Virtual Reality for Enhancement of Vision
Phase: NA
Conditions: Glaucoma, Vision Disorder
Sponsor: Stanford University

Virtual Reality for Enhancement of Vision 
Dr. Jeffrey L. Goldberg 
Professor of Ophthalmology, Stanford University 
NCT07071129 
February 12, 2020 
1. 
PURPOSE OF THE STUDY 
a. 
Brief Summary 
This project aims to evaluate the use of Virtual Reality (VR) based visual stimulation for the 
treatment of blindness arising from Glaucoma and other retinal diseases or disorders of the visual 
system, through regeneration of axons of retinal ganglion cells (RGCs) in humans. In certain cases 
of blindness, such as in Glaucoma, or in certain injuries, the optic nerves behind the retina of our 
eyes get damaged, leading to partial blindness, mostly near the periphery of our eye. Recent 
research in Dr. Huberman's laboratory has identified visual stimulation as a non-invasive model 
for regeneration of such damaged axons in rodents, back to the vision centers of their brain. 
b. 
Objectives 
This project will help us to evaluate the feasibility of using virtual reality-based 
approaches for retinal regeneration in humans with glaucoma, retinal diseases or other 
optic injuries. We will use Best corrected visual acuity, Humphrey visual field test, 
Ocular Coherence Tomography to evaluate functional and structural changes and the 
National Eye Institute's visual functional questionnaire (VFQ-25). 
c. 
Rationale for Research in Humans 
The purpose of the study is to evaluate the effect of VR based stimulation on patients 
with glaucoma, other retinal diseases or disorders of the visual system and subjects with 
normal vision. 
2. 
STUDY PROCEDURES 
a. 
Procedures 
Screening visit will include eye exam, best corrected visual acuity (BCVA), Humphrey 
visual field test (HVF), and Ocular Coherence Tomography (OCT), all these tests will be 
performed as standard of care. Baseline visit will include HVF and VFQ25. VFQ25 could 
be also applied at screening visit. After subject complete Screening and Baseline visit 
within 8 weeks, the subject will be trained on how to do VR stimulation. And will be 
provided a VR headset to take home. The VR or VR stimulation will consist in up to 1 
hour per day session that will be done at home Monday through Friday for 12 weeks and 
the following week BCVA, HVF will be performed. The following week the study 
subject will start another cycle of 12 weeks of VR stimulation and the following week, 
will repeat test (BCVA, HVF) and so until the study subject complete up to 8 cycles. At 

February 12, 2020 
 
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least 8 weeks after completing the last cycle subject will do HVF, OCT, BCVA and 
VFQ25. VR 1-hour sessions will consist of an exposure to a non-invasive visual 
stimulation where the subject will be siting wearing a VR headset. After subjects 
complete 52 weeks of VR stimulation (4 cycles) they will be able to continue for another 
52 weeks (4 cycles), or stop the VR stimulation and we will follow them doing only the 
testing (Visual acuity, Visual field test, OCT) every 12 weeks for another 12 months. The 
VR or VR stimulation will be performed as part of research, at no cost, HVF, OCT an eye 
exam will be considered standard of care and billable to subject insurance. 
b. 
Procedure Risks 
The VR stimulation is a designed computational model developed by Stanford University 
researchers, this model aims to maximize the activity of the neurons in the retina, and it 
will pose no more than minimal risks involved with using any of the currently 
commercially available Virtual Reality platforms, such as the Oculus Rift 
(https://www3.oculus.com/en-us/rift/), or the HTC Vive (https://www.amazon.com/HTC-
VIVE-Virtual-Reality-System- Pc/dp/B00VF5NT4I), or the magic leap's system 
(https://www.magicleap.com/).  BCVA, HVF and OCT tests are currently performed at 
the clinic for regular patient care, and will be used to measure any structural or functional 
change.  The VFQ-25 will also tell us if there is any significant impact in the quality of 
life/vision of the study subjects. 
c. 
Use of Deception in the Study 
No deception will be used. 
d. 
Use of Audio and Video Recordings 
No audio or video recording will take place. 
e. 
Alternative Procedures or Courses of Treatment 
There are alternative treatments available for glaucoma including drug therapy and 
surgery that are used to reduce the intraocular pressure. Participants will be able to 
continue their current glaucoma treatment during their participation in the study and get 
any of these treatments as needed. 
f. 
Will it be possible to continue the more (most) appropriate therapy for the 
participant(s) after the conclusion of the study? 
Yes 
g. 
Study Endpoint(s) 
Primary and secondary efficacy endpoints will be measured by: 
-Change in visual field by any one of the following three indices: 
1. Visual Field Index(VFI) 
2.Meand Deviation (MD) 
3.Pointwise linear regression (PLR) analysis 
-Change in the OCT: retinal nerve fiber layer (RNFL), change in 
ganglion cell layer, changes in other retina cell layers 

February 12, 2020 
 
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-Change in BCVA 
3. 
BACKGROUND  
a. 
Past Experimental and/or Clinical Findings 
Recently, a groundbreaking paper came out from the Huberman lab (Lim, J. H. A., 
Stafford, B. K., Nguyen, P. L., Lien, B. V., Wang, C., Zukor, K., ... & Huberman, A. D. 
2016. Neural activity promotes long-distance, target-specific regeneration of adult 
retinal axons. Nature Neuroscience) identifying biased visual stimulation as an 
independent non- invasive modality for retinal regeneration in animal models. They also 
found that the effects of the visual stimulation were mediated through spiking in the 
retinal-ganglion cells in the animal models.  Also, very recently, Gall et al. (Gall, C., 
Schmidt, S., Schittkowski, M. P., Antal, A., Ambrus, G. G., Paulus, W., ... & Lux, A. 
2016. Alternating current stimulation for vision restoration after optic nerve damage: a 
randomized clinical trial. PloS one, 11(6), e0156134) has reported a mean improvement 
of 24% in the visual field when they applied repetitive transorbital alternating current 
stimulation to partially blind patients (optic nerve damage).  Earlier, EJ Chichilnsky's 
research (Pillow, J. W., Shlens, J., Paninski, L., Sher, A., Litke, A. M., Chichilnisky, E. 
J., & Simoncelli, E. P. 2008. Spatio-temporal correlations and visual signalling in a 
complete neuronal population. Nature, 454(7207), 995-999) has identified a model for 
generating stimulus leading to correlated spiking activity across a complete population of 
parasol RGCs in macaques.  Matsuura et al. (Matsuura, M., Hirasawa, K., Murata, H., & 
Asaoka, R. 2015. The Relationship Between Visual Acuity and the Reproducibility of 
Visual Field Measurements in Glaucoma Patients. VA and Visual Field Measurement 
ReproducibilityIOVS. Investigative ophthalmology & visual science, 56[9], 5630- 5635) 
recently reported that reproducibility of visual field tests becomes poor with the 
deterioration of visual acuity, suggesting a relation between the two.  A couple key 
animal studies have led to the formulation of this project, which we mention below. 
b. 
Findings from Past Animal Experiments 
Recently, a groundbreaking paper came out from the Huberman lab (Lim, J. H. A., 
Stafford, B. K., Nguyen, P. L., Lien, B. V., Wang, C., Zukor, K., ... & Huberman, A. D. 
2016. Neural activity promotes long-distance, target-specific regeneration of adult 
retinal axons. Nature Neuroscience) that identified biased visual stimulation as an 
independent non- invasive modality for retinal regeneration in animal models. They also 
found that the effects of the visual stimulation were mediated through spiking in the 
retinal-ganglion cells in the animal models.  A recent paper in animal models (Baden, T., 
Berens, P., Franke, K., Rosón, M. R., Bethge, M., & Euler, T. 2016. The functional 
diversity of retinal ganglion cells in the mouse. Nature, 529(7586), 345-350) has used a 
series of visual stimulation (chirp, moving bars, noise and color), leading to activation 
(through spiking) of more than 30 functional output channels in the mouse retina.  
Earlier, EJ Chichilnsky's research has identified a model for generating stimulus leading 
to correlated spiking activity across a complete population of parasol RGCs in macaques.   
 
We plan to tailor our visual stimulation based on these models. 

February 12, 2020 
 
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4. 
DEVICES USED IN THE STUDY 
a. 
Investigational Devices (Including Commercial Devices Used Off-Label) 
Investigational Device 1 
Name: 
Virtual Reality software 
Significant Risk? (Y/N) 
No 
 
5. 
DRUGS, BIOLOGICS, REAGENTS, OR CHEMICALS USED IN THE STUDY 
a. 
Investigational Drugs, Biologics, Reagents, or Chemicals 
N/A 
b. 
Commercial Drugs, Biologics, Reagents, or Chemicals 
Commercial Product 1 
Name: 
Proparacaine Hydrochloride 
Dosage: 
0.5% 
Source 
Byers Eye Institute Clinic 
Commercial Product 2 
Name: 
Tropicamide 
Dosage: 
0.5% 
Source 
Byers Eye Institute Clinic 
Commercial Product 3 
Name: 
Phenylephrine  
Dosage: 
2.5% 
Source 
Byers Eye Institute Clinic 
6. 
PARTICIPANT POPULATION 
a. 
Planned Enrollment 
200 subjects with glaucoma or other retinal diseases or disorders of the visual system 100 
normal controls (patients with normal vision) General population, above the age of 12, 
willing to take part in our study, with glaucoma or other retinal diseases or disorders of 
the visual system or normal controls. All subjects will be recruited at Byers Eye Institute 
Stanford University 
b. 
Age, Gender, and Ethnic Background 
Age >12 both sexes will be recruited. Any ethnic background. 
c. 
Vulnerable Populations 
No potentially vulnerable subjects will be actively recruited into this study. 
d. 
Rationale for Exclusion of Certain Populations 
Children 12 years old and older will be included in the study. Current VR systems have 
proven to be safe on children 12 years and older. 

February 12, 2020 
 
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e. 
Healthy Volunteers 
100 patients with normal vision (healthy volunteers) will be recruited for the study, as 
long as they satisfy screening, inclusion and exclusion criteria. 
 
The participants will be exposed to no more than minimal risk, associated with watching 
media on currently commercially available Virtual Reality platforms, such as the Oculus 
Rift (https://www3.oculus.com/en-us/rift/), or the HTC Vive 
(https://www.amazon.com/HTC-VIVE-Virtual-Reality-System-Pc/dp/B00VF5NT4I), or 
the magic leap's system (https://www.magicleap.com/).  Additionally, to protect the 
welfare of the participants, they will be clearly told in the informed consent, which they 
will sign before entering the study, that they are free to discontinue at any point if they 
want. 
f. 
Recruitment Details 
Participants will be identified from the Stanford Healthcare clinic population at the Byers 
Eye Institute at Stanford who meet the inclusion criteria. Participants who are identified 
during chart review will be notified of their eligibility, after the patient's physician has 
previously notified the potential research participant and obtained approval to be 
contacted. 
g. 
Eligibility Criteria 
i. 
Inclusion Criteria 
For subjects with glaucoma, other retinal diseases, or disorders of the visual system: 
1. Patient age > 12 years 
2. Compliance with investigator instructions, tests and visit during subject 
participation in the study. 
3. Sufficient fixation ability 
4.Best corrected visual acuity of 20/200 or better in at least one eye, or capable to see 
the visual stimulus at least in one eye. 
For healthy volunteers: 
1. Patient age > 12 years 
2. Compliance with investigator instructions, tests and visit during subject 
participation in the study. 
3.Best corrected visual acuity of 20/20 in both eyes. 
4. Sufficient fixation ability 
ii. 
Exclusion Criteria 
1. Electric or electronic implants (such as cardiac pacemaker) 
2. Any metal artifacts in the head or truncus area (with the exception of dental 
implants) 
3. Epilepsy and photo-sensibility; acute auto-immune diseases 
4. Acute conjunctivitis 
5. Pathological nystagmus 

February 12, 2020 
 
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h. 
Screening Procedures 
All screening test will be performed at the ophthalmology clinic, pre-screening of 
potential subjects will be done through Epic system. 
i. 
Participation in Multiple Protocols 
As part of the consent process, potential subjects will be asked if they are participating in 
any other studies. Participating in other studies will not be an exclusion criteria to 
participate in this study. 
j. 
Payments to Participants 
Subjects will not be paid. 
k. 
Costs to Participants 
The VR stimulation sessions will not have any cost to the participants, all other 
procedures (Eye exam, visual field, OCT) will be billable to patient insurance as standard 
of care, patient will be responsible of any copays. 
l. 
Planned Duration of the Study 
The estimated active participation of the study subjects is 24 months. 
Screening visit may take about 2-3 hours 
The data analysis of all study participants will be approximately 6-8 years. 
7. 
RISKS 
a. 
Potential Risks 
Non-invasive visual stimulation procedures frequency - Overall 40 sessions within 8 
weeks. Each session around one hour.  severity - The visual stimulation procedure will be 
no more severe than viewing content through any of the currently commercially available 
Virtual Reality systems, such as the Oculus Rift (https://www3.oculus.com/en-us/rift/), or 
the HTC Vive (https://www.amazon.com/HTC-VIVE-Virtual-Reality-System-
Pc/dp/B00VF5NT4I), or the magic leap's system (https://www.magicleap.com/)  There is 
a risk of experience motion sickness, however the investigators have reduce this at 
minimum, by ensuring that there is minimal, if any, mismatch of vergence-
accommodation and visual proprioceptive cues.  reversibility - We do not expect the 
commercially available VR system we shall use to produce any undesirable effect in any 
form.  Other procedures will be BCVA, HVF, OCT that are usually performed at the 
clinic as standard of care and possess minimal risk. Risks of Eye Examination and 
Dilation: A combination of eye drops (phenylephrine, tropicamide and proparacaine 
hydrochloride) will be used to widen your pupils. These drugs are used routinely in any 
dilated fundus exam in an ophthalmologist’s clinic. It is likely that your eyes may be 
sensitive to light after they are dilated, but wearing sunglasses helps this, and it will 
decrease in a matter of hours after you receive the drops. If you find it difficult to drive 
after receiving dilating eye drops, you should arrange for transportation home after the 
testing. You may experience temporary glare and blurry vision when eyes are dilated. 

February 12, 2020 
 
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Risk of Optical Coherence tomography (OCT) There are no known risks associated with 
OCT. Risk of Visual field test There are no known risks associated with visual field test. 
b. 
Procedures to Minimize Risk 
We plan to use commercially available Virtual Reality hardware, which goes through the 
standard safety protocols for testing before being available in the mass market. The 
investigator will keep the participant under active observation at all times during the VR 
sessions, and will discontinue promptly if the participant feels discomfort at any point.  
All confidential information will be kept in password-protected Stanford owned 
computers, accessible only to the investigators registered in this protocol. 
c. 
Study Conclusion 
In the event of premature withdrawal from the study, the termination date will be the last 
date the subject is seen at the clinic or the date of the last telephone contact with the 
subject. 
d. 
Data Safety Monitoring Plan (DSMC) 
i. 
Data and/or events subject to review 
Adverse events, protocol deviations, aggregate data analysis reports, progress toward 
study endpoint(s), participant consent forms. 
ii. 
Person(s) responsible for Data and Safety Monitoring 
The Protocol Director. 
e. 
Risks to Special Populations 
We will utilize current available VR system that has been already recommended to be used in 
children 13 years old and older. The Oculus Rift and Samsung's Gear VR headsets are 
recommended for ages 13+, while Sony's recommendation for its PlayStation VR is ages 12 and 
up. And Google cardboard headset should be used by kids under adult supervision. The headsets 
that we will be using will be similar to the current available on the market (Oculus Rift and 
Samsung's Gear VR headsets), while they use it, they will be sitting and under adult supervision. 
8. 
BENEFITS 
The participants may improve their visual acuity and visual field. The knowledge gained from 
this study can be combined in future with other therapies in patients suffering from lack of vision 
arising from glaucoma or other retinal diseases, as well as disorders of the visual system. 
9. 
PRIVACY AND CONFIDENTIALITY 
All participant information and specimens are handled in compliance with the Health Insurance 
Portability and Accountability Act (HIPAA) and privacy policies of Stanford University, Stanford 
Health Care, and Stanford Children’s Health.