gmail.com). ORIGINAL STUDY 450 | www.glaucomajournal.com J Glaucoma  Volume 21, Number 7, September 2012