Amblyopia, Anisometropic Amblyopia
Conditions
Keywords
Adult Amblyopia, Anisometropic Amblyopia, Dichoptic Therapy, Augmented Reality, Transcranial Direct Current Stimulation, High-Definition Transcranial Direct Current Stimulation, Noninvasive brain stimulation, Visual rehabilitation, Binocular vision, Neuroplasticity
Brief summary
The goal of this clinical trial is to learn whether adding noninvasive brain stimulation to augmented reality-based vision therapy can improve vision in adults aged 18 to 40 years with unilateral anisometropic amblyopia, commonly called "lazy eye." Anisometropic amblyopia develops during childhood when the two eyes have different focusing powers and the brain relies more on one eye than the other. The main questions this study aims to answer are: * Does active high-definition transcranial direct current stimulation (HD-tDCS) improve best-corrected visual acuity in the amblyopic eye and depth perception more than sham stimulation? * Does the combined treatment improve contrast sensitivity, suppression between the eyes, and measures of retinal and visual brain function? All participants will receive the same augmented reality-based dichoptic therapy. This therapy presents different visual information to each eye and lowers the contrast seen by the stronger eye. This gives the weaker, amblyopic eye a visual advantage and encourages both eyes to work together while participants carry out normal daily activities. During the first 2 weeks, participants will also receive either active HD-tDCS or sham stimulation immediately before the augmented reality therapy. Active HD-tDCS delivers a weak electrical current through small electrodes placed on the scalp. Sham stimulation uses the same equipment and procedures, but the current is applied only briefly at the beginning. Comparing the two groups will help researchers determine whether active brain stimulation provides additional benefits beyond those of augmented reality therapy alone. Participants will: * Complete 40-minute augmented reality therapy sessions four times per week for 10 weeks. * Receive eight 20-minute sessions of active or sham HD-tDCS during the first 2 weeks, immediately before the augmented reality therapy. * Attend assessment visits before treatment, after 2 weeks, and after 10 weeks. These visits will include vision tests, retinal imaging, tests of retinal function, and brain imaging.
Detailed description
Amblyopia is a neurodevelopmental visual disorder that usually begins during childhood and may persist into adulthood. Although it is often identified by reduced vision in one eye, amblyopia also involves abnormal interaction between the two eyes, including suppression of the amblyopic eye and impaired depth perception. Traditional treatments mainly rely on patching the stronger eye and are usually offered during childhood. However, growing evidence suggests that the adult visual system retains some capacity for plasticity and may respond to appropriately designed visual training. Dichoptic therapy aims to improve binocular vision by presenting different visual information to each eye. In this study, the therapy is delivered through an augmented reality headset. The contrast of the image presented to the stronger eye is reduced, giving the amblyopic eye a visual advantage while both eyes remain open. The level of contrast penalization is individualized and adjusted during treatment according to the visual performance of the amblyopic eye. Unlike fully immersive virtual reality, augmented reality allows participants to remain aware of and interact with their real surroundings while completing the visual training. This study is a randomized, double-blind, sham-controlled, parallel-group clinical trial. All participants will complete the same augmented reality-based dichoptic therapy for 10 weeks. During the first 2 weeks, they will also receive eight sessions of either active or sham high-definition transcranial direct current stimulation (HD-tDCS), delivered immediately before the visual training. Active HD-tDCS will be applied to the primary visual cortex using a 4 × 1 electrode configuration centered over the occipital region. A weak direct current of 2.0 mA will be delivered for 20 minutes. Sham stimulation will use the same equipment, electrode placement, and initial ramping procedure, but without sustained electrical stimulation. Participants and the researcher administering the stimulation will be unaware of the assigned condition. This design will allow the effect of active HD-tDCS to be evaluated while both groups receive the same visual therapy. The primary hypothesis is that active HD-tDCS will enhance the effects of augmented reality-based dichoptic therapy, leading to greater improvement in best-corrected visual acuity in the amblyopic eye than sham stimulation. The study will also examine whether the combined treatment improves stereopsis, interocular suppression, and contrast sensitivity. In addition to clinical vision measures, the study will investigate possible changes in retinal structure, retinal ganglion cell function, and visual cortex organization. Optical coherence tomography, pattern electroretinography, and functional magnetic resonance imaging will be used to explore the neural mechanisms associated with treatment response. These measures may also help identify retinal or cortical markers associated with greater visual improvement. The study will compare early changes after the initial 2 weeks of combined treatment with changes observed at the end of the 10-week therapy period. The broader aim is to determine whether noninvasive brain stimulation can strengthen adult visual plasticity and increase the effectiveness of binocular rehabilitation for amblyopia
Interventions
Active high-definition transcranial direct current stimulation will be delivered using a Soterix MxN-33 stimulator and a 4 × 1 electrode montage targeting the primary visual cortex. The central anodal electrode will be positioned at Oz, with four return electrodes positioned at PO3, PO4, PO7, and PO8. A current of 2.0 mA will be delivered for 20 minutes, including a 30-second ramp-up period at the beginning and a 30-second ramp-down period at the end of stimulation. Participants will receive eight sessions during the first 2 weeks, immediately before the augmented reality-based dichoptic therapy.
Sham high-definition transcranial direct current stimulation will use the same stimulator, electrode montage, electrode positions, and session duration as active stimulation. The current will be ramped up over 30 seconds at the beginning of the session and then ramped down over 30 seconds, with no sustained current delivered during the remainder of the session. Participants will receive eight 20-minute sessions during the first 2 weeks, immediately before the augmented reality-based dichoptic therapy.
DEVICEAugmented Reality-Based Dichoptic Therapy
Augmented reality-based dichoptic therapy will be delivered using a Meta Quest 3 headset. Participants will complete 40-minute sessions four times per week for 10 weeks. The therapy presents different visual information to each eye and reduces the contrast presented to the stronger eye, giving the amblyopic eye a visual advantage and encouraging both eyes to work together. Visual acuity in the amblyopic eye will be assessed within the headset to guide adjustment of the contrast presented to the stronger eye. The augmented reality environment allows participants to interact with their real surroundings and perform everyday activities during therapy.
Sponsors
Polytechnic Institute of Porto
University of Coimbra
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
Participants will be randomly assigned in a 1:1 ratio to one of two parallel groups. Both groups will receive the same augmented reality-based dichoptic therapy for 10 weeks. During the first 2 weeks, one group will receive active HD-tDCS and the other will receive sham HD-tDCS immediately before the dichoptic therapy.
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
* Age between 18 and 40 years. * Diagnosis of anisometropic amblyopia. * Unilateral amblyopia with an interocular difference of at least 2 lines in best-corrected visual acuity, with visual acuity worse than 20/32 in the worse-seeing eye.
Exclusion criteria
* Any type of amblyopia other than anisometropic amblyopia. * Bilateral amblyopia. * Ophthalmological or neuro-ophthalmological disease other than amblyopia. * Neurological disease. * Chronic pharmacological treatment. * Presence of an implanted medical device. * Any ocular surgery or treatment within the previous year. * Significant ocular media opacities. * Previous treatment with transcranial direct current stimulation or another non-invasive brain stimulation technique. * Pregnancy or planning to become pregnant during the study period. * Inability to provide informed consent. * History of head trauma, seizures, or frequent headaches. * Electrical or electronic implants, such as a cardiac pacemaker. * Metallic objects or implants in the head, except dental implants.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Best-Corrected Visual Acuity of the Amblyopic Eye at Week 2 | Baseline and Week 2 | 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 2 letter score minus the baseline letter score. A positive change indicates an improvement in visual acuity. |
| Change From Baseline in Best-Corrected Visual Acuity of the Amblyopic Eye at Week 10 | Baseline and 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. |
| Change From Baseline in Near Stereoacuity at Week 2 | Baseline and Week 2 | 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 2 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. |
| Change From Baseline in Near Stereoacuity at Week 10 | Baseline and 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Interocular Suppression at Week 2 | Baseline and Week 2 | 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 2 value minus the baseline value. |
| Change From Baseline in Interocular Suppression at Week 10 | Baseline and 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. |
| Change From Baseline in Static Achromatic Contrast Sensitivity of the Amblyopic Eye at Week 2 | Baseline and Week 2 | 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 2 value minus the baseline value. A positive change indicates improvement. |
| Change From Baseline in Static Achromatic Contrast Sensitivity in the Amblyopic and Fellow Eyes at Week 10 | Baseline and 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. |
| Change From Baseline in Retinal Neuronal Layer Thicknesses at Week 2 | Baseline and Week 2 | 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 2 value minus the baseline value for each thickness parameter. |
| Change From Baseline in Retinal Neuronal Layer Thicknesses at Week 10 | Baseline and 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. |
| Change From Baseline in Retinal Ganglion Cell Function Assessed by Pattern Electroretinography at Week 2 | Baseline and Week 2 | 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), N95 implicit time, measured in milliseconds (ms), and the N95/P50 amplitude ratio will be extracted and analyzed separately for each eye. Change from baseline will be calculated as the Week 2 value minus the baseline value for each PERG parameter. |
| Change From Baseline in Retinal Ganglion Cell Function Assessed by Pattern Electroretinography at Week 10 | Baseline and 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), N95 implicit time, measured in milliseconds (ms), and the N95/P50 amplitude ratio 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. |
| Change From Baseline in Cortical Population Receptive Field Size at Week 2 | Baseline and Week 2 | 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. |
| Change From Baseline in Cortical Population Receptive Field Size at Week 10 | Baseline and 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. |
| Change From Baseline in Cortical Contrast Sensitivity Function at Week 2 | Baseline and Week 2 | Cortical contrast sensitivity will be assessed using the NeuroCSF functional magnetic resonance imaging (fMRI) method. Derived parameters will include peak contrast sensitivity, peak spatial frequency, and spatial frequency bandwidth. |
| Change From Baseline in Cortical Contrast Sensitivity Function at Week 10 | Baseline and Week 10 | Cortical contrast sensitivity will be assessed using the NeuroCSF functional magnetic resonance imaging (fMRI) method. Derived parameters will include peak contrast sensitivity, peak spatial frequency, and spatial frequency bandwidth. |
Countries
Portugal
Contacts
CONTACTCatarina A Mateus, PhD
CONTACTRúben J Magalhães, MSc
Outcome results
None listed