Microinvasive pars plana vitrectomy combined with internal limiting membrane peeling versus anti-VEGF intravitreal injection for treatment-naïve diabetic macular edema (VVV-DME study): study protocol for a randomized controlled trial

Abstract

Background: Diabetic macular edema (DME) is the main cause of vision loss in diabetic patients. Currently, anti-vascular endothelial growth factor (VEGF) intravitreal injection stands as the first-line therapy for DME. However, some patients exhibit insufficient response to anti-VEGF agents and often require multiple injections, imposing psychological and economic burdens. While microinvasive pars plana vitrectomy (PPV) has been shown to be safe and effective in treating refractory DME, scant research has explored its application to treatment-naïve DME. The purpose of this study is to determine whether early PPV combined with internal limiting membrane (ILM) peeling can lessen the therapeutic burden of DME patients, prevent vision loss, and maintain long-term stabilization of diabetic retinopathy.

Methods: This is a single-center, prospective, parallel-group, non-inferiority randomized controlled trial involving 102 DME participants. Participants will be randomly assigned to either the study group (PPV combined with ILM peeling) or the control group (conbercept intravitreal injection (IVC)) at a 1:1 ratio, with a scheduled follow-up at 12 months post-operation. Comparative analysis of results between the two groups will be conducted at months 1, 3, 6, and 12 after the intervention. The primary outcomes involve evaluating the changes in central subfield thickness (CST) and best corrected visual acuity (BCVA). The secondary outcomes include assessment of optical coherence tomography (OCT) and OCT angiography (OCTA) biomarkers, re-treatment and adverse events rates, diabetic retinopathy (DR) development, cost-effectiveness analysis, and vision-related quality of life (VRQL).

Discussion: Some patients do not respond well to anti-VEGF drugs and repeated intravitreal injections increase the treatment burden for patients. The VVV study aims to explore whether PPV combined with ILM peeling could become an initial treatment option for treatment-naïve DME patients.

Trial registration: ClinicalTrials.gov NCT05728476. Registered on 15 February 2023.

Keywords: Anti-VEGF; Diabetic macular edema; Randomized controlled trial; Study protocol; Vitrectomy.