Visual Rehabilitation in a Pediatric Population of Patients With Homonymous Hemianopia: a Pilot Study on Virtual-reality Stimulation
Phase: NA
Conditions: Hemianopia, Brain Tumor, Children, Only
Sponsor: The Hospital for Sick Children

 
 
 
 
 
Visual rehabilitation in a pediatric population of 
patients with homonymous hemianopia: a pilot study 
on virtual-reality stimulation 
 
Principal Investigator/Sponsor: 
Eric BOUFFET, MD 
Hospital for Sick Children – Sickkids 
555 University Avenue 
Toronto, ON, M5G 1X8 
 
 
Co-investigators: 
Monica DAIBERT-NIDO, MD, CBO 
Toronto Western Hospital 
University Health Network 
399 Bathurst St, Toronto, ON M5T 2S8 
 
Arun REGINALD, MD 
Hospital for Sick Children – Sickkids 
555 University Avenue 
Toronto, ON, M5G 1X8 
 
Samuel N MARKOWITZ, MD, FRCS(C) 
Krembil Research Institute 
Toronto Western Hospital 
University Health Network 
399 Bathurst St, Toronto, ON M5T 2S8 
 
Michael REBER, PhD 
Krembil Research Institute 
University Health Network 
60 Leonard Av., Toronto, ON M5T 0S8 
 
 
 
Funded by: Meghan’s Hug Foundation 
Version Date: 
1 August 
2021 
 
 
 

HH- IVR Protocol v01- August 1st, 2021 

ii 
 
Table of Contents 
STATEMENT OF COMPLIANCE ................................................................................................................. 1 
1 
PROTOCOL SUMMARY ................................................................................................................... 2 
1.1 
Synopsis................................................................................................................................... 2 
1.2 
Schema .................................................................................................................................... 2 
1.3 
Schedule of Activities (SoA)..................................................................................................... 3 
2 
INTRODUCTION ............................................................................................................................... 3 
2.1 
Study Rationale ........................................................................................................................ 3 
2.2 
Background .............................................................................................................................. 4 
2.3 
Risk/Benefit Assessment ......................................................................................................... 4 
3 
OBJECTIVES AND ENDPOINTS ...................................................................................................... 5 
4 
STUDY DESIGN ................................................................................................................................ 6 
4.1 
Overall Design.......................................................................................................................... 6 
4.2 
Scientific Rationale for Study Design ....................................................................................... 8 
4.3 
End of Study Definition ............................................................................................................ 8 
5 
STUDY POPULATION ...................................................................................................................... 8 
5.1 
Inclusion Criteria ...................................................................................................................... 8 
5.2 
Exclusion Criteria ..................................................................................................................... 9 
5.3 
Lifestyle .................................................................................................................................... 9 
5.4 
Screen Failures ........................................................................................................................ 9 
5.5 
Strategies for Recruitment and Retention ................................................................................ 9 
6 
STUDY INTERVENTION ................................................................................................................... 9 
6.1 
Study Intervention(s) Administration ........................................................................................ 9 
6.1.1 
Study Intervention Description ............................................................................... 9 
6.1.2 
Dosing and Administration ..................................................................................... 9 
6.1.3 
Dose Escalation and Modifications ...................................................................... 10 
6.2 
Preparation/Handling/Storage/Accountability ........................................................................ 11 
6.2.1 
Acquisition and Accountability ............................................................................. 11 
6.2.2 
Formulation, Appearance, Packaging, and Labeling ... Error! Bookmark not defined. 
6.2.3 
Product Storage and Stability .............................................................................. 11 
6.3 
Measures to Minimize Bias: Randomization and Blinding ..................................................... 11 
6.4 
Study Intervention Compliance .............................................................................................. 11 
6.5 
Concomitant Therapy ............................................................................................................. 11 
7 
DISCONTINUATION and WITHDRAWAL....................................................................................... 12 
7.1 
Discontinuation of Study Intervention .................................................................................... 12 
7.2 
Participant Discontinuation/Withdrawal from the Study ......................................................... 12 
7.3 
Lost to Follow-Up ................................................................................................................... 13 
8 
STUDY ASSESSMENTS AND PROCEDURES ............................................................................. 13 
8.1 
Assessments .......................................................................................................................... 13 
8.2 
Adverse Events and Serious Adverse Events ....................................................................... 13 
8.2.1 
Definition of Adverse Events (AE) ....................................................................... 14 
8.2.2 
Definition of Serious Adverse Events (SAE) ........................................................ 14 
8.2.3 
Classification of an Adverse Event ...................................................................... 14 
8.2.4 
Time Period and Frequency for Event Assessment and Follow-Up .................... 15 
8.2.5 
Adverse Event Reporting ..................................................................................... 16 
8.2.6 
Serious Adverse Event Reporting ........................................................................ 16 
8.2.7 
Reporting Events to Participants.......................................................................... 16 

iii 
 
8.2.8 
Events of Special Interest ............................................ Error! Bookmark not defined. 
8.2.9 
Reporting of Pregnancy ....................................................................................... 16 
9 
STATISTICAL CONSIDERATIONS ................................................................................................ 16 
9.1 
Statistical Hypotheses ............................................................................................................ 16 
9.2 
Sample Size Determination ................................................................................................... 17 
9.3 
Populations for Analyses ....................................................................................................... 17 
9.4 
Statistical Analyses ................................................................................................................ 17 
9.4.1 
General Approach ................................................................................................ 17 
9.4.2 
Analysis of the Primary Endpoint(s) ..................................................................... 18 
9.4.3 
Analysis of the Secondary Endpoint(s) ................................................................ 18 
9.4.4 
Safety Analyses ................................................................................................... 18 
9.4.5 
Baseline Descriptive Statistics ............................................................................. 18 
9.4.6 
Planned Interim Analyses ............................................ Error! Bookmark not defined. 
9.4.7 
Sub Group Analyses .................................................... Error! Bookmark not defined. 
9.4.8 
Tabulation of Individual Participant Data ............................................................. 18 
9.4.9 
Exploratory Analyses ................................................... Error! Bookmark not defined. 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ........................... 19 
10.1 
Regulatory, Ethical, and Study Oversight Considerations ..................................................... 19 
10.1.1 
Study Discontinuation and Closure ...................................................................... 19 
10.1.2 
Confidentiality and Privacy ................................................................................... 19 
10.1.3 
Future Use of Stored Specimens and Data ......................................................... 20 
10.1.4 
Key Roles and Study Governance ....................................................................... 20 
10.1.5 
Safety Oversight ........................................................... Error! Bookmark not defined. 
10.1.6 
Study Monitoring .................................................................................................. 20 
10.1.7 
Quality Assurance and Quality Control ................................................................ 21 
10.1.8 
Data Handling and Record Keeping .................................................................... 21 
10.1.9 
Protocol Deviations .............................................................................................. 22 
10.1.10 
Conflict of Interest Policy...................................................................................... 22 
10.2 
Additional Considerations .............................................................. Error! Bookmark not defined. 
10.3 
Abbreviations ......................................................................................................................... 23 
11 
REFERENCES ................................................................................................................................ 25 

HH-IVR protocol v01 
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The trial will be conducted in accordance with this protocol, International Council on 
Harmonisation Good Clinical Practice (ICH GCP) and applicable regulatory requirements. The 
Principal Investigator (PI) will assure that no deviation from, or changes to the protocol will take 
place without prior agreement from the Sponsor and documented approval from the Research 
Ethics Board (REB), except where necessary to eliminate (an) immediate hazard(s) to the trial 
participants. 
 
The protocol, informed consent form(s), recruitment materials, and all participant materials will be 
submitted to the REB for review and approval. Approval of both the protocol and the consent 
form(s) must be obtained before any participant is enrolled. Any amendment to the protocol will 
require review and approval by the REB before the changes are implemented to the study. All 
changes to the consent form will be REB approved; a determination will be made regarding 
whether a new consent needs to be obtained from participants who provided consent, using a 
previously approved consent form. 
 
Name of Principal Investigator (Print):    
 
 
 
Signature of Principal Investigator: __  
 
 
Date: 
 
 
<DD Month YYYY> 
 
 
Site Address 
Krembil Research Institute 
University Health Network- Toronto Western Hospital 
60 Leonard Av., Toronto, ON M5T 0S8 
STATEMENT OF COMPLIANCE 

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1.2 
SCHEMA 
 
 
 
 
 
 
Title: 
Visual rehabilitation in a pediatric population of patients with 
homonymous hemianopia: a pilot study on virtual-reality stimulation. 
Study Description: 
Pilot, Open label, Non-randomized study to assess the feasibility of home- 
based audiovisual immersive virtual-reality stimulation in pediatric patients 
with homonymous hemianopia. 
Objectives: 
Primary Objective: Feasibility 
Secondary Objective: Visual acuity, reading speed, field of vision, quality of 
life. 
Endpoints: 
Primary Endpoint: Completion of the home-based audiovisual virtual-reality 
stimulation procedure (15 sessions). 
Study Population: 
Male and female patients > 8 years-old with diagnosed homonymous 
hemianopsia with no prior visual rehabilitation interventions. A total of 10 
patients (5 with chiasmatic lesions and 5 with lesions outside of the optic 
chiasma) 
Phase: 
Pilot Study 
Description of Study 
Intervention: 
Home-based audiovisual immersive virtual-reality stimulation (15 minutes 
every 2 day for 4 weeks) 
Study Duration: 
2 years 
Participant Duration: 
7 months 
 
 
 
1 
PROTOCOL SUMMARY 
1.1 
SYNOPSIS 

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2 
INTRODUCTION 
2.1 
STUDY RATIONALE 
 
 
 
 
 
 
Inclusion Baseline 
Treatment 
Follow-up 
Day 
0 
0 
1 
3 
5 
7 
9 
11 13 14 15 17 19 21 23 25 27 28 
58 
200 
Visit # 
1 
2 
3 
4 
5 
Fixation 
stability 
X 
X 
X 
X 
X 
BCVA 
X 
X 
X 
X 
X 
Contrast 
sensitivity 
X 
X 
X 
X 
X 
MNREAD 
test 
X 
X 
X 
X 
X 
CVFQ 
X 
X 
X 
X 
X 
Humphrey 
Full Field 
120 
X 
X 
X 
X 
Esterman 
binocular 
X 
X 
X 
X 
VRISE 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
IVR 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
Central nervous system tumors are the second most common malignancies in childhood1. A brain tumor 
and its treatment can affect the visual system at different levels, from the optic nerves (through compression 
or infiltration), to sub-cortical structures such as the superior colliculus (SC) and lateral geniculate nuclei 
(LGN) to optic tracts, optic radiations and visual cortices1,2. Children with brain tumors can present visual 
impairments like decreased visual acuity and contrast sensitivity, loss of color vision, and visual field loss 
such as hemianopias1–3. Hemianopia patients present difficulties in detecting stimuli in the defective visual 
field and show defective scanning and exploration4. Moreover, they show a rotation and compression of 
the auditory space leading to imprecise localization of sound across both hemispaces5. Hemianopia 
patients naturally develop oculo-motor strategies to compensate for visual field loss, but visual rehabilitation 
procedure must still be developed to optimize/improve visual perception in the blind field. Several studies 
demonstrated that hemianopia patients could improve visual perception in the damaged hemifield after a 
stimulation procedure where auditory and visual stimuli were temporally and spatially correlated6,7. Such 
1.3 
SCHEDULE OF ACTIVITIES (SOA) 

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2.2 
BACKGROUND 
2.3 
RISK/BENEFIT ASSESSMENT 
 
 
audiovisual stimulation programs induce a functional and anatomical reorganization of the visual 
connectivity in sub-cortical and cortical structures over time8–10. 
 
The current strategies rely on a significant workload, over 30 hours of audiovisual stimulation using static, 
spatially and temporally coherent stimuli displayed on large screens/panels in a clinical setting. These 
strategies require frequent visits to the clinic impeding the patients’ adherence and compliance and 
increasing the burden of disease. We seek to develop an audiovisual stimulation procedure using 
immersive virtual-reality (IVR) in head-mounted display (HMD). This is an emerging and very promising 
visual rehabilitation approach using high-technology devices11–15. It is developed to provide sensory 
stimulation with better ecological validity due to virtual-reality, greater flexibility due to home-based 
programs and improved efficiency due to patient-tailored protocols11,12. IVR is a versatile technology, 
allowing its potential use for the rehabilitation of a variety of low-vision conditions. There are currently limited 
practical results whether this technology is suitable for low-vision patients to use at home and if it can be 
deployed on a large scale. A few case report/series studies suggested a potential effectiveness of IVR on 
visual perception in teenagers, adults and elderly12,14,16 but more information as to the potential of use and 
effectiveness of this technology in children and young teenagers is necessary. 
 
 
 
Evidence in the literature11-16 support the hypothesis that an IVR audiovisual stimulation approach using the 
binocular 3D multiple object tracking (3D-MOT) in the head-mounted display (HMD) Oculus Go/Quest could 
provide a suitable visual rehabilitation approach for children with visual field defects. The central features 
of the 3D-MOT closely match attentionally demanding real-life situations17,18. The setup of the task is highly 
dynamic as the objects change their location over time, requiring a continuous deployment of visual 
attention to avoid confusions between the objects18. 3D-MOT can be combined with fixation (still or tracking) 
while allocating the attention in the visual space to track other moving objects (covert attention) with the 
peripheral retina, a situation found in complex dynamic scene recognition18,19. 3D-MOT stimulation 
programs displayed on monitors or TV screens have been shown to increase brain capacity for complex 
processes such as anticipation, eye-tracking, field of view and even decision-making in healthy and 
pathological participants20–22. Recent work in low-vision patients with homonymous hemianopsia indicated 
a beneficial effect of audiovisual 3D-MOT IVR stimulation program using the Oculus Go on contrast 
sensitivity, fixation stability, reading speed and field of vision23. 
There are currently no visual rehabilitation strategies for children presenting visual field defects consecutive 
to a brain tumor or its treatment. The use of IVR in children aged 4-10 years old has not raised any safety 
concerns24. Moreover, by using the remotely controlled and stand-alone Oculus Go, our strategy favors a 
home-based stimulation program which will increase compliance and adherence to the program. 
 
 
 
 
Potential Risks: 
 
There are no risks for patients enrolled in the study. The use of IVR may cause moderate dizziness, nausea 
or disorientation for continuous stimulation above 10 minutes25. If nausea, dizziness or disorientation is 
experienced during IVR stimulation, stopping the VR stimulation immediately restores normal condition25. 
A recent study on the effects of IVR in 4-10 years old children indicate great tolerability with a prevalence 
of discomfort and induced effect of IVR lower than reported in adults24. 

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3 
OBJECTIVES AND ENDPOINTS 
 
 
Patients will be assessed for IVR sensitivity using the Virtual-Reality Induced Symptoms and Effects 
(VRISE) questionnaire score at inclusion26 (exclusion criteria: three (3) consecutive VRISE score < 25). 
 
At-home VR stimulation will be 5 minutes of continuous stimulation as specified in the “Study Intervention” 
section, below the critical 10 minutes threshold inducing effects and symptoms25,26. 
 
There are no risks for the community/public nor for the institution. 
Potential Benefits: 
We anticipate the HH patients will be able to adhere and comply to the home-based audiovisual stimulation 
program without any symptoms or effects. 
We expect the potential benefits IVR stimulation will correspond to: 
- an improved fixation stability, 
- an enhanced reading speed. 
- an improved field of vision 
 
All together increasing self-dependency and quality of life which ultimately impact health care cost by: 
- reducing the burden of disease, 
- decrease of the global cost of vision impairment. 
 
 
 
No visual rehabilitation procedures are currently existing for children with visual field loss consecutive to 
brain tumor. The visual and auditory modalities of the 3D-MOT IVR stimulation program could potentially 
improve visual perception in the peripheral fields and saccades/volitional eye movements towards pre- 
designated targets. Improved oculomotor control will also result in better fixation stability which in turn 
ameliorates visual perception (reading, visual field). 
 
PRIMARY OBJECTIVE: 
Feasibility: 
 
- 
Adherence to the home-based stimulation protocol. Each time the patients performed an audiovisual 
IVR session, data about the session (device ID#, subject #, date/time, time to complete the task/block, 
number of tasks/blocks performed, total stimulation time, total duration of the session) are recorded by 
the NeurofyResearch application in the Oculus Go and sent through Wi-Fi to a dedicated and secured 
laboratory computer. 
- 
VRISE questionnaire scores recorded before and after each session and sent though Wi-Fi to a 
dedicated and secured laboratory computer in real-time. 
- 
Retention rate. 
 
SECONDARY OBJECTIVE: 
Secondary endpoint measures will be performed at Toronto Western hospital during baseline and final visit 
(visit 1 and 6) and at 1 month (visit 7) and 6 months (visit 8) follow-up. 
 
 
Visual acuity: 
- Best Corrected Visual Acuity (BCVA) scores for distance and near vision – ETDRS/Colenbrander charts. 
- Fixation stability - MAIA microperimeter, CentreVue 

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4 
STUDY DESIGN 
4.1 
OVERALL DESIGN 
 
- Contrast sensitivity – FACT test. 
Field of Vision: 
- Humphrey full field 120 – Humphrey Field Analyzer 3, Zeiss 
- Esterman binocular field - Humphrey Field Analyzer 3, Zeiss 
 
Reading Speed: 
- Minnesota Low Vision Reading - MNREAD test. 
 
Quality of life: 
- Children’s Vision Function Questionnaire (39 questions) 
 
 
 
 
We hypothesize that the home-based audiovisual 3D-MOT IVR stimulation program can be performed by 
HH pediatric patients and that this program will improve visual perception, reading speed and quality of life. 
For our trial design, we used the Pragmatic-Explanatory Continuum Indicator Summary (PRECIS-2) 
instrument, initiated and supported by the NIH Pragmatic Trials Collaborative Project to generalize 
knowledge about the conduct of pragmatic research. PRECIS-2 takes the innovative approach of translating 
ratings on nine domains related to trial design to a readily understood wheel format that communicates 
where the trial design falls on the explanatory (scored 1) - pragmatic (scored 5) continuum30,31 (Figure 1). 
All eligible patients in our study will be patients from care center at Sickkids, Toronto recruited through 
regular appointments made at the clinic (eligibility – recruitment). The setting of the trial corresponds to 
clinical visual care centers (setting). Information sheets will be given out to participants. Provider expertise 
corresponds to low-vision care center (organization). The group of patient will follow the study protocol from 
home, which can be usual practice in visual rehabilitation procedures. The delivery of the intervention is 
flexible with IVR stimulation every 2 days (± 1 day) at any time during the day (delivery). Adherence will be 
evaluated every 2 days; patients are free to “not-comply” and there will be no measures to improve 
adherence (adherence). Follow up of the primary 
outcome (adherence to the protocol) will be sent 
automatically through Wi-Fi to a dedicated and 
secured laboratory computer in real-time after each 
session. Secondary outcome will be assessed at the 
final visit after 4 weeks (follow-up secondary outcome 
at 1 month and 6 months). An Intention-to-treat will be 
performed for the analysis of the primary outcome 
(primary analysis). According to the PRECIS-2-wheel 
results (Figure 1), we propose an interventional, 
pragmatic, single center pilot study to assess the 
feasibility and potential effectiveness of IVR 
stimulation 
in 
pediatric 
population 
of 
homonymous hemianopia patients. 
Figure 1: PRECIS-2 wheel indicating that our 
study is a pragmatic trial (scores >3). 

HH-IVR protocol v01 
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Primary outcome corresponds to the feasibility of the study in terms of adherence, retention rates and 
recruitment. We specified, a priori, 4 feasibility objectives for our pilot study to be considered successful: 
1. ≥ 8/10 patient (80%) completed the protocol. 
2. IVR stimulation protocol is considered complete if the patient performed ≥12 sessions out of 15. 
3. ≤ 3 consecutive VRISE score < 25 per patient during the treatment period. 
4. ≤ 2 dropouts (20%) for cybersickness (discomfort symptoms experienced in VR) 
Completion of the sessions will be monitored in real-time. After each block, a data sheet (.csv, 2 kb) 
containing device ID#, subject #, date/time, time to complete the task/block, number of tasks/blocks 
performed, total stimulation time, total duration of the session will be sent though Wi-Fi to a dedicated and 
secured laboratory computer in real-time (if no Wi-Fi access is available at the end of each block, data are 
stored in the device and sent as soon as Wi-Fi is again available – data storage capacity 500 Mo. No extra 
costs are incurred to the patients’ Wi-Fi plan for sending data). Each session contains 3 data sheets. A 
session is considered complete when 3 blocks of 5 min stimulation are performed. If no data sheets are 
received on the lab’s computer for a period of 3 consecutive days or missed/incomplete sessions are 
observed, the participant’s parent will be contacted by phone and email to identify the cause (no Wi-Fi, 
Oculus Go malfunction, dropout) and appropriate action will be taken. Before and after each session, the 
participant will answer to the VRISE questionnaire (5 questions scored 1 to 7 using the Oculus Go). After 
the completion of the questionnaire, the detailed score will be sent though Wi-Fi to a dedicated and secured 
laboratory computer in real-time. 
Secondary outcome corresponds to potential effectiveness of IVR stimulation measured by visual 
perception and quality of life assessed following standard procedures used in low-vision rehabilitation27 and 
collected at the low-vision clinic by ophthalmologists. Endpoints will measure change from baseline at 2 
and 4 weeks in: 
- Best Corrected Visual Acuity, distance and near vision (ETDRS chart, Colenbrander chart). 
- Mean fixation stability (MAIA micro-perimeter). 
- Contrast sensitivity (FACT test). 
- Points not seen – Humphrey full field 120 (HFA3, Zeiss) 
- Points not seen – Esterman binocular field (HFA3, Zeiss) 
- Mean Reading speed (wpm – Minnesota Low Vision Reading test, MNREAD test28). 
- Quality of life scores (Children’s Vision Function Questionnaire29). 
 
There will be no measure to minimize bias as this study is a feasibility study testing the adherence and 
compliance to the visual rehabilitation procedure. 
 
INTERVENTION: 
Immersive virtual-reality stimulation (IVR): 1 session of 3 blocks of 15 trials of 20 seconds each. Rest time 
is 1-2 minute(s) between blocks. 1 session lasts 19 minutes.1 session every 2 days for 4 weeks (15 
sessions total). 
 
EXPECTED DURATION OF SUBJECT PARTICIPATION: 
 
The duration of subject’s participation is 7 months, including follow-up. 
Treatment period: 4 weeks 
Follow-up period: 6 months 
 
EXPECTED FREQUENCY AND DURATION OF STUDY VISITS FOR STUDY PARTICIPANTS 
 
Screening/inclusion visit: 1-1.5 hours 
Baseline assessment visit: 1.5 hours (visit 1) 

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4.2 
SCIENTIFIC RATIONALE FOR STUDY DESIGN 
4.3 
END OF STUDY DEFINITION 
5 
STUDY POPULATION 
5.1 
INCLUSION CRITERIA 
 
 
Intermediate assessment: 1.5 hours (visit 2) 
Final assessment visit: 1.5 hours (visit 3) 
Follow-up visit 1 month: 1.5 hours (visit 4) 
Follow-up visit 6 months: 1.5 hours (visit 5) 
 
 
 
Evidence in the literature11-16 support the hypothesis that an IVR audiovisual stimulation approach using the 
binocular 3D multiple object tracking (3D-MOT) in the head-mounted display (HMD) Oculus Go/Quest could 
provide a suitable visual rehabilitation approach for children with visual field defects. The central features 
of the 3D-MOT closely match attentionally demanding real-life situations17,18. The setup of the task is highly 
dynamic as the objects change their location over time, requiring a continuous deployment of visual 
attention to avoid confusions between the objects18. 3D-MOT can be combined with fixation (still or tracking) 
while allocating the attention in the visual space to track other moving objects (covert attention) with the 
peripheral retina, a situation found in complex dynamic scene recognition18,19. 3D-MOT stimulation 
programs displayed on monitors or TV screens have been shown to increase brain capacity for complex 
processes such as anticipation, eye-tracking, field of view and even decision-making in healthy and 
pathological participants20–22. Recent work in low-vision patients with homonymous hemianopsia indicated 
a beneficial effect of audiovisual 3D-MOT IVR stimulation program using the Oculus Go on contrast 
sensitivity, fixation stability, reading speed and field of vision23. 
There are currently no visual rehabilitation strategies for children presenting visual field defects consecutive 
to a brain tumor or its treatment. The use of IVR in children aged 4-10 years old has not raised any safety 
concerns24. Moreover, by using the remotely controlled and stand-alone Oculus Go, our strategy favors a 
home-based stimulation program which will increase compliance and adherence to the program. 
 
 
A participant is considered to have completed the study if he or she has completed all phases of the study 
including the last visit or the last scheduled procedure shown in Section 1.3, Schedule of Activities 
(SoA). The duration of participation for each individual participant who completes all study visits will be 7 
months. 
 
The end of the study is defined as completion of the last visit or procedure shown in the SoA in the trial 
globally. It is estimated that it will take 24 months from when the study opens to enrollment until the end 
of the study. 
 
 
 
Male and female patients > 8 years-old with diagnosed homonymous hemianopsia with no prior visual 
rehabilitation interventions. 
 
In order to be eligible to participate in this study, an individual must meet all of the following criteria: 
 
1. Homonymous hemianopsia 
2. Male and female. 
3. > 8 years old 
4. Interpupillary distance >=56 mm 

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5.2 
EXCLUSION CRITERIA 
5.3 
LIFESTYLE 
5.4 
SCREEN FAILURES 
5.5 
STRATEGIES FOR RECRUITMENT AND  RETENTION 
6 
STUDY INTERVENTION 
6.1 
STUDY INTERVENTION(S) ADMINISTRATION 
6.1.1 STUDY INTERVENTION DESCRIPTION 
5. 5. BCVA > 20/20 
6. Ability to follow the visual and auditory stimuli and training instructions. 
7. Home Wi-Fi access. 
 
 
An individual who meets any of the following criteria will be excluded from participation in this study: 
 
1. Ocular diseases 
2. Both eyes with media opacity that impairs microperimetry testing. 
3. Inability to perform during testing and training. 
4. Consumption of psychoactive drugs. 
5. 3 consecutive VRISE scores < 25 at inclusion. 
6. History of vertigo or dizziness 
7. Prior vision rehabilitation interventions. 
 
 
Psychoactive drugs consumption is not permitted (including medicinal cannabis). 
 
Screen failures are defined as participants who consent to participate in the clinical trial but are not 
subsequently randomly assigned to the study intervention or entered in the study. A minimal set of screen 
failure information is required to ensure transparent reporting of screen failure participants. Minimal 
information includes demography, screen failure details and eligibility criteria. 
 
Individuals who do not meet the criteria for participation in this trial (screen failure) because of a inability to 
follow the visual and auditory stimuli and training instructions may be rescreened after 4 weeks to a 
maximum of 3 times. Rescreened participants should be assigned the same participant number as for the 
initial screening. 
 
 
Dr. Bouffet and Dr. Reginald will identify potential participants among their patients at the Hospital for Sick 
Children. Drs. Bouffet and Reginald will make initial contact with potential participants. We will identify 
patients with homonymous hemianopia for a total of 10 participants. We will ensure 5 patients had lesions 
involving the optic chiasm and 5 not involving the optic chiasm 
 
 
 
 
 
 
The device used is the commercially available virtual-reality, standalone, head mounted display Oculus 
Quest 2 (Facebook Technologies, Qualcom, Xiaomi). There are currently 34 clinical trials registered on 
Clinicaltrials.gov using the Oculus Go or Quest: 12 in the US and 4 in Canada. Dr Reber’s lab (co-

HH-IVR protocol v01 
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6.1.2 DOSING AND ADMINISTRATION 
investigator) is currently running a clinical study using the Oculus Quest 2 in elderly patient with macular 
degeneration (NCT04685824, UHN REB approval 20-6143). The application uploaded in this device is the 
NeurofyResearch application, developed and owned jointly by UHN and Neuropowertrain (Research and 
Collaboration Agreement). It is a modified version of the Neurofy application, owned by Neuropowertrain, 
used for perceptual/cognitive training in professional athletes. 
 
 
 
Figure 2: representation of the 3D-MOT 
stimulation procedure: 
1. 8 spheres appear in the headset 2. One 
sphere is cued (red) and returns to yellow after 5 
seconds. 3. All spheres start moving randomly for 
20 seconds. 4. After 20 seconds, the spheres 
stop moving. 5. The patient must select using 
laser pointer (white) the ball corresponding to the 
cued one. 6. The result is displayed 
corresponding to either a hit (correct selection) or 
a miss (wrong selection). Sequence returns to 1. 
for the next trial. 
 
 
Audiovisual IVR stimulation procedure 
This procedure corresponds to: 
- 1 session every 2 days (± 1 day) for 4 weeks. 
- 1 session = 3 blocks of 15 audiovisual stimulation tasks (2 min break between each block). 
- 1 task = 20 seconds audiovisual IVR stimulation (3D-MOT + correlated sound). 
The audiovisual stimulation task (the NeurofyResearch application) involves the 3D multiple-object-tracking 
(3D-MOT) paradigm composed of 8 high-contrast spheres which features are adapted to the visual ability 
of low-vision patients (luminosity = 100cd/m2, size = 1.57° of visual angle). The spheres move for 20 
seconds following random linear paths, bouncing on one another and on the walls of a virtual 3D cube when 
collisions occur. The overall span of the movement of the spheres covers 80° and 60° of horizontal and 
vertical visual angle respectively. The initial speed of the spheres is adjustable, from 3°/s. to 240°/s. and 
determined during the inclusion visit (figure 2). 
 
 
 
The patient, comfortably seated, is asked to track the moving cued target (1 sphere) among moving 
distractors (7 spheres) for 20 seconds. A spatial sound (50Hz, 25-65dBHL) is correlated to the movement 
of the cued target. After 20 seconds, the movement stops and the patient is asked to select, using a laser 
pointer, the cued sphere among the distractors (mark-all procedure). If the selection is correct (i.e. 
corresponding to the cued target) a positive feedback sound is provided and the speed of the spheres in 
the next trial is increased by 0.05log. If the selection is incorrect (i.e. corresponding to a distractor) a 
negative feedback sound is provided and the speed of the spheres in the next trial is decreased by 0.05log 
(adaptative simple up-down staircase). After each block of 5 minutes, the system sends data relative to the 
time spent performing the tasks (primary outcome) to our dedicated and secured laboratory computer 
through Wi-Fi and resets. This procedure takes approximately 1 minute and can be stopped by the patient 
for a longer break in between blocks if necessary (time of the break is recorded). After 3 blocks, the system 

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6.2 
PREPARATION/HANDLING/STORAGE/ACCOUNTABILITY 
6.2.1 ACQUISITION AND ACCOUNTABILITY 
6.2.2 PRODUCT STORAGE AND STABILITY 
6.3 
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING 
6.4 
STUDY INTERVENTION COMPLIANCE 
6.5 
CONCOMITANT THERAPY 
 
 
stops and goes on stand-by mode until the next session. The next session (to be performed 48 hours later) 
will be automatically uploaded in the device and will be initiated by the patient. 
 
Audiovisual IVR stimulation, 1 session every 2 days for 4 weeks (15 sessions). 1 session = 3 x 5 minutes 
audiovisual stimulation. 
 
 
 
The study team will provide each participant a Virtual reality headset (Oculus Quest 2) to take home and 
perform the visual training intervention. At study completion, the participants will return the headset to the 
study team for cleaning and storage procedures as developed by IPAC. 
 
 
Standalone, virtual-reality, head-mounted display Oculus Go/Quest 2. 
 
To keep your Oculus Quest 2 safe, follow these tips: 
• 
To avoid damaging your lenses and display, keep your Quest 2 away from direct sunlight. 
Your headset can be permanently damaged from less than a minute of exposure to direct 
sunlight. 
• 
To avoid scratching your lenses, keep your Quest 2 away from sharp objects (example: cable 
tips, keys). 
• 
To avoid damaging your headset or straps, be gentle when adjusting your headset and tightening 
the straps. 
• 
Do not use or wear your headset while connected to the power adapter or charging. 
To avoid general damage: 
• 
Don’t leave your Quest 2 in extremely hot locations (example: inside of a car). 
• 
Don’t leave your Quest 2 near heat sources (example: furnace). 
• 
Don’t leave your Quest 2 near pets or small children. 
• 
Don’t eat, drink or smoke near your Quest 2. 
• 
Secure your Quest 2 in a safe place when you’re not using it. 
 
 
 
There will be no measure to minimize bias as this study is a feasibility study testing the adherence and 
compliance to the visual rehabilitation procedure. 
 
 
This corresponds to the primary objective and will be monitored in real-time after each blocks of tasks. 
 
 
Supportive care will be administered as needed in accordance with SickKids standard clinical practices. 
Medications to be reported in the Case Report Form (CRF) are concomitant prescription medications, 
over-the-counter medications and supplements. 
Use of psychoactive drugs is prohibited while participants are on the study intervention. 

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7 
DISCONTINUATION AND WITHDRAWAL 
7.2 
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY 
 
 
 
 
The participant, or the participant's legally acceptable representative(s) can withdraw consent for 
participation in the study at any time without prejudice. The investigator can withdraw a subject if, in his or 
her clinical judgment, it is in the best interest of the subject. 
 
 
 
Discontinuation from visual training does not mean discontinuation from the study, and remaining study 
procedures should be completed as indicated by the study protocol. If a clinically significant finding is 
identified (including, but not limited to changes from baseline) after enrollment, the PI or qualified designee 
will determine if any change in participant management is needed. Any new clinically relevant finding will 
be reported as an Adverse Event (AE). 
 
Withdrawn patient will go for a final visit at the clinic with primary and secondary outcome assessment. 
Primary outcomes (adherence, VRISE scores, retention) collected until the withdrawal date will be 
analyzed. Secondary outcomes (BCVA, fixation stability, contrast sensitivity, reading speed, visual fields 
and quality of life) will be assessed during final visit and analyzed. 
 
 
Participants are free to withdraw from participation in the study at any time upon request. 
An Investigator may discontinue or withdraw a participant from the study for the following reasons: 
 
• 
Withdrawal of informed consent (participant or parent/guardian withdraw for any reason) 
• 
If any clinical Adverse Event (AE), laboratory abnormality, or other medical condition or situation 
occurs such that continued participation in the study would not be in the best interest of the 
participant 
• 
Significant study intervention non-compliance 
• 
Disease progression which requires discontinuation of the study intervention 
• 
Requirement of prohibited concomitant medication(s) that requires discontinuation of the study 
intervention 
• 
Three consecutive VRISE scores < 25 during the 4-week home-based audiovisual IVR stimulation 
procedure will terminate the investigational intervention. 
 
The reason for participant discontinuation or withdrawal from the study will be recorded in the study “Study 
termination” CRF. Participants who sign the informed consent form and are randomized but do not receive 
the study intervention may be replaced. Participants who sign the informed consent form, and are 
randomized and receive the study intervention, and subsequently withdraw, or are withdrawn or 
discontinued from the study, will be replaced. The data from participants who are withdrawn or discontinued 
from the study will be used in the analysis unless the participant requests otherwise. 
 
The Oculus Quest 2 device will be turned off remotely preventing its use by the participant. The participant will 
return the Oculus Go/Quest including all the equipment (storage box, batteries, remote control, straps) at 
the final visit. 
 
Withdrawn patients will be replaced to reach a total number of 10 evaluable patients. 
Patients will be contacted after 24 hours by phone or email and evaluated for residual virtual-reality 
symptoms and effects (VRISE questionnaire). 
7.1 
DISCONTINUATION OF STUDY INTERVENTION 

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7.3 
LOST TO FOLLOW-UP 
8.1 
ASSESSMENTS 
8.2 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
 
 
 
A participant will be considered lost to follow-up if they fail to return for two scheduled visits and is unable 
to be contacted by the study site staff. 
 
The following actions must be taken if a participant fails to return to the clinic for a required study visit: 
• 
The site will attempt to contact the participant and reschedule the missed visit within 24 hours and 
counsel the participant on the importance of maintaining the assigned visit schedule and ascertain 
if the participant wishes to and/or should continue in the study. 
• 
Before a participant is deemed lost to follow-up, the Principal Investigator or designee will make 
every effort to regain contact with the participant (where possible, 3 telephone calls and, if 
necessary, a certified letter to the participant’s last known mailing address or local equivalent 
methods). These contact attempts should be documented in the participant’s medical record or 
study file. 
• 
Should the participant continue to be unreachable, they will be considered to have withdrawn from 
the study with a primary reason of lost to follow-up. 
 
 
 
We will assess feasibility of the study (primary outcome) and potential effectiveness (secondary outcome - 
visual acuity, reading speed, visual fields and quality of life) of IVR stimulation. A feasibility assessment is 
required as such home-based visual rehabilitation approach using IVR HMD for children has never been 
tested. 
 
 
 
Feasibility will be assessed in real-time every 2 days during and after home-based IVR stimulation. The 
device, the Oculus Quest 2 will record feasibility outcome measures, sent the data to a dedicated and 
secured laboratory computer through Wi-Fi. The number of completed trials, blocks and sessions will be 
compared to the protocol. 
 
Visual assessments performed at every study visit will include: 
 
- Best Corrected Visual Acuity, distance and near vision (ETDRS chart, Colenbrander chart). 
- Mean fixation stability (MAIA micro-perimeter). 
- Contrast sensitivity (FACT test). 
- Points not seen – Humphrey full field 120 (HFA3, Zeiss) 
- Points not seen – Esterman binocular field (HFA3, Zeiss) 
- Mean Reading speed (wpm – Minnesota Low Vision Reading test, MNREAD test28). 
- Quality of life scores (Children’s Vision Function Questionnaire29). 
 
 
 
Safety will be assessed by adverse events (AEs), premature withdrawals for AEs, rates of AEs. 
8 
STUDY ASSESSMENTS AND PROCEDURES 

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8.2.1 DEFINITION OF ADVERSE EVENTS (AE) 
8.2.3 CLASSIFICATION OF AN ADVERSE EVENT 
8.2.3.1     SEVERITY OF EVENT 
 
 
 
 
An Adverse Event (AE) is any untoward medical occurrence associated with the use of an intervention in a 
study participant, which does not necessarily have a causal relationship with the intervention. An AE can 
therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom or 
disease temporally associated with the use of the intervention, whether or not considered related to the 
investigational intervention. 
 
Stable chronic conditions which are present prior to entry in the study and do not worsen are not considered 
AE. These pre-existing conditions will be documented in the participant’s medical history. 
 
AEs will be the primary safety endpoints. Known AEs induced by IVR stimulation are nausea, dizziness and 
disorientation. The severity of these AEs will be scored using the validated VRISE questionnaire. A VRISE 
score < 25 is considered as an AE. Three (3) consecutive VRISE scores < 25 will lead to the withdrawal of 
the study. 
 
 
AE are classified as serious or non-serious.  A Serious Adverse Event is any AE that is: 
• 
fatal 
• 
life-threatening 
• 
requires or prolongs inpatient hospital stay 
• 
results in persistent or significant disability or incapacity 
• 
a congenital anomaly or birth defect 
• 
an important medical event 
 
The term “life-threatening” in the definition of “serious” refers to an AE in which the participant was at risk 
of death at the time of the event. It does not refer to an AE that hypothetically might have caused death if it 
were more severe. 
 
Serious Adverse Events will be documented for any incident that: 
(a) is related to a failure of the device or a deterioration in its effectiveness, or any inadequacy in its 
labeling or in its directions for use; and 
(b) has led to the death or a serious deterioration in the state of health of a patient, user or other 
person, or could do so were it to recur. “Serious deterioration in the state of health” means: a life- 
threatening disease, disorder or abnormal physical state; the permanent impairment of a body 
function or permanent damage to a body structure; or a condition that necessitates an unexpected 
medical or surgical intervention to prevent such a disease, disorder or abnormal physical state or 
permanent impairment or damage. 
 
 
VRISE questionnaire for assessing AEs related to audiovisual IVR stimulation will be recorded electronically 
(.csv file) after each home-based session (every 2 days) and sent though Wi-Fi to a dedicated and secured 
laboratory computer in real-time. 
 
 
The severity of an AE is assessed by VRISE questionnaire: 
 
• 
Three (3) consecutive VRISE scores < 25 will lead to the withdrawal of the study. 
8.2.2 DEFINITION OF SERIOUS ADVERSE EVENTS (SAE) 

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8.2.3.2      RELATIONSHIP TO STUDY INTERVENTION 
8.2.4 TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW -UP 
 
 
 
All Adverse Events (AEs) must have their relationship to the study intervention assessed by a qualified 
physician who is part of the study team based on temporal relationship and their clinical judgment. The 
degree of certainty about causality will be graded using the categories below. 
 
• 
Definitely Related – There is clear evidence to suggest a causal relationship, and other possible 
contributing factors can be ruled out. The clinical event, including an abnormal laboratory test result, 
occurs in a plausible time relationship to study intervention administration and cannot be explained 
by concurrent disease or other drugs or chemicals. The response to withdrawal of the study 
intervention should be clinically plausible. 
• 
Probably Related – There is evidence to suggest a causal relationship, and the influence of other 
factors is unlikely. The clinical event, including an abnormal laboratory test result, occurs within a 
reasonable time after administration of the study intervention, is unlikely to be attributed to 
concurrent disease or other drugs or chemicals, and follows a clinically reasonable response on 
withdrawal. 
• 
Possibly Related – There is some evidence to suggest a causal relationship (e.g., the event 
occurred within a reasonable time after administration of the study intervention). However, other 
factors may have contributed to the event (e.g., the participant’s clinical condition, other 
concomitant events). 
• 
Unlikely to be related – A clinical event, including an abnormal laboratory test result, whose 
temporal relationship to study intervention administration makes a causal relationship improbable 
(e.g., the event did not occur within a reasonable time after administration of the study intervention) 
and in which other drugs or chemicals or underlying disease provides plausible explanations (e.g., 
the participant’s clinical condition, other concomitant treatments). 
• 
Unrelated – The AE is completely independent of study intervention administration, and/or 
evidence exists that the event is definitely related to another etiology. 
 
 
A qualified physician who is part of the study team will be responsible for determining whether an Adverse 
Event (AE) is expected or unexpected. An AE will be considered unexpected if the nature, severity, or 
frequency of the event is not consistent with the risk information previously described for the study 
intervention. 
 
 
All Adverse Events (AEs) or Serious Adverse Events (SAEs) due to IVR stimulation resolve as soon as the 
stimulation stops25. Investigators will follow-up the participant at 24 hours by phone or email assessing the 
severity of the AEs using the VRISE questionnaire 
 
AE reporting will begin at the time of signing of the informed consent (screening) and will continue until 
discharge from the study. AEs will be elicited by: 
- spontaneous report by participants and/or parents, 
- by 3 consecutive VRISE scores < 25, 
- by observation (by the investigators and/or healthcare staff). 
AEs will be documented in the source documents and the eCRF within 24 hrs. 
 
 
All AEs and SAEs occurring while on study must be documented regardless of relationship. Information to 
be collected includes event description, date and time (if possible) of onset, date and time (if possible) of 
resolution/stabilization of the event, outcome, and the assessment of seriousness, expectedness, 
relationship to study intervention and severity by a delegated qualified physician. 
8.2.3.3      EXPECTEDNESS 

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8.2.5 ADVERSE EVENT REPORTING 
8.2.6 SERIOUS ADVERSE EVENT REPORTING 
8.2.7 REPORTING EVENTS TO PARTICIPANTS 
8.2.8 REPORTING OF PREGNANCY 
9.1 
STATISTICAL HYPOTHESES 
9 
STATISTICAL CONSIDERATIONS 
 
 
Any baseline condition recorded in the medical history that deteriorates at any time during the study, will 
be recorded as an AE or SAE. 
 
Changes in the severity of an AE will be documented to allow an assessment of the duration of the event 
at each level of severity to be performed. 
 
Events will be followed for outcome information until resolution or in the opinion of the PI or qualified 
physician delegate, the participant is stable and does not require further follow-up, or the participant is 
deemed lost to follow-up. 
 
 
AE will be reported to The Hospital for Sick Children Research Ethics Board according to The Hospital for 
Sick Children’s Adverse Event Reporting Requirements. 
 
Adverse events will be reported to The Hospital for Sick Children Research Ethics Board according to 
The Hospital for Sick Children’s Adverse Event Reporting Requirements. 
 
Participants and/or their parent/legal guardian will be informed in a timely manner of any new information, 
including safety information, that is relevant to that participant’s willingness to continue participation. The 
communication of this information will be documented through a revised REB approved Informed Consent 
Form, where possible, based on the timeliness of the information. 
 
In the event that a study procedure detects a new clinically important secondary finding/incidental finding, 
the qualified physician will notify the Most Responsible Physician (MRP) physician at SickKids (if the 
participant is being treated at SickKids) or request the participant’s family doctor’s name and contact 
information in order to arrange medical follow-up to interpret the significance of the findings. 
 
 
If a participant becomes pregnant, the study drug will be permanently discontinued, and the participant 
will complete the evaluations/procedures for the early termination visit. 
 
 
 
• 
Primary Endpoint(s): 
Feasibility is considered when the following primary endpoints criteria are met: 
 
1. ≥ 8/10 patient (80%) completed the protocol. 
2. IVR stimulation protocol is considered complete if the patient performed ≥12 sessions out of 15. 
3. ≤ 3 consecutive VRISE score < 25 per patient during the treatment period. 
4. ≤ 2 dropouts (20%) for cybersickness (discomfort symptoms experienced in VR) 

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9.2 
SAMPLE SIZE DETERMINATION 
9.3 
POPULATIONS FOR ANALYSES 
 
9.4.1 GENERAL APPROACH 
9.4 
STATISTICAL ANALYSES 
 
 
 
 
• 
Secondary Endpoint(s): 
 
Secondary endpoint measures will be performed at Toronto Western hospital during baseline (visit 1), after 
2 weeks (visit 2), after treatment at 4 weeks (visit 3) and at 1-month (visit 4) and 6 months (visit 5) follow- 
up. Results will be compared to basline. 
 
Visual acuity: 
- Best Corrected Visual Acuity (BCVA) scores for distance and near vision – ETDRS/Colenbrander charts. 
- Fixation stability - MAIA microperimeter, CentreVue 
- Contrast sensitivity – FACT test. 
Field of Vision: 
- Humphrey full field 120 – Humphrey Field Analyzer 3, Zeiss 
- Esterman binocular field - Humphrey Field Analyzer 3, Zeiss 
Reading Speed: 
- Minnesota Low Vision Reading - MNREAD test. 
Quality of life: 
- Children’s Vision Function Questionnaire (39 questions) 
 
• 
Exploratory Endpoint(s): 
None 
 
 
 
The CONSORT guidelines state that sample size calculations may not be required for feasibility studies, 
however it is important that the sample be representative of the target study population33. For this pilot 
study, we will recruit 10 patients. 
 
 
The following study populations are defined and will be analyzed as specified below. The population 
evaluable for safety will be the safety population. 
 
The Intent to Treat (ITT) population: the total population of patients registered in the study. 
Safety population: all registered participants who received at least one visual training session. 
 
Results will be reported using descriptive statistics (mean, 95%CI). 
Normality of the distribution will be assessed (skewness and kurtosis). If not normally distributed, data will 
be transformed (Log10) or non-parametric Kruskal-Wallis test will be used. 
Bayesian repeated measures ANOVA will be used to analyze and compare baseline, 2 weeks, 4 weeks, 
1 month and 6 months outcome measures. 

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9.4.2 ANALYSIS OF THE PRIMARY ENDPOINT(S) 
9.4.4 SAFETY ANALYSES 
9.4.5 BASELINE DESCRIPTIVE STATISTICS 
9.4.6 TABULATION OF INDIVIDUAL PARTICIPANT DATA 
 
 
 
 
As recommended by CONSORT guidelines, analysis will be performed following an Intention-To-Treat (ITT) 
approach32. 
 
Primary outcome corresponds to the feasibility of the study in terms of adherence, retention rates and 
recruitment. We specified, a priori, 4 feasibility objectives for our pilot study to be considered successful: 
1. ≥ 8/10 patient (80%) completed the protocol. 
2. IVR stimulation protocol is considered complete if the patient performed ≥12 sessions out of 15. 
3. ≤ 3 consecutive VRISE score < 25 per patient during the treatment period. 
4. ≤ 2 dropouts (20%) for cybersickness (discomfort symptoms experienced in VR) 
 
 
 
We will visualize and report results using descriptive statistics (including frequency distributions, a measure 
of central tendency and a measure of dispersion) of secondary outcomes. Statistical comparison between 
the 2 conditions (baseline and after treatment) for the secondary outcomes will be made using two-way 
ANOVA with repeated measures. Statistical analyses will be performed by our colleague biostatistician and 
epidemiologist Dr. Jin. 
 
 
We will report results using descriptive statistics (including frequency distributions, a measure of central 
tendency and a measure of dispersion) average VRISE scores. 
 
 
 
Summary statistics will be used to describe baseline characteristics and other outcomes of interest. 
Categorical endpoints will be summarized using proportions and frequencies. Continuous endpoints will 
be summarized using the mean, median, range or standard deviations. 
 
 
Raw data corresponding to primary outcome measures related to IVR stimulation (device ID#, subject #, 
date/time, time to complete the task/block, number of tasks/blocks performed, total stimulation time, total 
duration of the session) will be recorded in a digital table (file .csv size = 2 Ko) corresponding to source 
data. This .csv file, not containing any personal health information nor identification information, will be sent 
to a dedicated and secured laboratory computer through Wi-Fi and a copy will be stored on the Oculus. 
Once received on the laboratory computer, these data will be transferred electronically to eCRFs (the 
original .csv file will be kept on the UHN network and in a separate encrypted and password-secured hard 
drive in the investigators’ office). 
Raw data corresponding to secondary outcome measures related to fixation stability will be stored in the 
device (MAIA microperimeter) and a copy will be transferred electronically to eCRFs through encrypted 
uhn.ca/uhnresearch.ca emails. 
Raw data corresponding to secondary outcome measures related to BCVA, contrast sensitivity, reading 
speed, visual fields and quality of life will be recorded on dedicated sheet (source document) and 
transferred manually to eCRFs. 
9.4.3 ANALYSIS OF THE SECONDARY ENDPOINT(S) 

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10    SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
10.1.1 STUDY DISCONTINUATION AND CLOSURE 
10.1.2 CONFIDENTIALITY AND PRIVACY 
 
 
 
 
 
 
 
This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable cause. 
Written notification, documenting the reason for study suspension or termination, will be provided by the 
suspending or terminating party to <study participants, Investigator, funding agency, Sponsor and 
regulatory authorities>. If the study is prematurely terminated or suspended, the PI will promptly inform 
study participants, the REB and Sponsor and will provide the reason(s) for the termination or suspension. 
Study participants will be contacted, as applicable, and be informed of changes to study visit schedule. 
 
Circumstances that may warrant termination or suspension include, but are not limited to: 
• 
Determination of unexpected, significant, or unacceptable risk to participants 
• 
Demonstration of efficacy that would warrant discontinuing the trial 
• 
Insufficient compliance to protocol requirements 
• 
Data that are not sufficiently complete and/or evaluable 
• 
Determination that the primary endpoint has been met 
• 
Determination of futility 
 
Study may resume once concerns about safety, protocol compliance, and data quality are addressed, and 
satisfy the Sponsor, REB, DSMB, and/or regulatory agency. 
 
 
Participant confidentiality and privacy is strictly held in trust by the participating Investigators, their staff, 
and the Sponsor(s). This confidentiality is extended to cover testing of biological samples and genetic tests 
in addition to the clinical information relating to participants. Therefore, the study protocol, documentation, 
data, and all other information generated will be held in strict confidence. 
 
All research activities will be conducted in as private a setting as possible. 
 
Any research information obtained about the patient in this study will be kept confidential. A patient will not 
be identified by name, only by unique study ID number. The patient’s name or any identifying information 
will not appear in any reports published as a result of this study. All identifying information will be kept 
behind 2 security measures or as per equivalent institutional policy, under the supervision of the study/site 
PI and will not be transferred outside of the hospital. 
 
The study monitor, auditor and other authorized representatives of the Sponsor, representatives of the 
Research Ethics Board (REB) or regulatory agencies may inspect all documents and records required to 
be maintained by the Investigator, including but not limited to, medical records and pharmacy records for 
the participants in this study. The clinical study site will permit access to such records. 
 
Study participant research data, which is for purposes of statistical analysis and scientific reporting, will be 
transmitted to and stored at the UHN network. This will not include the participant’s contact or identifying 
information. Rather, individual participants and their research data will be identified by a unique study 
identification number. The study data entry and study management systems used by clinical sites and by 
UHN research staff will be secured and password protected. At the end of the study, all study databases 
will be de-identified and archived at UHN 
10.1  REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 

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10.1.3 FUTURE USE OF STORED SPECIMENS AND DATA 
10.1.5 STUDY MONITORING 
 
 
 
 
 
Data collected for this study will be analyzed and stored at UHN. After the study is completed, the de- 
identified, archived data will be transmitted to and stored at UHN for use by other researchers including 
those outside of the study. Permission to transmit data to UHN will be included in the informed consent. 
 
 
Principal Investigator 
Name, degree, title 
Eric Bouffet MD 
Institution Name 
The Hospital for Sick Children 
Address 
555 University Avenue 
Phone Number 
4168137500 
Email 
Eric.bouffet@sickkids.ca 
 
 
Monitoring of the trial will be performed to verify that: 
• 
The rights and well-being of participants are protected; 
• 
The reported trial data are accurate, complete, and verifiable from source documents; and 
• 
The conduct of the trial is in compliance with the currently approved protocol/amendment(s), 
ICH GCP, and local regulations and requirements. 
 
The Sponsor will be responsible for all monitoring activities. Any trial-related duty or function transferred 
to and assumed by a third party, including monitoring and auditing, will be specified in a clinical trial 
agreement and oversight provided by the Sponsor. 
 
The monitoring plan for the trial will be documented prior to the activation of the study and include the 
following; 
• 
Follow risk-based practices, 
• 
Document the rationale for the chosen monitoring strategy, 
• 
Reference the Sponsor’s process that will be followed to address situations of non-compliance, 
• 
Describe the monitoring responsibilities of all the parties involved, and 
• 
Outline the data and processes to be monitored. 
 
The site Investigator(s)/delegate(s) will allow direct access to source data/documents for the purposes 
of monitoring by the Sponsor, and inspection by regulatory authorities, both domestic and foreign (if 
applicable). It is important that the Sponsor, site Investigator and site personnel are available during 
monitoring visits and inspections, and that sufficient time is devoted to the process. 
 
Monitoring procedures will be implemented beginning with the data entry system and data checks that 
will be run on the database will be generated. Any missing data or data anomalies will be communicated 
to the site(s) for clarification/resolution. 
 
Monitoring reports will be issued after each monitoring visit for review and follow up by the Sponsor, site 
Investigator, and appropriate management and personnel responsible for trial and site oversight. 
10.1.4 KEY ROLES AND STUDY GOVERNANCE 

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10.1.6 QUALITY ASSURANCE AND QUALITY CONTROL 
10.1.7.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES 
 
 
 
 
Auditing of the trial will be performed independently from monitoring to evaluate trial conduct and 
compliance with the protocol/amendment(s), SOP, ICH GCP and local regulations and requirements. 
 
The Sponsor will be responsible for all auditing activities. Any trial-related duty or function transferred to 
and assumed by a third party, including auditing, will be specified in a clinical trial agreement and oversight 
provided by the Sponsor. 
 
The site Investigator(s)/delegate(s) will allow direct access to source data/documents for the purposes of 
auditing by the Sponsor, and inspection by regulatory authorities, both domestic and foreign (if applicable). 
It is important that the Sponsor, site Investigator and site personnel are available during audits and 
inspections, and that sufficient time is devoted to the process. 
 
Auditing reports will be issued after each audit for review and follow up by the Sponsor, site Investigator, 
and appropriate management and personnel responsible for trial and site oversight. 
 
 
 
We will comply with FDA’s ALCOA guidelines to ensure high quality data recording. The delegation of duties 
log will specify which tasks are delegated to which personnel. Data entered on dedicated source documents 
will be recorded legibly in black ballpoint pen and signed. Correction fluid or covering labels will not be 
used. 
 
 
 
Data collection is the responsibility of the clinical trial staff at the site under the supervision of the site 
Investigator. The Investigator is responsible for ensuring the accuracy, completeness, legibility, and 
timeliness of the data reported. 
 
All paper sheets recording BCVA, contrast sensitivity, reading speed, quality of life, and adherence log 
sheet will be considered source documents. 
All digital tables (.csv files) generated by and recorded from the IVR stimulation program in the Oculus Go 
will be considered source data. 
All digital data recorded by MAIA microperimeter will be considered source data. 
 
All source documents should be completed in a neat, legible manner to ensure accurate interpretation of 
data. 
 
Where the source data is not collected as part of the participant’s medical record, hardcopies of the study 
visit worksheets will be provided for use as source document worksheets for recording data for each 
participant enrolled in the study. Data recorded in the case report form (CRF) derived from source 
documents should be consistent with the data recorded on the source documents. 
 
Study data will be entered into REDCap (Research Electronic Data Capture), a secure, web-based 
application designed exclusively to support data capture for research studies. REDCap is developed and 
maintained by a team at Vanderbilt University and licensed free of charge by the Research Institute at UHN. 
The application and data are housed on servers provided by UHN. These servers are located within UHN 
secure data center. Local support for REDcap is provided UHN Research IT. 
10.1.7 DATA HANDLING AND RECORD KEEPING 

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10.1.7.2 STUDY RECORDS RETENTION 
10.1.9 CONFLICT OF INTEREST POLICY 
 
 
 
To enable evaluations and/or audits from Health Canada and/or the Sponsor, the Principal Investigator 
agrees to keep records, including the identity of all participating patients (sufficient information to link 
records, CRFs and hospital records), all original signed informed consent forms, copies of all CRFs, source 
documents, and detailed records of treatment disposition in a secure location for a minimum of 10 years. 
 
If the Principal Investigator relocates, retires, or for any reason withdraws from the study, then the Sponsor 
should be prospectively notified. The study records must be transferred to an acceptable designee, such 
as another Investigator, another institution, or to the Sponsor. 
 
A protocol deviation is any noncompliance with the clinical trial protocol or Manual of Procedures (MOP) 
requirements, if applicable. The Principal Investigator will assure that no deviation from, or changes to the 
protocol will take place without prior agreement from the Sponsor and documented approval from the 
Research Ethics Board (REB), except where necessary to eliminate an immediate hazard(s) to the trial 
participants. The noncompliance may be either on the part of the participant, the Investigator, or the study 
site staff. As a result of deviations, corrective actions are to be developed by the site and implemented 
promptly. All protocol deviations will be documented; the Principal Investigator will assess each protocol 
deviation to determine the impact to the patient’s rights, safety or welfare, study efficacy and data integrity. 
If there is any uncertainty regarding the impact of the protocol deviation, the Principal Investigator will 
consult with the Medical Monitor. 
 
It is the responsibility of the Principal Investigator to use continuous vigilance to identify and report 
deviations within 5 working days of identification of the protocol deviation, or within 2 working days of the 
scheduled protocol-required activity. All deviations must be addressed in study source documents and 
reported to the Sponsor. Protocol deviations must be sent to the reviewing REB in accordance with their 
policies. The Principal Investigator is responsible for knowing and adhering to the reviewing REB 
requirements. 
 
 
 
The independence of this study from any actual or perceived influence, such as by the pharmaceutical 
industry, is critical. Therefore, any actual conflict of interest of persons who have a role in the design, 
conduct, analysis, publication, or any aspect of this trial will be disclosed and managed. Furthermore, 
persons who have a perceived conflict of interest will be required to have such conflicts managed in a way 
that is appropriate to their participation in the design and conduct of this trial. The Hospital for Sick Children 
has established policies and procedures to disclose all conflicts of interest and will establish a mechanism 
for the management of all reported dualities of interest. 
10.1.8 PROTOCOL DEVIATIONS 

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AE 
Adverse Event 
ADR 
Adverse Drug Reaction 
CIOMS 
Council for International Organizations of Medical Sciences 
CLIA 
Clinical Laboratory Improvement Amendments 
CONSORT 
Consolidated Standards of Reporting Trials 
CRF 
Case Report Form 
DCC 
Data Coordinating Center 
DSMB 
Data Safety Monitoring Board 
DRE 
Disease-Related Event 
eCRF 
Electronic Case Report Forms 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practices 
GMP 
Good Manufacturing Practices 
IB 
Investigator’s Brochure 
ICH 
International Council on Harmonization 
ICMJE 
International Committee of Medical Journal Editors 
IND 
Investigational New Drug Application 
ISM 
Independent Safety Monitor 
ISO 
International Organization for Standardization 
ITT 
Intention-To-Treat 
LSMEANS 
Least-squares Means 
MOP 
Manual of Procedures 
MRP 
Most Responsible Physician 
MSDS 
Material Safety Data Sheet 
NCT 
National Clinical Trial 
PHIPA 
Personal Health Information Protection Act 
PI 
Principal Investigator 
QA 
Quality Assurance 
QC 
Quality Control 
REB 
Research Ethics Board 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SMC 
Safety Monitoring Committee 
SoA 
Schedule of Activities 
SOP 
Standard Operating Procedure 
SUADR 
Serious unexpected adverse drug reaction 
3D-MOT 
3D Multiple-Object Tracking 
BCVA 
Best Corrected Visual Accuity 
CVFQ 
Children Visual Function Questionnaire 
dBHL 
Decibels hearing level 
ETDRS 
Early treatment Diabetic Retinopathy 
FACT 
Functional Acuity Contrast Test 
HH 
Homonymous Hemianopia 
ITT 
Intention to treat 
IVR 
Immersive Virtual Reality 
LVR 
Low Vision Rehabilitation 
MAIA 
Macular Integrity Assessment 
MNREAD 
Minnesota Low Vision Reading 
11    REFERENCES 

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PRECIS 
Pragmatic-Explanatory Continuum Indicator Summary 
QoL 
Quality of Life 
VR 
Virtual Reality 
VRISE 
Virtual-reality Induced Symptoms and Effects 

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10.2  
ABBREVIA
TIONS