Conditions: Cataract
Keywords: cataract surgery Prophylaxis
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 35
Healthy volunteers: no

Brief summary:
To compare the use of a compounded eye drop containing an antibiotic, a non-steroidal and steroidal anti-inflammatory to standard of care that is the use of 3 different topical medications to prevent inflammation and infection after routine cataract surgery.

Detailed description:
Cataract surgery is one of the most commonly performed surgeries in the world today. To improve the overall procedure outcome, prophylactic topical antibiotics and anti-inflammatories (steroidal and non-steroidal, NSAID) are frequently used to decrease the risk of postoperative infection (e.g., endophthalmitis) and intraocular inflammation (e.g., macular edema, CME).

Even though, the large body of literature that supports the significance of prophylactic eye drops prior to surgery, patient compliance is a common problem. Different factors have been associated with patient's lack of compliance. It could be due to patient's inability to self- administer the drops, lack of understanding of the importance of using the prophylactic treatment as well as understanding the instructions of how to administer the drops and its storage, or just forgetfulness or the fact that they don't like to put the drops multiple times a day for 2-4 weeks, therefore they just avoid doing it. About 64% of patients adhere to the prescribed treatment.

There is a new alternative that combines the most commonly used antibiotic and anti-inflammatories into a single drop. The use of a single drop compounded ophthalmic solution may offer advantages such as increased compliance, patient comfort and reduced ocular toxicity. T

The purpose of this study is to compare the Pred-Gati-Brom formulation to the standard topical drops regimen that includes the topical use of Gatifloxacin, Bromfenac and Prednisolone acetate 1%.

Arms:
arm 1: Compounded eye drop containing Gatifloxacin (antibiotic), bromfenac (non-steroidal anti-inflammatory), and prednisolone acetate 1% used three times a day (TID) starting 1 day prior to surgery and continuing after surgery for 2 weeks then twice a day for a week and once a day for another week. arm 2: * Gatifloxacin 0.5%, 1 drop, QID for 3 days prior to surgery and will continue for 2 weeks after surgery and then discontinue.
* Bromfenac 0.07%: 1 drop QD starting 3 days before surgery, continue QD for 4 weeks after surgery and then discontinue.
* Prednisolone acetate 1% will be started after surgery QID for 2 weeks, tapered to BID for 2 weeks, and then discontinue.

Interventions: intervention 1: Pred-Gati-Brom intervention 2: Prednisolone acetate 1% ophthalmic suspension intervention 3: Gatifloxacin Ophthalmic intervention 4: Bromfenac 0.075% Oph Solution
Intervention descriptions: intervention 1: The combination drop therapy containing prednisolone acetate 1%, gatifloxacin 0.5%, and bromfenac 0.075% intervention 2: Steroidal anti-inflammatory intervention 3: Antibiotic intervention 4: Non-steroidal anti-inflammatory

Protocol document:
Prot_SAP_000.pdf: 
 
Solomon KD, Sandoval HP 
 
1 
 
 
CONFIDENTIAL 
CEP 16-001 
Version 2.0 – 16.OCT.17 
 
 
Cover page 
 
 
Official title: Lessdrops™ Prophylactic Treatment after Routine 
   Phacoemulsification Compared to Standard Drops 
   Regimen. 
 
NCT number: 03578276 
 
Document date: 16.Oct.2017 
 
 
 
 
 
 
 
 
 
 
 


 
Solomon KD, Sandoval HP 
 
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CONFIDENTIAL 
CEP 16-001 
Version 2.0 – 16.OCT.17 
 
Lessdrops™ Prophylactic Treatment after Routine Phacoemulsification Compared to Standard 
Drops Regimen. 
 
Sponsor:  
 
 
Carolina Eyecare Physicians, LLC 
 
 
 
 
1101 Clarity Rd., Suite 100 
 
 
 
 
Mt. Pleasant, SC 29466 
(843) 881 3937 
Kerry D. Solomon, MD, Principal Investigator 
Helga P. Sandoval, MD, MSCR, Research Manager 
 
Study Product:  
 
PRED-GATI-BROM 
 
Protocol Number: 
 
CEP-16-001 
 
 
 
 
Initial version date: 26. Jul.2016 
 
 
 
 
Final version date: 16.Oct.2017 
 
 
 
 
 
 
Principal Investigator: 
Kerry D. Solomon, MD 
 
 
 
 
 
 
 
 
 
 
Investigator Agreement: 
I have read the clinical study described herein, recognize its 
confidentiality and agree to conduct the described trial in 
compliance with Good Clinical Practices (GCP), the Declaration of 
Helsinki, this protocol and all applicable regulatory requirements. 
Additionally, I will comply with all procedures for obtaining 
informed consent, data recording and reporting, will permit 
monitoring, auditing, and inspection of my research center, and 
will retain all records until notified by the sponsor. 
 
Principal Investigator: 
______________________________________________________ 
Signature 
 
 
 
 
 
Date 
 
Name of the Investigator: 
_________________________________________________ 
Site Number: 
_________________________________________________ 
Address: 
_________________________________________________ 
_________________________________________________ 
Telephone: 
   
  
_________________________________________________ 
 
 


 
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Lessdrops™ Prophylactic Treatment after Routine Phacoemulsification Compared to Standard 
Drops Regimen. 
 
 
INTRODUCTION 
Cataract surgery is one of the most commonly performed surgeries in the world today. To 
improve the overall procedure outcome, prophylactic topical antibiotics and anti-
inflammatories (steroidal and non-steroidal, NSAID) are frequently used to decrease the risk of 
postoperative infection (e.g., endophthalmitis) and intraocular inflammation (e.g., macular 
edema, CME).  
Although the incidence of endophthalmitis has been reported to be less than 0.25% (range 
0.02% to 0.25%);1-9 its consequences can be devastating. To prevent endophthalmitis, the use 
of prophylactic antibiotics has become the standard of care.10-12 The type of prevention used 
varies from surgeon to surgeon and from Country to Country. Some surgeons prefer to use 
topical drops, others intracameral antibiotics, and some others rather use subconjuctival 
injections. Factors that could influence the ophthalmologist’s selection include antibiotic 
spectrum, efficacy, side effects, cost, and experience, among others. Chang et al11 reported that 
91 % of American Society of Cataract and Refractive Surgery members used prophylactic 
antibiotics starting prior to surgery and 98% used them postoperatively. The use of 
intracameral antibiotics alone or in conjunction with the topical one has shown to further 
reduce the incidence of endophthalmitis.3, 9, 13  
The incidence of pseudophakic cystoid macular edema (CME) has been reported from 0.1% up 
to 4% and it depends on the method used to diagnose it. The incidence of angiographic CME is 
higher (up to 70%) than the incidence of clinically significant CME.14, 15 There are different 
factors that affect its incidence: type of surgery,15 presence of predisposing conditions such as 
intraocular inflammation (i.e. uveitis)16, 17 and systemic diseases (i.e. diabetes).18   
Several studies have shown the effectiveness of steroids and NSAIDs in the prevention of CME 
after cataract surgery not just in diabetic patients. Furthermore, some studies have shown a 
greater reduction in the incidence of CME when using NSAIDs compared to steroid alone.19-21 
Even though, the large body of literature that supports the significance of prophylactic eye 
drops prior to surgery, patient compliance is a common problem. Different factors have been 
associated with patient’s lack of compliance. It could be due to patient’s inability to self- 


 
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administer the drops, lack of understanding of the importance of using the prophylactic 
treatment as well as understanding the instructions of how to administer the drops and its 
storage,22 or just forgetfulness or the fact that they don’t like to put the drops multiple times a 
day for 2-4 weeks, therefore they just avoid doing it.  About 64% of patients adhere to the 
prescribed treatment.23, 24 
There is a new alternative that combines the most commonly used antibiotic and anti-
inflammatories into a single drop. The use of a single drop compounded ophthalmic solution 
may offer advantages such as increased compliance, patient comfort and reduced ocular 
toxicity. Three combinations are available today: Pred-Gati, Prednisolone acetate and 
gatifloxacin hydrochloride; Pred-Nepaf, Prednisolone acetate and nepafenac; and Pred-Gati-
Nepaf, Prednisolone acetate, gatifloxacin hydrochloride, and nepafenac. Different studies have 
shown the safety and efficacy of topical antibiotic/steroid combination with comparable results 
to standard single component topical medication used prophylactically pre and post cataract 
surgery.25-28   Additionally, in a recent study, Pred-Moxi-Ketor used three times a day for one 
week followed by Pred-Ketor twice a day for 2 – 4 weeks was compared to an intravitreal 
injection containing triamcinolone, moxifloxacin and vancomycin (Tri-Moxi-Vanc). Results 
showed similar outcomes with good control of postoperative inflammation and patient comfort 
without any unexpected adverse events. 29 
The purpose of this study is to evaluate the efficacy of Pred-Gati-Brom and compare it to the 
standard topical drops regimen used for routine cataract surgery. 
 
1. OBJECTIVE: 
 
To assess the efficacy of a formulation containing prednisolone acetate, gatifloxacin 
hydrochloride, and bromfenac used as combination drop therapy before and after routine 
cataract surgery and intraocular (IOL) implantation compared to standard prophylactic 
treatment that includes the topical use of Gatifloxacin, Bromfenac, and Prednisolone acetate 
1%.   
 
2. STUDY DESIGN AND METHODS: 
2.1. Assessed article: Formulation containing prednisolone acetate, gatifloxacin 
hydrochloride, and bromfenac. 
 
2.2. Study Design:  Prospective, randomized, single site, contralateral eye study. 
 
2.3. Subjects:  


 
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2.3.1. Inclusion Criteria: 
Subjects MUST fulfill the following conditions to qualify for enrollment into the trial 
1. Subject is undergoing bilateral cataract extraction or refractive lens exchange with 
intraocular lens implantation.  
2. Gender: both males and females.  
3. Age: 50 years and older. 
4. Willing and able to provide written informed consent for participation in the study. 
5. Willing and able to comply with scheduled visits and other study procedures.  
6. Willing and able to administer eye drops and record the times the drops were instilled. 
7. Scheduled to undergo standard cataract surgery with topical anesthesia in both eyes 
within 6-15 days between surgeries. 
8. Potential postoperative best-corrected visual acuity of 20/30 or better. 
 
2.3.2. Exclusion Criteria: 
Subjects with ANY of the following conditions on the eligibility exam may NOT be 
enrolled into the trial. 
1. Severe preoperative ocular pathology:  amblyopia, rubella cataract, proliferative 
diabetic retinopathy, shallow anterior chamber, macular edema, aniridia or iris 
atrophy, uveitis, history of iritis, iris neovascularization, medically uncontrolled 
glaucoma, microphthalmos or macrophthalmos, optic nerve atrophy, advanced 
macular degeneration, advanced glaucomatous damage, etc. 
2. Uncontrolled diabetes.  
3. Use of any systemic or topical drug known to interfere with visual performance. 
4. Contact lens use during the active treatment portion of the trial. 
5. Any concurrent infectious/noninfectious conjunctivitis, keratitis or uveitis. 
6. History of chronic intraocular inflammation. 
7. History of retinal detachment. 
8. Pseudoexfoliation syndrome or any other condition that has the potential to weaken 
the zonules. 
9. Any additional ocular surgical procedures at time of cataract extraction (i.e. iStent) 
except corneal incisions for the correction of astigmatism. 
10. Anesthesia other than topical anesthesia (i.e. retrobulbar, general, etc). 
11. Any clinically significant, serious or severe medical or psychiatric condition that may 
increase the risk associated with study participation or may interfere with the 
interpretation of study results. 
12. Participation in (or current participation) any ophthalmic investigational drug or 
device trial within the previous 30 days prior to the start date of this trial. 
13. Intraocular conventional surgery within the past three months or intraocular laser 
surgery within one month. 
 


 
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The principal investigator reserves the right to declare a patient ineligible or non-
evaluable based on medical evidence that indicates the patient is unsuitable for the 
trial. 
 
2.3.3. Exclusion Criteria during surgery 
If any of the following exclusion criteria are applicable to the study eye, the subject 
should not continue in the study. 
 
1. Significant vitreous loss. 
2. Significant anterior chamber hyphema. 
3. Uncontrollable intraocular pressure. 
4. Zonular or capsular rupture. 
5. Bag-sulcus, sulcus-sulcus or unknown placement of the haptics. 
6. Suturing of incision required at time of surgery. 
7. Significant sedation or retrobulbar block during surgery. 
8. Other procedure, such as pupil stretch, expanders, iris hooks during surgery.   
 
 
Note: Any subject in which surgery has been aborted for either eye should immediately 
be discontinued from the study and an exit form completed for that subject. These 
subjects will be followed up as per the clinic standard of care, monitored for safety, and 
their data will be excluded from the study efficacy analysis (obtained from FDA 
Database Research Results Feb, 05, 2009). All adverse events will be appropriately 
documented and reported. 
 
Additionally, participants who are considered to be a vulnerable subject population are 
not to be enrolled into the study without prior written authorization from both the 
Sponsor and the IRB to ensure that a description of additional safeguards are in place 
during the consenting and enrollment processes. Vulnerable populations include, but 
are not limited to, the following: 
1. 
Prisoners 
2. 
Nursing home residents /institutionalized individuals 
3. 
Mentally disabled /cognitively impaired individuals 
4. 
Sponsor employees and their family members 
5. 
Site employees and their family members that are directly and indirectly 
involved with the study 
6. 
Students of the university or the principal investigator participating in the study 
7. 
Economically and/or educationally disadvantaged individuals 
8. 
Comatose individuals / traumatized individuals 
9. 
Adults who do not read and/or write 
10. 
Hearing impaired individuals 


 
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11. 
Terminally ill individuals / individuals with life-threatening conditions 
 
3. Study Procedures 
 
3.1. Informed Consent / Subject enrollment 
No subject will be enrolled into the study that does not meet the inclusion/exclusion 
criteria and does not sign the current approved informed consent document. Informed 
consent will be obtained prior to collecting any data for the study. The original signed 
documents will be maintained by the investigator as a permanent part of the subject's 
medical records. A signed copy will be provided to the subject. 
 
3.2. Surgery Procedures: 
 
Eyes of the study participants will be randomly assigned to one of two groups:  
 
• Group A, test eye: Combination Drop Therapy (Pred-Gati-Brom) 
The combination drop therapy containing prednisolone acetate 1%, gatifloxacin 
0.5%, and  bromfenac 0.075% used three times a day (TID) starting 1 day prior to 
surgery and continuing after surgery for 2 weeks then twice a day for a week and 
once a day for another week. 
• Group B, control eye:  
o Gatifoxacin 0.5%, 1 drop, QID for 3 days prior to surgery and will continue 
for 2 weeks after surgery and then discontinue. 
o Bromfenac 0.09%: 1 drop TID starting 3 days before surgery and TID for 2 
weeks after surgery, tapered to BID for 2 weeks, and then discontinued. 
o  Prednisolone acetate 1% will be started after surgery QID for 2 weeks, 
tapered to BID for 2 weeks, and then discontinued. 
 
Additional Preoperative/Intraoperative Medications: 
a. Routine medications including OVD, intracameral antibiotic (same to be used in 
both eyes), etc. 
 
The use of antibiotics in the bottle is not allowed. 
 
3.3. Study Visit Schedule and Assessments (Table 1). 
 
3.3.1. Visit Schedule: Subjects will be examined at the following intervals: 
 
1. Visit 1: Screening and enrollment: Preoperative evaluation completed not more 
than eight weeks before surgery 


 
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2. Visit 2: Day of Surgery 
3. Visit 3: Day 1  
3. Visit 4: Day 15 ±2 days postoperative after second eye surgery 
4. Visit 5: Month 1: 30 ±5 days postoperative after second eye surgery 
 
3.3.2. Measurements and evaluations 
 
1. Visit 1:  Informed consent process will be conducted at this visit. Assessments 
include uncorrected and best-corrected ETDRS visual acuity at 4 m (UCVA / BCVA), 
manifest refraction, intraocular pressure (IOP) using Goldman tonometer, and slit 
lamp examination including dilated fundus exam, cataract density and type, 
ultrasonic central corneal pachymetry (UCCP), and optical coherence tomography 
(OCT). Symptoms (foreign body sensation (FBS) and burning/stinging) and pain in 
each eye will be assessed and compared with that of the fellow eye. Any testing that 
is part of the site’s standard of care preoperative cataract surgery evaluation may be 
performed prior to the informed consent being signed provided these tests are 
conducted within 90 days of the surgery and notation of the date performed is 
entered onto the source document. 
 
The first eye undergoing surgery will be randomized to either Group A (test) or 
Group B (control). Randomization will ensure that an equal number of first eyes are 
test and control. 
 
2. Visit 2: The surgeon may use his preferred cataract extraction technique (manual or 
laser). The lens will be implanted in the bag.  The following information will be 
captured the day of surgery: phaco technique (manual or laser), phacoemulsification 
time, cumulative dissipated energy (CDE), estimated fluid used, and duration of 
surgery (from opening/creating the incision to hydration of the wound).  
 
3. Visit 3: Slit lamp examination, UCVA, IOP, UCCP, patient satisfaction, symptoms and 
pain will be assessed.  
 
4. Visit 4 and 5: Slit lamp examination, UCVA, BCVA, IOP, UCCP, OCT, patient 
satisfaction, symptoms and pain will be assessed as well as presence of rebound 
inflammation. Rebound inflammation will be diagnosed based on the following symptoms: 
ocular pain, blurry vision, light sensitivity and redness; and slit lamp examination showing 
anterior chamber cells and/or flare. Rebound inflammation will be treated with 
Prednisolone acetate 1% to QID for 2 days, continued BID for a week and QD for one 
additional week then discontinued. 
 
All adverse events and complaints will be monitored and recorded at all study visits. 


 
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Appendix 1 summarizes the standard evaluation procedures.  
 
Table 1.  Visits and Study Assessments 
 
Study Assessments 
Visit 1 
Preoperative 
Visit 2 
Operative 
Visit 3 
Day 1 
Visit 4 
Day 15 ±2 
Visit 5 
Day 30 ±5 
Inclusion/Exclusion Criteria 
x 
 
 
 
 
Consent Subject 
x 
 
 
 
 
Patient demographics (age, 
gender, race, ethnicity) 
x 
 
 
 
 
Manifest Refraction 
x 
 
x 
x 
x 
UCDVA 
x 
 
x 
x 
x 
BCDVA 
x 
 
 
x 
x 
Goldman Tonometry (IOP) 
x 
 
x 
x 
x 
Complete slit lamp exam 
x 
 
x 
x 
x 
Dilated fundus exam 
x 
 
 
 
† 
Cataract density 
x 
 
 
 
 
Ultrasonic central corneal 
pachymetry 
x 
 
x 
x 
x 
Central macular thickness 
(OCT) 
x 
 
 
x 
x 
Use of femtosecond laser 
 
x 
 
 
 
Phacoemulsification time 
 
x 
 
 
 
CDE 
 
x 
 
 
 
Estimated fluid used 
 
x 
 
 
 
Duration of surgery 
 
x 
 
 
 
Record Lens Model 
Implanted  
 
x 
 
 
 
Patient satisfaction 
 
 
 
 
x 
Symptoms (FBS & 
burning/stinging) 
x 
 
x 
x 
x 


 
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Pain 
x 
 
x 
x 
x 
Adverse events / device 
deficiency 
 
x 
x 
x 
x 
x To be performed as scheduled 
† To be performed as deem necessary by the investigator. 
 
4. Study Completion Criteria 
 
4.1. Patient Completion of Study: If a study patient has completed the final visit (Visit 5) of 
the study, he/she is considered to have completed the study. 
 
4.2. Patient Discontinuation/Withdrawal: Each study patient may voluntarily discontinue 
the study at any time they choose.  Study patients who cannot complete the study for 
administrative reasons (e.g., non-compliance, failure to meet visit schedule, etc.) will be 
discontinued from the study.  Study patients discontinued during the enrollment phase 
(prior to surgery) of the study will be replaced. 
 
4.3. Patient Termination: A study patient will be terminated if the study patient develops 
any severe adverse event that may be related to the study.  A study patient will receive 
appropriate treatment at the discretion of the investigator.  Notification of termination 
will be clearly documented.  These study patients are considered to have completed 
the study and will not be replaced. 
 
4.4. Study Termination: The investigator with appropriate notification may terminate the 
study.  If, after clinical observations, the investigator feels that it may be unwise to 
continue the study, he may stop the study. 
 
4.5. Study Completion: The study will be complete when all enrolled patients have 
completed Visit 5 or have been terminated from the study. 
 
 
5. STATISTICAL CONSIDERATIONS 
5.1. Sample size 
We estimate that the ability of the Cirrus OCT to measure changes in macular thickness 
has a standard deviation around 6 microns. For sample size calculation we set the 
statistical significance to alpha = 0.05 with a power (beta) of 0.9. Using a dependent 
model, detecting a 5 micron difference in the change in retinal thickness between eyes 
is estimated to require 30 subjects. To allow for 15% dropout, 35 subjects will be 
enrolled. 
 


 
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5.2. Statistical Analysis  
All data will be collected by the site and entered into a database.  Subjects will be 
assigned an ID number. Data analysis will be performed without patient identification. 
Statistical analysis will be performed using standard descriptive statistics and other 
tests as deemed appropriate based on the characteristics of the data to be analyzed. All 
statistical tests will be two-sided and interpreted at a 5% significance level.  
Comparisons between the groups will be made.  Data analysis will be conducted by a 
third party consultant. 
 
5.3. Study Endpoints:  
Comparisons between the groups: 
 
5.3.1. Primary Endpoints:  
• Change from baseline (preoperative exam) in macular thickness at Days 15±2 
and 30 ±5. 
 
5.3.2. Secondary Endpoints: 
• The change from baseline in corneal thickness at Day 1, Day15 ± 2, and Day 
30 ± 3. 
• Slit lamp (cornea exam) changes at all times points.  
• The proportion of subjects reporting no eye pain/discomfort (“0” on the eye 
pain/discomfort) at all time points. 
• The change from baseline in eye pain/discomfort score at all time points.  
• The proportion of subjects reporting FBS (“0”) at all time points. 
• The change from baseline in FBS at all time points.  
• The proportion of subjects reporting burning/stinging (“0”) at all time points. 
• The change from baseline in burning/stinging at all time points.  
• The proportion of subjects with a corneal pachymetry change from baseline 
at all time points. 
• The change from baseline in corneal pachymetry measurements at all time 
points. 
• The proportion of subjects with patient satisfaction score of 3 or higher at 
Day 30 visit. 
 
5.4. Safety Analyses 
The type, severity, duration and frequency of reported ocular adverse events will be 
tabulated for each group.  Adverse events will also be summarized for events that were 


 
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considered treatment-related.  Comparison of treatment groups with respect to the 
proportion of study patients reporting adverse events will be made using Fisher’s Exact 
Test. 
 
6. DATA HANDLING AND RECORD KEEPING 
6.1. Confidentiality 
To ensure confidentiality in this study, records of the participants will be examined only 
by the principal investigator and research staff involved in the study.  Study records will 
be kept on file at each site.  Any statistical analysis and publication will not include any 
subject identifiers.  Medical records will be made available only for review by the 
investigators, study Monitor or Auditor, Sponsor Company or Research Institution, the 
IRB, and other State or Federal Regulatory Agencies, if necessary.  All information in 
these records will be kept confidential. 
 
6.2. Records Retention 
The PI is accountable for the integrity, retention and security of all study related data. 
The investigator must maintain accurate, complete and current records relating to the 
clinical study. The investigator must maintain the required records during the 
investigation and for a period of 1 year after the date on which the investigation is 
terminated or completed. 
 
7. STUDY MONITORING, AUDITING, AND INSPECTING 
7.1.1. The nature and location of all source documents will be identified to ensure that 
original data required to complete the case report forms (CRFs) exist and are 
accessible for verification by the monitor.  If electronic source records are 
maintained, these records must be 21 CFR Part 11 compliant and will be printed 
and certified for verification by the monitor as needed.  
 
7.1.2. Required examination must be recorded on the CRFs. CRFs can be used as source 
document.  All data reported must have corresponding entries in the source 
documents. The principal investigator or sub-investigator must review the reported 
data and certify that the CRFs are accurate and complete. No subject identifiers 
should be recorded on the CRFs beyond subject number, subject initials and study 
specific identifiers. 
 


 
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7.1.3. Data from CRFs will be entered into a database. Database access is limited to 
study personnel and it is saved in the server.   
 
7.1.4. Upon completion of the CRFs, the data will be reviewed and statistician for 
accuracy and completeness. If corrections and/or any additions to the data are 
deemed necessary, queries will be generated. Designated research staff expected 
to respond to data queries in a timely manner and ensure that the corrections and 
changes made to the data in the database are reflected in the subjects’ source 
documentation. Any changes will need to be initialed and dated by the authorized 
personnel making such changes. 
 
7.1.5. Data will not be sold to third parties nor will it be used for future research. 
 
7.1.6. Electronic data will be stored and accessed on a portable device. However, the 
file is saved in the server that can be only accessed using a VPN private connection. 
 
8. INVESTIGATIONAL PRODUCT  
8.1. Description  
The Symfony Toric IOL (ZXTx) is an extended depth of focus (EDOF) IOL design to 
improve the sharpness of vision at near, intermediate and far distances reducing the 
need of glasses after cataract surgery in patients with astigmatism. The EDOF IOL, 
similarly to a monofocal IOL, has one focal point, it is elongated in the EDOF, having 
less of a halo and glare problem compared to multifocal IOLs.   
 
8.2. Treatment/Dosing Regimen 
The Symfony Toric IOL (ZXTx) is intended for primary implantation for the visual 
correction of aphakia secondary to removal of a cataractous lens in adult patients. The 
IOL will be implanted at time of uncomplicated routine cataract surgery. Intraocular 
lenses are implantable medical devices and are intended for long term use over the 
lifetime of the patient. 
 
8.3. Method for Assigning Subjects to Treatment/Dosing Groups 
The statistician will provide randomization envelopes. The envelopes will be 
sequentially numbered and they will be provided to each site. 


 
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8.4. Subject Compliance Monitoring  
Since the IOL is implanted at time of cataract surgery, subject compliance will not be an 
issue in this particular study. 
 
8.5. Packaging, Receiving, Storage, Dispensing and Return 
An account will be set up with the manufacturer of the lens (Abbott Medical Optics - 
AMO) that will provide the lens at no cost to the participants. IOLs will be ordered once 
the subjects qualification for the study has been confirmed. IOLs will be shipped to the 
site or ambulatory surgery center and will be stored and dispensed following the 
routine standard of care for cataract surgery. Unused IOLs will be returned to AMO 
following their instructions. 
 
9. ETHICAL CONSIDERATIONS 
This clinical trial will be conducted in accordance with the principles of the Declaration of 
Helsinki, and Good clinical practice.  The Investigator and all clinical trial staff will conduct 
the clinical trial in compliance with this protocol. The Investigator will ensure that all 
personnel involved in the conduct of the clinical trial are qualified to perform their assigned 
duties through relevant education, training, and experience. Deviations from the clinical 
protocol must be documented in each subject’s study records including the dates and 
reasons for each deviation. The PI must ensure that all aspects of the trial are in compliance 
with the applicable regulatory laws and conditions of approval imposed by the IRB. 
 
10. IN CASE OF AN INJURY RELATED TO THIS RESEARCH STUDY 
Every effort to prevent study-related injury will be taken by the study doctor and staff. In 
the event a patient is injured as a direct result of the study while following the study 
instructions and requirements, the patient will be instructed to immediately contact the 
principal investigator and/or study staff.  Treatment will be provided as needed for those 
injuries caused directly by this research study. In the event of injury or illness caused by or 
occurring during the participation in this study, all charges for medical care provided will be 
billed to the patient’s insurance company. The medical care costs for injuries or illnesses 
that are not caused directly by the research study will not be covered. 
 
11. CONFIDENTIALITY/PUBLICATION OF THE STUDY 


 
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The existence of this Study is confidential and should not be discussed with persons outside 
of the Study.  Results will be submitted for publication and presentation at national and/or 
international meetings. A manuscript will be submitted to peer-review journals for 
publication but there is no guarantee of acceptance. 
 
12. REFERENCES 
1. Assia E, Blumenthal M. [Cataract surgery and incidence of postoperative endophthalmitis in 
Israel]. Harefuah. 2005;144: 768-71, 823. 
2. Cao XR, Gong LL, Yang Y, Ai BJ, Sun Y. [Endophthalmitis after phacoemusification surgery]. 
Zhonghua Yan Ke Za Zhi. 2005;41: 519-22. 
3. Friling E, Lundström M, Stenevi U, Montan P. Six-year incidence of endophthalmitis after 
cataract surgery: Swedish national study. J Cataract Refract Surg. 2013; 39:15-21. 
4. Al-Mezaine HS, Kangave D, Al-Assiri A, Al-Rajhi AA. Acute-onset nosocomial endophthalmitis 
after cataract surgery: incidence, clinical features, causative organisms, and visual outcomes. J 
Cataract Refract Surg. 2009;35: 643-9. 
5. Ravindran RD, Venkatesh R, Chang DF, et al. Incidence of post-cataract endophthalmitis at 
Aravind Eye Hospital: outcomes of more than 42,000 consecutive cases using standardized 
sterilization and prophylaxis protocols. J Cataract Refract Surg. 2009;35: 629-36. 
6. Wu Y, Yan XM. [Retrospective analysis of the clinical characteristics and visual outcomes of 
postoperative endophthalmitis of cataract between 2001 and 2012]. Beijing Da Xue Xue Bao. 
2014; 46:215-9. 
7. West ES, Behrens A, McDonnell PJ, et al. The incidence of endophthalmitis after cataract 
surgery among the U.S. Medicare population increased between 1994 and 2001. 
Ophthalmology 2005;112: 1388–1394 
8. Rudnisky CJ, Wan D, Weis E. Antibiotic choice for the prophylaxis of post-cataract extraction 
endophthalmitis. Ophthalmology. 2014 Apr;121(4):835-41. doi: 10.1016/j.ophtha.2013.08.046. 
Epub 2013 Dec 8. 
9. Rodríguez-Caravaca G, García-Sáenz MC, Villar-Del-Campo MC, et al.  Incidence of 
endophthalmitis and impact of prophylaxis with cefuroxime on cataract surgery. J Cataract 
Refract Surg. 2013;39: 1399-403.  
10. Ng JQ, Morlet N, Bulsara MK, et al. Reducing the risk for endophthalmitis after cataract 
surgery: population-based nested case-control study: endophthalmitis population study of 
Western Australia sixth report. J Cataract Refract Surg 2007; 33: 269-80 


 
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11. Chang DF, Braga-Mele R, Mamalis N, et al. Prophylaxis of postoperative endophthalmitis 
after cataract surgery: results of the 2007 ASCRS member survey. J Cataract Refract Surg 2007; 
33: 1801-5 
12. Matsuura K, Mori T, Miyamoto T, et al. Survey of Japanese ophthalmic surgeons regarding 
perioperative disinfection and antibiotic prophylaxis in cataract surgery. Clin Ophthalmol. 
2014;8: 2013—2018 
13. Endophthalmitis Study Group, European Society of Cataract & Refractive Surgeons. 
Prophylaxis of postoperative endophthalmitis following cataract surgery: results of the ESCRS 
multicenter study and identification of risk factors. J Cataract Refract Surg. 2007;33: 978-88. 
14. Mentes J, Erakgun T, Afrashi F, Kerci G. Incidence of cystoid macular edema after 
uncomplicated phacoemulsification. Ophthalmologica. 2003 Nov-Dec;217(6):408-12 
15. Chaudhary C, Bahadhur H, Gupta N. Study of cystoid macular edema by optical coherent 
tomography following uneventful cataract surgery. Int Ophthalmol. 2014 Sep 10. Accessed on 
17.Oct.2014 
16. Ram J, Gupta A, Kumar S, et al. Phacoemulsification with intraocular lens implantation in 
patients with uveitis. J Cataract Refract Surg 2010; 36:1283–1288 
17. Bélair ML, Kim SJ, Thorne JE, et al. Incidence of cystoid macular edema after cataract 
surgery in patients with and without uveitis using optical coherence tomography. Am J 
Ophthalmol. 2009 Jul; 148:128-35 
18. Schmier JK, Halpern MT, Covert DW, et al: Evaluation of cost for cystoid macular edema 
among patients after cataract surgery. Retina 2007;27:621–628 
19. Wittpenn JR, Silverstein S, Heier J, et al. A randomized, masked comparison of topical 
ketorolac 0.4% plus steroid vs steroid alone in low-risk cataract surgery patients. Am J 
Ophthalmol 2008; 146:554–560 
20. Asano S, Miyake K, Ota I, et al. Reducing angiographic cystoid macular edema and blood-
aqueous barrier disruption after small-incision phacoemulsification and foldable intraocular 
lens implantation: multicenter prospective randomized comparison of topical diclofenac 0.1% 
and betamethasone 0.1%. J Cataract Refract Surg. 2008;34 :57-63 
21. Kessel L, Tendal B, Jørgensen KJ, et al. Post-cataract Prevention of Inflammation and 
Macular Edema by Steroid and Nonsteroidal Anti-inflammatory Eye Drops: A Systematic 
Review. Ophthalmology 2014; 121:1915-24 
22. Tsai, T., Robin, A.L., and Smith III, J.P. “An Evaluation of How Glaucoma Patients Use Topical 
Medications: A Pilot Study.” Transactions of the American Ophthalmological Society. (2007); 
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23. Dreer LE, Girkin C, Mansberger SL. Determinants of medication adherence to topical 
glaucoma therapy. J Glaucoma. 2012;21: 234-40 
24. Cate H, Bhattacharya D, Clark A, et al. Patterns of adherence behaviour for patients with 
glaucoma. Eye 2013;27: 545-53 
25. Cunha PA, Shinzato FA, Tecchio GT, Weber SL, Brasil A, Avakian A. Efficacy and tolerability of 
a gatifloxacin/prednisolone acetate fixed combination for topical prophylaxis and control of 
inflammation in phacoemulsification: a 20-day-double-blind comparison to its individual 
components. Clinics (Sao Paulo). 2013; 68:834–839. 
26. Russo S, Papa V, Di Bella A, et al. Dexamethasone–netilmicin: a new ophthalmic steroid–
antibiotic combination. Efficacy and safety after cataract surgery. Eye 2007; 21:58-64 
27. Freitas LL, Soriano E, Muccioli C, Höfling-Lima AL, Belfort R Jr. Efficacy and tolerability of a 
combined moxifloxacin/dexamethasone formulation for topical prophylaxis and reduction of 
inflammation in phacoemulsification: a comparative, double masked clinical trial. Curr Med Res 
Opin. 2007; 23:3123–3130. 
28. Notivol R, Amin D, Whitling A, et al.; and the International TobraDex Study Group. 
Prophylactic effectiveness of tobramycindexamethasone eye drops compared with 
tobramycin/vehicle eye drops in controlling post-surgical inflammation in cataract patients: 
prospective, randomised, double-masked, two-arm, parallel-group, placebo-controlled, 
multicentre study. Clin Drug Invest 2004; 24:523-33 
 
29. Fisher B, Potvin R. Transzonular vitreous injection vs a single drop compounded topical 
pharmaceutical regimen after cataract surgery. Clinical Ophthalmology 2016; in press. 
 
 
 


 
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Appendix 1: Standard Evaluation Procedures. 
 
1. Uncorrected and Best-corrected Visual Acuity: To be evaluated preoperatively, at 
days 1, 15 and 30.  
 
Visual acuity will be measured before tonometry or any other test that would affect 
vision. Visual acuity is measured using the ETDRS chart 1 at 4 m. If the subject cannot read at 
least 4 letters on the 20/200 line then the chart or the patient need to be moved to 1 meter 
and visual acuity recorded.  
 
a. ETDRS technique: 
i. 
Testing starts with right eye; therefore, left eye is occluded. 
ii. 
The patient is seated and his/her back should firmly touch the back of the 
chair. The examiner should ensure that the patient is sitting comfortably, 
that the head does not move forward or backward during testing, and that 
the patient's eyes remain at the same distance. 
iii. 
The patient should be told that the chart has letters only and no numbers. If 
the patient forgets the instructions and reads a number, he or she should be 
reminded that the chart does not have numbers and the examiner should 
request a letter instead of a number.  
iv. 
The patient should be asked to read slowly (at a rate not faster than about 
one letter per second) in order to achieve the best identification of each 
letter and to not proceed until the patient has given a definite response. If 
the patient loses his or her place in reading or the examiner loses his or her 
place, the examiner should ask the patient to go back to the line where the 
place was lost. Examiners should not point to the chart or to specific letters 
on the chart or read any of the letters during the test. When the patient says 
he/she cannot read a letter, he/she should be encouraged to guess. If the 
patient identifies a letter as one of two or more letters, he/she should be 
asked to choose one letter. When it becomes evident that no further 
meaningful readings can be made, the examiner should stop the test for that 
eye. Each letter is scored as right or wrong. Once a patient has identified a 
letter with a definite single-letter response and has read the next letter, a 
correction of the previous letter cannot be accepted. If the patient changes a 
response aloud (e.g. "That was a "C," not an "0") before he or she has read 
aloud the next letter, then the change should be accepted. If the patient 


 
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changes a response after beginning to read the next letter, the change is not 
accepted.  
v. 
Ask the patient to read the smallest line that he/she could comfortably read. 
If patient misses one letter, ask the patient to read the line before and 
continue from there until patient misses 3 or more letters in a single line.  
vi. 
After the test of the right eye is completed, occlude the right eye. The test is 
repeated for the left eye following the same instructions.  
 
b. ETDRS visual acuity scoring 
i. 
The examiner records letters read incorrectly and letters for which the 
patient makes no guesses with an "x".  
ii. 
The examiner underlines the last line on which the patient read any letter. 
iii. 
Each letter read incorrectly is scored as one point. The total number of 
missed letters is multiply by 0.02 to this result, the last line that the patient 
read correctly added and the log MAR score calculated and recorded on the 
source document for that visit 
 
2. Manifest Refraction: will be done with a plus cylinder phoropter or trial lenses and the 
ETDRS chart R using the "Push plus" refraction technique. If refracting at 1 m, add a +0.75 D 
sphere lens to compensate for the closer distance. 
1. Sphere   
a. Plus   
 
 
Clearer  
 
 Increase plus.  
    (lowest line read) 
 
No Change 
 
 Increase plus  
  
 
 
 
 
Blurrier  
 
STOP 
b. Minus  
 
 
Clearer   
 
Increase minus if additional letter(s) read.  
 
   (lowest line read) 
 
No Change 
 
 STOP  
Blurrier  
 
STOP  
c. Plus   
 
 
Clearer  
 
Increase plus.  
  
   (lowest line read)  
 
No Change 
 
 Increase plus.  
  
 
 
 
 
Blurrier  
 
STOP  
 
2. Cylinder   
a. Axis  
 
 
Clearer at 1 or 2  
Move axis toward preferred plus axis 
(C or O above lowest          
                                            until position 1 and 2 are equal. 
 line read) 
 
3. Cylinder 
  
a. Power  
 
 
Clearer at 1 or 2  
Increase or decrease plus power until  


 
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 (C or O on or above lowest 
 
 
             neither position 1 or 2 is better. If power  
 line read)  
 
 
 
 
 
changes by ≥0.50 adjust sphere.  
 
(Not present)  
 
 
JCC at 90/180   
Place 0.25 D cylinder at preferred axis. 
JCC at 45/135  
Then, check cylinder axis and power as 
above.  
 
4. Refine sphere  Refine with +/- spheres as in step #1 until no improvement in vision. 
 
3. Corneal Edema: Postoperatively at day 1, 15 and 30, corneal edema evaluation will be 
divided in stromal edema/folds and epithelial edema and it will be measured before 
tonometry or any other test that would affect examination. Both will be graded by the 
examiner using the following scale: 
 
0 - no edema 
1 - trace (0% - 5%) 
2 - mild (5% - 25%) 
3 - moderate (26% - 50%) 
4 - severe (>50%) 
 
4. Anterior Chamber Cells and Flare: Postoperatively at day 1, 15 and 30, anterior chamber 
cells and flare wi ll be evaluated before tonometry or any other test that would affect 
examination. Both wi ll be graded by the examiner using the following scale: 
 
Number of Cells 
Flare 
0- none 
0- none 
1 - 1-5 cells 
1 - Tyndall effect barely discernible 
2 - 6-15  
2 - mild Tyndall effect 
3 - 16-30 
3 - stronq Tyndall effect 
4- > 30 
4 - intense Tyndall effect - aqueous has milky white 
appearance 
 
 
5. Macular thickness (preop, days 15 and 30): It will be measured before tonometry or any 
other test that would affect OCT measurements. Macular thickness will be performed using 
SD-OCT (Cirrus [Zeiss]) following the manufacturer's recommendations. One 512 x 128 
Macular Cube scan will be acquired per eye. 
 
6. Central corneal ultrasound pachymetry: To be measured preop, and at day 1, 15 and 30. 
Three measurements will be taken and recorded as well as the average of the 3 
measurements taken. 


 
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7. Intraocular pressure measurements: IOP measurements will be measured at the Screening 
visit and at day 1, 15 and 30 postoperatively using Goldmann tonometry.  
 
8. Questionnaires: Examiner will read aloud the questions to the subject and will record the 
response given by the subject in the source document. For the Visual Analog Scale (VAS), 
the examiner will ask the patient to place a vertical mark on the line for each question then 
use ruler (cm) to calculate the score with 1 mm equal to 0.1 cm. A decimal value should be 
recorded (i.e., 2.1, 4.0). Questions 4 to 6 will be asked only at the Day 30 visit. 
 
9. Dilated fundus examination: To be performed preoperatively and at Day 30 (if deemed 
necessary by the investigator) using the investigator's preferred technique. 
 
 
 


 
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Appendix 1: Symptoms and Pain Questionnaire 
 
1. Have you experienced foreign body sensation? 
 
  Yes 
 No  If yes,  
 OD  
 OS  
 OU  
 
If yes, did it start immediately after drop instillation? 
       OD:  
  Yes 
 
  No  
 
  Don’t remember 
       OS:  
  Yes 
 
  No  
 
  Don’t remember 
 
      How long did it last? 
  OD: 
  1 min or less 
 
  2 to 5 min 
 
  6-10 min  
  > 10 min 
  OS: 
  1 min or less 
 
  2 to 5 min 
 
  6-10 min  
  > 10 min 
 
      How severe was it? 
  OD: 
  Mild  
 
 
  Moderate 
  Severe 
 
 
  OS: 
  Mild  
 
 
  Moderate 
  Severe 
 
 
 
Place a vertical mark on the line below to indicate the severity. 
OD 
No pain  ׀ 
 
 
   
 
 
 
 
 ׀ Very Severe Pain 
 
OS 
No pain  ׀ 
 
 
   
 
 
 
 
 ׀ Very Severe Pain 
 
 
2. Have you experienced stinging/burning? 
 
  Yes 
 No  If yes,  
 OD  
 OS  
 OU  
 
If yes, did it start immediately after drop instillation? 
       OD:  
  Yes 
 
  No  
 
  Don’t remember 
       OS:  
  Yes 
 
  No  
 
  Don’t remember 


 
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      How long did it last? 
  OD: 
  1 min or less 
 
  2 to 5 min 
 
  6-10 min  
  > 10 min 
  OS: 
  1 min or less 
 
  2 to 5 min 
 
  6-10 min  
  > 10 min 
 
      How severe was it? 
  OD: 
  Mild  
 
 
  Moderate 
  Severe 
 
 
  OS: 
  Mild  
 
 
  Moderate 
  Severe 
 
 
 
Place a vertical mark on the line below to indicate the severity. 
OD 
No pain  ׀ 
 
 
   
 
 
 
 
 ׀ Very Severe Pain 
 
OS 
No pain  ׀ 
 
 
   
 
 
 
 
 ׀ Very Severe Pain 
 
 
3. Have you experienced any pain/discomfort? 
 
  Yes 
 No  If yes,  
 OD  
 OS  
 OU  
 
If yes, did it start immediately after drop instillation? 
       OD:  
  Yes 
 
  No  
 
  Don’t remember 
       OS:  
  Yes 
 
  No  
 
  Don’t remember 
 
      How long did it last? 
  OD: 
  1 min or less 
 
  2 to 5 min 
 
  6-10 min  
  > 10 min 
  OS: 
  1 min or less 
 
  2 to 5 min 
 
  6-10 min  
  > 10 min 
 
      How severe was it? 
  OD: 
  Mild  
 
 
  Moderate 
  Severe 
 
 
  OS: 
  Mild  
 
 
  Moderate 
  Severe 
 
 
 


 
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Place a vertical mark on the line below to indicate the severity. 
OD 
No pain  ׀ 
 
 
   
 
 
 
 
 ׀ Very Severe Pain 
 
OS 
No pain  ׀ 
 
 
   
 
 
 
 
 ׀ Very Severe Pain 
 
4. Overall, how satisfied have you been with the results of your cataract surgery in your …? 
OD 
 
 
 
 
 
OS 
 
 Very dissatisfied  
 
 
 Very dissatisfied 
  Dissatisfied 
 
 
 
  Dissatisfied 
  Neither satisfied nor dissatisfied  
  Neither satisfied nor dissatisfied 
 Satisfied 
 
 
 
 
 Satisfied 
 Very satisfied 
 
 
 
 Very satisfied 
 
5. Given your postoperative vision/outcome, if you had to do it all over again, would you 
select: 
  LessDrops  
  3-Drops 
 
6. Given your postoperative experience, if you had to do it all over again, would you select: 
  LessDrops 
  3-Drops