Virtual Reality System for Cross-modal Rehabilitation of Hemianopia
Phase: NA
Conditions: Hemianopia, Homonymous, Hemianopsia, Homonymous
Sponsor: Wake Forest University Health Sciences

Protocol version: 2 
Protocol updated 7.01.20 
1 
NCT04230486 
IRB Approved Date: 7/20/20 
Study Title: Visual-Auditory Stimulus Training to Restore Visual Functions in Homonymous 
Hemianopia Patients 
 
Principal Investigator, Co-investigator(s): Huai Jiang, PhD 
 
Sponsor or funding source: Wake Forest University of Health Sciences 
 
Background, Rationale and Context 
Hemianopia (also known as hemianopsia or haemianopia) is characterized by blindness in one 
hemifield and is a common consequence of stroke or trauma-induced injury to visual cortex. Hemianopia 
has profound effects on activities of daily living, robbing those affected of their independence [1, 2, 3, 4]. 
Current commercial rehabilitation techniques used to treat hemianopia patients are based on learning 
oculomotor compensation strategies and only focus on helping patients manage the condition, rather than 
recovering the lost visual field [5, 6, 7]. There is little disagreement that more effective rehabilitative 
strategies are needed [3. 6-14]. 
 
More recently, the topic of cross-modal induced plasticity has attracted growing attention with 
respect to treating hemianopia [15-20,]. Studies of hemianopia animal models at Wake Forest School of 
Medicine by Dr. Huai Jiang and his colleagues have provided insight into an important mechanism of 
visual field recovery [21, 22]. In these studies, hemianopia cats were induced by large unilateral visual 
cortex ablation and then rehabilitated using auditory and visual stimuli to activate the subcortical visual 
pathway to restore the lost visual functions. While fixated on a central point, the cats were tasked with 
making repeated, food-rewarded orienting movements to a salient, concurrent auditory and visual cue 
delivered at a single peripheral location (45°) within the anopic hemifield [21, 22]. After 1 month of 
rehabilitation, all rehabilitated animals were capable of responding to visual cues at azimuths of up to 
105° left to right. This powerful technique was also successful in rehabilitating anesthetized hemianopic 
animals [23, 24]. 
 
These studies have found: 1) Concurrent auditory-visual stimulation is essential for successful 
rehabilitation. 2) Using a single peripheral location (45°) within the anopic hemifield can be more 
effective in reinstating the entire hemifield than using multiple locations. 3) Two weeks is the minimum 
time needed for the rehabilitation to yield effects. 4) A rehabilitative strategy, using an asymmetric trials 
ratio of 9:1 (hemianopia:intact stimulus location) can shift patient attention to the “blind” side and 
facilitate the rehabilitation [10]. 
 
Such training reinstates the visual hemifield and basic visuomotor competencies within several 
weeks by facilitating the re-emergence of visual activity in the deep layers of the superior colliculus via 
training-induced alterations to inputs that these neurons receive from lesion-spared regions of an 
association cortex [21]. In hemianopia animals, rehabilitative training with auditory-visual cues induced 
intrinsic plasticity via the involvement of the subcortical visual pathway [21].  
Currently there are several different approaches to the rehabilitation of hemianopia, however 
most focus on helping patients adapt to their condition, and none of these strategies are capable of 
restoring significant areas of the patient’s visual field. There is little disagreement that more effective 
rehabilitative strategies are urgently needed. 
This non-invasive training technique has the potential of being the first treatment capable of 
significantly restoring the visual field in hemianopia patients. This protocol details the initial steps needed 
to translate the technique from animal models to humans. 
 
Objectives 
Recent findings in animal hemianopia models have led to developments of a novel rehabilitation 
strategy that uses spatiotemporally coincident cross-modal (auditory-visual) cues, focused 45° in the 

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hemianopic field, to initiate responses to events in the ‘blind’ hemifield. Training the hemianopic animals 
with this non-invasive rehabilitation strategy dramatically reversed experimentally-induced hemianopia. 
Improvements in the visual field could be observed just 2 weeks after the start of daily rehabilitation 
training, and full recovery (animals could detect stimuli over 75° in the hemianopic field) took place after 
1 month. The visual field expansion from rehabilitation persisted without further training sessions when 
cats were tested 12 to 21 months following the rehabilitation. 
We hypothesize this rehabilitation strategy will also be successful in human subjects. The proposed 
project aims to translate animal hemianopia research to a noninvasive rehabilitation system for use by 
human visual hemianopia patients. The specific objectives of the program can be enumerated as follows: 
 
Specific Aim 1: Determine the efficacy of an intervention using cross-modal stimulation training to 
restore visual function in homonymous hemianopia patients. 
 
Specific Aim 2: Assess the long-term effects of rehabilitation through follow-up visits after the 
completion of rehabilitation. 
 
Methods and Measures 
 
Design 
This study will test a rehabilitation technique for treating visual hemianopia and compare results against 
measures from patients pre-intervention. We will recruit all interested patients with visual hemianopia and 
will assess visual field, visual capabilities, quality of life, and brain images as part of our research 
measures. 
 
Setting 
Rehabilitation training sessions and progress tests will be performed on the Wake Forest Baptist Medical 
Center Campus and in subjects’ homes. Since administering the Humphrey visual field test requires 
specific equipment, subjects will visit an optometrist’s office for these tests. Subjects will perform the 
remaining visual tests on the Wake Forest Baptist Medical Center Campus.  
 
Subjects selection criteria 
• 
Inclusion Criteria 
• 
Adult volunteers diagnosed with homonymous visual hemianopia / hemianopsia 
(ages 18-99)  
• 
MRI or CT scan demonstrating lesion in the occipital lobe of the brain and/or 
affecting white matter tracts that provide visual input to the occipital lobe of the 
brain 
• 
Brain injury due to ischemic or hemorrhagic causes that occurs after age 18 and 
at least 6 months prior to screening visit 
• 
Demonstration of good fixation on visual training task 
 
• 
Exclusion Criteria 
• 
Volunteers who are unable to complete the study tasks or understand instructions 
• 
 Subjects that are not able to provide written consent or verbal assent 
• 
Subjects who are not available to complete all rehabilitation sessions 
• 
Physical, neurological or mental disability that would interfere with study 
intervention 
• 
Concurrent participation in "vision therapy" other than standard occupational or 
physical therapy 
 

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• 
Sample Size 
The goal of this project is to obtain proof the rehabilitation technique has the potential to be 
successfully translated to humans. To achieve this goal, we will recruit a sample size of 10 
hemianopia subjects in this study in hopes of having at least 5 participants complete all study 
sessions. This study is exploratory; the findings from this study will be used to design future 
studies.  The observed treatment response pattern will be reported, and those data used for 
informed estimates of incidence for future research. Prior animal model studies demonstrated a 
high success rate in the rehabilitation strategy, with 100% of 11 hemianopic cats regaining visual 
field. Assuming that 80% of subjects will have a successful result, using n=5 subjects will allow 
for estimation of a 95% confidence interval with width 0.35 units either side of the estimate [22]. 
 
Interventions and Interactions 
 
Interventions 
Cross-Modal Visual Auditory Rehabilitation - Cross-modal visual auditory rehabilitation is based on 
the rehabilitation paradigm derived from previous animal model studies. The rehabilitation will be carried 
out using a virtual reality rehabilitation (VR) system. The rehabilitation system uses a customized 
commercial wireless VR headset, the Samsung Gear VR, to run custom-made rehabilitation software. 
The cross-modal rehabilitation software provides a gray colored, neutral environment for patients, 
with minimal distractions from rehabilitation. Subjects will be asked to fixate on a colored fixation spot in 
the center of the visual field for 1 second before being randomly presented with either a visual stimulus in 
the normal intact visual field or a spatiotemporally coincident audio-visual stimulus in the hemianopic 
side. Auditory-visual stimulus and visual stimulus will be presented at a ratio of 9:1 respectively. The 
design of the fixed, predictable timing and 9:1 ratio will help subjects shift their attention to the blind 
field. 
 
Auditory stimulus consists of a brief burst of white noise, lasting approximately 100 ms. Visual 
stimulus is a white colored orb positioned against the dark, neutral background and will be displayed for 
1-2 seconds. The longer duration of the visual stimulus will serve to provide stimulus location feedback 
for patients. Patients will be instructed to orient their eyes and head toward stimuli in the hemianopic field 
and to push a button on a controller upon detecting stimuli. This part of the task will serve to boost 
motivation and maintain attention during training. The software will also record these responses and 
reaction times, based on the button presses, and store this data for later review. The next trial will begin 3-
4 seconds after the visual or auditory-visual stimulus disappears and when the patient re-fixates on the 
fixation point. 
Cross-modal visual auditory rehabilitation consists of a total of 200 trials / day (about 30 min) 
over 1 month. Given the results from animal model studies, we expect progress to be observable after 2-3 
weeks of cross-modal rehabilitation, and completion of rehabilitation 1 month after the start of cross-
modal training. 
While we expect most patients will perform rehabilitation using the virtual reality rehabilitation 
system, patients may also complete rehabilitation with a free-field frame device if they are not 
comfortable with using a VR headset. The free-field frame device uses a semi-circular frame to hold LED 
lights (visual stimulus) and speakers (auditory stimulus) in front of the patient. These lights and speakers 
can be used to deliver the same cross-modal visual auditory rehabilitation paradigm. The device is also 
used to perform peripheral visual field tests, and is described in more detail below in peripheral visual 
field test.  
 
Tests 
 

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Humphrey Visual Field (HVF) Test - The HVF test is a common test given to map the visual field. 
During the HVF test, light is projected into a white bowl with a standardized background light intensity to 
form a circular stimulus, around 30 cm away from the patient’s eye. The overall field mapping technique 
used is a form of static perimetry, where a stimulus appears in various areas of the field of vision. The 
patient indicates when they can see the stimulus and the perimetrist then records the point where the 
stimulus was seen. These datapoints are used to determine the patient’s visual field.  
 
Peripheral Visual Field Test - Since the Humphrey 
visual field test only measures up to 30° in the 
periphery, an additional peripheral visual field test 
will be administered using a semi-circular frame 
device (fig. 1) set 50 cm in front of the subject with 
LED lights acting as visual stimulus, located at 
azimuths of 15°, 30°, 45°, 60°, and 75°, as well as a 
center fixation light. Lights will be presented at a 
random time with a fixation period between each 
trial and locations selected randomly. Subjects will 
be asked to fixate on the center fixation light while 
lights are presented at random locations at random 
times (0-1.5 seconds). Upon detecting a light, 
subjects will press a button. Subject responses will 
be used to determine how far in the periphery, up to 
75°, a subject can see. The test will present a total of 
5 trials at each location in both the intact and 
hemianopic side, as well as 5 trials with no stimuli.  
 
 
Sound Localization and Visual Fixation Test - 
This test uses the free-field frame device to position visual and auditory stimuli, in the form of LED lights 
and speakers, at different angles of the patient. The patient is asked to maintain visual fixation on a lit 
LED light straight ahead during the test. Speakers will play a brief burst of white noise from a random 
location 15° or 45° on either the left or right side. The subject will be asked to identify where the sound is 
originating from either verbally or using a button response pad. During this test, subjects’ eyes may be 
videotaped or photographed. These recordings or photos will be reviewed by a member of the study team 
to confirm the subject is able to properly maintain visual fixation.  
 
Virtual Reality (Visual Field) Progress Test - At 
the end of each rehabilitation session, subjects will 
perform a brief 5-minute test using the VR system to 
track rehabilitation progress. The test consists of 30 trials with visual stimulus presented either 15°, 30°, 
45° in either the hemianopia field or the intact field at random time intervals.  
 
Grating Acuity Test - Visual acuity will be tested using a standard grating test. Subjects will be 
presented with a 10°x10° square window filled with either a horizontal or vertical grating, located 5° from 
the fixation point on a computer screen in their hemianopic or intact side. Gratings will start from 0.2 
cycles per degree and progress to larger sizes of 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, then 5.0 cycles per degree. 
The test will comprise of 5 trials for each grating. Subjects will be asked to identify whether the grating is 
horizontal or vertical by either pushing buttons on a response pad or verbally. Responses will be recorded 
for each question. 
 
Figure 1: Free-field frame device 

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Color Vision Test - The color vision test will be administered on a computer. While focused on a central 
fixation point, subjects will be presented with a colored 10° x 10° block located 5° in the anopic hemifield 
and be asked to verbally identify the color. A member of the research team will record these responses. 
The color in each trial will be randomly picked among the color choices of white, black, red, orange, 
yellow, green, blue, and violet. Each color will be displayed at least 3 times. 
 
Shape Recognition Test - Subjects will be presented with basic shapes in their hemianopic side on a 
computer monitor. Shapes will be colored black and be displayed on a white background in a 10° x 10° 
square window located 5° in the previously hemianopic side. Subjects will be asked to fixate on a central 
point and verbally identify each object or express uncertainty. Verbal responses will be recorded for later 
analysis. During this test, subject responses may be audiotaped in order to capture their responses. This 
test will consist of 20 trials. 
 
Questionnaires 
The NEI VFQ-25 and VA LV VFQ-48 questionnaires are designed to assess the taker’s quality of life 
regarding limitations due to low vision.   
National Eye Institute Visual Function (NEI VFQ-25) Questionnaire - The NEI VFQ-25 is a reliable 
25-item version of the 51-item National Eye Institute Visual Function Questionnaire (NEI-VFQ). It is 
especially useful in settings such as clinical trials, where interview length is a critical consideration to 
measure the influence of visual impairment on quality of life. NEI-VFQ questions patients regarding the 
quality of general vision, social functioning, visual dependency, near vision and color vision. 
 
Veterans Affairs Low Vision Visual Function (VA LV VFQ-48) Questionnaire- The VA LV VFQ-
48 is a self-report instrument designed to measure difficulty visually impaired persons have performing 
daily activities. The VA LV VFQ-48 has been used to measure low vision outcomes for individual 
patients and programs, and to compare treatment protocols across diverse settings.  
 
 

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Interactions 
Interactions with subjects are 
outlined in the included timeline (Fig 2).  
 
Study Session 1: Consent, Screening, and 
Pre-Intervention Tests (2 hours) 
Consent documents will be provided ahead of 
the first visit through email or mail for 
subjects to review ahead of time to help them 
make an informed decision about 
participating in the study. Prior to this visit, 
subjects will be contacted by phone or email 
by a study member to answer any questions 
they may have. Upon arrival in this initial 
consent and screening visit, subjects will be 
given time to read through the consent form 
so they may make an informed decision on 
their study participation. A study team 
member will then review the consent form 
verbally with the patient and make sure the 
patient understands the study. Subjects will 
be informed of the requirements of the study, 
and of the time commitment needed to 
perform rehabilitation before signing.  
 
Once patients have agreed to participate in 
the study and have signed the consent form, 
patients will be asked to perform a sound 
localization and visual fixation test.  
 
Sound Localization and Visual Fixation 
Testing: Possessing the ability to localize 
sound is essential in properly implementing 
the rehabilitation strategy, which relies on 
subjects to respond to auditory and visual 
training stimuli. As part of the screening 
process, subjects’ ability to detect the 
approximate location of sound will be 
assessed. Subjects will be asked to fixate on a light straight ahead and be presented with sound from 15° 
or 45° on either the left or right side. The location of the sound will be randomly picked by a computer 
program. Subjects will be asked to identify the side the sound originated from and the approximate 
location. Study staff will log these responses on a computer. Subjects with responses accurate 90% or 
higher will be considered to have passed the test and be eligible for the study.  
 
This test will be conducted using the free-field frame device (fig 1), which uses a semicircular frame to 
hold LED lights and 4 speakers fixed to 15° and 45° positions. Eye tracking or a camera recording of the 
subject’s eyes may be used to ensure the subject is properly fixating on the light. The eye tracking camera 
may take photographs and video for the study team to later review. If a subject cannot maintain visual 
fixation or identify the origin of sound, the visit and study will end and they will be compensated $40 for 
their travel. 
Figure 2: Study 
Timeline 

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To verify their hemianopia condition, subjects will be asked to provide relevant medical records, which 
will be used to confirm diagnosis. Subjects will be instructed to bring their medical records, with proof of 
hemianopia diagnosis, to the screening visit. After they have passed the sound localization and visual 
fixation test, a study member will review these records to make sure the subject is eligible to continue the 
study. Since the effects of hemianopia can vary between patients due to the extent and location of brain 
damage, copies of relevant records may be kept to aid data analysis. These copies will be kept in a locked 
and secure storage location. Patients will be assigned a subject id and any identifying personal 
information will be redacted from these copies. If the patient is deemed ineligible during the study, any 
copies made of these records will be promptly destroyed.  
 
During this visit, baseline measurements for subjects will be obtained. Subjects will undergo a peripheral 
visual field test and be asked to complete 2 quality of life questionnaires: the National Eye Institute 
Visual Function Questionnaire (NEI VFQ-25) and the Veterans Affairs Low Vision Visual Function 
Questionnaire (VA LV VFQ-48). Subjects are expected to spend up to 2 hours for this visit. 
 
(Optional) Study Session 2: Pre-Intervention Test - Humphrey Visual Field Test (1 hour) 
 
Subjects will report to an optometrist, who will administer the Humphrey Visual Field Test, using 
a size V stimulus. This visit will be separate from the other pre-intervention tests due to the special 
equipment needed for the Humphrey Visual Field Perimetry. This visit is expected to take up to 1 hour. 
This visit may be omitted if subjects have a recent Humphrey Visual Field Perimetry test result and gives 
the study team permission to view and keep a copy of the result. 
 
Study Sessions 3 – 32: Cross-Modal Rehabilitation Training (30 minutes each day) 
Each cross-modal rehabilitation training session will take place either on the Wake Forest Baptist 
Medical Center Campus or in subjects’ homes, if subjects find traveling to the Wake Forest campus to be 
too difficult to do daily. For patients who are performing rehabilitation at home, the study team will 
regularly call and check-in with the subject in order to make sure the patient is not experiencing any 
problems. The VR rehabilitation system will send data such as duration of rehabilitation and progress test 
results through a cellular network, in order to monitor compliance and track rehabilitation progress. The 
data will only be linked to a study identifier to maintain privacy. Initial rehabilitation sessions will be 
done at the Wake Forest Baptist Medical Center campus to ensure subjects understand how to use the 
rehabilitation device and are capable of performing rehabilitation at home. 
In each rehabilitation session, subjects will sit down, put on a virtual reality headset with a pair of 
headphones, and use a button on a handheld controller to interact with the rehabilitation system. In order 
to make sure subjects are correctly performing rehabilitation, the headset may be outfitted an eye tracking 
system consisting of a camera and low intensity infrared lights to collect data on patient’s eye 
movements. 
The virtual reality headset and headphones will provide visual and auditory stimulation used in 
the rehabilitation training. Each rehabilitation session will consist of 200 trials. At the end of each 
rehabilitation session, subjects will perform a brief 2-minute VR visual field progress test with the VR 
system to track rehabilitation progress. The rehabilitation will be considered complete once patients can 
reliably detect stimuli 45° in the hemianopic field.  
If patients cannot detect stimuli at 15° by the end of 30 days of rehabilitation, they will repeat the 
rehabilitation for one more month, in order to determine if the slow progress or lack of progress is caused 
by simply not spending enough time performing rehabilitation. 
  
Study Session 63: Post Rehabilitation Tests - Subject visual field did not increase (1 hour)  
If no visual field improvement (measured by virtual reality visual field progress tests) has occurred at the 
end of the 2nd round of rehabilitation, subjects will complete one last visit, where they will be given the 

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NEI VFQ-25 and VA LV VFQ-48 questionnaires to complete. This visit will occur on the Wake Forest 
Baptist Medical Center campus. 
 
Study Session 33: Post Rehabilitation Tests - Subject visual field increase (1.5 hours) 
If a subject shows visual field expansion in the virtual reality visual field progress test, subjects will be 
given a Peripheral Visual Field Test, NEI VFQ-25 and VA LV VFQ-48 Questionnaires in order to 
measure visual field expansion and improvements in quality of life.  
In previous animal studies, rehabilitated hemianopic animals could only detect spatial frequencies 
of 2 cycles/degree compared to over 5 cycles/degree in the (normal) intact animals. We hypothesize the 
subcortical visual pathway mediating the restored visual functions may not have the same capabilities as 
the visual cortex it is replacing. Therefore, recovered vision may have lower visual acuity. The different 
pathways involved in cross-modal rehabilitation may also affect abilities for shape recognition in the 
newly recovered visual field. We will explore whether this is the case with a simple shape recognition 
test, visual acuity test, and color vision test during this visit. Subjects will complete this visit on the 
Wake Forest Baptist Medical Center campus.  
 
Study Session 34: Humphrey Visual Field Post-Intervention Test (1 hour) 
Subjects will report to an optometrist for a Humphrey Visual Field perimetry test.  
 
Study Session 35: 3 Month Post-Intervention Follow-up Tests (1 hour) 
Subjects will complete a follow-up visit 3 months after the end of rehabilitation on the Wake Forest 
Baptist Medical Center campus. The follow-up visit will consist of a peripheral visual field test, and NEI 
VFQ-25 and VA LV VFQ-48 questionnaires.  
 
Study Session 36: 6 Month Post-Intervention Follow-up Tests (1 hour) 
Subjects will complete a final follow-up visit 6 months after the end of rehabilitation on the Wake Forest 
Baptist Medical Center campus. The follow-up visit will consist of a peripheral visual field test, and NEI 
VFQ-25 and VA LV VFQ-48 questionnaires.  
 
Outcome Measure(s) 
The primary outcomes for all participants will be the visual field measurements from Humphrey 
Visual Field and peripheral frame test, with comparisons made before (visits 1 and 2)  and after treatment 
(visits 34 and 35 or visits 63 and 64).  
Secondary outcome measures will include differences in quality of life questionnaire results from 
before (visit 1) and after treatment (visit 33 or 63) and changes in VR progress test results during the 
course of rehabilitation (visits 3-32 and 33-62 if a subject repeats rehabilitation).  
Exploratory outcome measures will be collected in subjects with restored visual fields. The 
qualities of recovered visual field will be examined with visual acuity, color recognition, and shape 
recognition tests after rehabilitation (visit 33 or 63). 
 
Analytical Plan  
Results will be analyzed initially using descriptive statistics. The improvement of visual detections will be 
assessed by using a two-way ANOVA on the percentages of visual detections to stimuli presented in the 
hemianopic hemifield in the peripheral visual field tests before and after rehabilitation. Comparisons for 
subjects will be done using chi square tests for proportions, and t-tests or ANOVA procedures for 
continuous variables.  Other inferential statistical analysis will be conducted as appropriate. 
 
Human Subjects Protection 
 
Subject Recruitment Methods 

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Subjects with homonymous hemianopia on either the left and right side of the visual field 
will be recruited using resources from Wake Forest University Health Sciences’ Clinical and 
Translational Science Institute (CTSI). Members of the PI’s research team will perform 
recruitment. Coordination of potential participants’ visit will be done by phone or in person 
conversation or by email. 
Subjects may be recruited for the study via internet advertisements. Advertisements will 
include listings on researchmatch.org, and Wake Forest School of Medicine’s online study 
recruitment website (www.wakehealth.edu/beinvolved). Potential participants may also be 
identified through several means including, but not limited to, physician/health professional 
referral and utilization of Wake Forest CTSI Data Extraction services. The study team will 
contact homonymous hemianopia patients who may be interested in participating in the study 
using Wake Forest’s i2b2 database, from which the study team will pull contact information and 
relevant medical information of past patients. Contact information, age, gender, and the date of 
hemianopia diagnosis may be obtained in order to find patients who fit the inclusion criteria. All 
contact information will be stored on password-protected computers that are kept behind locked 
doors for which only the PI’s research team will have access keys and passwords. 
 
Monetary Compensation 
Subjects will receive $200 compensation for their travel costs upon completing rehabilitation and test 
visits. To increase study schedule adherence, each subject will be compensated at a fair market 
value for their research follow up visits to reduce attrition rates and to ensure that there is no 
coercion. Subjects will be paid $50 for each completed follow-up visit. 
 
Study-related barriers 
 
A possible concern with the use of virtual reality headsets is motion sickness [25]. Motion sickness may 
occur due to conflicting sensory inputs from the visual system and vestibular system. This may occur in 
virtual reality games where the user is rapidly moving their head and the virtual reality hardware fails to 
keep up with displaying matching visuals. We have made efforts to minimize the risk of patient 
discomfort by keeping rehabilitation sessions short and eliminating any movements in the program that 
patients are not initiating. The rehabilitation consists of 20-30 minutes sessions and the device has been 
previously tried by a hemianopia patient, who gave positive feedback regarding it’s comfort and ease of 
use. We have also made sure the virtual reality system we are using contains more than enough 
processing power to run the rehabilitation software. However, in case subjects are unable to perform 
rehabilitation in the virtual reality environment provided by the VR headset, subjects can also complete 
rehabilitation using the free-field frame device mentioned earlier, used to administer the peripheral frame 
test. While less portable, the device is capable of delivering the same rehabilitation treatment using led 
lights and speakers. 
 
Participants may be discouraged by the large time commitment required for the study. However, when 
compared to current available clinical treatments, the time commitment required for the cross-modal 
rehabilitation study is less time intensive. Current treatments, such as visual restoration therapy, require 
time commitments of around 30 minutes of twice daily therapy for 6 or more months and may not offer 
much improvement in visual field expansion [13, 15, 16]. The study is designed with the assumption that 
subjects will be motivated to continue rehabilitation by the potential benefits, though subjects will also be 
compensated for their travel.  
  
Participants may find daily travel to Wake Forest campus difficult. To reduce barriers from travel, 
subjects may perform rehabilitation in their homes to minimize the strain and time commitment required 

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from travel. Patients who perform any rehabilitation session at home will be provided with a phone 
number on which a member of the research team could be contacted during working hours if they need 
any advice or if the equipment fails. If needed, a study team member will also be available to visit 
patients’ homes to help set-up the rehabilitation system and troubleshoot any issues. 
 
To encourage continued participation, subjects will also be allowed to miss up to 3 consecutive 
rehabilitation sessions without affecting the course of rehabilitation in the first 2 weeks. If subjects do 
miss over 3 consecutive sessions, the 30 days of rehabilitation will be restarted. The days since the start of 
rehabilitation will be reset to 0 once rehabilitation restarts, and the event will be noted. This will be 
explained to subjects before the start of rehabilitation. Subjects will be allowed the chance to restart the 
rehabilitation twice before being excluded for noncompliance. If subjects cannot do rehabilitation 
treatments for more than 5 consecutive days and cannot be contacted, they will be withdrawn from the 
study and considered lost to follow-up. 
 
Informed Consent 
 
Signed informed consent will be obtained from each subject prior to the start of any interventions. The 
consent form will be written in plain language so that individuals will be able to understand the 
information in the consent form. In addition to providing individuals with a consent form, members of the 
research team will verbally outline each aspect of the consent form with subjects to make sure each 
subject understands the study requirements, purpose, and potential risks and benefits. If the subject has 
any questions, they will be referred to the investigator for answers. Consent will be obtained within the 
Wake Forest Baptist Medical Center by members of the study team. 
 
Confidentiality and Privacy 
Confidentiality will be protected by collecting only information needed to assess study outcomes, 
minimizing to the fullest extent possible the collection of any information that could directly identify 
subjects, and maintaining all study information in a secure manner.  To help ensure subject privacy 
and confidentiality, only a unique study identifier will appear on the data collection form. Any 
collected patient identifying information corresponding to the unique study identifier will be 
maintained on a linkage file, store separately from the data.  The linkage file will be kept secure, with 
access limited to designated study personnel. Following data collection subject identifying 
information will be destroyed three years after closure of the study. Paper documents will be 
shredded, electronic documents will be securely deleted using software that will delete and overwrite 
sensitive disk space), consistent with data validation and study design, producing an anonymous 
analytical data set.  Data access will be limited to study staff. Data and records will be kept locked 
and secured, with any computer data password protected.  No reference to any individual participant 
will appear in reports, presentations, or publications that may arise from the study. 
 
Data and Safety Monitoring 
The principal investigator will be responsible for the overall monitoring of the data and safety of 
study participants.  The principal investigator will be assisted by other members of the study staff. 
 
Reporting of Unanticipated Problems, Adverse Events or Deviations 
Any unanticipated problems, serious and unexpected adverse events, deviations or protocol changes 
will be promptly reported by the principal investigator or designated member of the research team to 
the IRB and sponsor or appropriate government agency if appropriate. 
 

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Appendix 
1. Copy of the National Eye Institute Visual Function (NEI VFQ-25) Questionnaire 
2. Copy of the Veterans Affairs Low Vision Visual Function (VA LV VFQ-48) Questionnaire 
3. Consent form 
4. Advertisement text