Visual Restoration for Hemianopia
Phase: NA
Conditions: Stroke Induced Vision Loss, Hemianopia, Quadrantanopia
Sponsor: University of Rochester

 
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Title: 
Visual Restoration for Hemianopia  
 
RSRB No.: 
RSRB00069879 
 
Sponsor-Investigator: 
Steven E. Feldon, M.D. M.B.A. 
 
Principal Investigator (Study Site 1): 
Steven E. Feldon, M.D. M.B.A. 
 
 
 
Professor and Chair, Flaum Eye Institute 
 
 
 
University of Rochester 
 
 
 
601 Elmwood Avenue, Box 659 
 
 
 
Rochester, NY, 14642 
 
 
 
USA 
Daytime Phone Number: 
 
 
(585) 275-1126 
 
Sub-Investigator 1 (Study Site 2): Byron Lam, M.D. 
 
 
 
Robert Z. & Nancy J. Greene Professor of Ophthalmology 
 
 
 
Bascom Palmer Eye Institute 
 
 
 
University of Miami Health Services 
 
 
 
900 N.W. 17th Street  
 
 
 
Miami, Florida 33136  
Daytime Phone Number: 
 
(305) 326-6021 
 
Sub-investigator 2 (Study Site 3):  Madhura Tamhankar, M.D 
Scheie Eye Institute 
Department of Ophthalmology 
University of Pennsylvania 
Philadelphia, PA 19104 
Daytime Phone Number: 
 
215-662-8042 
 
 
 
 
 
 
 

 
2 Version Date 5/9/18 (b) 
 
Purpose: This project will collect data to quantify the effect of visual training on visual defects 
resulting from damage to the primary visual cortex. Subjects will be recruited, undergo baseline 
visual testing, undergo visual training designed to reduce their visual deficit, and perform post-
training visual tests. This research is designed to determine if different visual training treatments 
are capable of reducing visual defects in a large population of adult subjects with cortical blindness 
in a double blind clinical trial. 
 
Background and Motivation for the study: When brain damage is incurred in adulthood, through 
stroke, trauma, or other neurodegenerative conditions, functional deficits result depending on the 
brain region that was affected. As roughly half of the human cerebral cortex is devoted to visual 
processing, many people who suffer brain damage experience consequent impairments in vision. 
When damage affects the primary visual cortex (V1), the visual deficits are severe and are 
described as cortical blindness (CB), or hemianopia/quadrantanopia, depending on the size of the 
defect. CB dramatically impacts the lives of those affected, decreasing quality of life (Gall et al., 
2008; Gall et al., 2009; Gall et al., 2010). CB subjects often lose the ability to drive (de Jong and 
Warmink, 2003; Papageorgiou et al., 2007), reducing their independence, while others who 
continue to drive pose a potential danger to themselves and others (Bowers et al., 2009, 2010; 
Bowers et al., 2014). Those suffering from CB also have other types of impaired daily functioning 
(Ramrattan et al., 2001), and reduced independence (Jongbloed, 1986).  
Currently, there is no accepted treatment for cortical blindness. Some spontaneous recovery 
of vision was reported in a portion of subjects during the first 2-3 months following a stroke (Zhang 
et al., 2006).  However, after this period the visual deficit is believed to become stable and 
permanent (Horton, 2005; Pollock et al., 2011). As such, in the rare instances when subjects are 
prescribed rehabilitation, it is essentially limited to substitution (Rossi et al., 1990; Peli, 2000) or 
compensation therapies (Weinberg et al., 1977; Kerkhoff, 1999, 2000; Spitzyna et al., 2007). In the 
limited number of subjects who benefit from these therapies, quality of life and daily functioning 
are improved (Weinberg et al., 1977; Spitzyna et al., 2007). However, neither therapy is able to 
restore any of the lost vision; instead, they are designed to teach subjects how to make use of what 
vision they have left more effectively (Lane et al., 2010). 
In order to restore lost vision, subjects need to undergo restitution therapy. Multiple 
research studies have shown visual training to recover particular functions within chronic CB fields 
(See Melnick et al., 2016 for review). These studies have shown that in addition to improving 
performance on the trained tasks, such training can also recover untrained aspects of vision, such 
as those measured by standard, clinical visual perimetry (Cavanaugh and Huxlin, 2017). However, 
none of these studies were unbiased (i.e., subjects were not randomized and no blinding was used). 
To fill this important gap in the field, we have designed the present double blind clinical trial to 
assess whether visual restitution training using visual discrimination tasks presented in the blind 
field are clinically relevant and obtainable in a larger patient population. The trial will involve 
recruiting CB patients, measuring their baseline visual performance, randomizing them to one of 
two treatment groups, training them with one of two types of visual discrimination training therapy 
and bringing them back for a repeat of all baseline visual measurements. The results of this study 
will be submitted for publication to scientifically and clinically relevant journals, and they will be 
submitted to the Food and Drug Administration for approval. 
 
Criteria for subject selection 
1.   Number of subjects: 20 subjects will be recruited at each of three study sites, leading to a total of 
60 subjects. The subjects will be divided randomly into two training cohorts, with 30 subjects 
receiving one form of visual discrimination training therapy, while the other 30 will receive another 
form of visual discrimination training. 
 

 
3 Version Date 5/9/18 (b) 
 
2.   Gender and age range: Subject gender is intended to have an even distribution. Women and men 
are both susceptible to the conditions that would qualify participation as study subjects in the 
proposed research. All subjects who have sustained vision losses as a result of brain damage, that 
are able to give informed consent and are willing and able to undergo testing and training will be 
eligible for inclusion in this study, subject to the limitations described in the following paragraph. 
Since vision losses as a result of brain damage do occur in women, we will aim to recruit equal 
numbers of men and women in the proposed study.  
 
Since the goals of the proposed research are to examine the effects of visual retraining on 
visual performance following adult-onset visual cortical damage, children will not be recruited as 
subjects.  Only adults ranging in age between 21 and 75 years of age will be recruited. The upper 
limit of 75 years of age is included to ensure that subjects are able to properly fixate during the 
course of training. Children under the age of 21 will be excluded from enrollment as they rarely 
develop brain injury affecting the visual system.  Very young children (<10 years of age) may also 
not be able to understand the study components/requirements or maintain the discipline 
necessary to participate correctly in daily visual training.  Moreover, on the rare occasion that 
children develop V1 damage, because their brain is more plastic than that of adults, and because 
long range connections are still forming in their visual system, they are sometimes able to recover 
from their hemianopic deficit (see work by Tinelli et al., 2013). This may occur because after such 
damage, children can more easily develop abnormal connectivity between visual areas within and 
between their two brain hemispheres (Bridge et al., 2008), endowing their residual vision with 
properties that are not seen in subjects who sustain V1 damage in adulthood.  As such, children do 
not form a suitable population for the proposed study.  Finally, teenagers and younger children 
have not been subjects in our preliminary studies, so it is unknown whether their perceptual 
learning after cortical damage is comparable to that in adults.  Whether and what kind of visual 
retraining may be beneficial to children and teenagers requires completely separate and novel 
scientific investigations, which are outside the scope of the proposed application.   
 
References 
 
Bowers A, Mandel A, Goldstein R, Peli E (2009) Driving with hemianopia: I. Detection 
performance in a driving simulator. Invest Ophthalmol Vis Sci 50:5137-5147. 
Bowers A, Mandel A, Goldstein R, Peli E (2010) Driving with hemianopia: II. Lane position and 
steering in a driving simulator. Invest Ophthalmol Vis Sci 51:6605-6613. 
Bowers A, Ananyev E, Mandel A, Goldstein R, Peli E (2014) Driving with hemianopia: IV. Head 
Scanning and detection at intersections in a simulator. Invest Ophthalmol Vis Sci 
55:1540-1548. 
Bridge H, Thomas O, Jbabdi S, Cowey A (2008) Changes in connectivity after visual cortical 
brain damage underlie altered visual function. Brain 131:1433-1444. 
Cavanaugh M, Huxlin K (2017) Visual discrimination training improves Humphrey perimetry in 
chronic cortically induced blindness. Neurology 88:1856 - 1864. 
de Jong P, Warmink H (2003) Homonymous hemianopia and driving. Eye 17:545. 
Gall C, Franke G, Sabel B (2010) Vision-related quality of life in first stroke patients with 
homonymous visual field defects. Health and Quality of Life Outcomes 8. 
Gall C, Lucklum J, Sabel B, Franke G (2009) Vision- and health- related quality of life in 
subjects with visual field loss after postchiasmatic lesions. Invest Ophthalmol Vis Sci 
50:2765-2776. 
Gall C, Mueller I, Kaufmann C, Franke G, Sabel B (2008) Visual field defects after cerebral 
lesions from the subject's perspective: Health- and vision-related quality of life assessed 
by SF-36 and NEI-VFQ. Nervenarzt 79:185-194. 
Horton J (2005) Disappointing results from Nova Vision's visual restortation therapy. Br J 

 
4 Version Date 5/9/18 (b) 
 
Ophthalmol 89:1-2. 
Jongbloed L (1986) Prediction of Function After Stroke: A Critical Review. Stroke 17:765-776. 
Kerkhoff G (1999) Restorative and compensatory therapy approaches in cerebral blindness - a 
review. Restorative Neurology and Neuroscience 15:255-271. 
Kerkhoff G (2000) Neurovisual rehabiliation: recent developments and future directions. Journal 
of Neurology, Neurosurgery and Psychiatry 68:691 - 706. 
Lane A, Smith D, Ellison A, Schenk T (2010) Visual exploration training is no better than 
attention training for treating hemianopia. Brain 133:1717-1728. 
Melnick M, Tadin D, Huxlin K (2016) Relearning to see in cortical blindness. The Neuroscientist 
22:199-212. 
Papageorgiou E, Hardiess G, Schaeffel F, Wiethoel H, Karnath H, Mallot H, Schoenfisch B, 
Schiefer U (2007) Assessment of vision-related quality of life in subjects with 
homonymous visual field defects. Graefes Arch Clin Exp Ophthalmol 245:1749-1758. 
Peli E (2000) Field expansion for homonymous hemianopia by optically induced peripheral 
exotropia. Optom Vis Sci 77:453-464. 
Pollock A, Hazelton C, Henderson C, Angilley J, Dhillon B, Langhorne P, others. a (2011) 
Interventions for visual field defects in patients with stroke. The Cochrane Library:1-83. 
Ramrattan R, Wolfs R, Panda-Jonas S, Jonas J, Bakker D, Pols H, Hofman A, de Jong P (2001) 
Prevalence and causes of visual field loss in the elderly and associations with 
impairment in daily functioning: the Rotterdam Study. Arch Ophthalmol 119:1788-1794. 
Rossi P, Khefyets S, Reding M (1990) Fresnel prisms improve visual perception in stroke 
patients with homonymous hemianopia or unilateral visual neglect. Neurology 40:1597-
1599. 
Spitzyna G, Wise R, McDonald S, Plant G, Kidd D, Crewes H, Leff A (2007) Optokinetic therapy 
improves test reading in patients with hemianopic alexia. Neurology 68:1922-1930. 
Tinelli F, Cicchini GM, Arrighi R, Tosetti M, Gioni G, Morrone MC (2013) Blindsight in children 
with congenital and acquired cerebral lesions. Cortex 49:1636 - 1647. 
Weinberg J, Diller L, Gordo W, Gerstman L, Lieberman A, Lakin P, Hodges G, Ezrachi O (1977) 
Visual scanning training effect on reading-related tasks in acquired right brain damage. 
Archives of Physical Medicine and Rehabilitation 58. 
Zhang X, Kedar S, Lynn M, Newman N, Biousse V (2006) Natural history of homonymous 
hemianopia. Neurology 66:901-905. 
 
3.   Racial and ethnic distribution: Subjects will be included in the study regardless of race or ethnic 
origin. All minorities are susceptible to the conditions that would qualify participation as either 
study or as control subjects. The Universities of Rochester, Miami and Pittsburg are all in 
metropolitan areas with some degree of ethnic diversity; therefore recruitment of minorities is 
likely and anticipated. 
 
 
  
Ethnic Categories 
  
Not Hispanic or Latino 
Hispanic or Latino 
  
Racial 
Categories 
Female 
Male 
Female 
Male 
Total 
American 
Indian/Alaska 
Native 
0 
0 
0 
0 
0 
Asian 
1 
2 
1 
1 
5 

 
5 Version Date 5/9/18 (b) 
 
Native 
Hawaiian or 
Other Pacific 
Islander 
0 
0 
0 
0 
0 
Black or 
African 
American 
5 
6 
2 
2 
15 
White 
12 
14 
3 
4 
33 
More than 
One Race 
1 
2 
2 
2 
7 
Total 
19 
24 
8 
18 
60 
 
 
4.   Inclusion and exclusion criteria 
Inclusion Criteria at Screening Visit 
1. Ages 21-75 years old 
2. Ability and willingness to sign informed consent 
3. Willingness to participate in both the training and evaluation sessions 
4. 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. 
5. Brain injury due to ischemic or hemorrhagic causes that occurs after age 18 and at least 
90 days prior to the screening visit. 
6. At least two reliable HVF’s demonstrating good fixation and a stable homonymous 
incomplete (e.g., quadrantanopia or relative defect) or complete hemianopia  
7. Reliable HVFs with repeat HVFs if randomization takes place more than 4 weeks after 
screening visit 
8. A homonymous, contiguous visual deficit measured by the 24-2 HVF to be a minimum of 
two testing locations high and two testing locations wide, where impaired locations are 
any that measure a threshold of less than 15 dB 
9. Demonstration of good fixation on visual training task – able to fixate the small targets 
presented as fixation letters reliably for 1000ms with jitter over less than 1 degree of 
visual angle in any direction away from target edge 
 
Exclusion Criteria at Screening Visit 
1. Physical, neurological or mental disability that would interfere with study intervention 
2. Concurrent participation in “vision therapy” other than standard occupational or physical 
therapy 
3. Unreliable visual fields on prior testing, indicated by greater than 20% fixation losses, 
false positives, or false negatives. 
4. Inability to discontinue medications judged to affect training and/or assessment (e.g., 
Ritalin, amphetamines, dopamines, or chemotherapeutic agents) 

 
6 Version Date 5/9/18 (b) 
 
5. Physical condition likely to preclude completion of the clinical trial (e.g. end-stage or 
uncontrolled cancer, uncontrolled epilepsy, or end-stage heart disease) 
6. Ocular or neurological condition that would interfere with training or assessment (e.g. 
damage to the optic nerves or lateral geniculate nucleus, any degenerative ocular 
condition)  
7. Best corrected vision worse than 20/40 in either eye 
8. Impaired foveal Humphrey sensitivity as indicated by the HVF tests. 
9. Presence of vision loss resulting from ocular disease or disorder 
10. Presence of bilateral visual acuity loss from any source 
 
Additional Exclusion Criteria at Randomization Visit 
1. Inability to demonstrate fixation stability on eye movement monitored testing 
2. Inability to follow training instructions 
 
Concomitant Medications  
1.  No medication is required for participation in the study 
2.  Allowed Concomitant Medications:  Any medications that do not affect learning or motor 
performance are allowed.  All concomitant medications must be used according to the 
prescriber’s instructions. 
3. Disallowed Medications:  Ritalin, amphetamines, dopamines, or chemotherapeutic agents are 
specifically disallowed.  Other medications may be disallowed based upon subject’s 
individual side-effects (e.g. severe drowsiness, tardive dyskinesia, etc.).  The site PI should 
contact the enrollment center to discuss findings and appropriate action in the event use of 
any disallowed medication is discovered.  In all cases, the use of any disallowed medication 
should be documented along with any applicable instructions to the subject.  
 
Discussion of Eligibility Criteria 
Adults were chosen because the incidence of stroke-induced hemianopia is most frequent in adults, 
and because reliability and persistence are required for following the training regime.  Older adults 
(65-75 years) were not excluded as they performed equally well in pilot perceptual training 
compared to younger adults. However, adults older than 75 years old are excluded from enrollment 
because they present with a greater incidence of ocular, physical, and/or mental conditions that can 
interfere with their ability to train effectively.  In addition, our preliminary studies over the last 10 
years show that hemianopic subjects older than 75 years have increased problems with 
concentration and maintaining steady fixation, both of which are absolutely necessary for 
successful training in the present trial.   
Methods and procedures 
1 - Screening Visit (Visit SC) 
Informed consent:  At the screening visit, a signed informed consent document will be completed. 
This consent form describes the interventions and enumerates the risks and benefits of 
participation. It will include consent for screening evaluation as well as consent for 
randomization if subject is found to be eligible. Potential subjects will have the opportunity 
to ask questions and receive answers prior to signing the consent. 

 
7 Version Date 5/9/18 (b) 
 
Eye examination:  A complete medical history, eye history, and eye examination will be performed 
in order to determine eligibility for the study. A comprehensive, routine dilated eye exam 
that includes slit lamp examination and retinal optical coherence tomography (OCT), will 
be performed on each patient by a qualified ophthalmologist or neuro-ophthalmologist at 
each site to verify ocular health. OCT should have a signal strength of at least 6, otherwise 
the test should be repeated. If any problems or signs of ongoing, developing or progressing 
eye disease are observed, this will constitute grounds for exclusion from the study. The eye 
examination will include Snellen best corrected acuity, intraocular pressure measurement, 
exophthalmometry, motility, external examination, slit lamp examination, dilated fundus 
examination and OCT imaging of the retina.  
Visual field testing:  Certified technicians will perform 24-2 Humphrey visual fields on each 
subject. Fixation and pupil monitoring will be “on” for each test. The examination will be 
performed twice with a 30-minute rest period after each test. Examinations need to be 
done twice at baseline, with the second test used for future analysis, to ensure that patients 
are proficient in performing the tests at baseline, so that we can rule out practice on the 
test as a reason for post-training improvements. During Humphrey perimetry, the eye 
tracker will be engaged at all times. Tests will be repeated if the patient fails to generate 
acceptable test reliability (in terms of rate of fixation breaks, false positives and false 
negatives). If repeated perimetry tests fail to yield acceptable reliability measures (as per 
device specifications), this will constitute grounds for excluding the subject from the study. 
Our research to date shows that accurate fixation is critical both to generate reliable 
perimetry results (our primary outcome measure) and to elicit training-induced 
improvements in the blind field. All excluded subjects will be replaced with a new 
enrollment.  
Determination of eligibility:  Sites having potential subjects for inclusion into the study will collect 
the required documentation at the Screening visit and forward relevant medical history, 
two sets of Visual Fields and an MRI or CT scan of the brain. The medical history will be 
sent to the Principal Study PI who will, jointly with the Site PIs, review the records for 
eligibility criteria. The visual fields will be sent to the Visual Field Reading Center for 
confirmation of visual field defect and reliability/stability of testing. The reading center 
will forward its information to the Principal Study PI who will jointly determine with the 
Site PIs whether the subject should appear for a Baseline Visit. 
 
2 - Baseline Visit (Visit BL; 2-4 weeks post SC) 
 
Eye examination:  The history and eye examination as described in Visit SC will only be repeated if 
more than four weeks has elapsed between the Visit SC and Visit BL.   
Visual field testing:  Humphrey visual field testing as described above will only be repeated if 
more than four weeks has elapsed between Visit SC and Visit BL.  
Eye fixation testing and restoration protocol training: Each subject will undergo MAIA perimetry in 
order to assess fixation quality and patterns. MAIA testing is a fundus-controlled form of 
perimetry, and as such, is the most precise way of performing gaze-contingent stimulus 
presentation. The test output includes a detailed mapping of each patient’s fixation 
locations during stimulus presentation, allowing us to quantify the spread of their eye 
movements around the fixation spot.  
 
In addition to performing the MAIA, we will assess the ability to visually process complex 
visual stimuli in the normal and abnormal portions of the visual field in each subject, using 

 
8 Version Date 5/9/18 (b) 
 
computerized tests developed at the University of Rochester. These tests present visual 
stimuli consisting of drifting random dots. The subject is required to indicate (by pressing 
the corresponding keys on the computer's keyboard) the global direction of motion in the 
stimulus. While simple visual perception can be assessed during routine visual testing in 
the clinic, complex aspects of visual processing cannot. This is a significant shortcoming of 
the field right now and one that we will address in the present study. When sequentially 
measuring global direction discrimination performance at different locations across the 
intact field, and into the blind field, the blind field location where the patient’s direction 
discrimination performance falls to chance (~50% correct) in a 100 trial block will be 
designated as the first training location. The potential subject will sit comfortably and be 
instructed on how to correctly position him/her self in the head/chin rest. The subject’s 
laptop computer (or one provided for the subject) will be set up in front of the subject. 
After an explanation by the technician, eye movement fixation monitor will be adjusted. A 
full explanation of the task, including need for steady fixation, response to fixation “catch 
trials”, alternative test stimuli and appropriate responses will be given. The subject will 
then be asked to perform both training tasks at fixation and then at peripheral locations in 
their blind field selected for training based on the Humphrey visual field test results. 
Feedback will be provided by the technician during training until independence is 
achieved. 
The National Eye Institute Visual Functioning Questionnaire – 25 (VFQ-25) version 2000: This 
questionnaire will be completed online in the self-administered format by the subject, in 
the presence of qualified site personnel. The subject may ask for assistance from site 
personnel as needed. A fully validated neuro-ophthalmologic disease supplement of 10 
items, also on line, will be used in addition to the standard VFQ-25.   
Randomization:  Eligible subjects will receive their randomization assignment. All subjects will be 
double masked. Treatment locations and training cohort will be pre-assigned for all 
subject ID numbers and given to each subject at the end of visit BL. The site will then call 
the DCBC to obtain the subject ID to be used for each randomized subject and enter this 
number into the training software, which includes the randomized stimulus sequence.   
 
3 – Post training visit (28 week visit +/- 2 weeks) 
Eye fixation testing and restoration protocol testing:  The eye fixation testing and protocol 
testing will be repeated as described for visit BL. 
The National Eye Institute Visual Functioning Questionnaire – 25 (VFQ-25) version 2000 and 
supplement will be repeated, as described for Visit BL. 
 
4 – Post training clinic visit (29 week visit +/-2 weeks) 
Eye examination:  The history and eye examination will be repeated as described for Visit 
SC. 
Visual field testing:  Visual field testing will be repeated as described for Visit SC. 
 
 
 
 

 
9 Version Date 5/9/18 (b) 
 
Assessment Schedule 
Visit Number 
1 
(screening) 
2  
(2-4 weeks 
post 
screening) 
3  
(28 weeks 
+/- 2weeks) 
4  
(29 weeks 
+/-2 weeks) 
Informed Consent 
Y 
 
 
 
Inclusion/Exclusion 
Criteria 
Y 
 
 
 
Demographics 
Y 
 
 
 
Medical History 
X 
 
 
X 
Concomitant 
Medications 
X 
 
 
X 
Slit-lamp exam  
X 
 
 
X 
Retinal Optical 
Coherence 
Tomography 
X 
 
 
X 
24-2 Humphrey 
X 
 
 
X 
24-2 Humphrey 
repeated 
X 
 
 
X 
MRI/CT 
Z 
 
 
 
Comprehensive 
routine dilated eye 
exam* 
X 
 
 
X 
Visual Functioning 
Questionnaire 
  
Y 
Y 
 
VFQ supplement 
 
Y 
Y 
 
MAIA perimetry 
 
Y 
Y 
 
Eye fixation testing 
and restoration 
protocol 
 
Y 
Y 
 
X Performed by clinician 
Y Performed by study personnel 
Z From patient chart 
*dilated fundus exam, Snellen best corrected acuity, intraocular pressure, exopthalmometry, motility, external exam 
 
Unscheduled telephone contacts: These contacts may be initiated by the sites in response to contact 
from the TC indicating compliance (e.g. missed training sessions) or performance issues (e.g. 
fixation losses).  These contacts may be initiated by the subject for any reason, including equipment 
failure, motivational issues, or notification of inter-current events that may affect training.  The date 
and reason for the unscheduled telephone contact will be recorded in the source documentation. 
 
Unscheduled visits:  These visits may be initiated by the sites in response to contact from the TC 
indicating compliance (e.g. missed training sessions) or performance issues (e.g. fixation losses).  

 
10 Version Date 5/9/18 (b) 
 
These visits may be initiated by the subject for any reason, including equipment failure, 
motivational issues, or notification of inter-current events that may affect training.  The date and 
reason for the unscheduled visit will be recorded in the source documentation, along with whatever 
portions of the visit protocol were conducted.   
 
Premature withdrawal:  Subjects have the right to withdraw from the study at any time without 
prejudice.  The Site Investigator may withdraw training from a subject in the study in the event of 
inter-current illness, adverse events, or other reasons concerning the health or well-being of the 
subject, or in the case of lack of cooperation, non-compliance, protocol violation or other 
administrative reasons.  In the event of premature withdrawal from the study, the Premature 
Withdrawal (PW) Visit procedures and evaluations should be completed whether or not the 
withdrawal is determined at a regularly scheduled study visit or at an unscheduled visit.  In 
instances where the subject refuses to return for a PW visit, the Steering Committee may 
recommend an attempt to obtain outcome data by a visit to a non-participating ophthalmologist.  
Reasons for withdrawal of the subject prior to completion of the study must be stated in the case 
report form and in the site source documentation for all study subjects who were enrolled in the 
study.  The DCBC must be informed within 24 hours of all study subjects who are withdrawn due to 
an adverse event. 
 
Early Discontinuation of Study Training:  In the instance that subjects refuse to continue specified 
training but choose to remain in the study, then scheduled visits should by designated as a 
NOTRAIN visit and all regular visit activities will be completed.  
 
Re-Entry Visits: In the instance that subjects who opted for Early Discontinuation of Study Training 
or Premature withdrawal decide to re-enter the study, then a Re-Entry visit with a protocol 
identical to a Baseline Visit (BV) will be performed, except that the subject’s original randomization 
schedule will be utilized. 
 
Adverse events: An adverse event is any symptom, sign, illness, or experience which develops or 
worsens during the course of the study, whether or not the event is considered related to the study 
intervention. A serious adverse event is defined as any adverse medical experience that results in 
any of the following outcomes: 
• 
death; 
• 
is life-threatening; 
• 
requires inpatient hospitalization or prolongation of existing hospitalization; 
• 
is a congenital anomaly/birth defect; or 
• 
requires medical or surgical intervention to prevent permanent impairment or damage. 
 
At each subject visit the site study staff will assess adverse events by recording all voluntary 
complaints of the subject and by assessment of clinical and laboratory features. At each study visit, 
the subject should be questioned directly regarding the occurrence of any adverse experience since 
his/her last visit. 
All adverse events, whether observed by the Investigator, elicited from or volunteered by the 
subject, should be documented. Each adverse event will include a brief description of the 
experience, the date of onset, the date of resolution, the duration and type of experience, the 

 
11 Version Date 5/9/18 (b) 
 
severity, the relationship to investigational product, contributing factors, and any action taken with 
respect to the study device. All adverse events occurring between the time of consenting and 
subject completion or withdrawal from the study will be recorded. Follow up will continue until the 
adverse event is resolved, including those unresolved at the time of subject concluding study 
participation. 
 
Data analysis and data monitoring: HVF test results will be analyzed using a custom program in 
Matlab. Changes in HVF over time will be mapped across the visual field and the area of the visual 
field that increases or decreases in sensitivity by >6dB will be quantified. Subject age, lesion age, 
visual deficit size, and type of precipitating neurologic event will be analyzed using linear 
regression and ANOVA to determine if any of these factors are correlated with change; when 
appropriate, post-hoc analyses will be conducted using Tukey’s HSD and a family-wise Type I error 
rate of 0.05.  
 
Data storage and confidentiality 
a. Data will be stored on a secure, encrypted server hosted on the URMC private network. Only 
study personnel directly involved in raw data processing and analysis will have access to 
data files containing protected health information. 
b. A separate key will be created linking the subject identifiers with a unique study ID number 
to avoid any direct identifiers stored with the collected data.  
c. Data collected will be used for future research studies.  
 
Risks/benefit assessment 
a. Risk Category: Minimal risk 
b. Potential Risks: There are no known risks of the visual tests and examinations used in this 
study. There are also no known risks of the visual training to be used. Subjects may become 
tired during the course of testing and/or training. There is a risk that subject confidentiality 
will be breached. In addition, as the visual training used in this study is experimental, there 
may be unknown risks. 
c. Protection against risks: If a subject becomes tired during the course of testing or training, 
they will be allowed to rest until they feel ready to continue. Subject confidentiality will be 
protected as well as possible through the use of de-identified ID numbers and secure data 
transmission. 
d. Benefits: We cannot promise any benefits of taking part in this research. However, possible 
benefits include an expansion of the subjects’ visual fields through the reduction of the 
cortically blind deficit, and improved visual functioning in portions of the visual field. 
e. Alternatives to participation: Alternatives may include visual training programs or other 
research studies. 
 
Subject identification, recruitment, and consent/assent 
1. Method of subject identification and recruitment: Subjects will be recruited for this study 
from the clinical practices of the three sites, as well as from waiting lists of subjects who 
have previously contacted the study sites. If additional subjects are required, we will widen 
the search to include the clinical practices in the immediate areas near each study site.  
Examples of the expanded recruitment pool include online hospital recruitment databases 
such as Iconnect and other forms of digital recruitment. Candidate subjects will then be 
randomly selected for screening by our inclusion/exclusion criteria. If a subject fails the 
screening process they will be replaced with a new subject randomly selected from the 
waiting pool. 

 
12 Version Date 5/9/18 (b) 
 
2. Process of consent: This study will be conducted in accordance with the provisions of 21 
Code of Federal Regulations (CFR) Part 50. In accordance with relevant regulations, an 
informed consent agreement explaining the procedures and requirements of the study, 
together with any potential hazards/risks will be read and/or explained to each subject.  
Each subject will sign such an informed consent form. In this consent, the study will be 
adequately described in addition to all procedures subjects will need to do, how their 
confidentiality will be maintained. The subject will be assured of the freedom to withdraw 
from participation in the study at any time. The consent process for each subject who signs 
informed consent will be documented in the subject’s source (e.g., research file, research 
progress note) and will include the title of the study, that the consent was discussed with an 
opportunity for questions and answers, how the subject demonstrated comprehension, that 
the consent was signed prior to the first study procedure, and that the subject received a 
signed copy of the consent. 
3. Subject capacity: Subjects will only be considered for this study if they are capable of 
understanding the study, its burdens and risks, their responsibilities, and giving informed 
consent. Subject capacity will be determined at the time of consent by the person obtaining 
consent. 
4. Costs to the subject: There is no cost to participate in this research study except that subjects 
will be expected to provide their own transportation and/or accommodation to and from 
the study site for study visits. 
 
 
Payment for participation:  Subjects will receive $30.00 for each completed study visit. There will be 
a total of four paid visits. Payment will be received at the end of each visit. This payment may be in 
the form of a pre-paid debit card, gift card or check at our discretion.  Subjects will not be paid for 
visits that they do not complete. Each subject will be paid up to a total of $120.00.