a practical look at the role of nsaids in ophthalmology
DESCRIPTION
A Practical Look at the Role of NSAIDs in OphthalmologyTRANSCRIPT
In joint sponsorship with MedEdicus LLC
Sponsored by The New York Eye and Ear Infirmary
In association with
This continuing medical education activity issupported through an unrestricted educationalgrant from ISTA Pharmaceuticals, Inc.
A CME MONOGRAPH
Role of NSAIDsA Practical Look AT THE
IN OPHTHALMOLOGY
ORIGINAL RELEASE: MARCH 1, 2011
LAST REVIEW: FEBRUARY 16, 2011
EXPIRATION: MARCH 31, 2012
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LEARNING METHOD AND MEDIUMThis educational activity consists of a supplement and seven (7) study questions. The participantshould, 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 andevaluation form. This educational activity should take a maximum of 1.5 hours to complete.
CONTENT SOURCEThis continuing medical education (CME) activity captures content from a CME roundtablediscussion held October 2010.
TARGET AUDIENCEThis educational activity is intended for comprehensive ophthalmologists, cataract andrefractive surgeons.
OVERVIEWUse of nonsteroidal anti-inflammatory drugs (NSAIDs) is highly prevalent in anterior segmentprocedures, which have grown dramatically in the last decade. The number of Americans withcataracts is expected to increase to 30 million by the year 2020 as the population ages; andthose with pseudophakia/aphakia will rise to 9 million. This represents a 50% increase fromthe year 2000. The number of refractive procedures performed annually in the United Statesis approximately 1 million; while this number has remained relatively unchanged over the pastseveral years, it is a large volume of surgery.
With these developments, the expectations on the surgeon have increased and the margin forcomplications narrowed. Inflammation has always been accepted as a natural consequence ofcataract surgery and it is accepted to be the pathogenesis for cystoid macular edema, whichremains the most common cause of vision loss after cataract surgery. Prevention and controlof inflammation therefore is key to a successful outcome. Recent US Food and DrugAdministration approvals of new NSAID formulations make it timely for a practical update onthe role of NSAIDs for today’s practice.
LEARNING OBJECTIVES: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 proceduresto optimize patient results
ACCREDITATION STATEMENTThis activity has been planned and implemented in accordance with the Essential Areas andPolicies of the Accreditation Council for Continuing Medical Education through the jointsponsorship of The New York Eye and Ear Infirmary andMedEdicus LLC. The New York Eye andEar Infirmary is accredited by the ACCME to provide continuing medical education for physicians.
AMA CREDIT DESIGNATION STATEMENTThe New York Eye and Ear Infirmary designates this enduring material for a maximum of 1.5AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate withthe extent of their participation in the activity.
GRANTOR STATEMENTThis continuing medical education activity is supported through an unrestricted educationalgrant from ISTA Pharmaceuticals, Inc.
MISSION STATEMENTIt is The New York Eye and Ear Infirmary Institute for Continuing Medical Education’s statedmission to create medical education activities that will serve to increase the knowledge, skills,professional performance, and relationships that a physician uses to provide services forpatients, the public, or the chosen profession.
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DISCLOSURESElizabeth A. Davis MD, FACS: Dr Davis has had a financial agreement or affiliation duringthe past year with the following commercial interests in the form of Consultant/AdvisoryBoard: Abbott Medical Optics, Bausch + Lomb Incorporated, Inspire Pharmaceuticals, andISTA Pharmaceuticals, Inc; Fees for promotional, advertising, or non-CME services receiveddirectly from commercial interest or their Agents (e.g., Speakers Bureaus): Allergan, Inc;Ownership Interest: Refractec, Inc.
Uday Devgan, MD: Dr Devgan has had a financial agreement or affiliation during the pastyear 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 SirionTherapeutics; Fees for promotional, advertising, or non-CME services received directly fromcommercial interest or their Agents (e.g., Speakers Bureaus): Abbott Medical Optics; Alcon,Inc; Allergan, Inc; Bausch + Lomb Incorporated; Carl Zeiss Meditec; Haag-Streit; Hoya SurgicalOptics; Inspire Pharmaceuticals; and ISTA Pharmaceuticals, Inc; Contracted Research: AbbottMedical Optics; Bausch + Lomb Incorporated; and Gerson Lehrman Group; OwnershipInterest: Alcon, Inc; ISTA Pharmaceuticals, Inc; Renaissance Surgical; and Specialty Surgical.
Johnny Gayton, MD: Dr Gayton has had a financial agreement or affiliation during the pastyear with the following commercial interests in the form of Honoraria: Alcon, Inc; InspirePharmaceuticals; and ISTA Pharmaceuticals, Inc; Consultant/Advisory Board: ISTAPharmaceuticals, Inc; Fees for promotional, advertising, or non-CME services received directlyfrom commercial interest or their Agents (e.g., Speakers Bureaus): Inspire Pharmaceuticals, andISTA Pharmaceuticals, Inc.
James P. Gills, MD: Dr Gills has had a financial agreement or affiliation during the past yearwith 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; Ownership: Abbott Medical Optics; Alcon, Inc; Allergan, Inc; and Lenstec, Inc.
PEER REVIEW DISCLOSURESBrandon Ayres, MD: Dr Ayres has had a financial agreement or affiliation during the pastyear 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., SpeakersBureaus): Alcon, Inc; Allergan, Inc; Inspire Pharmaceuticals; ISTA Pharmaceuticals, Inc; andBausch + Lomb Incorporated.
Harry Koster, MD: Dr Koster has had a financial agreement or affiliation during the past yearwith the following commercial interests in the form of Honoraria: EyeSys Vision Inc.
EDITORIAL SUPPORT DISCLOSURESDominique Walton Brooks, MD; Cynthia Tornallyay, RD, MBA; Kimberly Corbin,CCMEP; and Barbara Lyon have no relevant commercial relationships to disclose.
DISCLOSURE ATTESTATIONEach 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 herinvolvement in this activity;
2) that practice recommendations given relevant to the companies with whom he orshe 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 practicerecommendations.
OFF-LABEL DISCUSSIONThis activity includes off-label discussion of nonsteroidal anti-inflammatory agents for cystoidmacular edema, retinal disorders, episcleritis, and dry eye.
TO OBTAIN AMA PRA CATEGORY 1 CREDIT™To obtain AMA PRA Category 1 Credit™ for this activity, read the material in its entirety andconsult referenced sources as necessary. Complete the evaluation form along with the post testanswer box within this supplement. Remove the Activity Evaluation page from printedsupplement or print the Activity Evaluation page from Digital Edition. Return via mail or faxto Kim Corbin, Director, ICME, The New York Eye and Ear Infirmary, 310 East 14th Street,New York, NY 10003 or fax to (212) 353-5703. Your certificate will be mailed to the addressthat you provide on the evaluation form. Please allow 3 weeks for mailed/faxed forms toprocess. Note: You must score a 70% or higher to receive credit for this activity.
DISCLAIMERThe views and opinions expressed in this educational activity are those of the faculty and do notnecessarily represent the views of The New York Eye and Ear Infirmary; MedEdicus LLC; ISTAPharmaceuticals, Inc; orOphthalmology Times. Please refer to the official prescribing informationfor each product for discussion of approved indications, contraindications, and warnings.
©2011 MedEdicus LLC. All rights reserved.
Uday Devgan, MD (PROGRAM CHAIR AND MODERATOR)Private PracticeDevgan Eye SurgeryChief of OphthalmologyOlive View–UCLA Medical CenterUCLA School of MedicineLos Angeles, California
Elizabeth A. Davis MD, FACSPartnerMinnesota Eye ConsultantsAdjunct Clinical Assistant ProfessorUniversity of MinnesotaMinneapolis, Minnesota
Johnny Gayton, MDFounderEyesight AssociatesWarner Robins, GeorgiaAdjunct FacultyMercer University School of MedicineMacon, Georgia
James P. Gills, MDFounder and DirectorSt. Luke’s Cataract & Laser InstituteAffiliate Professor of OphthalmologyUniversity of South FloridaTampa, Florida
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Mechanism and Efficacy of NSAIDsThere are several topical ocular NSAIDs approved by the FDA forthe 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 dosingBoth ketorolac, 0.4% and 0.5%, and diclofenac, 0.1%, areavailable in generic formulations (Table 1).
One of the mechanisms of action of all NSAIDs is to inhibitcyclooxygenase (COX) enzymes; thus, the formation of excessiveprostaglandins that include PGE2, PGD2, PGF2a, and PGI2 are alsoinhibited.1 According to some studies, ketorolac may be the mostpotent inhibitor of COX-1 enzymes,5 while both bromfenac6 andamfenac*5 claim to be the most potent inhibitor of the COX-2enzymes. COX-2 may be more responsible for inflammation, andthe anti-inflammatory actions of NSAIDs may be associated withtheir inhibition of COX-2. This relationship has not been provenconsistently in clinical trials; as an added point, it is thought thatCOX-1 may play a role in inflammation as well.1
Ocular penetration and potency are key factors in the efficacy of ocularmedications. Several studies have evaluated the degree of penetration
Focus on Cataract and Refractive Procedures
Role of NSAIDsA Practical Look AT THE
IN OPHTHALMOLOGY
Drug Manufacturer Dosing Indications
Bromfenac, 0.09% (Bromday) ISTA Pharmaceuticals, Inc 1x/day • 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 dropeach ½ 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
• treatment of postoperative inflammation following cataract extraction
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
• temporary relief of pain and photophobia following corneal refractive surgery
Suprofen, 1% (Profenal®) Alcon Laboratories, Inc 2 drops 3, 2, and 1 hourbefore surgery
• inhibition of intraoperative miosis
Diclofenac, 0.1% generic 4x/day • 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
• treatment of postoperative inflammation following cataract extraction
Ketorolac, 0.4% generic 4x/day • reduction of ocular pain and burning/stinging following corneal refractive surgery
Table 1. Available NSAIDs
INTRODUCTIONNonsteroidal anti-inflammatory drugs (NSAIDs) are amongthe most frequently prescribed types of medications in theworld.1 These medications have been used for their analgesicand anti-inflammatory qualities for many decades;ophthalmic preparations of NSAIDs are increasingly beingused to manage postoperative inflammation, prevent andtreat cystoid macular edema (CME), and maintainintraoperative mydriasis.1 Ophthalmic NSAIDs can also beused to manage pain and photophobia after refractivesurgery1 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 betreated with NSAIDs in the coming years.3,4
Recent US Food and Drug Administration (FDA) approvalsof new NSAID formulations make it timely for a practicalupdate on the role of NSAIDs for today’s practice. Mostoften, NSAIDs are used as part of a standard regimen incataract and refractive procedures. Recently, a roundtablediscussion among leading cataract and refractive surgeonswas held to gain their insight and recommendationsregarding the role of NSAIDs in ophthalmology.
*nepafenac is the prodrug of amfenac and converts to amfenac in the eye
4into the anterior chamber and the time frame of penetration of thevarious NSAIDs. One study looked at the in vivo pharmacokinetics andin vitro pharmacodynamics of nepafenac, amfenac, ketorolac, andbromfenac. In this study, nepafenac had the shortest time to peakconcentration as well as the greatest peak aqueous humorconcentration of the NSAIDs studied.5 Another study demonstrated asignificantly higher mean aqueous concentration of ketorolac, 0.4%,compared with nepafenac, 0.1%.7 A pharmacokinetic study, in whichsamples were collected over 4 hours after 1 dose of bromfenac, 0.1%,suggested that the aqueous humor concentrations stayed at effectivelevels for more than 12 hours,8 while another study in New ZealandWhite rabbits found that measurable amounts of bromfenac werefound in all tissues of the eye after 24 hours—including the posteriorsegment.9 The data in these studies demonstrate that all ocular NSAIDshave significant penetration into the anterior chamber. Because thevarious NSAIDs have different abilities to bind and block COX enzymes,the concentration achieved is a less useful measurement of clinicalefficacy than the level of enzymatic inhibition (bromfenac had thehighest level).10
Topical administration of NSAIDs provides adequate concentrationsin the aqueous at levels that can suppress prostaglandin productionin the iris/ciliary body; this same ability in the retina/choroid,however, is not as clear for all NSAIDs.1 Further research is needed toestablish the efficacy of NSAIDs in the posterior segment of the eye.
Two new formulations of existing NSAIDs have been approved bythe FDA recently: ketorolac in a 0.45% formulation, dosed twice aday, and bromfenac, 0.09%, in a once-a-day formulation. Clinicalstudies evaluating these newest versions of NSAIDs in cataractsurgery demonstrate their effectiveness. A poster presentation at the2010 American Academy of Ophthalmology (AAO) meetingshowed that the once-a-day dosing of bromfenac was effective atreducing inflammation and pain after cataract surgery.11 Additionaldata showed that ketorolac, 0.45%, was more effective at clearinganterior chamber inflammation and ocular pain than was vehicle.12
Uses of NSAIDsBesides their use in prevention of inflammation after cataract surgery,the management of CME, and for inflammation and pain control inrefractive surgery, NSAIDs have been investigated for use in theprevention of inflammation after various other types of surgeries andin other ocular conditions.
DR DEVGAN:What has been your historical use of topical NSAIDs inophthalmology?
DR GAYTON: I actually was an early adopter of NSAIDs; I began usingNSAIDs in cataract surgery primarily for the prevention of CME. Thatuse is off-label and the indication is for control of pain and forinflammation. But, we had an excellent experience using diclofenacunder the branded form of Voltaren. Then, along came genericdiclofenac, which was found to cause significant corneal melting.13,14
Both Dr Gills and I studied our practices and found that we had asignificant increase in corneal melting with generic diclofenac, butwhen we discontinued using NSAIDs because of those problems, weboth noticed a spike in CME. This increase in CME convinced me ofthe importance of NSAIDs in cataract surgery. Manyophthalmologists actually abandoned the use of nonsteroidals. It hastaken some time to get eye surgeons back on board using theseuseful adjuncts and improving patient outcomes.
DR DEVGAN: Prevention of intraoperative miosis was a very earlyindication as well for flurbiprofen (Ocufen).15 Since then, studieshave shown that diclofenac, 0.1%, and ketorolac, both 0.4% and0.5%, as well as bromfenac, all demonstrate this property.16,17,18
DR GILLS: We were part of an unpublished study that usednonsteroidals for that purpose. In approximately 100,000 cases, we
injected the NSAID into the anterior chamber to decreaseinflammation and to dilate the pupil early during surgery.
DR DEVGAN: I think that is one of the original indications andcertainly we still have that benefit, but that is not our primary reasonfor using them today.
DR GAYTON: It is not a primary reason, but it has become a moreimportant reason because of the problems with intraoperative floppyiris syndrome.19 There are more patients who have floppy iris, andanything that gives you a larger preoperative and intraoperativepupil is advantageous. So mydriatics, nonsteroidals, and viscoelasticagents can all be helpful here. Things that are going to decreasepupillary constriction during cataract surgery have become evenmore important.
DR DEVGAN: Allergic conjunctivitis was another use for flurbiprofen.Other NSAIDs have been found to be useful for the treatment ofthe allergic symptoms, although this is an off-label use. A meta-analysis found that the NSAIDS ketorolac and diclofenac areeffective in managing the itching of allergic conjunctivitis2; 1 studydemonstrated similar findings for bromfenac.20 NSAIDs have alsobeen used after trabeculectomy surgery for glaucoma. Using eithertopical ketorolac or fluorometholone for 1 month before surgeryproduced improved trabeculectomy outcomes and less need forpostoperative needling.21 This shows that we have a broad variety ofocular conditions in which inflammation is involved and thus whereNSAIDs may be clinically useful.
DR DAVIS: I use an NSAID for episcleritis22 and for corneal abrasionsor recurrent erosions for pain control. I also use NSAIDs to treat dryeyes (off-label). Primarily, I was using it for the discomfort of dryeye, but there may be evidence that it actually has some therapeuticbenefit with dry eye associated with inflammation.23-25 One studyshowed the benefit of using ketorolac during the induction phase ofcyclosporine in patients with dry eye.26 The use of the NSAIDimproved the signs and symptoms of dry eye during the start oftherapy and might have improved compliance with the cyclosporinetreatment during this time.
DR DEVGAN: Another study by Schechter, which was presented atthe 2010 American Society of Cataract and Refractive Surgerymeeting, compared the use of ketorolac and bromfenac during theinduction phase with cyclosporine for patients with dry eye.27 Thechanges in Schirmer scores, ocular surface staining, and tear break-up time improved with both NSAIDs, but these findings weresignificantly better with bromfenac.
DR GAYTON: I think there is another benefit with dry eye. One ofthe biggest complaints that I hear from patients with dry eye is justreflex tearing. If you give them some corneal analgesia, reflex tearingdecreases. I use NSAIDs in my conjunctivitis patients almostexclusively and frequently cover them with a topical antibiotic ofsome type as well. It is extremely rare that I end up having to use asteroid drop for those patients.
DR DEVGAN: Before using NSAIDs in dry eye patients,ophthalmologists need to screen patients closely. Patients withunderlying conditions like autoimmune disorders are at higher risk ofadverse events.28
I would like to point out that NSAIDs are also being explored in retinaldiseases. Some early data suggest that therapeutic inhibition of COX-2 in the retina may be possible.9,29,30 An animal study demonstratednepafenac, 0.1%, inhibited diabetic retinopathy,31 and in ananecdotal report, Hariprasad and colleagues used nepafenac, 0.1%,in patients with CME and diabetic retinopathy, finding someimprovement in retinal thickness in the patients with diabetic macularedema (DME).4 An ongoing clinical trial is evaluating the use ofbromfenac with ranibizumab (Lucentis®) in the treatment of AMD.3
It will be interesting to see what the results of these studies are.
5Practical Uses of NSAIDs inCataract SurgeryCataract surgeons have long tried to find ways to reduceinflammation after cataract surgery. Each of the approved ocularNSAIDs is effective for reducing postoperative inflammation.15,32-35
NSAIDs have also been used as an off-label indication to preventand treat CME after cataract surgery.36-39 Our panel discusses NSAIDuse in cataract surgery and the special circumstances or patientfactors that might influence choice of NSAID as well as duration ofNSAID use during cataract procedures.
How Aggressive Should NSAID Use Be?DR DEVGAN: I think we can agree that, in general, ophthalmologistsroutinely give patients steroids and antibiotics after surgery. Shouldwe be giving NSAIDs to all patients after cataract surgery?
DR DAVIS: For those of us who do use antibiotics, there have not beenany good studies showing that topical antibiotics preventendophthalmitis.40 However, the incidence of endophthalmitis is farlower than the incidence of CME, which in severe cases can have aprofound effect on best corrected visual acuity (BCVA). A recentanalysis of Medicare data showed that the incidence ofendophthalmitis after cataract surgery was 2.15 per each 1000surgeries for the 8-year study period.41 By contrast, the incidence ofCME can range up to 19% when measured with fluoresceinangiography42 and up to 41%when measured with optical coherencetomography (OCT).43 So if surgeons are going to rationalize that theyought to use an antibiotic to prevent a far less common complication,then one would rationalize that medications to prevent something thatis 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 noendophthalmitis 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 withdexamethasone in the anterior chamber. I have followed thisprotocol for nearly 30 years. Once I started doing lens implants, Ihad several cases of sterile endophthalmitis, so we startedadministering a steroid along with the antibiotics; since then I havenot seen sterile endophthalmitis cases. Therefore, it is my opinionthat you do not need antibiotics outside the eye; you need theminside the eye where the infection might occur. I think we do moreharm using topical drops that may produce resistant organisms. Thealternative is that we use intraocular antibiotics such as ceftazidimeor vancomycin that will control infection and limit the chance ofproducing a resistant organism. Resistance rarely occurs if anantibiotic is used inside the eye.
DR DEVGAN: Several studies have demonstrated that pretreatingwith NSAIDs can be effective in preventing or reducingpseudophakic CME after cataract surgery.37-39,44-46 The length oftreatment with the various NSAIDs ranges from 1 day before surgeryto 21 days after the procedure for nepafenac46 to 2 days beforesurgery to 8 weeks postoperatively for ketorolac.38 For bromfenac,the NSAID was started 3 days before cataract surgery and continueduntil the supply was finished.37 Which patients do you pretreat?
DR GAYTON: I pretreat every cataract patient with NSAIDs. When Iconsider a patient to be high risk for the development of CME, Ibegin the NSAID earlier and continue it longer. Even though patientsreceiving a multifocal lens are not at a higher risk for CME, I placethem in the high-risk group. This is because a small amount of CMEcan significantly affect the quality and quantity of vision. I considerthe following patients to be high-risk: those with diabetes, uveitispatients, patients with epiretinal membranes, patients who have hadvitreoretinal surgery, patients who had CME in their contralateraleye, and patients with retinitis pigmentosa.
DR GILLS:What is your experience with the use of nonsteroidals forlong periods of time in patients with DME and other conditions thatmay cause chronic inflammation?
DR DEVGAN: Here in Los Angeles, we have a large diabeticpopulation in certain areas. Some of these patients do not havestrong maculas and they will end up on an NSAID topically for amonth after the cataract surgery. On the follow-up visit, the retinalsurgeon often has a hard time weaning the patient. Once weanedoff the NSAIDs, they may get a recurrence of their DME. Thesepatients are sometimes on a drop of NSAID, 1 drop a day, or 1 dropevery other day, for many months or even a year.
DR GAYTON: Likewise, I have some patients on bromfenac who havebeen on 1 drop a day for 2 years. These are patients who have eitherchronic inflammation or recurrent macular edema. I am sure all of thenonsteroidals would work in the same fashion for these uses, exceptthat once-a-day dosing in a chronic condition is advantageous.47
DR DAVIS: Do you consider patients with either non-neovascular orneovascular macular degeneration high-risk patients for cataractsurgery?
DR GILLS: We routinely pretreat patients with nonsteroidals for 2 to4 days prior to surgery. If we do not have a chance to pretreat, weload the eye with multiple series of nonsteroidal drops on the day ofsurgery. Certainly, patients with any retinal elevation evident on theOCT are at risk. I pretreat those patients with 0.10 of intravitrealbevacizumab (Avastin®) and 0.10 cc of triamcinolone 1 week priorto surgery. I have pretreated thousands of patients with diabetes andthen tracked and measured the retina and found that the retina thinsfor several weeks after the injection. These data are in line with theKorean 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 timeof cataract surgery in patients with diabetic retinopathy andapproximately 1.5 cc to others who have borderline thickness.
Pain After Cataract SurgeryDR DEVGAN: Dr Davis, what about the pain after cataract surgery?I know you insert a lot of presbyopic lenses, which may requirelimbal relaxing incisions at the time of surgery. Sometimes patientsfeel these incisions. One of the indications of the various NSAIDs isthe reduction of pain after surgery. How important is it to use anNSAID for postop pain? And how many days do you treat prior toand after surgery for pain or discomfort?
DR DAVIS: I think it is very important to realize that general cataractsurgery is not terribly painful, but there is that scratchiness anddiscomfort that patients will mention in the early postoperativeperiod. This is probably incisional pain or temporary dry eye pain, orpossibly toxicity from the medications. When I used ketorolac aftercataract surgery, patients complained about burning and foreignbody 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 everycommercially available NSAID in my own practice. The recent data onbromfenac show that the once-daily formulation is effective inmanaging pain in cataract patients on postop day 1.11 Nepafenac,diclofenac, and ketorolac are also effective in managing pain in thesepatients.34,49,50 Maxwell and colleagues found that nepafenac, 0.1%,dosed either QD, BID, or TID was effective in improving ocular painafter cataract surgery; the BID- or TID-dosing pain resolution, however,began on postop day 1, whereas patients onQD dosing were pain-freestarting postop day 3.51 I have chosen bromfenac for both clinicalefficacy as well as compliance due to the easy dosing schedule.
DR GAYTON: Thankfully, modern cataract surgery patients usuallydo not have a lot of pain. The pain is generally controlled by topical
6
References Acular (ketorolac) Voltaren (diclofenac) Nevanac (nepafenac) Xibrom (bromfenac) Diclofenac (generic)
Lin et al. (2000)74 2 cases 3 cases
Congdon et al. (2001)79 22 cases 32 cases 63 cases
Flach (2001)14 4 cases 7 cases
Asai et al. (2006)71 3 cases
Mian et al. (2006)75 1 case
Bekendam et al. (2007)72 1 case
Isawi et al. (2007)76 1 case
Wolf et al. (2007)77 1 case 1 case
Di Pascuale et al. (2008)78 1 case
Table 2. Examples of Published Cases of Corneal Melts With NSAIDs
NSAIDs. I also use NSAIDs to manage pain in patients withaccidental or surgically induced epithelial defects. NSAIDs have madesurface laser vision correction a much more comfortable procedure.
NSAIDs and Postoperative Visual AcuityDR DEVGAN:What are your thoughts about the effect of NSAIDs onvisual acuity postop? Do you think there is a benefit?
DR GILLS: As a purely clinical gauge, I think patients who are givennonsteroidals are happier with their outcomes than those who arenot, particularly those who choose presbyopic intraocular lenses(IOLs).52 The lenses are very good, but if the patients have anyinflammation and if the lenses are not centered, then they are nothappy. The fact that we are pretreating them prior to surgery isalmost as important as the posttreatment.
DR DAVIS: I definitely believe NSAIDs improve visual acuitypostoperatively. I believe the ocular surface is enhanced with theiruse, anterior chamber inflammation is minimized, and the incidenceof CME is reduced. All these things lead to better acuity, both inquantity (Snellen acuity) and quality (contrast acuity, sharpness, etc).
DR GAYTON: I agree wholeheartedly with Dr Davis. The use ofNSAIDs improves the likelihood of our patients achieving theirmaximum potential acuity as quickly as possible.
DR DEVGAN: Most recently, Eric Donnenfeld, MD, did a study withthe new formulation of ketorolac, 0.45%, that indeed shows NSAIDscan help improve visual acuity postop.53 In the study, 60.5% ofpatients 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 indelivering the best results to my patients.
Combination of NSAIDs and SteroidsDR DEVGAN: Is there a benefit to using steroids and NSAIDsconcurrently?
DR DAVIS: There have been studies showing that the combinationof a nonsteroidal and a steroid works better than either alone fortreating CME.54 As for prevention, Raizman and colleagues showedthat patients receiving only steroids had more postop CME thanpatients receiving steroid and diclofenac.55 Other studies have shownthe efficacy of nepafenac and ketorolac, 0.4%, in combination withsteroids in the prevention of CME.56,57 There is definitely evidencethat supports using the combination both in the prevention and inthe treatment of CME.
DR GILLS: I concur that it is important to use concomitant steroidsand nonsteroidals prior to surgery, at the time of surgery, andpostoperatively. It certainly is beneficial.
DR GAYTON: If you look at the inflammatory pathways and applysome basic biochemistry, it is apparent that the drugs—the steroidand the nonsteroidal—are synergistic in controlling inflammation.
The steroid decreases the amount of available arachidonic acid byblocking the phospholipase enzyme.28 It is impossible for the steroidto completely block the formation of arachidonic acid, whichbecomes the substrate for the COX enzymes to form variousinflammatory by-products. The NSAID comes into play by inhibitingthis conversion by the COX enzymes. The steroid and the NSAIDwork together to give rapid and excellent control of inflammation.
Practical Uses of NSAIDs inRefractive Surgery
NSAIDs are also used in managing the pain following refractivesurgery; only ketorolac, 0.4%,58 and diclofenac, 0.1%,59 areapproved for treatment of pain after refractive surgery. Bromfenacand nepafenac have also been studied for this indication. Sher andcolleagues found bromfenac was as effective as ketorolac in relievingdiscomfort after photorefractive keratectomy (PRK)60; and Caldwelland colleagues showed that nepafenac also reduced pain afterPRK.61 Our panel discusses use of NSAIDs in refractive procedures.
DRDEVGAN:How are you using NSAIDs in your refractive procedures?
DR DAVIS: I limit use of NSAIDs to the first 3 days after PRK and thenstop. There are some patients who have absolutely no discomfortand even though we give them a prescription for pain pills, theydon’t use any. I do not use it in LASIK (laser assisted in situkeratomileusis) although 1 study has shown that treatment beforeand during LASIK with ketorolac, 0.5%, reduces postoperative painin that procedure.62 The discomfort in LASIK is so limited, usually tothe first 2 hours, that I do not think it is necessary.
DR GAYTON: I exclusively do surface laser treatment, so I usenonsteroidals quite a bit. I actually start a nonsteroidal the day beforesurgery and then continue it for 3 days after the procedure. Wepresented a paper63 in which we compared all 3 of the mainnonsteroidals: ketorolac, 0.4%, nepafenac, and bromfenac. Wefound that the nepafenac group had a statistically significantlyslower rate of epithelialization when compared with the ketorolacand bromfenac groups; the pain control was in favor of bromfenac.
NSAID use has actually made PRK a much more acceptableprocedure among patients now that you can better control pain.
DR DEVGAN: A similar study from Trattler and colleagues on post-PRKepithelial healing found similar results.64 This study was halted becauseof safety concerns. Another study, however, which looked at patientsreceiving PRK, did not show the same results with nepafenac,65 so thisfinding of epithelial problems has not been confirmed.
Improving NSAID AdherenceDR DEVGAN: One of the major factors affecting outcomes is thepatient's adherence to postsurgical therapy. What can you do tooptimize the outcome of the patients on NSAIDs? When looking atpatient adherence, prescriptions that are dosed fewer times per dayshow a higher rate of adherence.
7DR DAVIS: I think, obviously, the ideal postoperative state is patientsnot taking anything. The closer you can get to that in terms ofdecreasing frequency and duration of medication, the higher theadherence you are going to have. I use bromfenac exclusively nowbecause of the once-a-day dosing.
DR DEVGAN: Many of us are giving patients topical anti-inflammatories for many weeks—6, or even more—after 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 olderpatients. Sometimes patients forget to tell us that they have othermedical problems and that they are taking other medications atvarious times throughout the day. This is an added burden for them.Some of them have limited mobility issues, such as arthritis. We haveall seen the videos of patients attempting to hit their eye with aneyedrop, and many aren’t very successful. Multiply that with amedication given 3 or 4 times a day. You just wonder how muchthey are actually getting—if they even remember to do it. I thinkmidday doses of any medication are very inconvenient and are themost likely to be missed. If patients are out of the house and notcarrying medications with them, it is highly likely that those doses aregoing to be forgotten.
DR GAYTON: Often our patients have caregivers who are either avisiting 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 certainlyhas a huge effect on caregivers as well as on the individuals. If youhave to use something 1 to 2 times a day, your likelihood of using itpushes around 90%. If you have to use something 4 times a day,your likelihood of using it is maybe under 60%, simply because ofthe number of times.66 But when you figure a caregiver into thatequation, I think it is very important to try to prescribe medicationsthat patients can use less often.67
DR GILLS: To address compliance and adherence to medicationroutines, I use 1 drop of a nonsteroidal medication, 1 drop of asteroid, and 1.0 cc retrobulbar triamcinolone.68 If the patients forgetto use any of the drops, they still do fine because the triamcinolonewill carry them. Maybe a third or more of our patients do not takemedicines as directed.
DR DEVGAN: Of course, the use of retrobulbar triamcinolone is nottypical or standard practice. For the majority of surgeons, deliveringmedications topically is the preferred route and it’s also the leastinvasive, and it can be stopped in cases of issues such as steroid-induced glaucoma. For my patients, I have found the most successwith using a simplified topical regimen consisting of a once-dailyNSAID for a few weeks, a once-daily steroid for a couple of weeks,and a twice-daily antibiotic for 1 week.
Safety of NSAIDsWith the increased length of treatment after cataract surgery—especially in patients who receive premium IOLs, or those who are athigh risk for CME—there is more concern over toxicities of NSAIDsthan would occur with shorter durations of therapy. Temporarystinging and burning is common after instillation of NSAIDeyedrops.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 genericform of diclofenac caused the recall of the generic agent.14 It isunclear how much inappropriate use or inadequate follow-upcontributed 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 anyNSAID? There are reported cases for every NSAID now (Table 2,page 6).14,71,72,74-79
Individual RegimensEach of the panelists listed their individual regimens forcataract surgery. The agents mentioned here are thepreferences of each surgeon. Some of these medicationsare being used for off-label indications.
Uday Devgan, MD:I like to keep it simple:
1. Preoperatively: bromfenac once-daily formulation andfluoroquinolone antibiotic 3 days before surgery
2. Postoperatively: fluoroquinolone for a week, steroidfor 3 weeks, and bromfenac once-daily formulationfor 6 weeks
For high-risk patients: Postop OCT with referral toretinal surgeon if persistent thickening on OCT
James P. Gills, MD:1. Pretreat with bromfenac twice a day for 3 days prior
to surgery2. At the end of surgery, I give vancomycin, ceftazidime,
and dexamethasone in the anterior chamber3. Retrobulbar triamcinolone acetonide (Kenalog®) 1.0 cc4. Postoperatively:1 drop of bromfenac once daily and
1 drop of prednisolone acetate (Pred Forte®) for 6 to7 weeks
Elizabeth A. Davis, MD:1. Preoperatively: azithromycin 1 week prior to surgery;
bromfenac once daily 1 day before surgery2. 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 coveragedictates another agent)
a. 1 week before for a higher-risk caseb. 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 usegatifloxacin and moxifloxacin interchangeably
• Bromfenac once daily for at least 6 weeks. I will golonger than 6 weeks if I feel a person is at higher riskor 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 weeksb. If using difluprednate (Durezol™), twice a day
for 2 weeks and then once a day for 2 weeks
8DR GILLS: I believe the statistics today are much better comparedwith what we have seen in the past. The use of NSAIDs in low tomoderate dosages should decrease the occurrence of corneal melts.I believe it is important to shy away from patients who have severetear deficiency syndromes and do not have good lid closure. I haveseen several corneal melts that came from the use of genericdiclofenac; this occurred in patients with dry eyes (15+ years ago),and the vehicle that was used to carry the diclofenac appeared to beone of the problems. I have not seen the same problem with meltswhen using nonsteroidals other than generic diclofenac.
DR DEVGAN: All the more reason, I think, to use an NSAID at a lowerconcentration and lower dose, if possible. With any NSAID, thesurgeon should take extra caution with patients who are at higherrisk, such as those with corneal epithelial defects, poorly controlleddiabetes, severe dry eye syndrome, or rheumatoid arthritis. Luckily,the benefits of NSAIDs far outweigh the potential risks in the vastmajority of our patients.
As for long-term use, a recent presentation at AAO 2010 found thatpatients using the NSAIDs ketorolac, nepafenac, or bromfenac coulduse these agents safely for at least 3 months. The study includedsome patients who were treated with NSAIDs for up to 120 months.The patients who had problems with corneal melts may have hadother underlying health issues, like diabetes or autoimmune diseases,that put them more at risk.80 The incidence of corneal melts was 1in 500,000 in this report.
Case Vignettes: Roles of NSAIDs AfterSurgical Procedures*
CASE VIGNETTE 1: PATIENTS WHO RECEIVE SPECIALTYLENSES AFTER CATARACT EXTRACTION
DR DEVGAN: What is the importance of using NSAIDs for thesepatients postsurgery?
DR DAVIS: You do not want to set up the expectations of gooduncorrected visual acuity only to have it derail because you failed toprescribe a nonsteroidal. I think using a nonsteroidal would help innumerous ways—not just in comfort, not just in reduced anteriorchamber 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 orreducing it in patients who get an accommodating lens? I think thata longer regimen of anti-inflammatories may help to preventexcessive capsular bag fibrosis, and that can help prevent lensshifting and malposition.
DR GILLS: It is hard to know whether the steroids decrease fibrosisbecause it is difficult to carry out a study. But there have been manycases of capsular bag fibrosis, which is why some people stoppedusing that lens. It is a little better now since the availability ofbiaspheric lenses. I believe that patients with the biaspheric lenses arenot at as high risk for CME as patients who receive multifocal lenses.
CASE VIGNETTE 2: PATIENTS WITH DENSE ORWHITE CATARACTS
DR DEVGAN: What about a dense cataract? Do you expect morepostop inflammation? Do you change your medicine regimen?
DR GILLS: Not much, because a dense cataract is not much differentfrom a routine case. If I do expect more inflammation, I just increasemy dose of steroids and nonsteroidals to BID and increase the doseof retrobulbar triamcinolone to 1.5 cc.
DR DEVGAN:What about a white cataract where you put trypan bluein? I often suspect that even a little trypan blue can cause moreinflammation. For these patients, particularly when the cataract isdense and more phaco energy is used, I have come to expect morepostop inflammation and so I keep these patients on the steroid andNSAID for a longer period.
DR DAVIS: It depends on whether it is a liquefied cataract, whethera lot of ultrasound energy is going to be used, and on what was thecause of the cataract. Why is it a white cataract? Is it from retinalsurgery, in which case the patient is at increased risk of CME? Or isit from an epiretinal membrane? Is it a traumatic cataract, in whichcase it is going to be a more complex surgery? There may be otherthings going on behind the eye. I think it is best to be prepared andto treat a white cataract as if it has potential to be at greater risk forpostoperative inflammation. This is definitely a case in which youneed an NSAID postop.
DR GAYTON: One of the nice things that I have noticed about theimprovement in technology and the improvement in preoperativeand postoperative medications is that even with these relatively densecataracts, we are having significantly less postoperative cornealedema. I put these larger cataracts, especially patients with white,black, or red cataracts, into a higher-risk category and treat them withNSAIDs a week ahead of time.
CASE VIGNETTE 3: RETINAL PATHOLOGY AT THE TIME OFCATARACT SURGERY
DR DEVGAN: Case Vignette 3 focuses on patients with posteriorsegment disease like diabetic retinopathy or patients with dry AMD.What do you do differently in terms of your NSAIDs, steroids, orpostop management?
DR GILLS: That depends on the OCT results and if the OCT is relativelyflat. I treat diabetic patients about a week ahead with a nonsteroidaldrop, and follow with intravitreal injections when necessary. If theOCT indicates significant retinal edema—more than 300 microns—I
Figure 1b. Accommodating LensFigure 1a.Multifocal Lens
Figure 2b.White CataractFigure 2a. Dense Cataract
Figure 3b. AMD (dry)Figure 3a. Diabetic Retinopathy
*All ocular photos are provided courtesy of Uday Devgan, MD.
9will give an intravitreal triamcinolone and bevacizumab injection. Ithen re-measure the OCT and make sure the retina is flat. The effectfrom the treatment usually peaks at about 3 weeks, and then theedema typically recurs. These patients need to see a retinal surgeon forfurther photocoagulation because the injections are just temporarymeasures. So you have to treat the diabetic retinopathy temporarilywhile you do the cataract extraction, and then direct the patient backto a retinal specialist to do the laser therapy.
DR DEVGAN: My preferred approach is to get the clearance of aretinal colleague before the cataract surgery. At this preoperativevisit, the retinal specialist can also inject any intravitreal medicationsand start the patient on topical NSAIDs.
CASE VIGNETTE 4: CATARACT SURGERY IN EYES WITHIRIS PATHOLOGY
DR DEVGAN: Case Vignette 4 is a cataract surgery in the uveitic eye.Do you expect more postop inflammation? How do you changeyour medication regimen?
DR GAYTON: The one thing that I do differently in my chronicinflammation patients is that at the time of cataract surgery, I willgive them intravitreal triamcinolone in addition to using frequenttopical steroids and the nonsteroidal eyedrops.81
DR DEVGAN: There may be more inflammation in eyes in which theiris is manipulated more than in typical surgeries, as after lysingposterior synechiae. In addition, uveitic eyes have a higher incidenceof postoperative CME compared with normal eyes. This is the typeof patient that I will sometimes keep on bromfenac for months aftercataract surgery.
DR DAVIS: This is a case in which you certainly expect to see moreinflammation. Manipulation of uveal tissues not only increases risk ofanterior chamber inflammation, but posterior inflammation (such asCME) as well. So these are the patients you want to load up onNSAIDs and frequent steroids.
CASE VIGNETTE 5: GLAUCOMATOUS EYES/PIGMENT DISPERSION
DR DEVGAN: Is this an eye in which you would be more inclined tostop steroids and perhaps prescribe stronger or more NSAIDs forcontrol of inflammation?
DR GILLS: Patients with glaucomatous disc optic nerve disease arevery challenging. I follow them with corneal topography during the
postoperative period and keep them on nonsteroidals and steroidsfor the duration of their case. Patients with glaucoma have to bemonitored more closely to make sure their pressure does not get outof control. It is hard to measure accurately intraocular pressure (IOP)in patients who have had previous RKs; thus, it is important that welook at the disc carefully and monitor the pressure as best we can. Ithink it is important to be very careful in what you do with them. Itis very difficult to evaluate and treat these patients.
RKs will usually create a hyperopic shift for 2 to 4 weeks after surgerybecause of the edema in the radial cuts. Therefore, I typically add0.5 D to 1 D more power to the lens than the formula calls for since80% of eyes operated on with RKs end up hyperopic. I inform thepatient about this and during the postop period prescribe sodiumchloride and steroids 6 times a day until I can titer the refraction andget it to where it needs to be.
DR DAVIS: Depending on the medications, such as prostaglandinanalogs, those glaucoma patients are on preoperatively, they maybe at greater risk of postoperative inflammation and CME. Idefinitely think these patients need nonsteroidals, and in certaincases, 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 worryabout patients with split fixation or patients who have a very smallvisual field left. One of the things that I do is a significant amount ofendolaser cycloablation/endoscopic cyclophotocoagulation (ECP). Ihave found the combination of steroids and nonsteroidals to be veryhelpful in controlling inflammation following cycloablation. You reallyhave to watch these patients closely for pressure spikes. We usuallysee them a few hours after surgery and may even check them againlater that same day—to be absolutely sure that they are not spiking—and then see them the next day. Of course, if the patient’s pressure isspiking, we do an anterior chamber decompression. The nonsteroidalshave, in my opinion, made the use of ECP much better because ofthe ability to better control the inflammation. One of the problemswith cyclodestructive or cycloablative procedures is postoperativeinflammation. Having an NSAID that can be used safely for a longperiod of time helps to better control this inflammation.
DR GILLS: We follow every patient’s postop pressures in the earlypostop period after cataract surgery. An IOP check is done at 20minutes postop using the noncontact tonometer (NCT). If unable toobtain 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 secondtime at 1 hour postop.
CONCLUSIONSThe role of NSAIDs in the management of eye disorders and followingophthalmic surgical procedures is growing. The increased rationalefor the use of NSAIDs is further bolstered by the safety of the currentNSAID formulations and the increased usage is also likely attributableto the availability of simplified-dosing regimens. Patient adherenceis key to improving patient outcomes; simplification of theseregimens can increase adherence.
Lowering the incidence of CME after cataract surgery is a veryimportant consideration in this procedure because the occurrence ofCME can be visually devastating and can lead to complex andlonger-term therapy to improve the subsequent visual acuity. Theincreased use of premium IOLs may also require the incorporationof NSAIDs into the postsurgical regimen because inflammation inthese patients can lead to worse outcomes.
NSAIDs may also make surface ablation refractive surgery morecomfortable for the patient. The addition of NSAIDs to the surgicalregimen for either cataract surgery or refractive surgery can improvethe outcomes of these procedures; the discussion is now shifting tolength of treatment and selection of patients for optimal outcomes.
Figure 4b. Iris Pigment Loss FromIOL Edge
Figure 4a. Uveitis
Figure 5b. Glaucomatous OpticNerve Dispersion Glaucoma, andCortical Cataract
Figure 5a. Radial keratotomy(RK) Incisions and KrukenbergSpindle of Pigment
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54. Heier JS, Topping TM, Baumann W, Dirks MS, Chern S. Ketorolac versus prednisoloneversus combination therapy in the treatment of acute pseudophakic cystoid macularedema. Ophthalmology. 2000;107(11):2034-2038.
55. Trattler W. Topical NSAIDs for pain and inflammation. Review of Ophthalmology.2006;13(4). http://www.revophth.com/index.asp?page=1_924.htm. AccessedDecember 2, 2010.
56. Wittpenn JR, Silverstein S, Heier J, Kenyon KR, Hunkeler JD, Earl M; Acular LS forCystoid Macular Edema (ACME) Study Group. A randomized, masked comparison oftopical 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 significantpseudophakic macular edema after uneventful phacoemulsification in patients treatedwith 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 bromfenac0.09% vs ketorolac 0.4% for the control of pain, photophobia, and discomfortfollowing PRK. J Refract Surg. 2009;25(2):214-220.
61. Caldwell M, Reilly C. Effects of topical nepafenac on corneal epithelial healing timeand 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.
11
1. For which of the following indications have NSAIDs not beenFDA approved ?
a. Postoperative painb. Management of dry eye syndromec. Treatment of allergic conjunctivitisd. Ocular inflammation after surgery
2. NSAIDs are often used after refractive surgery. Whichophthalmic 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 andpenetration. Which ophthalmic NSAID is approved for once-a-day dosing?
a. Ketorolac, 0.4%b. Nepafenac, 0.1%c. Bromfenac, 0.09%d. Ketorolac, 0.5%
4. Hariprasad and colleagues found that ____________mayimprove 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 afterophthalmic surgery. An 85-year-old man is scheduled forcataract extraction in his left eye. What factor is not asimportant when planning his medication regimen after surgery?
a. Number of eye medications already takingb. Need for a caregiverc. Number of ophthalmic follow-up visits neededd. History of arthritis
6. A 45-year-old woman with rheumatoid arthritis develops aposterior capsular cataract in her left eye after several years ofcorticosteroid treatments to manage her condition. In planningfor her cataract extraction to lessen the risk of adverseoutcomes, the ophthalmologist should:
a. Evaluate the patient for dry eye and epithelial defectsb. Completely avoid NSAID use under any circumstancesc. Plan to use a typical NSAID regimen in this patient
7. Corneal melts have been seen with several different types ofNSAIDs. Patients who may be at higher risk for thedevelopment of corneal melts do not include patients with:
a. Autoimmune diseasesb. Severe dry eyec. Diabetesd. A history of contact lens wear
Focus on Cataract and Refractive Procedures
A Practical Look AT THE Role of NSAIDs IN OPHTHALMOLOGYCME POST TEST
63. Gayton J. Bromfenac, nepafenac, and ketorolac in surface laser ablation.Paper presented at: American Society of Cataract and Refractive Surgery AnnualMeeting; April 3-8, 2009; San Francisco, CA.
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 eyesundergoing surface ablation. Cornea. 2007;26(6):665-669.
65. Jalali S, Boxer Wachler BS. Comparison study of the effect of Nevanac on epithelializationand haze in PRK. Poster presented at: American Academy of Ophthalmology AnnualMeeting; November 10-13, 2007; New Orleans, LA. Poster 183.
66. Ikeda H, Sato M, Tsukamoto H, et al. Evaluation and multivariate statistical analysis offactors influencing patient adherence to ophthalmic solutions. J Pharm Soc Jpn.2001;121(11):799-806. [Article in Japanese]
67. Lau HS, Beuning KS, Postma-Lim E, Klein-Beenink L, de Boer A, Porsius AJ. Non-compliance in elderly people: evaluation of risk factors by longitudinal data analysis.Pharm World Sci. 1996;18(2):63-68.
68. Kahook MY, Camejo L, Noecker RJ. Trabeculectomy with intraoperative retrobulbartriamcinolone acetonide. Clin Ophthalmol. 2009;3:29-31.
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 cornealmelting after instillation of a new nonsteroidal anti-inflammatory drug. Cornea. 2006;25(2):224-227.
72. Bekendam PD, Narváez J, Agarwal M. Case of corneal melting associated with the useof topical nepafenac. Cornea. 2007;26(8):1002-1003.
73. Tai MC, Chang JH, Chang CJ. Corneal melting associated with the use of topicalketorolac: successful treatment with tissue adhesive. J Med Sci. 2003;23(4):227-230.
74. Lin JC, Rapuano CJ, Laibson PR, Eagle RC Jr, Cohen EJ. Corneal melting associatedwith use of topical nonsteroidal anti-inflammatory drugs after ocular surgery. ArchOphthalmol. 2000;118:1129-1132.
75. Mian SI, Gupta A, Pineda R 2nd. Corneal ulceration and perforation with ketorolactromethamine (Acular) use after PRK. Cornea. 2006;25(2):232-234.
76. Isawi H, Dhaliwal DK. Corneal melting and perforation in Stevens Johnson syndromefollowing 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 RefractSurg. 2007;33(11):1974-1975.
78. Di Pascuale MA, Whitson JT, Mootha VV. Corneal melting after use of nepafenac in apatient 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. Cornealcomplications associated with topical ophthalmic use of nonsteroidal antiinflammatorydrugs. 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 inuveitic eyes having cataract surgery: pilot study. J Cataract Refract Surg. 2007;33(7):1278-1283.
82. Arcieri ES, Santana A, Rocha FN, Guapo GL, Costa VP. Blood-aqueous barrier changesafter the use of prostaglandin analogues in patients with pseudophakia and aphakia: a6-month randomized trial. Arch Ophthalmol. 2005;123(2):186-192.
To obtain AMA PRA Category 1 Credit™ for this activity, you must complete the CME Post Test by writing the best answer to eachquestion in the Answer Box located on the Activity Evaluation/Credit Request form on the following page.
A Practical Look AT THE Role of NSAIDs IN OPHTHALMOLOGY
ACTIVITY EVALUATION/CREDIT REQUEST
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 Boxlocated below. Mail or Fax this completed page to The New York Eye and Ear Infirmary–ICME, 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 timelyand pertinent future activities. Please provide all the requested information below. This ensures that your certificate is filled out correctly and is mailed to theproper 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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� Yes � No I and/or my family member have a financial relationship with the The New York Eye and Ear Infirmary and/or referMedicare/Medicaid patients to it.
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Outcomes MeasurementCircle 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 DisagreeAfter successfully completing this activity, I have improved my ability to:
1. Review the current and emerging major uses for NSAIDs in ocular conditions 5 4 3 2 1
2. Review recent clinical evidence on the use of NSAIDs in cataract and refractive procedures 5 4 3 2 1
3. Discuss the strategies for incorporating NSAIDs into cataract and refractive procedures 5 4 3 2 1to 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 throughparticipation 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
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Post Test Answer Box 1 2 3 4 5 6 7
Focus on Cataract and Refractive Procedures
ORIGINAL RELEASE: MARCH 1, 2011LAST REVIEW: FEBRUARY 16, 2011
EXPIRATION: MARCH 31, 2012