A Randomized, Double-Blind, Placebo-Controlled Pilot Study to Evaluate Non-invasive Brain Stimulation Effects on Orientation and Mobility Performance in Adults With Visual Impairments
Phase: NA
Conditions: Retinitis Pigmentosa (RP), Rod Cone Dystrophy, Visually Impaired Persons, Peripheral Visual Field Defect of Both Eyes, Low Vision, Both Eyes, Vision Loss Partial, Orientation, Mobility Difficulty, Mobility Limitation, Mobility and Independence, Glaucoma
Sponsor: University of Waterloo

 
Official Title: A Randomized, Double-Blind, Placebo-Controlled Pilot Study to Evaluate Non-invasive 
Brain Stimulation Effects on Orientation and Mobility Performance in Adults with Visual 
Impairments. 
 
Date: 17th December, 2025 
 
Protocol outline 
Note: Items in BLUE are meant to indicate when the clinician is acting. 
 
Population of interest and eligibility criteria 
 
Individuals with constricted visual fields (those who use a white cane for traveling daily and those who 
do not use a white cane). 
Individuals with constricted visual fields will be considered eligible to participate in the study if they: 
• 
Are healthy, capacitated adults with binocular constricted visual field loss (due to either retinitis 
pigmentosa (RP), rod-cone dystrophy, or advanced glaucoma) resulting in functional vision losses. 
These individuals with visual impairments can be those who have been previously trained by an 
Orientation and Mobility (O&M) specialist to independently travel with the long white cane daily (since 
the length of the white cane and tip at the base are based on personal preference, they should be willing 
to use their own white cane for the study), and those who do not necessarily use a cane for travelling. 
• 
Have binocular visual acuity or best corrected binocular visual acuity no better than 6/12 or 20/40 or 
+0.30 logMAR (inclusive) with no eccentric viewing, and visual fields no better than 70 degrees in 
total in each eye. 
• 
Are over the age of 18 (inclusive) and has full legal capacity to provide informed consent.   
• 
Have read and fully comprehends the information in the consent letter. 
• 
Are willing and capable of adhering to instructions and maintaining the outlined appointment schedule. 
 
Individuals with constricted visual fields will be considered ineligible and therefore excluded from the 
study if they: 
• 
Are involved in other recent eye-related studies, either clinical or research-related. To be eligible 
they would have to wait at least one week for studies not involving brain stimulation, and four 
weeks for studies in which they receive brain stimulation before they could participate in this study. 
• 
Have been diagnosed with dementia or self-reported dementia with no formal diagnosis. 
• 
Have been diagnosed with a cognitive impairment or self-reported cognitive impairment with no 
formal diagnosis. 
• 
Have been diagnosed with physical or motor impairments resulting in walking and/or balancing 
issues or self-reported physical or motor impairments resulting in walking and/or balancing issues 
with no formal diagnosis. 

• 
Have been diagnosed with vestibular disorders or dysfunctions which affects one’s balance and/or 
mobility or self-reported vestibular disorders or dysfunctions which affects one’s balance and/or 
mobility with no formal diagnosis. 
• 
Are unable to follow the researcher’s instructions. 
• 
Are anticipating treatment (including ocular surgery) for any eye disease within the duration of the 
study. 
• 
Have any ocular pathology in addition to retinitis pigmentosa (RP), rod-cone dystrophy, or 
advanced glaucoma, which can diminish their visual acuity and/or their visual field, however 
wearing glasses or contact lenses, as well as mild cataract of grade 2 or below is acceptable. 
• 
Have severe hearing impairment. 
• 
Are pregnant or trying to get pregnant. 
• 
Fit any of the typical contraindicators for brain stimulation. See contraindicator section below. 
 
For all participants the contraindications for brain stimulation are: 
• 
Diagnosed with epilepsy or have previously experienced an epileptic seizure. 
• 
Implanted medication pump or implanted electronic device, including defibrillator or pacemaker. 
• 
Any metal implants in the head (excluding tooth fillings). 
• 
Active electric implants anywhere in the body (especially the head region). 
• 
On psychoactive medication for any psychiatric or neurological conditions including but not limited 
to depression and schizophrenia. 
• 
Areas of sensitive skin located on the face or head, or a skin condition on the face, or regularly use 
medication to alleviate skin irritation on the face.  
• 
Recurring headaches. 
• 
Previous head injury or skull fracture or head/brain surgery. 
• 
Heart disease, neurological condition, or a history of cardiac or neurological surgery. 
• 
Current or historical cancerous or noncancerous brain tumor, or other abnormalities in brain 
structure. 
 
The goal is to recruit 20 participants.  
 
 
Initial phone screening 
1. Complete the Preliminary Screening Form by kindly requesting a response for each item. 
2. If potential participants come from the practices of local optometrists and ophthalmologist within 
the Region of Waterloo as well as nearby regions of Ontario, they will be asked to complete the 
“Consent to Disclose Personal Information, Pursuant to the Personal Health Information Protection 
Act, 2004 (PHIPA)” letter in order to obtain a report consisting of ocular diagnoses including their 
duration, as well as any treatment they may be receiving. The purpose of obtaining this report is to 
document their diagnoses (including duration and treatment). 
3. Confirm ocular health by reviewing health records in VisualEyes if the participant is a patient at 
the University of Waterloo Optometry Clinic or by reviewing report if participant is not a patient 
at the University of Waterloo Optometry Clinic. 
 
 

Visit/Session 1:  Screening 
 
1. Present and discuss contents of the Consent form and obtain participant’s signature. Ensure that the 
participant indicates: (i) whether or not they wish to be informed of incidental findings; (ii) whether 
or not they allow the researchers to videorecord them as they complete the O&M course during 
visits 2 and 3. 
 
2. Perform clinical tests: 
• 
Measure corrected distance and near visual acuity (VA) binocularly. 
• 
Measure contrast sensitivity (CS) binocularly. 
• 
Perform Hirschberg test. * 
• 
Perform extraocular motilities test. * 
• 
Measure peripheral visual fields with Humphrey Field Analyzer (HFA).  
 
*Tests to be performed by clinicians. 
 
Prior to performing the aforementioned clinical tests, the clinician will remind the participant 
that the tests are not meant to substitute an eye examination, and it is crucial that they see their 
primary eye care provider for a comprehensive assessment as often as their optometrist 
advises.  
 
4. Re-screen contraindications for brain stimulation. For individuals with constricted visual fields ask 
questions regarding whether or not they use a long white cane for travel, and any orientation and 
mobility (O&M) training they may have received. 
 
Note:  
• 
If their VisualEyes record or external report reveals additional eye issues that can have an 
impact on their visual acuity and/or visual field, they will not be invited to participate in the 
study. 
• 
The purpose of the Hirschberg and motility tests is solely for documentation purposes, so that 
the researchers know the variables, which may be impacting vision. However, the results of the 
visual acuity and visual field tests will be used to confirm eligibility of both groups. 
• 
If the brain stimulation questionnaire indicates that it is not safe to perform brain stimulation, 
then they will be reimbursed for their time and removed from the study.  
• 
If an incidental/atypical finding is found on the Humphrey Field Analyzer visual field test, and 
the participant indicated that they wish to be notified of such findings, the research team will 
report the finding to the ethics board by submitting form 108. Upon the board’s 
recommendation, the research team will inform the participant in-person during the 
participant's subsequent visit and explain that "as the visual field test was purely for research 
purposes, the research team are not able to provide diagnoses, but the visual field test results 
came back with a potentially atypical finding. Sometimes, these findings are harmless and 
represent normal human variation, but sometimes they may be indicative of some pathology." 
We will then provide them a copy of the visual field results, which contains the incidental 
finding and will encourage the participant to discuss the finding with their optometrist or 

ophthalmologist so that they can explore whether additional care is warranted. In some cases, 
we can also directly send the results to their clinician if we have this information.  
o If they indicate on the consent form that they do not want to be told of 
atypical/incidental findings, then no letter will be issued, and they will not be notified. 
 
 
 
 
IF PATIENT QUALIFIES FOR STUDY: 
• 
Randomly select stimulation codes to determine active and placebo/sham schedule for next two 
visits. The order of active and placebo presentation will be randomised so that neither the 
participant nor the researcher will know what the subject will receive on each day. The 
researcher will only unmask the type of stimulation after the entire study is completed. 
 
 
 
Visits/Sessions 2-3:  Brain stimulation and completion of O&M tasks (recall that one day is active 
stimulation and the other is sham/placebo (order randomized)). 
Note:  
• 
Visits/sessions 2 and 3 must be separated by at least 48 hours (no more than a week). 
• 
The same mobility course will be tested 6 times (3 measuring time points (pre, post1, post 2) x 
2 treatment days (active and placebo)). The location of the obstacles in each trial (pre, post 1, 
and post 2) will not be varied, but rather the location of the obstacles on each treatment day 
for courses 2 to 4 will be randomized. Moreover, given that courses 3 and 4 only have one 
obstacle each, it would also help to change what the actual object is for both courses on both 
treatment days. Whilst course section #1 must be done first, the order of completing the other 
three courses will also be randomized. In addition, for each course section, the start and end 
points/direction will also be varied. For example, the participant will start at the usual staring 
point in “pre” but in “post 1” they will start the course from the end point, that is, in the 
opposite direction. These should all help to minimize practice effects. 
 
1. Verify that their general health has not changed since their last visit. 
 
2. Verify that their vision/eyesight has not changed since their last visit. 
 
3. Verify that they got close to full night of sleep, that is more than 5 hours; and they have refrained 
from consuming more than 2 alcoholic beverages within the past 24 hours. 
 
 
4. Complete orientation and mobility (O&M) course→ these results will serve as an “O&M pretest” 
set of results.  
• 
O&M parameters to measure include: 
o Time taken to complete a specific section of the course, 
o Number of errors,  
o Percentage preferred walking speed (PPWS),  

o Visual detection distance (VDD),  
o Visual identification distance (VID). 
 
5. Stimulation (either active or sham/placebo; using the two different codes generated at the first visit) 
for 20 minutes whilst the patient is quietly seated. Since we cannot have more than one orientation 
and mobility (O&M) course, and we are concerned about the learning effect from repeatedly doing 
the course, we will stimulate the participant for 20 minutes, and then have them wait for 2 minutes 
before moving on to step 5 below. 
 
 
6. Complete orientation and mobility (O&M) course 2 mins after stimulation→ these results will serve 
as an “O&M post-test 1/immediately after stimulation” set of results. 
• 
O&M parameters to measure include: 
o Time taken to complete a specific section of the course, 
o Number of errors,  
o Percentage preferred walking speed (PPWS),  
o Visual detection distance (VDD),  
o Visual identification distance (VID). 
 
7. Complete orientation and mobility (O&M) course 30 mins after stimulation→ these results will 
serve as an “O&M post-test 2/30 minutes after stimulation” set of results. 
• 
O&M parameters to measure include: 
o Time taken to complete a specific section of the course, 
o Number of errors,  
o Percentage preferred walking speed (PPWS),  
o Visual detection distance (VDD),  
o Visual identification distance (VID). 
 
8. Participant fills out brain stimulation adverse effects form. The form consists of a 3-point 
questionnaire whereby participants record their subjective sensation during stimulation with 1 
indicating no sensation at all, and 3 indicating an extremely strong sensation. Sensations include, 
itching, headache, trouble concentrating, and pain to name a few. Clinician consulted if participant 
fills out any of the categories with a rating of 3, which indicates severity. These will be reported to 
the Office of Research Ethics (ORE) as an adverse event, and the ORE will be consulted for 
guidance to ensure safety of all study participants. 
 
9. Complete renumeration. 
 
10. Thank the participant for their participation in the study. 
 
11. To determine the effectiveness of sham/placebo, ask the participant at the end of visit/session 3 
which of the two visits they thought they received active stimulation. 
 
 
 
 
Brain stimulation details 
 
• 
High frequency tRNS (hf-tRNS) stimulation of V1 within the occipital pole (2 mA peak to 
peak, current intensity bounded between -1mA and +1mA with 0 mean, 20 minutes, 30 seconds 

ramp up and down; Placebo: 30 second ramp-up and down periods, with no current applied 
otherwise) (Pavan et al., 2019) using a neuroConn DC Stimulator Plus or neuroConn DC 
Stimulator MC (neurocaregroup.com) and two 5 cm x 5 cm rubber electrodes either placed 
inside 0.9% saline homogeneously soaked sponges  or covered in a 1-2 mm thick layer of 
Ten20 conductive paste. Both electrodes will be positioned on either side of Oz, more 
specifically over O1 and O2, as given by the International 10-20 EEG electrode placement 
system, in a lengthwise manner and separated by 2-3 finger widths (van der Groen et al., 2022). 
The location of each electrode, namely the anode or cathode will be randomized in terms of 
which is positioned over O1 and O2. This randomization will be done for each participant, 
however, once the order is selected, it will be kept constant on both treatment days for the 
participant. Care will be taken to ensure a dry section of scalp between electrodes. Maximum 
impedance  15 kilo- ohms. Electrodes will be secured using rubber straps. 
 
 
 
 
 
 
O&M measures of performance 
 
 
The following mobility performance parameters will be measured: 
• 
Time taken to complete a specific section of the course- this will be measured for each course 
section using a stopwatch. 
• 
Number of errors-  
o Mobility errors are essentially any unintentional contact of any part of the body 
and/or collisions with static (fixed/steady/stable obstacles) objects, obstacles, or 
boundaries (stumbles, bumping into objects, brushing into branches, and high 
stepping (anticipating a step that is not present)). 
o Orientation errors include incorrect turns, taking a wrong direction, deviation 
errors (such as veering or zig-zagging), corrections, not navigating the course 
correctly after making contact with an obstacle. 
o Other errors related to travel include abrupt changes in walking speed, changes in 
gait or abnormal foot placement, loss of balance, hesitating/stopping, interventions 
of instructors or bystanders. 
o The use of one’s hand to search or trail along a wall, as well as cane-contact with 
an obstacle, inner or outer shoreline will not be regarded as errors as they are 
strategies used to maintain one’s orientation and mobility (O&M) in the 
environment using tactile senses. However, to avoid any ambiguity, both 
participants with constricted visual field who use a white cane, as well as those 
with constricted visual fields who do not need a white cane  for travelling, will be 
asked to verbalize any orientation and mobility (O&M) strategies, such as trailing, 
for example, that they apply on the orientation and mobility (O&M) course (Chang 
et al., 2020; Leat & Lovie-Kitchin, 2006; Roentgen & Gelderblom, 2012). 
o Throughout the entire orientation and mobility (O&M) course (sections 1-4), the 
subject will be instructed to walk the respective pathways without touching any 
obstacles at a pace that is comfortable to them. The researcher will carefully 
observe them and will note the number of each kind of error mentioned above. 
 

• 
Percentage preferred walking speed (PPWS)- The walking speed of the individual who is 
visually impaired in an environment with obstacles expressed as a percentage of their preferred 
walking speed in an unobstructed path. 
o Walking speed- total distance travelled divided by the total time to completion. Travel 
distance can be measured using a portable digital laser range finder, and time using a 
stopwatch.  
o Subjects will be instructed to walk along a straight, flat, obstacle-free path (Course 
section #1) at a pace, which is comfortable to them. They will be informed that there 
are no obstacles or steps on the path. The time to complete the path and the distance of 
the path will be measured in order to calculate their preferred walking speed (PWS). 
The participants will be asked to walk the course four times, twice in either direction, 
and the average speed of the four trials will be recorded as their preferred walking 
speed (Chang et al., 2020; Leat & Lovie-Kitchin, 2006). 
o Subjects will then be instructed to walk along a pathway in which there may be 
obstacles (Course section #2), and safely negotiate them without touching any of the 
obstacles. They will also be asked to verbally inform the researcher of  any orientation 
and mobility (O&M) strategies, such as trailing, they apply on the orientation and 
mobility (O&M) course (Chang et al., 2020; Leat & Lovie-Kitchin, 2006). The time to 
complete the path and the distance of the path will be measured in order to calculate 
their preferred walking speed (PWS) in an obstructed path, and together with the 
preferred walking speed (PWS) in an unobstructed path (obtained from course section 
#1) their percentage preferred walking speed (PPWS) can be calculated. 
 
• 
Visual detection distance (VDD) and Visual identification distance (VID)-  
o VDD-The distance (in meters) at which an individual detects an obstacle in their travel 
path, even if they cannot identify it.  
o VID- The distance (in meters) at which an individual can correctly identify an obstacle 
in their travel path. 
o For both course sections # 3 and 4, the participant will be instructed to walk along a 
pathway in which there will be a single obstacle. They will be told to avoid touching 
the obstacle when navigating the course. Course section #3 is meant to be training, 
whilst course section #4 is meant to collect visual detection distance (VDD) and visual 
identification distance (VID) data. Both sections will be marked in meters so that 
distances can be easily measured. Alternatively, a portable digital laser range finder 
can be used for measuring the two distances. As they start the course a stopwatch will 
be started so the time it takes to detect the obstacle can be measured. The participant 
will be asked to stop the moment they detect the obstacle on the course. At that point, 
the experimenter will pause the stopwatch, and record the distance as the visual 
detection distance (VDD). The participant will then be asked to continue along the 
path, and the stopwatch will be resumed. They will be told to stop the moment they 
can correctly identify the obstacle. The researcher will then stop the stopwatch and 
record the distance as the visual identification distance (VID). To ensure that the 

participant does not look at their feet and wait until there are within a few meters of 
the obstacle before stopping, they will be instructed to look ahead at all times when 
navigating the course. It is important to note that visual detection distance (VDD) and 
visual identification distance (VID) can be the same if the participant can identify the 
obstacle at the same point, they detect it. 
o As previously mentioned, course section #3 is a form of training, whereas in course 
section # 4 data is collected. To facilitate sufficient practice, whilst also allowing the 
data to be collected within the planned time points, the participants will complete 
course section #3 twice (once in either direction).  
o Two researchers will be needed for sections# 1-4. One will be with the participant to 
provide instructions and record data; whilst the other will be ahead of the participant 
to make sure that the path is clear, record the times, and confirm that the obstacle is 
still in place (if that section has obstacles), as well as videorecord the session once 
consent was obtained from the participant at the first visit thereby allowing us to do so. 
By videorecording the participant as they complete the course task we will be able to 
obtain more accurate measures of time, and the number of errors (Leat & Lovie-
Kitchin, 2006).  
 
 
 
O&M Course details 
 
Course design  
• 
Orientation and mobility (O&M) course will be composed of an array of static natural and artificial 
(man-made) obstacles. Static natural obstacles refer to fixed/steady/stable obstacles that are either 
readily found in the environment (e.g., potted plants) or form part of the architecture of the building 
(e.g., a pole or a sealed doorway). Artificial obstacles are made of light materials such as 
polystyrene, rubber foam, soft cardboard, or paper. The course will be divided into 4 sections, each 
section geared towards evaluating a different measure of orientation and mobility (O&M) 
performance.  
 
Course details 
• 
Course section #1, no obstacles- A straight, flat, obstacle and pedestrian-free path such as a 
corridor. It will be used primarily to measure preferred walking speed. Using a corridor will allow 
a natural yet bounded travel path with a defined shoreline (Roentgen & Gelderblom, 2012). 
o Measurements- Time taken to complete the course, Number of errors, Preferred walking 
speed which will be used to calculate PPWS (Percentage preferred walking speed) after 
completing course section #2.  
• 
Course section #2, obstacles- An indoor space leading to the outdoors or a more opened space still 
within the building. It will consist of potted plants, overhanging palm frond, chairs, door frames, 
and doors to negotiate. There will be no physical steps, but it is possible that there may be changes 
in the contrast of the floor or a wooden meter rule will be placed on the floor in order to stimulate 

contrast changes or create a false step (Leat & Lovie-Kitchin, 2006; Roentgen & Gelderblom, 
2012). Since is not feasible to have two O&M courses (one for each of the two treatment days), we 
will position all moveable obstacles at different distances/locations during visits 2 and 3, as well as 
record the different distances/location of each item. In addition, the start and end points/direction 
will also be varied. For example, the participant will start at the usual staring point in “pre” but in 
“post 1” they will start the course from the end point, that is, in the opposite direction. This will aid 
to reduce practice effects whilst maintaining the complexity of the course. 
o Measurements- Time taken to complete the course, Number of errors, Preferred walking 
speed in an obstructed path which will be used to calculate PPWS (Percentage preferred 
walking speed) after completing course section #2.  
 
• 
Course section #3, training for VDD and VID- A straight indoor corridor consisting of one 
obstacle. Given that courses 3 and 4 only have one obstacle each, the actual object use for both 
courses on both treatment days may be changed. In addition, the start and end points/direction will 
also be varied. For example, the participant will start at the usual staring point in “pre” but in “post 
1” they will start the course from the end point, that is, in the opposite direction. These should all 
help to minimize practice effects. To measure distances, the course will be marked in meters, so 
the object detection and object recognition distances can be easily measured and recorded. 
Alternatively, a portable digital laser range finder can be used for measuring the two distances (Leat 
& Lovie-Kitchin, 2006; Roentgen & Gelderblom, 2012). 
o Measurements- Time taken to complete the course, Number of errors, Visual detection 
distance (VDD), and Visual identification distance (VID). 
 
• 
Course section #4, measuring VDD and VID- Another straight indoor corridor different from 
that used in section 3. Given that courses 3 and 4 only have one obstacle each, the actual object use 
for both courses on both treatment days may be changed. In addition, the start and end 
points/direction will also be varied. For example, the participant will start at the usual staring point 
in “pre” but in “post 1” they will start the course from the end point, that is, in the opposite direction. 
These should all help to minimize practice effects. To measure distances, the course will be marked 
in meters, so the object detection and object recognition distances can be easily measured and 
recorded. Alternatively, a portable digital laser range finder can be used for measuring the two 
distances (Leat & Lovie-Kitchin, 2006; Roentgen & Gelderblom, 2012). 
o Measurements- Time taken to complete the course, Number of errors, Visual detection 
distance (VDD), and Visual identification distance (VID). 
 
 
 
 
 
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