Combining Noninvasive Brain Stimulation and Augmented Reality-based Dichoptic Therapy for Treating Amblyopic Adults

Обзор

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.

Подробное описание

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

Вмешательства

• Устройство Active High-Definition Transcranial Direct Current Stimulation
  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 eig
• Устройство Sham High-Definition Transcranial Direct Current Stimulation
  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 th
• Устройство Augmented 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

Первичные конечные точки

• Change From Baseline in Best-Corrected Visual Acuity of the Amblyopic Eye at Week 2 [Срок оценки: Baseline and Week 2]
• Change From Baseline in Best-Corrected Visual Acuity of the Amblyopic Eye at Week 10 [Срок оценки: Baseline and Week 10]
• Change From Baseline in Near Stereoacuity at Week 2 [Срок оценки: Baseline and Week 2]
• Change From Baseline in Near Stereoacuity at Week 10 [Срок оценки: Baseline and Week 10]

Вторичные конечные точки (12)

• Change From Baseline in Interocular Suppression at Week 2 [Срок оценки: Baseline and Week 2]
• Change From Baseline in Interocular Suppression at Week 10 [Срок оценки: Baseline and Week 10]
• Change From Baseline in Static Achromatic Contrast Sensitivity of the Amblyopic Eye at Week 2 [Срок оценки: Baseline and Week 2]
• Change From Baseline in Static Achromatic Contrast Sensitivity in the Amblyopic and Fellow Eyes at Week 10 [Срок оценки: Baseline and Week 10]
• Change From Baseline in Retinal Neuronal Layer Thicknesses at Week 2 [Срок оценки: Baseline and Week 2]
• Change From Baseline in Retinal Neuronal Layer Thicknesses at Week 10 [Срок оценки: Baseline and Week 10]
• Change From Baseline in Retinal Ganglion Cell Function Assessed by Pattern Electroretinography at Week 2 [Срок оценки: Baseline and Week 2]
• Change From Baseline in Retinal Ganglion Cell Function Assessed by Pattern Electroretinography at Week 10 [Срок оценки: Baseline and Week 10]
• Change From Baseline in Cortical Population Receptive Field Size at Week 2 [Срок оценки: Baseline and Week 2]
• Change From Baseline in Cortical Population Receptive Field Size at Week 10 [Срок оценки: Baseline and Week 10]
• Change From Baseline in Cortical Contrast Sensitivity Function at Week 2 [Срок оценки: Baseline and Week 2]
• Change From Baseline in Cortical Contrast Sensitivity Function at Week 10 [Срок оценки: Baseline and Week 10]

Критерии участия

Критерии включения

• Age between 18 and 35 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

Португалия · 1 центр

• RISE-Health, Center for Translational Health and Medical Biotechnology Research (TBIO), Sc — Porto

Публикации

• 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. PMID 31704700
• d'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. PMID 23684869
• Mendola 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. PMID 29868445
• Silva 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. PMID 34245381
• Arif 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. PMID 34997673
• Castillo-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. PMID 36816499
• Ding 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. PMID 26763954
• Spiegel 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. PMID 23857313

Идентификаторы

NCT: NCT07752433 · ORT-2026-002 · 2023.16131.ICDT

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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