AmblyopiaNiBS4VisionNCT07752433
Combining Noninvasive Brain Stimulation and Augmented Reality-based Dichoptic Therapy for Treating Amblyopic Adults
A study testing Active High-Definition Transcranial Direct Current Stimulation and Augmented Reality-Based Dichoptic Therapy in people with Amblyopia and Anisometropic Amblyopia, run by Polytechnic Institute of Porto at 2 sites in Portugal.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 40 years
- Conditions the study is for
- Amblyopia, Anisometropic Amblyopia
- What is being tested?
- Active High-Definition Transcranial Direct Current Stimulation and Augmented Reality-Based Dichoptic Therapy
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 2 sitesPortugal
- Study dates
- 1 May 2025to 30 Apr 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 14Show fewer
- 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.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Portugal2 sites, 2 recruiting
- Recruiting
Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), University of Coimbra
Coimbra, Coimbra District, 3000-548
Miguel Castelo-Branco, MD, PhD, +351 239488510, mcbranco@fmed.uc.pt
Miguel Castelo-Branco, MD, PhD
- Recruiting
RISE-Health, Center for Translational Health and Medical Biotechnology Research (TBIO), School of Health, Polytechnic of Porto
Porto, Porto District, 4200-072
Nuno B Rocha, PhD, +351 913474780, nrocha@ess.ipp.pt
Catarina Mateus, PhD
About this study
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:
Read more
- 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.
Read the 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
- Conditions
- Amblyopia, Anisometropic Amblyopia
- Being tested
- Active High-Definition Transcranial Direct Current Stimulation, Sham High-Definition Transcranial Direct Current Stimulation, Augmented Reality-Based Dichoptic Therapy
- 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
- Medical subject headings
- Amblyopia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active High-Definition Transcranial Direct Current StimulationDevice
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 StimulationDevice
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.
Augmented Reality-Based Dichoptic TherapyDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| Active HD-tDCS + AR-Based Dichoptic Therapy | Experimental | Participants will receive augmented reality-based dichoptic therapy for 10 weeks, with 40-minute sessions four times per week. During the first 2 weeks, participants will also receive eight 20-minute sessions of active HD-tDCS applied to the primary visual cortex immediately before the augmented reality-based dichoptic therapy. Receives: Device: Active High-Definition Transcranial Direct Current Stimulation; Device: Augmented Reality-Based Dichoptic Therapy |
| Sham HD-tDCS + AR-Based Dichoptic Therapy | Sham comparator | Participants will receive the same augmented reality-based dichoptic therapy for 10 weeks, with 40-minute sessions four times per week. During the first 2 weeks, participants will also receive eight 20-minute sessions of sham HD-tDCS immediately before the augmented reality-based dichoptic therapy. Sham stimulation will use the same equipment, electrode placement, and initial ramping procedure as active stimulation, but no sustained current will be delivered. Receives: Device: Sham High-Definition Transcranial Direct Current Stimulation; Device: Augmented Reality-Based Dichoptic Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Best-Corrected Visual Acuity of the Amblyopic Eye at 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.
Measured: Baseline and Week 2
Change 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.
Measured: Baseline and Week 10
Change From Baseline in Near Stereoacuity at 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.
Measured: Baseline and Week 2
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.
Measured: Baseline and Week 10
Secondary outcomes (12)
Change From Baseline in Interocular Suppression at 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.
Measured: Baseline and Week 2
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.
Measured: Baseline and Week 10
Change From Baseline in Static Achromatic Contrast Sensitivity of the Amblyopic Eye at 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.
Measured: Baseline and Week 2
Change From Baseline in Static Achromatic Contrast Sensitivity in the Amblyopic and Fellow Eyes 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.
Measured: Baseline and Week 10
Change From Baseline in Retinal Neuronal Layer Thicknesses at 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.
Measured: Baseline and Week 2
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.
Measured: Baseline and Week 10
Change From Baseline in Retinal Ganglion Cell Function Assessed by Pattern Electroretinography at 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.
Measured: Baseline and Week 2
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), 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.
Measured: Baseline and Week 10
Change From Baseline in Cortical Population Receptive Field Size at 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.
Measured: Baseline and Week 2
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.
Measured: Baseline and Week 10
Change From Baseline in Cortical Contrast Sensitivity Function at 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.
Measured: Baseline and Week 2
Change From Baseline in Cortical Contrast Sensitivity Function at 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.
Measured: Baseline and Week 10
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2026
- Study start1 May 2025
- Primary completion31 Dec 2027 (estimated)
- Study completion30 Apr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for AmblyopiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Polytechnic Institute of Porto
- Sponsor type
- University, hospital or other
- Collaborators
- University of Coimbra
- Responsible party
- Principal investigator, Catarina Mateus, PhD, Polytechnic Institute of Porto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07752433
- Sponsor's protocol ID
- ORT-2026-002
- Other IDs
- 2023.16131.ICDT, 2023
- Acronym
- NiBS4Vision
- Status last verified
- Sep 2026
- First submitted
- 3 Aug 2026
- Last updated
- 18 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data will not be shared because the approved data protection plan limits the use of coded study data to this project and does not permit their transfer to other institutions, investigators, or countries. Study findings may be disseminated only in aggregated, non-identifiable form.
Publications
Fu Z, Hong H, Su Z, Lou B, Pan CW, Liu H. Global prevalence of amblyopia and disease burden projections through 2040: a systematic review and meta-analysis. Br J Ophthalmol. 2020 Aug;104(8):1164-1170. doi: 10.1136/bjophthalmol-2019-314759. Epub 2019 Nov 8.
PubMed 31704700d'Almeida OC, Mateus C, Reis A, Grazina MM, Castelo-Branco M. Long term cortical plasticity in visual retinotopic areas in humans with silent retinal ganglion cell loss. Neuroimage. 2013 Nov 1;81:222-230. doi: 10.1016/j.neuroimage.2013.05.032. Epub 2013 May 16.
PubMed 23684869Mendola JD, Lam J, Rosenstein M, Lewis LB, Shmuel A. Partial correlation analysis reveals abnormal retinotopically organized functional connectivity of visual areas in amblyopia. Neuroimage Clin. 2018 Jan 31;18:192-201. doi: 10.1016/j.nicl.2018.01.022. eCollection 2018.
PubMed 29868445Silva MF, Harvey BM, Jorge L, Canario N, Machado F, Soares M, d'Almeida OC, Castelo-Branco M. Simultaneous changes in visual acuity, cortical population receptive field size, visual field map size, and retinal thickness in healthy human aging. Brain Struct Funct. 2021 Dec;226(9):2839-2853. doi: 10.1007/s00429-021-02338-0. Epub 2021 Jul 10.
PubMed 34245381Arif Y, Embury CM, Spooner RK, Okelberry HJ, Willett MP, Eastman JA, Wilson TW. High-definition transcranial direct current stimulation of the occipital cortices induces polarity dependent effects within the brain regions serving attentional reorientation. Hum Brain Mapp. 2022 Apr 15;43(6):1930-1940. doi: 10.1002/hbm.25764. Epub 2022 Jan 7.
PubMed 34997673Castillo-Astorga R, Del Valle-Batalla L, Mariman JJ, Plaza-Rosales I, de Los Angeles Juricic M, Maldonado PE, Vogel M, Fuentes-Flores R. Combined therapy of bilateral transcranial direct current stimulation and ocular occlusion improves visual function in adults with amblyopia, a randomized pilot study. Front Hum Neurosci. 2023 Feb 3;17:1056432. doi: 10.3389/fnhum.2023.1056432. eCollection 2023.
PubMed 36816499Ding Z, Li J, Spiegel DP, Chen Z, Chan L, Luo G, Yuan J, Deng D, Yu M, Thompson B. The effect of transcranial direct current stimulation on contrast sensitivity and visual evoked potential amplitude in adults with amblyopia. Sci Rep. 2016 Jan 14;6:19280. doi: 10.1038/srep19280.
PubMed 26763954Spiegel DP, Li J, Hess RF, Byblow WD, Deng D, Yu M, Thompson B. Transcranial direct current stimulation enhances recovery of stereopsis in adults with amblyopia. Neurotherapeutics. 2013 Oct;10(4):831-9. doi: 10.1007/s13311-013-0200-y.
PubMed 23857313Spiegel DP, Byblow WD, Hess RF, Thompson B. Anodal transcranial direct current stimulation transiently improves contrast sensitivity and normalizes visual cortex activation in individuals with amblyopia. Neurorehabil Neural Repair. 2013 Oct;27(8):760-9. doi: 10.1177/1545968313491006. Epub 2013 Jun 17.
PubMed 23774122Meqdad Y, El-Basty M, Awadein A, Gouda J, Hassanein D. Randomized Controlled Trial of Patching versus Dichoptic Stimulation Using Virtual Reality for Amblyopia Therapy. Curr Eye Res. 2024 Feb;49(2):214-223. doi: 10.1080/02713683.2023.2275531. Epub 2024 Jan 18.
PubMed 37878538Ziak P, Holm A, Halicka J, Mojzis P, Pinero DP. Amblyopia treatment of adults with dichoptic training using the virtual reality oculus rift head mounted display: preliminary results. BMC Ophthalmol. 2017 Jun 28;17(1):105. doi: 10.1186/s12886-017-0501-8.
PubMed 28659140Sterkin A, Yehezkel O. Binocular treatment of amblyopia: current state and recent advances. Curr Opin Ophthalmol. 2025 May 1;36(3):237-246. doi: 10.1097/ICU.0000000000001121. Epub 2025 Feb 13.
PubMed 39945356Pineles SL, Aakalu VK, Hutchinson AK, Galvin JA, Heidary G, Binenbaum G, VanderVeen DK, Lambert SR. Binocular Treatment of Amblyopia: A Report by the American Academy of Ophthalmology. Ophthalmology. 2020 Feb;127(2):261-272. doi: 10.1016/j.ophtha.2019.08.024. Epub 2019 Oct 13.
PubMed 31619356Levi DM. Rethinking amblyopia 2020. Vision Res. 2020 Nov;176:118-129. doi: 10.1016/j.visres.2020.07.014. Epub 2020 Aug 28.
PubMed 32866759Bui Quoc E, Kulp MT, Burns JG, Thompson B. Amblyopia: A review of unmet needs, current treatment options, and emerging therapies. Surv Ophthalmol. 2023 May-Jun;68(3):507-525. doi: 10.1016/j.survophthal.2023.01.001. Epub 2023 Jan 18.
PubMed 36681277
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combining Noninvasive Brain Stimulation and Augmented Reality-based Dichoptic Therapy for Treating Amblyopic Adults
- ClinicalTrials.gov ID
- NCT07752433
- Acronym / sponsor ID
- NiBS4Vision / ORT-2026-002
- Conditions
- Amblyopia, Anisometropic Amblyopia
- Keywords
- Adult Amblyopia, Anisometropic Amblyopia, Dichoptic Therapy, Augmented Reality, Transcranial Direct Current Stimulation, High-Definition Transcranial Direct Current Stimulation, Noninvasive brain stimulation, Visual rehabilitation
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Polytechnic Institute of PortoUniversity, hospital or other
- Collaborators
- University of Coimbra
- Study start
- 1 May 2025 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 30 Apr 2028 (estimated)
- First posted
- 7 Aug 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Active HD-tDCS + AR-Based Dichoptic Therapy | Experimental | Device: Active High-Definition Transcranial Direct Current Stimulation, Device: Augmented Reality-Based Dichoptic TherapyParticipants will receive augmented reality-based dichoptic therapy for 10 weeks, with 40-minute sessions four times per week. During the first 2 weeks, participants will also receive eight 20-minute sessions of active HD-tDCS applied to the primary visual cortex immediately before the augmented reality-based dichoptic therapy. |
| Sham HD-tDCS + AR-Based Dichoptic Therapy | Sham comparator | Device: Sham High-Definition Transcranial Direct Current Stimulation, Device: Augmented Reality-Based Dichoptic TherapyParticipants will receive the same augmented reality-based dichoptic therapy for 10 weeks, with 40-minute sessions four times per week. During the first 2 weeks, participants will also receive eight 20-minute sessions of sham HD-tDCS immediately before the augmented reality-based dichoptic therapy. Sham stimulation will use the same equipment, electrode placement, and initial ramping procedure as active stimulation, but no sustained current will be delivered. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (14 listed)
- Any type of amblyopia other than anisometropic amblyopia.
- Bilateral amblyopia.
- Ophthalmological or neuro-ophthalmological disease other than amblyopia.
- Neurological disease.
- Chronic pharmacological treatment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Active High-Definition Transcranial Direct Current StimulationActive 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. | Device | Active HD-tDCS + AR-Based Dichoptic Therapy |
| Sham High-Definition Transcranial Direct Current StimulationSham 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. | Device | Sham HD-tDCS + AR-Based Dichoptic Therapy |
| Augmented Reality-Based Dichoptic TherapyAugmented 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. | Device | Active HD-tDCS + AR-Based Dichoptic Therapy, Sham HD-tDCS + AR-Based Dichoptic Therapy |
Primary outcome
Change From Baseline in Best-Corrected Visual Acuity of the Amblyopic Eye at Week 2
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
12 secondary outcomes
Change From Baseline in Interocular Suppression at Week 2
Time frame: Baseline and Week 2
Change From Baseline in Interocular Suppression at Week 10
Time frame: Baseline and Week 10
Change From Baseline in Static Achromatic Contrast Sensitivity of the Amblyopic Eye at Week 2
Time frame: Baseline and Week 2
Change From Baseline in Static Achromatic Contrast Sensitivity in the Amblyopic and Fellow Eyes at Week 10
Time frame: Baseline and Week 10
Change From Baseline in Retinal Neuronal Layer Thicknesses at Week 2
Time frame: Baseline and Week 2
Change From Baseline in Retinal Neuronal Layer Thicknesses at Week 10
Time frame: Baseline and Week 10
Change From Baseline in Retinal Ganglion Cell Function Assessed by Pattern Electroretinography at Week 2
Time frame: Baseline and Week 2
Change From Baseline in Retinal Ganglion Cell Function Assessed by Pattern Electroretinography at Week 10
Time frame: Baseline and Week 10
Change From Baseline in Cortical Population Receptive Field Size at Week 2
Time frame: Baseline and Week 2
Change From Baseline in Cortical Population Receptive Field Size at Week 10
Time frame: Baseline and Week 10
Change From Baseline in Cortical Contrast Sensitivity Function at Week 2
Time frame: Baseline and Week 2
Change From Baseline in Cortical Contrast Sensitivity Function at Week 10
Time frame: Baseline and Week 10
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2026.
- Background: PubMed 31704700Fu Z, Hong H, Su Z, Lou B, Pan CW, Liu H. Global prevalence of amblyopia and disease burden projections through 2040: a systematic review and meta-analysis. Br J Ophthalmol. 2020 Aug;104(8):1164-1170. doi: 10.1136/bjophthalmol-2019-314759. Epub 2019 Nov 8.
- Background: PubMed 23684869d'Almeida OC, Mateus C, Reis A, Grazina MM, Castelo-Branco M. Long term cortical plasticity in visual retinotopic areas in humans with silent retinal ganglion cell loss. Neuroimage. 2013 Nov 1;81:222-230. doi: 10.1016/j.neuroimage.2013.05.032. Epub 2013 May 16.
- Background: PubMed 29868445Mendola JD, Lam J, Rosenstein M, Lewis LB, Shmuel A. Partial correlation analysis reveals abnormal retinotopically organized functional connectivity of visual areas in amblyopia. Neuroimage Clin. 2018 Jan 31;18:192-201. doi: 10.1016/j.nicl.2018.01.022. eCollection 2018.
- Background: PubMed 34245381Silva MF, Harvey BM, Jorge L, Canario N, Machado F, Soares M, d'Almeida OC, Castelo-Branco M. Simultaneous changes in visual acuity, cortical population receptive field size, visual field map size, and retinal thickness in healthy human aging. Brain Struct Funct. 2021 Dec;226(9):2839-2853. doi: 10.1007/s00429-021-02338-0. Epub 2021 Jul 10.
- Background: PubMed 34997673Arif Y, Embury CM, Spooner RK, Okelberry HJ, Willett MP, Eastman JA, Wilson TW. High-definition transcranial direct current stimulation of the occipital cortices induces polarity dependent effects within the brain regions serving attentional reorientation. Hum Brain Mapp. 2022 Apr 15;43(6):1930-1940. doi: 10.1002/hbm.25764. Epub 2022 Jan 7.
- Background: PubMed 36816499Castillo-Astorga R, Del Valle-Batalla L, Mariman JJ, Plaza-Rosales I, de Los Angeles Juricic M, Maldonado PE, Vogel M, Fuentes-Flores R. Combined therapy of bilateral transcranial direct current stimulation and ocular occlusion improves visual function in adults with amblyopia, a randomized pilot study. Front Hum Neurosci. 2023 Feb 3;17:1056432. doi: 10.3389/fnhum.2023.1056432. eCollection 2023.
- Background: PubMed 26763954Ding Z, Li J, Spiegel DP, Chen Z, Chan L, Luo G, Yuan J, Deng D, Yu M, Thompson B. The effect of transcranial direct current stimulation on contrast sensitivity and visual evoked potential amplitude in adults with amblyopia. Sci Rep. 2016 Jan 14;6:19280. doi: 10.1038/srep19280.
- Background: PubMed 23857313Spiegel DP, Li J, Hess RF, Byblow WD, Deng D, Yu M, Thompson B. Transcranial direct current stimulation enhances recovery of stereopsis in adults with amblyopia. Neurotherapeutics. 2013 Oct;10(4):831-9. doi: 10.1007/s13311-013-0200-y.
- Background: PubMed 23774122Spiegel DP, Byblow WD, Hess RF, Thompson B. Anodal transcranial direct current stimulation transiently improves contrast sensitivity and normalizes visual cortex activation in individuals with amblyopia. Neurorehabil Neural Repair. 2013 Oct;27(8):760-9. doi: 10.1177/1545968313491006. Epub 2013 Jun 17.
- Background: PubMed 37878538Meqdad Y, El-Basty M, Awadein A, Gouda J, Hassanein D. Randomized Controlled Trial of Patching versus Dichoptic Stimulation Using Virtual Reality for Amblyopia Therapy. Curr Eye Res. 2024 Feb;49(2):214-223. doi: 10.1080/02713683.2023.2275531. Epub 2024 Jan 18.
- Background: PubMed 28659140Ziak P, Holm A, Halicka J, Mojzis P, Pinero DP. Amblyopia treatment of adults with dichoptic training using the virtual reality oculus rift head mounted display: preliminary results. BMC Ophthalmol. 2017 Jun 28;17(1):105. doi: 10.1186/s12886-017-0501-8.
- Background: PubMed 39945356Sterkin A, Yehezkel O. Binocular treatment of amblyopia: current state and recent advances. Curr Opin Ophthalmol. 2025 May 1;36(3):237-246. doi: 10.1097/ICU.0000000000001121. Epub 2025 Feb 13.
- Individual participant dataSharing planned: No. Individual participant data will not be shared because the approved data protection plan limits the use of coded study data to this project and does not permit their transfer to other institutions, investigators, or countries. Study findings may be disseminated only in aggregated, non-identifiable form.
Related trials for Amblyopia
Recruiting
OCT Eccentric Fixation and Amblyopia in Children
Amblyopia
Not yet recruiting
Non-invasive Induction of Metaplasticity for Amblyopia
Amblyopia, Amblyopia Unilateral
Recruiting
Evaluation of AmblyoFix for the Treatment of Unilateral Amblyopia in Children
Amblyopia
Recruiting
Augmented Reality-Based Binocular Therapy for Visual Rehabilitation in Adults With Amblyopia
Amblyopia, Anisometropic Amblyopia
Not yet recruiting
Attention-based Binocular Training for Impaired Stereopsis (BRAVE)
Amblyopia, Strabismus
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Active High-Definition Transcranial Direct Current Stimulation and Augmented Reality-Based Dichoptic Therapy in people with Amblyopia and Anisometropic Amblyopia, run by Polytechnic Institute of Porto at 2 sites in Portugal.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 18 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Portugal. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Catarina A Mateus, PhD (+351 913474780, cms@ess.ipp.pt), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Best-Corrected Visual Acuity of the Amblyopic Eye at Week 2 (time frame: Baseline and Week 2). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07752433, which also lists 15 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Sep 2026.