Prevention of Recurrent Pterygium with Topical Bevacizumab 0.05% Eye Drops: A Randomized Controlled Trial

Abstract

Purpose

We assessed the efficacy and tolerability of topical bevacizumab 0.05% when used as an adjunctive therapy after excision of primary pterygia.

Methods

This randomized double-masked study included 22 patients (22 eyes) with primary pterygia who underwent pterygium surgery with the use of the bare sclera technique. After pterygium excision, 22 patients were randomized to receive the topical bevacizumab 0.05% (12 eyes) or the placebo (10 eyes) with the use of the block of four randomization method. Topical bevacizumab and placebo were applied in the respective groups 4 times daily for 3 months. Follow-up evaluations for recurrence by slit-lamp photography were conducted once monthly. Ocular and systemic adverse events were assessed every 2 weeks during the 3 months of treatment. The slit-lamp photographs were masked and analyzed. The primary and secondary outcomes were the differences in the pterygial recurrence rates between the groups and adverse events at 3 months, respectively. Corneal recurrence was defined as recurrent fibrovascular tissue invading the cornea; conjunctival recurrence was defined as either recurrent vessels or fibrous tissue in the excised area without corneal invasion.

Findings

All 22 patients completed follow-up at 3 months after the start of the trial medications. After 3 months of treatment, 1 patient (8.33%) and 3 patients (30.00%) from the bevacizumab and placebo groups, respectively, had a corneal recurrence. No significant (P = 0.293) differences were found between the groups as determined by Fisher’s exact test. However, conjunctival and corneal recurrences were found in 4 (33.33%) and 9 (90.00%) patients, respectively, in the bevacizumab and placebo groups, a difference that reached significance (P = 0.01). No significant adverse events developed.

Implications

Topical bevacizumab, as an adjunctive treatment after pterygium excision, was well tolerated. The trend for recurrence was lower in the topical bevacizumab group. ClinicalTrials.gov identifier: NCT01311960.

Introduction

Pterygium is a degenerative and proliferative fibrovascular disorder of the ocular surface, usually a triangular- or wing-shaped tissue, extending from the conjunctiva onto the cornea. Various adjunctive measures are applied to prevent recurrence of pterygia after excision, including medical methods (ie, mitomycin-C [MMC], β-irradiation) and surgical methods (ie, conjunctival graft, amniotic membrane graft). Both MMC and β-irradiation are associated with recurrence rates that range from 0% to 38%. However, their use was associated with serious sight-threatening adverse events, including necrotizing scleritis and perforation.¹ Many studies have reported that conjunctival and limbal autografts with MMC reduce the rates of pterygial recurrence (0%–7%). However, various factors, including primary or recurrent status of the pterygia, patient age, surgeon, or patient preference, affect the surgical outcomes. Until now, the data could not definitively recommend a specific adjuvant as a beneficial choice.²

In the past 2 decades, studies of vascular endothelial growth factor (VEGF) drugs have led to the development of new ophthalmic therapies, including those for pterygia. The overexpression of VEGF in the pterygium tissue suggested that this factor was involved in the pathogenesis of the disorder.³ Bevacizumab (Avastin, Genentech Inc, South San Francisco, CA), a monoclonal antibody to VEGF-A, prevents attachment of VEGF-A to its receptors. Because bevacizumab inhibits proliferation of endothelial cells and formation of new blood vessels,⁴ the drug was suggested as a potential adjunctive treatment after pterygial excision. This randomized, double-masked controlled trial was designed to evaluate the efficacy and tolerability of topical bevacizumab 0.05% eye drops as an adjunctive therapy after excision of primary pterygia via the bare sclera technique.