Use of a Novel, Objective Optokinetic Contrast Device to Determine Scotopic Range Visual Function and Discriminate Between Patients With and Without Glaucoma
Phase: NA
Conditions: Glaucoma
Sponsor: Benjamin Frankfort, MD, PhD

 
 
 
 
Use of a Novel, Objective Optokinetic Contrast Device to Determine 
Scotopic Range Visual Function and Discriminate between Patients with 
and Without Glaucoma 
 
NCT02014597 
 
 
 
Document Date: March 11, 2020 

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Institutional Review Board for Baylor College of Medicine and Affiliated
Hospitals
 
Protocol Number:    H-30109
Status:                        Approved
Initial Submit Date:  4/9/2012
Approval Period:       3/11/2020 - 3/10/2021
 
Section Aa:  Title & PI
A1.  Main Title
     USE OF A NOVEL, OBJECTIVE OPTOKINETIC CONTRAST DEVICE TO DETERMINE SCOTOPIC RANGE VISUAL
FUNCTION AND DISCRIMINATE BETWEEN PATIENTS WITH AND WITHOUT GLAUCOMA
A2.  Principal Investigator
 
     Name:  
BENJAMIN FRANKFORT
Phone:  
713-798-5952
     Id:  
038374
Fax:  
713-798-4364
     Department:  OPHTHALMOLOGY
Email:   
frankfor@bcm.tmc.edu
     Center:  
Mail Stn:  NC205
A3.  Administrative Contact
 
     Name:
APRIL M LEGER
Phone:  
713-798-4123
     Id:  
044552
Fax:  
     
Email:   
aharp@bcm.tmc.edu
     
Mail Stn:  BCM633
A3a.  Financial Conflict of Interest
Does any member of study personnel (Investigator (including investigator’s spouse and/or dependent children)) that are
involved in the design, conduct, or reporting of the research have a Significant Financial Interest (SFI) that would reasonably
appear to be affected by the research for which funding is sought and/or associated with an entity/business that would
reasonably appear to be affected by the research?
          No
 
Section Ab:  General Information    
A4.  Co-Investigators
 
     Name:  
SILVIA ORENGO-NANIA
Phone:  
713-798-5055
Id:  
011996
Fax:  
713-798-4802
Department:  OPHTHALMOLOGY
Email:   
silviao@bcm.tmc.edu
Center:  
Mail Stn:  NC205
 
     Name:  
SAMUEL WU
Phone:  
713-798-5966
Id:  
017234
Fax:  
713-798-6457
Department:  OPHTHALMOLOGY
Email:   
swu@bcm.tmc.edu
Center:  
Mail Stn:  NC205
 
     Name:  
PETER CHANG
Phone:  
713-798-9165
Id:  
130181
Fax:  
Department:  OPHTHALMOLOGY
Email:   
ptchang@bcm.tmc.edu
Center:  
Mail Stn:  NC205
 
     Name:  
MARGARET OLFSON
Phone:  
713-798-4037

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Id:  
145118
Fax:  
Department:  OPHTHALMOLOGY
Email:   
molfson@bcm.tmc.edu
Center:  
Mail Stn:  BCM633
 
     Name:  
ROBERT SEILHEIMER
Phone:  
713-798-4600
Id:  
168183
Fax:  
Department:  STUDENT AFFAIRS
Email:   
seilheim@bcm.tmc.edu
Center:  
Mail Stn:  BCM368
 
     Name:  
MITCHELL WEIKERT
Phone:  
713-798-4766
Id:  
691429
Fax:  
Department:  OPHTHALMOLOGY
Email:   
mweikert@bcm.tmc.edu
Center:  
Mail Stn:  
 
     Name:  
YVONNE CHU
Phone:  
713-798-5077
Id:  
691699
Fax:  
Department:  OPHTHALMOLOGY
Email:   
ychu@bcm.tmc.edu
Center:  
Mail Stn:  NC205
 
     Name:  
CAMERON COWAN
Phone:  
+41 61 69 78681
Id:  
Non-Baylor
Fax:  
+41 61 69 73976
Institution:  
Friedrich Miescher Institute for Biomedical Research
Email:   
Cameron.Cowan@gmail.com
Address:  
Maulbeerstrasse 66 P.O. Box 3775 4002 Basel
A5.  Funding Source:
     Baylor College of Medicine (Internal Funding Only)
A6a.  Institution(s) where work will be performed:
     Baylor College of Medicine -- Alkek Eye Center
A6b.  Research conducted outside of the United States:
     
Country:  
Facility/Institution:  
Contact/Investigator:  
Phone Number:  
If documentation of assurances has not been sent to the Office of Research, please explain:
A7.  Research Category:
     
A8. Therapeutic Intent
Does this trial have therapeutic intent?
     No
 
A9. ClinicalTrails.gov Registration
Does this protocol/trial require registration on ClinicalTrials.gov due to it: meeting the definition of an Applicable Clinical Trial,
being required under the terms and conditions of an award, or being proposed to be published in ICMJE journals?
     Yes
 
Who will be responsible for registering and maintaining the registration of this Applicable Clinical Trial?
     The BCM PI will register the trial because either:
     -   the trial is BCM PI-initiated,
     -   BCM is the lead site of this multicenter trial, or,
     -   the industry sponsor has instructed the BCM PI to register the trial, or,
     -   registration of this trail is required as a term and condition of the reward by the funding agency.
 

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ClinicalTrials.gov Identifier:
     NCT02014597
 
Section B:  Exempt Request
B.  Exempt From IRB Review
     Not Applicable
 
Section C:  Background Information
     Glaucoma is the second leading cause of blindness in the world, and estimates for 2010 hold that there are approximately
60.5 million people with either open angle glaucoma (OAG) or angle closure glaucoma (ACG). OAG makes up about 75%
of disease and is the most common form encountered in the United States. In the U.S., OAG is a major cause of
progressive, irreversible blindness, affecting approximately 2.22 million adults, including 700,000 aged 80 or greater. As
the prevalence of OAG increases with age and the overall United States population is becoming older, the number of
United States citizens expected to have OAG in 2020 is approximately 3.36 million. There are many known risk factors for
glaucoma, but both disease onset and progression are most strongly associated with elevated intraocular pressure (IOP).
Accordingly, all accepted treatment strategies center on IOP reduction, and this approach can be a successful
management strategy even in cases where the IOP is initially measured in the normal range.
All forms of glaucoma lead to a common phenotypic endpoint of optic nerve cupping (thinning of the neuroretinal rim at the
optic nerve head) and progressive functional deficit as measured by psychophysical testing such as perimetry (also known
as visual field testing). Typical perimetric changes include an early and mild diffuse loss of retinal sensitivity and a later
denser focal loss of retinal sensitivity in classic patterns. Contrast sensitivity is also decreased in early glaucoma, and
there is evidence that it is decreased with ocular hypertension (elevated IOP without glaucomatous optic nerve changes)
as well. Despite these mild changes in retinal sensitivity, central visual acuity is typically spared in the early and even
moderate to advanced stages of the disease. Therefore, the early diagnosis of glaucoma is often circumstantial, based on
suspicious appearance of the optic nerve head, and many patients present to an ophthalmologist with advanced disease.
Furthermore, perimetry, or visual field testing, is subjective in nature and dependent on patient motor responses (such as
clicking a button) in response to specific visual stimuli. In many patients, due to inattention, poor motor coordination, or the
length of the test (typically 5-7 minutes of full attention per eye), the reliable and accurate assessment of visual function by
perimetry is difficult. 
Human disease is characterized by a loss of retinal ganglion cell (RGC) axons and their associated cell bodies in both
human cadaveric and animal studies. Currently, it is not known if the observed decrease in retinal sensitivity is caused by
RGC death, dysfunction, or both. Animal studies using both genetic and inducible models are similarly inconclusive and
have largely focused on anatomic changes rather than functional studies. Details about RGC dysfunction in glaucoma are
critical as RGCs represent the final cell type in the retinal signaling network, integrating the various signals from rod and
cone photoreceptors via various interneurons including amacrine, horizontal, and bipolar cells. The distinct signaling
pathways active under light (photopic) and dark (scotopic) conditions are well-understood. Cones dominate the photopic
pathway and signal via cone bipolar cells directly to RGCs. Rods dominate the scotopic pathway and signal via rod bipolar
cells to amacrine cells, which indirectly relay the rod-mediated signal to RGCs through cone bipolar cells. There is
crosstalk between the two pathways at the level of both amacrine cells and RGCs. Thus, when RGCs are damaged by
glaucomatous disease, it is very likely that both cone and rod information is lost.
Ophthalmologists are therefore presented with several challenges: increasing disease burden, the lack of objective
assessments of visual function, and the need for improved early disease detection. We have developed a new device
which has the potential to help meet all of these significant challenges. This device provides a rapid, automated, non-
invasive and purely objective assessment of visual function (specifically contrast sensitivity) under both cone- and rod-
dominated conditions. It is potentially able to not only track glaucoma progression over time, but also to detect glaucoma in
its very earliest stages. Finally, it is portable, easy to use, and inexpensive. This proposal aims to optimize the testing
parameters of this new device, and to determine contrast sensitivity levels under both scotopic and photopic conditions in
a normal population and compare this population to patients at risk for glaucoma or with glaucoma as part of a pilot study.
Human studies of glaucoma have focused almost exclusively on photopic (cone) pathways and only very few published
manuscripts address rod-mediated scotopic retinal function in patients with glaucoma. In animal models of glaucoma,
however, several groups have reported abnormalities in amacrine cell numbers. We have studied single cell
electrophysiology in a mouse model for elevated IOP and acute glaucoma. RGC and amacrine cell light sensitivity are both
decreased within 1-2 weeks of elevation of IOP and RGC death occurs similarly to that seen in other animal models. Since
amacrine cells are the critical relay station of rod cell signaling, these findings support the hypothesis that rod function is
also abnormal in glaucoma. Importantly, these early abnormalities in light sensitivity precede overt evidence of RGC
structural damage. In human glaucoma, central visual acuity is often preserved in even advanced disease, but many
patients have decreased contrast sensitivity thresholds very early in the disease course. This reduction may provide an
opportunity to identify patients with early disease. We hypothesize that a similar process occurs in both experimental and
human glaucoma, and that patients will display decreased retinal sensitivity prior to large-scale damage to RGCs.
Furthermore, we believe that it is possible to detect and measure these early changes in contrast sensitivity in patients at

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risk for glaucoma or with very early disease.
The optokinetic reflex (OKR) requires both visual function and cortical function. When presented with a drifting image of
sinusoidally modulated gratings, the eye will reflexively track the stimulus (slow phase). At a certain point, the eyes will
rapidly re-fixate in the opposite direction (fast phase) and then begin to track again. By adjusting the characteristics of the
drifting image, contrast sensitivity thresholds can be measured. Others have attempted to use the OKR under photopic
conditions to assess contrast sensitivity thresholds differences between normal patients and patients with glaucoma.
These data suggest that it is possible to use contrast sensitivity to distinguish between these groups, but the investigators
were restricted by the technologies available at the time and the cumbersome techniques used to track and record OKR-
induced eye movements. Our new device takes advantage of a high resolution monitor, real time infrared light eye
tracking, and intelligent software that adjusts the monitor-presented sinusoidally modulated gratings in response to patient
eye movements to rapidly determine contrast sensitivity levels in 3-5 minutes per eye.
 
Section D:  Purpose and Objectives
     
This proposal has the potential to define a novel and clinically relevant testing strategy for the diagnosis and monitoring of
glaucoma. The strategy is based on the assessment of contrast sensitivity and is objective, rapid, automated, and simple.
It has potential utility as a testing strategy to establish a diagnosis of glaucoma very early in the disease process, as well
as an alternative testing strategy for those unable to perform standard perimetry. This device can potentially be used to
uncover some of the most basic concepts of glaucoma disease by assessing visual function in dark-adapted patients, and
to integrate these findings into a comprehensive testing strategy. Furthermore, this device will allow us to explore the limits
of human scotopic contrast detection - a topic that has not been previously addressed. Lastly, development of this device
as an objective and automated assessment of visual function has many potential benefits beyond the initial scope of this
protocol, including: detection of visual function in pre-verbal children, detection of visual function in poorer functioning
adults, detection of visual function in stroke victims, and detection of visual function in paralyzed individuals. These just
scratch the surface and many situations where the device is useful can easily be imagined.
 
Section E:  Protocol Risks/Subjects
E1.  Risk Category
     Category 1: Research not involving greater than minimum risk.
E2.  Subjects
Gender:
     Both
Age:
     Adult (18-64 yrs), Geriatric (65+ yrs)
Ethnicity:
     All Ethnicities
Primary Language:
     English
Groups to be recruited will include:
     Both patients and healthy, non-patient, normals
Which if any of the following vulnerable populations will be recruited as subjects?
     Employees or lab personnel, Students
Vulnerable populations require special protections.  How will you obtain informed consent, protect subject confidentiality, and
prevent undue coercion?
     
In some cases, for the first study of the protocol, lab or clinic staff may be asked to participate or request to participate. All
participation will be completely voluntary and there will be no penalties for not participating. There will be no coercion at
any point and there will be no benefit, real or implied, in participation.
In some cases, medical or graduate students may be asked to participate or request to participate. All participation will be
completely voluntary and there will be no penalties for not participating. There will be no coercion at any point and there
will be no benefit, real or implied, in participation.
E3.  Pregnant woman/fetus
Will pregnant women and/or fetuses (as described in 45 CFR 46 Subpart B) be enrolled in the research?
     No

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E4.  Neonates
Will neonates of uncertain viability or nonviable neonates (as described in 45 CFR 46 Subpart B) be enrolled in the research?
     No
E5.  Children
Will children be enrolled in the research?
     No
 
Section F:  Design/Procedure
F1.  Design
Select one category that most adequately describes your research:
     i) Device, Phase I, Single Center
Discuss the research design including but not limited to such issues as: probability of group assignment, potential for subject
to be randomized to placebo group, use of control subjects, etc.
     
This protocol is divided into 2 studies. Study 1 involves the optimization of the device parameters. Study 1 will test adult
subjects with no history of ocular disease (Study 1A) to assess the limits of human contrast sensitivity and subjects with
definite glaucoma (Study 1B) by gathering preliminary data for comparison. These two pilot sub-studies intend to provide
rapid data in regard to the device testing results to support the study hypothesis. This strategy will help rule out false
negatives and false positives so that any adjustments can be made prior to the start of Study 2 for longitudinal data
collection. Study 2 involves determination of baseline population parameters for an older population more likely to be age-
matched with patients with glaucoma, as well as performance of patients with various levels of glaucoma severity.
Enrollment of participants in Study 1B will begin after the first 5 participants have been enrolled and tested in Study 1A.
Study 2 will begin after Study 1A and B are complete.
Study 1: 20 adult subjects with no history of ocular disease and 20 adults subjects with definite glaucoma will be recruited
to assist with optimization of device parameters. Study 1A: The individuals will not be patients of the co-investigators but
rather volunteers who are recruited by word of mouth (co-employees, residents, research staff, etc.) and are willing to
volunteer their time to assist in the development of the project. No coercion or implied benefits will be applied to recruit
participants (see section E2). Volunteers can be of any age >18, male or female, and must be of self-reported excellent
ocular health. Best spectacle corrected visual acuity of 20/40 or better is required (verified by Snellen acuity testing on the
day of participation) and the participant must have no reported history of glaucoma, retinal disease, amblyopia, ocular
trauma, or ocular surgery of any kind with the exception of refractive surgery (LASIK, PRK, or equivalent). Study 1B:
These individuals will be recruited from the Alkek Eye Center patient population with confirmed diagnosis of glaucoma and
of any age > 18.
Study 2: Potential subjects will be recruited from the Alkek Eye Center of the Department of Ophthalmology at Baylor
College of Medicine and their families we will recruit 100 patients for this study in the following distribution:
1) 20 normal controls age 50 or older
2) 20 patients age 50 or older with ocular hypertension 
3) 20 patients age 50 or older who are glaucoma suspects
4) 20 patients age 50 or older with early to moderate glaucoma 
5) 20 patients age 50 or older with moderate to advanced glaucoma
Inclusion Criteria:
     Normals for Study 1
1. Male or Female
2. age 18 or older
3. Corrected visual acuity 20/40 or better in both eyes.
Normal Controls for Study 2
1. Male or Female
2. age 50 or older

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3. IOP 21 or less in both eyes
4. Corrected visual acuity 20/40 or better in both eyes. 
Subjects with ocular hypertension 
1. Male or Female
2. Age 50 or older
3. Defined as IOP> 21 without medication on two or more clinic visits in one or both eyes 
4. Corrected visual acuity 20/40 or better
5. Normal optic nerves
6. Normal automated perimetry in both eyes
Subjects who are glaucoma suspects
1. Male or Female
2. Age 50 or over
3. Increased optic nerve cupping in one or both eyes regardless of IOP
4. Corrected visual acuity 20/40 or better
5. Normal automated perimetry in both eyes
Subjects with early to moderate glaucoma
1. Male or female
2. Age 50 or over
3. Increased optic nerve cupping regardless of IOP in one or both eyes
4. Corrected visual acuity 20/40 or better in both eyes
5. Early to moderate perimetric changes defined as a mean deviation (MD) no less than -7.5 and a pattern standard
deviation (PSD) no greater than +7.5 in the worse eye.
Subjects with moderate to advanced glaucoma
1. Male of Female
2. Age 50 or older
3. Increased optic nerve cupping regardless of IOP in one or both eyes
4. Grossly abnormal automated perimetry (MD less than -7.5 or PSD greater than +7.5 in the worse eye)
5. Best-corrected visual acuity of 20/40 or better in both eyes
Exclusion Criteria:
     Normal Controls:
1. glaucoma or glaucoma suspicion in either eye
2. IOP > 21 in either eye
3. History of use of IOP-reducing drops in either eye except temporarily following cataract extraction
4. History of any ocular surgery except cataract extraction or refactive surgery (LASIK, ORK, or equivalent) in either eye
5. Retinal disease in either eye
6. Abnormal measured automated perimetry in either eye

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7. Abnormal measured contrast sensitivity in either eye
F2.  Procedure
     The protocol is divided into two studies that will have two separate consent forms (Study 1A and B, and Study 2). 
All participants requiring spectacle correction will will use their own glasses or contact lenses or a pair of provided trial
glasses (if needed) during the research study.
Study 1: Subjects participating in this portion of the study will attend one single visit: 
1) Informed consent will be obtained and inclusion/exclusion criteria will be confirmed. Demographic information, ocular
history, refraction, and visual acuity information will be collected for all patients. Additional clinical data will also be
collected for Study 1B participants only. Information to be collected will include name, date of birth, ethnicity, gender, ocular
history (surgery, etc), type of glaucoma (study 1B), current visual acuity, refraction, central corneal thickness (study 1B),
intraocular pressure (study 1B), recent slit lamp exam including lens status (study 1B), recent dilated exam including optic
nerve appearance (study 1B), and recent automated perimetry results (Humphrey visual field, study 1B)
2) Snellen visual acuity will be measured while wearing current spectacle correction to ensure acuity of 20/40 or better.
The current spectacle correction (refraction) and acuity will be recorded.
3) OKR-based contrast testing will be performed with the OCD - optokinetic contrast device (the device in study with this
protocol). Subjects will be shown a brief demonstration of the OCD under infrared light (to begin dark adaptation) to
familiarize themselves with the device and the expected testing strategy. 
4) Subjects will then be dark adapted for 20-30 minutes. During this time they will be sitting in a darkened room. If the
room is not dark enough a loose blindfold may be used. Music options will be available to help pass the time and ease
potential discomfort. 
5) After 20-30 minutes, the blindfold will be removed (if used) and patient will have monocular dark-adapted (scotopic)
testing done with the OCD, left eye followed by right eye. The non-tested eye may be covered during testing. After
scotopic testing, the light of the OCD will be increased and light-adapted (photopic) testing will be performed in the same
manner.
6) Debriefing. Subjective assessments of the testing modality and dark adaptation process will be collected.
This visit should take approximately 60 minutes to complete.
*************************
Study 2:
Study subjects participating in this portion of the study will require two study visits. 
Potential participants will be approached by the PI to ask if they are willing to participate in this study. If the subject agrees
to participate, during their next scheduled clinic visit, the PI will also do a slit lamp examination including lens status using
the AREDS 2008 Clinical Lens Opacity Grading Standards in addition to their standard of care clinic eye visit. The slit lamp
examination including lens status using the AREDS 2008 Clinical Lens Opacity Grading Standards is the only research
related activity in this clinic visit. Potential participants who are the "normals" for Study 2 will be recruited from one of the
co-investigator's clinic who is their treating physician. If interested, their physician (co-investigator) will contact the
research coordinator to meet or call the patient and explain the study. If he/she agrees to participate, the PI will do a slit
lamp examination at their next scheduled visit in the same manner as the other Study 2 participants, except the central
corneal thickness will also be determined by ultrasonic pachymetry (standard testing for patients with glaucoma but not
normal controls). Data from these clinic visits will be used as baseline information for the study. The baseline clinical and
demographic data to be collected in the study will be:
1. Date of Birth 2. Ethnicity 3. Gender 4. Ocular History (surgery, etc) 5. Type of Glaucoma 6. Current visual acuity 7.
Refraction 8. Central corneal thickness 9. Intraocular Pressure 10. Slit lamp examination including lens status by methods
above 11. Dilated examination including optic nerve appearance 12. Recent automated perimetery results (Humphrey
visual field)
Research Study Visit 1 (within 2 months of clinic visit from which clinical data is obtained):
1) Humphrey standard automated perimetry (visual field testing). This is a form of static perimetry used to assess retinal
function and sensitivity. It is a commonly used photopic testing modality for the diagnosis and status of glaucoma and used
frequently throughout ophthalmology and many ophthalmologic clinical studies. We hypothesize that there will be
similarities in performance between Humphrey automated perimetry and OKR testing which will help validate our testing
strategy. For patients with glaucoma, for whom visual field testing is frequently performed, this test will not be performed if
a high-quality visual field test has been obtained within the last 6 months. For such patients, the visual field test from the

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clinical record will be used in the study.
2) OKR-based contrast testing will be performed with the OCD - optokinetic contrast device (the device in study with this
protocol). Subjects will be shown a brief demonstration of the OCD under infrared light (to begin dark adaptation) to
familiarize themselves with the device and the expected testing strategy. 
3) Subjects will then be dark adapted for 20-30 minutes. During this time they may be blindfolded (depending on darkness
of the room) and sitting in a dark room. Music options will be available to help pass the time and ease potential discomfort. 
4) After 20-30 minutes, the blindfold will be removed (if used) and patient will have monocular dark-adapted (scotopic)
testing done with the OCD, left eye followed by right eye. The non-tested eye may be covered during testing. 
5) After scotopic testing, the light of the OCD will be increased and light-adapted (photopic) testing will be performed in the
same manner.
This visit should take approximately 90 minutes to complete.
Second Research Visit (approximately 1 month after the first research visit):
1) Pelli-Robson Contrast Sensitivity Testing. This is a form of stationary central vision contrast sensitivity that is a
commonly used testing modality for photopic contrast in many ophthalmologic clinical studies. We hypothesize that there
will be similarities in contrast performance between Pelli-Robson and OKR testing which will help validate our testing
strategy.
2) OKR-based contrast testing. This will be performed as in the second visit described above except that the testing order
will be the right eye first, followed by the left eye.
3) Debriefing. Subjective assessments of the testing modality and dark adaptation process will be collected.
This visit should take approximately 90 minutes to complete.
For those participating in Study 2, participants will be asked if they will allow the study staff to review their medical records
to track clinical outcomes for 5 years. Participants will be asked to allow review of their medical records related to their
developing or not developing glaucoma or other eye conditions to collect longitudinal data. This is an optional portion of
the test for which they can opt out.
The following information will be re-reviewed: 1. Date of Birth 2. Ethnicity 3. Gender 4. Ocular History (surgery, etc) 5. Type
of Glaucoma 6. Visual acuity 7. Refraction 8. Central corneal thickness 9. Intraocular Pressure 10. Slit lamp examinations
including lens status 11. Dilated examinations including optic nerve appearance 12. Automated perimetery results
(Humphrey visual field)
 
Section G:  Sample Size/Data Analysis
G1.  Sample Size
How many subjects (or specimens, or charts) will be used in this study?
     Local: 140              Worldwide: 140
Please indicate why you chose the sample size proposed:
     
Study 1: 20 healthy non-patients and 20 patients with definite glaucoma will offer a very large sample size to optimize
testing parameters and provide information about scotopic and photopic range constrast sensitivity in healthy adults.
Because of the speed of testing, a moderate sample size is desirable. It is difficult to predict the sample size required since
this is a new device and the range of results are unknown. In smaller studies in the laboratory, similar contrast ranges were
seen among most test subjects (all of whom were believed to be normal) so a very large normative database is unlikely to
be required. As a point of reference, previous studies of optokinetic-based contrast have showed a rather tight range of
human performance and have published peer-reviewed studies with fewer than 10 participants. 5 healthy non-patients will
be enrolled before the 15 remaining healthy non-patients and the 20 glaucoma patients are enrolled to ensure appropriate
procedures are used and to identify any issues yet to be identified. Study 1 subjects may be retested if technical problems
are identified with the device.
20 normal patients and 20 participants with definite glaucoma should provide enough of a baseline for the 4 disease
groups as the number of participants in each of the disease groups is of relatively large size.
Study 2: 20 participants will be enrolled in each of the five groups described in the Section F2 Procedures section (N=100).
If the study team is able to establish intrasubject reliability of testing, the number of subjects needed in Study 2 may be
decreased with a future amendment submission.
G2.  Data Analysis

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Provide a description of your plan for data analysis. State the types of comparisons you plan (e.g. comparison of means,
comparison of proportions, regressions, analysis of variance). Which is the PRIMARY comparison/analysis? How will the
analyses proposed relate to the primary purposes of your study?
     
Study 1 and 2: Statistical comparison of the study groups will be performed using a combination of pairwise and
multivariate analyses. A sample size estimate is not possible at this time as the ranges of contrast sensitivity are not yet
determined due to uncertainty of the testing parameters. The normative database will be critical for the design of larger
scale future studies.
The primary expected comparisons are as follows:
Intra-patient:
1) Comparison of scotopic constrast between the two eyes
2) Comparison of photopic contrast between the two eyes
3) Comparison of scotopic to photopic contrast within each eye
4) Comparison of intraocular scotopic to photopic contrast ratio (3 above) between the two eyes
5) Comparison of 1-4 to automated perimetry testing (Study 2 only)
6) Comparison of 1-4 to Pelli-Robson testing (Study 2 only)
Interpatient:
Comparison of 1-6 above among all patients and groups.
For subjects in Study 2, longitudinal data will be collected for 5 years after participation to track clinical progression of
glaucoma where present.
Interim analysis will be performed after the first 5 patients of Study 1A have been enrolled to ensure that the device
hardware and software are properly functioning.
Interim analysis will be performed after the first 10 patients for both Study 1A and Study 1B have been enrolled to ensure
that the device hardware and software are properly functioning .
Interim analysis will be performed after the completion of Study 1 to determine if the study sample size of Study 2 is
appropriate.
 
Section H:  Potential Risks/Discomforts
H1.  Potential Risks/Discomforts
Describe and assess any potential risks/discomforts; (physical, psychological, social, legal, or other) and assess the likelihood
and seriousness of such risks:
     
Only minimal risk is present as there is a small chance of loss of confidentiality as with any study. Study personnel attempt
to minimize this risk.
The only contact the participant has with the device is via the chin rest and forehead rest, which are standard equipment
purchased from an ophthalmic device supplier. There is no other contact with the device required. 
There is no risk associated with the small infrared (IR) light used in this protocol, A dim LED-generated infrared (IR) light
source is used during examination. The amount of light, power and thermal levels emitted from the device used in this
study is less than international standards (IEC 60825-1) set for this type of light (IR exempt).
The use of a blindfold during dark-adaptation is potentially uncomfortable. This will be positioned very gently and the
ambient light dark as well with music of the participant's choice playing to minimize discomfort. It may be possible to use a
patch instead of a blindfold for participants who are particularly uncomfortable, but this will slow the process down slightly.
H2.  Data and safety monitoring plan
     Do the study activities impart greater than minimal risk to subjects?
          No
H3.  Coordination of information among sites for multi-site research
Is the BCM Principal Investigator acting as the SPONSOR-INVESTIGATOR for this multi-site research?
          No or Not Applicable

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Is BCM the COORDINATING CENTER for this multi-site research?
          No or Not Applicable
 
Section I:  Potential Benefits
Describe potential benefit(s) to be gained by the individual subject as a result of participating in the planned work.
     There is no direct benefit to subjects for their participation in the study.
Describe potential benefit(s) to society of the planned work.
     
As the OCD is a fully automated and objective device, it may provide a significant improvement in our ability to monitor and
diagnose glaucoma. It is also likely to be very helpful in the monitoring of patients with retinal disease, especially in
situations where visual acuity is diminished, although this is not being directly assesed in the current proposal. It also may
provide an opportunity to assess visual performance in various individuals who are unable to effectively communicate with
examiners (children, extreme elderly, stroke victims, ICU patients), although this is not being directly assessed in the
current proposal.
Do anticipated benefits outweigh potential risks? Discuss the risk-to-benefit ratio.
     There is huge potential benefit with no appreciable risk.
 
Section J:  Consent Procedures
J1.  Waiver of Consent
Will any portion of this research require a waiver of consent and authorization?
     No
 
J1a.  Waiver of requirement for written documentation of Consent
Will this research require a waiver of the requirement for written documentation of informed consent?
     No
J2.  Consent Procedures
Who will recruit subjects for this study?
     PI
PI's staff
Describe how research population will be identified, recruitment procedures, any waiting period between informing the
prospective participant and obtaining consent, steps taken to minimize the possibility of coercion or undue influence and
consent procedures in detail.
     
Study 1: Participants will be recruited from volunteers among the co-PIs clinical and research staff, associates, etc. without
any coercion, according to the inclusion criteria previously delineated. There will be no professional benefit, real or implied,
to participation in the study and this will be made very clear. Once identified, informed consent will be obtained. The
minimal risk associated with maintaining a research file and infrared light used will be discussed. The minimal discomfort
associated with dark-adaptation (sitting in dark for 20-30 minutes) will be addressed. The non-contact nature of the device
will be explained. Subjects may be retested if technical problems occur with the device or software.
Study 2: Patients will be identified by the PI and the co-PIs and recruited to the study. It will be made clear that there is no
financial or medical benefit to participation in the study, real or implied. If the patient agrees to participate then they will be
scheduled for the initial visit which will include informed consent. The minimal risk associated with maintaining a research
file and infrared light used will be discussed. The minimal discomfort associated with dark-adaptation (sitting in dark for 20-
30 minutes) will be addressed. The non-contact nature of the device will be explained.
Are foreign language consent forms required for this protocol?
     No
J3.  Privacy and Intrusiveness
Will the research involve observation or intrusion in situations where the subjects would normally have an expectation of
privacy?
     No
J4.  Children
Will children be enrolled in the research?
     No

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J5.  Neonates
Will non-viable neonates or neonates of uncertain viability be involved in research?
     No
J6.  Consent Capacity - Adults who lack capacity
Will Adult subjects who lack the capacity to give informed consent be enrolled in the research?
     No
J7.  Prisoners
Will Prisoners be enrolled in the research?
     No
 
Section K:  Research Related Health Information and Confidentiality
Will research data include identifiable subject information?
     Yes
Information from health records such as diagnoses, progress notes, medications, lab or radiology findings, etc.
     Yes
Specific information concerning alcohol abuse:
     No
Specific information concerning drug abuse:
     No
Specific information concerning sickle cell anemia:
     No
Specific information concerning HIV:
     No
Specific information concerning psychiatry notes:
     No
Demographic information (name, D.O.B., age, gender, race, etc.):
     Yes
Full Social Security #:
     No
Partial Social Security # (Last four digits):
     No
Billing or financial records:
     No
Photographs, videotapes, and/or audiotapes of you:
     No
Other:
     No
At what institution will the physical research data be kept?
     Physical PHI data will be kept at Baylor College of Medicine.
How will such physical research data be secured?
     Physical PHI data will be kept in locked cabinets at all times in a Research suite that is closely monitored during business
hours and locked at all other times.
At what institution will the electronic research data be kept?
     Electronic PHI data will be kept at Baylor College of Medicine.
Such electronic research data will be secured via BCM IT Services- provided secured network storage of electronic research
data (Non-Portable devices only):

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     Yes
Such electronic research data will be secured via Other:
     
Yes, (describe below):
Electronic PHI data will be secured via password-protected files, encrypted devices, secure servers identified by
institution/owner, and restricted shared drive permissions
Will there be anyone besides the PI, the study staff, the IRB and the sponsor, who will have access to identifiable research
data?
     No
Please describe the methods of transmission of any research data (including PHI, sensitive, and non-sensitive data) to
sponsors and/or collaborators.
     Transmission of PHI to collaborators will be via secure/encrypted e-mail and SSL encrypted web portals.
 
Will you obtain a Certificate of Confidentiality for this study?
     No
Please further discuss any potential confidentiality issues related to this study.
     We do not forsee any potential confidentiality issues related to this study.
 
Section L:  Cost/Payment
Delineate clinical procedures from research procedures. Will subject's insurance (or subject) be responsible for research
related costs? If so state for which items subject's insurance (or subject) will be responsible (surgery, device, drugs, etc). If
appropriate, discuss the availability of financial counseling.
     
Participants will not be charged for any research related activities. Participants and/or their insurance carrier will be
responsible for the Study 2 clinic visit as this is standard of care and not being done for research purposes. All other
activities are research related and will not be charged to the participant.
If subjects will be paid (money, gift certificates, coupons, etc.) to participate in this research project, please note the total
dollar amount (or dollar value amount) and distribution plan (one payment, pro-rated payment, paid upon completion, etc) of
the payment.
Dollar Amount:
     30
Distribution Plan:
     Participants in Study 1B will receive a total parking disbursement of up to $15 for the single visit. Participants in Study 2 of
the protocol will receive a total parking disbursement of up to $30 for up to 2 visits.
 
Section M:  Genetics
How would you classify your genetic study?
     
Discuss the potential for psychological, social, and/or physical harm subsequent to participation in this research. Please
discuss, considering the following areas: risks to privacy, confidentiality, insurability, employability, immigration status,
paternity status, educational opportunities, or social stigma.
     
Will subjects be offered any type of genetic education or counseling, and if so, who will provide the education or counseling
and under what conditions will it be provided? If there is the possibility that a family's pedigree will be presented or published,
please describe how you will protect family member's confidentiality?
     
 
Section N:  Sample Collection
None
 
Section O:  Drug Studies
Does the research involve the use of ANY drug* or biologic? (*A drug is defined as any substance that is used to elicit a

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pharmacologic or physiologic response whether it is for treatment or diagnostic purposes)
     No
Does the research involve the use of ANY gene transfer agent for human gene transfer research?
     No
O1.  Current Drugs
 
Is this study placebo-controlled?
     No
Will the research involve a radioactive drug?
     No
 
Section P:  Device Studies
     Does this research study involve the use of ANY device?
          Yes
Device 1:  Optokinetic Contrast Detector (OCD)
Name of Device (Including HDE # if applicable): 
  Optokinetic Contrast Detector (OCD)
 
FDA intended use of the device in use 
  Not applicable at this time
 
Actual use of the device in this clinical trial 
  Objective determination of human contrast sensitivity
 
Manufacturer of the device :
  One of a kind, conceived and constructed at BCM
 
FDA number for the device (IDE for investigational device, HDE #, or 510K #) : 
  Not applicable
 
Method of proof of the validity of this IDE, HDE, or 510K (check all that apply):
 
Sponsor Investigator
 
Is the BCM investigator serving as sponsor/investigator for this study?
  No
 
Device Risk
 
This is a non-significant risk device and will fulfill all of the abbreviated requirements of an IDE found in 21 CFR 812.2(b)
Please enter a brief explanation of why the device is not a significant risk device below:
  This device qualifies as a non-significant device for several reasons in accordance with 812.2: A) It is not a significant risk
device. Study participants will only have contact with a chin and forehead rest and eye movements recorded with a camera
in response to a stimulus on a screen about 1 meter away. The device consists of the following: A computer monitor (old
CRT), a camera to observe the eye, an infrared (IR) lighting source, a chin rest (from an old ophthalmic slit lamp), a screen
to block one of the eyes, and an adjustable table (from an ophthalmic retailer). This IR source is a series of readily available
low intensity IR LEDs that are mounted together and powered in unison. A commercially available ground glass diffuser sits
in front of the LEDs to spread the light. There is no opportunity for pain, discomfort, or damage to the eyes in any way. The
device is investigational and will not be used to make a clinical diagnosis. It is one of a kind and not currently meant for
distribution. There is no more than minimal risk to subject. B) The device will be labeling in accordance with 812.5, stating:
"CAUTION--Investigational device. Limited by Federal (or United States) law to investigational use." C) Informed consent
will state clearly that this is an investigational device only. D) Investigators will comply with the requirements of 812.46 with
respect to monitoring investigations and notify the IRB immediately of any unexpected finding or realization that the device
may represent more than minimal risk. E) The study coordinator will maintains the records required under 812.140(b) (4)
and (5) - The name and intended use of the device and the objectives of the investigation; - A brief explanation of why the
device is not a significant risk device: - The name and address of each investigator: - The name and address of each IRB

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that has reviewed the investigation: - A statement of the extent to which the good manufacturing practice regulation in part
820 will be followed in manufacturing the device; and - Any other information required by FDA. - Records concerning
adverse device effects (whether anticipated or unanticipated) and complaints and will make the reports required under
812.150(b) (1) through (3) and (5) through (10); F) The study coordinator and investigators will ensure that participating
investigators maintain the records required by 812.140(a)(3)(i) and make the reports required under 812.150(a) (1), (2), (5),
and (7);
 
Control, storage, and use of the device
How does the PI plan to store, control, and use the device?
 
Storage, control and use under supervision of the Principal Investigator
 
Section Q:  Consent Form(s)
Study 1A and 1B
Study 2
 
Section R:  Advertisements
None