AR Training Versus Patching in Unilateral Amblyopia

Official title

Dichoptic Augmented Reality (AR) Training Versus Patching for Unilateral Amblyopia in Children and Adults

Overview

This is a multi-center, randomized controlled trial to compare the effectiveness of AR training with patching for the treatment of 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 unilateral amblyopia. Specific Aim 2 (Secondary): To compare the improvement of visual functions between AR training and patching for the treatment of unilateral amblyopia.

Detailed description

Poor compliance, limited improvement of visual functions, and regression after recovery of visual acuity have been observed in the management of amblyopia using conventional patching. Recently, dichoptic/binocular digital therapy has been developed, but no widely accepted binocular treatments with superiority available for children and adults with 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, 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, we present differentially-processed images to each eye of the patients in real time, allowing them to interact with the surrounding environment during the visual training. Using a Butterworth filter with the cutoff at 2 cycle pre degree, the images captured in real time are divided into information with high and low spatial frequencies (SFs) corresponding to the P and M pathways, respectively. For the AE, original low SF phase of captured images is scrambled into random noise with the refresh rate of the display, while the original information with high SF is retained completely. As a result, the function of the P pathway is pulled while the function of the M pathway is pushed, actively encouraging the interaction with the surrounding environment through high SF information. For the fellow eye (FE), original high SF phase of captured images is scrambled into random noise with increased contrast and reduced temporal frequency, while the contrast of the original high SF information is reduced. As a result, in addition to the push-pull in monocular P\&M pathways, the function of the P pathway in the FE is pulled and while the function of the P pathway in the AE is pushed, actively improving the rebalance of binocular inhibition.

The proposed trial will be conducted in 4 different 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.

Interventions

• Other 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 unilateral amblyopia.
• Other Patching
  Conventional patching therapy.

Primary outcome measures

• Total effective rate [Time frame: 13 weeks]

Secondary outcome measures (7)

• Change in best-corrected visual acuity [Time frame: 2 weeks, 4 weeks, 9 weeks, 13 weeks]
• Effective rate [Time frame: 2 weeks, 4 weeks, 9 weeks]
• Change in habitual visual acuity [Time frame: 2 weeks, 4 weeks, 9 weeks, 13 weeks]
• Change in stereopsis [Time frame: 2 weeks, 4 weeks, 9 weeks, 13 weeks]
• Change in contrast sensitivity [Time frame: 2 weeks, 4 weeks, 9 weeks, 13 weeks]
• Compliance rate [Time frame: 2 weeks, 4 weeks, 9 weeks, 13 weeks]
• Safety reports [Time frame: 2 weeks, 4 weeks, 9 weeks, 13 weeks]

Eligibility criteria

Inclusion criteria

• Aged 5-55 years (including 5 years and 55 years);
• 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;
• Patients have applied optical refractive correction for more than 3 months;
• Ability attend visits and complete the treatment;
• Normal binocular alignment including strabismic amblyopia with orthotropia after surgical correction, or intermittent exotropia within a range of -15 to 0 prism diopters measured by the prism cover test.

Exclusion criteria

• 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);
• Lesions of the brain preventing the establishment of good vision (e.g. cortical visual impairment);
• Implantable electronic device;
• A history of ocular surgery (except strabismus surgery) affecting vision (e.g. retinal detachment repair);
• A history of ocular trauma affecting vision;
• Receiving amblyopia therapy (except wearing glasses) within 2 weeks prior to presentation;
• History of epilepsy or mental illness, or cognitive defects;
• Currently taking medications or needing to take medications during the study period that may affect vision;
• Inability to comply with the treatments or follow-up visits required;
• Participation in clinical trials on drugs within 3 months prior to presentation, or clinical trials on other medical devices within 30 days prior to presentation.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

China · 1 center

• Eye & ENT Hospital of Fudan University — Shanghai

Publications

• 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. PMID 31619356
• 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. PMID 36526450
• 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. PMID 34910903
• 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. PMID 24852148
• Von Noorden GK. Binocular vision and ocular motility. Theory and Management of Strabismus. 1996.
• 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. PMID 18547600
• Holopigian K, Blake R, Greenwald MJ. Clinical suppression and amblyopia. Invest Ophthalmol Vis Sci. 1988 Mar;29(3):444-51. PMID 3343099
• 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. PMID 21447685

Identifiers

NCT: NCT06498206 · 2024-ARTA

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗