The Effects of Mirtogenol® With Bimatoprost on Intraocular Pressure in Hispanics With Open-Angle Glaucoma: A Double-Blind, Randomized Controlled Trial
Phase: NA
Conditions: Glaucoma
Sponsor: University of Puerto Rico

 
STUDY TITLE: 
The Effects of Mirtogenol® with Bimatoprost on Intraocular Pressure in Hispanics with Open-
Angle Glaucoma: A Double-Blind, Randomized Controlled Trial 
NCT Number: Not available 
Document Date: December 12, 2019 
 

1 
 
INVESTIGATORS AND INSTITUTION OF AFFILIATION  
• Jorge R. Miranda-Massari, PharmD, Professor at the School of Pharmacy in the Medical 
Science Campus, University of Puerto Rico 
 
• Marino Blasini, M.D., Ophthalmologist and Glaucoma subspecialist, Professor at the 
School of Medicine in the Medical Science Campus, University of Puerto Rico 
 
• Jennifer Acevedo-Rodriguez, BS Biol, PharmDc, School of Pharmacy in the Medical 
Sciences Campus, University of Puerto Rico 
 
• Kyle Melin, PharmD, Professor at the School of Pharmacy in the Medical Science Campus, 
University of Puerto Rico 
 
• Jonathan Hernandez, Ed. D, Professor at the School of Pharmacy in the Medical Science 
Campus, University of Puerto Rico 
 
STUDY TITLE  
The Effects of Mirtogenol® with Bimatoprost on Intraocular Pressure in Hispanics with Open-
Angle Glaucoma: A Double-Blind, Randomized Controlled Trial  
 
RESEARCH QUESTION   
Can Mirtogenol® have an additive effect on the reduction of intraocular pressure when combined 
with bimatoprost in the Hispanic population with primary open-angle glaucoma? 
 
HYPOTHESIS & SPECIFIC AIM   
The combination of Mirtogenol® and bimatoprost will have a superior reduction on intraocular 
pressure than bimatoprost with a placebo in Hispanic patients with primary open-angle glaucoma. 
Null hypothesis: The combination of Mirtogenol®  and bimatoprost will have no difference on the 
reduction of intraocular pressure when compared to bimatoprost with a placebo in the Hispanic 
population with primary open-angle glaucoma (POAG). The specific aim of the study is to 
determine if the addition of Mirtogenol®  to the bimatoprost 0.01% for open-angle glaucoma will 
have an additive effect on the intraocular pressure in the Hispanic population as compared to 
bimatoprost plus placebo. The continuous variable of intraocular pressure (IOP) will be compared 

2 
 
using a t-test to determine statistical significance.  In addition, the safety of the combination of 
Mirtogenol® with bimatoprost will be evaluated, but no statistical analysis will be performed.  
BACKGROUND/SIGNIFICANCE  
Glaucoma is a progressive condition caused by the degeneration and death of retinal 
ganglion cells and their axons that form the optic nerve, resulting in irreversible visual field 
reduction and blindness. Glaucoma is the second cause of legal blindness in the United States1 and 
consists of several eye disorders, the most common being open-angle glaucoma. In primary open-
angle glaucoma (POAG), there is a malfunction in the ocular drainage system resulting in the 
accumulation of aqueous fluid that exerts pressure and may damage the optic nerves. 3 It affects 
up to 4 million individuals in the United States, up to 70 million individuals worldwide and is 
found primarily in patients older than 50 years of age. 2,3 Symptoms are not present until 25 to 
35% of the nerve fibers are damaged. 3 The American Academy of Ophthalmology states that the 
prevalence of POAG in Hispanics is thought to be between that of African-Caribbean and 
Caucasian populations. The risk of developing glaucoma increases with older age, female gender, 
family history of glaucoma, lower ocular perfusion pressure, lower blood pressure, thinner central 
cornea, optic disk hemorrhage, larger cup-to-disk ratio, and specific visual fields findings.3 
Glaucoma is multifactorial and is affected by both intraocular pressure (IOP) dependent and non-
dependent factors such as vascular damage, ocular blood flow and free radicals.4 Intraocular 
pressure can be controlled with glaucoma medications such as bimatoprost, with a successful rate 
between 60% to 80% of patients over a 5-year period. Progression of visual field loss still occurs 
in 8% to 20% of patients despite reaching standard therapy IOP goals.3  
Elevated intraocular pressure is considered the most significant modifiable risk factor for 
the development of glaucoma and ocular hypertension. 3 The normal IOP is below 21 mmHG and 
the mean is around 15.5 mmHg, but POAG patients may have normal or elevated IOP reaching 
more than 30 mmHg.3 The increased IOP in all types of glaucoma may result from the decreased 
facility for aqueous humor outflow.3 The reduction of IOP at any point along the spectrum of the 
disease severity may reduce progression. 3,10 Each 1 mm Hg in IOP reduction reduces risk of 
disease progression by at least 10%.3 The American Academy of Ophthalmology recommends the 
target IOP should be a 25% reduction and states that reduced risk of progression was noted with 
IOP consistently below 18 mmHg or largely below 14 mmHg. Prostaglandin analogs, including 
bimatoprost, are often recommended as first-line therapy and are considered the most potent 

3 
 
topical medications for reducing IOP. They works to lowering intraocular pressure by increasing 
both uveoscleral and trabecular aqueous humor outflow.2 Mirtogenol® is a potent antioxidant and 
free radical scavenger supplement, which has been shown to lower intraocular pressure and 
improve blood flow with minimal side effects. 6,7,8 Mirtogenol® once daily oral capsule contain a 
synergistic combination formula of 80 mg of standardized bilberry extract, Mirtoselect® and 40 
mg of the French maritime pine bark extract, Pycnogenol®.4  
New strategies to prevent retinal ganglion cell death are necessary, since current 
medications are not completely effective in halting the progression of the condition. Mirtogenol®  
is a supplement with antioxidant properties and free radical scavenger, which has  shown to lower 
intraocular pressure with minimal side effects.6,7,8 The purpose of the study is to evaluate the 
efficacy and safety of the combination of Mirtogenol® and bimatoprost on intraocular pressure in 
POAG. Since prostaglandin analogs decrease IOP by increasing the drainage of aqueous humor, 
while Mirtogenol® is assumed to act on humor secretion, the combination of both may have an 
additive response.7 The objective of this study is to determine if Mirtogenol®  has an additive effect 
on the reduction of IOP when combined with bimatoprost in the Hispanic population with primary 
open-angle glaucoma. To date, there have been no studies identified by the researchers in the 
literature review conducted, that evaluate the effect of Mirtogenol® with bimatoprost in the 
reduction of intraocular pressure with POAG patients in the Hispanic population. Due to current 
medication not being able to cure or detain POAG progression, this study may advance our 
knowledge on new complementary alternatives and pave the way for more studies to halt the 
progress of the condition in order to preserve the patient's visual function and improve quality of 
life.9   
LITERATURE REVIEW   
Both constituents of Mirtogenol®, Bilberry11,12,13 and Pycnogenol, 14,15,16 are powerful 
antioxidants. The active components of Bilberry (Mirtoselect®) are flavonoid anthocyanosides 
(anthocyanins). Anthocyanosides are the only flavonoids able to reach the eye as a target organ in 
experimental animals. Unchanged anthocyanosides demonstrated after oral administration that it 
is absorbed and distributed into ocular tissues, showing its ability to pass through the blood-
aqueous and blood retinal barriers.6 A meta-analysis of preliminary clinical research shows that 
taking bilberry anthocyanin 60 mg twice daily for at least 12 months improves visual function in 
patients with normal tension glaucoma when compared to pretreatment.11 Anthocyanins are 

4 
 
involved in the stabilization of collagen fibers, promotion of collagen biosynthesis, decrease 
capillary permeability and fragility.12      
Pycnogenol® major actions include antioxidant as radical scavenger, anti-inflammatory 
effects, and stimulation of eNOS synthesis.13 It has shown to improve pathologic permeability of 
blood vessels and has been extensively studied for enhancing capillary resistance and integrity in 
retinopathy.6  Pycnogenol® has also been found to significantly lower plasma endothelin-1,  a 
vasoconstrictor peptide that affects the trabecular meshwork contractility, which allows for 
regulatory mechanisms controlling fluid outflow.6 Pycnogenol® has previously been shown to 
significantly enhance the generation of endothelial nitric oxide, involved pulsatile choroidal and 
total choroidal blood flow.6 Bilberry and Pycnogenol® may interact with immunosuppressant 
therapy and anticoagulant drugs. Pycnogenol® and bilberry may cause minor side effects that 
include gastrointestinal discomfort, dizziness, headache and nausea.11 Serious side-effects have 
never been reported for Mirtoselect® and Pycnogenol®, despite their long use in ophthalmology, 
predominantly for diabetic retinopathy.7  
Previous studies on human subjects found that Mirtogenol® alone or in combination with 
prostaglandin analogues can reducing IOP. 6,7 A six-month study titled “Effects of Mirtogenol® on 
ocular blood flow and intraocular hypertension in asymptomatic subjects”, used 38 asymptomatic 
nonglaucoma participants with high intraocular pressure ranging from 22 to 26 mmHg. It 
concluded that Mirtogenol® decreased intraocular pressure from 25.2 to 22.2 mmHg and no side 
effects were observed. Another six-month study titled, “Mirtogenol® potentiates latanoprost in 
lowering intraocular pressure and improves ocular blood flow in asymptomatic subjects” evaluated 
the effects in three groups using Mirtogenol®, latanoprost  or both with 79 asymptomatic 
participants with high intraocular pressure ranging from > 35 to < 40 mmHg without glaucoma. It 
concluded that the combination of both, Mirtogenol® and latanoprost, was more effective for 
lowering IOP from 38.0 to 24.2 mmHg and no serious side effects occurred during the study, apart 
from standard side effects in patients related to latanoprost. In 2017, a 12 week study titled 
“Mirtogenol® supplementation in association with dorzolamide-timolol or latanoprost improves 
the retinal microcirculation in asymptomatic patients with increased ocular pressure”, used three 
group with dorzolamide-timolol plus Mirtogenol®, latanoprost drops plus Mirtogenol® or 
latanoprost with 88 asymptomatic participants with high intraocular pressure > 28 mmHg without 
glaucoma. It concluded that supplementation with Mirtogenol® in addition to local ophthalmic 

5 
 
treatments was safe and may lower IOP to normal levels and was well-tolerated without side 
effects.  
In conclusion, we know that no data exist using Mirtogenol® on the Hispanic population, 
which has a high prevalence for glaucoma. No studies on the effect on stable IOP glaucoma 
patients and no studies have been done on a population that were already using antiglaucoma 
medication. Furthermore, there exist the need for data on new alternatives that may detain the 
progression of glaucoma. We do know that Mirtogenol® may lower intraocular pressure alone or 
in combination and has minimal side effects. 6,7 That each 1 mm Hg in IOP reduction reduces risk 
of disease progression by at least 10% 3 and progression of visual field loss still occurs in 8% to 
20% of patients despite reaching standard therapy IOP goals. Our study will provide data on 
Hispanic population and an insight on the effects of Mirtogenol® on stable IOP in glaucoma 
patients. Furthermore, it will evaluate efficacy and safety of Mirtogenol® with bimatoprost 0.01% 
and may pave the way for more studies om new alternatives to reduce intraocular pressure and 
detain the progression of glaucoma.  
METHODOLOGY AND STUDY DESIGN 
A prospective, parallel-group, double-blind, randomized placebo-controlled clinical trial will be 
conducted with an estimated 72 primary open-angle glaucoma patients. A double blind RCT was 
chosen to minimize bias and yield similar groups with the same prognostic at baseline to avoid 
compromising the validity of the study results. The primary efficacy endpoint of the study will be 
IOP and the secondary endpoint will be the safety analysis. Qualifying participants will be 
evaluated for inclusion and exclusion criteria by their ophthalmologist (Dr. Marino Blasini) and 
informed about the study objectives. If they agree to participate, relevant baseline clinical data will 
be collected for each participant and they will be assigned to a treatment or a control group by 
stratified randomization based on their age, intraocular pressure and cup-to-disk ratio. This 
stratified randomization will allow comparability of randomized study groups at baseline. 
Participants will be randomized in a 1:1 ratio to treatment group (bimatoprost 0.01% and 
Mirtogenol®) or control group (bimatoprost 0.01% and placebo) and be assigned a participant ID 
number. Once the randomization process has concluded, participants will be notified to pass by 
the office to receive the product and to start using the Mirtogenol® or placebo the next day. Both 
Mirtogenol® and placebo bottles will label drug of study and be registered with a number 
identification for each patient. Mirtogenol and the placebo will be stored in a destinated area in the 

6 
 
primary investigator’s pharmacy under a cool, dry environment that protects them from extreme 
temperature changes and light. Oral and written instructions on drug regimen, including route of 
administration, frequency, proper storage and mode of administer will be provided. The groups 
will self-instill one drop of bimatoprost 0.01% in the affected eye(s) once daily as instructed by 
the ophthalmologist. In addition, participants will use one (1) capsule of Mirtogenol® or one (1) 
placebo capsule orally daily in the morning with food. Mirtogenol® will be funded by Life 
Extension Clinical Research, Inc.  Placebo capsules will be similar in appearance, size, and route 
of administration to Mirtogenol®.   
The study will have five visits: screening and baseline, week 4, week 8, week 12 and week 24 
of approximate 30-60 minutes of duration and an addition visit for pickup of the product after the 
randomization process. An ophthalmological evaluation will be conducted by a glaucoma specialist 
at each visit. At the baseline visit, the following tests will be performed: visual acuity, visual field 
evaluation, applanation tonometry, optical coherence tomography (OCT), and pachymetry. At week 
4, and week 8 the following tests will be performed: visual acuity and applanation tonometry. At 
week 12, the following tests will be performed: visual acuity, visual field evaluation and applanation 
tonometry.  At week 24, assessments will include the following: visual acuity, visual field evaluation, 
applanation tonometry, optical coherence tomography and pachymetry.  
The same equipment will be used throughout the study for measurement consistency. Each 
test will be measured in the morning and the patient will be resting, sitting for at least 10 minutes 
before measurement.  The tests will always be performed by the same person to rule out variations. 
At each visit, the IOP will be measured twice, with 10-minute intermissions between measurements, 
and mean values will be recorded. If only one eye is determined eligible as trial eye (meeting the 
diagnostic criteria for glaucoma), then all assessments will be performed only for the trial eye. If both 
eyes are eligible, only the eye with highest baseline mean IOP will be included in the statistical 
analysis. Patients will be instructed not to take any medications within two hours before 
measurements. Any therapy considered necessary for the patient’s welfare will be given at the 
discretion of the treating physician and will be documented.  
Safety measures include non-invasive techniques, standard of care treatment during the 
duration of the study, ophthalmological evaluations and assessment tests. Side effects or adverse 
effects will be reported and evaluated by the ophthalmologist at each visit and if deemed necessary 
the trial medication (Mirtogenol® or matching placebo) will be discontinued and therapy adjusted as 

7 
 
appropriate by the clinician. Adverse effects will be recorded at each study visit as well as the 
probability of possible association of the adverse effects to the treatment. Compliance will be 
reinforced with daily reminder for a month by email or text messages and then weekly reminders until 
the termination of the study. A monthly calendar will be provided to keep track of doses and possible 
miss doses. Patient must bring their supplement or placebo bottles and monthly track calendar to each 
visit and a pill count will be performed. Participants will be contacted one month after discontinuing 
the trial medication to assess for any prior changes or side effects.  
 
The expected duration of the subject’s participation shall be 24 weeks. The duration of the 
study will be one year. Timeline: Study January 2020- January 2021 
● IRB Submission in December 2019- January 2020 
● Project approval in January – January - February 2020 
● Subjects recruitment process in February 2020- March 2020 
● Study and data collection begin in April 2020- December 2020 
● Data analysis in December 2020 – April 2021 
● Final report and presentation in May 2021 
STUDY SUBJECTS   
 
The data selection will be using a non-probabilistic sample with convenience sampling, 
preferably with a consecutive design. The individuals recruited will be Hispanic who receive 
services in a private ophthalmology glaucoma specialist office in San Juan, Puerto Rico. 
Inclusion criteria include patients with:  
1. Diagnosed with primary open-angle glaucoma (POAG) 
2. > 21 years old 
3. Patient must be Hispanics (self-identified) 
4. Current glaucoma treatment regimen of monotherapy with bimatoprost 0.01% 
administered into affected eye(s) once daily with stable IOP < of 21 mmHG  
Exclusion criteria include patients with: 
1. < 21 year old,  
2. Pregnant women or those who are planning to become pregnant in the next six 
(6) months,  

8 
 
3. Women who are breastfeeding,  
4. Individuals with cardiovascular diseases that have required medical intervention in the 
past three (3) months,  
5. Patients that required any kind of surgery, radiotherapy or chemotherapy in the past 
three (3) months, 
6. Patients with advanced glaucoma with a cup to disk ratio > 0.9, previous glaucoma 
surgeries or other abnormalities of the eye that affect the visual pathway,  
7. Patients with uveitis, diabetic retinopathy, macular edema or degenerative eye,  
8. Patients with a history of adverse side effects of prostaglandin inhibitors,   
9. Patients planning to undergo trabeculectomy or cataract surgery during the next six (6) 
months,  
10. Patients using immunosuppressant therapy and anticoagulant, 
11. Patients currently using Mirtogenol®.   
 
Both bimatoprost 0.01% and Mirtogenol® have been shown to have a good tolerability profile 
and a low incidence of side effects in previous studies. 6,7,8 The risks and discomfort that may result 
because of this study are mild and minimal. Mirtogenol® contains bilberry and Pycnogenol® which 
may theoretically interact with immunosuppressive therapies and anticoagulant. 52  Mirtogenol® may 
cause gastrointestinal discomfort, dizziness, headache and nausea. The ophthalmic solution of 
bimatoprost can cause an increase in the pigmentation of the iris, periorbital tissue (eyelid) and 
eyelashes, conjunctival hyperemia, conjunctival edema, conjunctival hemorrhage, eye irritation, eye 
pain, eye itching, eyelid sprain, pruritus eyelids, blurred vision and reduced visual acuity. All visual 
tests will be noninvasive, but some may cause discomfort and a small chance of cornea abrasion, 
which usually heals in a few days. 
Benefits of the study may include intraocular pressure improvement, visual examinations and 
tests at no cost and the results of each test performed will be provided at the end of the study.  The 
information in this research study may lead to better treatments in the future for people with glaucoma. 
Safety measures include non-invasive techniques, standard of care treatment during the duration of 
the study, ophthalmological evaluations, and assessment tests. Side effects or adverse effects will be 
reported and evaluated by a specialist and discontinuation of the trial medication will occur if deemed 
necessary by the treating ophthalmologist. Adverse effects will be documented at each study visit and 
the treating ophthalmologist will assess possible association of all adverse effects to the trial 

9 
 
medication. A visual acuity score indicating a loss of two or more lines or a cup to disk ratio from 
mild (<0.65) to moderate (0.7-0.85) or moderate to severe (>0.9) will be considered relevant and a 
possible discontinuation of the study of participant from the study. Any changes in visual field, central 
corneal thickness or increase in IOP will be considered relevant and will be evaluated for a possible 
discontinuation of the participant.  
To ensure confidentiality, all information will be coded so that it cannot be associated with 
any individual. A separate document (code sheet) will have the participant full name and the code 
assigned and will be destroyed as soon as data collection has completed. The data collection form 
will only have the code number to avoid direct connection with the participant’s personal information. 
All data entered into the computerized database will be identifiable by subject code number only.  
The individuals recruited for this study will be informed of the purpose of the investigation and 
treatment procedure in accordance with the Declaration of Helsinki and asked to provide written 
consent for their participation. All participants are required to read and sign detailed consent forms 
before participating in the study. Participants are advised of the voluntary nature of participation and 
of their right to withdraw from the project at any time and to require that information about them be 
removed from data analysis. Each study participant will receive a verbal and written description of 
the study. Contact information will include name, phone number, address, and email address of the 
patient and one emergency contact. All information will be kept confidential and protected under the 
Privacy Rule of the Health Insurance Portability and Accountability Act (HIPAA). The experimental 
design will be submitted to the Institutional Review Board (IRB) of the Medical Sciences Campus of 
the School of Medicine of Puerto Rico for approval. 
 
 
VARIABLES   
Variable  
Type 
Description  
Measurement  
Treatment 
Groups: 
(Bimatoprost 
0.01% with 
Mirtogenol® 
or Bimatoprost 
0.01% with 
Placebo) 
Independent 
variable 
(Dichotomus) 
Bimatoprost is a prostaglandin 
inhibitor used to lower IOP.  
Mirtogenol®, a potent antioxidant 
and free radical scavenger 
supplement, or matching placebo 
to take daily in addition to 
bimatoprost.   
Mirtogenol® or 
Matching Placebo 
One capsule orally, 
once daily in the 
morning  

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Intraocular 
pressure  
Dependent 
variable  
(Quantitative - 
Continuous) 
The fluid pressure inside the eye 
created by the continual renewal 
within the eye. 
Goldmann 
Applanation 
Tonometry  
Visual acuity 
Dependent 
variable 
(ordinal) 
Measures the clarity of vision. 
 
Snellen chart 
 
 
Cup-to-disc 
ratio  
 
Dependent 
variable  
(ordinal) 
Measures the progression of 
glaucoma.  
Staging glaucomatous damage: 
Mild: <0.65 
Moderate: 0.7-0.85 
Severe: >0.9  
OCT  
Central 
Corneal 
Thickness 
Dependent 
variable  
(Quantitative - 
Continuous) 
Is the thickness of the cornea of 
the eye. 
 
Pachymetry 
 
Visual field 
changes 
Dependent 
variable  
(Dichotomus) 
Any type of visual field changes 
in the participants.  
Perimetry  
Adverse effects Dependent 
variable  
(Dichotomus) 
Adverse effects include:  
● Conjunctival hyperemia 
● Periocular skin 
pigmentation  
● Itching 
● Eye irritation 
● Foreign body sensation 
● Growth of lashes 
● Skin rash 
● Headache  
● Nausea 
● Vomiting 
● Diarrhea 
● Dizziness (vertigo) 
● Hyperglycemic episode 
● Hypoglycemic episodes 
Patients will be 
questioned on the 
presence or absence 
of adverse effects.  

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● Bleeding 
● Other 
 
ANALYTIC PLAN  
A minimum sample of 72 participants will be used based on the primary efficacy endpoint 
of intraocular pressure to have an 80% probability to detect a difference between treatments at a 
two-sided 0.05 significance level.  This is based on the assumption that the within-patient standard 
deviation of the response variable is 3.9 mmHg. Approximately 72 patients will be randomized in 
a 1:1 ratio to bimatoprost with Mirtogenol® or bimatoprost with placebo (intent-to-treat [ITT] 
population). There will be 36 patients enrolled in each population. Data will be presented as mean 
values with standard deviation to describe the population. The 95% confidence intervals 
assessments will be provided for descriptive purposes. The inferential statistical analysis to be 
conducted for the primary efficacy endpoint of IOP will be a t-test. All statistical tests will be 
performed with a significance level set at P<0.05. The statistical software to be use will be Minitab. 
The safety analysis includes presence of adverse effects, changes in visual acuity, visual field, 
central corneal thickness and cup-to-disk ratio, but no correlation for multiple comparisons will be 
performed. The intention-to-treat method will be used where all participants who were randomized 
are included in the data analysis regardless of whether they received their assigned treatment for 
the entire study. Missing data will not be replaced, instead the last observation or value will be 
carried forward to account for patients who dropped out and for the statistical analysis.  
Sample Size: We used the standardized effect size to estimate the sample size needed for 
the primary efficacy endpoint of IOP. The standardized effect size is the effect size divided by 
the standardized deviation of the variable. A previous study has reported that the mean on 
intraocular pressure in treated glaucoma patients is 15.1 mmHg, with a standard deviation of 3.9 
mmHg.20 We would like to be able to detect a difference of 15% or more in the mean intraocular 
pressure between the two treatment groups. The effect size was calculated to be 0.39 and the 
standardized effect size is 0.60. Using a two-sided α of 0.05 and power of 80%, the estimated 
sample size needed was 36 patients for each group, and 72 patients in total.21   
LIMITATIONS   
The limitations that may affect the internal validity may be malfunction in equipment, 
misinterpretation of the data, or errors in the input of the data. Factors that may affect the external 
validity are use of other drugs that may affect the IOP, nonadherence, or discontinuation of the 

12 
 
participant in the study. There may be relevant confounding elements that remain unidentiﬁed and 
the potential confounding impact of both ocular and systemic medications warrants further 
investigation. A longer duration of study is required to determine long term effects and the effects 
on the progression in glaucoma patients.  
 
 
 
APPENDIX  
Table 1:  Assessment Template 
Assessment Template for Study Inclusion 
Patients Name:  
 
Check ⬜ with an X  
A. Inclusion criteria  
⬜ Diagnosed with primary open-angle 
glaucoma (POAG) 
 
⬜ Patient over 21 years old 
⬜ Hispanic 
⬜ Using only bimatoprost 0.01% 
⬜ Consent from patient 
 
 
 
 
B. Exclusion criteria include patients 
with: 
 
⬜ Patient under 21 years old 
⬜ Pregnant women or those who are 
planning to become pregnant in the next six 
(6) months 
 
⬜ Women who are breastfeeding, 
⬜ Cardiovascular diseases that have 
required medical intervention in the past 
three (3) months, 
 
⬜ Patients that required any kind of 
surgery, radiotherapy or chemotherapy in 
the past three (3) months 
 
⬜ Patients with advanced glaucoma with a 
cup to disk ratio > 0.9, previous glaucoma 
surgeries or other abnormalities of the eye 
that affect the visual pathway 
 

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⬜ Patients with uveitis, diabetic 
retinopathy, macular edema or degenerative 
eye 
 
⬜ Patients with a history of adverse side 
effects of prostaglandin inhibitors 
 
⬜ Patients planning to undergo 
trabeculectomy or cataract surgery during 
the next 6 months. 
 
⬜ Patients using immunosuppressant 
therapy, and anticoagulant. 
 
⬜ Patients who are currently using 
Mirtogenol®. 
 
 
 
 
 
Table 2: Data Collection Form 
Data Collection Form 
Code number: ________ 
 
Gender 
     [   ] Male           [   ] Female  
Age 
_______ years 
 
Baseline  
Week 4 
Week 8 
Week 12 
Week 24  
IOP  
Mean 
(two takes 10 
min. apart)  
1) 
 
__________ 
 
2) 
1) 
 
__________ 
 
2) 
1) 
 
__________ 
 
2) 
1) 
 
__________ 
 
2) 
1) 
 
__________ 
 
2) 

14 
 
 
 
 
 
 
 
Cup to disk 
ratio  
N/A 
N/A 
N/A 
 
Central 
Corneal 
Thickness 
(CCT) 
 
N/A 
N/A 
N/A 
 
Visual acuity ____/____ 
____/____ 
____/____ 
____/____ 
____/____ 
Visual field 
changes 
[   ] Yes      
[   ] No 
N/A 
N/A 
[   ] Yes      
[   ] No 
[   ] Yes      
[   ] No 
Adverse Effects 
-Conjunctival 
hyperemia 
 
-Periocular 
skin 
pigmentation 
 
-Itching 
 
-Eye 
irritation 
 
-Foreign 
body 
sensation 
 
-Growth of 
lashes 
 
-Skin rash 
 
-Headache 
 
[   ] Y  [   ] N 
 
 
[   ] Y  [   ] N 
 
[   ] Y  [   ] N 
   
[   ] Y  [   ] N 
 
 
[   ] Y  [   ] N 
 
 
[   ] Y  [   ] N 
 
 
[   ] Y  [   ] N 
 
 
[   ] Y  [   ] N 
 
[   ] Y  [   ] N 
 
[   ] Y  [   ] N 
 
 
[   ] Y  [   ] N 
 
[   ] Y  [   ] N 
   
[   ] Y  [   ] N 
 
 
[   ] Y  [   ] N 
 
 
[   ] Y  [   ] N 
 
 
[   ] Y  [   ] N 
 
 
[   ] Y  [   ] N 
 
[   ] Y  [   ] N 
 
[   ] Y  [   ] N 
 
 
[   ] Y  [   ] N 
 
[   ] Y  [   ] N 
   
[   ] Y  [   ] N 
 
 
[   ] Y  [   ] N 
 
 
[   ] Y  [   ] N 
 
 
[   ] Y  [   ] N 
 
 
[   ] Y  [   ] N 
 
[   ] Y  [   ] N 
 
[   ] Y  [   ] N 
 
 
[   ] Y  [   ] N 
 
[   ] Y  [   ] N 
   
[   ] Y  [   ] N 
 
 
[   ] Y  [   ] N 
 
 
[   ] Y  [   ] N 
 
 
[   ] Y  [   ] N 
 
 
[   ] Y  [   ] N 
 
[   ] Y  [   ] N 
 
[   ] Y  [   ] N 
 
 
[   ] Y  [   ] N 
 
[   ] Y  [   ] N 
   
[   ] Y  [   ] N 
 
 
[   ] Y  [   ] N 
 
 
[   ] Y  [   ] N 
 
 
[   ] Y  [   ] N 
 
 
[   ] Y  [   ] N 
 
[   ] Y  [   ] N 
 

15 
 
-Nausea 
 
-Vomiting 
 
-Diarrhea 
 
-Dizziness 
(vertigo) 
 
-Hyperglyce-
mic episode   
 
-Hypoglyce-
mic episode 
 
-Bleeding 
 
 
-Other 
 
 
[   ] Y  [   ] N 
 
[   ] Y  [   ] N 
 
[   ] Y  [   ] N 
 
[   ] Y  [   ] N 
 
 
[   ] Y  [   ] N 
 
 
[   ] Y  [   ] N 
 
 
[   ] Y  [   ] N 
 
 
___________ 
 
[   ] Y  [   ] N 
 
[   ] Y  [   ] N 
 
[   ] Y  [   ] N 
 
[   ] Y  [   ] N 
 
 
[   ] Y  [   ] N 
 
 
[   ] Y  [   ] N 
 
 
[   ] Y  [   ] N 
 
 
___________ 
 
[   ] Y  [   ] N 
 
[   ] Y  [   ] N 
 
[   ] Y  [   ] N 
 
[   ] Y  [   ] N 
 
 
[   ] Y  [   ] N 
 
 
[   ] Y  [   ] N 
 
 
[   ] Y  [   ] N 
 
 
___________ 
[   ] Y  [   ] N 
 
[   ] Y  [   ] N 
 
[   ] Y  [   ] N 
 
[   ] Y  [   ] N 
 
 
[   ] Y  [   ] N 
 
 
[   ] Y  [   ] N 
 
 
[   ] Y  [   ] N 
 
 
___________ 
[   ] Y  [   ] N 
 
[   ] Y  [   ] N 
 
[   ] Y  [   ] N 
 
[   ] Y  [   ] N 
 
 
[   ] Y  [   ] N 
 
 
[   ] Y  [   ] N 
 
 
[   ] Y  [   ] N 
 
 
___________ 
 
Table 3: Code Sheet 
Code Sheet 
First and last names                                                                      Code number:   
1.  
 
2.  
 
3.  
 
4.  
 
5.  
 
6.  
 
7.  
 

16 
 
8.  
 
9.  
 
10.  
 
11.  
 
12.  
 
13.  
 
14.  
 
15.  
 
16. …72 
 
 
Table 3: Baseline Characteristics 
Baseline Characteristics 
Description 
Bimatoprost with 
Mirtogenol® (n=36) 
Bimatoprost with Placebo 
(n=36) 
Age, mean (SD), yrs 
 
 
Gender, No. (%) 
 
 
IOP, mean (SD), mmHg 
 
 
Cup to disk ratio, mean (SD)  
 
CCT, mean (SD) mm 
 
 
Visual acuity, mean (SD) 
 
 
 
Table 4: Primary Efficacy Endpoint 
Primary Efficacy Endpoint 

17 
 
Time of 
Assessment and 
End Point 
(Week 12) 
Bimatoprost 
with 
Mirtogenol® 
(n=36) 
Bimatoprost 
with Placebo 
(n=36) 
Difference 
[95% CI]  
P-value 
IOP 
 
 
  
Table 5: Safety Analysis 
Table 3. Safety Analysis   
Variable  
Bimatoprost with 
Mirtogenol® (n=36) 
Bimatoprost with Placebo 
(n=36) 
Changes in Vision and progression of glaucoma -no (%) 
Cup to disk ratio  
 
 
Central Corneal Thickness 
 
 
Visual acuity  
 
 
Visual field changes  
 
 
Adverse Effects Reported- no. (%) 
Conjunctival hyperemia 
 
 
Periocular skin pigmentation  
 
Itching 
 
 
Eye Irritation 
 
 
Foreign Body Sensation 
 
 
Growth of lashes 
 
 
Skin Rash 
 
 
Headache  
 
 

18 
 
Nausea 
 
 
Vomiting 
 
 
Diarrhea 
 
 
Dizziness (vertigo) 
 
 
Hyperglycemic episode   
 
 
Hypoglycemic episode 
 
 
Bleeding 
 
 
Other 
 
 
 
Consent form: Spanish and English (See separate attachment) 
 
 
 
 
 
 
Calendar for Monthly Compliance Assessment:   
March 2020 
Sunday 
Monday 
Tuesday 
Wednesday 
Thursday 
Friday 
Saturday 
1 
⬜ Used 
 
⬜ Miss 
 
2 
⬜ Used 
 
⬜ Miss 
 
3 
⬜ Used 
 
⬜ Miss 
 
4 
⬜ Used 
 
⬜ Miss 
 
5 
⬜ Used 
 
⬜ Miss 
 
6 
⬜ Used 
 
⬜ Miss 
 
7 
⬜ Used 
 
⬜ Miss 
 
 

19 
 
8 
⬜ Used 
 
⬜ Miss 
 
 
9 
⬜ Used 
 
⬜ Miss 
 
10 
⬜ Used 
 
⬜ Miss 
 
11 
⬜ Used 
 
⬜ Miss 
 
12 
⬜ Used 
 
⬜ Miss 
 
13 
⬜ Used 
 
⬜ Miss 
 
14 
⬜ Used 
 
⬜ Miss 
15 
⬜ Used 
 
⬜ Miss 
 
 
 
16 
⬜ Used 
 
⬜ Miss 
 
17 
⬜ Used 
 
⬜ Miss 
 
18 
⬜ Used 
 
⬜ Miss 
 
19 
⬜ Used 
 
⬜ Miss 
 
20 
⬜ Used 
 
⬜ Miss 
 
21 
⬜ Used 
 
⬜ Miss 
22 
⬜ Used 
 
⬜ Miss 
 
 
23 
⬜ Used 
 
⬜ Miss 
 
24 
⬜ Used 
 
⬜ Miss 
 
25 
⬜ Used 
 
⬜ Miss 
 
26 
⬜ Used 
 
⬜ Miss 
 
27 
 ⬜ Used 
 
⬜ Miss 
 
28  
⬜ Used 
 
⬜ Miss 
29 
⬜ Used 
 
⬜ Miss 
 
 
 
30 
⬜ Used 
 
⬜ Miss 
Instructions:  
 
Mark ⬜ Used- If drug of study was used  
 
Mark ⬜ Miss- If drug of study was Not used  
 
Use one (1) capsule of drug of study capsule orally daily in the 
morning with food. 
 
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