The goal of this clinical trial is to evaluate a home-based augmented reality-based binocular therapy designed to improve visual function in adults aged 18 to 40 years with unilateral anisometropic amblyopia, commonly called "lazy eye." The therapy is designed to be used during everyday activities, allowing visual training to be integrated into the participant's normal home routine. The main questions this study aims to answer are: * Does the Ambly4Home augmented reality-based binocular therapy improve visual acuity in the amblyopic eye and binocular vision compared with placebo visual training? * Are any improvements in visual function maintained 6 months after the treatment has ended? * Is the treatment associated with changes in other measures of visual function, retinal structure and function, and visual brain function? Participants will be randomly assigned to receive either active binocular therapy or placebo visual training. Both groups will use the same mixed-reality device, follow the same training schedule, and carry out similar daily activities while viewing their real-world surroundings through the device. In the active treatment, the image presented to the amblyopic eye will remain close to the natural scene, while the contrast of the image presented to the stronger eye will be selectively lowered. This gives the amblyopic eye a relative visual advantage, helping to rebalance the input from the two eyes and encouraging them to work together. In the placebo group, participants will use the same device under the same conditions, but without the selective contrast reduction used in the active treatment. This comparison will allow researchers to isolate the specific effect of selectively lowering the contrast seen by the stronger eye. Participants will: * Complete 40-minute training sessions four times per week for 10 weeks. * Learn how to use the system in a clinical setting before continuing the training at home. * Attend assessment visits before treatment, after 10 weeks of treatment, and 6 months after treatment has ended. * Complete tests of visual acuity, depth perception, suppression between the eyes, and contrast sensitivity, as well as retinal imaging, retinal function testing, and brain imaging.
Amblyopia is a neurodevelopmental disorder characterized not only by reduced visual acuity in the amblyopic eye but also by abnormal interaction between the two eyes, including interocular suppression and impaired binocular integration. Although treatment has traditionally focused on childhood, evidence of residual visual plasticity in adults has supported the development of binocular and dichoptic approaches aimed at restoring a more balanced contribution from both eyes. Dichoptic therapy simultaneously stimulates both eyes while presenting different visual inputs to each eye. A common strategy is to reduce the strength of the image presented to the stronger eye, allowing the amblyopic eye to contribute more effectively during binocular viewing. This approach differs from conventional occlusion because visual information from both eyes remains available throughout treatment. The intervention evaluated in this study is designed to adapt this therapeutic principle to the daily life of adults with amblyopia. In contrast to fully immersive virtual reality approaches that require participants to interrupt their usual activities and engage in dedicated virtual tasks or games, the intervention uses a Meta Quest 3 mixed-reality headset operating in passthrough mode. Participants can therefore continue to view and interact with their real-world environment while controlled visual processing is applied separately to each eye. The intervention is intended to integrate binocular visual rehabilitation into functional activities performed in the home environment. During active treatment, the real-world scene presented to the amblyopic eye is preserved as close as possible to natural viewing conditions. The dominant eye receives the same spatially corresponding scene, but with a controlled reduction in contrast. This contrast manipulation reduces the functional advantage of the dominant eye without completely removing its visual information, creating a relative visual advantage for the amblyopic eye and encouraging its more active participation during binocular viewing. The intervention therefore aims to progressively rebalance the contribution of the two eyes rather than replace binocular vision with monocular viewing. The degree of contrast modulation will be individualized according to the participant's visual function and adjusted throughout treatment according to visual performance. As visual function improves, the contrast difference between the eyes can be progressively reduced, bringing the visual inputs closer to natural binocular viewing conditions. This adaptive approach is intended to maintain an appropriate therapeutic challenge while avoiding unnecessary or excessive penalization of the dominant eye. The study uses a randomized, placebo-controlled design in which both groups use the same mixed-reality device and follow the same training routine. The placebo condition preserves the device experience, duration, tasks, instructions, and home-use context but does not include the selective interocular contrast manipulation that produces active binocular rebalancing. This design allows the specific effect of the dichoptic treatment mechanism to be distinguished from nonspecific effects related to repeated visual activity, familiarity with the device, attention, and treatment expectations. The home-based intervention is also designed to support objective monitoring of treatment exposure. Information such as session completion, effective training duration, interruptions, visual settings, task performance, adherence, and tolerability may be recorded to characterize the actual treatment dose and support individualized progression. Functional activities will be selected according to the participant's visual ability and safety, allowing the difficulty of the training to increase gradually as adaptation and visual performance improve. In addition to determining the clinical effect of the binocular intervention, the study uses a multimodal assessment approach to characterize visual, retinal, and cortical changes associated with treatment and to investigate whether any improvements persist after treatment has ended. This approach is intended to provide a broader understanding of the functional and neurobiological response to home-based augmented reality binocular rehabilitation in adults with anisometropic amblyopia.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
60
Active augmented reality-based binocular therapy will be delivered using a Meta Quest 3 mixed-reality headset operating in passthrough mode. Participants will complete 40-minute sessions four times per week for 10 weeks, initially learning to use the system in a clinical setting and subsequently continuing the training at home. The real-world scene presented to the amblyopic eye will remain close to natural viewing, while the contrast presented to the dominant eye will be selectively reduced. This controlled contrast reduction gives the amblyopic eye a relative visual advantage, encouraging its more active contribution during binocular viewing and promoting binocular integration. The degree of contrast modulation will be adjusted according to visual performance over the course of treatment.
Placebo augmented reality-based visual training will be delivered using the same Meta Quest 3 mixed-reality headset operating in passthrough mode, with the same session duration, training schedule, and home-based setting as the active intervention. Participants will view and interact with their real-world surroundings while carrying out similar visual activities. Unlike the active intervention, the contrast presented to the dominant eye will not be selectively reduced. The visual information presented to both eyes will remain equivalent or will be only minimally and symmetrically modified, without providing active binocular rebalancing or a therapeutic visual advantage to the amblyopic eye.
Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), University of Coimbra
Coimbra, Coimbra District, Portugal
RECRUITINGRISE-Health, Center for Translational Health and Medical Biotechnology Research (TBIO), School of Health, Polytechnic of Porto
Porto, Porto District, Portugal
RECRUITINGChange From Baseline in Best-Corrected Visual Acuity of the Amblyopic Eye at Week 10
Best-corrected visual acuity of the amblyopic eye will be assessed monocularly using a standardized ETDRS chart and recorded as the number of letters correctly identified. Higher ETDRS letter scores indicate better visual acuity. Change from baseline will be calculated as the Week 10 letter score minus the baseline letter score. A positive change indicates an improvement in visual acuity.
Time frame: Baseline and Week 10
Change From Baseline in Best-Corrected Visual Acuity of the Amblyopic Eye at 6-Month Follow-up
Best-corrected visual acuity of the amblyopic eye will be assessed monocularly using a standardized ETDRS chart and recorded as the number of letters correctly identified. Higher ETDRS letter scores indicate better visual acuity. Change from baseline will be calculated as the 6-month follow-up letter score minus the baseline letter score. A positive change indicates an improvement in visual acuity.
Time frame: Baseline and 6 months after treatment completion
Change From Baseline in Near Stereoacuity at Week 10
Near stereoacuity will be assessed binocularly using a graded circles stereotest with polarized glasses and recorded in seconds of arc. Measurable stereoacuity ranges from 400 to 20 seconds of arc. Lower values indicate better stereoacuity. Change from baseline will be calculated as the Week 10 value minus the baseline value. A negative change indicates an improvement. Participants unable to identify the largest disparity will be classified as having no measurable stereoacuity.
Time frame: Baseline and Week 10
Change From Baseline in Near Stereoacuity at 6-Month Follow-up
Near stereoacuity will be assessed binocularly using a graded circles stereotest with polarized glasses and recorded in seconds of arc. Measurable stereoacuity ranges from 400 to 20 seconds of arc. Lower values indicate better stereoacuity. Change from baseline will be calculated as the 6-month follow-up value minus the baseline value. A negative change indicates an improvement. Participants unable to identify the largest disparity will be classified as having no measurable stereoacuity.
Time frame: Baseline and 6 months after treatment completion
Change From Baseline in Interocular Suppression at Week 10
Interocular suppression will be assessed under binocular viewing conditions using a standardized suppression test. The outcome will be the filter level at which binocular perception changes. Change from baseline will be calculated as the Week 10 value minus the baseline value.
Time frame: Baseline and Week 10
Change From Baseline in Interocular Suppression at 6-Month Follow-up
Interocular suppression will be assessed under binocular viewing conditions using a standardized suppression test. The outcome will be the filter level at which binocular perception changes. Change from baseline will be calculated as the 6-month follow-up value minus the baseline value.
Time frame: Baseline and 6 months after treatment completion
Change From Baseline in Static Achromatic Contrast Sensitivity in the Amblyopic Eye at Week 10
Static achromatic contrast sensitivity will be assessed monocularly in the amblyopic and fellow eyes using the MonCV3 system (Metrovision). Sinusoidal gratings will be presented at a temporal frequency of 0 Hz and at spatial frequencies of 0.55, 1.1, 2.2, 3.4, 7.1, and 14.2 cycles per degree. Results will be recorded in decibels (dB) separately for each eye and spatial frequency, with higher values indicating better contrast sensitivity. Change from baseline will be calculated as the Week 10 value minus the baseline value. A positive change indicates improvement.
Time frame: Baseline and Week 10
Change From Baseline in Static Achromatic Contrast Sensitivity in the Amblyopic Eye at 6-Month Follow-up
Static achromatic contrast sensitivity will be assessed monocularly in the amblyopic and fellow eyes using the MonCV3 system (Metrovision). Sinusoidal gratings will be presented at a temporal frequency of 0 Hz and at spatial frequencies of 0.55, 1.1, 2.2, 3.4, 7.1, and 14.2 cycles per degree. Results will be recorded in decibels (dB) separately for each eye and spatial frequency, with higher values indicating better contrast sensitivity. Change from baseline will be calculated as the 6-month follow-up value minus the baseline value. A positive change indicates improvement.
Time frame: Baseline and 6 months after treatment completion
Change From Baseline in Retinal Neuronal Layer Thicknesses at Week 10
Retinal structure will be assessed in the amblyopic and fellow eyes using the CIRRUS HD-OCT 5000 (ZEISS). The outcome measures will include total macular thickness, macular ganglion cell-inner plexiform layer (GCIPL) thickness, and peripapillary retinal nerve fiber layer (RNFL) thickness. Measurements will be recorded in micrometers (µm) and analyzed separately for each eye and prespecified retinal sector. Change from baseline will be calculated as the Week 10 value minus the baseline value for each thickness parameter.
Time frame: Baseline and Week 10
Change From Baseline in Retinal Neuronal Layer Thicknesses at 6-Month Follow-up
Retinal structure will be assessed in the amblyopic and fellow eyes using the CIRRUS HD-OCT 5000 (ZEISS). The outcome measures will include total macular thickness, macular ganglion cell-inner plexiform layer (GCIPL) thickness, and peripapillary retinal nerve fiber layer (RNFL) thickness. Measurements will be recorded in micrometers (µm) and analyzed separately for each eye and prespecified retinal sector. Change from baseline will be calculated as the 6-month follow-up value minus the baseline value for each thickness parameter.
Time frame: Baseline and 6 months after treatment completion
Change From Baseline in Retinal Ganglion Cell Function Assessed by Pattern Electroretinography at Week 10
Retinal ganglion cell function will be assessed in the amblyopic and fellow eyes using pattern electroretinography (PERG) recorded with the Tomey EP-1000 Pro system. N95 amplitude, measured in microvolts (µV), and N95 implicit time, measured in milliseconds (ms), will be extracted and analyzed separately for each eye. Change from baseline will be calculated as the Week 10 value minus the baseline value for each PERG parameter.
Time frame: Baseline and Week 10
Change From Baseline in Retinal Ganglion Cell Function Assessed by Pattern Electroretinography at 6-Month Follow-up
Retinal ganglion cell function will be assessed in the amblyopic and fellow eyes using pattern electroretinography (PERG) recorded with the Tomey EP-1000 Pro system. N95 amplitude, measured in microvolts (µV), and N95 implicit time, measured in milliseconds (ms), will be extracted and analyzed separately for each eye. Change from baseline will be calculated as the 6-month follow-up value minus the baseline value for each PERG parameter.
Time frame: Baseline and 6 months after treatment completion
Change From Baseline in Cortical Population Receptive Field Size at Week 10
Cortical population receptive field (pRF) size will be assessed using functional magnetic resonance imaging (fMRI)-based retinotopic mapping. Mean pRF size will be estimated separately for the early visual areas V1, V2, and V3.
Time frame: Baseline and Week 10
Change From Baseline in Cortical Population Receptive Field Size at 6-Month Follow-up
Cortical population receptive field (pRF) size will be assessed using functional magnetic resonance imaging (fMRI)-based retinotopic mapping. Mean pRF size will be estimated separately for the early visual areas V1, V2, and V3.
Time frame: Baseline and 6 months after treatment completion
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