Bahrami B, Hong T, Schlub T, Chang A. Aflibercept for persistent diabetic macular oedema: 48 week outcomes. Retina. 1 Jan 2019.
Over one-third of patients with diabetic macular edema (DME) have an incomplete response to intravitreal bevacizumab therapy. A clinical trial assessing the efficacy of switching therapy to aflibercept among treatment-resistant patients was performed over 48-weeks.
Forty-three patients with persistent DME following at least 4 intravitreal injections of bevacizumab in the prior 6 months were recruited in a single-armed, prospective clinical trial. Five initial loading doses of 2mg of intravitreal aflibercept were administered every 4-weeks until week 20, then the treatment interval was extended to 8-weekly until week 48. Participants underwent a full ophthalmic assessment every 4 weeks including best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) to assess central macular thickness (CMT). Ultra-widefield fluorescein angiography (UWFA) and ultra-widefield imaging were performed at baseline and at 48 weeks. Ischaemic index was calculated based on UWFA images. Diabetic retinopathy (DR) severity was graded using a 9-step ETDRS scale on ultra-widefield images. Paired t-tests were used to assess changes in outcomes.
At baseline study eyes had received 16.9±11.5 intravitreal anti-VEGF injections over a period of 26.9±23.8 months prior to switch. During the study mean CMT reduced from 417±91µm at baseline to 357±108µm at 48 weeks (60µm reduction, p<0.01). Mean BCVA improved from 67.8±10.3 letters at baseline to 71.8±10.6 letters at 48 weeks (4.0 letter gain, p=0.03). Patients gaining 5 or more letters following the first injection of aflibercept had better BCVA at 48 weeks (5.4±4.9 vs. 1.3±5.6 letters, p=0.03). DR severity remained stable in 79% of participants, improved by 1-step in 18% and worsened by 1-step in 3%. Ischemic index was 0.24±0.30 at baseline and 0.22±0.30 at week 48 (change -0.03, p>0.05). Baseline ischemic index was not associated with change in BCVA or CMT at week 48.ck.
Switching therapy from bevacizumab to aflibercept resulted in improved visual and anatomical outcomes in this cohort of refractory DME patients. Treatment with aflibercept may have a disease modifying effect of DR in patients with refractory DME and significant prior anti-VEGF treatment.