GlaucomaSurgicalTreatments

MurrayFingeret,ODJustinSchweitzer,OD

JoeSowka,OD

Disclosures

• MurrayFingeret• ConsultantBausch&Lomb,Alcon,Allergan

• JustinSchweitzer• Allergan,Glaukos,BauschandLomb,Bio-Tissue,Alcon,TearScience,Reichert

• JosephSowka

GlaucomaSurgicalTreatments

• Whataretheindicationsforglaucomasurgery?(Murray)• SelectiveLaserTrabeculoplasty – Isitbestsuitedasaprimaryorsecondarytreatmentoption?(Murray)

• TheTrabeculectomy – Hasitbecomearelic?(Joe)• MIGS– TheiStent whatisitsrole?HasitbecomearelicwiththeintroductionofnewMIGSdevices?(Justin)

• MIGS- TheCypass andXengelimplant– WhataretheyandhowdotheydifferfromtheiStent? (Justin)

• Bimatoprost SR– Areinjectionsintotheanteriorchamberaviabletherapeuticoption?(Joe)

Whataretheindicationsforglaucomasurgery?

Whenissurgeryindicated?

• PoorIOPcontrol• Afterexhaustingmedicaltherapy,IOPisabovetargetpressure

• Glaucomatousdamagegettingworse• Poorcompliance

• Duetoahostofreasonsincludingcannotaffordmedication,cannotremembertotakethem

• Inabilitytoinstilleyedrops• Ie Parkinson'sdisease

• Medicationsideeffects• Thesemayalsobethereasonstoconsideradrugdeliverydevicewhenavailable

• Ring,punctal plug,contactlens,injection

Whenissurgeryindicated?

• IndicationsfordoingSLTaredifferentthanFiltrationsurgerywhicharedifferentfromimplantingaMIGSdevice

• Insurancecoveragemustbeconsidered• MuchquickertodoSLTorMIGS(ifcataractpresent)thanthetrabeculectomy

• SLTandMIGSareoftenconsideredasamedicationinregardstoindicationsandcomplications

Surgery• Lasertrabeculoplasty

• Selective• MIGS

• Istent• Cypass• Xengelimplant

• FilteringProcedures• Filteringprocedureswithanti-fibroblasticagents• Expressimplant• Canaloplasty• Implants

• Molteno,AhmedGlaucomaValve,Baerveldt GlaucomaImplant• Cyclophotocoagulation procedures

• Endocyclophotocoagulation

SelectiveLaserTrabeculoplastyIsitbestsuitedasaprimaryorsecondarytreatmentoption?

SelectiveLaserTrabeculoplasty (SLT)

• Q-switched,frequencydoubledNd:Yag 532nmlaser• Targetspigmentedcellsintrabecularmeshwork

• littledamagetonon-pigmentedcells• lessdestructiveprocedure

• 400µmspotsizew50spotsto180o ofTM• ascomparedto50µmspotsizeforALT• spansentireheightofTM• selectivelytargetspigmentedcellswocausingstructuralorcoagulationdamage

• eliminatesscarring• Reducedenergylevels- 0.6- 1.2mJ

Courtesy M. Latina, M.D.

The Differences between ALT & SLT Treatments

LaserSpotSizeDifferencesofALTandSLT

• ALT(greenarea)• RequiresfocusonTM

• SLT(redarea)• CoversTM• DoesnotrequiresamesensitivefocusasALT

• Larger beam diameter •reduces need for focus•evenly distributes laser energy

SelectiveLaserTrabeculoplasty(SLT)

• Advantage• LittledestructiontoTMsupportsbiologictheory

• Nocoagulationeffects• reducedincidenceofIOPspikesandcomplications

• Reliesonselectivephotothermolysis

• targetsmelaningranuleswithincell

• celldeathoccurs• Lessneedforpigmentedtissue

• 20-22%IOPreduction• Worksover24hourperiod• ReducedstructuraldamagetoTM

• IOPreducedat1week

SelectiveLaserTrabeculoplasty(SLT)

• Patienttype• Effectiveasadjunctiveorreplacementtx• Alsomaybeusedasprimarytherapy• Beingusedearlyinsteppedmedicaltherapy

• Donotwaituntilpatientexhaustedallmedicaloptions

• Contraindications• Secondaryglaucomas

• Traumaticanglerecession• Inflammatory• Neovascular

SLTResults

Author/Yr Eyes Response IOP Decrease

Latina,1998 53 70% 23.5%

Gracner,01 50 88% 21.6%

Melamed, 2003

45 96% 30%

Cvenkel,04 44 62% 17.1%

McIlraith, 2006

74 83% 31.0%

ShouldSLTbeusedasPrimaryTherapy?

• Advantagestoprimaryuse• Cost• Adherence• IOPloweringeffectwearsoffandquestionableifrepeatable• Lastsin50%approximately5years• Fewsideeffectsandrelativelysafe• Worksover24hourperiod

• Disadvantagestoprimaryuse• OnlyreducesIOP20%

• Advantagestosecondaryuse• Additivetoallothermedications• Canbeutilizediffirstlinetherapyunsuccessfulorneedsadditionalreduction

• Explainoptionstopatientandletthemhavevoiceinwheretherapyfits

IsitRepeatable?

Trabeculectomy– Hasitbecomearelic?

Trabeculectomy– Hasitbecomearelic?§Whatfilter(trabeculectomy)surgeryis

- FistulizationbetweenACandsubconjunctivalspace§ Indications

- Moderate/advanceddisease,veryhighinitialIOP,progressingdisease,needforlowandstableIOP

• (CIGTSprimaryprocedure?)

§ Risksandcomplications- Several

§ IsitbeingdonelesswithMIGSnowavailable?- Yes,butnotforthereasonsthatyouthink

Trabeculectomy

• Trabeculectomy(1968)+/- anti-metabolite• Blebformingprocedure• Longestablishedprocedurewithvastexperience

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Antifibrotic Agents§ Inhibitfibroblastproliferation

§ 5FU- Intraoperative: 50mg/mlfor5min- Postoperative: 5mgsubconj

§MMC- 100timesmorepotentthan5FU- Intraoperative: 0.2-0.5mg/mlfor2-5min

Antifibrotic Agents§ Inhibitfibroblastproliferation

- MMC;5-FU

§ Indications- Neovascularglaucoma- Uveiticglaucoma- Previousocularsurgery(e.g.CE,failedfilter)- AfricanAmericanrace- Youngage

• Goodhealing- NeedforaverylowIOP

• Veryadvanceddisease

Outcomes:TrabeculectomySuccessAfter20Years:

- 57%=completesuccess- 88%=qualifiedsuccess(w/meds)

Complications:- Cataract:55%- Lossof≥3linesofacuity:21%- Bleb-relatedproblems:10%- Infection:4%

Jampel HD. Ophthalmol 2012Gedde SJ. Arch Ophthal 2012

IstrabeculectomyaPanacea?§ TrabeculectomywillgivelowIOP

- Singledigits§ Longhistoryofsuccess§ Technicallystraightforwardprocess§ Eyeneverlooks/feelsthesame§ Potentialcomplications

EarlyComplications§ FailuretocontrolIOP- scarring§ Malignantglaucoma§ Hyphema§ Hypotonyresultingmaculopathy,suprachoroidalhemorrhage,choroidaleffusion,orshallowanteriorchamber

§ Woundleak,mayrequireadditionalsutures§ Endophthalmitisorblebitis§ Lossofvision

- “wipe-out”• Hypotonymaculopathy,choroidaleffusionanddetachment,pressurespike,idiopathic

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LateComplications§ Cataract

- Trabscausecataracts§ Ptosis§ Blebleak,duetobreakdownofconjunctivaoverthebleb,cancausehypotony

§ EndophthalmitisandBlebitis- riskincreaseswithblebleak

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Trabeculectomy§ Historicallyperformedbygeneralophthalmologists§ Asophthalmologyhasevolved,mostgeneralophthalmologistshaveabandonedtrabstoglaucomaspecialists

§ Establishedglaucomaspecialistshavenowlearnedtubesandseatons(drainageimplants)

§ Newerglaucomaspecialistsareincreasinglylearningdrainageimplants

§ So,yestraditionaltrabeculectomyisbecomingareliccomparedtodrainagedevices(notMIGS)

Drainagedevices/TubeShunts§ ACtube

- ShuntsaqueousfromACtoplate- Maintainspatencyoffistula

§ Episcleralplate(explant)- Locatedinequatorialregionofglobe

- Formsanonadherentcapsule

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DrainageDevices§ Ahmedvalve;Baerveldtimplant§Goodwhenprevioustrabfailedorisexpectedtofail§Nowbecomingpopularasaprimaryprocedure§ TVTStudy

- TrabwithMMCandtubeshuntcangivesustainedlowteenIOP

- TubeshunthasgreatersuccessthantrabwithMMCineyeswithpriorcataractand/orglaucomasurgery

- Similarsafetyprofiles- tubesbecomingpopular

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Drainagedevices§ Indications

- Neovascularglaucoma- Uveiticglaucoma- Previousocularsurgery(e.g.CE,failedfilter)- Perilimbalconjunctivalscarring- ICEsyndrome- Congenitalglaucomarefractorytoanglesurgery

Glaucomasurgicalprocedures

Glaucoma not well controlled

Mild disease,Concurrent cataract, desire to reduce med load

MIGS

Moderate/ advanced disease,High baseline IOP,Secondary glaucomasLow target IOP

Trabeculectomy Tube Implant

istrabeculectomybeingdonelesswithMIGSnowavailable?YesandNo

§MIGS≠Trabeculectomy- Easierwithfewercomplications- LesserIOPreduction- Inducementforalesserproceduretobedone?

• Delaysmoreneededprocedure?

§ Trabeculectomymaybegivingwaytotubes§ Trabeculectomywillbearoundforawhilelonger

MinimallyInvasiveGlaucomaSurgery(MIGS)

TheiStent - whatisitsrole?HaveyouMIGSdevicesreduceditsvalue?

SafetyFirstiStent

8%postopcornealedema3%elevatedIOP

SafetyprofilesimilartoCEx

Unmatchedsafetyprofilecomparedtonewlyapproveddevices?

TheCyPass andXenGelImplant

CyPass Micro-Stent

COMPASSStudy374SubjectsCyPass +CataractSurgery

IOP

Medications

Baseline 12Months

24.4mmHg

1.4

17mmHg

0.2

72.5% stent+cataractachieveda> 20%reductioninunmedicated diurnalIOPat2yearsvs58%incataractalone

Hypotony 2.9%@30daysOverallsaftey profilewassimilartoCEx

DUETTEStudy

65EyeswithmedicatedIOPgreaterthan21atbaseline

IOP

Medications

Baseline 12Months

24.5+/-2.8

2.2+/- 1.1

Mostcommonadverseevents:IOP>30beyond1month(11%),transienthyphema (6%)andcataractprogression(12%)

16.4+/-5.5

1.4+/-1.3

Xen

Xen 45GelStent:USPivotalClinicalTrialVisits– IOP andMedications Mean

Baseline

MedicatedIOP 25.1(3.7)

GlaucomaMeds 3.5(1.0)

12 Month

IOP 15.9(5.2)

GlaucomaMeds 1.7 (1.5)

76.3%ofpatientsreportedameandiurnalIOPreductionof

> 20%frommedicatedbaselineat12months

Hypotony 16(24.6%)(IOP<6mmHgatanytime)

Anteriorchambershallow 1(1.5%)withperipheralirido-cornealtouch

Anteriorchamberfill 1(1.5%)

Bleb Needling 21(32.3%)

PostoperativeAdverseEvents

Areinjectionsintotheanteriorchamberaviabletherapeutic

option?

Optionsfordrugdelivery

Evolutionofsustaineddelivery

§ Allerganiscurrentlyperformingphase3clinicaltrialsonitsbimatoprostsustained-releaseimplant(bimatoprostSR),whichisanintracameraldepotimplantinjectedintotheanteriorchamber.

§ Implantcomprisingaprostamideassociatedwithabiodegradablepolymermatrixthatreleasesanamountofaprostamide

bimatoprostSR§ Phase2trialsoftheimplantshowedmeanoverallIOPreductionsfrombaselinethroughweek16afterthefirstimplantationofthebimatoprostsustained-releasedevice

- 7.2,7.4,8.1,and9.5mmHgwiththe6-,10-,15-,and20-microgramdosescomparedwithan8.4mmHgdecreaseinthepooledfelloweyestreatedwithtopicalbimatoprost(0.03%).

bimatoprostSR• TheimplantloweredIOPin92%ofpatientsat4monthsand71%at6months.

• Didnotneedadditionalrescuetherapy

• Therewerenoseriousadverseocularevents• Themostcommonadverseeventwastransientconjunctivalhyperemia(mediandurationof5days),whichdevelopedwithin2daysaftertheimplantwasinjected.

• In24eyesthatdidrequireanothertreatmenttocontrolIOP,theoverallmeanIOPreductionfromthebaselineIOPwas8.0mmHgthrough16weeksaftertherepeatbimatoprostsustained-releasetreatment.

TravoprostSR

TravoprostSR

TravoprostSR§ ENV515- phase2aopen-label,28-daydose-rangingstudyof21patientsyielded28%IOPloweringatday25inonegroup,whichwascomparabletoonce-dailyTravatanZ

§ Envisiaisplanningtoadvancetoa12-monthstudytoevaluatethelong-termIOPloweringofENV515.

NotSoGreatThingsAboutSustainedDelivery

§ Injectablemedsandimplants- ifmeddoesn’tworktopicallyorhasadverseeffects,dropisstopped;can’teasilystopimplantabledevices.

§ Implantscantheoreticallyblockpartsoftheangle§ Complicationswithinvasiveoptions

- Endophthalmitis

§ Decreasedaccesstocare?

NotSoGreatThingsAboutSustainedDelivery• Limitations- howmanydrugscanyouloadintotheanteriorchamber?

• Drugsmayworkbetterinpulsatileformandnotsowellinconstantdelivery

• PGAslesseffectiveatBIDdosing- receptorsupersaturationanddesensitization

• Downtimebetweendropspreventsdesensitization• SomeconcentrationsofbimatoprostSRwerelesseffectivethantopical0.03%

NotSoGreatThingsAboutSustainedDelivery• SRproductsseemlesseffectivethandrops• Willinsurancepayforitjusttoincreasecompliance?

Anti-VEGFmodelforamd§ Comparedtoclinicaltrials,VAoutcomesareworseandtherearefewerinjectionsdoneintherealworld.Patientslosttofollow-uparedoingpoorly.

§ Dropoutrate20%-30%

Willpatientsgoforit?