The Effects of Intraocular Phenylephrine/Ketorolac Infusion on Retinal Thickness and Macular Edema in Cataract Surgery
Phase: PHASE4
Conditions: Cataract
Sponsor: Wake Forest University Health Sciences

 
 
Title:  No Drop Cataract Surgery: The effect of Intraocular Phenylephrine/Ketorolac 
Infusion on Retinal Thickness and Macular Edema in Cataract Surgery 
 
 
Protocol ID:  IRB00050415 
 
 
 
NCT03864133 
 
 
 
IRB-Approved Date:  3/12/2019 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Study Title: No Drop Cataract Surgery: The effect of Intraocular 
Phenylephrine/Ketorolac Infusion on Retinal Thickness and Macular Edema in Cataract 
Surgery.   
 
Principle Investigator, Co-investigator(s): Keith Walter MD, Ken Weinlander, MD; 
Amber Hoang, MD 
 
Sponsor or funding source: Omeros Corporation, Seattle WA.  
 
Background, Rationale and Context 
 
Patient compliance and insurance coverage with eye drops in cataract surgery has become 
a major hurdle in successful cataract surgery. One of the major complications of cataract 
surgery is post-operative pain and cystoid macular edema (CME).1,2 Multiple topical 
drugs have been used to prevent pain and macular edema in cataract surgery and include 
both topical steroid eye drops as well as non-steroidal anti-inflammatory agents 
(NSAIDs). Issues with these drops include patient difficulty in application, compliance, 
generic substitution and insurance coverage. A large percentage of patients aren’t able to 
afford these drops or often aren’t covered by their insurance. In addition, pharmacists 
often substitute the intended therapy for a generic version or inadequate drug alternative.3 
Recently, Omidria (phenylephrine and ketorolac injection 1% / 0.3%) was FDA approved 
for post-operative pain and inflammation in patients undergoing cataract surgery. It is 
also indicated to maintain pupil dilation during cataract surgery, and is therefore the main 
reason it is used. Omidria is not a topical drug but a constant infusion of phenylephrine 
and ketorolac added to the irrigate used during cataract surgery.  
 
Topical NSAIDs have been known to reduce post-operative CME as well as control pain 
and inflammation, whether alone or with a steroid.4 Reduction of CME is a major goal of 
cataract surgery safety. Typically, routine cataract surgery without the protection of a 
topical NSAID results in 3-4 percent of patient with reduced visual acuity from CME and 
up to 30% with macular thickening.4 Prostaglandins formed as a result of the activation 
of the inflammatory cascade during cataract surgery have been implicated in producing 
pain, inflammation and macular edema.5 Prostaglandin formation is drastically reduced 
by NSAIDs via inhibition of cyclo-oxygenase enzymes (COX 1&2)6. In animal studies, 
sustained suppression of COX enzymes has been shown in all ocular tissues measured up 
to 12 hours after cataract surgery with the use of Omidria.7 
 
All FDA guided studies regarding approval of a topical NSAID, have included a control 
arm where no anti-inflammatory agents are used. Typically, the control arm subjects 
require a rescue drug at 2-8%, despite having more anterior chamber inflammation than 
the study subjects.8 
 
We propose to observe whether treating patients with Omidria (phenylephrine and 
ketorolac injection 1% / 0.3%) during cataract surgery, will not only control post-
operative pain and inflammation but also reduce or eliminate cystoid macular edema 
without adjunctive topical NSAIDs. Potentially all of Dr. Walter’s patients undergoing 

cataract surgery would be recruited by a study team member, as Omidria is beneficially 
in maintaining pupil dilation during cataract surgery, and makes the surgery less risky. 
Only patients which meet an exclusion criterion, such as an allergy to NSAIDs, would 
not be recruited to participate in the study.  
 
Objectives 
 
Primary Objective:  To determine whether intracameral infusion of Omidria is sufficient 
alone to prevent post-operative CME and macular thickening. 
• Hypothesis 1: The administration of Omidria will be sufficient to reduce 
macular thickening without topical NSAIDs or corticosteroids. 
• Hypothesis 2: The administration of Omidria will be sufficient to prevent 
post-operative cystoid macular edema (CME) after routine cataract 
surgery.  
 
Secondary Objective: To observe whether any patients need additional topical therapy 
besides the intraoperative medication.  
• Hypothesis 1.  The administration of Omidria during cataract surgery will 
preclude any additional need for topical anti-inflammatory drops. 
 
Methods and Measures  
 
• Design 
 
A prospective interventional study looking at whether Omidria infusion alone during cataract 
surgery is effective at eliminating post-operative cystoid macular edema and/or macular 
thickening. We will recruit 200 volunteers undergoing elective routine cataract surgery. Patients 
may elect to enroll one or both eyes as desired, with both eyes undergoing surgery a week or two 
apart according to standard cataract surgery protocol. Patients will have no topical anti-
inflammatory drops used or provided during the perioperative period. Macular scans via OCT 
will be taken pre-operatively for baseline measurements, then at about 2 weeks and 6 weeks post-
operatively. 
 
We will collect the following demographic data:  age, gender, and race. In addition, the presence 
of macular cysts will be recorded, as well as central macular thickness. Best corrected spectacle 
acuity will be recorded as well and all data will be stored on a password protected and encrypted 
computer.  
 
• Setting 
 
The study will be performed at Davie Medical Center at Bermuda Run and will only 
involve patients undergoing cataract surgery by Dr. Walter. 
 
Subject selection criteria  
 

Subjects will be recruited through direct asking by a study team member (not Dr. Walter) at the 
time of cataract diagnosis and selected to participate based on the following inclusion and 
exclusion criteria.  
 
• Inclusion criteria:    
o Adults age 55-90 years with visual significant cataracts in one or both eyes.   
o Healthy individuals able to tolerate outpatient cataract surgery under local 
anesthesia via either phacoemulsification and/or femtosecond assisted cataract 
surgery. Well-controlled diabetes, hypertension will be included.  
o Females of childbearing potential must agree to use a reliable method of birth 
control while participating in this study. Reliable methods of birth control are: 
abstinence, oral contraceptives, intrauterine device (IUD), DepoProvera, tubal 
ligation or vasectomy of the partner (with confirmed negative sperm counts) 
in monogamous relationship (same partner). An acceptable, although less 
reliable, method involves the careful use of condoms and spermicidal foam or 
gel and/or cervical cap or sponge. A pregnancy test is required at least 10 days 
from the last normal menstrual period, if the patient is a sexually active female 
of childbearing potential. 
 
 
• Exclusion criteria:  
o Allergy to Phenylephrine or NSAIDs.  
o Inability to sit steady and upright for the OCT.  
o Complications during surgery, including posterior capsular rupture, vitreous 
loss, zonular dialysis, or iris trauma.  
o Macular thickness above 300 microns at baseline 
o Currently taking a prostaglandin analogue  
o Presence of an epiretinal membrane on the preoperative OCT.  
o Retained lens fragment post-operatively.  
o Inability to return for follow appointments 
o Female patients who are pregnant, lactating or planning to become pregnant 
during the course of treatment.  
 
Sample size: 200 patients total.  
 
 
Study Procedure  
 
• 
Informed Consent Process: After the patient has been evaluated and meets all of the 
inclusion and exclusion criteria, a study team member besides Dr. Walter will introduce 
the study at the time of the subjects’ cataract evaluation or at the pre-operative work up. 
This typically will occur 1 to 8 weeks prior to surgery. The study will be discussed in 
detail and consent form (appendix 1) will be provided for the patient to review. Written 
informed consent will be obtained at either at the pre-op holding area or the week prior at 
the work up for surgery. Written informed consent will only be obtained once the patient 
has been given time to fully understand the study. If the patient agrees, patients will plan 
to forsake topical NSAIDs during the perioperative period and will agree to have Omidria 

infusion during cataract surgery. As per standard for cataract surgery, patients will return 
the following day, where the usual measurements will be taken including visual acuity, 
intraocular pressure, and measurement of anterior cell and flare. The subjects will also 
return for post op visits at 2 and 6 weeks, where in addition to the above measurements, 
the macular OCT will be obtained.  
• 
Study Procedure: The enrolled subjects will undergo standard topical 
phacoemulsification (with or without laser assistance) using Omidria, as labeled by the 
FDA, throughout the cataract surgery.  The Omidria will be provided at no cost to the 
patient nor the hospital, and will be provided by Omeros. The subjects will be monitored 
for any usual or atypical outcomes post-operatively. If the patients have atypical eye pain, 
anterior chamber cell greater than 2+, or macular thickening greater than 50 microns 
above baseline as documented via the OCT, the patients will be instructed to start a 
topical NSAID, like bromfenac, and will be used as per standard cataract surgery.   
 
Outcome Measures  
 
• Best corrected visual acuity at baseline (pre-op), 2 weeks and 6 weeks.  
• Presence of Cystoid Macular Edema at 2 weeks and 6 weeks 
• Macular thickness at baseline (pre-op), 2 weeks and 6 weeks 
• Need for a topical NSAID (rescue med) and reason 
• Anterior chamber cell and flare at 1 day, 2 weeks and 6 weeks.   
 
Analytical Plan 
 
Results will be analyzed initially using descriptive statistics where applicable.  This is not 
intended to be a comparative study but a utilization, efficacy and safety study. Results will 
be compared to historical controls with known outcomes in the general population 
undergoing routine cataract surgery. For example, a recent peer-reviewed paper with a 
large cohort where bromfenac was used in routine cataract showed an incidence of CME at 
3.6%9. Dr. Walter, with unpublished data using Omidria on routine cataract surgery, has 
noted a low incidence of CME at less than 0.5%. We are hoping to show that the use of 
Omidria is accounting for this reduced rate of CME and macular thickening.  
 
Human Subjects Protection 
  
Subject Recruitment Methods 
 
Subjects will be recruited though direct asking at the time of scheduling their cataract surgery. 
Patients who decline to participate will be treated exactly the same during and after surgery as 
those that consent to participate.  Participants will be not compensated directly but will likely 
benefit from not having to pay a co-pay on the normally used topical NSAID. Because of the 
potential conflict of interest with Omeros, Dr. Walter will not participate in recruiting nor during 
the consenting process. Dr. Mathew Giegengack will be the medical safety monitor and will 
review charts and insure no patients were inappropriately recruited or consented. 
 
Informed Consent  
 
Signed informed consent will be obtained from each subject. The study will be introduced by the 
study coordinator and informed consent will be obtained formally by a study team member once 

the patient fully understands the study. Informed consent will be given 1 or more weeks prior to 
the patient’s surgery, giving them plenty of time to decide and fully understand the study. Final 
written consent will be obtained by the day the surgery or at the pre-operative work up.  
 
Confidentiality and Privacy  
 
Confidentiality will be protected by collecting only information needed to assess study 
outcomes, minimizing to the fullest extent possible the collection of any information that 
could directly identify subjects, and maintaining all study information in a secure manner.  
To help ensure subject privacy and confidentiality, only a unique study identifier will 
appear on the data collection form.  Any collected patient identifying information 
corresponding to the unique study identifier will be maintained on a linkage file, store 
separately from the data.  The linkage file will be kept secure, with access limited to 
designated study personnel.  Following data collection subject identifying information will 
be destroyed 3 years after the study is published. They will be destroyed by deleting all files 
and shredding any documents consistent with data validation and study design, producing 
an anonymous analytical data set.  Data access will be limited to study staff.  Data and 
records will be kept locked and secured, with any computer data password protected.  No 
reference to any individual participant will appear in reports, presentations, or publications 
that may arise from the study. 
 
Data and Safety Monitoring  
 
Dr. Giegengack will be responsible for the overall monitoring of the data and safety of study 
participants.  The principal investigator will be assisted by other members of the study 
staff. The study will cease to enroll patients if the CME rate rises above 20%, or if more 
than half of the patients have atypical pain and/or inflammation requiring a topical NSAID. 
Greg Russell or a member of his team will help with statistical analysis as we begin data 
collection.  
 
Pregnancy in Female Patients 
 
Female patients of childbearing potential will be instructed to notify the investigator 
immediately (no more than 24 hours after learning of the pregnancy) if pregnancy occurs 
during the study. If pregnancy occurs, the patient will be withdrawn from the study, and 
the investigator will discuss the risk of pregnancy and the possible effects to the fetus. 
Monitoring of the pregnancy will occur until the conclusion of the pregnancy. 
 
 
Reporting of Unanticipated Problems, Adverse Events, or Deviations  
 
Any unanticipated problems, serious and unexpected adverse events, deviations or protocol 
changes will be promptly reported by the principal investigator or designated member of 
the research team to the IRB and sponsor or appropriate government agency if 
appropriate. Dr. Giegengack has agreed to serve as an unbiased medical monitor.  
 
 
References. 

1) Yang J, et al. Risk factors for and diagnosis of pseudophakic 
cystoid macular edema after cataract surgery in diabetic 
patients. J Cataract Refract Surg. 2017 Feb;43(2):207-214. 
2) Wielders LH, et al. Prevention of Cystoid Macular Edema After 
Cataract Surgery in Nondiabetic and Diabetic Patients: A 
Systematic Review and Meta-Analysis. Am J Ophthalmol. 2015 
Nov;160(5):968-981 
3) Novack GD. Quality of generic ophthalmic drugs. Ocul Surf. 2013 
Jan;11(1):54-6. 
4) Kessel L, et al. Post-cataract prevention of inflammation and 
macular edema by steroid and nonsteroidal anti-inflammatory eye 
drops: a systematic review. Ophthalmology. 2014 Oct;121(10):1915-
24 
5) Henderson BA, et al. Clinical pseudophakic cystoid macular edema. 
Risk factors for development and duration after treatment. J 
Cataract Refract Surg. 2007 Sep;33(9):1550-8. 
6) Bucci FA Jr, Waterbury LD. Comparison of ketorolac 0.4% and 
bromfenac 0.09% at trough dosing: aqueous drug absorption and 
prostaglandin E2 levels. J Cataract Refract Surg. 2008 
Sep;34(9):1509-12. 
7) Waterbury LD. Alternative Drug Delivery for Patients Undergoing 
Cataract Surgery as Demonstrated in a Canine Model. J Ocul 
Pharmacol Ther. 2018 Jan/Feb;34(1-2):154-160 
8) Kim SJ, Flach AJ, Jampol LM. Nonsteroidal anti-inflammatory drugs 
in ophthalmology. Surv Ophthalmol. 2010 Mar-Apr;55(2):108-33 
9) Wielders LHP, et.al. European multicenter trial of the prevention 
of cystoid macular edema after cataract surgery in nondiabetics: 
ESCRS PREMED study report 1. J Cataract Refract Surg. 2018 
Apr;44(4):429-439