AR Training in Adults With Unilateral Amblyopia

Dichoptic Augmented Reality (AR) Training Versus Patching in Adults With Unilateral Amblyopia

This is a single-center, non-randomized controlled trial to compare the effectiveness of binocular AR training with patching for the treatment of adults with unilateral amblyopia.

Specific Aim 1 (Primary): To compare the improvement of visual acuity in the amblyopic eye between AR training and patching for the treatment of adults with unilateral amblyopia.

Specific Aim 2 (Secondary): To compare the changes of visual functions and pathway selective neural activity in the early visual and cortex subcortical nuclei including the lateral geniculate nucleus between AR training and patching for the treatment of adults with unilateral amblyopia.

Study Overview

• Status: Active, not recruiting
• Conditions: Amblyopia Unilateral; Amblyopia Functional
• Intervention / Treatment: Device: AR training; Device: Patching

Detailed Description

Patching the fellow eye (FE) is typically the first line of amblyopia therapy. Patching treatment has been thought to be effective only when started before the age of eight and might bring limited benifits for adults who have decreased visual cortex plasticity (Bhola et al., 2006). However, recent animal and human studies have demonstrated that visual cortex plasticity and visual functions can be enhanced later in life (Kind et al., 2002; Pineles et al., 2020), paving the way for new strategies for amblyopia treatment.

Dichoptic/binocular digital therapy has been developed with hope to improve visual functions in amblyopia post the critical period. However, no widely accepted binocular treatments with superiority to patching is available in adults with unilateral amblyopia (Pineles et al., 2020; Oscar et al., 2023). Here, we designed an innovative binocular therapy using augmented reality (AR) training, based on neural deficits in amblyopia, in order to achieve better outcomes.

Selective deficits were found in the parvocellular pathway (P pathway) compared to the magnocellular pathway (M pathway) in the monocular processing of visual information in the amblyopic eye (AE) (Wen et al., 2021). In addition to monocular deficits, imbalanced binocular suppression may also play important roles in the visual deficits of amblyopia as suggested by clinical evidence (DeSantis, 2014; Von Noorden, 1996) and psychophysical studies (Baker et al., 2008; Holopigian et al., 1988; Li et al., 2011; Zhou et al., 2013). Based on the neural deficits in unilateral amblyopia, we first apply the push-pull approach (Xu, He & Ooi, 2010; Ooi et al., 2013), which was aimed to reduce sensory eye dominance in previous literatures, into the rebalance of functions of M and P pathways in the AE and the rebalance of binocular interaction, to improve the high spatial detail perception of the AE in daily life under binocular viewing condition, as well as binocular functions.

Using AR technique combined with dichoptic device, images are processed differently and dichopticaly presented to each eye of the patients in real time, same in the content but different in contrast, spatial frequency, temporal frequency, and signal-to-noise ratio, allowing them to interact with the surrounding environment in real time during the visual training. We aim to achieve push-pull in monocular M-P pathways in the AE and interocular P-P pathways in the FE and the AE, in order to selectively improve the function of the P pathway in the AE under binocular viewing condition.

The proposed trial will be conducted in one study sites in China. For the AR training group, patients need to perform AR training for 2 hours per day at home. For the patching group, patients need to patch the FE for 2 hours per day at home.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Eye & ENT Hospital of Fudan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Aged 18-50 years (including 18 years and 50 years);
2. Best-corrected visual acuity worse than 20/30 but no worse than 20/200 in the amblyopic eye, interocular difference of 2 or more lines, with the better eye within the normal range;
3. Patients with deprivation amblyopia should have relieved the deprivation factors such as opacification of the ocular media (e.g. cataract, nonclearing vitreous opacity, corneal opacities) or other occlusion of the visual axis (e.g. blepharoptosis).
4. Normal binocular alignment including strabismic amblyopia with orthotropia after optical refractive correction or surgical correction, or intermittent exotropia within a range of -15 to 0 prism diopters measured by the prism cover test.
5. Patients should have been applyng optical refractive correction for more than 3 months before enrollment.

Exclusion Criteria:

1. Organic eye diseases preventing the establishment of good vision (e.g. ptosis, media opacity, nystagmus, paracentral fixation, acute inflammation like keratitis, optic nerve diseases like glaucoma, retinal diseases);
2. Lesions of the brain preventing the establishment of good vision (e.g. cortical visual impairment);
3. A history of ocular surgery (except strabismus surgery) affecting vision (e.g. retinal detachment repair);
4. A history of ocular trauma affecting vision;
5. Receiving amblyopia therapy (except wearing refractive correction glasses) within 2 weeks before enrollment;
6. History of epilepsy or mental illness, or cognitive defects;
7. Currently taking medications or needing to take medications during the study period that may affect vision;
8. Contraindications to magnetic resonance imaging such as implantable electronic device, metal implants (e.g. metal dentures, craniofacial titanium plates), claustrophobia and pregnancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Patching group; Conventional patching therapy.	Device: Patching; Conventional patching therapy.
Experimental: AR training group; Dichoptic augmented reality training with dual-pathway (parvocellular pathway and magnocellular pathway) and interocular push-pull paradigms developed based on neural deficits in adults with unilateral amblyopia.	Device: AR training; Dichoptic augmented reality training with dual-pathway (parvocellular pathway and magnocellular pathway) and interocular push-pull paradigms developed based on neural deficits in adults with unilateral amblyopia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in visual acuity at far	Best-corrected visual acuity in the amblyopic eye measured at the distance of 2.5 meters using standardized logMAR visual charts.	1 week, 1month, 3month, 6month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in visual acuity at near	Best-corrected visual acuity in the amblyopic eye measured at the distance of 2.2 meters using the Freiburg Visual Acuity test.	1 week, 1month, 3month, 6month
Change in visual acuity with single tumbling E	Best-corrected uncrowded and crowded visual acuity in the amblyopic eye measured at the distance of 30 centimeters.	1 week, 1month, 3month, 6month
Change in contrast sensitivity	Contrast sensitivity in each eye measured with forced-choice test under binocular viewing.	1 week, 1month, 3month, 6month
Change in faxation stability	Fixation stability in each eye measured with EyeLink 1000.	1 week, 1month, 3month, 6month
Change in binocular phase combination	Binocular integration measured with phase combination test .	1 week, 1month, 3month, 6month
Change in binocular rivalry ratio	Binocular rivalry ratio measured with binocular rivalty test	1 week, 1month, 3month, 6month
Change in stereopsis	Near stereopsis measured with Titmus Fly Stereotest pattern.	1 week, 1month, 3month, 6month
Change in neural activity corresponding to visual inputs in SSVEP	Pathway-selective neural activity in the early visual cortex revealed by SSVEP.	1 week, 1month, 3month, 6month
Change in neural activity corresponding to visual inputs in fMRI	Pathway-selective neural activity in the early visual cortex and subcortical nuclei including lateral geniculate nucleus revealed by fMRI.	1 week, 1month, 3month, 6month

Collaborators and Investigators

• Sponsor: Eye & ENT Hospital of Fudan University
• Investigators: Study Chair: Wen Wen, MD, PhD, Eye & ENT Hospital of Fudan University, Shanghai, China

Publications and helpful links

General Publications

• Ooi TL, Su YR, Natale DM, He ZJ. A push-pull treatment for strengthening the 'lazy eye' in amblyopia. Curr Biol. 2013 Apr 22;23(8):R309-10. doi: 10.1016/j.cub.2013.03.004.
• Xu JP, He ZJ, Ooi TL. Effectively reducing sensory eye dominance with a push-pull perceptual learning protocol. Curr Biol. 2010 Oct 26;20(20):1864-8. doi: 10.1016/j.cub.2010.09.043. Epub 2010 Oct 14.
• Zhou J, Huang PC, Hess RF. Interocular suppression in amblyopia for global orientation processing. J Vis. 2013 Apr 22;13(5):19. doi: 10.1167/13.5.19.
• Li J, Thompson B, Lam CS, Deng D, Chan LY, Maehara G, Woo GC, Yu M, Hess RF. The role of suppression in amblyopia. Invest Ophthalmol Vis Sci. 2011 Jun 13;52(7):4169-76. doi: 10.1167/iovs.11-7233.
• Holopigian K, Blake R, Greenwald MJ. Clinical suppression and amblyopia. Invest Ophthalmol Vis Sci. 1988 Mar;29(3):444-51.
• Baker DH, Meese TS, Hess RF. Contrast masking in strabismic amblyopia: attenuation, noise, interocular suppression and binocular summation. Vision Res. 2008 Jul;48(15):1625-40. doi: 10.1016/j.visres.2008.04.017. Epub 2008 Jun 10.
• Von Noorden GK. Binocular vision and ocular motility. Theory and Management of Strabismus. 1996.
• DeSantis D. Amblyopia. Pediatr Clin North Am. 2014 Jun;61(3):505-18. doi: 10.1016/j.pcl.2014.03.006. Epub 2014 Apr 14.
• Wen W, Wang Y, Zhou J, He S, Sun X, Liu H, Zhao C, Zhang P. Loss and enhancement of layer-selective signals in geniculostriate and corticotectal pathways of adult human amblyopia. Cell Rep. 2021 Dec 14;37(11):110117. doi: 10.1016/j.celrep.2021.110117.
• Cruz OA, Repka MX, Hercinovic A, Cotter SA, Lambert SR, Hutchinson AK, Sprunger DT, Morse CL, Wallace DK; American Academy of Ophthalmology Preferred Practice Pattern Pediatric Ophthalmology/Strabismus Panel. Amblyopia Preferred Practice Pattern. Ophthalmology. 2023 Mar;130(3):P136-P178. doi: 10.1016/j.ophtha.2022.11.003. Epub 2022 Dec 14. No abstract available.
• Pineles 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.
• Kind PC, Mitchell DE, Ahmed B, Blakemore C, Bonhoeffer T, Sengpiel F. Correlated binocular activity guides recovery from monocular deprivation. Nature. 2002 Mar 28;416(6879):430-3. doi: 10.1038/416430a.
• Bhola R, Keech RV, Kutschke P, Pfeifer W, Scott WE. Recurrence of amblyopia after occlusion therapy. Ophthalmology. 2006 Nov;113(11):2097-100. doi: 10.1016/j.ophtha.2006.04.034.

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2023
• Primary Completion (Estimated): December 20, 2024
• Study Completion (Estimated): December 20, 2024

Study Registration Dates

• First Submitted: November 22, 2024
• First Submitted That Met QC Criteria: November 22, 2024
• First Posted (Estimated): November 26, 2024

Study Record Updates

• Last Update Posted (Estimated): November 26, 2024
• Last Update Submitted That Met QC Criteria: November 22, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Adult; Patching; Augmented reality training; Neural deficit
• Additional Relevant MeSH Terms: Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Eye Diseases; Vision Disorders; Sensation Disorders; Amblyopia
• Other Study ID Numbers: EENTAR20230225

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: We concerns about patient privacy issues and it's better to protect the publication potential.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No