Clinical trial NCT03959176
Conditions: Intraocular Pressure
Keywords: Brimonidine Pupil Effects
Sponsor: Wake Forest University Health Sciences
Start date: 2019-07-20; Completion date: 2019-07-20
Enrollment: 13 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study will evaluate whether pre-treating patients with Brimonidine 0.2% before and/or after dilating the pupils will help to control the changes in intraocular pressure often seen when using dilating drops. The study will also evaluate the effects of different sequences of administering dilating drops along with Brimonidine on pupil size and reactivity.

Detailed description:
Intraocular pressure (IOP) can fluctuate due to various external factors such as exercise, medications, and eye movements. Although it is considered natural for IOP to fluctuate daily, prolonged increases in IOP can be harmful. Sustained elevated IOP has been linked to optic nerve damage and glaucoma. Mydriatic drops routinely given to dilate pupils in patients in need of an eye exam have been known to increase IOP. In practice, a combination of drugs are used to achieve pupil dilation needed for routine eye exams or in perioperative situations. The use of Tropicamide 1% and Phenylephrine 2.5% are known to be safe and effective options for dilating the pupils when used in conjunction with one another, but these drugs can increase IOP. Drugs such as Brimonidine, a selective alpha-2 agonist, are known to reduce IOP through several different methods. This study seeks to understand the effects of Brimonidine used along with Tropicamide and Phenylephrine to control IOP.

Arms: arm 1: The right eye will receive a sham drop followed by 1 drop of Tropicamide 1%/Phenylephrine 2.5% five minutes after the sham drop is administered. A one minute wait will occur followed by a second drop of Tropicamide 1%/Phenylephrine 2.5%.

The left eye will receive 2 drops of Brimonidine 0.2% followed by a five minute wait time. One drop of Tropicamide 1%/Phenylephrine 2.5% will then be administered followed by a one minute wait time. A second drop of Tropicamide 1%/Phenylephrine 2.5% will be administered. arm 2: The right eye will receive 1 drop of Tropicamide 1%/Phenylephrine 2.5% followed by a one minute wait. A second drop of Tropicamide 1%/Phenylephrine 2.5% will be administered followed by a 15 second wait after which a sham drop will be administered.

The left eye will receive 1 drop of Tropicamide 1%/Phenylephrine 2.5% followed by a one minute wait. A second drop of Tropicamide 1%/Phenylephrine 2.5% will then be administered followed by a 15 second wait after which 2 drops of Brimonidine will be administered.
Interventions: intervention 1: Brimonidine intervention 2: Tropicamide intervention 3: Phenylephrine Ophthalmic Product
Intervention descriptions: intervention 1: 2 drops administered once in the left eye in both study arms intervention 2: 1 drop administered at two different times points in both eyes in both study arms intervention 3: 1 drop administered at two different time points in both eyes in both study arms

Protocol documents:
Prot_SAP_001.pdf: 
Official Title: The Effect of Brimonidine on Intraocular Pressure When Dilating Routine 
Patients, Pressure Control and Pupil Effects 
 
NCT03959176 
 
IRB-Approved Date:  7/1/2019 
 
 


Study Title: The Effect of Brimonidine on Intraocular Pressure When Dilating Routine 
Patients, Pressure Control and Pupil Effects.  
 
Principle Investigator, Co-investigator(s): Keith Walter MD, Chaunhi Van MD, Ken 
Weinlander MD, Eva Kiehl, Richard Hesse, Eloise Joubert 
 
Sponsor or funding source: Wake Innovations 
 
Background, Rationale and Context 
 
Many biological parameters are dynamic and vary within a 24-hour cycle. Intraocular 
pressure (IOP) is one of these parameters. In addition to natural fluctuations, IOP can 
vary in relation to external factors such as exercise, medications, and eye movements [1]. 
Although patients experience daily IOP fluctuates, prolonged elevated IOP can be 
harmful. Sustained elevated IOP levels have been linked to optic nerve damage and 
diseases such as glaucoma. If IOP is not controlled, damage to the optic nerve can cause 
multiple disease states culminating in blindness. In patients with no disease, normal IOP 
ranges from 8-21 mm Hg, while glaucoma patients’ have range 20 – 50+ mm Hg. Due to 
the damage that elevated IOP can have, it is highly important for physicians to monitor 
IOP. 
 
Mydriatic eye drops that are routinely used to dilate pupils in patients presenting to 
ophthalmology clinics have also been shown to increase IOP [2]. Increased IOP has been 
seen with both parasympatholytic and sympathomimetic mydriatics [3-5].  In practice, a 
combination of tropicamide, an anticholinergic drug, and phenylephrine, an alpha-1-
adrenergic drug, is used to achieve the pupil dilation needed for routine eye exams or 
perioperative situations [6, 7]. The combination of tropicamide 1% and phenylephrine 
2.5% has been safe, effective and reliable in clinical use to adequately dilate the pupil for 
clinical examination and procedures [12]. However, these drugs have shown to increase 
IOP, and drugs such brimonidine, a selective alpha-2 agonist, have shown to reduce IOP 
[8, 9]. Brimonidine can lower IOP through a few methods. Chronic use of brimonidine 
acts through stimulating aqueous humor outflow, while using brimonidine in an acute 
setting will reduce IOP by reducing the amount of aqueous humor produce [10, 11].  
 
We propose to observe whether pre-treating patients with Brimonidine 0.2% 
(brimonidine) prior to pupil dilation and/or post-treating will be effective in controlling 
the fluctuations in IOP seen when using mydriatics. In addition to observing IOP, we will 
also observe the effects of how differing the sequence of administration of Tropicamide 
1%/Phenylephrine 2.5% combined (standard dilation drops) and brimonidine 
impacts pupil size and reactivity.  
 
Objectives 
 
Primary Objective:  To observe how differing the sequence of administration of  
Tropicamide 1%/Phenylephrine 2.5% and Brimonidine 0.2% (brimonidine 0.2%) 
influences intraocular pressure. 


• Hypothesis 1: The administration of Brimonidine 0.2% prior to 
Tropicamide 1%/Phenylephrine 2.5% will result in lower intraocular 
pressure rise than when administering Brimonidine 0.2% after initiating 
dilation with Tropicamide 1%/Phenylephrine 2.5%. 
• Hypothesis 2: The administration of both Brimonidine 0.2% and 
Tropicamide 1%/Phenylephrine 2.5% will result in lower intraocular 
pressure rise than when just administering Tropicamide 
1%/Phenylephrine 2.5% alone.  
 
Secondary Objective: To observe effect of differing the sequence of administration of 
Tropicamide 1%/Phenylephrine 2.5% and Brimonidine 0.2% on pupil size and pupil 
reactivity 
• Hypothesis 1: The administration of Brimonidine 0.2% prior to 
Tropicamide 1%/Phenylephrine 2.5% will blunt or block, or delay pupil 
dilation compared to just using Tropicamide 1%/Phenylephrine 2.5% 
alone 
• Hypothesis 2: The administration Tropicamide 1%/Phenylephrine 2.5% 
prior to Brimonidine 0.2% will lead to large pupil dilation with quicker 
reversal in pupil size than just Tropicamide 1%/Phenylephrine 2.5%. 
 
Methods and Measures  
 
• Design 
 
An interventional study looking at what order of eye drops is more effective in reducing 
intraocular pressure with pupil dilation. We will recruit 10 volunteers in each of the two groups 
(20 subjects total). In both groups, the participant’s right eye will serve as a control with only 
Tropicamide 1%/Phenylephrine 2.5% given. In the first group, the left eye will receive 
Brimonidine 0.2% prior to Tropicamide 1%/Phenylephrine 2.5%. The second group will 
receive Tropicamide 1%/Phenylephrine 2.5% prior to Brimonidine 0.2%, in their left eye. We 
will observe and record the IOP lowering benefits of the addition of brimonidine over the 
Tropicamide 1%/Phenylephrine 2.5% alone and determine if pre-treating is any better than 
post-treating. In addition, we will monitor pupil response, as we know that brimonidine may have 
some effect on the pupil dilation.  
 
We will collect the following demographic data:  age, gender, and iris color. In addition, non-
identifying color photos of the pupils may be recorded on a few representative patients in each 
group. Photos will be taken in a manner to protect patient confidentiality. Photos will be framed 
from the participants lower eyebrow, to the sides of their faces, and to the uppers nose. Photos 
will be stored on a password protected and encrypted computer or cloud-type website.  
 
• Setting 
 
The study will be performed at Wake Forest Baptist Hospital and/or Davie Medical Center. Each 
subject will be consented and have their measurements taken in a private exam room.  They will 
be returned to a waiting area in between measurements.  All concerns with measurements will be 
handled privately in the respective examination to ensure subject privacy.  
 


Subject selection criteria  
 
Subjects will be recruited through recruitment flyers and internet methods (email) (appendix 2) 
and selected to participate based on the following inclusion and exclusion criteria.  
 
• 
Inclusion criteria: Ages 18-50. Healthy with no major medical conditions. Contact lens 
wear is ok but must be not worn on the day of the study.  
• 
Females of childbearing potential must agree to use a reliable method of birth control 
while participating in this study. Reliable methods of birth control are: abstinence, oral 
contraceptives, intrauterine device (IUD), DepoProvera, tubal ligation or vasectomy of 
the partner (with confirmed negative sperm counts) in monogamous relationship (same 
partner). An acceptable, although less reliable, method involves the careful use of 
condoms and spermicidal foam or gel and/or cervical cap or sponge. A pregnancy test is 
required at least 10 days from the last normal menstrual period, if the patient is a sexually 
active female of childbearing potential. 
 
• Exclusion criteria: Diabetic, history of glaucoma, history of iris trauma, history of eye 
surgery except LASIK or PRK, pregnancy, anisocoria (unequal pupils).  
 
Sample size: 20 patients total.  
 
Study Procedure  
 
• 
Informed Consent Process: After the patient has been evaluated and meets all of the 
inclusion and exclusion criteria, Dr. Walter, or another investigator will introduce the 
study. This will occur 10 min to 24 hours before pupil dilation. The study will be 
discussed in detail and consent (appendix 1) will only be obtained once the patient has 
been given time to fully understand the study. If the patient agrees, patients will be 
dilated and intraocular pressure and pupil size will be measured at 6 time points: Baseline 
(pre drop), 15 min, after last Tropicamide 1%/Phenylephrine 2.5% drop given, 
30 min, 1 hour, 2 hours, 4 hours 
• 
Study Procedure (Approximately 4 hours): Participants will be come to the 
ophthalmology clinic where the study will be completed. Participants will be randomized 
and separated into two groups. In both groups, the participant’s right eye will serve as a 
control with only Tropicamide 1%/Phenylephrine 2.5% given. In the first group, the 
left eye will receive Brimonidine 0.2% prior to Tropicamide 1%/Phenylephrine 
2.5%. The second group will receive Tropicamide 1%/Phenylephrine 2.5% prior to 
Brimonidine 0.2.  
o IOP will be measured using the iCare tonometer device 
o Pupil size and reactivity will be measured under bright lights using a pupil gauge, 
and slit-lamp micrometer.  
• 
To prevent the dilution of the eye drops through tearing, 0.5% proparacaine 
hydrochloride (Alcaine®, Alcon Co., USA) will be delivered to each eye 5 minutes 
before administering the dilating drugs. All eye drops will be placed within the 
conjunctival sac of the lower eyelid, and patients will be directed to close their eyes 
approximately 1 minute after drop delivery to prevent loss of medication through the 
punctum in the conjunctival sac. 
  
 


Study Schematic: 1 X 4 hour participant visit  
 
Group 1 
Group 2 
Right Eye 
Left Eye 
Right Eye 
Left Eye 
 
Sham drop (none) 
 
Wait 5 minutes 
 
1 drop Tropicamide 
1%/Phenylephrine 
2.5% 
 
1 minute 
 
2nd drop 
Tropicamide 
1%/Phenylephrine 
2.5% 
 
2 drops Brimonidine 
0.2% 
 
5 minutes 
 
1 drop Tropicamide 
1%/Phenylephrine 
2.5% 
 
1 minute 
 
2nd drop 
Tropicamide 
1%/Phenylephrine 
2.5% 
 
1 drop 
Tropicamide1% 
/Phenylephrine 
2.5%  
 
Wait 1 minute 
 
2nd drop 
Tropicamide 
1%/Phenylephrine 
2.5% 
 
15 secs later 
 
Sham drop (none) 
 
1 drop Tropicamide 
1% /Phenylephrine 
2.5% 
 
Wait 1 minute 
 
2nd drop Tropicamide 
1%/Phenylephrine 
2.5% 
 
15 secs later 
 
2 drops Brimonidine 
0.2% 
 
15 min. collect Data 
set 
 
15 min. collect Data 
set 
15 min. collect Data set 
 
15 min. collect Data 
set  
 
Outcome Measures  
 
• Intraocular pressure at 6 time points: Baseline (pre-drops), 15 min after last drop 
given, then 30 min, 1 hour, 2 hours, and 4 hours 
• Pupil size at 6 time points: Baseline (pre drop), 15 min, 30 min, 1 hour, 2 hours, 4 
hours. We will measure the pupils under bright light conditions (photopic) and 
dim light conditions (scotopic). 
• Pupil’s reaction to light will be measure at 6 time points: Baseline (pre drop), 15 
min, 30 min, 1 hour, 2 hours, 4 hours. Pupil reaction will be measure either as 
none, poor, or brisk.  
 
Analytical Plan 
 
Results will be analyzed initially using descriptive statistics.  Comparison between groups 
will be done using chi square tests for proportions, and t-tests or ANOVA procedures for 
continuous variables.  Regression analysis will be performed to identify independent 
outcome predictors.  Other inferential statistical analysis will be conducted as appropriate. 
 
Human Subjects Protection  
 
Pregnancy testing will be done on all female patients, after consent and prior to 
enrollment to ensure no pregnant participates are included in the study.   
  
Subject Recruitment Methods 
 
Subjects will be recruited though placed recruitment flyers as well as electronically through an 
email with wordage directly from the flyer (appendix 2) and no students or residents will be 
recruited that are under the direct supervision of Dr. Walter. If any ophthalmology residents wish 
to volunteer (not recruited), no credit will be given for participating and their evaluations will not 
be affected. Participants will be compensated with a $30.00 Starbucks gift card. 
 
 
 


Informed Consent  
 
Signed informed consent will be obtained from each subject. The study will be introduced by 
both Dr. Walter and the study coordinator and informed consent will be obtained formally by Dr. 
Walter once the subject fully understands the study. Informed consent will be given 1-2 days or 
more prior to the subject eyes being dilated, giving them plenty of time to decide and fully 
understand the study. Final written consent will be obtained on the day the study.  
 
Confidentiality and Privacy  
 
Confidentiality will be protected by collecting only information needed to assess study outcomes, 
minimizing to the fullest extent possible the collection of any information that could directly 
identify subjects, and maintaining all study information in a secure manner.  To help ensure 
subject privacy and confidentiality, only a unique study identifier will appear on the data 
collection form.  Any collected patient identifying information corresponding to the unique study 
identifier will be maintained on a linkage file, store separately from the data.  The linkage file 
will be kept secure, with access limited to designated study personnel.  Following data collection 
subject identifying information will be destroyed 3 years after the study is published. They will be 
destroyed by deleting all files and shredding any documents consistent with data validation and 
study design, producing an anonymous analytical data set.  Data access will be limited to study 
staff.  Data and records will be kept locked and secured, with any computer data password 
protected.  No reference to any individual participant will appear in reports, presentations, or 
publications that may arise from the study. 
 
Data and Safety Monitoring  
 
The principal investigator will be responsible for the overall monitoring of the data and safety of 
study participants.  The principal investigator will be assisted by other members of the study staff. 
 
Reporting of Unanticipated Problems, Adverse Events, or Deviations  
 
Any unanticipated problems, serious and unexpected adverse events, deviations or protocol 
changes will be promptly reported by the principal investigator or designated member of the 
research team to the IRB and sponsor or appropriate government agency if appropriate. 
 
 
1. 
Bakke, E.F., J. Hisdal, and S.O. Semb, Intraocular pressure increases in parallel 
with systemic blood pressure during isometric exercise. Invest Ophthalmol Vis 
Sci, 2009. 50(2): p. 760-4. 
2. 
Kim, S.H. and K.S. Choi, Changes of intraocular pressure during experimental 
vitrectomy. Curr Eye Res, 2012. 37(8): p. 698-703. 
3. 
Siam, G.A., et al., The amount of intraocular pressure rise during 
pharmacological pupillary dilatation is an indicator of the likelihood of future 
progression of glaucoma. Br J Ophthalmol, 2007. 91(9): p. 1170-2. 
4. 
Harris, L.S., Cycloplegic-induced intraocular pressure elevations a study of 
normal and open-angle glaucomatous eyes. Arch Ophthalmol, 1968. 79(3): p. 
242-6. 


5. 
Rengstorff, R.H. and C.B. Doughty, Mydriatic and cycloplegic drugs: a review of 
ocular and systemic complications. Am J Optom Physiol Opt, 1982. 59(2): p. 
162-77. 
6. 
Ishikawa, S. and S. Oono, [Comparative study on mydriatic effects of tropicamide 
and its combination with phenylephrine (author's transl)]. Nippon Ganka Gakkai 
Zasshi, 1977. 81(9): p. 1515-20. 
7. 
Mitsui, Y. and T. Miki, [A trial of new diagnostic mydriatic]. Nihon Ganka Kiyo, 
1961. 12: p. 1026. 
8. 
Cantor, L.B., Brimonidine in the treatment of glaucoma and ocular hypertension. 
Ther Clin Risk Manag, 2006. 2(4): p. 337-46. 
9. 
Walters, T.R., Development and use of brimonidine in treating acute and chronic 
elevations of intraocular pressure: a review of safety, efficacy, dose response, and 
dosing studies. Surv Ophthalmol, 1996. 41 Suppl 1: p. S19-26. 
10. 
Toris, C.B., C.B. Camras, and M.E. Yablonski, Acute versus chronic effects of 
brimonidine on aqueous humor dynamics in ocular hypertensive patients. Am J 
Ophthalmol, 1999. 128(1): p. 8-14. 
11. 
Toris, C.B., et al., Effects of brimonidine on aqueous humor dynamics in human 
eyes. Arch Ophthalmol, 1995. 113(12): p. 1514-7. 
12.  
Eyeson-Annan ML, Hirst LW, Battistutta D, Green A. Comparative pupil dilation 
using phenylephrine alone or in combination with tropicamide. 
Ophthalmology. 1998 Apr; 105(4):726-32. 
 
 
 
 

ICF_000.pdf: 
Study Title
The Effect of Brimonidine on Intraocular Pressure When Dilating Routine Patients; 
Pressure Control and Pupil Effects. 
Keith Walter, MD Principal Investigator
Summary
You are invited to participate in a research study. The purpose of this research is to evaluate the 
effect of Brimonidine on intraocular pressure when dilating routing patients.  You are invited to 
be in this study because you meet the eligibility criteria. Your participation in this research will 
involve one visit and last about 4.5 hours.
Participation in this study will involve receiving a series of eye drops and having your 
intraocular pressure, pupil size, and pupil reactivity measured.  All research studies involve some 
risks.  A risk to this study that you should be aware of is a possible reaction to the administered 
drops although rare.  There is not the possibility that you may benefit from participation in this 
study.  
Your participation in this study is voluntary.  You do not have to participate in this study if you 
do not want to.  There may be other choices available to you.  Some other choices may include 
not participating.  You will not lose any services, benefits, or rights you would normally have if 
you choose not to participate. 
The remainder of this form contains a more complete description of this study. Please read this 
description carefully. You can ask any questions if you need help deciding whether to join the 
study. The person in charge of this study is Keith Walter, MD. If you have questions, 
suggestions, or concerns regarding this study or you want to withdraw from the study his/her 
contact information is: 
 or email at 
If you have any questions, suggestions or concerns about your rights as a volunteer in this 
research, contact the Institutional Review Board at 
 or the Research Subject 
Advocate at Wake Forest at 
Introduction
You are invited to be in a research study. Research studies are designed to gain scientific 
knowledge that may help other people in the future. You are being asked to take part in this 
study because the study needs healthy volunteers. Your participation is voluntary. Please take 
your time in making your decision as to whether or not you wish to participate. Ask your study 
doctor or the study staff to explain any words or information contained in this informed consent 
document that you do not understand. You may also discuss the study with your friends and 
family.
Why Is This Study Being Done?
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00058366
Meeting Date Approved 6/24/2019          
Version Valid Until: 6/23/2020


The purpose of this research study is to investigate whether pre-treating participants with an eye 
drop called Alphagan (brimonidine; an FDA approved drug for lowering intraocular eye 
pressure) prior to pupil dilation and/or post-treating will be effective in controlling the 
fluctuations in intraocular pressure (IOP) seen when using mydriatics (pupil dilating drops) such 
as tropicamide/phenylephrine (commonly used drops to dilate pupils in the eye clinic).
How Many People Will Take Part in the Study?
We anticipate enrollment of up to 20 participants in the study at this site. 
What Is Involved in the Study?
If you agree to be in the research study, you can choose to remain enrolled from when you sign 
the consent form to approximately 4 hours after the eye drops are given.
If you take part of this study, you will have the following tests and procedures in one session 
depending on which group you are in:
Drops will be given to you according to the group you are randomized to and will follow the 
schedule below. Randomization means you are put into a group by chance. It is like flipping a 
coin.
Group 1
Group 2
Right Eye
Left Eye
Right Eye
Left Eye
•
Sham drop (none)
•
Wait 5 minutes
•
1 drop Tropicamide 
1%/Phenylephrine 
2.5%
•
1 minute
•
2nd drop 
Tropicamide 
1%/Phenylephrine 
2.5%
•
2 drops Brimonidine 
0.2%
•
5 minutes
•
1 drop Tropicamide 
1%/Phenylephrine 
2.5%
•
1 minute
•
2nd drop 
Tropicamide 
1%/Phenylephrine 
2.5%
•
1 drop 
Tropicamide1% 
/Phenylephrine 2.5% 
•
Wait 1 minute
•
2nd drop Tropicamide 
1%/Phenylephrine 
2.5%
•
15 secs later
•
Sham drop (none)
•
1 drop Tropicamide 1% 
/Phenylephrine 2.5%
•
Wait 1 minute
•
2nd drop Tropicamide 
1%/Phenylephrine 
2.5%
•
15 secs later
•
2 drops Brimonidine 
0.2%
•
15 min. collect Data 
set
•
15 min. collect Data 
set
15 min. collect Data set
•
15 min. collect Data set 
Following the drops, we will begin data collection including measuring your intraocular 
pressure, pupil size, and pupil reaction to light at 6 different time points: baseline (pre-drop), 15 
minutes after the last drop was given, 30 minutes, 1 hour, 2 hours, and 4 hours.
As part of this research study, you may be photographed. This is done to have a visual 
representation of difference in pupil size. You understand that you may request the filming or 
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00058366
Meeting Date Approved 6/24/2019          
Version Valid Until: 6/23/2020


recording be stopped at any time during the course of the research study. You can also withdraw 
your consent to use and disclose the photograph before it is used. You should also understand 
that you will not be able to inspect, review, or approve the photographs before they are used in 
this study. 
The photograph will be of just your eyes and will be taken in a method to protect your 
confidentiality. The photograph will be framed from the lower part of your eyebrows, to the 
sides of your face, and your upper nose. 
Please choose one of the following regarding the use and disclosure of the photograph used in 
this research study:
_____ I would like the photographs of me to be destroyed once their use in this study is finished.
____ The photographs of me can be kept for use in future studies provided they are kept secure 
and any future study will be reviewed by an IRB.   I understand that I will not be able to inspect, 
review or approve their future use.
How Long Will I Be in the Study?
If you agree to be in the research study you can chose to remain enrolled from when you sign the 
consent form to approximately 4 hours after the eye drops are given.
You can stop participating at any time. If you decide to stop participating in the study we 
encourage you to talk to the investigators or study staff first to learn about any potential health or 
safety consequences, however, we do not anticipate any serious consequences of sudden 
withdrawal from the study. 
What Are the Risks of the Study?
Being in this study involves some risk to you. You should discuss the risk of being in this study 
with the study staff. Risks and side effects related to the use of Tropicamide/Phenylephrine and 
Alphagan (brimonidine) we are studying include:
Risks for Alphagan (brimonidine):
Risks and side effects related to the brimonidine we are studying include:
Adverse reactions occurring in approximately 10-20% of the subjects receiving brimonidine 
ophthalmic solution (0.1-0.2%) included: allergic conjunctivitis, conjunctival hyperemia (eye 
redness), and eye pruritus (itching). Adverse reactions occurring in approximately 5-9% of the 
subjects receiving brimonidine ophthalmic solution (0.1-0.2%) included: burning sensation, 
conjunctival folliculosis (inflammation), hypertension (high blood pressure), ocular allergic 
reaction, dry mouth, and visual disturbance (blurred vision).
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00058366
Meeting Date Approved 6/24/2019          
Version Valid Until: 6/23/2020


Adverse reactions occurring in approximately 1-4% of the subjects receiving brimonidine 
ophthalmic solution (0.1-0.2%) included: abnormal taste, allergic reaction, asthenia (weakness), 
blepharitis (eyelid inflammation), blurred vision, bronchitis (cough), cataract, conjunctival 
edema (eye swelling), conjunctival hemorrhage (bleeding of the eye), conjunctivitis 
(inflammation of the eye), cough, dizziness, dyspepsia (indigestion), dyspnea (trouble breathing), 
epiphora (tearing), eye discharge, eye dryness, eye irritation, eye pain, eyelid edema, eyelid 
erythema (redness), fatigue, flu syndrome, follicular conjunctivitis (inflammation of the front 
part of the eye), foreign body sensation, gastrointestinal disorder (upset stomach), headache, 
hypercholesterolemia (high cholesterol), hypotension (low blood pressure), infection (primarily 
colds and respiratory infections), insomnia (unable to sleep), keratitis (inflammation of the front 
covering of the eye), lid disorder, pharyngitis (sore throat), photophobia (light sensitivity), rash, 
rhinitis (running nose), sinus infection, sinusitis, somnolence (sleepiness), stinging, tearing, 
visual field defect (loss of part of vision), vitreous detachment (the jelly in the eye comes off the 
retina), vitreous floaters (black spots in vision), and worsened visual acuity.  The following 
reactions were reported in less than 1% of subjects: corneal erosion (loss of the front covering of 
the eye), hordeolum (swelling of eyelid), nasal dryness, and taste perversion (abnormal taste in 
the mouth). 
Risks for Tropicamide/Phenylephrine (dilating drops): 
Frequency Not Defined: Blurred vision (especially at near), burning sensation in eye, 
hypersensitivity reactions such as allergic itching or rash, sensitivity to light, headache or brow 
ache, eye redness, temporary burning or stinging.
Rare:  Increased blood pressure, rapid heartbeat, abnormal heart rhythm, flushing, poor 
coordination, confusion, headache, raised eye pressure, seizure, trembling or tremors, increased 
sweating, pale skin or blanching.
In addition, there is a slight risk of a breach of confidentiality.  We will do our best to protect 
your confidential information.  There also may be other side effects that we cannot predict. You 
should tell the research staff about all the medications, vitamins and supplements you take and 
any medical conditions you have. This may help avoid side effects, interactions and other risks.
Taking part in this research study may involve providing information that you consider 
confidential or private.  Efforts, such as coding research records, keeping research records secure 
and allowing only authorized people to have access to research records will be made to keep 
your information safe.
Reproductive Risks and other Issues to Participating in Research
Pregnant women are excluded from participation in this study. Because NO method of birth 
control is 100% reliable, a pregnancy test is required at least 10 days from your last normal 
menstrual period, if you are a sexually active woman of childbearing potential.
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00058366
Meeting Date Approved 6/24/2019          
Version Valid Until: 6/23/2020


Are There Benefits to Taking Part in the Study?
You are not expected to receive any direct benefit from taking part in this research study. We 
hope the information learned from this study will benefit other people in the future. 
What Other Choices Are There?
This is not a treatment study. Your alternative is to not participate in this study.
What Are the Costs?
All study costs, including any study medications and procedures related directly to the study, will 
be paid for by the study.
Will Your Research Records be Confidential?
The results of this research study may be presented at scientific or medical meetings or published 
in scientific journals.  Your identity and/or your personal health information will not be disclosed 
unless it is authorized by you, required by law, or necessary to protect the safety of yourself or 
others.  There is always some risk that even de-identified information might be re-identified. 
Participant information may be provided to Federal and other regulatory agencies as required.  
The Food and Drug Administration (FDA), for example, may inspect research records and learn 
your identity if this study falls within its jurisdiction.
The photo that will be taking of your pupils will be done in a method to uphold confidentiality. 
Photos will be taken by study staff and will be framed by the sides of your face, eyebrows, and 
upper nose. We will follow these guidelines in order to protect your security and maintain 
confidentiality. We will also store the photos in a securely on a password protected and 
encrypted computer.
Will You Be Paid for Participating?
You will be given a Starbucks gift card in the amount of $30 at the end of the 4-hour study
Who is Sponsoring this Study?
There are no current financial sponsors of this study.  The Wake Forest University Innovations is 
the sponsor of this study.
What Happens if You Experience an Injury or Illness as a Result of 
Participating in this Study?
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00058366
Meeting Date Approved 6/24/2019          
Version Valid Until: 6/23/2020


Should you experience a physical injury or illness as a direct result of your participation in this 
study, Wake Forest University School of Medicine maintains limited research insurance 
coverage for the usual and customary medical fees for reasonable and necessary treatment of 
such injuries or illnesses. To the extent research insurance coverage is available under this policy 
the reasonable costs of these necessary medical services will be paid, up to a maximum of 
$25,000. Wake Forest University Baptist Medical Center holds the insurance policy for this 
coverage. It provides a maximum of $25,000 coverage for each claim and is limited to a total of 
$250,000 for all claims in any one year. The Wake Forest University School of Medicine, and 
the North Carolina Baptist Hospitals, Incorporated do not assume responsibility to pay for these 
medical services or to provide any other compensation for such injury or illness. Additional 
information may be obtained from the Medical Center’s Director of Risk and Insurance 
Management, at 
If you are injured, the insurer may require information such as your name, social security 
number, and date of birth in order to pay for your care.  This is because the insurer is required by 
law to report any payments made to cover the care of any persons who are members of a 
government insurance plan to the Department of Health and Human Services.
You do not give up any legal rights as a research participant by signing this consent form. For 
more information on medical treatment for research related injuries or to report a study related 
illness, adverse event, or injury you should call Keith Walter at telephone number 
 this number is available 24 hours a day)
What About My Health Information?
In this research study, any new information we collect from you about your health or behaviors is 
considered Protected Health Information. The information we will collect for this research study 
includes: your name, medical record number, age, gender, pupil size, eye color, eye pressure, and 
a photo of your eyes. 
If this research study involves the diagnosis or treatment of a medical condition, then Protected 
Health Information collected from you during this study may be placed in your medical record, 
and may be used to help treat you, arrange payment for your care, or assist with Medical Center 
operations. 
We will make every effort to keep your Protected Health Information private. We will store 
records of your Protected Health Information in a cabinet in a locked office or on a password 
protected computer. 
Your personal health information and information that identifies you (“your health information”) 
may be given to others during and after the study. This is for reasons such as to carry out the 
study, to determine the results of the study, to make sure the study is being done correctly, to 
provide required reports and to get approval for new products.  
Some of the people, agencies, and businesses that may receive and use your health information 
are the research sponsor; representatives of the sponsor assisting with the research; investigators 
at other sites who are assisting with the research; central laboratories, reading centers or analysis 
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00058366
Meeting Date Approved 6/24/2019          
Version Valid Until: 6/23/2020


centers; the Institutional Review Board; representatives of Wake Forest University Health 
Sciences and North Carolina Baptist Hospital; representatives from government agencies such as 
the Food and Drug Administration (FDA), the Department of Health and Human Services 
(DHHS) and similar agencies in other countries.
Some of these people, agencies, and businesses may further disclose your health information. If 
disclosed by them, your health information may no longer be covered by federal or state privacy 
regulations.  Your health information may be disclosed if required by law. Your health 
information may be used to create information that does not directly identify you. This 
information may be used by other researchers. You will not be directly identified in any 
publication or presentation that may result from this study unless there are photographs or 
recorded media which are identifiable.
If required by law or court order, we might also have to share your Protected Health Information 
with a judge, law enforcement officer, government agencies, or others. If your Protected Health 
Information is shared with any of these groups it may no longer be protected by federal or state 
privacy rules.
Any Protected Health Information collected from you in this study that is maintained in the 
research records will be kept for at least six years after the study is finished. At that time any 
research information not already in your medical record will either be destroyed or it will be de-
identified. You will not be able to obtain a copy of your Protected Health Information in the 
research records until all activities in the study are completely finished. 
You can tell Dr. Keith Walter MD that you want to take away your permission to use and share 
your Protected Health Information at any time by sending a letter to this address:
Dr. Keith Walter MD
However, if you take away permission to use your Protected Health Information you will not be 
able to be in the study any longer. We will stop collecting any more information about you, but 
any information we have already collected can still be used for the purposes of the research 
study.
By signing this form you give us permission to use your Protected Health Information for this 
study.
If you choose to participate in this study, your medical record at Wake Forest University Baptist 
Medical Center will indicate that you are enrolled in a clinical trial.  Information about the 
research and any medications or devices you are being given as a participant may also be 
included in your medical record.  This part of the medical record will only be available to people 
who have authorized access to your medical record.  If you are not a patient at this Medical 
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00058366
Meeting Date Approved 6/24/2019          
Version Valid Until: 6/23/2020


Center, a medical record will be created for you anyway to ensure that this important information 
is available to doctors in case of an emergency.
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by U.S. Law.  This website will not include information that can identify you.  At most, the 
website will include a summary of the results.  You can search this Web site at any time.
Laboratory test results and other medical reports created as a result of your participation in the 
research study may be entered into the computer systems of Wake Forest University Health 
Sciences and North Carolina Baptist Hospital.  These will be kept secure, with access to this 
information limited to individuals with proper authority, but who may not be directly involved 
with this research study.
A North Carolina Baptist Hospital (NCBH) medical record will be created for all study 
participants. Information about your participation in the study may be placed in the NCBH 
medical record, along with any routine medical test results that were obtained at NCBH as part 
of this study. 
What Are My Rights as a Research Study Participant?
Taking part in this study is voluntary. You may choose not to take part or you may leave the 
study at any time. Refusing to participate or leaving the study will not result in any penalty or 
loss of benefits to which you are entitled. If you decide to stop participating in the study we 
encourage you to talk to the investigators or study staff first to learn about any potential health or 
safety consequences. The investigators also have the right to stop your participation in the study 
at any time. 
You will be given any new information we become aware of that would affect your willingness 
to continue to participate in the study.
 
Possible Conflict of Interests:
This study will be enrolling students from the Wake Forest University and/or Wake Forest 
University Medical Center. In addition to your rights as a research participant noted in the 
previous section, as a student, you are under no obligation to participate in this study. You may 
refuse to participate or withdraw from the study at any time and for any reason without affecting 
your grades, performance evaluations, or assignments. You will not be pressured into 
participating in this research study by any statements or implied statements that your grades, 
performance evaluations, or assignments will be affected by your willingness to enroll in the 
study. Your medical records/information will not be used by the faculty, administration, or study 
staff to make decisions regarding the status of your medical benefits. If you have questions 
regarding your enrollment in the study and your status as a medical student, please contact the 
Office of Student Services for additional information.
No students or residents will be recruited that are under the direct supervision of Dr. Walter. If any 
ophthalmology residents wish to volunteer (not recruited), no credit will be given for participating and 
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00058366
Meeting Date Approved 6/24/2019          
Version Valid Until: 6/23/2020


their evaluations will not be affected. In addition, an independent party will look at your medical 
record that has no affiliation or connect to any student in at the Wake Forest University School 
of Medicine. 
Whom Do I Call if I Have Questions or Problems?
For questions about the study or in the event of a research-related injury, contact the study 
investigator, Dr. Keith Walter MD at 
or email at
.  This 
number can be used to contact us 24 hours a day.
The Institutional Review Board (IRB) is a group of people who review the research to protect 
your rights. If you have a question about your rights as a research participant, or you would like 
to discuss problems or concerns, have questions or want to offer input, or you want to obtain 
additional information, you should contact the Chairman of the IRB at 
.
You will be given a copy of this signed consent form. 
Signature page follows…
 
Signatures
I agree to take part in this study. I authorize the use and disclosure of my health information as 
described in this consent and authorization form.  If I have not already received a copy of the 
Privacy Notice, I may request one or one will be made available to me.  I have had a chance to 
ask questions about being in this study and have those questions answered.   By signing this 
consent and authorization form, I am not releasing or agreeing to release the investigator, the 
sponsor, the institution or its agents from liability for negligence.
Subject Name (Printed):_____________________________
Subject Signature: _________________________________ Date: ________Time:_______ am pm 
Person Obtaining Consent (Printed):_____________________________
Person Obtaining Consent: ___________________________ Date:_________ Time:________ am pm
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00058366
Meeting Date Approved 6/24/2019          
Version Valid Until: 6/23/2020