Clinical trial NCT05114252: Amblyopia and Stereoptic Games for Vision
Official title: Stereoptic Serious Games as a Visual Rehabilitation Tool for Individuals With Residual Amblyopia: A Crossover Randomized Controlled Trial - AMBlyopia and stEReoptic Games for Vision
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Amblyopia
Healthy
Lead sponsor: HES-SO Valais-Wallis
Sponsor class: OTHER
Collaborators: name: University Hospital, Geneva
name: University of Lausanne Hospitals
name: Eye Hospital Jules Gonin
First posted: 2021-11-09
Enrollment: 30
Sex: ALL
Minimum age (years): 6
Maximum age (years): 35
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Monocentric blinded crossover randomised controlled trial
Primary purpose: TREATMENT

Brief summary: Amblyopia is the most common developmental vision disorder in children, caused by abnormal visual experience in early life, especially a difference in refraction between the eyes, a misalignment of the eye axes, a combination of both. Besides a significant reduced visual acuity, the patients show deficits in 3D vision and functional vision impairment like reduced reading speed, selective attention or motor control skills. The gold standard treatment for amblyopia, occlusion therapy, can lead to relapses or residual amblyopia (i.e., amblyopia that persist into adulthood). The current study aims to test the efficacy of a novel home-based child-friendly rehabilitation program for amblyopia, Vivid Vision Home, involving playing serious videogames on a virtual reality (VR) headset at home. The VR training will be compared to standard care (wearing a spectacle correction) and to age-matched typically developing individuals. A cross-over design will be used so that each participant will receive both treatments (games, spectacles). There is a growing number of studies showing benefits of binocular stimulation for visual acuity and stereovision, but provided mainly by level III studies, with a need for rigorous level I or II studies, using more engaging therapies, to confirm or refute the efficacy of this approach as an adjunct or replacement for current amblyopia treatments. Embedding binocular stimulation in engaging, immersive serious games delivered on VR headsets at home, as implemented by Vivid Vision Home, can address this question.

Detailed description: Amblyopia is the most common developmental vision disorder in children, affecting 1-5% of the population in developed countries. It mostly results from a difference in refraction between the eyes (anisometropia), a misalignment of the eye axes (strabismus), a combination of both, or visual deprivation (due to congenital cataract, e.g.). Besides a significant reduced visual acuity, the patients show binocular dysfunction leading to functional vision impairment like reduced reading speed, selective attention or motor control skills.

Whilst the disorder is commonly diagnosed around the age of 3-5 years, up to 50% of children will be left with residual amblyopia mainly due to a late diagnosis and start of treatment, poor compliance with treatment, not diagnosed or considered eccentric fixation. The gold standard treatment consists of the occlusion therapy, patching the dominant/healthy eye for 2-6 hours/day every day for several months up to years. However, an eye patch and the demand to use the weaker eye for visual tasks is challenging and so poorly complied with by pediatric patients. These problems in compliance lead to relapses (14-25%) or residual amblyopia (i.e., poor vision that persist into adulthood) creating multiple medical and social problems for the patients (including cognitive and emotional processing), their families and the society.

Serious videogames delivered on tablets have been developed with a more engaging strategy to effectively treat amblyopia. These games focus on binocular stimulation, which targets visual acuity of the amblyopic eye and three-dimensional vision (stereovision), through the presentation of dichoptic images. Such dichoptic image presentation consists of showing a different but complementary image in each eye so that the task can only be performed if information across eyes is combined. Binocular stimulation signifies that both eyes are challenged but the devices are programmed in a way so that the weaker eye is primarily performing a given visual task.

The objective of this project is to improve visual function of the amblyopic eye using image-fusion and stereopsis through playing videogames in a Virtual Reality (VR) environment. Also, besides the improvements of visual acuity and potentially stereovision, such VR-based serious games interventions can positively impact other aspects like cognitive and motor functions. The visual deficits seen in amblyopia are thought to be related to problems in attending to visual task-relevant objects, suggesting that such deficits in selective-attentional skills can hamper vision recovery. Similarly, poor stereovision will be reflected in deficits in motor control skills as seen in individuals with amblyopia. Our VR-based serious games training will have similar ingredients to those that are supposed to improve attentional skills and may have a positive impact on motor control skills. The VR-based technology developed by Vivid Vision to be used in the present study is FDA approved and CE (Conformité Européene) certified. They are offering virtual reality videogames with headsets, which may increase the beneficial treatment effect by a reduction of the misperception of 3-dimensional movement.

The present project aims to test the described benefit in a home-based, child-friendly rehabilitation program involving serious video games in a virtual reality environment in children, adolescents, and young adults with residual amblyopia, compared to standard care (refractive correction) and to age-matched healthy individuals. The study has been designed as a blinded randomized cross-over trial to increase the available evidence allowing for a qualified evaluation of the benefit of binocular stimulation and for demonstrating a beneficial effect also in residual amblyopia in childhood and in older patients.

Eligibility criteria: AMBLYOPIC COHORT

Inclusion Criteria:

* Aged between 6 and 35 years old,
* Residual amblyopia defined as Best-Correct Visual Acuity (BCVA) of ≤ 20/20 in the amblyopic eye, an impairment of ≥ 2 lines in the amblyopic eye persisting even after refraction correction,
* Stable BCVA for at least 2 consecutive measurements over 6 months,
* Signed Informed Consent from the child's legal representative, by both the child and his/her legal representative for participants older than 14 years, or by full-aged participants themselves.

Exclusion Criteria:

* Untreated or newly diagnosed anisometropic, strabismic or combined amblyopia, that is a child with BCVA interocular difference of ≥ 2 lines,
* Current atropine treatment or atropine treatment 3 months prior to enrolment in the study,
* Auditory deficits or loss,
* Eye surgery except those to correct strabismus,
* Strabismus over 20 dioptres (D) or with large eccentric fixation,
* Coexistence of ocular or neurological disease (e.g., seizure or epilepsy, incomitant strabismus, nerve palsy, horror fusionis),
* Developmental delay or disorder (e.g., dyslexia, dyspraxia, attention deficity hyperactivity disorder, autism spectrum disorders),
* Inability to follow and complete the procedures of the study (e.g., psychological or sensorimotor disorders).

HEALTHY INDIVIDUALS COHORT

Inclusion Criteria:

* Aged between 6 and 35 years old,
* Signed Informed Consent from the child's legal representative, by both the child and his/her legal representative for participants older than 14 years, or by full-aged participants themselves.

Exclusion Criteria:

* Auditory deficits or loss,
* Eye surgery except those to correct strabismus,
* Strabismus over 20D or with large eccentric fixation,
* Coexistence of ocular or neurological disease (e.g., seizure or epilepsy, incomitant strabismus, nerve palsy, horror fusionis),
* Developmental delay or disorder (e.g., dyslexia, dyspraxia, ADHD, ASD),
* Inability to follow and complete the procedures of the study (e.g., psychological or sensorimotor disorders).

Primary outcomes:
measure: Best Corrected Visual Acuity
timeFrame: Baseline for Treatment A
measure: Best Corrected Visual Acuity
timeFrame: Post-test for Treatment A (2 months)
measure: Best Corrected Visual Acuity
timeFrame: Follow-up for Treatment A (2 months)/Baseline for Treatment B
measure: Best Corrected Visual Acuity
timeFrame: Post-test for Treatment B (2 months)
measure: Best Corrected Visual Acuity
timeFrame: Follow-up after Treatment B (2months)
Secondary outcomes:
measure: Binocular vision measured in arc sec with clinical tests
timeFrame: Baseline, every week during experimental treatment, after experimental treatment (2 months) and 2 months follow-up
measure: Binocular vision measured in arc sec with a tablet test
timeFrame: Baseline, every week during experimental treatment, after experimental treatment (2 months) and 2 months follow-up
measure: Binocular vision (interocular misalignment) measured with clinical tests
timeFrame: Baseline, every week during experimental treatment, after experimental treatment (2 months) and 2 months follow-up
measure: Stereoacuity estimated with Vivid Vision Home software
timeFrame: Baseline, every week during experimental treatment, after experimental treatment (2 months) and 2 months follow-up
measure: Binocular vision estimated with Vivid Vision Home software
timeFrame: Baseline, every week during experimental treatment, after experimental treatment (2 months) and 2 months follow-up
measure: Ocular posture adjustment estimated with Vivid Vision Home software
timeFrame: Baseline, every week during experimental treatment, after experimental treatment (2 months) and 2 months follow-up
measure: Vergence facility estimated with Vivid Vision Home software
timeFrame: Baseline, every week during experimental treatment, after experimental treatment (2 months) and 2 months follow-up
measure: Vergence range estimated with Vivid Vision Home software
timeFrame: Baseline, every week during experimental treatment, after experimental treatment (2 months) and 2 months follow-up
measure: Reading skills
timeFrame: Baseline, after each treatment (2 months) and 2 months follow-up
measure: Visual selective attention: Behavioral processes
timeFrame: Baseline, after each treatment (2 months) and 2 months follow-up
measure: Visual selective attention: Traditional EEG/ERP processes
timeFrame: Baseline, after each treatment (2 months) and 2 months follow-up
measure: Visual selective attention: Topographic EEG/ERP processes
timeFrame: Baseline, after each treatment (2 months) and 2 months follow-up
measure: Visual selective attention: Global Field Power of EEG/ERP processes
timeFrame: Baseline, after each treatment (2 months) and 2 months follow-up
measure: Audiovisual selective attention: Behavioral processes
timeFrame: Baseline, after each treatment (2 months) and 2 months follow-up
measure: Audiovisual selective attention: Traditional EEG/ERP processes
timeFrame: Baseline, after each treatment (2 months) and 2 months follow-up
measure: Audiovisual selective attention: Topographic EEG/ERP processes
timeFrame: Baseline, after each treatment (2 months) and 2 months follow-up
measure: Audiovisual selective attention: Global Field Power of EEG/ERP processes
timeFrame: Baseline, after each treatment (2 months) and 2 months follow-up
measure: Motor control: movement duration
timeFrame: Baseline, after each treatment (2 months) and 2 months follow-up
measure: Motor control: reaction time
timeFrame: Baseline, after each treatment (2 months) and 2 months follow-up
measure: Motor control: smoothness
timeFrame: Baseline, after each treatment (2 months) and 2 months follow-up
measure: Motor control: maximum grip aperture
timeFrame: Baseline, after each treatment (2 months) and 2 months follow-up
measure: Motor control: time to maximum grip aperture
timeFrame: Baseline, after each treatment (2 months) and 2 months follow-up
measure: Motor control: cortical responses of motor planning
timeFrame: Baseline, after each treatment (2 months) and 2 months follow-up
measure: Motor control: cortical responses of motor execution
timeFrame: Baseline, after each treatment (2 months) and 2 months follow-up
measure: Cortical visual responses
timeFrame: Baseline, after each treatment (2 months) and 2 months follow-up
measure: Pediatric Eye Questionnaire (PedEyeQ)
timeFrame: Baseline, after each treatment (2 months) and 2 months follow-up
Other outcomes:
measure: Adherence
timeFrame: Baseline, after experimental treatment (2 months)
measure: Adverse events
timeFrame: Baseline, after experimental treatment (2 months)
Locations:
city: Geneva
country: Switzerland
facility: Geneva University Hospitals
Study officials:
affiliation: University Hospital, Geneva
name: Heimo Steffen, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Gambacorta C, Nahum M, Vedamurthy I, Bayliss J, Jordan J, Bavelier D, Levi DM. An action video game for the treatment of amblyopia in children: A feasibility study. Vision Res. 2018 Jul;148:1-14. doi: 10.1016/j.visres.2018.04.005. Epub 2018 May 12.
citation: Ziak 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.
citation: Verghese P, McKee SP, Levi DM. Attention deficits in Amblyopia. Curr Opin Psychol. 2019 Oct;29:199-204. doi: 10.1016/j.copsyc.2019.03.011. Epub 2019 Mar 22.
citation: Grant S, Suttle C, Melmoth DR, Conway ML, Sloper JJ. Age- and stereovision-dependent eye-hand coordination deficits in children with amblyopia and abnormal binocularity. Invest Ophthalmol Vis Sci. 2014 Aug 5;55(9):5687-57015. doi: 10.1167/iovs.14-14745.