Interferon alpha-2b addition to intravitreal bevacizumab for diabetic macular edema: a randomized controlled trial

Abstract

BACKGROUND: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents are the standard of care in DME, a sight-threatening complication of diabetic retinopathy. However, many patients show suboptimal response to anti-VEGF agents alone. This study aimed to investigate the effect of adding interferon alpha 2b eye drops to intravitreal bevacizumab (IVB) in treating patients with DME. METHODS: In this double-blind, placebo-controlled, parallel clinical trial, eligible eyes of DME patients were randomized into two treatment arms: (1) three monthly doses of intravitreal bevacizumab (IVB) (2) three monthly doses of IVB plus interferon alpha 2b eye drops (IVB + IFN). Outcome measures were changes in central macular thickness (CMT) and best corrected visual acuity (BCVA) over four months. Intraocular pressure (IOP) and possible adverse events were also documented. RESULTS: A total of 87 eyes of 87 patients with DME were included (mean age: 64.1, female-to-male ratio ~ 1:1). Anatomical and visual improvements were significant in both groups (p-value < 0.001). CMT reduction and BCVA improvement were greater in the IVB + IFN compared to the IVB group (-117 mum vs. -54 mum, 0.2 vs. 0.1 LogMAR, p-values = 0.004 and < 0.001, respectively). Final IOP was lower in the IVB + IFN group (p value = 0.02), but within groups changes were not significant in either arm (p-value > 0.05). No serious side effects associated with IFN alpha 2b were observed. CONCLUSIONS: Adjunction of topical IFN alpha 2b to standard IVB therapy may result in superior functional and structural improvements in eyes with DME in short-term follow-up. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (irct.behdasht.gov.ir), IRCT20230103057035N1, March 18th, 2023.