A CME MONOGRAPH

A Practical Look AT THE

Role of NSAIDs
IN OPHTHALMOLOGY

ORIGINAL RELEASE: MARCH 1, 2011

LAST REVIEW: FEBRUARY 16, 2011
EXPIRATION: MARCH 31, 2012
Sponsored by The New York Eye and Ear Infirmary

In joint sponsorship with MedEdicus LLC

In association with

This continuing medical education activity is

supported through an unrestricted educational
grant from ISTA Pharmaceuticals, Inc.

Uday Devgan, MD (PROGRAM CHAIR AND MODERATOR)

Johnny Gayton, MD

Private Practice
Devgan Eye Surgery
Chief of Ophthalmology
Olive ViewUCLA Medical Center
UCLA School of Medicine
Los Angeles, California

Founder
Eyesight Associates
Warner Robins, Georgia
Adjunct Faculty
Mercer University School of Medicine
Macon, Georgia

Elizabeth A. Davis MD, FACS

James P. Gills, MD

Partner
Minnesota Eye Consultants
Adjunct Clinical Assistant Professor
University of Minnesota
Minneapolis, Minnesota

Founder and Director

St. Lukes Cataract & Laser Institute
Affiliate Professor of Ophthalmology
University of South Florida
Tampa, Florida

LEARNING METHOD AND MEDIUM

DISCLOSURES

This educational activity consists of a supplement and seven (7) study questions. The participant
should, in order, read the learning objectives contained at the beginning of this supplement,
read the supplement, answer all questions in the post test, and complete the evaluation form.
To receive credit for this activity, please follow the instructions provided on the post test and
evaluation form. This educational activity should take a maximum of 1.5 hours to complete.

Elizabeth A. Davis MD, FACS: Dr Davis has had a financial agreement or affiliation during
the past year with the following commercial interests in the form of Consultant/Advisory
Board: Abbott Medical Optics, Bausch + Lomb Incorporated, Inspire Pharmaceuticals, and
ISTA Pharmaceuticals, Inc; Fees for promotional, advertising, or non-CME services received
directly from commercial interest or their Agents (e.g., Speakers Bureaus): Allergan, Inc;
Ownership Interest: Refractec, Inc.

CONTENT SOURCE
This continuing medical education (CME) activity captures content from a CME roundtable
discussion held October 2010.

TARGET AUDIENCE
This educational activity is intended for comprehensive ophthalmologists, cataract and
refractive surgeons.

OVERVIEW
Use of nonsteroidal anti-inflammatory drugs (NSAIDs) is highly prevalent in anterior segment
procedures, which have grown dramatically in the last decade. The number of Americans with
cataracts is expected to increase to 30 million by the year 2020 as the population ages; and
those with pseudophakia/aphakia will rise to 9 million. This represents a 50% increase from
the year 2000. The number of refractive procedures performed annually in the United States
is approximately 1 million; while this number has remained relatively unchanged over the past
several years, it is a large volume of surgery.
With these developments, the expectations on the surgeon have increased and the margin for
complications narrowed. Inflammation has always been accepted as a natural consequence of
cataract surgery and it is accepted to be the pathogenesis for cystoid macular edema, which
remains the most common cause of vision loss after cataract surgery. Prevention and control
of inflammation therefore is key to a successful outcome. Recent US Food and Drug
Administration approvals of new NSAID formulations make it timely for a practical update on
the role of NSAIDs for todays practice.

Uday Devgan, MD: Dr Devgan has had a financial agreement or affiliation during the past
year with the following commercial interests in the form of Honoraria: Abbott Medical Optics;
Allergan, Inc; Bausch + Lomb Incorporated; Hoya Surgical Optics; and ISTA Pharmaceuticals,
Inc; Royalty: Accutome, Inc; Consultant/Advisory Board: Abbott Medical Optics; Allergan,
Inc; Bausch + Lomb Incorporated; Hoya Surgical Optics; ISTA Pharmaceuticals, Inc; and Sirion
Therapeutics; Fees for promotional, advertising, or non-CME services received directly from
commercial interest or their Agents (e.g., Speakers Bureaus): Abbott Medical Optics; Alcon,
Inc; Allergan, Inc; Bausch + Lomb Incorporated; Carl Zeiss Meditec; Haag-Streit; Hoya Surgical
Optics; Inspire Pharmaceuticals; and ISTA Pharmaceuticals, Inc; Contracted Research: Abbott
Medical Optics; Bausch + Lomb Incorporated; and Gerson Lehrman Group; Ownership
Interest: Alcon, Inc; ISTA Pharmaceuticals, Inc; Renaissance Surgical; and Specialty Surgical.
Johnny Gayton, MD: Dr Gayton has had a financial agreement or affiliation during the past
year with the following commercial interests in the form of Honoraria: Alcon, Inc; Inspire
Pharmaceuticals; and ISTA Pharmaceuticals, Inc; Consultant/Advisory Board: ISTA
Pharmaceuticals, Inc; Fees for promotional, advertising, or non-CME services received directly
from commercial interest or their Agents (e.g., Speakers Bureaus): Inspire Pharmaceuticals, and
ISTA Pharmaceuticals, Inc.
James P. Gills, MD: Dr Gills has had a financial agreement or affiliation during the past year
with the following commercial interests in the form of Fees for promotional, advertising, or nonCME services received directly from commercial interest or their Agents (e.g., Speakers Bureaus):
Alcon, Inc; Ownership: Abbott Medical Optics; Alcon, Inc; Allergan, Inc; and Lenstec, Inc.

LEARNING OBJECTIVES:

PEER REVIEW DISCLOSURES

After successfully completing this activity, you will have improved your ability to:
Review the current and emerging major uses for NSAIDs in ocular conditions
Review recent clinical evidence on the use of NSAIDs in cataract and refractive procedures
Discuss the strategies for incorporating NSAIDs into cataract and refractive procedures
to optimize patient results

Brandon Ayres, MD: Dr Ayres has had a financial agreement or affiliation during the past
year with the following commercial interests in the form of Fees for promotional, advertising,
or non-CME services received directly from commercial interest or their Agents (e.g., Speakers
Bureaus): Alcon, Inc; Allergan, Inc; Inspire Pharmaceuticals; ISTA Pharmaceuticals, Inc; and
Bausch + Lomb Incorporated.

ACCREDITATION STATEMENT

Harry Koster, MD: Dr Koster has had a financial agreement or affiliation during the past year
with the following commercial interests in the form of Honoraria: EyeSys Vision Inc.

This activity has been planned and implemented in accordance with the Essential Areas and
Policies of the Accreditation Council for Continuing Medical Education through the joint
sponsorship of The New York Eye and Ear Infirmary and MedEdicus LLC. The New York Eye and
Ear Infirmary is accredited by the ACCME to provide continuing medical education for physicians.

AMA CREDIT DESIGNATION STATEMENT

The New York Eye and Ear Infirmary designates this enduring material for a maximum of 1.5
AMA PRA Category 1 Credits. Physicians should claim only the credit commensurate with
the extent of their participation in the activity.

GRANTOR STATEMENT
This continuing medical education activity is supported through an unrestricted educational
grant from ISTA Pharmaceuticals, Inc.

MISSION STATEMENT
It is The New York Eye and Ear Infirmary Institute for Continuing Medical Educations stated
mission to create medical education activities that will serve to increase the knowledge, skills,
professional performance, and relationships that a physician uses to provide services for
patients, the public, or the chosen profession.

EDITORIAL SUPPORT DISCLOSURES

Dominique Walton Brooks, MD; Cynthia Tornallyay, RD, MBA; Kimberly Corbin,
CCMEP; and Barbara Lyon have no relevant commercial relationships to disclose.

DISCLOSURE ATTESTATION
Each of the contributing physicians listed above has attested to the following:
1) that the relationships/affiliations noted will not bias or otherwise influence his or her
involvement in this activity;
2) that practice recommendations given relevant to the companies with whom he or
she has relationships/affiliations will be supported by the best available evidence or,
absent evidence, will be consistent with generally accepted medical practice; and
3) that all reasonable clinical alternatives will be discussed when making practice
recommendations.

OFF-LABEL DISCUSSION
This activity includes off-label discussion of nonsteroidal anti-inflammatory agents for cystoid
macular edema, retinal disorders, episcleritis, and dry eye.

DISCLOSURE POLICY STATEMENT

TO OBTAIN AMA PRA CATEGORY 1 CREDIT

The New York Eye and Ear Infirmary requires that each teacher/contributor or individual in a
position to control the content of a CME activity accredited by The New York Eye and Ear
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To obtain AMA PRA Category 1 Credit for this activity, read the material in its entirety and
consult referenced sources as necessary. Complete the evaluation form along with the post test
answer box within this supplement. Remove the Activity Evaluation page from printed
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DISCLAIMER
The views and opinions expressed in this educational activity are those of the faculty and do not
necessarily represent the views of The New York Eye and Ear Infirmary; MedEdicus LLC; ISTA
Pharmaceuticals, Inc; or Ophthalmology Times. Please refer to the official prescribing information
for each product for discussion of approved indications, contraindications, and warnings.
2011 MedEdicus LLC. All rights reserved.

INTRODUCTION

A Practical Look AT THE

Role of NSAIDs
IN OPHTHALMOLOGY
Focus on Cataract and Refractive Procedures

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among

the most frequently prescribed types of medications in the
world.1 These medications have been used for their analgesic
and anti-inflammatory qualities for many decades;
ophthalmic preparations of NSAIDs are increasingly being
used to manage postoperative inflammation, prevent and
treat cystoid macular edema (CME), and maintain
intraoperative mydriasis.1 Ophthalmic NSAIDs can also be
used to manage pain and photophobia after refractive
surgery1 and in the treatment of allergic conjunctivitis.2
Other diseases, such as age-related macular degeneration
(AMD) and diabetic retinopathy, may also be able to be
treated with NSAIDs in the coming years.3,4
Recent US Food and Drug Administration (FDA) approvals
of new NSAID formulations make it timely for a practical
update on the role of NSAIDs for todays practice. Most
often, NSAIDs are used as part of a standard regimen in
cataract and refractive procedures. Recently, a roundtable
discussion among leading cataract and refractive surgeons
was held to gain their insight and recommendations
regarding the role of NSAIDs in ophthalmology.

Mechanism and Efficacy of NSAIDs

There are several topical ocular NSAIDs approved by the FDA for
the treatment of postoperative inflammation after cataract surgery:
Acular LS (ketorolac, 0.4%) with QID dosing
Acular (ketorolac, 0.5%) with QID dosing
Acuvail (ketorolac, 0.45%) with BID dosing
Xibrom (bromfenac, 0.09%) with BID dosing
Bromday (bromfenac, 0.09%) with once/day dosing
Nevanac (nepafenac, 0.1%) with TID dosing
Voltaren (diclofenac, 0.1%) with QID dosing
Both ketorolac, 0.4% and 0.5%, and diclofenac, 0.1%, are
available in generic formulations (Table 1).

One of the mechanisms of action of all NSAIDs is to inhibit

cyclooxygenase (COX) enzymes; thus, the formation of excessive
prostaglandins that include PGE2, PGD2, PGF2a, and PGI2 are also
inhibited.1 According to some studies, ketorolac may be the most
potent inhibitor of COX-1 enzymes,5 while both bromfenac6 and
amfenac*5 claim to be the most potent inhibitor of the COX-2
enzymes. COX-2 may be more responsible for inflammation, and
the anti-inflammatory actions of NSAIDs may be associated with
their inhibition of COX-2. This relationship has not been proven
consistently in clinical trials; as an added point, it is thought that
COX-1 may play a role in inflammation as well.1
Ocular penetration and potency are key factors in the efficacy of ocular
medications. Several studies have evaluated the degree of penetration

Table 1. Available NSAIDs

Drug

Manufacturer

Dosing

Bromfenac, 0.09% (Bromday)

ISTA Pharmaceuticals, Inc

1x/day

Indications
treatment of postoperative inflammation following cataract extraction
reduction of ocular pain in patients who have undergone cataract extraction

Bromfenac, 0.09% (Xibrom)

ISTA Pharmaceuticals, Inc

2x/day

treatment of postoperative inflammation following cataract extraction

reduction of ocular pain in patients who have undergone cataract extraction

Flurbiprofen, 0.03% (Ocufen )

Allergan, Inc

2 hours before surgery, 1 drop

each hour; 4 drops total

inhibition of intraoperative miosis

Ketorolac, 0.45% (Acuvail)

Allergan, Inc

2x/day

treatment of pain and inflammation following cataract surgery

Ketorolac, 0.5% (Acular)

Allergan, Inc

4x/day

temporary relief of ocular itching due to seasonal allergic conjunctivitis

Ketorolac, 0.4% (Acular LS)

Allergan, Inc

4x/day

reduction of ocular pain and burning/stinging following corneal refractive surgery

Nepafenac, 0.1% (Nevanac)

Alcon Laboratories, Inc

3x/day

treatment of pain and inflammation associated with cataract surgery

Diclofenac, 0.1% (Voltaren)

Novartis Pharmaceuticals, Inc

4x/day

treatment of postoperative inflammation following cataract extraction

Suprofen, 1% (Profenal)

Alcon Laboratories, Inc

2 drops 3, 2, and 1 hour

before surgery

Diclofenac, 0.1%

generic

4x/day

treatment of postoperative inflammation following cataract extraction

temporary relief of pain and photophobia following corneal refractive surgery

inhibition of intraoperative miosis
treatment of postoperative inflammation in patients following cataract extraction
temporary relief of pain and photophobia following corneal refractive surgery
Ketorolac, 0.5%

generic

4x/day

temporary relief of ocular itching due to seasonal allergic conjunctivitis

Ketorolac, 0.4%

generic

4x/day

reduction of ocular pain and burning/stinging following corneal refractive surgery

treatment of postoperative inflammation following cataract extraction

*nepafenac is the prodrug of amfenac and converts to amfenac in the eye

into the anterior chamber and the time frame of penetration of the
various NSAIDs. One study looked at the in vivo pharmacokinetics and
in vitro pharmacodynamics of nepafenac, amfenac, ketorolac, and
bromfenac. In this study, nepafenac had the shortest time to peak
concentration as well as the greatest peak aqueous humor
concentration of the NSAIDs studied.5 Another study demonstrated a
significantly higher mean aqueous concentration of ketorolac, 0.4%,
compared with nepafenac, 0.1%.7 A pharmacokinetic study, in which
samples were collected over 4 hours after 1 dose of bromfenac, 0.1%,
suggested that the aqueous humor concentrations stayed at effective
levels for more than 12 hours,8 while another study in New Zealand
White rabbits found that measurable amounts of bromfenac were
found in all tissues of the eye after 24 hoursincluding the posterior
segment.9 The data in these studies demonstrate that all ocular NSAIDs
have significant penetration into the anterior chamber. Because the
various NSAIDs have different abilities to bind and block COX enzymes,
the concentration achieved is a less useful measurement of clinical
efficacy than the level of enzymatic inhibition (bromfenac had the
highest level).10
Topical administration of NSAIDs provides adequate concentrations
in the aqueous at levels that can suppress prostaglandin production
in the iris/ciliary body; this same ability in the retina/choroid,
however, is not as clear for all NSAIDs.1 Further research is needed to
establish the efficacy of NSAIDs in the posterior segment of the eye.
Two new formulations of existing NSAIDs have been approved by
the FDA recently: ketorolac in a 0.45% formulation, dosed twice a
day, and bromfenac, 0.09%, in a once-a-day formulation. Clinical
studies evaluating these newest versions of NSAIDs in cataract
surgery demonstrate their effectiveness. A poster presentation at the
2010 American Academy of Ophthalmology (AAO) meeting
showed that the once-a-day dosing of bromfenac was effective at
reducing inflammation and pain after cataract surgery.11 Additional
data showed that ketorolac, 0.45%, was more effective at clearing
anterior chamber inflammation and ocular pain than was vehicle.12

Uses of NSAIDs
Besides their use in prevention of inflammation after cataract surgery,
the management of CME, and for inflammation and pain control in
refractive surgery, NSAIDs have been investigated for use in the
prevention of inflammation after various other types of surgeries and
in other ocular conditions.
DR DEVGAN: What has been your historical use of topical NSAIDs in
ophthalmology?
DR GAYTON: I actually was an early adopter of NSAIDs; I began using

NSAIDs in cataract surgery primarily for the prevention of CME. That

use is off-label and the indication is for control of pain and for
inflammation. But, we had an excellent experience using diclofenac
under the branded form of Voltaren. Then, along came generic
diclofenac, which was found to cause significant corneal melting.13,14
Both Dr Gills and I studied our practices and found that we had a
significant increase in corneal melting with generic diclofenac, but
when we discontinued using NSAIDs because of those problems, we
both noticed a spike in CME. This increase in CME convinced me of
the importance of NSAIDs in cataract surgery. Many
ophthalmologists actually abandoned the use of nonsteroidals. It has
taken some time to get eye surgeons back on board using these
useful adjuncts and improving patient outcomes.
DR DEVGAN: Prevention of intraoperative miosis was a very early

indication as well for flurbiprofen (Ocufen).15 Since then, studies

have shown that diclofenac, 0.1%, and ketorolac, both 0.4% and
0.5%, as well as bromfenac, all demonstrate this property.16,17,18
DR GILLS: We were part of an unpublished study that used
nonsteroidals for that purpose. In approximately 100,000 cases, we

injected the NSAID into the anterior chamber to decrease

inflammation and to dilate the pupil early during surgery.
DR DEVGAN: I think that is one of the original indications and
certainly we still have that benefit, but that is not our primary reason
for using them today.
DR GAYTON: It is not a primary reason, but it has become a more

important reason because of the problems with intraoperative floppy

iris syndrome.19 There are more patients who have floppy iris, and
anything that gives you a larger preoperative and intraoperative
pupil is advantageous. So mydriatics, nonsteroidals, and viscoelastic
agents can all be helpful here. Things that are going to decrease
pupillary constriction during cataract surgery have become even
more important.
DR DEVGAN: Allergic conjunctivitis was another use for flurbiprofen.
Other NSAIDs have been found to be useful for the treatment of
the allergic symptoms, although this is an off-label use. A metaanalysis found that the NSAIDS ketorolac and diclofenac are
effective in managing the itching of allergic conjunctivitis2; 1 study
demonstrated similar findings for bromfenac.20 NSAIDs have also
been used after trabeculectomy surgery for glaucoma. Using either
topical ketorolac or fluorometholone for 1 month before surgery
produced improved trabeculectomy outcomes and less need for
postoperative needling.21 This shows that we have a broad variety of
ocular conditions in which inflammation is involved and thus where
NSAIDs may be clinically useful.
DR DAVIS: I use an NSAID for episcleritis22 and for corneal abrasions

or recurrent erosions for pain control. I also use NSAIDs to treat dry
eyes (off-label). Primarily, I was using it for the discomfort of dry
eye, but there may be evidence that it actually has some therapeutic
benefit with dry eye associated with inflammation.23-25 One study
showed the benefit of using ketorolac during the induction phase of
cyclosporine in patients with dry eye.26 The use of the NSAID
improved the signs and symptoms of dry eye during the start of
therapy and might have improved compliance with the cyclosporine
treatment during this time.
DR DEVGAN: Another study by Schechter, which was presented at
the 2010 American Society of Cataract and Refractive Surgery
meeting, compared the use of ketorolac and bromfenac during the
induction phase with cyclosporine for patients with dry eye.27 The
changes in Schirmer scores, ocular surface staining, and tear breakup time improved with both NSAIDs, but these findings were
significantly better with bromfenac.
DR GAYTON: I think there is another benefit with dry eye. One of
the biggest complaints that I hear from patients with dry eye is just
reflex tearing. If you give them some corneal analgesia, reflex tearing
decreases. I use NSAIDs in my conjunctivitis patients almost
exclusively and frequently cover them with a topical antibiotic of
some type as well. It is extremely rare that I end up having to use a
steroid drop for those patients.
DR DEVGAN: Before using NSAIDs in dry eye patients,
ophthalmologists need to screen patients closely. Patients with
underlying conditions like autoimmune disorders are at higher risk of
adverse events.28

I would like to point out that NSAIDs are also being explored in retinal
diseases. Some early data suggest that therapeutic inhibition of COX2 in the retina may be possible.9,29,30 An animal study demonstrated
nepafenac, 0.1%, inhibited diabetic retinopathy,31 and in an
anecdotal report, Hariprasad and colleagues used nepafenac, 0.1%,
in patients with CME and diabetic retinopathy, finding some
improvement in retinal thickness in the patients with diabetic macular
edema (DME).4 An ongoing clinical trial is evaluating the use of
bromfenac with ranibizumab (Lucentis) in the treatment of AMD.3
It will be interesting to see what the results of these studies are.

DR GILLS: What is your experience with the use of nonsteroidals for

Practical Uses of NSAIDs in

Cataract Surgery

long periods of time in patients with DME and other conditions that
may cause chronic inflammation?

Cataract surgeons have long tried to find ways to reduce

inflammation after cataract surgery. Each of the approved ocular
NSAIDs is effective for reducing postoperative inflammation.15,32-35
NSAIDs have also been used as an off-label indication to prevent
and treat CME after cataract surgery.36-39 Our panel discusses NSAID
use in cataract surgery and the special circumstances or patient
factors that might influence choice of NSAID as well as duration of
NSAID use during cataract procedures.

DR DEVGAN: Here in Los Angeles, we have a large diabetic

population in certain areas. Some of these patients do not have
strong maculas and they will end up on an NSAID topically for a
month after the cataract surgery. On the follow-up visit, the retinal
surgeon often has a hard time weaning the patient. Once weaned
off the NSAIDs, they may get a recurrence of their DME. These
patients are sometimes on a drop of NSAID, 1 drop a day, or 1 drop
every other day, for many months or even a year.

How Aggressive Should NSAID Use Be?

DR DEVGAN: I think we can agree that, in general, ophthalmologists

routinely give patients steroids and antibiotics after surgery. Should

we be giving NSAIDs to all patients after cataract surgery?
DR DAVIS: For those of us who do use antibiotics, there have not been
any good studies showing that topical antibiotics prevent
endophthalmitis.40 However, the incidence of endophthalmitis is far
lower than the incidence of CME, which in severe cases can have a
profound effect on best corrected visual acuity (BCVA). A recent
analysis of Medicare data showed that the incidence of
endophthalmitis after cataract surgery was 2.15 per each 1000
surgeries for the 8-year study period.41 By contrast, the incidence of
CME can range up to 19% when measured with fluorescein
angiography42 and up to 41% when measured with optical coherence
tomography (OCT).43 So if surgeons are going to rationalize that they
ought to use an antibiotic to prevent a far less common complication,
then one would rationalize that medications to prevent something that
is more frequent and equally as vision-threatening should be used.
DR GILLS: My son, also an ophthalmologist, uses topical antibiotics,

but I do not. In fact, I have performed 70,000 cases with no

endophthalmitis without using topical antibiotics; he and I both,
however, use antibiotics intraocularly at the time of cataract surgery.
We use a combination of vancomycin and ceftazidime along with
dexamethasone in the anterior chamber. I have followed this
protocol for nearly 30 years. Once I started doing lens implants, I
had several cases of sterile endophthalmitis, so we started
administering a steroid along with the antibiotics; since then I have
not seen sterile endophthalmitis cases. Therefore, it is my opinion
that you do not need antibiotics outside the eye; you need them
inside the eye where the infection might occur. I think we do more
harm using topical drops that may produce resistant organisms. The
alternative is that we use intraocular antibiotics such as ceftazidime
or vancomycin that will control infection and limit the chance of
producing a resistant organism. Resistance rarely occurs if an
antibiotic is used inside the eye.
DR DEVGAN: Several studies have demonstrated that pretreating
with NSAIDs can be effective in preventing or reducing
pseudophakic CME after cataract surgery.37-39,44-46 The length of
treatment with the various NSAIDs ranges from 1 day before surgery
to 21 days after the procedure for nepafenac46 to 2 days before
surgery to 8 weeks postoperatively for ketorolac.38 For bromfenac,
the NSAID was started 3 days before cataract surgery and continued
until the supply was finished.37 Which patients do you pretreat?
DR GAYTON: I pretreat every cataract patient with NSAIDs. When I
consider a patient to be high risk for the development of CME, I
begin the NSAID earlier and continue it longer. Even though patients
receiving a multifocal lens are not at a higher risk for CME, I place
them in the high-risk group. This is because a small amount of CME
can significantly affect the quality and quantity of vision. I consider
the following patients to be high-risk: those with diabetes, uveitis
patients, patients with epiretinal membranes, patients who have had
vitreoretinal surgery, patients who had CME in their contralateral
eye, and patients with retinitis pigmentosa.

DR GAYTON: Likewise, I have some patients on bromfenac who have

been on 1 drop a day for 2 years. These are patients who have either
chronic inflammation or recurrent macular edema. I am sure all of the
nonsteroidals would work in the same fashion for these uses, except
that once-a-day dosing in a chronic condition is advantageous.47
DR DAVIS: Do you consider patients with either non-neovascular or

neovascular macular degeneration high-risk patients for cataract

surgery?
DR GILLS: We routinely pretreat patients with nonsteroidals for 2 to

4 days prior to surgery. If we do not have a chance to pretreat, we

load the eye with multiple series of nonsteroidal drops on the day of
surgery. Certainly, patients with any retinal elevation evident on the
OCT are at risk. I pretreat those patients with 0.10 of intravitreal
bevacizumab (Avastin) and 0.10 cc of triamcinolone 1 week prior
to surgery. I have pretreated thousands of patients with diabetes and
then tracked and measured the retina and found that the retina thins
for several weeks after the injection. These data are in line with the
Korean study that also advocates pretreatment for diabetic patients.48
I also give extra subconjunctival triamcinolone to diabetic patients.
We routinely inject 1.0 cc of triamcinolone retrobulbarly at the time
of cataract surgery in patients with diabetic retinopathy and
approximately 1.5 cc to others who have borderline thickness.

Pain After Cataract Surgery

DR DEVGAN: Dr Davis, what about the pain after cataract surgery?
I know you insert a lot of presbyopic lenses, which may require
limbal relaxing incisions at the time of surgery. Sometimes patients
feel these incisions. One of the indications of the various NSAIDs is
the reduction of pain after surgery. How important is it to use an
NSAID for postop pain? And how many days do you treat prior to
and after surgery for pain or discomfort?
DR DAVIS: I think it is very important to realize that general cataract

surgery is not terribly painful, but there is that scratchiness and

discomfort that patients will mention in the early postoperative
period. This is probably incisional pain or temporary dry eye pain, or
possibly toxicity from the medications. When I used ketorolac after
cataract surgery, patients complained about burning and foreign
body sensation. When I began using bromfenac to simplify dosing,
I found that the complaints diminished.
DR DEVGAN: Yes, I agree with you, and I have done trials of every

commercially available NSAID in my own practice. The recent data on

bromfenac show that the once-daily formulation is effective in
managing pain in cataract patients on postop day 1.11 Nepafenac,
diclofenac, and ketorolac are also effective in managing pain in these
patients.34,49,50 Maxwell and colleagues found that nepafenac, 0.1%,
dosed either QD, BID, or TID was effective in improving ocular pain
after cataract surgery; the BID- or TID-dosing pain resolution, however,
began on postop day 1, whereas patients on QD dosing were pain-free
starting postop day 3.51 I have chosen bromfenac for both clinical
efficacy as well as compliance due to the easy dosing schedule.
DR GAYTON: Thankfully, modern cataract surgery patients usually

do not have a lot of pain. The pain is generally controlled by topical

NSAIDs. I also use NSAIDs to manage pain in patients with

accidental or surgically induced epithelial defects. NSAIDs have made
surface laser vision correction a much more comfortable procedure.

NSAIDs and Postoperative Visual Acuity

DR DEVGAN: What are your thoughts about the effect of NSAIDs on

The steroid decreases the amount of available arachidonic acid by

blocking the phospholipase enzyme.28 It is impossible for the steroid
to completely block the formation of arachidonic acid, which
becomes the substrate for the COX enzymes to form various
inflammatory by-products. The NSAID comes into play by inhibiting
this conversion by the COX enzymes. The steroid and the NSAID
work together to give rapid and excellent control of inflammation.

visual acuity postop? Do you think there is a benefit?

DR GILLS: As a purely clinical gauge, I think patients who are given

nonsteroidals are happier with their outcomes than those who are
not, particularly those who choose presbyopic intraocular lenses
(IOLs).52 The lenses are very good, but if the patients have any
inflammation and if the lenses are not centered, then they are not
happy. The fact that we are pretreating them prior to surgery is
almost as important as the posttreatment.
DR DAVIS: I definitely believe NSAIDs improve visual acuity
postoperatively. I believe the ocular surface is enhanced with their
use, anterior chamber inflammation is minimized, and the incidence
of CME is reduced. All these things lead to better acuity, both in
quantity (Snellen acuity) and quality (contrast acuity, sharpness, etc).

Practical Uses of NSAIDs in

Refractive Surgery
NSAIDs are also used in managing the pain following refractive
surgery; only ketorolac, 0.4%,58 and diclofenac, 0.1%,59 are
approved for treatment of pain after refractive surgery. Bromfenac
and nepafenac have also been studied for this indication. Sher and
colleagues found bromfenac was as effective as ketorolac in relieving
discomfort after photorefractive keratectomy (PRK)60; and Caldwell
and colleagues showed that nepafenac also reduced pain after
PRK.61 Our panel discusses use of NSAIDs in refractive procedures.
DR DEVGAN: How are you using NSAIDs in your refractive procedures?

DR GAYTON: I agree wholeheartedly with Dr Davis. The use of

DR DAVIS: I limit use of NSAIDs to the first 3 days after PRK and then

NSAIDs improves the likelihood of our patients achieving their

maximum potential acuity as quickly as possible.

stop. There are some patients who have absolutely no discomfort

and even though we give them a prescription for pain pills, they
dont use any. I do not use it in LASIK (laser assisted in situ
keratomileusis) although 1 study has shown that treatment before
and during LASIK with ketorolac, 0.5%, reduces postoperative pain
in that procedure.62 The discomfort in LASIK is so limited, usually to
the first 2 hours, that I do not think it is necessary.

DR DEVGAN: Most recently, Eric Donnenfeld, MD, did a study with

the new formulation of ketorolac, 0.45%, that indeed shows NSAIDs
can help improve visual acuity postop.53 In the study, 60.5% of
patients had an improvement in 3 lines of BCVA by 14 days postop.
This area of BCVA has not been as widely studied for all NSAIDs.
Anything that improves vision after cataract surgery is important in
delivering the best results to my patients.

Combination of NSAIDs and Steroids

DR DEVGAN: Is there a benefit to using steroids and NSAIDs

concurrently?
DR DAVIS: There have been studies showing that the combination
of a nonsteroidal and a steroid works better than either alone for
treating CME.54 As for prevention, Raizman and colleagues showed
that patients receiving only steroids had more postop CME than
patients receiving steroid and diclofenac.55 Other studies have shown
the efficacy of nepafenac and ketorolac, 0.4%, in combination with
steroids in the prevention of CME.56,57 There is definitely evidence
that supports using the combination both in the prevention and in
the treatment of CME.
DR GILLS: I concur that it is important to use concomitant steroids
and nonsteroidals prior to surgery, at the time of surgery, and
postoperatively. It certainly is beneficial.
DR GAYTON: If you look at the inflammatory pathways and apply

some basic biochemistry, it is apparent that the drugsthe steroid

and the nonsteroidalare synergistic in controlling inflammation.

DR GAYTON: I exclusively do surface laser treatment, so I use

nonsteroidals quite a bit. I actually start a nonsteroidal the day before

surgery and then continue it for 3 days after the procedure. We
presented a paper63 in which we compared all 3 of the main
nonsteroidals: ketorolac, 0.4%, nepafenac, and bromfenac. We
found that the nepafenac group had a statistically significantly
slower rate of epithelialization when compared with the ketorolac
and bromfenac groups; the pain control was in favor of bromfenac.
NSAID use has actually made PRK a much more acceptable
procedure among patients now that you can better control pain.
DR DEVGAN: A similar study from Trattler and colleagues on post-PRK

epithelial healing found similar results.64 This study was halted because
of safety concerns. Another study, however, which looked at patients
receiving PRK, did not show the same results with nepafenac,65 so this
finding of epithelial problems has not been confirmed.

Improving NSAID Adherence

DR DEVGAN: One of the major factors affecting outcomes is the

patient's adherence to postsurgical therapy. What can you do to

optimize the outcome of the patients on NSAIDs? When looking at
patient adherence, prescriptions that are dosed fewer times per day
show a higher rate of adherence.

Table 2. Examples of Published Cases of Corneal Melts With NSAIDs

References

Acular (ketorolac)

Lin et al. (2000)74

Congdon et al. (2001)79

22 cases

Flach (2001)14

Voltaren (diclofenac)

Nevanac (nepafenac)

3 cases
63 cases

4 cases

7 cases
3 cases

1 case

Bekendam et al. (2007)72

1 case

Isawi et al. (2007)76

Wolf et al. (2007)77
Di Pascuale et al. (2008)78

1 case
1 case

Diclofenac (generic)

32 cases

Asai et al. (2006)71

Mian et al. (2006)75

Xibrom (bromfenac)

2 cases

1 case
1 case

DR DAVIS: I think, obviously, the ideal postoperative state is patients

not taking anything. The closer you can get to that in terms of
decreasing frequency and duration of medication, the higher the
adherence you are going to have. I use bromfenac exclusively now
because of the once-a-day dosing.
DR DEVGAN: Many of us are giving patients topical anti-

inflammatories for many weeks6, or even moreafter surgery.

How do we address adherence in cases of long-term NSAID use?
DR DAVIS: It is a major issue, especially in a population of older

patients. Sometimes patients forget to tell us that they have other

medical problems and that they are taking other medications at
various times throughout the day. This is an added burden for them.
Some of them have limited mobility issues, such as arthritis. We have
all seen the videos of patients attempting to hit their eye with an
eyedrop, and many arent very successful. Multiply that with a
medication given 3 or 4 times a day. You just wonder how much
they are actually gettingif they even remember to do it. I think
midday doses of any medication are very inconvenient and are the
most likely to be missed. If patients are out of the house and not
carrying medications with them, it is highly likely that those doses are
going to be forgotten.
DR GAYTON: Often our patients have caregivers who are either a

visiting nurse or a family member. They are able to come by once,

sometimes twice, a day to help, but not many more times than that.
Having medications that can be used fewer times per day certainly
has a huge effect on caregivers as well as on the individuals. If you
have to use something 1 to 2 times a day, your likelihood of using it
pushes around 90%. If you have to use something 4 times a day,
your likelihood of using it is maybe under 60%, simply because of
the number of times.66 But when you figure a caregiver into that
equation, I think it is very important to try to prescribe medications
that patients can use less often.67
DR GILLS: To address compliance and adherence to medication
routines, I use 1 drop of a nonsteroidal medication, 1 drop of a
steroid, and 1.0 cc retrobulbar triamcinolone.68 If the patients forget
to use any of the drops, they still do fine because the triamcinolone
will carry them. Maybe a third or more of our patients do not take
medicines as directed.
DR DEVGAN: Of course, the use of retrobulbar triamcinolone is not

typical or standard practice. For the majority of surgeons, delivering

medications topically is the preferred route and its also the least
invasive, and it can be stopped in cases of issues such as steroidinduced glaucoma. For my patients, I have found the most success
with using a simplified topical regimen consisting of a once-daily
NSAID for a few weeks, a once-daily steroid for a couple of weeks,
and a twice-daily antibiotic for 1 week.

Safety of NSAIDs
With the increased length of treatment after cataract surgery
especially in patients who receive premium IOLs, or those who are at
high risk for CMEthere is more concern over toxicities of NSAIDs
than would occur with shorter durations of therapy. Temporary
stinging and burning is common after instillation of NSAID
eyedrops.47,58,59,69,70 Corneal melts have been reported with diclofenac,
0.1%, ketorolac, 0.5%, nepafenac, 0.1%, and bromfenac, 0.09%.71-73
In 1999, multiple reports of corneal melt after the use of a generic
form of diclofenac caused the recall of the generic agent.14 It is
unclear how much inappropriate use or inadequate follow-up
contributed to these cases.
DR DEVGAN: Are the side-effect profiles different for these NSAIDs?

Are they similar? Is it possible to have a corneal melt with any

NSAID? There are reported cases for every NSAID now (Table 2,
page 6).14,71,72,74-79

Individual Regimens
Each of the panelists listed their individual regimens for
cataract surgery. The agents mentioned here are the
preferences of each surgeon. Some of these medications
are being used for off-label indications.

Uday Devgan, MD:

I like to keep it simple:
1. Preoperatively: bromfenac once-daily formulation and
fluoroquinolone antibiotic 3 days before surgery
2. Postoperatively: fluoroquinolone for a week, steroid
for 3 weeks, and bromfenac once-daily formulation
for 6 weeks
For high-risk patients: Postop OCT with referral to
retinal surgeon if persistent thickening on OCT

James P. Gills, MD:

1. Pretreat with bromfenac twice a day for 3 days prior
to surgery
2. At the end of surgery, I give vancomycin, ceftazidime,
and dexamethasone in the anterior chamber
3. Retrobulbar triamcinolone acetonide (Kenalog) 1.0 cc
4. Postoperatively:1 drop of bromfenac once daily and
1 drop of prednisolone acetate (Pred Forte) for 6 to
7 weeks

Elizabeth A. Davis, MD:

1. Preoperatively: azithromycin 1 week prior to surgery;
bromfenac once daily 1 day before surgery
2. Postoperatively: bromfenac once daily and
prednisolone (for 4-6 weeks) and moxifloxacin
(for 2-3 weeks)

Johnny Gayton, MD:

Preoperatively:
Azithromycin for 1 week
Bromfenac once daily (unless insurance coverage
dictates another agent)
a. 1 week before for a higher-risk case
b. 2 days before for a routine case
Postoperatively:
A fluoroquinolone every 2 hours the day of surgery,
then 3 times a day for an additional 13 days. I use
gatifloxacin and moxifloxacin interchangeably
Bromfenac once daily for at least 6 weeks. I will go
longer than 6 weeks if I feel a person is at higher risk
or is showing any signs of macular edema
Steroid every 2 hours the day of surgery, then:
a. If using prednisolone acetate, 4 times per day
for 2 weeks, then twice a day for 2 weeks
b. If using difluprednate (Durezol), twice a day
for 2 weeks and then once a day for 2 weeks

DR GILLS: I believe the statistics today are much better compared

with what we have seen in the past. The use of NSAIDs in low to
moderate dosages should decrease the occurrence of corneal melts.
I believe it is important to shy away from patients who have severe
tear deficiency syndromes and do not have good lid closure. I have
seen several corneal melts that came from the use of generic
diclofenac; this occurred in patients with dry eyes (15+ years ago),
and the vehicle that was used to carry the diclofenac appeared to be
one of the problems. I have not seen the same problem with melts
when using nonsteroidals other than generic diclofenac.

CASE VIGNETTE 2: PATIENTS WITH DENSE OR

WHITE CATARACTS

DR DEVGAN: All the more reason, I think, to use an NSAID at a lower

concentration and lower dose, if possible. With any NSAID, the

surgeon should take extra caution with patients who are at higher
risk, such as those with corneal epithelial defects, poorly controlled
diabetes, severe dry eye syndrome, or rheumatoid arthritis. Luckily,
the benefits of NSAIDs far outweigh the potential risks in the vast
majority of our patients.

Figure 2a. Dense Cataract

Figure 2b. White Cataract

DR DEVGAN: What about a dense cataract? Do you expect more

postop inflammation? Do you change your medicine regimen?
DR GILLS: Not much, because a dense cataract is not much different

As for long-term use, a recent presentation at AAO 2010 found that

patients using the NSAIDs ketorolac, nepafenac, or bromfenac could
use these agents safely for at least 3 months. The study included
some patients who were treated with NSAIDs for up to 120 months.
The patients who had problems with corneal melts may have had
other underlying health issues, like diabetes or autoimmune diseases,
that put them more at risk.80 The incidence of corneal melts was 1
in 500,000 in this report.

DR DEVGAN: What about a white cataract where you put trypan blue

Case Vignettes: Roles of NSAIDs After

Surgical Procedures*

DR DAVIS: It depends on whether it is a liquefied cataract, whether

CASE VIGNETTE 1: PATIENTS WHO RECEIVE SPECIALTY

LENSES AFTER CATARACT EXTRACTION

Figure 1a. Multifocal Lens

Figure 1b. Accommodating Lens

DR DEVGAN: What is the importance of using NSAIDs for these

patients postsurgery?
DR DAVIS: You do not want to set up the expectations of good
uncorrected visual acuity only to have it derail because you failed to
prescribe a nonsteroidal. I think using a nonsteroidal would help in
numerous waysnot just in comfort, not just in reduced anterior
chamber inflammation, but also in reduction of subclinical CME,37-39
which is going to enhance quality of vision, contrast, and acuity.
DR DEVGAN: What about preventing capsular bag fibrosis or
reducing it in patients who get an accommodating lens? I think that
a longer regimen of anti-inflammatories may help to prevent
excessive capsular bag fibrosis, and that can help prevent lens
shifting and malposition.
DR GILLS: It is hard to know whether the steroids decrease fibrosis
because it is difficult to carry out a study. But there have been many
cases of capsular bag fibrosis, which is why some people stopped
using that lens. It is a little better now since the availability of
biaspheric lenses. I believe that patients with the biaspheric lenses are
not at as high risk for CME as patients who receive multifocal lenses.
*All ocular photos are provided courtesy of Uday Devgan, MD.

from a routine case. If I do expect more inflammation, I just increase

my dose of steroids and nonsteroidals to BID and increase the dose
of retrobulbar triamcinolone to 1.5 cc.
in? I often suspect that even a little trypan blue can cause more
inflammation. For these patients, particularly when the cataract is
dense and more phaco energy is used, I have come to expect more
postop inflammation and so I keep these patients on the steroid and
NSAID for a longer period.
a lot of ultrasound energy is going to be used, and on what was the
cause of the cataract. Why is it a white cataract? Is it from retinal
surgery, in which case the patient is at increased risk of CME? Or is
it from an epiretinal membrane? Is it a traumatic cataract, in which
case it is going to be a more complex surgery? There may be other
things going on behind the eye. I think it is best to be prepared and
to treat a white cataract as if it has potential to be at greater risk for
postoperative inflammation. This is definitely a case in which you
need an NSAID postop.
DR GAYTON: One of the nice things that I have noticed about the
improvement in technology and the improvement in preoperative
and postoperative medications is that even with these relatively dense
cataracts, we are having significantly less postoperative corneal
edema. I put these larger cataracts, especially patients with white,
black, or red cataracts, into a higher-risk category and treat them with
NSAIDs a week ahead of time.

CASE VIGNETTE 3: RETINAL PATHOLOGY AT THE TIME OF

CATARACT SURGERY

Figure 3a. Diabetic Retinopathy

Figure 3b. AMD (dry)

DR DEVGAN: Case Vignette 3 focuses on patients with posterior

segment disease like diabetic retinopathy or patients with dry AMD.
What do you do differently in terms of your NSAIDs, steroids, or
postop management?
DR GILLS: That depends on the OCT results and if the OCT is relatively

flat. I treat diabetic patients about a week ahead with a nonsteroidal

drop, and follow with intravitreal injections when necessary. If the
OCT indicates significant retinal edemamore than 300 micronsI

will give an intravitreal triamcinolone and bevacizumab injection. I

then re-measure the OCT and make sure the retina is flat. The effect
from the treatment usually peaks at about 3 weeks, and then the
edema typically recurs. These patients need to see a retinal surgeon for
further photocoagulation because the injections are just temporary
measures. So you have to treat the diabetic retinopathy temporarily
while you do the cataract extraction, and then direct the patient back
to a retinal specialist to do the laser therapy.

postoperative period and keep them on nonsteroidals and steroids

for the duration of their case. Patients with glaucoma have to be
monitored more closely to make sure their pressure does not get out
of control. It is hard to measure accurately intraocular pressure (IOP)
in patients who have had previous RKs; thus, it is important that we
look at the disc carefully and monitor the pressure as best we can. I
think it is important to be very careful in what you do with them. It
is very difficult to evaluate and treat these patients.

DR DEVGAN: My preferred approach is to get the clearance of a

RKs will usually create a hyperopic shift for 2 to 4 weeks after surgery
because of the edema in the radial cuts. Therefore, I typically add
0.5 D to 1 D more power to the lens than the formula calls for since
80% of eyes operated on with RKs end up hyperopic. I inform the
patient about this and during the postop period prescribe sodium
chloride and steroids 6 times a day until I can titer the refraction and
get it to where it needs to be.

retinal colleague before the cataract surgery. At this preoperative

visit, the retinal specialist can also inject any intravitreal medications
and start the patient on topical NSAIDs.

CASE VIGNETTE 4: CATARACT SURGERY IN EYES WITH

IRIS PATHOLOGY

DR DAVIS: Depending on the medications, such as prostaglandin

analogs, those glaucoma patients are on preoperatively, they may
be at greater risk of postoperative inflammation and CME. I
definitely think these patients need nonsteroidals, and in certain
cases, a more extensive course of therapy. I would still use steroids,
but certainly monitor IOP closely.82
DR GAYTON: In glaucoma cases, I agree that you really have to worry
Figure 4a. Uveitis

Figure 4b. Iris Pigment Loss From

IOL Edge

DR DEVGAN: Case Vignette 4 is a cataract surgery in the uveitic eye.

Do you expect more postop inflammation? How do you change

your medication regimen?
DR GAYTON: The one thing that I do differently in my chronic

inflammation patients is that at the time of cataract surgery, I will

give them intravitreal triamcinolone in addition to using frequent
topical steroids and the nonsteroidal eyedrops.81
DR DEVGAN: There may be more inflammation in eyes in which the

iris is manipulated more than in typical surgeries, as after lysing

posterior synechiae. In addition, uveitic eyes have a higher incidence
of postoperative CME compared with normal eyes. This is the type
of patient that I will sometimes keep on bromfenac for months after
cataract surgery.
DR DAVIS: This is a case in which you certainly expect to see more
inflammation. Manipulation of uveal tissues not only increases risk of
anterior chamber inflammation, but posterior inflammation (such as
CME) as well. So these are the patients you want to load up on
NSAIDs and frequent steroids.

CASE VIGNETTE 5: GLAUCOMATOUS EYES/

DR GILLS: We follow every patients postop pressures in the early

postop period after cataract surgery. An IOP check is done at 20
minutes postop using the noncontact tonometer (NCT). If unable to
obtain an IOP using the NCT, it is measured in clinic applanation.
Patients receiving premium lenses are kept for 1 hour in recovery,
where the IOP is recorded twice: once at 20 minutes and a second
time at 1 hour postop.

CONCLUSIONS
The role of NSAIDs in the management of eye disorders and following
ophthalmic surgical procedures is growing. The increased rationale
for the use of NSAIDs is further bolstered by the safety of the current
NSAID formulations and the increased usage is also likely attributable
to the availability of simplified-dosing regimens. Patient adherence
is key to improving patient outcomes; simplification of these
regimens can increase adherence.

PIGMENT DISPERSION

Figure 5a. Radial keratotomy

(RK) Incisions and Krukenberg
Spindle of Pigment

about patients with split fixation or patients who have a very small
visual field left. One of the things that I do is a significant amount of
endolaser cycloablation/endoscopic cyclophotocoagulation (ECP). I
have found the combination of steroids and nonsteroidals to be very
helpful in controlling inflammation following cycloablation. You really
have to watch these patients closely for pressure spikes. We usually
see them a few hours after surgery and may even check them again
later that same dayto be absolutely sure that they are not spiking
and then see them the next day. Of course, if the patients pressure is
spiking, we do an anterior chamber decompression. The nonsteroidals
have, in my opinion, made the use of ECP much better because of
the ability to better control the inflammation. One of the problems
with cyclodestructive or cycloablative procedures is postoperative
inflammation. Having an NSAID that can be used safely for a long
period of time helps to better control this inflammation.

Figure 5b. Glaucomatous Optic

Nerve Dispersion Glaucoma, and
Cortical Cataract

DR DEVGAN: Is this an eye in which you would be more inclined to

stop steroids and perhaps prescribe stronger or more NSAIDs for
control of inflammation?
DR GILLS: Patients with glaucomatous disc optic nerve disease are
very challenging. I follow them with corneal topography during the

Lowering the incidence of CME after cataract surgery is a very

important consideration in this procedure because the occurrence of
CME can be visually devastating and can lead to complex and
longer-term therapy to improve the subsequent visual acuity. The
increased use of premium IOLs may also require the incorporation
of NSAIDs into the postsurgical regimen because inflammation in
these patients can lead to worse outcomes.
NSAIDs may also make surface ablation refractive surgery more
comfortable for the patient. The addition of NSAIDs to the surgical
regimen for either cataract surgery or refractive surgery can improve
the outcomes of these procedures; the discussion is now shifting to
length of treatment and selection of patients for optimal outcomes.

10

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32. Heier J, Cheetham JK, Degryse R, et al. Ketorolac tromethamine 0.5% ophthalmic
solution in the treatment of moderate to severe ocular inflammation after cataract
surgery: a randomized, vehicle-controlled clinical trial. Am J Ophthalmol. 1999;
127(3):253-259.
33. Lane SS, Modi SS, Lehmann RP, Holland EJ. Nepafenac ophthalmic suspension 0.1% for
the prevention and treatment of ocular inflammation associated with cataract surgery.
J Cataract Refract Surg. 2007;33(1):53-58.
34. Donnenfeld ED, Holland EJ, Stewart RH, Gow JA, Grillone LR; Bromfenac Ophthalmic
Solution 0.09% (Xibrom) Study Group. Bromfenac ophthalmic solution 0.09% (Xibrom) for
postoperative ocular pain and inflammation. Ophthalmology. 2007;114(9):1653-1662.
35. Miyanaga M, Miyai T, Nejima R, Maruyama Y, Miyata K, Kato S. Effect of bromfenac
ophthalmic solution on ocular inflammation following cataract surgery. Acta
Ophthalmol. 2009;87(3):300-305.
36. Warren KA, Bahrani H, Fox JE. NSAIDs in combination therapy for the treatment of
pseudophakic cystoid macular edema. Retina. 2010;30(2):260-266.
37. Cable MM (as reported by Charters L). Bromfenac reduces CME in cataract;
Ophthalmology Times. June 1, 2010:10.
38. 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(1):57-63.
39. Almeida DR, Johnson D, Hollands H, et al. Effect of prophylactic nonsteroidal
antiinflammatory drugs on cystoid macular edema assessed using optical coherence
tomography quantification of total macular volume after cataract surgery. J Cataract
Refract Surg. 2008;34(1):64-69.
40. Schein OD. Prevention of endophthalmitis after cataract surgery: making the most of
the evidence. Ophthalmology. 2007;114(5):831-832.
41. West ES, Behrens A, McDonnell PJ, Tielsch JM, Schein OD. The incidence of
endophthalmitis after cataract surgery among the U.S. Medicare population increased
between 1994 and 2001. Ophthalmology. 2005;112(8):1388-1394.
42. Ursell PG, Spalton DJ, Whitcup SM, Nussenblatt RB. Cystoid macular edema after
phacoemulsification: relationship to blood-aqueous barrier damage and visual acuity.
J Cataract Refract Surg. 1999;25(11):1492-1497.
43. Lobo CL, Faria PM, Soares MA, Bernardes RC, Cunha-Vaz JG. Macular alterations after
small-incision cataract surgery. J Cataract Refract Surg. 2004;30(4):752-760.
44. Yavas GF, Oztrk F, Ksbeci T. Preoperative topical indomethacin to prevent
pseudophakic cystoid macular edema. J Cataract Refract Surg. 2007;33(5):804-807.
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Accessed December 1, 2010.
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triamcinolone acetonide on the progression of diabetic retinopathy and visual outcomes
after cataract surgery. J Cataract Refract Surg. 2008;34(5):823-826.
49. Fry LL. Efficacy of diclofenac sodium solution in reducing discomfort after cataract
surgery. J Cataract Refract Surg. 1995;21(2):187-190.
50. Acuvail [package insert]. Irvine, CA: Allergan, Inc. 2009.
51. Maxwell WA, Reiser HJ, Stewart RH, et al. Nepafenac dosing frequency for ocular pain
and inflammation associated with cataract surgery. J Ocul Pharmacol Ther. 2008;24(6):
593-599.
52. Aker AB. Get in the game of premium IOLs. Cataract Refract Surg Today. May 2010
Supplement.
53. Donnenfeld ED (as reported by Charters L). Ketorolac improves visual acuity.
Ophthalmology Times. June 1, 2010:17-18.
54. Heier JS, Topping TM, Baumann W, Dirks MS, Chern S. Ketorolac versus prednisolone
versus combination therapy in the treatment of acute pseudophakic cystoid macular
edema. Ophthalmology. 2000;107(11):2034-2038.
55. Trattler W. Topical NSAIDs for pain and inflammation. Review of Ophthalmology.
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December 2, 2010.
56. Wittpenn JR, Silverstein S, Heier J, Kenyon KR, Hunkeler JD, Earl M; Acular LS for
Cystoid Macular Edema (ACME) Study Group. 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(4):554-560.
57. Wolf EJ, Braunstein A, Shih C, Braunstein RE. Incidence of visually significant
pseudophakic macular edema after uneventful phacoemulsification in patients treated
with nepafenac. J Cataract Refract Surg. 2007;33(9):1546-1549.
58. Acular LS [package insert]. Irvine, CA: Allergan, Inc; 2009.
59. Voltaren [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2009.
60. Sher NA, Golben MR, Bond W, Trattler WB, Tauber S, Voirin TG. Topical bromfenac
0.09% vs ketorolac 0.4% for the control of pain, photophobia, and discomfort
following PRK. J Refract Surg. 2009;25(2):214-220.
61. Caldwell M, Reilly C. Effects of topical nepafenac on corneal epithelial healing time
and postoperative pain after PRK: a bilateral, prospective, randomized, masked trial.
J Refract Surg. 2008;24(4):377-382.
62. Dougherty PJ. Acular LS before and during LASIK for the control of pain: a randomized,
masked contralateral eye trial. J Refract Surg. 2009;25(2):210-213.

63. Gayton J. Bromfenac, nepafenac, and ketorolac in surface laser ablation.

Paper presented at: American Society of Cataract and Refractive Surgery Annual
Meeting; April 3-8, 2009; San Francisco, CA.

74. Lin JC, Rapuano CJ, Laibson PR, Eagle RC Jr, Cohen EJ. Corneal melting associated
with use of topical nonsteroidal anti-inflammatory drugs after ocular surgery. Arch
Ophthalmol. 2000;118:1129-1132.

64. Trattler W, McDonald M. Double-masked comparison of ketorolac tromethamine 0.4%

versus nepafenac sodium 0.1% for postoperative healing rates and pain control in eyes
undergoing surface ablation. Cornea. 2007;26(6):665-669.

75. Mian SI, Gupta A, Pineda R 2nd. Corneal ulceration and perforation with ketorolac
tromethamine (Acular) use after PRK. Cornea. 2006;25(2):232-234.

65. Jalali S, Boxer Wachler BS. Comparison study of the effect of Nevanac on epithelialization
and haze in PRK. Poster presented at: American Academy of Ophthalmology Annual
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66. Ikeda H, Sato M, Tsukamoto H, et al. Evaluation and multivariate statistical analysis of
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67. Lau HS, Beuning KS, Postma-Lim E, Klein-Beenink L, de Boer A, Porsius AJ. Noncompliance in elderly people: evaluation of risk factors by longitudinal data analysis.
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68. Kahook MY, Camejo L, Noecker RJ. Trabeculectomy with intraoperative retrobulbar
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69. Nevanac [package insert]. Fort Worth, TX: Alcon Laboratories, Inc; 2007.
70. Xibrom [package insert]. Irvine, CA: ISTA Pharmaceuticals, Inc; 2010.
71. Asai T, Nakagami T, Mochizuki M, Hata N, Tsuchiya T, Hotta Y. Three cases of corneal
melting after instillation of a new nonsteroidal anti-inflammatory drug. Cornea. 2006;
25(2):224-227.
72. Bekendam PD, Narvez J, Agarwal M. Case of corneal melting associated with the use
of topical nepafenac. Cornea. 2007;26(8):1002-1003.
73. Tai MC, Chang JH, Chang CJ. Corneal melting associated with the use of topical
ketorolac: successful treatment with tissue adhesive. J Med Sci. 2003;23(4):227-230.

A Practical Look AT THE Role

76. Isawi H, Dhaliwal DK. Corneal melting and perforation in Stevens Johnson syndrome
following topical bromfenac use. J Cataract Refract Surg. 2007;33(9):1644-1646.
77. Wolf EJ, Kleiman LZ, Schrier A. Nepafenac-associated corneal melt. J Cataract Refract
Surg. 2007;33(11):1974-1975.
78. Di Pascuale MA, Whitson JT, Mootha VV. Corneal melting after use of nepafenac in a
patient with chronic cystoid macular edema after cataract surgery. Eye Contact Lens.
2008;34(2):129-130.
79. Congdon NG, Schein OD, von Kulajta P, Lubomski LH, Gilbert D, Katz J. Corneal
complications associated with topical ophthalmic use of nonsteroidal antiinflammatory
drugs. J Cataract Refract Surg. 2001;27(4):622-631.
80. Singer MA, Trattler WB, Boyer DS, et al. Are nonsteroidal drops safe for long-term use?
Poster presented at: American Academy of Ophthalmology Meeting; October 24-27,
2009; San Francisco, CA. Poster 624.
81. Okhravi N, Morris A, Kok HS, et al. Intraoperative use of intravitreal triamcinolone in
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1278-1283.
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6-month randomized trial. Arch Ophthalmol. 2005;123(2):186-192.

of NSAIDs IN OPHTHALMOLOGY

CME POST TEST

Focus on Cataract and Refractive Procedures

To obtain AMA PRA Category 1 Credit for this activity, you must complete the CME Post Test by writing the best answer to each
question in the Answer Box located on the Activity Evaluation/Credit Request form on the following page.
1. For which of the following indications have NSAIDs not been
FDA approved ?
a. Postoperative pain
b. Management of dry eye syndrome
c. Treatment of allergic conjunctivitis
d. Ocular inflammation after surgery
2. NSAIDs are often used after refractive surgery. Which
ophthalmic NSAID is approved for use after refractive surgery?
a. Ketorolac, 0.4%
b. Nepafenac, 0.1%
c. Bromfenac, 0.09%
d. Ketorolac, 0.5%
3. NSAIDs are dosed differently based on their potency and
penetration. Which ophthalmic NSAID is approved for once-aday dosing?
a. Ketorolac, 0.4%
b. Nepafenac, 0.1%
c. Bromfenac, 0.09%
d. Ketorolac, 0.5%
4. Hariprasad and colleagues found that ____________may
improve retinal thickness in the patients with DME.
a. Ketorolac, 0.4%
b. Nepafenac, 0.1%
c. Bromfenac, 0.09%
d. Ketorolac, 0.5%

5. Improving adherence is an important issue in patients after

ophthalmic surgery. An 85-year-old man is scheduled for
cataract extraction in his left eye. What factor is not as
important when planning his medication regimen after surgery?
a. Number of eye medications already taking
b. Need for a caregiver
c. Number of ophthalmic follow-up visits needed
d. History of arthritis
6. A 45-year-old woman with rheumatoid arthritis develops a
posterior capsular cataract in her left eye after several years of
corticosteroid treatments to manage her condition. In planning
for her cataract extraction to lessen the risk of adverse
outcomes, the ophthalmologist should:
a. Evaluate the patient for dry eye and epithelial defects
b. Completely avoid NSAID use under any circumstances
c. Plan to use a typical NSAID regimen in this patient
7. Corneal melts have been seen with several different types of
NSAIDs. Patients who may be at higher risk for the
development of corneal melts do not include patients with:
a. Autoimmune diseases
b. Severe dry eye
c. Diabetes
d. A history of contact lens wear

11

ACTIVITY EVALUATION/CREDIT REQUEST

A Practical Look AT THE Role

of NSAIDs IN OPHTHALMOLOGY

ORIGINAL RELEASE: MARCH 1, 2011

LAST REVIEW: FEBRUARY 16, 2011
EXPIRATION: MARCH 31, 2012

Focus on Cataract and Refractive Procedures

To receive AMA PRA Category 1 Credit, you must complete this Evaluation form and the Post Test. Record your answers to the Post Test in the Answer Box
located below. Mail or Fax this completed page to The New York Eye and Ear InfirmaryICME, 310 East 14th Street, New York, NY 10003 (Fax: 212-353-5703).
Your comments help us to determine the extent to which this educational activity has met its stated objectives, assess future educational needs, and create timely
and pertinent future activities. Please provide all the requested information below. This ensures that your certificate is filled out correctly and is mailed to the
proper address. It also enables us to contact you about future CME activities. Please print clearly or type. Illegible submissions cannot be processed.

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I certify that I have participated in the entire activity and claim 1.5 AMA PRA Category 1 Credits.
Signature Required ________________________________________________________________________ Date Completed _______________________________
Yes No Did you perceive any commercial bias in any part of this activity? If yes, please specify content and/or contributor.
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Outcomes Measurement
Circle the number that best reflects your opinion on the degree to which the following learning objectives were met:
5 = Strongly Agree
4 = Agree
3 = Neutral
2 = Disagree
1 = Strongly Disagree
After successfully completing this activity, I have improved my ability to:
1. Review the current and emerging major uses for NSAIDs in ocular conditions

2. Review recent clinical evidence on the use of NSAIDs in cataract and refractive procedures

3. Discuss the strategies for incorporating NSAIDs into cataract and refractive procedures
to optimize patient results

1. Please list one or more things, if any, you learned from participating in this educational activity that you did not already know.
________________________________________________________________________________________________________________________________________
2. As a result of the knowledge gained in this educational activity, what changes, if any, do you plan to make in your practice?
________________________________________________________________________________________________________________________________________
3. Related to what you learned in this activity, what barriers to implementing these changes or achieving better patient outcomes do you face?
_______________________________________________________________________________________________________________________________________
4. Please check the Core Competencies (as defined by the Accreditation Council for Graduate Medical Education) that were enhanced for you through
participation in this activity. Patient Care
Practice-Based Learning and Improvement
Professionalism
Medical Knowledge
Interpersonal and Communication Skills
Systems-Based Practice
5. What other topics would you like to see covered in future CME programs?
_______________________________________________________________________________________________________________________________________
Additional Comments
_______________________________________________________________________________________________________________________________________

Post Test Answer Box