1

LeoSemes,OD,FAAOUABOptometry

OptoWest NewportBeach

CaliforniaOptometricAssociation2016

Thisisthequestionyoushouldbeabletoanswerattheconclusionis…HowwillthisinformationhelpmewhenIseemynextpatient?

2

78AA/FwithsuspectedAlphaganallergy

♦ Topicalhydrocortisone(1%)failed

ContactAllergy/Derma11sTreatmentwithOralSteroids

Prednisone5mgPOqidX7d–goodresults♦ Finaldiagnosis:nickelallergy

ContactAllergy/Derma11sTreatmentwithOralSteroids

� Skineffects�  Thinningandbruisingmayoccurduringapplicationwithdose-responseeffect

LipworthBJ.Systemicadverseeffectsofinhaledcorticosteroidtherapy:Asystematicreviewandmeta-analysis.ArchIntMed1999159(9):941-55.

� ElevatedBP

� PSCcataract

� ElevatedIOP(?)

OralSteroids–SideEffects60mgoralprednisone(35D)

OD

OS

Tham CCY, et al. Am J Ophthalmol 2004;137:198–201.

2

10mgoralprednisone(28D)(same9yof)

OD

OS

Tham CCY, et al. Am J Ophthalmol 2004;137:198–201.

Prostaglandins� Ubiquitous�  Initiateandmodulatecell&tissueresponses

�  Plateletaggregation�  Reninrelease�  INFLAMMATION

� Synthesizedondemand� Notstored�  Shorthalf-life

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MechanismofNSAIDAction

InhibitionofProstaglandinsynthesis*�  Arachadonicacidpathway�  Leukotrienearm(steroids)�  CycloxygenaseIandII(COX-II)/NSAIDS

*Mechanismsmayoverlap14

Avideoisworthathousandwordshttp://www.youtube.com/watch?v=8v1H2N-9Hf4

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NSAIDInhibitionofProstaglandinsynthesis*

� CycloxygenaseIandII(COX-II)�  COX-I

�  inhibitthromboxaneproduction&�  thusplateletaggregation(leadstobloodthinning)

�  SelectiveCOX-IIisoenzymes,(doNOTinterferewithplateletaggregation)�  mayadverselyaffecthemostaticbalance&�  favorthrombosisbutmaybelessdisruptivetomucosalmembranes

*Mechanismsmayoverlap16

GeneralFeatures(Oral)� Metabolizedrapidly(30minto2hrs)� Generallyrapideffect[anti-inflammatory,painrelief,feverreduction]

� Peakplasmalevels:4-6hrsfollowingdosing

� Metabolizedinthekidneys

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3

OralNSAIDProper1es� Anti-inflammatory� Anti-pyretic� Analgesic

� Widelyusedforarthritispainmanagement(chronic)1.4millionregularusers(USA)

�  MechanismofactionisinhibitionofCOX-1andCOX-2enzymes

� Aspirinistheprototype

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NSAIDActions(the3As)� Acttoreduceinflammation(requireshigherdosagethanforanalgesia)

� Alsoofferanalgesia

� Mostareanti-pyretic

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Precautions/WarningsEverysilverlininghasacloud…

�  Elderly:renalclearanceisreduced;resultinginhigherplasmalevels

�  Renallyimpaired:samescenario[⇓pl.clearance]�  Hepaticallyimpaired:nosignificantdifferencefromabove2examples*(cyclooxygenaseisneededforrenalbloodflow)

*Useminimumdosage[⇑unbound%]

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Precautions/WarningsGIToxicityw/chronicTX

�  Ulceration�  Bleeding;canalsoaggravatepre-existingdisorders(diverticulosis)

�  PerforationPrevalence:1-2%(3-6mo);2-4%@1yr

maybeasymptomatic 21

ContinuumofNSAID-relatedupperGIinjury

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Precautions/Warnings� Peripheraledema(2%prevalence)

�  Caution:�  fluidretention�  hypertension�  heartfailure

LMayinterferewithß-blockers&ACEinhibitors

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Precautions/Warnings� HypersensitivityreactionsCaution:

� asthma� rashesandurticaria� photosensitivity� Stevens-Johnsonsyndrome…

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Precautions/Warnings� Stevens-Johnsonsyndrome

X 12 years

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→

Precautions/Warnings� Druginteractions

�  Aspirin(⇑unbound%)

�  Warfarin(may⇓plateletformation)

� Gingkobiloba!!!�  Antacids(nointerference,ex.,Pepcid)�  Diuretics(reducedK+,Cl-excretion)� Digoxin

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Druginteractions-ophthalmic� Brimonidine(Alphagan)

� Maybeineffectivewiththeconcomitantadministrationofindomethacin(25mg.QID)

� Notsoforlatanaprost(Xalatan)

SponselWE,etal.AmJOphthalmol.2002;133:11-18.

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Precautions/Warnings� Miscellaneous

�  Pregnancy:GenerallyCategoryB;Lodine,Motrin,Vioxx,Voltaren[C]

�  Notrecommendedduringlactation/nursing

�  NEASforpediatricuse(<6months)

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IndicationsforOralNSAIDs� MildtoModeratePain� RheumatoidArthritis� OsteoArthritis� AnkylosingSpondylitis� Tendinits� PrimaryDysmenorrhea(600mg,qid)(Ibuprofenarginate:Castelo-BrancoC,CasalsG,HayaJ.EfficacyandSafetyofIbuprofen

ArginineintheTreatmentofPrimaryDysmenorrhoea.ClinDrugInvest24(7):385-393,2004.)

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5

OralNSAIDS(O-T-C)–Ibuprofen[“Escape,”or“rescue”drugs]Motrin,Advil,Nuprin-200mg.

♦ DOSAGE(Rx):2tabs(400mg)q4-6h(managementofadultpain)

� Ophthalmicapplicationinkeratitis,uveitis,eg.

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OralNSAIDS(O-T-C)-Ibuprofen� Standarddosage:400mgq4-6h� Pediatricdosing:10mg/Kgq6-8h

(upto40mg/Kg/D;ages6mo.to12yrs.)

�  Alsoavailableassuspension(100mg/5ml)Children'sElixsureIB�  Chewabletabs50,100mg�  Capsules100mg

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OralNSAIDS(O-T-C)-KetoprofenOrudis12.5mg.

♦ DOSAGE:4caps/tabs(50mg.)q4-6h

♦ Orudis(Ketoprofen)CapsulesandExtended-releaseCapsules(approved08/13/03)

Ketoprofen:analgesic,anti-pyretic,anti-inflammatory

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Ketoprofen(12.5,25,50mg)12.5-25mgmaybefasterthanibuprofen200mgSunshineA,OlsonNZ,MarreroI,TiradoS.Onsetanddurationofanalgesiaforlow-dose

ketoprofeninthetreatmentofpostoperativedentalpainClinPharmacol.1998Dec;38(12):1155-64.

Butsimilaronsetcomparedtoibuprofenliquigel200mg

OlsonNZ,OteroAM,MarreroI,TiradoS,CooperS,DoyleG,JayawardenaS,SunshineA.Onsetofanalgesiaforliquigelibuprofen400mg,acetaminophen1000mg,ketoprofen25mg,andplacebointhetreatmentofpostoperativedentalpain.ClinPharmacol.2001Nov;41(11):1238-47.

25-50mgmaybeasuperioranalgesictoketorolac10or20mg

OlmedoMV,GalvezR,VallecilloM.Double-blindparallelcomparisonofmultipledosesofketorolac,ketoprofenandplaceboadministeredorallytopatientswithpostoperativedentalpain.Pain.2001Feb1;90(1-2):135-41.

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NSAIDSasalternativestonarcoticanalgesics

� mayoffersuperioranalgesiatonaturalandsyntheticnarcoticsinavarietyofsituations

MalanTPJr,GordonS,HubbardR,SnabesM.Thecyclooxygenase-2-specific

inhibitorparecoxibsodiumisaseffectiveas12mgofmorphineadministeredintramuscularlyfortreatingpainaftergynecologiclaparotomysurgery.AnesthAnalg.2005Feb;100(2):454-60.

LovellSJ,TairaT,RodriguezE,WackettA,GullaJ,SingerAJ.Comparisonof

valdecoxibandanoxycodone-acetaminophencombinationforacutemusculoskeletalpainintheemergencydepartment:arandomizedcontrolledtrial.AcadEmergMed.2004Dec;11(12):1278-82.

BrillS,PlazaM.Non-narcoticadjuvantsmayimprovethedurationandqualityof

analgesiaafterkneearthroscopy:abriefreview.CanJAnaesth.2004Dec;51(10):975-8.

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OralNSAIDS(O-T-C)-Naproxen�  Naprosyn220mg.

♦  DOSAGE:1-2tabs(220-440mg.)q4-6h

[foranalgesiceffect;lowerdosagethanforanti-inflammatoryeffect]

�  Anaprox,Aleve220mg.♦  DOSAGE:2tabs(440mg.)initially,

then1tabq4-6h[foranalgesiceffect]

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Semes’Anti-inflammatorySiege� 600mgIbuprofenAM� 440mgNaprosynmid-AM� 600mgIbuprofenPM� 440mgNaprosynqhs

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RelativeriskofUGIbleedingw/NSAIDadministration

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Oral“NSAID”(O-T-C)–Acetaminophen� Acetaminophen325mg.(Tylenol)

�  requires500–1000mgtoreachanalgesicdosage;andhigherforanti-inflammatoryeffect

� MayhavemorerapidonsetthanibuprofenSunshineA,OlsonNZ,MarreroI,TiradoS.Onsetanddurationofanalgesiaforlow-dose

ketoprofeninthetreatmentofpostoperativedentalpainClinPharmacol.1998Dec;38(12):1155-64.

� Metabolizedintheliver!

DOSAGE:q4-6h39

OralNSAIDS(Byprescription)–Ketoprofen

Oruvail100,150,200mgCapsOrudis25,50,75mgCaps♦ DOSAGE:

♦ Oruvail(sustainedrelease)200mgqD♦ Orudis50-75mgqid/tid[respectively]♦ Maximum200/300mg/day

Ketoprofen:ThethreeA’s

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OralNSAIDS(Rx)–EtodolacLodine200,300mgCaps;400,500mgTabs

DOSAGE:♦  foranalgesia200-400mgq6-8h♦  (higherforOA,RA;anti-inflammatoryeffect)♦ Maximum1000-1200mg/day

LodineXL♦  400-100mg/day

•  ThethreeA’s

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OralNSAIDS(Rx)–Naproxen�  Naprelan412.5,550mg.(equivalentto375/500mg)

DOSAGE:1000mgqD,then500-1000mgqDHasbeenshownin3studiestoreducetheriskofacutemyocardialinfarction(AMI)probablybyblockingplateletaggregation;advantageoverCOX-II’s

•  ThethreeA’sSolomonDA,etal.ArchIntmed2002;162:1099-1104.WatsonDJetal.ArchIntmed2002;162:1105-1110.RahmeE,etal.ArchIntmed2002;162:1111-1115.

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NSAIDSandAMD� 2334participantsintheBMES� 5-yearFU� NSAIDandsteroidusewasmeasured@baseline

� Results:2.0%late,4.9%earlyAMDbutnoassociationwithNSAID/Steroiduse

WangJJ,etal.OphthalmicEpidemiol2003;10:37-47.43

NSAIDSandAMD,too� 551VApatientsw/AMDdiagnosis(ICD-9)

� 5500controls

PatientswithaprescriptionfilledforAnti-inflammatorymedswere81%lesslikelytohaveadisgnosisofAMD

Swanson MW, McGwin G Jr. Anti-inflammatory drug use and age-related macular degeneration. Optom Vis Sci. 2008 Oct;85(10):947-50.

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NSAIDSandAMD,IIIConclusion:InpatientswithneovascularAMDmanifestingpersistentexudationdespitemonthlyintravitrealantivascularendothelialgrowthfactoranti-VEGFtherapy,wecouldnotdetectabeneficialeffectofaddingtopicalbromfenac(0.09%)twicedailyover2months.

(n=22eyeswithpersistentsubmacularfluid)

Zweifel SA, et al. Retrospective review of the efficacy of topical bromfenac (0.09%) as an adjunctive therapy for patients with neovascular age-related macular degeneration. RETINA 29:1527–1531, 2009

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OralNSAIDS(Rx)–DiclofenacVoltaren25,50,75mgCaps.

♦ DOSAGE:♦ Voltaren50-100mginitially;50mgq8h♦ Maximum200mg/day

� ThethreeA’s

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OralNSAIDS(Rx)–Others�  Tramadol(Ultram)100mg.

DOSAGE:q4-6h�  Ketorolactromethamine(Toradol)10mg.

DOSAGE:q4-6h(highestriskofbleeding,

∴notonhospitalformularies)�  Ibuprofen400mg.

DOSAGE:1-2tabs,q4-6h

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OralNSAIDS(Rx)–Others� Ultracet(37.5mg.tramadol+325mg.,acetaminophen)

� Dosing� 2tabsq4-6hrs.

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8

Onofrey’sAlternative� 400mgIbuprofen

+� 325mgAcetaminophen� Dosing

� 2tabsq4-6hrs.

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OralPainMeds(Rx)–Miscellaneous�  Vicoprofen(ibuprofen200mg,hydrocodone7.5mg)

�  DOSAGE:1-2tabsq4-6h(for10D)Ibuprofen:The3A’sHydrocodone:centrallyactingsyntheticopioid�  VICODINcontains5mghydrocodoneand500mgacetaminophen

�  VICODIN-EScontains7.5mghydrocodoneand750mgacetaminophen

�  VICODIN-HPcontains10mghydrocodoneand660mgacetaminophen

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IndicationsforTopicalNSAIDs� Maintenanceofpupillarydilationatcataractsurgery;but...

�  ProphylaxisforpseudophakicCME

�  Topicalanti-inflammatory(pre-andpost-op[indomethacin,1984*]

SandersDR,KraffM.ArchOphthalmol1984;102:1453-56.

�  Intraoperativepain(PRP)

�  And,and,and…

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Indomethacin&CME� TopicalINDOMETHACINFIRSTREPORTEDIN1982ASPROPHYLAXISKraffM,etal.Prophylaxisofpseudophakiccystoidmacularedemawithtopical

indomethacin.Ophthalmology.1982;89:885-90.

� And,topicaladministrationproducedhigherintraocularlevelsthanoraldosingSandersDR,etal.,Aqueouspenetrationoforalandtopicalindomethacininhumans.

ArchOphthalmol.1983Oct;101(10):1614-6.

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Indomethacin&CMEAND,topicalindomethacinreducedpost-opCMEbetterthanplacebo(pre-opand9moS/P)

KraffMC,etal.Factorsaffectingpseudophakiccystoidmacularedema:fiverandomizedtrials.JAmIntraoculImplantSoc.1985Jul;11(4):380-5.

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9

ProphylaxisforPseudophakicCME

RossettiL,et.al.Ophthalmology1998;105:397-405.Solomon,LD.Efficacyoftopicalflurbiprofenandindomethacininpreventingpseudophakic

cystoidmacularedema.Flurbiprofen-CMEStudyGroupI.CataractRefractSurg.1995;21:73-81.

6 worldwide studies 1980-88; outcome criterion = VA </= 20/40 Drugs: indomethacin, suprofen, ketorolac, diclofenac, piroxicam, hydroxyethyl-rutoside, flurbiprofen

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BrJOphthalmoldoi:10.1136/bjophthalmol-2014-305803Update

Comparisonofketorolac0.4%andnepafenac0.1%forthepreventionofcystoidmacularoedemaafterphacoemulsification:prospectiveplacebo-controlledrandomisedstudy.Tzelikis1,Petal.(Brazil)

PublishedOnlineFirst10November2014ConclusionsUsedprophylacticallyafteruneventfulcataractsurgery,non-steroidalanti-inflammatorydrugswerenotefficaciousinpreventingmacularoedemacomparedwithplacebo.

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Topicalindomethacinapplication�  Inflamedptyergium/pinguecula

�  50consecutivepatientsevaluated�  Signs+symptoms=Totalscore�  Treatment:0.01%indomethacinor0.01%dexamethasonephosphate(14days)

� Results�  EquallyeffectiveforSigns,SymptomsandTotal� Dexamethasonehadmorerebound

� Contemporaryalternatives....

Frucht-PeryJ,etal.AmJOphthalmol1999;127:148. 57

Ocufen(0.03%Flurbiprofen,Allergan)

� Approvedindication[12/31/86]–inhibitpupillarydilationduringcataractsurgery� Dosing:1gtq½hforthe2hourspriortosurgery

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Ocufen(0.03%Flurbiprofen,Allergan)

� Additionalapplications�  Post-operativepseudophakicCMESolomon,LD.Efficacyoftopicalflurbiprofenandindomethacininpreventingpseudophakic

cystoidmacularedema.Flurbiprofen-CMEStudyGroupI.CataractRefractSurg.1995;21:73-81.

�  *Refractivesurgery-Maintenanceofpupillarydilationduringclearlensimplantation

� DryEye/OSD?

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OcufenforDryEye?

Symptom scores Avunduk AM, et al. Am J Ophthalmol 2003;136:593–602.

ATS + STD*

ATS ATS + NSAID

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10

OcufenforDryEye–NOT!Buttopicalsteroiddrops[FML]areeffective!

RB staining

Fl staining

TS+NSAID

TS

TS + STD

TS+NSAID

TS

TS + STD

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Topicalsteroiddropsfordryeye� DESisaninflammatorycondition

� Studieshaveshownefficacyfortopicalsteroiddrops�  1%methylprednisone(KCS,SjÖgren)�  Loteprednoletabonate(âtearclearance,KCS)/introtoRestasis?

YoshidaT,etal.NeurolRes1999;21:509-12MarshP,PflugfelderS.Ophthalmology1999;106:811-16.PaivaCS,PflugfelderSC.Rationaleforanti-inflammatorytherapyindryeyesyndrome.ArqBrasOftalmol.2008Nov-Dec;71(6Suppl):89-95.

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Leo’sdirtylittledryeyesecrets

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Voltaren(diclofenacsodium0.1%;Ciba)

�  TopicalNSAIDsolutionspecificallyforthetreatmentofpost-cataractsurgeryinflammation[7/28/88]1

�  Applicationinpostrefractive-surgery(PRK,LASIK)pain;2,3andbetterthandiclofenacforphotophobia,too3

[initialapproval-preventionofpupillaryconstrictionduringcataractsurgery]

1.GinsburgAP,et.al.JCatRefractSurg1995;21:82-92.1.RossettiL,et.al.JCatRefractSurg1996;22(S):794-796.2.BowerKS.AmFamPhys2001;64(7):1-10.2.FrangouliA,etal.JRefractSurg1998;14(2Suppl):S207-8.2.,3.AssoulineM,etal.OphthaomicSurgLasers1998;29:365.[France]

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Voltaren(diclofenacsodium0.1%;Ciba)

�  ControlofintraoperativepainduringPRP[30-135minbeforetreatmentsession]

WeinbergerD,etal.,BrJOphthalmol.2000;84(2):135-37.

�  Anti-bacterialaction[Salmonellatyphimurium]

DastidarSG,etal.,IntJAntimicrobialAgents.2000;14(3):249-51.

�  FilamentaryKeratitisinSjÖgrensyndrome[1gt.QIDX28D]

AvisarR,etal.,Cornea2000;19(2):145-47.

Additional ophthalmic applications

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Voltaren(diclofenacsodium0.1%;Ciba)�  Routinelyusedforpostincisionalrefractive-surgerypaincanbepre-medicated�  Dosingschedule(RK,PRK):

�  1drop1hrpriortotheprocedure;�  1drop@15minpost;�  q.i.d.X3da.dependingonhealing.

�  Dosageschedule(cataractsurgery):�  1dropbeginning@24hrspost-opandq.i.d.X2wks.)

Controversy:Whataboutcornealmelting???

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Controversy� Doeslatanoprost(oranyoftheprostaglandinanalogs)causepost-opuveitisand/orpseudophakicCME?

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Contemporaryworkinghypothesisforpseudophakic[“preservative”]CME

Miyake K, et al. J Cataract Refract Surg 2003; 29:1800–1810. 71

Thelatest!� Studydesign

�  163eyesof64consecutivepatientswithuveitisandelevatedIOPwerereviewed

�  ControlsweretheeyesofpatientswithuveitisbutNOTtreatedwithaprostaglandinanalog

�  Pre-treatmentIOPanduveitiswasmonitored

Chang JH, et al. Use of ocular hypotensive prostaglandin analogues in patients with uveitis: does their use increase anterior uveitis and cystoid macular oedema? Br J Ophthalmol. 2008; 92: 916-21. 72

Results� SignificantIOPreductionwasobservedinthePAgroup

� Andthefrequencyofuveitiswassimilarbetweenthegroups(p=0.87)

� Ofthe69uveitiseyeswithahistoryofCME,therewasnodifferencebetweenthosetakingaPAthanthosenottakingone.(p=0.19)

Chang JH, et al. Use of ocular hypotensive prostaglandin analogues in patients with uveitis: does their use increase anterior uveitis and cystoid macular oedema? Br J Ophthalmol. 2008; 92: 916-21.

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Xibrom(bromfenacsodiumsolution,0.1%)

�  Istapharmaceuticals� AvailableinJapansince2000)

� Statisticallysignificantsuppressionofocularinflammation(vs.placebo)followingcataractsurgery

� FDA-approvedMarch2005

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Xibrom(bromfenacsodiumsolution,0.1%)

�  Burningandstingingoninstillation1.5%(vs.40%forAcular;20-40%A-LS)

�  Nosystemicabsorptionfromtopicalinstillation

� OralequivalentisDuract(50mgdosing;1dropXibrom(60ug);potentiallytoxic[GI]

�  FewAE’sinpost-marketsurveillance(Japan)�  6milliontreatedpatients/13AE’s

�  4cornealerosions�  3cornealperforations�  0cornealmelts

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12

Xibrom(bromfenacsodiumsolution,0.1%)

� Topicalforpost-oppainresolvedin2daysvs.5daysforplacebo

DonnenfeldE.,etal.BromfenacOphthalmicSolution0.09%(Xibrom)forPostoperativeOcularPainandInflammation.Ophthalmology.2009;114;9:1653-1662.

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Bromday� qDdosing

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NevanacTM(nepafenacophthalmicsuspension0.1%,Alcon)

�  Theenhancedpermeabilityofnepafenac,combinedwithrapidbioactivationtoamfenacbytheiris/ciliarybodyandretina/choroid,makeitatargetspecificNSAIDforinhibitingprostaglandinformationintheanteriorandposteriorsegmentsoftheeye.

�  FDA-ApprovedAugust24,2005fortreatmentofpainandinflammationassociatedwithcataractsurgery

KeTL,etal.Nepafenac,auniquenonsteroidalprodrugwithpotentialutilityinthetreatmentoftrauma-inducedocularinflammation:II.InvitrobioactivationandpermeationofexternalocularbarriersInflammation.2000Aug;24(4):371-84.

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NevanacTM(nepafenacophthalmicsuspension0.1%,Alcon)–

anotherpotentialapplication

�  TopicalnepafenacinhibitsCNVandischemia-inducedretinalneovascularizationbydecreasingproductionofVEGF

�  Topicalnepafenacmayprovideaneffectivenewtreatmentforocularneovascularization

�  Theexcellentcornealpenetrationofnepafenaccertainlyplaysanimportantroleinthiseffect(mousemodel)

TakahashiK,etal.Topicalnepafenacinhibitsocularneovascularization.InvestOphthalmolVisSci.2003Jan;44(1):409-15.

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46AsianMale�  “blurryvision”11/20/2012

�  X3moOS;beganonlylastnightOD� BegannewBPmedlastweek� Hasneverhadeyeexam� CentralblurinOShasimprovedsomewhat�  +floatersX1yr�  -flashes,discharge,pain

46AsianMale� Previousocularhistoryisnegativeforrefractivecorrection,injury,glaucoma,cataract,strabismus,amblyopia,etc.

�  Familymedical/ocularhistoriesnegative� Noknownallergies� BeganlisinoprilqDX1wk.[ACEinhibitor]� BP150/100

13

46AsianMale� VA20/40-20/400(PHNI)�  -RAPD�  IOP:14/14� NoEOMrestrictions� ConfrontationFTFCOD,OS�  -1.50/-2.25-0.50X070VANI� AnteriorsegmentunremarkableOD,OS

11/20/12

Note serous sub-retinal fluid and cystic macula

Note RPE intact and serous sub-retinal fluid

46AMwithCSR,RPED,HR�  InitiatedNevanacbid(11/20/12)� RTCX1wk� CorrespondwithPCP

� @1-wkF/U(11/27/12)� BP=138/92� VA20/25,20/40!!!

�  (-1.00/-0.75–0.50X070)� ContinueNevanacbid

14

46AMwithCSR,RPED,HR�  InitiatedNevanacbid(11/20/12)

� @2-wkF/U(12/4/12)� BP=140/92� VA20/20-,20/20-!!!

�  (refractionunchanged;)� ContinueNevanacbid� RTCX1Wk

12/11/12

D/C Nevanac

12/11/12

D/C Nevanac

12/11/12

12/11/12 12/11/12

15

12/11/12 12/11/12

Ilevro(nepafenacophthalmicsuspension0.3%)� qddosingforpost-opinflamma1onandpainfollowingcataractsurgery*

*

110

ThisproducthasbeenevaluatedbytheFDAandanyotherapplica1onisconsideredtobe“off-label”

111

Acular(Acuvail)� KetorolacisthemostwidelyprescribedtopicalNSAID.

�  FDA-approvedfortheameliorationofpost-oprefractivesurgerypain.

� Off-labelindicationsinclude(withevidence)�  Acuteandchronicpost-opCME�  Seasonalallergicconjunctivitis�  Inflamedpterygia�  � 

112

Acular(Acuvail)� Recentlyavailableinnon-preservedformulation(Acuvail)–FDA-approvedforreductionofpainfollowingcataractsurgery.

� Doesnotprolongcornealabrasionhealingandreducespain.

113

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AcularPrecaution�  Asthma�  Exacerbationofsymptoms[44F]following1dose;

requiredhospitalization�  Recommendations

�  avoidwhenaspirin-orNSAID-sensitive�  avoidwithasthma+nasalpolyps

SitegnaGL,etal.Ophthalmology1996;103:890-92.

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Addi1onalpoten1alapplica1onoftopicalNSAIDs� Allergicconjunctivitis� Uveitisandotherinflammatoryoculardiseases

� Uveitis� Orbitalpseudotumor�  Episcleritisandscleritis�  Inflamedpinqueculaandpterygia�  Viralconjunctivitis� Ocularinflammationindryeyepatients

115

Addi1onalpoten1alapplica1onoftopicalNSAIDs� Retinalandchoroidaldisease

� Diabeticretinopathy� Age-relatedmaculardegeneration� Oculartumors

116

Kim SJ, Flach AJ, Jampol LM. Nonsteroidal anti-inflammatory drugs in ophthalmology. Surv Ophthalmol. 2010 Mar 4;55(2):108-33.

Restasis(cyclosporin0.05%ophthalmicemulsion� Mechanismsofaction

�  InhibitionofT-cellmediatedcalcineurinproduction

� Whichinturninhibitsupregulationofinflammatoryproteins(notablyIL-2)

�  Andmayinhibitapoptosis(conjunctivalepithelialcells)

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Restasis(cyclosporin0.05%ophthalmicemulsion� Systemicapplicationasanimmuno-suppressant/-modoulator�  Limbalstem-cellgrafts

�  Supplementarytochemotherapyforretinoblastoma

� Originallyappliedinsolid-organtransplants(kidney,liver,lung,heart

� NOsystemicabsorptionfromtopicaldosing

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RestasisClinicaleffects(documentedoff-label)� Ocularrosacea–2/3ofpts.reducedoralantibioticuse

� LASIK-associateddryeye(decreasedsymptomsattributedtoreducedinflammatoryupregulation

� CLintolerance–increasedwearingtime

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� KCS(T-cellmediatedinflammatoryinhibition)� PosteriorblepharitisandMGD(anti-inflammatoryeffects)�  Improvedclinicalsigns

�  Meibomianglandinclusions�  Stainingscores�  Viscosityofglandsecretions�  TBT�  Schirmerscore�  Resolutionoflidteleangiectasia

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RestasisClinicaleffects(documentedoff-label)

RestasisClinicaleffects(documentedoff-labeleffects)� AtopicKeratoconjunctivitis–saferoptionthansteroids

[therefore,ofgreatestbenefitforsteroid-resistantpatients]� OcularHerpesSimplex(stromal)–mechanismisprobablyinhibitionofT-cellsandVEGF

� Graft-versus-Hostdisease

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Otheroff-labelophthalmicapplications� Allforextemporaneouslycompoundedformulations

�  VKC(1,1.25%,2%inoil;for2wks–4months)withefficacyandwithoutSEs

�  Atopickeratoconjunctivitis(2%qid))–reducedsteroiddependence

�  Phlyctenularkeratoconjunctivis(childhoodrosacea)�  SLK(Theodore)0.5%qid� HSK(stromal)2%�  TSPK(2%)–suppressedepithelialopacitiesin¾ofpts.

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Futuredirec1onsforimmunosuppression�  Foruveitis

�  Anti-TNF-α�  Cytokinereceptorantibodies�  Anti-IFN-α2a(interferon)

� Ocularsurface�  Cyclosporineþ�  Tacrolimus(systemicdosingforcornealgrafts,atopicKC)

� Overall–lowerdosingofcurrentlyapprovedmolecues

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Cor1costeroidsI.TherapeuticapplicationsA.UveitisB.KeratitisC.EpiscleritisD.Iritis

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Topicalophthalmiccor1costeroidsI.TherapeuticapplicationsE.CornealtraumaF.IridocyclitisG.Prophylaxis&post-operativeanti-inflammatoryH.Allergicandseasonalconjunctivitis

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Choicesfortreatment(highestpotencyandpenetra.on)

A.Prednisoloneacetate1%suspension(PredForte®,Allergen,andothers) 1.Potenttopicalanti-inflammatorysteroids

2.Bestpenetrationintothe

anteriorchamber;haspostsurgicalapplication

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Prednisoloneacetate3.Dosingisbasedontheseverityofthe

inflammation(ratchetupfromqid(orq4h);taperingwheninflammationisundercontrolandthetreatmenthasbeen>severalweeks

RemembertogetbaselineIOPandF/UIOP4.PredMildis0.125%predacetateformilder

inflammationsBothareBAKpreserved

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loteprednoletabonate0.5%(Lotemax®,B&L)Uniquechemicalformulation

(estervs.ketoneforothertopicalcorticosteroids) a.minimizespotentialforadversesideeffects b.allowspotentialforuseinchronicconditions(butprobablynotthebestforrecurrent)

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loteprednoletabonate0.5%(Lotemax®,B&L)c.avoidscomplicationsofelevatedIOPinsteroidresponders

d.reducesriskofPSCinlong-termuse*

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PosteriorSegmentapplica1onoftopicalNSAIDs(???)�  Inpatientswithneovascularage-relatedmaculardegenerationmanifestingpersistentexudationdespitemonthlyintravitrealanti-VEGFtherapy,wecouldnotdetectabeneficialeffectofaddingtopicalbromfenac(0.09%)twicedailyover2months.

�  Implication:intraocularpenetrationorefficacyisdifferentfrombromfenac/nepafenac

ZweifelSA,EngelbertM,KhanS,FreundKB.Retrospectivereviewoftheefficacyoftopicalbromfenac(0.09%)asanadjunctivetherapyforpatientswithneovascularage-relatedmaculardegeneration.Retina.2009Nov-Dec;29(10):1527-31.

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Durezol(difluprednateophthalmicemulsion)0.05%�  FDA-approvedforthetreatmentofpostoperativeinflammationandpainassociatedwithocularsurgery

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Durezol–safetyandefficacy(difluprednateophthalmicemulsion)0.05%� Difluprednate,administered2timesdailystarting24hoursbeforecataract-surgery,washighlyeffectiveformanagingocularinflammationandrelievingpainanddiscomfortpostoperatively.

� Difluprednatewaswelltoleratedandprovidesaconvenienttwice-dailyoptionformanagingpostoperativeocularinflammation.

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Smith S, et al., Difluprednate ophthalmic emulsion 0.05% (Durezol) administered two times daily for managing ocular inflammation and pain following cataract surgery. Clin Ophthalmol. 2010 Sep 7;4:983-91.

Durezol(anterioruvei1s)(difluprednateophthalmicemulsion)0.05%� DifluprednateadministeredQIDisatleastaseffectiveasprednisoloneadministered8x/dayinresolvingtheinflammationandpainassociatedwithanterioruveitis.

� Difluprednateprovideseffectivetreatmentforanterioruveitisandrequireslessfrequentdosingthanprednisoloneacetate.

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Foster CS, et al. Durezol (Difluprednate Ophthalmic Emulsion 0.05%) compared with Pred Forte 1% ophthalmic suspension in the treatment of endogenous anterior uveitis. J Ocul Pharmacol Ther. 2010 Oct;26(5):475-83.

Durezol(anterioruvei1s)(difluprednateophthalmicemulsion)0.05%�  Instillationofdifluprednateophthalmicemulsion0.05%isasafeandeffectivetreatmentthatdoesnotrequiresurgicalinterventionanddoesnotproducesevereside-effects.

(comparabletosub-Tenoninjectionofsteroid)

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Nakano S, et al. Steroid eye drop treatment (difluprednate ophthalmic emulsion) is effective in reducing refractory diabetic macular edema. Graefes Arch Clin Exp Ophthalmol. 2010 Jun;248(6):805-10.

Actinic(UV)-AssociatedConditions–adnexalapplicationsofNSAIDs• Actinicdamage• Secondarytosun-damagedskin• Histologically-alossofcollagenandelastictissue

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TopicalVoltaren(gel)�  Solaraze(declofenacsodium3%gel)�  actinickeratosis(FDAapproved2000;

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Anti-inflammatories in Ocular Allergy Treatment Steroids used to be reserved for non-responsive cases. But now many optometrists are using them as a first-line therapy for allergic conjunctivitis. By A.J. DeVivo, OD, and Terry Scheid, OD 2/15/2013, Review of Optometry

Thelatestinpreven1ngintraopera1vemiosisandreducingpostopera1vepainincataractsurgery

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OMIDRIA is a sterile solution concentrate containing 1% w/v of phenylephrine and 0.3% w/v ketorolac in a single-patient-use vial. 1 INDICATIONS AND USAGE Omidria™ is added to an ophthalmic irrigation solution used during cataract surgery or intraocular lens replacement and is indicated for maintaining pupil size by preventing intraoperative miosis and reducing postoperative ocular pain. 2 DOSAGE AND ADMINISTRATION Omidria must be diluted prior to intraocular use. For administration to patients undergoing cataract surgery or intraocular lens replacement, 4 mL of Omidria is diluted in 500 mL of ophthalmic irrigation solution. Irrigation solution is to be used as needed for the surgical procedure. The storage period for the diluted product is not more than 4 hours at room temperature or 24 hours under refrigerated conditions.

NSAIDSandSteroids�  Questions

� Comments

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