Clinical trial NCT03782701
Conditions: Eyelid Droop
Sponsor: University of Miami
Start date: 2019-06-18; Completion date: 2020-04-01
Enrollment: 43 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of the research is to see if Lumify™ has an effect on eyelid position.

Detailed description:

Arms: arm 1: Participants will be randomized to receive a single drop of Lumify to either the left or right eye. arm 2: Participants will be randomized to receive a single drop of sterile balanced saline solution to either the left or right eye.
Interventions: intervention 1: Brimonidine tartrate ophthalmic solution 0.025% intervention 2: Sterile balanced saline solution
Intervention descriptions: intervention 1: One time dosing of brimonidine tartrate ophthalmic solution 0.025% (1 drop applied to ocular surface) intervention 2: One time dosing of sterile balanced saline solution (1 drop applied to ocular surface)

Protocol documents:
Prot_SAP_001.pdf: 
 
 
 
 
 
 
 
 
Protocol Title: The effect of LumifyTM (Brimonidine Tartrate 
Ophthalmic Solution 0.025%) on palpebral fissure height. 
 
Protocol Version: Version 1 27 September 2018 
 
Principal Investigator: Wendy Lee, MD 
 
NCT Number: NCT03782701 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


1) 
Protocol Title 
 
The effect of LumifyTM (Brimonidine Tartrate Ophthalmic Solution 0.025%) on palpebral 
fissure height. 
 
2) 
Objectives* 
 
Aim 1: To determine the in vivo effect of LumifyTM  (Brimonidine Tartrate Ophthalmic 
Solution 0.025%) on palpebral fissure height.  
 
Hypothesis: We hypothesize application of LumifyTM Brimonidine Tartrate Ophthalmic 
Solution 0.025% will cause an increase in subjects’ palpebral fissure height. 
 
3) 
Background* 
 
 
Eyelid ptosis most commonly results from malfunctioning levator palpebrae superior 
muscle or Müller’s muscle. Müller’s muscle, a smooth muscle with a predominance of -
1D adrenergic receptors, contracts in response to sympathetic stimulation or topical 
adrenergic agonists. (Skibell 2007) Therefore, topical ocular administration of 
compounds that agonize adrenergic receptors causes an increase in interpalpebral fissure 
height via contraction of Müller’s muscle, which helps mitigate ptosis effects as well as 
lending the cosmetically beneficial effect of an eye that is more open. (Munden 1991) 
Compounds such as apraclonidine, a medication with mixed and 1 properties, have been 
shown to reverse ptosis caused by Horner’s syndrome and botulinum injections, and to 
help assess blepharoptosis preoperatively. Although the primary mechanism of 
apraclonidine is 2 agonism, which inhibits norepinephrine release from sympathetic 
nerve terminals, it is also a weak agonist, and allows for direct stimulation of smooth 
muscle. Multiple studies have observed the abilty of topical apraclonidine to increase 
palpebral fissure height by elevating the upper lid. (Kirkpatrick 2018, Yazici 2008, Koc 
2005)  Brimonidine is a very similar medication; like apraclonidine, it is a selective 
adrenergic agonist with a much weaker affinity for the receptor. (Torkildsen 2017) 
Brimonidine was originally used to treat patients with open-angle glaucoma and ocular 
hypertension (brimonidine 0.2%). It decreases intraocular pressure by intensifying 
uveoscleral outflow and reducing aqueous humor inflow. (Derrick 1997) Its uses have 
since expanded to vasoconstriction for the skin and ocular tissue, which make it an 


effective compound to reduce ocular redness (brimonidine 0.025%), and pupillary 
dilation, which can help camouflage anisocoria associated with Horner’s syndrome. 
(Torkildsen 2017; McLaurin 2018; DeSouza 2007) In addition, when used as a glaucoma 
medication, brimonidine has been observed to elevate patients’ eyelids via its αactivation 
of Müller’s muscle. (Burroughs 2007) Although apraclonidine is also effective at 
lowering intraocular pressure, as well as causing conjunctival blanching and mydriasis, it 
is not a recommended as long term therapy due to its high rate of side effects—the most 
common being loss of Snellen acuity—and tachyphylaxis. (Yuksel 2002; Araujo 1995) In 
contrast, a study of 0.025% brimonidine for relief of ocular redness observed no serious 
adverse effects (the most common side effect was instillation site pain and dry eye) and 
no tachyphylaxis during the treatment period. (Torkildsen 2017) For this reason, although 
Kirkpatrick et al studied apraclonidine as a potential substitute for surgical treatment of 
mild upper eyelid ptosis, brimonidine may be an even safer alternative. (Kirkpatrick 
2018) Patients suffering from ptosis who are either poor candidates for surgical repair or 
who do not want a surgery, in addition to patients who underwent surgery but still have a 
small amount of residual ptosis, would benefit from a safe and effective medical 
treatment. In addition, there may be a beneficial cosmetic effect in patients without 
significant ptosis. To the authors’ knowledge, there is currently no study objectively 
observing the effects of brimonidine on upper eyelid position and the potential variability 
of this effect in different individuals. In this randomized controlled study, we aim to 
record changes in palpebral fissure height before and after administration of 0.025% 
brimonidine, in hopes to gain a deeper understanding of brimonidine’s therapeutic 
potential.  
 
Bibliography and References Cited [1-11] 
  
 
1. 
Skibell, B.C., et al., Adrenergic receptors in the ptotic human eyelid: correlation 
with phenylephrine testing and surgical success in ptosis repair. Ophthalmic Plast 
Reconstr Surg, 2007. 23(5): p. 367-71. 
2. 
Munden, P.M., et al., Palpebral fissure responses to topical adrenergic drugs. 
Am J Ophthalmol, 1991. 111(6): p. 706-10. 


3. 
Kirkpatrick, C.A., et al., Upper Eyelid Response to Topical 0.5% Apraclonidine. 
Ophthalmic Plast Reconstr Surg, 2018. 34(1): p. 13-19. 
4. 
Yazici, B. and U. Beden, Use of 0.5% apraclonidine solution in evaluation of 
blepharoptosis. Ophthalmic Plast Reconstr Surg, 2008. 24(4): p. 299-301. 
5. 
Koc, F., et al., The sensitivity and specificity of 0.5% apraclonidine in the 
diagnosis of oculosympathetic paresis. Br J Ophthalmol, 2005. 89(11): p. 1442-4. 
6. 
Torkildsen, G.L., et al., Evaluation of Efficacy and Safety of Brimonidine Tartrate 
Ophthalmic Solution, 0.025% for Treatment of Ocular Redness. Curr Eye Res, 
2018. 43(1): p. 43-51. 
7. 
McLaurin, E., et al., Brimonidine Ophthalmic Solution 0.025% for Reduction of 
Ocular Redness: A Randomized Clinical Trial. Optom Vis Sci, 2018. 95(3): p. 
264-271. 
8. 
deSousa, J.L. and R. Malhotra, Brimonidine for anisocoria. Ophthalmology, 
2007. 114(7): p. 1419. 
9. 
Burroughs, J.R., et al., Preoperative assessment of the eye and periocular region. 
Semin Plast Surg, 2007. 21(1): p. 5-17. 
10. 
Yuksel, N., et al., A comparison of the short-term hypotensive effects and side 
effects of unilateral brimonidine and apraclonidine in patients with elevated 
intraocular pressure. Ophthalmologica, 2002. 216(1): p. 45-9. 
11. 
Araujo, S.V., et al., Long term effect of apraclonidine. Br J Ophthalmol, 1995. 
79(12): p. 1098-101. 
 
 


 
 
4) 
Inclusion and Exclusion Criteria* 
 
A total of 40 eligible participants will be recruited for inclusion in the study. 
 
Inclusion Criteria 
- 
Adults age 18 and above able to provide informed consent to participate 
- 
Subject with stable ocular health, defined as no ocular conditions requiring 
ongoing topical therapy or recent surgical intervention 
 
Exclusion Criteria 
- 
Adults unable to consent 
- 
Individuals less than 18 years of age 
- 
Prisoners 
- 
Pregnant women. 
o Patients will be asked if they are pregnant by research staff before 
participation in the study.  
- 
Known contradictions or sensitivities to study medication (brimonidine) 
- 
Ocular surgery within the past 3 months or refractive surgery within the past six 
months 
- 
Grossly abnormal lid margins, anatomical abnormalities, previous eyelid or 
orbital surgery 
- 
Variable ptosis or eyelid position (e.g., myasthenia gravis, thyroid eye disease, or 
blepharospasm)  
- 
Significant pre-existing ptosis of any cause (defined as MRD1 < 1mm) 
- 
Any ocular or systemic condition that, in the opinion of the investigator, would 
confound study data, interfere with the subject’s study participation, or affected 
the subject’s safety or trial parameters 
- 
Presence of an active ocular infection  
- 
Prior (within 5 days of beginning study treatment) use of eye whiteners (eg, 
vasoconstrictors), decongestants, antihistamines (including over the counter and 
herbal topical ophthalmic medications), phenylephrine dilating drops, any other 
topical ophthalmic agents 
- 
Inability to sit comfortably for 15 – 30 minutes 
 


5) 
Procedures Involved* 
Subject Identification and Recruitment 
Potential subjects will be identified during their normal clinic visit at the Bascom Palmer 
Eye Institute, primarily within the oculoplastics department. The attending physician will 
ask eligible patients if they are interested in hearing about the study. No phone calls for 
recruitment will be made prior to the regular clinic visit. Patients may additionally be 
referred from other providers within the Bascom Palmer Eye Institute during their regular 
visits or from the emergency room. Bascom Palmer employees and University of Miami 
Miller School of Medicine students would also be invited to participate if interested. 
 
Patients who qualify for the study and express an interest in participating will have the 
study explained to them by a research study member and have the opportunity to ask 
questions. They will receive information on risks and benefits to research participation. 
They will receive a copy of the consent form and if desired may be able to take the 
consent form home prior to signing for further consultation. Those who are interested in 
participation will be given a scheduled appointment to meet with research staff. 
 
Number of Subjects  
The time and resource constraints of our current pilot study allow for only approximately 
40 participants.  
 
Study Timelines 
Recruitment will occur for 1 year and will end once 40 patients are accrued. The study 
length for the patient is expected to be only the length of clinic visit. The study is 
expected to last about 1 year from time of IRB approval to completion of all study 
activities, including analysis of identifiable data. 
 
LumifyTM Drug Product 
 
LumifyTM is FDA approved drug for the treatment of ocular redness due to minor eye 
irritation available for use without a prescription. It is available in a drop formulation. 
This agent should be considered exempt from IND requirements as the study is using the 
drug in realm of FDA indications. Drug insert is available attached to the IRB protocol.  
 
Procedures Involved 
We anticipate that procedures listed below will take about 30 to 40 minutes per patient. 
The procedures below are not considered standard of care and are being conducted for the 
study alone.  
 
A. Part 1: Photographing subjects  
o All images will be taken by the same examiner, in a room with the same 
conditions.  
o With a modified slit lamp, the subjects’ heads will be placed on a chin rest 
with forehead support to position them on a consistent plane in relation to 
the camera and to generate standardized images of the eyelids. A 
dedicated camera mounted at a fixed distance and height will be used to 


photograph the patients. A clamp will be affixed to the brow bar, and will 
be used to hold the camera at a standardized distance from the patients and 
aligned vertically with respect to their lateral canthus. Subjects will be 
instructed to relax. A small circular sticker will be placed on the back of 
the iPhone, facing the patients. The subjects will focus on the sticker with 
their eyes in primary gaze. The camera zoom will be adjusted so that the 
eyes take up the full width of the frame –from lateral canthus to lateral 
canthus- thus limiting the acquired photograph to the eyes and rendering it 
unidentifiable.  
o  All photographs will be taken with the dedicated camera. The aperture, 
shutter speed, and exposure time will be based on the external lighting 
conditions. A camera flash will be used in order to standardize the light 
reflex in the eyes of subjects.  
o Photographs will be interfaced to a personal computer (PC) and saved as 
JPG files (1200 9 797 pixels, 24-bit, RGB) in a locked folder. When not in 
use the camera will be secured in a locked drawer. 
B. Part 2: LumifyTM application 
o The left and right eye of each subject will be randomized to receive either 
LumifyTM or balanced saline placebo. 
o Based on the randomization results, the examiner will apply LumifyTM eye 
drops and saline to subject’s eyes.  
C. Part 3: Photographing subjects 
o Subjects will wait 5 minutes after they receive eye drops in the waiting 
area. 
o After time has elapsed, subjects will be photographed again according to 
the procedure described above.  
o The two steps described above will be repeated at 15 minutes and 30 
minutes after the patients received the eye drops. 
D. Part 4: Measuring Intraocular Pressure 
o Subjects will have their intraocular pressure measured using a Tonopen 
prior to applying LumifyTM, and 30 minutes after receiving LumifyTM and 
after being photographed.  
o Measuring intraocular pressure using a Tonopen is a standard of care 
procedure during ophthalmic examinations. 
E. Part 5: Data analysis 
o Data will be recorded and stored in a secure Microsoft Office Excel 
(Microsoft Corporation, Redmond, WA, U.S.A.) spreadsheet. Data will be 
graphically analyzed and represented with Adobe Photoshop (Adobe, Inc., 
San Jose, CA, U.S.A). 
o User performing analysis will be blinded to which eye received study 
drug. 
 
No additional follow-up outside of the patient’s next routine clinic visit will be needed. 
Patients who do have symptoms concerning any post-procedural complications will be 
instructed to notify study staff immediately. A phone number will be provided. Clinical 
examination post-procedure will be at Bascom Palmer Eye Institute.  


 
Withdrawal of Subjects 
Patients may withdraw at any time at their discretion. Subject withdrawn from and/or 
terminated from research with or without their consent are those who are found to not 
meet inclusion/exclusion criteria, and/or are not able to complete the research protocol in 
its entirety. For any subjects who withdraw from research, including partial withdrawal 
from procedures, study data of the withdrawn subject will not be included in statistical 
analysis and will be shredded.  
 
6) 
Data and Specimen Banking* 
Not applicable. 
 
7) 
Data Management* 
 
Steps to Secure Data 
The study coordinator will assign each patient a specific ID number and place this 
information on a separate spreadsheet. The study coordinator will collect the sex, 
patient’s age, and dates of service, but no other identifiable information. No names will 
be used in the forms. Presentations and publications will not identify individual patients. 
Data from the subjects’ medical records will be encrypted and stored securely as detailed 
below. Identifiable data will not be stored for future use beyond the timeframe of this 
study.  The release of data will be only to study members and no other outside 
organization.  
 
Data will be kept under lock and key in Dr. Wendy Lee’s office at the Bascom Palmer 
Eye Institute Oculoplastics Research Laboratory on the 4th floor (900 NW 17th Street, 
Miami, FL 33136), data encoded in the computer will be password-protected and will be 
available only to study personnel, and protected health information will not be re-used or 
disclosed for other purposes. Study members will be trained on how to log in and log out 
of the computers. The study coordinator will assign each patient a specific ID number 
and the sex, patient’s age and date of on a separate spreadsheet. The study coordinator 
will record the study results including which eye received the study medication with the 
specific sample ID on another spreadsheet. 
 
Data Analysis 
Statistical analysis will be performed by the Oculoplastics Research Laboratory research 
fellow. A paired t-test will be used to analyze the difference in palpebral fissure height. 
Forty subjects will be required to perform perimetric statistics.  
 
8) 
Risks to Subjects* 
 
The primary risks to the subjects are adverse reactions to the medication. These risks are 
explained to patients prior to their arrival to the Oculoplastics Clinic.  Previously 
described potential adverse reactions to brimonidine include instillation site discomfort 
and dry eye symptoms. However, the incidence of these side effects has been shown to be 
very low (up to 7.9% for dry eye). (Torkildsen 2017) Potential psychosocial risks to 


subjects include time taken from their day to undergo tests, potentially missing work, and 
anxiety or discomfort from the eye drop instillation process. This study is not collecting 
sensitive information, thus no potential risk to reputation or legal risks should occur.  
 
Subjects will be instructed to call immediately for an appointment if they notice a change 
in their vision, eye redness or the development of pain in either eye. Care will be taken by 
all study members to prevent the occurrence of any adverse events.  
 
There are no well-controlled studies of brimonidine in pregnant women, and the risks to 
the fetus or embryo are unknown/unforeseen. Brimonidine is classified as AU TGA 
pregnancy category B3, and US FDA pregnancy category B.  
• AU TGA pregnancy category B3: Drugs which have been taken by only a limited 
number of pregnant women and women of childbearing age, without an increase 
in the frequency of malformation or other direct or indirect harmful effects on the 
human fetus having been observed. Studies in animals have shown evidence of an 
increased occurrence of fetal damage, the significance of which is considered 
uncertain in humans. 
• US FDA pregnancy category B: Animal reproduction studies have failed to 
demonstrate a risk to the fetus and there are no adequate and well-controlled 
studies in pregnant women. 
Participants will be informed of the above information, and reserve the right to decline 
participation in the study.  
 
Risks to measuring intraocular pressure using a Tonopen are extremely low, and include 
risk of infection and corneal abrasion.  
 
Unanticipated problems or complications will be reported to the IRB according to posted 
guidelines.  
 
Risks of the study are listed above and will be minimized by the following:  
- 
Intraocular pressure measurements with a Tonopen will be performed according 
to the standard of care procedure by a trained member of the research staff.  
- 
Study will be discontinued if subjects experience any negative effect from the 
medication 
- 
Patients with a known sensitivity or history of adverse reaction to brimonidine or 
similar medications will be excluded from the study 
 
As with any study, there is a risk of confidentiality breach. The research members will 
assign each patient a specific ID number and place this information on a separate 
spreadsheet. No names will be used in the forms. Presentations and publications will not 
identify individual patients. 
 
9) 
Potential Benefits to Subjects* 
 
There will be no direct benefit to patients participating in the study. Their involvement 
may provide satisfaction for aiding in future research, particularly if they would be 


interested in personally using the agent to increase their own palpebral fissure height in 
the future. 
 
10) Vulnerable Populations* 
 
Bascom Palmer employees and Miller School of Medicine students are considered 
vulnerable populations as they would be invited to participate in the study if they were 
interested.  
 
11) Setting 
 
Study location will be at the Bascom Palmer Eye Institute, primarily within the 4th floor 
Oculoplastics clinic. 
 
12) Resources Available 
 
Principal investigator will be in charge of the studies and has been involved in multiple 
human clinical trials at the University of Miami. 
 
Resident physician has experience in clinical research, slit lamp examination, and 
obtaining clinical photographs. 
 
Research fellow at the Bascom Palmer Eye Institute has years of experience with data 
collection and analysis.  
 
 
13) Prior Approvals 
 
None. 
 
14) Recruitment Methods 
 
 
Wendy Lee, MD, the principle investigator of this study, will assess patients for study 
eligibility by reviewing the medical record. These patients will be coming in during their 
normal visit at the Bascom Palmer Eye Institute Oculoplastics Clinic. Dr. Lee will ask 
eligible patients if they are interested in hearing about the study. No phone calls for 
recruitment will be made prior to the regular clinic visit. Patients may additionally be 
referred from other providers within the Bascom Palmer Eye Institute during their regular 
visits. No payment will be provided to patients for their participation.  
 
Patients who qualify for the study and express an interest in participating will have the 
study explained to them by a research study member and have the opportunity to ask 
questions. They will receive information on risks and benefits to research participation. 
They will receive a copy of the consent form and if desired may be able to take the 


consent form home prior to signing for further consultation. Those who are interested in 
participation will be given a scheduled appointment to meet with research staff. 
 
 
 
15) Local Number of Subjects 
 
The goal of this pilot study is to assess the ability of LumifyTM in patients as an agent to 
increase eyelid height. The time and resource constraints of our current pilot study allow 
for only approximately 40 participants.  
  
 
16) Confidentiality 
 
An adequate plan to protect identifiers from improper use and disclosure is included in 
our study.  Minimal risk for use of protected health information will be followed.  Patient 
data will be collected under patient initials only.  Data will be kept under lock and key in 
Dr. Wendy Lee’s office at the Bascom Palmer Eye Institute Oculoplastics Research 
Laboratory on the 4th floor (900 NW 17th Street, Miami, FL 33136), data encoded in the 
computer will be password-protected and will be available only to study personnel, and 
protected health information will not be re-used or disclosed for other purposes. 
Certificates of confidentiality and separation of identifiers and data during storage, use 
and transmission will be implemented. Additionally, paper shredding and erasure of 
electronic data will be done at the earliest opportunity. Data collected from medical 
charts includes patient age, gender, race, and initials. Study records, consents and data 
will be stored as detailed below, and will be stored beyond the study completion date for 
six years following study closure.  
 
17) Provisions to Protect the Privacy Interests of Subjects 
 
An adequate plan to protect identifiers from improper use and disclosure is included in 
our study. Patient data will be collected under patient initials only.  Data will be kept 
under lock and key in Dr. Wendy Lee’s office at the Bascom Palmer Eye Institute 
Oculoplastics Research Laboratory on the 4th floor (900 NW 17th Street, Miami, FL 
33136), data encoded in the computer will be password-protected and will be available 
only to study personnel, and protected health information will not be re-used or disclosed 
for other purposes. Separation of identifiers and data during storage, use and transmission 
will be implemented. Additionally, paper shredding and erasure of electronic data will be 
done at the earliest opportunity. 
 
18) Consent Process 
 
After identifying eligible study subjects, those who are interested in participating will be 
given a scheduled appointment to meet with research staff to review the consent form. 
The consent process will take place in Oculoplastics Clinic at Bascom Palmer Eye 
Institute.  Adequate time will be devoted to the consent discussion; the patients will be 


given ample time to review the consent form and ask questions. If patients have a 
different language than English, such as Spanish as their native language, a translator will 
be used to explain the research process.  A separate consent translated in that appropriate 
language will be made prior to signing the consent. A witnessed will be used if the 
patient has vision impairment and is unable to read the consent.  
 
19) Process to Document Consent in Writing 
 
This research is no more than minimal risk of harm to subject. Witten documentation of 
consent will be provided.