BackgroundAmblyopia is the most common developmental vision disorder in children. The initial treatment consists of refractive correction. When insufficient, occlusion therapy may further improve visual acuity. However, the challenges and compliance issues associated with occlusion therapy may result in treatment failure and residual amblyopia. Virtual reality (VR) games developed to improve visual function have shown positive preliminary results. The aim of this study is to determine the efficacy of these games to improve vision, attention, and motor skills in patients with residual amblyopia and identify brain-related changes. We hypothesize that a VR-based training with the suggested ingredients (3D cues and rich feedback), combined with increasing the difficulty level and the use of various games in a home-based environment is crucial for treatment efficacy of vision recovery, and may be particularly effective in children.MethodsThe AMBER study is a randomized, cross-over, controlled trial designed to assess the effect of binocular stimulation (VR-based stereoptic serious games) in individuals with residual amblyopia (n= 30, 6–35 years of age), compared to refractive correction on vision, selective attention and motor control skills. Additionally, they will be compared to a control group of age-matched healthy individuals (n= 30) to account for the unique benefit of VR-based serious games. All participants will play serious games 30 min per day, 5 days per week, for 8 weeks. The games are delivered with the Vivid Vision Home software. The amblyopic cohort will receive both treatments in a randomized order according to the type of amblyopia, while the control group will only receive the VR-based stereoscopic serious games. The primary outcome is visual acuity in the amblyopic eye. Secondary outcomes include stereoacuity, functional vision, cortical visual responses, selective attention, and motor control. The outcomes will be measured before and after each treatment with 8-week follow-up.DiscussionThe VR-based games used in this study have been conceived to deliver binocular visual stimulation tailored to the individual visual needs of the patient, which will potentially result in improved basic and functional vision skills as well as visual attention and motor control skills.Trial registrationThis protocol is registered on ClinicalTrials.gov (identifier: NCT05114252) and in the Swiss National Clinical Trials Portal (identifier: SNCTP000005024).