Northeast Florida Medicine - Summer 2011 - Ophthamology

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www . DCMS online . org Northeast Florida Medicine Vol. 62, No. 2 2011 3

Features

11 FocusontheEye JanetA.Betchkal,MD,GuestEditor

12 OcularSignsofNon-ocularCancersinChildrenandAdults DavidA.Kostick,MD

15 AdvancesinCataractSurgery:AReviewfortheNon-ophthalmicPhysicianWalterR.Gilbert,Jr.,MD

20 TheHistoryofRefractiveSurgeryJerryW.Maida,MD25 TakingonGlaucoma:TheRoleofthePrimaryCarePhysicianTinaN.Tillis,MD

32UseofVascularEndothelialGrowthFactorInhibitorsforRetinalDisease FredH.Lambrou,Jr.,MDandGregoryM.Lewis,MD

37 EvaluationandTreatmentoftheLowVisionPatientDianeCates,ODandKimRigdon,CLVT SpecialArticles

Insert ImpactofHIVonVision MichaelW.Stewart,MD(CME)

VOLUME 62, NUMBER 2OphthalmologySummer2011

MANAGING EDITORLeoraLegacy

ASSOCIATE EDITORSRaedAssar,MDStevenCuffe,MDRupleGalani,MDKathyHarris(Alliance)SunilJoshi,MDJamesJoyce,MDNeelKarnani,MDMobeenRathore,MDJamesSt.George,MD

Executive Vice PresidentJayW.Millson

DCMS FOUNDATION BOARD OF DIRECTORSBenjaminMoore,MD,PresidentToddL.Sack,MD,VicePresidentKayM.Mitchell,MD,SecretaryJ.EugeneGlenn,MD,TreasurerGuyI.Benrubi,MD,ImmediatePastPresidentMohamedH.Antar,MDRaedAssar,MDAshleyBoothNorse,MDJ.BrackenBurns,DOLTOrlandoCabrera,MC,USN,ResidentMalcolmT.Foster,Jr.,MDJeffreyM.Harris,MDMarkL.Hudak,MDSunilN.Joshi,MDDanielKantor,MDNeelG.Karnani,MDHeatherKearney,MD,ResidentJohnW.KilkennyIII,MDHarryM.Koslowski,MDEliN.Lerner,MDJeannineMauney,MD,ResidentJesseP.McRae,MDJasonD.Meier,MD,ResidentNiteshN.Paryani,MD,ResidentNathanP.Newman,MDMobeenH.Rathore,MDRonaldJ.Stephens,MDJeffreyH.Wachholz,MDDavidL.Wood,MD

Northeast Florida Medicineispub-lishedbytheDCMSFoundation,Jacksonville,Florida,onbehalfoftheCountyMedicalSocietiesofDuval,Clay,Nassau,Putnam,andSt.Johns.Exceptforofficialannouncementsfrom the County Medical Societ-ies, no material or advertisementspublishedinNEFMaretobeseenasrepresentingthepolicyorviewsof the DCMS Foundation or itscolleague Medical Societies. Alladvertisingissubjecttoacceptanceby the Editor in Chief. Addresscorrespondenceandadvertisingto:555BishopgateLane,Jacksonville,FL32204(904-355-6561),oremail:[email protected].

COVER: Image courtesy of Abbott Medical Optics, Inc.

Inside this issue of

Departments4 FromtheEVP’sDesk5 FromthePresident’sDesk8 TrendsinPublicHealth9 Residents’Corner

Northeast Florida Medicine

[email protected].

4 Vol. 62, No. 2 2011 Northeast Florida Medicine www . DCMS online . org

From the EVP’s Desk

WHTDFYL? - A 2011 Legislative RecapThelanguagemykidsandthoseacrossthecountryusetocommunicateisadizzyingarrayofacronymsthatleavemostadults

dazed,confused,andmaybefeelingevenalittlebitinsulted.Thatis,ofcourse,untiltheytellusthat‘TMI’hastodowithinformationandnotourwaistlineand‘LOL’hopefullymeanstheyarelaughingwithus,notatus.

Whatdoesthishavetodowiththe2011FloridaLegislativeSession?Sufficeittosay,theterm‘WHTDFML’isthemostaccuratedescriptionofwhattheFloridaMedicalAssociation(FMA),statespecialtyandyourcountymedicalsocieties(DCMS)

accomplishedonbehalfofthemedicalprofessionwhenthelegislatureadjournedonMay7.So,nexttimeyouponderpaymentofyourmembershipdues,takealookatexactly“WhatHaveThey(organizedmedicine)DoneForYouLately”.

Medical Liability Reform (HB 479)Arguably themost significantpieceof legislationpassedbyorganizedmedicine inover20

years,HB479goesalongwayinthebattletoachievemeaningfultortreforminFlorida.Thelegislation:1)RequiresMD,DO,orDDS,licensedinanotherstate,toobtainanexpertwit-nesscertificatebeforebeingabletoprovideexperttestimonyinFlorida;2)GivestheBoardsofMedicine,OsteopathicMedicine,andDentistrythespecificauthoritytodisciplineanyexpertwitness,boththoselicensedinstateandthosewithanexpertwitnesscertificate,whoprovidedeceptiveorfraudulentexpertwitnesstestimony;3)RequirestheBoardofMedicineandtheBoardofOsteopathicMedicinetocreateastandardinformedconsentformthatsetsforththerecognizedrisksrelatedtocataractsurgery. Providesthatanincidentresultingfromarecognizedspecificriskisnotconsideredanadverseincident;4)Deletestheprovisionincurrentlawthatprohibitsaninsurancecompanyfromsellingamalpracticeinsurancepolicytoaphysicianthatgivesthephysiciantheauthoritytocontrolsettlementdecisions;5)Excludesfromevidenceinanymedicalnegligenceactionanyinformationregardinganinsurer’sreimbursementpoliciesorreimbursementdeterminations;6)Providesthatthebreachof,orfailuretocomplywith,anyfederalrequirementisnotadmissibleasevidenceinamedicalnegligencecase;7)Providesthatthe

expertwitnesswhosubmitsthepre-suitverifiedexpertmedicalopinionisnolongerimmunefromdiscipline;and8)Providesthatvolunteerteamphysiciansareimmunefromsuitwhengratuitouslyrenderingcareataschoolathleticeventorscreening.

Medicaid Reform (HB 7107 & 7109)FloridaMedicaidisgrowingatanuncontrollablepace,withapproximately35%oftheentirestatebudgetbeingdedicated

totheprogram($21of$59billion).Withestimatesofover$25billionincostsby2014,theFloridalegislaturepassedHR7107and7109transitioningMedicaidintoamanagedcaresystembyOctober2013. Althoughtherearesomecarveoutsformedicallyneedyanddisabilities,theprogramwillbebrokeninto11regionsutilizingcapitatedpaymentstocontrolcosts.BeneficiarieswillselectorbeassignedaPCPandtheplansmustpromotehealthylifestylebehaviors(e.g.,propernutrition,smokingcessation,exercise,etc.).

Themostsignificantnegativescomeinthewayofunknownphysicianpaymentratesandtheprospectofanincreasingben-eficiarypopulation.Positivesincludethefactthatphysiciansarenotrequiredtoparticipateintheprogram,ProviderServiceNetworks(PSN)likeUF&ShandsJacksonvilleweremaintainedtocompetewithfor-profitplans,andtheinclusionofa$200,000(individual)or$300,000(group)medicalliabilitycaponnoneconomicdamagesforpractitioners(physiciansandhospitals).Moreimportantly,theevidentiarystandardwasraisedto“clearandconvincingstandard”ratherthana“preponderanceoftheevidence”.ImplementationwilldependuponreceiptofafederalwaiverfromCMStotransitionmatchingfundsintoaman-agedcaremodel.

Otherkeyprovisions:

• SovereignImmunityforteachinghospitalsandextensionclinics• PillMills/PainClinics(HB7095)-1)MaintainsPrescriptionDrugMonitoringProgramdatabasepostingrequirement

ofsevendays,willhelppreventdoctorshopping;2)Limitsphysicianofficedispensingmostabusednarcotics,exceptsurgicalprocedures,clinicaltrials,methadoneclinicsandhospice;and3)Newregistrationprocessesforpractitionersandpharmaciesprescribingcontrolled,mostabusedsubstances

• GunBill–BoardsofMedicinedetermineifaskingaboutgunownershipismedicallynecessary,notthecivilcourtsystem• ScopeofPractice (bills defeated) -1)ARNPindependentpracticeandability toprescribecontrolledsubstances;2)

Optometristsbeingabletoprescribeoralmedications;and3)Pharmacistsbeingabletoprovideimmunizationsbeyondinfluenza(e.g.,shingles)

Shouldyouwantmoredetailsregardinganyaspectofthelegislativesession,sendanemailtojmillson@dcmsonlineandI’llgetbacktoyouASAP(evenusoldfolksunderstandthisone!)

Jay W. MillsonExecutive Vice President/DCMS

mailto:jmillson%40dcmsonline.org?subject=


From the President’s Desk

Reflecting on Healthcare Improvements

RecentlyIwasreflectingontheimprovementsmadeinhealthcareinourcountrysinceIbeganpracticingmedicine.Manyofthemimprovementsareduetothediscoveryofvaccinesandthedevelopmentofpublichealthefforts.

Forexample,DPT,measles,mumps,varicella,andrubellahavenearlydisappearedaswellassmallpox.AnewvaccineforRotavirus isnowrecommendedas isavaccinetopreventcertainmeningococcal infections.BCGhasnotbeenparticularlysuccessful,butperhapsitpreventsmiliarytuberculosisinchildren.Pneumovaxhasnotproventobeeffectivealthoughitmay

preventinvasivepneumococcaldisease.Influenzaevaccinationis80%effective,althoughitlosessomeeffectivenessinolderpatients,andothervaccinesareusedselectivelysuchasrabiesforanimalhandlers,anthraxforthemilitary,andstillothersforinternationaltravelers.

Therehavealsobeenkeypublichealthmeasuresoverthedecades.Theseinclude:1)ThecontrolofhookwormintheSouth,startinginthelate1930s,byaneducationprogramandtheuseofoutdoortoilets;2)ThereductionofsyphilisafterWorldWarIIbyrapidtreatmentcenters,requiredscreeningbloodtestsandlaterbyepidemiologicinvestigations;3)Improvementinfoodsafetythroughinspectionoffoodestablishments,educationoffoodhandlers,refrigerationandmostrecentlyirradiationoffood.(Theseeffortsmustbecontinued—thinkE.coli,E.coli,E.coli);4)DuringthegreatdepressiontheWPAandCCCdrainedtheswampsinthesoutheasternUnitedStatesvirtuallyeliminatingmalariaandelephantiasis;5)OralrehydrationprogramsreducedthedeathrateinCholeravictims,particularlychildren;6)Fluorinationofthepublicwatersupplyhelpedtopreventdentalcarries;7)Theadditionofiodinetosalttopreventsgoiters,andthe

additionofvitaminDinmilktopreventsRicketts.Infact,vitamindeficiencyisrarelyseennow;8)TuberculosiscontrolhasbeensetbackbyHIVandinpersonsbornoutsidetheUnitedStates.

DirectObservedTreatment(DOT)hasbeenasuccessfulprogram;and9)Asofyet,wehavenotbeensuccessfulincontrollingmostvenerealdiseases.

Thesepublichealtheffortsshouldbecelebratedandcontinuedwhenappropriate,however,wehavetoaddressmanychronicconditionsinapopulationthatcontinuestoage.Theseconditionsinclude:

1. COPDisstillgrowingasamajorproblem.CigarettesmokingshouldbePublicEnemy#1andairpollutionshouldbe#2;2. Diabetesmellitus,sometimesdisguisedasthe“metabolicsyndrome”isagrowingproblem.Therootcasuesaregenetics,

obesity,andsedentarylifestyle.Weshouldembracealleffortstofightobesityandinactivity.Themorediabetics,themorerenalfailureanddialysiswewillhave;

3. Atherosclerosisrequiresanentirearticle,buttheeffortstotreathypercholesterolemiaarebearingfruitasistherecognitionandtreatmentofhypertension;

4. Dementiaisjustenteringourmedicalradarscope,butoverthenext30yearsitwillbecomeamajorsocietalproblem;5. Asthepopulationages,moreandmorepatientswillhaveoncologicaldiseases.TheMKSAPsuggeststhat60orgreater

percentofthesemalignanciesareenvironmentallyrelated;6. Osteoarthritis-everyoneseemstohaveOA;7. HIVisstillamajorhealthandsocietalconcern.Theonlyeffectivecontrolforviraldiseaseshasbeenvaccination.Itistrue

thatHIVhasbeenconvertedfroma“deathsentence”toachronicdiseasethatrequirescontinuoustherapy.

Recentlytwonewvaccineswereintroduced:Zostavaxforpatientsover60yearsofage.ItpromisestoreduceclinicalHerpesZosterinfectionsby50%andlesseningposthepaticneuralgiaswilljustifythevaccine’sexpense.Inaddition,Medicarewillpayustoadministerthevaccine.Also,Gardisilforgirlsandwomenage9-26promisestopreventHPviralinfectionsandthereforepresumablycarcinomaofthecervix.Thisvaccineisamajorpublichealthadvance.Therearemanyquestionstobeansweredaboutthisvaccine,mostnotablyisshouldweadministerittomenaswellandwillboosterimmunizationsbeneeded?Thesignificanceofthisvaccineforwomen’shealthrivalstheintroductionofthebirthcontrolpill50yearsago.

Allof theseproblemscallout forprevention, earlydiagnosis,andaggressive treatment, including lifestyle changes.WhatcanDCMSasanorganizationdo?Whatcanyouasanindividualpractitionerdo?Certainlywecancontinuetoeducateourmembers,thepublic,andourlegislators.

Malcolm T. Foster, Jr., MD2011 DCMS President


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Trends in Public Health

Vision screening is a cost-effective and efficient publichealthpreventivetechniqueto identifypeoplewithvisionimpairmentsearlyinthecourseofthedisease.Itisespeciallyimportantinyoungchildren,sincetheyareoftenunawarethattheyarenotseeingaswellasothersandtheirvisionproblemscangoundetected.Visionscreeningismosteffectivewhenperformedperiodicallythroughoutinfancyandchildhoodtodetectconditionssuchasamblyopia,strabismus,anddefectsinvisualacuity.Thefirstvisionscreeningmusttakeplaceinthenewbornperiodatthenursery,withthedoctorcheckingtheeyes,pupilandtheredreflex.

In2009,thereweremorethan12,000clinicvisitsduetoeyeorvisionrelatedproblems inDuvalCounty.Ofthesevisits,75%ofclinicvisitsinDuvalCountybothadultsandchildrenwereforcataracts.

FloridaStatute381.0056(5)(2002)requiresadocumentedvisionscreeningorcomprehensiveeyeexaminationbeforechildrenbeginschool.Itrequiresthecountyhealthdepart-menttopartnerwiththedistrictschoolboardandthelocalschoolhealthadvisorycommitteetodevelopacomprehen-siveschoolhealthservicesplan,whichmustincludevisionscreening.Healthdepartmentsarealsorequiredtoarrangereferralsandfollow-upsforchildrendiagnosedwithvisionproblemsafterconsultingthestudent’sparentorguardianandmaintainrecordsregardingtheproblem,thecorrectivemeasurestaken,andotherinformation.

The Duval County Health Department (DCHD) hasinitiatedpartnershipstoaddressvisionscreeningforchildreninDuvalCounty.DCHDclinicshaveestablishedprotocolsrequiringthatvisionscreeningbeconductedduringallwell-childexamsforchildrenages5andolder.In2010,DCHDclinicstaffconductedmorethan5,300oftheseexams.DuvalCountyPublicSchools(DCPS)partnerwiththeDCHDtoprovideschoolhealthservicesinJacksonvilleinaccordancewithFloridaStatutes.

A critical health service is the DCPS Vision ScreeningProgram,undertheleadershipofDotMathias,whichscreenedalmost70,000studentsinDuvalCountyduring2009-2010.Duringthisperiod,morethan1,500volunteersweretrainedto conduct vision screening and provided free eye examand/or glasses to ~300 referred students from financially

disadvantaged families. In addition, the program notifiedparentsandreferredmorethan6,000ofthesestudentsforfurtherevaluation.DCHDnursesprovidedfollow-upservicesforallthestudentsreferredforfurthercareandmaintainedhealthrecords.

DCHD pediatricians and clinic staff received trainingforvisionacuityscreeningthroughtheNemoursChildren’sClinic Jacksonville and its “See by Three” program. ThisprogramwasstartedbyAmericanAssociationforPediatricOphthalmologyandStrabismus(AAPOS)andhassucceededin Florida andWestVirginia by screening almost 10,000childrenin2009-2010.

AsimilarprogramistheNortheasternEarlyStepsprogramthroughtheUniversityofFloridaCollegeofMedicine–Jack-sonville, which provides vision services, along with otherdevelopmentallysupportiveservices,forinfantsandtoddlersfrombirth to36monthswhohaveormaybe at risk fordevelopmentaldelay.ThisprogramservesfamilieslivinginDuval,Clay,St.Johns,Nassau,Baker,andBradfordcounties.

Visionscreeningandeyeexaminationsareanimportantpartofhealthmaintenanceforeveryone.Theyarerecom-mendedbytheU.S.PreventiveServicesTaskForceasakeycomponentoftheperiodichealthexam.Adultsshouldhavetheireyescheckedtokeeptheirvisionprescriptionscurrentandtocatchearlysignsofeyediseaseslikecataracts.

Forchildren,visionscreeningsandeyeexamsarecriticalnotonlytopreventpermanentblindness,butalsotoensurenormal vision development and academic achievements.Visionscreeningiscloselylinkedtolearningskills.Childrenwhohavedifficultyseeingandinterpretingwhattheysee,can start their education at a disadvantage and are ofteninappropriately labeledashavinga learningdisabilityandsometimesplacedinSpecialEducation.

Visionscreeningwillhelpensurethatchildren’svisualis-suesareidentifiedandtreatedearly,helpingthemtoadvanceacademically, athletically and socially. It is important thatschools,daycares,medicalpracticesandhospitalsincorporatevisionscreeningintoroutinecare.Itisalsotheresponsibil-ityofparentsandfamiliestotakeadvantageofcommunityprogramsandtheirinsurancebenefits.

Vision Screening in Duval CountyNiketaWalawalkar,MD,MPH;ThomasBryantIII,MSWandRobertHarmon,MD


Residents’ Corner: Mayo Clinic’s Graduate School of Education

Editor’s Note: In an effort to connect more Duval County Medical Society members with residents, in each 2011 issue, there will be a “Residents’ Corner” with information about a residency program in the area, details about research being done and a list of achievements/accomplishments of the program’s residents. This “Residents’ Corner” features Mayo Clinic Jacksonville’s Graduate School of Education.

Overview of Residency ProgramMayoClinicisathree-campusacademicmedicalcenterwithadistinguishedhistoryofpreparingphysiciansandscientiststo

succeedasleadersintheirchosenfields.

Mayo’spracticesinPhoenix/Scottsdale,Arizona;Jacksonville,Florida,andRochester,Minnesota,offerresidencyandfellow-shipprogramsinvirtuallyallmedicalandsurgicalspecialties.

Morethan1,500residentsandfellowsparticipateinMayoClinicgraduatemedicaleducationprogramseachyear.AttheJacksonvillecampus,thereare160residentsandfellowsspanning38specialties.

MayoClinicHospital,whichopenedinApril2008, integrates inpatientandoutpatientservicesontheMayocampusinJacksonville.Ithas214bedsand22operatingroomsandofferscarein20medicaland15 surgicalspecialties.Italsoincludesafull-serviceEmergencyDepartment.Residentsandfellowsrotatethroughvirtuallyeverypartofthehospital,aswellasthroughoutpatientclinicsontheMayocampus,theprimarycarecenterinJacksonvilleBeach,andatthestudenthealthcenterattheUniversityofNorthFlorida.SeveralresidentsalsoparticipateinrotationsattheNemoursChildren’sClinicaswellastheWolfonChildren’sHospitalindowntownJacksonville.

Thecampusisalsohometotwolargeresearchbuildings.TheBirdsallMedicalResearchBuildinghas10laboratorieswherescientistsinvestigateneurologicaldiseasessuchasAlzheimer’s.TheGriffinCancerResearchBuildingwascompletedin2002andisthefirstbuildingontheJacksonvillecampusdevotedprimarilytocancerresearch.

Resident Leadership RolesMayoresidentsareinvolvedinmanyleadershiprolesbothinternallyattheClinicaswellasonnationalcommittees.Some

ofthenationalleadershiprolesare:

• NeurologyresidentsRachelDiTrapani,MDandRyanWalsh,MD,areinvolvedwithanationalClinicalSkillsExaminationCommittee,aworkgroupaimingtoimprovethetrainingavailabletoadministratorsoftheAmericanBoardofPsychiatryandNeurologyClinicalSkillsExamination.

• NicoleChiota,MD,alsoaresidentinthedepartmentofneurology,playsanactiveroleintheFloridaSocietyofNeurology,servingontheirexecutiveboardaswellastheiradvocacyandeducationcommittees.

• RossGoldberg,MD,afellowinthedepartmentofsurgery,takesanactiveroleinshapingnationallegislativepolicy.HeservesontheBoardofDirectorsfortheAmericanCollegeofSurgeon’sPoliticalActionCommittee(SurgeonsPAC).HealsoservesontheLegislativeCommitteefortheSocietyofAmericanGastrointestinalandEndoscopicSurgeons.

• RadiationOncologyresidentKatherineTzouMD,servesontheAnnualMeetingandProgramCommitteefortheAmericanSocietyforRadiationOncology.Heresheworkswithphysiciansfromacrossthecountrytoplantheannualconventionattendedbyover12,000oncologists,medicalphysicists,dosimetrists,andnursesfromallovertheworld.

Resident ResearchMayotraineesarealsoheavilyinvolvedinresearchactivitiesandareconstantlypublishingcuttingedgeresearcharticlesacross

manydifferentspecialties.Publishingthetitlesaloneofallofthearticlesauthoredbyresidentsandfellowsinthelastyearwouldtakemorespacethanthisentirejournal!Nevertheless,highlightedarejustafewofthemanyimpressiveaccomplishmentsofresidentsandfellows:

• FamilyMedicineresidentsRamonCancino,MDandScottSimmons,MD,haveauthoredseveralabstractsfocusingonqualityimprovementprojectsindiabetes,residenteducation,andMedicare/MedicaidPQRIinitiatives.

• RadiationOncologyChiefResidentJenniferPeterson,MD,hasauthoredthreepublications,onebookchapter,andmorethansixabstractsduringherfour-yearresidency.Herpublicationsfocusontopicsincludingbreastcancer,prostatecancer,andtreatmentoflivermetastases.Shehasevenreceivedseveralinstitutionalgrantstosupportherresearchefforts.

• InternalMedicineChiefResidentLynseyCassidy,MD,recentlypublishedanarticle inThe Journal of General Internal Medicinefocusingonasymptomaticpatentductusarteriosis(PDA)inadults.

Mayoresidentsarealwayslookingfornewresearchprojectsandleadershipopportunities,includingopportunitiestopartnerwithcommunityphysicians.TheyappreciatethecontinuedsupportandmentorshipoftheDuvalCountyMedicalSocietyphysicians.

Residents’ Corner written by: Dr. Nitesh Paryani, a transitional year resident at Mayo Clinic Jacksonville. He will begin his radiation oncology residency at Mayo in July. Dr. Paryani serves as Mayo’s resident representative to the DCMS Board of Directors and is also on the Board of Governors of the Florida Medical Association. He is a graduate of the University of Florida College of Medicine.

http://www.mayo.edu/msgme/history.html

http://www.mayo.edu/msgme/sct-campus.html

http://www.mayo.edu/msgme/jax-campus.html

http://www.mayo.edu/msgme/rch-campus.html

http://www.mayo.edu/msgme/programs.html

http://www.mayoclinic.org/mayo-clinic-hospital-jax/


Keep an eye out in 2012 for the DCMS History Book What you will see in its pages?

Watch for 200+ great historic photographs Focus on 8 intriguing chapters with facts from bygone days Look for interesting tidbits in numerous sidebars

View DCMS from its past and gaze into its future Special thanks to Mrs. Lee-Margaret Borland for her photograph entitled “Flirt.” Taken in the Tucson, Arizona desert, it shows an injured owl who was recuperating in a desert animal hospital. The owl had a broken wing and was on a perch, so Mrs. Borland could get close to it for this great photo. She watched the owl for a long time and saw it close one eye and then the other, turn its head and then close both eyes. For more of Mrs. Borland’s photographs, go to www.throughthelensoflee-margaret.com.

http://www.throughthelensoflee-margaret.com


This Issue’s Focus: Ophthalmology

Focus on the EyeWhiletheeyeseemssosmall,itmakesupanentireorgansystemofthehumanbody.YetwhenIwasinmedi-

calschoolIthinkspentonlyonehalfdaystudyingtheembryologyoftheeyeandanotherhalfdayonthevisualsystem.Therestofthetimerelegatedtotheotherorgansystemsofthebody.Nowonderophthalmologists’reportsseemlikea“foreign”languagetootherareasofmedicine.Arecentsurveyof4,352peoplein7countriesfoundthattwiceasmanypeoplefearblindnessastheydoaprematuredeathorheartdisease,soitisimportantthatphysiciansunderstanddiseasesthataffectsight.

ThepurposeofthisissueofNortheast Florida Medicineistoprovideinsightintosomeofthemorecommonophthalmicdiseasesandprocedures,helpidentifysomeofthecausesandmanifestations,explainhowtheyaretreatedanddiscusshowtheyaffecttheoverallhealthofthepatient.

David A. Kostick,MD,describes“OcularSignsofNon-OcularCancersinChildrenandAdults.”Itisimportantthatbothophthalmologistsandothermedicalprovidersbeawareoftheseimportantfindingsastheymayrepresenttheearliestoronlyoccultsignofsomeofthesecancers.Walter R. Gilbert, Jr., MD,givesabriefhistoryofcataractsurgeryin“AdvancesinCataractSurgery:AReviewfortheNon-ophthalmicPhysician.”HeprovidesanexcellentsummaryofthecurrentstateofcataractsurgerycommonlyperformedintheMedicarepopulation,andalsodescribesthemanychoicesthatpatientsnowhavewhenitcomesto“customizing”theirfunctionalvisualoutcomes.

Jerry W. Maida, MD, discussestheevolutionofthespecialtyofrefractivesurgeryin“TheHistoryofRefractiveSurgery.”Apioneerinrefractivesurgery,Dr.Maidahasper-

formedrefractivesurgeryfromtheearlydaysofradialkeratotomy(RK)uptopresentdayLASIKprocedures.Tina N. Tillis, MD, takessomeofthemysteryoutofglaucomain“TakingonGlaucoma:TheRoleofthePrimaryCarePhysician”.Shedescribeshowthenon-ophthalmologistcanhelpidentifyriskfactors,understandtreatmentoptions,andhelpmaketheglaucomadiagnosis.

Fred H. Lambrou, Jr., MD, and Gregory M. Lewis, MD, writein“UseofVascularEndothelialGrowthFactorInhibitorsforRetinalDisease”abouthowVEGFinhibitorscansafelybeinjectedintravitreallyinthetreatmentofmanypotentiallyblinding retinaldiseases, includingdiabetic retinopathyandage-relatedmaculardegeneration.In“EvaluationandTreatmentoftheLowVisionPatient,”Diane Cates, OD, and Kim Rigdon, CLVT,provideimportantfunctionalandlegaldefinitionsanddescriptionsofthevarioustypesofvisualimpairmentfromminordecreasesinvisualacuitytototalblackness.Theydescribevisualaides, localresourcesandassistanceavailabletovisually-impairedchildrenandadults.

TheCMEarticleforthisissuealsofocusesontheeye. Michael W. Stewart, MD,in“ImpactofHIVonVision,”providesahistoricalperspectiveofAIDSandtheeyeaswellasacomprehensivediscussionofcurrentcausesofvisionlossinHIVpatientssincetheintroductionofanti-retroviraltherapy(HAART).

It ismyhopethatafterreadingthisOphthalmologyissueyouwillnotonlybeabletospell“ophthalmology”correctly(everyoneleavesoutthefirst“h”),butwillhaveabetterunderstandingofsomethemorecommonocularconditionsaffectingyourpatients.

Note: See a related Trends in Public Health article on page 8 entitled “Vision Screening in Duval County.”

Janet A. Betchkal, MDThe Gilbert Cataract CenterJacksonville, FL


Ocular Signs of Non-ocular Cancer in Children and AdultsDavidA.Kostick,MD,FACS

AddressCorrespondenceto:DavidA.Kostick,MD,FACS,MayoClinic, Department of Ophthalmology, 2-West Davis Building,4500SanPabloRoad,Jacksonville,Florida32224.Email:[email protected].

Abstract: Systemic malignancies may cause a variety of ocular symp-toms, resulting from either direct invasion of ocular tissue by the tumor cells or by secondary phenomena related to tumor-induced pathological processes. Both ophthalmologists and non-ophthalmologist should be aware of the clinical findings during the ophthalmic evaluation that may suggest systemic malignancies.

IntroductionCicero(106-43B.C.)isquotedassaying,“Ut imago est

animi voltus sic indices oculi”…Theface isapictureof themindastheeyesareitsinterpreter.Thetopicofthispaperisanexampleofthisgeneralization.Manysystemicmalignan-ciesmayproduceocularmanifestations,eitherfromdirectinvasionofthetumororfromcomplexneuro-physiologicresponses.1Thisarticlewillhelpophthalmologistsandnon-ophthalmologistsrecognizefindingsduringtheophthalmicevaluationthatmaysuggestunderlyingsystemicmalignancyineithertheadultorthepediatricpatient.

Eyelid FindingsAn“S-shaped”eyelidasshowninFigure 1suggestsalacri-

malglandfossatumor.Themostcommonmalignancyinthisareaislymphomawhichhasatypicalappearanceoneithercomputedtomography(CT)ormagneticresonanceimaging(MRI).2Theoblongmassconformstothesurroundingstruc-tureswithoutsofttissueorbonedestruction.Thelymphomamaybelocalizedorsystemic.Toconfirmthediagnosisatissuebiopsyisrequired.Dependingonthelocationsinvolvedwithlymphoma,thelacrimalglandfossalesionmaybethebestchoiceforobtainingtissuetobiopsy.

Periocularlesionsarecommonfindings.Theriskofma-lignancyisgreaterifthelesiondisplaystheclassictriad:lossoflashes,lidmargindestruction,andincreasedvascularity(Figure 2).Basalcellcarcinomaisthemostcommonmalig-nancyoftheeyelid.It israreforabasalcellcarcinomatobeassociatedwithsystemicdisease.However,ifpresentinapatientunderageof30yearsold,thentheNevoidBasalCellCarcinoma(Gorlin’ssyndrome)shouldbeconsidered.3Thepalmsofthesepatientsshouldbecarefullyinspectedbecauseapproximately80%willhavepalmarpitsorcysts.Anothercommonfeatureisodontogeniccysts.Itisalsoimportanttorememberthatbraincancer(medulloblastoma)mayoccurin1-4%ofpatientswithGorlin’ssyndrome.4

Signetcellcarcinoma(Figure 3) willoftenhavesimilarclinical findings of basal cell carcinoma, but, if present,requiressystemicevaluationforadenocarcinomaelsewhere.5

Another exampleof eyelid lesions indicatinga systemicmalignancy is the Muir-Torre syndrome. This autosomaldominantdisorderischaracterizedbysebaceousglandtumorsthatareassociatedwithgastrointestinalmalignancies (Figure 4).6 Ifmultipleperiocularsebaceous-appearinglesionsarepresent,abiopsyshouldbeperformedtoexcludelocalseba-ceousglandcarcinoma.Inaddition,referralforevaluationofpossiblevisceralmalignanciesisindicated.6,7,8

Figure 1

A. “S-Shaped” eyelid in patient with left lacrimal gland fossa lesion.

B. CT scan show-ing enlarged lacrimal gland with oblong mass conforming to adjacent structures. Biopsy of lesion proved to be lymphoma.

Figure 2

Clinical photograph showing basal cell car-cinoma involving the margin of the left lower eyelid. Note: triad of irregular eyelid mar-gin, loss of lashes, and increased vascularity (arrow).

Figure 3

Photograph of specimen showing multiple “sig-net cells”. (H&E stain)

Figure 4

Muir-Torre Syndrome: multiple periorbital sebaceous adenomas (white arrows) in a pa-tient with known colon cancer.

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Xanthelasmaarecommonperiocularlesionsthatcanbeassociatedwithsystemichypercholesterolemia.Thesebenignlesionsarecharacterizedbytheiryellowcolor,sharplydemar-catededge,consistentthicknessandrelativelysmoothsurface.However,notallyellowperiorbitallesionsarebenign.Iftheyellow lesionhas anodular-like appearancewith irregularthickness and texture, then necrobiotic xanthogranuloma(NXG)shouldbeconsidered.1TheseNXGlesionsareoftenassociatedwithasystemicdysproteinemiasuchasmultiplemyeloma.9Oncethediagnosisisestablished,evaluationforhe-matologicmalignancyandlife-longfollow-upisindicated.9,10

Paraneoplastic SyndromeAbitemporalquadrantvisualfielddeficitsuggestsalesion

inthepituitaryglandfossaarea;anexampleofdirectinvolve-mentofatumorintothevisualpathways.However,thereareseveralunusualneurologicdisordersthathavesymptomsand/orclinicalfindingsanatomicallyunrelatedtothesiteofthetumor.Thesuspectedmechanismsinthese“ParaneoplasticSyndromes” are auto-immune and antibody abnormali-ties.11,12 Thesecomplexneurophysiologicresponsestothecancermayinvolvetheretina,visualpathwaysand/orbrainstem.11-15Multipletumortypeshavebeenreportedincludinglung cancer and melanoma.11-15 Paraneoplastic syndromesshouldbeconsideredinanypatientwithunexplainedvisualloss,opticneuropathyand/orocularmotilitydisorderssinceofteninthesesituationsthereisanoccultmalignancy.ThecommonserologicmarkersforparaneoplasticsyndromesarelistedinTable 1.(p.14)

Cancer-AssociatedRetinopathy(CAR)isanexampleofanocularparaneoplasticsyndrome.TheclinicalfindingsinCARincludedecreasedvisualacuity,decreasedcolorperception,andcentralscotomas(blindspots).Fundusfindingsincludearteriolarnarrowing,opticnervepallor,andabnormalpig-mentationoftheposteriorpole.1,11,13

Opsoclonus,unusual,jerkingtypemovementsoftheeye,isanotherexampleofanocularparaneoplasticsyndrome.Ops-oclonushasbeenassociatedwithvariousmalignanciesinclud-ingneuroblastomainchildren.Myasthenia-likesyndromeswithfatigableptosisandstrabismusareanotherexampleofparaneoplasticsyndromesaffectingocularmotility.11-15

Ophthalmic Manifestations of Pediatric Cancers

Leukemiaisthemostcommonmalignancyofchildhood.Whencomparedtoadults,childrenaremorelikelytohaveacuteformsofthediseaseratherthanchronicforms.Fur-thermore,inchildrenacutelymphoblasticleukemia(ALL)ismorecommonthanacutemyelogenousleukemia(AML).OphthalmicmanifestationsofALLinchildrenaremorelikelytohaveintra-ocularandopticnerveinvolvementratherthanorbitalinvolvement.Theseophthalmicmanifestationstypi-callyoccurinpatientswithknownALLdisease.

Pediatric patients who develop recurrence of ALL withophthalmicmanifestationshaveamuchlower5-yearsurvivalrate(21%)comparedtothosewhohaverecurrenceofALL

withoutophthalmicmanifestations(46%).16ChildrenwithAMLcommonlyhaveorbitalinvolvement(versusintra-ocularoropticnerveinvolvement)andthismaybetheinitialpre-sentationofthedisease.17A“chloroma”isagreenish-coloredmassfromprimitivemyeloblastdepositsinAML.18Thismayoccurintheorbitalboneorsofttissues.

Neuroblastomaisthemostcommonmetastaticlesiontotheorbitinchildren.Theageofonsetmayrangefrombirthto16yearswiththeaverageage1.5-3years.Theprimarylesionistypicallyadrenal,retroperitoneal,orfromthesym-patheticganglion.Twentypercentofneuroblastomapatientswillhaveophthalmicfindingsandinapproximately10%ofthesepatientstheophthalmicfindingsrepresenttheinitialpresentationofthedisease.

Facialflushingmayindicatetheabnormalcatecholamineproduction associated with neuroblastoma. The mass ef-fectofthemetastaticlesiontotheorbitalbonemaycauseproptosis,periorbitalecchymosis,andptosis.Indicationoforbitalinvolvementportendsaworseprognosiswitha3-yearsurvivalofapproximately11%.19ThepresenceofHorner’ssyndrome(triadofptosis,miosis,andunilateralanhidrosis)issuggestiveofmediastinalorcervicalsympatheticgangliainvolvementwhichisassociatedwithabetter3-yearsurvivalofapproximately79%.19Asmentionedearlier,opsoclonusisaparaneoplasticphenomenonthatcanoccurinpatientswithneuroblastoma.Sincethefindingofopsoclonusmayleadtoanearlierdiagnosis,the3-yearsurvivalrateisalmost100%inthesepatients.19

SummarySystemicmalignanciesmaycauseavarietyofocularsymp-

toms,resultingeitherfromtumorcellsdirectlyinvadingtheoculartissuesorfromaparaneoplasticresponse.Bothoph-thalmologistsandnon-ophthalmologistshouldbeawareoftheophthalmicfindingsandsymptomsthatmaysuggestanunderlyingsystemicmalignancyastheabilitytodiagnosetheconditionearlyoftenleadstoanoverallincreasedsurvivalrate.

References1. RobertsonDM.Non-cancerousophthalmiccluestonon-

ocularcancer.Surv Ophthalmol.2002;47(5):397-430.

2. JakobiecFA,YeoJH,TrokelSLetal.Combinedclinicalandcomputedtomographicdiagnosisofprimarylacrimalfossalesions.Am J Ophthalmol.1982;94:785-807.

3. GorlinRJ. Nevoidbasal-cellcarcinomasyndrome. Medicine.1987;66(2):98-113.

4. EvansDG,FarndonPA,BurnellLD,GattamaneniHR,BirchJM. TheincidenceofGorlinsyndromein173consecutivecasesofmedulloblastoma. Br J Cancer. 1991;64(5):959-61.

5. LangelDJ,YeattsRP,WhiteWL.Primarysignetringcellcarcinomaoftheeyelid:reportofacasedemonstratingfurtheranalogytolobularcarcinomaofthebreastwithaliteraturereview.Am J Dermatopathol.2001;23(5):444–449.


6. DemicriH,NelsonCC,ShieldsCL,etal.EyelidsebaceouscarcinomaassociatedwithMuir-Torresyndromeintwocases.Ophthal Plast Reconstr Surg.2007;23(1):77-78.

7. Dores GM, Curtis RE, Toro JR, et al. Incidence ofcutaneous sebaceous carcinomaand riskof associatedneoplasms:insightintoMuir-Torresyndrome.Cancer.2008;113:3372–3381.

8. KoCJ.Muir-Torresyndrome:factsandcontroversies.Clinic Dermatol.2010;28(3):324-9.

9. Ugurlu S, Bartley GB, Gibson LE. Necrobioticxanthogranuloma: long-term outcome of ocularand systemic involvement. Am J Ophthalmol. 2000;129(5):651-7.

10. Guo J, Wang J. Adult orbital xanthogranulomatousdisease:reviewoftheliterature.Arch Pathol Lab Med.2009;133(12):1994-7.

11. SolomonSD,SmithJH,O’BrienJ.Ocularmanifestationsofsystemicmalignancies.Curr Opin Ophthalmol. 1999;10:447–451.

12. Braik T, Evans AT, Telfer M, et al. Paraneoplastic

neurologicalsyndromes:unusualpresentationsofcancer:apracticalreview.Am J Med Sci.2010;340(4):301–308.

13. Chan JW. Paraneoplastic retinopathies and opticneuropathies.Surv Ophthalmol.2003;48:12–38.

14. Ray D, Nigam A. Paraneoplastic effects onneurophthalmologic function. Otol Neurotol. 2007; 28:860-2.

15. Leavitt JA. Myasthenia gravis with a paraneoplasticmarker.J Neuro-Ophthalmol.2000;20(2):102-5.

16. Kishiko O, William GT. Prognostic importance ofophthalmicmanifestationsinchildhoodleukaemia.Br J Ophthalmol1992;76:651-655.

17. SharmaT,GrewalJ,GuptaS,MurrayPI.Ophthalmicmanifestationsofacuteleukaemias:theophthalmologist’srole.Eye2004;18:663–672.

18. ZimmermanLE,FontRL.Ophthalmologicmanifestationsofgranulocyticsarcoma(myeloidsarcomaorchloroma).Am J Ophthalmol1975;80(6):975-90.

19. MusarellaMA,ChanHS,DeBoerG,GallieBL.Ocularinvolvementinneuroblastoma:prognosticimplications.Ophthalmol1984;91:936–940.

Antibody Associated Cancer Paraneoplastic SyndromeAnti-Hu Smallcelllung Encephalomyelitis

CerebellardegenerationSensoryneuropathy

Anti-Yo GynecologicBreast

Cerebellardegeneration

Anti-Ri BreastGynecologicSmallcelllung

CerebellardegenerationOpsoclonus-myoclonus

Anti-CV2 Hodgkinlymphoma EncephalomyelitisCerebellardegenerationSensoryneuropathy

Anti-Ma Smallcelllung LimbicencephalitisCerebellardegeneration

Anti-amphiphysin Smallcelllung Stiff-mansyndromeEncephalomyelitis

AVGCC* Smallcelllung Lambert-EatonmyasthenicsyndromeCerebellardegeneration

ACHR** Thymoma MyastheniagravisAVGPC*** Thymoma Limbicencephalitis

*AVGCC = Anti-variable-gated calcium channel

**ACHR = Anti-acetylcholine receptor***AVGPC = Antivariable-gated potassium channel

Adapted from Braik T, “Paraneoplastic Neurological Syndromes: Unusual Presentations of Cancer. A Practical Review”. The American Journal of the Medical Sciences; Volume 340, Number 4, October 2010

Table 1 Paraneoplastic Auto-antibodies and Associated Cancers and Syndromes


Advances in Cataract Surgery: A Review for the Non-ophthalmic Physician

WalterR.Gilbert,Jr.,MD,FACS

AddressCorrespondenceto:WalterR.Gilbert,Jr.,M.D.,F.A.C.S.,GilbertCataractCenter,3ShircliffWaySuite122,Jacksonville,FL32204.Email:[email protected].

Abstract: More than 3 million cataract operations are performed annually in the United States.1 The rapid visual rehabilitation of these patients has been one of the most spectacular achievements of modern medicine. The two developments most responsible for this advance are small incision surgery using phacoemulsification and intraocular lens implants (IOL). This is a review for the non-ophthalmic physician of the advances in cataract surgery in the last few decades.

IntroductionJustfortyyearsagocataractpatientswerehospitalizedfor

5-7days.Theentirecataractwasremovedthrougha12mmsuperiorcorneal-scleralincisionthatrequired6-10suturesandcausedastigmatism.Theeyeswerevulnerabletohemorrhageand/orwounddehiscence.Patientactivitieswererestrictedforweeks.Complicationssuchasretinaldetachment,macularedemaandcornealcloudingwerefarmoreprevalent.Follow-ingsurgery,“best”visualacuitywasachievedwitheitherthickglassesorcontactlenseswhichcausedopticalaberrationsthatoftenprecludedreturningtoanormallifestyle.

Themovetowardsmallincisioncataractextractionbeganwiththeinventionofultrasonicemulsificationandaspirationin1967.2Thetechnologybecamecommerciallyavailablein1970.3However,itwasslowtobeacceptedandwasnotbeingusedbymorethan50%ofcataractsurgeonsuntil1990.4-5Todayitispreferredbyanoverwhelmingmajorityofsurgeonsthroughouttheindustrializedworld.6

Incisionsarenowconstructedtoself-sealsothatsuturesarerarelyneeded,thuseliminatingforeignbodysensations,fluctuatingastigmatismandrefractiveinstability.Thisoutpa-tientsurgeryismostoftendoneundereithertopicalorlocalinjectionanesthesia.7Patientsareoftendischargedwithoutaneyepatchandmayreturntonormalactivitiesin1-2days.

Smallincisionshavealsoreducedoreliminatedtheneedtodiscontinueanticoagulantspreoperatively.Areviewof11,685cataractsurgicalpatientsreceivingsharpneedleorsubtenonanesthesia while taking anticoagulants and/or antiplateletmedications,showednoincreaseinserioussight-threateninghemorrhagiccomplications.8

ThefirstIOLwasimplantedinEnglandin1949andintheUSin1958,butitwasnotuntilafterFDAapprovalin1978thatIOLsmovedintothemainstream.EarlyIOLsweremadeofhardplasticandinsertionrequiredrelativelylargeincisions,negatingsomeofthebenefitsofphacoemulsifica-tion.Soft,foldableIOLusagesurpassedhardplasticIOLsby1998.9SmallincisionswithfoldableIOLsledtothealmostinstantvisualrehabilitationachievedtoday.

Thelastdecadehasbroughtevenmorerefinementsandadvances.Themostsignificantofthesehavebeeninareasofmoreefficientultrasonicenergydelivery,improvedsurgicalcontrolofanteriorchamber(AC)stability,newandmorerefinedmicrosurgical instruments, improvedIOLdesigns,andmoreaccurateIOLpowercalculations.

Advances in Phacoemulsification TechnologyTheenergyforbreakingupcataractsisusuallydelivered

byabluntedtitaniumneedleattachedtoanultrasonictrans-ducer.Theneedletendstobecomehotandiscooledbythecontinuousinflowofsalineaswellasbythemovementofaspiratedfluidandlensemulsionuptheneedleboreandoutoftheeye.Manyadvanceshavebeenmadeinthisultrasonictechnologyoverthelastdecade.Theseincludemodulatingpowerdeliverytoreduceheatandimprovelensaspirationaswellaspreciselycontrollingfluidinflow,outflowandpressuretopreserveACstabilityduringtheoperation.

Modulating Power Delivery–Earlymachinesrancontinu-ouslywhenactivatedbythefootswitchanditwasnecessarytorapidlytapthefootswitchcausinginterruptionsinpowerdeliveryinordertokeeptheneedlecooler.Recentadvancesenablemachinestodeliverextremelyshortdurationpulsesof energy interrupted by extremely brief cooling periods.Thesealternatingperiodsaretypicallyintherangeof30-70msecandthetime“on”totime“off”ratiocanbecustomized(“WhitestarTM”AbbottMedicalOptics)toreduceheating,retaincuttingabilityandimproveflowabilityoflensparticlesintotheneedlebore.Cataractscannowberemovedmoreefficientlybydeliveringlessenergyandminimizingcornealendothelialdamageandtrauma.

Traditionallongitudinalneedlemovementsareinefficientbecausetheyonlycutontheforwardstroke.Forwardstrokestendtorepelorknockawaysmalllensparticleswhichmaydamage the cornea and increase inflammation. Torsional(OzilTMAlconLaboratories)andhorizontalorellipticalneedlemovements(EllipsTMAbbotMedicalOptics)allowcuttinginbothdirectionseliminatingtheinefficiencyofthebackstroke.OzilTMhasbeenreportedtoemulsifyhardnucleimoreef-ficientlythanlongitudinalultrasound.9,10Thesedevelopmentsreduceenergyrequirements,reducerepulsionofparticlesandrequirelesstimethantraditionalultrasound.

Preserving AC Stability–Sensorsthatregulateandcontrolvacuumandaspirationcanbeprogrammedtoreducevacuumuponocclusionoftheneedletipthusminimizingthesuddeninflowor“surge”thatmayoccurwhenanoccludingparticleissuddenlysuckedthroughthesmallneedlebore.ThisreducesthefrequencyofACcollapseandforwardbouncingoftheposteriorcapsule.Thetechnologyimprovesefficiency,lessens

mailto:wrgilbert%40comcast.net?subject=


Figure 1 IOL Implantation(Reprinted with permission from Advanced Medical Optics)

thermaldamage,avoidspost-occlusionsurges,andproducesclearereyes.

Advances in Surgical Instruments and Techniques

Mostcataractsurgeryinthedevelopedworldisnowdonebyphacoemulsificationthroughaself-sealing<3mmtemporalcornealincision.Preexistingastigmatismmayrequirechang-ingtheincisionlocation.Evensmallerincisionsurgeryusesseparateincisions(0.9–1.5mm)foraninfusioncannulaand a sleeveless ultrasonicneedle.11,12Such small incisionsmustbeenlargedtoadmitconventionalfoldableIOLsbutanimplant(AkreosM160AO)hasbeendevelopedtopassthrougha1.8mmincision.Advocatesofthismicro-incisioncataractsurgery(“MICS”)claimbetterACstabilityaswellasreductioninastigmatismandrefractivecornealaberrations.13Thetrendistowardfurtherreductioninincisionsize.

Theopeninginthelensanteriorcapsulehastraditionallybeenmadewiththebenttipofa23-27gaugeneedleorfor-ceps.NewlydevelopedsmallerforcepsandscissorscanentertheACthrough1mmincisionsimprovingchamberstabilityforintraocularmaneuverssuchasiridectomyoririssuturing.

“Viscoelastics”, including hyaluronic acid, chondroitinsulfateandmethylcellulose,aretransparent,clear,jelly-likesubstancesthatnowcomeinavarietyofviscosities.Theyareuseful inprotectingthecornealendotheliumanddeepen-ingtheACfordelicatesurgicalmaneuvers includingIOLimplantation (Figure 1).

Cataractsarebestremovedthroughawidelydilatedpupilfor goodvisualizationof theperipheral lens.Smallpupilsincreasetherisksoftearingthecapsuleoriris.Flomaxandotheralpha-adrenergicblockersarenowknowntocausepoorpupildilationand(possibly)atrophyoftheirisdilatormuscleleadingtoalossofirisrigidity(“floppyiris”)andasignifi-cantlyincreasedriskofirisdamageduringcataractsurgery.

TheMalyugenRing(Figure 2),acollapsibleplasticsquareshaped ring for insertion into the pupil through a smallincisionisnowbeingusedinthese“floppyiris”cases.Itcre-atesa6mmpupil,preventspupilcontraction,andreducescomplications.Pupilsize,shape,andcontractilityareusuallynotpermanentlyalteredbythisdevice.

Advances in Lens Implant DesignInadditiontoultravioletfilteringcapabilityandinjection

systems for inserting IOLs through small incisions, threemajor developments have occurred in the optics of lensimplants.Theseincludetoriclensestocorrectastigmatism;aspheric optic design to improve contrast sensitivity; andmorepresbyopia-correctingIOLstoallowbetternearvision.

Astigmatism Correction – Corneal astigmatismisconsequenttodifferentsurfacecurvaturespresentindifferentmeridians.Theglobeisnotaperfectsphere,causinglighttoberefracteddifferentlyindifferentmeridians.Astigmatismcausesblurringbecauseraysoflightarenotbroughttoasinglefocalpointontheretina.Itcanbecorrectedbyglasses,contactlensesor

refractivesurgery.AveryeffectivetoricIOL(differentcurvesindifferentmeridians)hasbeendevelopedbyAlconLabora-tories.14,15Itmaintainspositionintheeyebetterthanpriortoricimplants.Althoughitcannotalwayscompletelycorrectpre-existing corneal astigmatism, it improves uncorrectedvisionbetter thanother IOL types. It ismorepredictablethancornealsurgeryforcorrectingastigmatismandrequiresnoadditionalincisions.Patientsseebetterandrequirelessopticalcorrectionpostoperatively.

Aspheric Optics–Thenormalcorneabendsparallelraysoflightenteringitsperipherytoashorterfocallengththanraysoflightenteringitscenter.Thisphenomenonisknownaspositivesphericalaberration.Itcandecreaseimagequalityandreducecontrastsensitivityparticularlyindimlightingconditionswhenthepupildilates.Thecrystallinelensofayoungpersonnormallyoffsetsthiscornealeffectwithnega-tivesphericalaberration(bendingperipheralraystoalongerfocallengththancentralrays).AstandardsphericalIOLhaspositivesphericalaberrationandaddstothetotalsphericalaberrationoftheeye.Asphericlensimplantshavenegativeorneutral spherical aberrationand reduceoverallpositivespherical aberration in the eye.Visualbenefits fromthesecan be shown by contrast sensitivity testing.16,17,18 Theseaspheric implants accounted for70%of implanted lensesinarecentsurvey.19

Figure 2 Malyugen Ring(Reprinted with permission from Advanced Medical Optics)

Lens implant placed within the capsule of the natural lens

Pupil dilated by a Malyugen plastic ring in phacoemulsification cataract surgery


Presbyopia Correction –Thelensisfocusedatdistancewhentheeyeis intherestingstate.Itcanquicklyre-focusonanearobjectbychangingitsshapeandmovinganteriorlyinresponsetocontractionoftheciliarymuscle,called“accom-modation”.Patientslosetheabilitytoaccommodateandstartrequiringreadingglassesatapproximatelyage43,aprocessknownaspresbyopia.

Byage72,theaverageageofcataractsurgerypatientsintheUS,thepatienthaslostalmostallabilitytoaccommodate.Presbyopia-correctingIOLshavebeengaininginpopularitysincethefirstmultifocalIOLwasFDAapprovedin1997.TheFDAapprovedpresbyopia-correctingIOLsfallintothreebasictypes:refractivemultifocal;diffractivemultifocal;andaccommodatingIOLs.

Refractive Multifocal IOLsThemostpopularofthisgrouphavebeenthefirstgenera-

tionsiliconeAMOArrayTM(1997)andthesecond-generationrefractivehydrophilicacrylicAMOReZoomTM(2005).TheopticoftheArrayTMlensisdesignedsothat4differentopticalzonesarearrangedwithinthecentral4.7mmofthe6mmlensas4concentricringsaroundasmallcentralzonepoweredfordistance.Thefirstandthirdsurroundingringsarefornearwhilethesecondandfourtharefordistancecausingvisualfunctiontobedependentuponpupilsize.

ThezonalrefractiveringsoftheArrayTMweremodifiedintheReZoomTMinanefforttoreduceglareandimprovenearvision.FDAstudiesshowthateyeswitheitheroftheselenseshaveequallygooddistantvisionandmuchbetterreadingvi-sionthaneyeswithstandardmonofocalIOLs.Theresultislessspectacle(glasses)dependenceandhighlevelsofpatientsatisfaction.20,21Patientsmustacceptsomehalosandglare,reported by >50% of patients, in exchange for improvedreadingability.Aftersixmonthsfewerthan10%ofpatientsstillwerebotheredbyglare.20,21

Diffractive Multifocal Lens ImplantsThetwomostpopulardiffractivemultifocallensesintheUS

aretheAlconReSTORTMandtheAMOTechnisZM900TM.The ReSTORTM is a single piece hydrophyllic acylic lenswitha3.7mmcentralringeddiffractivezonecontaining12ringsonthefrontsurface.InanFDAtrial,80%ofpatientsbilaterallyimplantedwiththislensachievedtotalspectacleindependence(versus20%withstandardmonofocalIOLs)and96.9%saidtheywouldhavethesamelensagain.22

TheTechnisZM900TM,anasphericsiliconelenswith36concentricdiffractiveringsontheposteriorsurface,islesspupilsizedependentthantheReSTORTM.Bothoftheselensestendtogiveexcellentreadingvisionwhichisusuallybetterthanthatachievedwiththerefractivemultifocals.Reportsonintermediatevisionvaryfromequivalenttonotasgoodaswiththerefractivemultifocals.23,24Halosandglarearepres-entwithdiffractivejustaswiththerefractivemultifocalsandreportscomparingthetwomultifocaltypesareatvarianceastowhichstyleproducesfewerphoticphenomena.24,25Patientsmustbewillingtotoleratesomeglareandreducedcontrastsensitivityforenhancedreadingability.

Accommodating Lens ImplantsAlthoughotherIOLsarebeingimplantedabroad,theonly

accommodatingFDA-approvedIOLtodateisthesiliconeCrystalensTM,(Eyeonics)witha5mmopticwhichis1mmsmallerthanthe6mmopticonmostotherlenses.Ithastwosolidsiliconeplatehapticsforfixationinthecapsularbag.Theseextendoutfromtheoptictogiveitan11.5or12mmoveralllengthdependentuponthepowerrequired(longerimplantforthelargernear-sightedeyes).Eachofthesiliconeplatehapticsisscoredbyatransversegroovethat“hinges”thehapticallowing the lens tomoveposterior toanteriorinsidetheeye.Whenthelensopticmovesforwardtowardthecorneawithciliarymusclecontraction,itseffectivepowerincreasesmakingittruly“accommodating”.However,stud-iesofforwardmovementhavegenerallynotshownsufficientmovementtoallowforreadingatthemostpopularreadingdistances.26,27ThisisespeciallytrueforlowerpoweredlenseswhichmustmovefartherthanhigherpoweredIOLstoachieveacomparableopticaleffect.

Thisaccommodativeeffectmightbeachievedbyanincreasein anterior curvatureof the IOLwith ciliary contraction,socalled“accommodativearching”.ThereisnoconsensusabouthowtheCrystalensTMworks.However,FDAstudieshaveshownthatthesepatientsdoreadbetterthanthosewithstandardmonofocalIOLs.28Theyusuallyhavegoodinter-mediatevisionbutnearreadingvisionlagsbehindthosewithmultifocals.UnlikemultifocalIOLs,theCrystalensTMrarelycauseshalosorglare.

AlthoughnoIOLcanapproachtheopticalperformanceofthenaturalcrystallinelensinahealthyyoungeye,thesenewdevelopmentsareallowingmorepatientstobeless-spectacledependentthaninthepast.

Advances in Lens Implant Power CalculationsRefractiveoutcomedependsonpreoperativeIOLpower

selection.This requires accuratemeasurementofboth theopticalpowerofthecentral3mmofthecorneaandoftheaxiallengthoftheeye(corneatoretina).Thesepowermeasure-mentshavebeenautomatedandcomputerizedinrecentyearstoproducemoredatapointsandeventoproduceelaboratedetailedmapsof thecorneal surface (corneal topography)leadingtogreateraccuracy.

Errorsof0.5mminaxiallengthmayresultinpostoperativerefractiveerrorsupto1.4diopters.Untilrecently,axiallengthwasmeasuredwithultrasoundwhichrequiredcornealcontact,waslessreproducible,andmoreoperator-dependentthananewertechnique,partialcoherenceinterferometry.Itrequiresnophysicalcontact,iseasyforthepatient,isoperator-friendlyandtheresultsarehighlyreproducible,makingitpossibleforophthalmologistsallovertheworldtocompareresults.

ThemajordifficultywithIOLpowercalculationsisthatthedistancefromcornealsurfacetoIOL,criticalfordeter-miningaccuratepoweroftheIOL,cannotbedeterminedpreoperatively.Statisticalaveragevaluesandothermeasure-mentswhichcorrelatewithandhelpustopredictthisdistance


(such as axial length, corneal diameter, and preoperativeACdepth)areemployed.Adeviationfromexpectedof0.5mmincornealtoIOLdistancecanresultina1.25diopterpostoperativerefractiveerror.

ThemathematicalformulasforpredictingrequiredIOLpower have been replaced by empirical linear regressionformulasusingconstantsderivedfromlargecaseseries.Evenwithcurrentpredictionaccuracy(error<0.5diopter),10%ofeyeshaveresidualrefractiveerrors>1diopter.29Theseeyes,aswellassomeofthosehavingrefractiveerrorsbetween0.50and1.00diopter,willneedglassesiftheydesiretoobtain“best-corrected”distancevision.Allpatientscannotexpecttoseewithoutglassesaftercataractsurgery.Ifbeingfreeofglassesisthegoal,refractivecornealsurgerymayberequiredafterthecataractoperation.

Laser Cataract SurgeryMuchexcitementtodayisbeinggeneratedinophthalmol-

ogybytalkof“lasercataractsurgery”.Lasercataractsurgeryismisleadingterminologybecauselaserscannotremovecataracts.The excimer laser canbeused tomake surgical excisions,anteriorcapsulotomies,andtobreakuporsoftencataractsinpreparationforsurgicalremoval.However,usingthelasertoperformtheseportionsofthecataractsurgerydoesnoteliminateatriptotheoperatingroom.30,31,32,33

ConclusionSmallincisionsurgeryandlensimplantshavebeenthetwo

mostimportantdevelopmentsofmoderncataractsurgery.Patientstodayhaveoutpatientsurgery,usuallywithoutastitchorpatch,andmayreturntoworkin1-2days.Improvementsinultrasonictechnologyandfluiddynamicsaswellasmorerefined surgical instruments, have enabled cataracts to beremovedwith lessenergy, lessheatproduction,betterACstabilityandgreatersafety.

ContinuingimprovementsinIOLshaveincludedasphericlensesaswellasnewermultifocalandaccommodatinglensimplantswhichimprovetheabilitytoreadwithoutglassesandlessenspectacledependence.Theresultoftheseadvancesisthatcataractsurgeryismoresafeandeffectivetodaythaneverbefore.

References1. LeamingD.Highlightsofthe2008ASCRSmemberpractice

stylesurvey.www.leamingsurveys.com.AccessedApril2008.

2. Kelman C D. Phacoemulsification and aspiration; a newtechnique of cataract removal: a preliminary report. Am J Ophthalmol.1967;64:23-35.

3. KelmanCD.Thegenesisofphacoemulsification.Cataract & Refractive Surgery Today.2004;4:57-58.

4. LeamingDV.PracticestylesandpreferencesofASCRSmembers–1985survey. J Cataract Refract Surg. 1986;12:380-384.

5. LeamingDV.PracticestylesandpreferencesofASCRSmembers1990survey. J Cataract Refract Surg. 1991;17:495-502.

6. Jaycock P, Johnston RL, Taylor H, Adams M, et al. TheCataract National Dataset electronic multi-centre audit of55,567 operations: updating benchmark standards of care

in the United Kingdom and internationally. Eye. Advanceonline publication. November 23, 2007; doi:10.1038/sj.eye.6703015.www.medscape.com/viewarticle/587071.AccessedJanuary2009.

7. El-HindyN,JohnstonRL,JaycockP,et.al.TheCataractNational Dataset electronic multicenter audit of 55,567operations: anesthetic techniques and complications. Eye. 2009;23:50-55.

8. BenzimraJD,JohnstonRL,JaycockP,etal.TheCataractNational Dataset electronic multicenter audit of 55,567operations:antiplateletandanticoagulantmedications. Eye. 2009;23:10-16.

9. Leaming D V. Practice styles and preferences of ASCRSmembers 1998 survey. J Cataract Refract Surg. 1999; 25:851-859.

10. ZengM.LiuX,LiuY,etal.Torsionalultrasoundmodalityforhardnucleusphacoemulsificationcataractextraction.Br J Ophthalmol. 2008;92:1092-1096.

11. AgarwalA,AgarwalA,AgarwalS. et al.Phakonit:phaco-emulsificationthrougha.9mmcornealincision.J Cataract Refract Surg.2001;27:1548-1552.

12. WeikertMP.Updateonbimanualmicroincisionalcataractsurgery.Curr Opin Ophthalmol.2006;17:62-67.

13. Denoyer A, Denoyer L, Marotte D, et al. Intraindividualcomparativestudyofcornealandocularwavefrontaberrationsafterbiaxialmicroincisionversuscoaxilsmall-iincisioncataractsurgery. Br J Ophthalmol.2008;92:1679-1684.

14. MendicuteJ,IrigoyenC,AramberriJ,etal.Foldabletoricintraocularlensforastigmatismcorrectionincataractpatients.J Cataract Refract Surg.200834:601-607.

15. Bauer NJ, deVries NE, Webers CA, et al. Astigmatismmanagement in cataract surgery with the AcrySof toricintraocularlens. J Cataract Refract Surg. 2008;34:1483-1488.

16. KershnerRM.Retinalimagecontrastandfunctionalvisualperformancewithaspheric,silicone,andacrylicintraocularlenses.Prospectiveevaluation.J Cataract Refract Surg.2003;29:1684-1694.

17. Shentu X, Tang X, Yao K. Spherical aberration, visualperformanceandpseudoaccommodationofeyesimplantedwith different aspheric intraocular lens. Clinical andExperimentalOphthalmol. 2008;36:620-624.

18. BellucciR,ScialdoneA,BurattoL,etal.VisualacuityandcontrastsensitivitycomparisonbetweenTecnisandAcrySofSA60ATintraocularlenses:Amulticenterrandomizedstudy.J Cataract Refract Surg.2005;31:712-717

19. Harmon D, Thomas D. “Market Scope”, The Ophthalmic Surgeon’s Quarterly Survey Report.September30,2010,p.14.

20. Steinert RF, Aker BL, Trentacost BS, et al. A prospectivecomparative studyof theAMOARRAYzonal-progressivemultifocal silicone intraoculaar lens and a monofocalintraocularlens.Ophthalmology.1999;106:1243-1255.

21. MesterU,HunoldW,WesendahlT,KaymakH.Functionaloutcomes after implantation of Tecnis ZM900 and ArraySA40multifocal intraocular lenses.J Cataract Refract Surg. 2007;33:1033-1040.

22. Davison, JA. Managing Cataract Patients’ RefractiveExpectations:SixAreas toEmphasize forSuccess.Cataract Refract Surg Today.March2006;3:71-78.

http://www.leamingsurveys.com

http://www.medscape.com/viewarticle/587071


23. Lane,SS,MorrisM,NordanL,etal.Multifocalintraocularlenses.Ophthalmol Clin N Am.2006;19:89-105.

24. CillinoS,CasuccioA,DiPaceF,etal.Oneyearoutcomeswithnew-generationmultifocalintraocularlenses.Ophthalmology. 2008;115:1508-1516.

25. GoesF.VisualresultsfollowingimplantationofarefractivemultifocalIOLinoneeyeandadiffracivemultifocalIOLinthecontralateraleye.J Refract Surg.2008;24:300-305.

26. Findl O, Leydolt C. Meta-analysis of accommodatingintraocularlenses.J Cataract Refract Surg. 2007;33:522-527.

27. MenapaceR,FindlO,KriechbaumK,Leydold-Koeppl,Ch.Accommodatingintraocularlenses:acriticalreviewofpresentandfutureconcepts.Graefe’s Arch Clin Exp Ophthalmol. 2007;245:473-489.

28. OlsenT.Calculationofintraocularlenspower:areview.Acta Ophthalmologica Scand. 2007;August85(5):472-85.

29. Alio JL,PineroDP,Plaza-PucheAB.VisualoutcomesandOptical Performance with a Monofocal Lens and a NewGenerationSingle-opticAccommodatingIntraocularLens.J Cataract Refract Surg.October2010;36(10):1656-64.

30. Nanevicz TM, Prince MR, Gawande AA, Puliafito CA.Excimerlaserablationofthelens.Arch Ophthalmol.1986;104:1825-1829.

31. MaguenE,MartinezM,GrundfestW,etal.Excimerlaserablationofthehumanlensat308nmwithafiberdeliverysystem.J Cataract Refract Surg.1989;15:409-414.

32. Dodick JM, Sperber LTD, Lally JM. Neodymium YAGlaserphacolysisofthehumancataractouslens(letter).Arch Ophthalmol. 1993;111:903-904.

33. Kanellopoulos AJ, and the Photolysis Investigative Group.LaserCataraactSurgery:Aprospectiveclinicalevaluationof1000consecutivelasercataractproceduresusingtheDodickphotolysisNd:YAGsystem.Ophthalmology.2001;108:649-655.

Student Athletic Screenings

The DCMS needs YOUR help with the

Share your expertise at the JSMP Athletic Screenings

Saturday, August 6 – high school boys and middle and high school girls

Saturday, August 13 – middle school boys

Nemours Children’s Clinic & Wolfson Children’s Hospital

JSMP coordinates free pre-participation athletic screenings for student-athletes in Duval County. Primary care physicians, orthopedic surgeons, cardiologists, pulmonologists, other medical specialists, physician assistants, and allied health professionals participate in the screenings. Physician and PA volunteers are coordinated through the DCMS.

These screenings are provided at no charge to student athletes, most from homes with limited means, and are not intended to replace annual physical exams performed by pediatricians and primary care physicians. Follow up care with individual physicians is encouraged when screenings indicate potential problems which may impact the athlete’s participation in sports activities.

Want to Help?Watch your email or fax for

registration forms, visit our website, or contact Barbara Braddock at [email protected]

or 355-6561 ext. 107.

3rd Annual Quality & Safety Forum Attracts 160 Participants

Over160participantsattendedthe3rdAnnualQuality&SafetyForumonTheEnginesofExcellence:Professional-

ism,Collaboration&Leadership,attheUniversityofNorthFloridaUniversityCenter,April26,2011.

KeynoteaddressesweregivenbyJoShapiro,MD,FACSandDavidPryor,MD.Dr.Shapiro,Director,Center for Professionalism and

PeerSupportatBrigham&Women’sHospitalinBoston,MA, focusedon the importanceof professionalism.Dr.Pryor,ChiefMedicalOfficerforAscensionHealth,spokeaboutleadershipandthecreationofacultureofexcellence,qualityandaccountability.

TheforumwassponsoredjointlybytheCenterforGlobalHealthandMedicalDiplomacyattheUniversityofNorthFlorida and Duval County Medical Society. The photoaboveshows(LtoR)YankD.Coble,Jr.,MD,DirectoroftheCenterandCapt.LynnWelling,MD,CommandingOfficeratNavalHospitalJacksonville.


The History of Refractive Surgery: Past, Present and Future JerryW.Maida,MD,MBA

AddressCorrespondenceto:JerryW.Maida,MD,MBA,Direc-tor–MAIDACustomVision,11945SanJoseBlvd.,Suite102,Jacksonville,FL32223.Email:[email protected].

Abstract: Scientists have been trying to understand the basis for refractive errors since the time of Leonardo DaVinci. Now, with the latest innovations, over a period of fifty years, myopia, hyperopia and astigmatism can be treated with safety and predictability using lasers. Presbyopia, the last great challenge, is on the brink of being conquered. Extensive research has provided invaluable refinements and advance-ments of laser technology and diagnostic tools to develop safe and appropriate treatment options for patients with a myriad of refractive disorders. Laser-assisted in situ keratomileusis (LASIK) is presently the most performed elective procedure in the modern world. This review will discuss the history of refractive surgery, past and present technologi-cal advances, surgical procedures, risks, complications and the future of refractive surgery.

Introduction Thefunctionofanormalcornea is to refract incoming

light raysonto theretina. Inamyopic (near-sighted)eye,lightraysarefocusedinfrontoftheretinacausingblurringatadistance,whereasinahyperopic(far-sighted)eye,thelightraysarefocusedbehindtheretinacausingblurringatclosedistance.Duringthelasthalfcentury,severallaserandnon-laserrefractiveprocedureshavebeenexperimentedwithand developed to correct these vision abnormalities. Theproceduresthatweredevelopedthroughtheyearschangetheshapeofthecorneatofocuslightrayssharplyontheretina.Inmyopia,correctionisachievedbyflatteningthesurfaceofthecornea,whileinhyperopiathecornealsurfaceissteepened.

History of Refractive SurgeryThefirstpersontoutilizeincisionalsurgerytocorrectam-

metropia(refractiveerror)wasHjalmarSchiotzin1885.1Inthe1940s,TatsuhikoSatoattemptedtorefinehistechnique.1In1948,JoseBarraquerofBogotá,Colombia,consideredbymanytobethefatherofrefractivesurgery,firstperformedcorneal lamellar surgery to reshape thecornea.1Barraquerremovedaportionofthecornea,frozeandreshapeditinalathe,andthensuturedittotheeyewithveryfinesutures,theprecursor toLASIK surgery.Few surgeonsother thanBarraquerwereabletomasterthattechnique.Today,laserswithaccuracytoamillionthofaninch,replacethelatheandtheneedforsutures.

Inthe1970sand1980s,therewasarapidinfusionofnewtechnologies for treating refractive errors including radialkeratotomy(RK).SlavaFyodorovofRussiadevelopedRK,aprocedureinwhich4to16equallydistancedincisionsweremadeintotheanteriorcorneaatadepthofapproximately90%leavingaclearcentralzone.2Fyodorovnoted,aftertreatingamyopicboywhohadanaccidentalcornealpenetratinginjury,thatwhenthecorneahealed,nearsightednesswascorrected.

In1978,theprocedurewasintroducedintotheU.S.andfirstperformedbyLeoBoresinSantaFe,NewMexico.3

During the1980s, therewas a revolutionary change intreatmentof refractive errorsdeparting from incisional tolaser-assisted refractive surgery with the inception of ex-cimerlasertechnology.Argonlasershadbeenusedtotreatglaucomaand retinaldisorders and theneodymiumYAGlasertotreatpost-cataractsurgicalcomplications,butlasershadneverbeenusedtotreattheclear,transparentcornea.In1983,StephenTrokelutilizedtheexcimerlasertoablate(vaporize) corneal tissue.4 Argon and fluoride gases mixcreatinganunstablebondcalledan“exciteddimer”–hencetheacronym,Excimer laser–thatreleasesUVlightinthe193nmspectrum.Unlikeotherlasers,itdoesnotpenetratethecorneaorhaveanythermalaffects.Itseparatesthebondsthat hold the corneal cells together with sub-micrometerprecisionremoving0.25micronsoftissuewitheachpulse.Itissoprecisethatitcanetchacleanpatternintoahumanhair(Figure 1). Thefirststudieswiththeexcimerlaserwereperformedbyphoto-chemist,R.Srinivasan,atIBM.Hewasexperimentingwithexcimerlaserstoetchplasticsandrealizedthatfinecutscouldbemadeintoahumanhair.4Sinceheappliedforthefirstpatent,mostlasercompaniesmustlicensethistechnologyfromIBM.5

SummitTechnologyandVISXalsohadpatents,sotoresolvelawsuitsoverthepatents,theyformedPillarPointPartnershipwhichsub-licensesthetechnologytoophthalmologists.Tothisday,refractivesurgeons,evenaftertheyhavepurchasedanexcimerlaser,arerequiredtopayaroyaltyfee,i.e.,aperusefeeforeacheyethatistreated.5

TheoSeiler,aphysicistandophthalmologistfromBerlin,Germany,whosecoursethisauthorattendedinearly1989,performedthefirstexcimerlasertreatmentonablindeyeinthemid-1980s.6Thiswasfollowedin1988intheU.S.byMargueriteMcDonaldwhoperformedthefirsttreatmentonasighted-eyewithmyopia.7FDAtrialsbeganafewmonthslater.In1989,thisauthor,participatinginanFDAstudy,

Figure 1 Laser Pattern in a Human Hair(Reprinted with permission from Slack Incorporated)

Citation: Krueger, RR, Rabinowitz, YS and Binder, PS. The 25th Anniversary of Excimer Lasers in Refractive Surgery: Historical Review.

The Journal of Refractive Surgery. 26(10):749-760.

[email protected].


performedthefirstexcimerlaserprocedure(forglaucoma)inFlorida.

Photo Refractive Keratectomy

Michael Gordon performed the first Photo RefractiveKeratectomy(PRK)8procedureintheU.S.withtheSum-mitExcimerLaserin1989.8InPRK,theanteriorsurface(epithelium),isremovedandthentheexcimerlaserremovesBowman’smembraneandafewmicronsofanteriorstroma(dependingonthedegreeofmyopia).Inthoseearlyyears,refractive surgeons were not aware of the importance ofpupil size, corneal thickness, curvatureof the cornea,dryeye syndromeor even thedegreeof refractive error.And,inmostcases,theydidnothavethetechnologytoevaluatethoseparameters.

PRKobtainedFDAapprovalfortreatingmyopiainlate1995 (Table 1). It is stillperformed today in10-20%ofrefractivesurgerypatients.

LASIK LaserAssistedIn-SituKeratomileusis(LASIK)iscurrently

thepredominanttypeofrefractivesurgeryintheU.S.,whilePRKismorepopularinsomeEuropeancountries.(See further discussion in later section.)

ConcurrentwiththedevelopmentofPRK,varioustech-niquesnotinvolvingthecornealsurfacewerebeingdeveloped.Barraquer’sthree-hourintralamellarcornealsurgerypreservedthe corneal surface. Luis Ruiz, modified Dr. Barraquer’stechnique by developing a geared automated instrumenttocreateaflapinpreparationfortherefractivesurgery(in-situkeratomileusis).9 Thishand-heldmicrokeratomeusedanoscillating razorblade tomake a lamellar cut into thecornealstroma.

Intheearly1990s,LucioBurattoofItalydescribedatech-niquecombiningthetwotechnologies,i.e.,usingthebladeofthemicrokeratometomakeacornealflap(anadvanceofBarraquer’sworkinthe1950s),withthemicronaccuracyoftheexcimerlasertoremovetissue,10insteadofremovingabuttonofcornealstromaltissuewithablade.IoannisPal-likariscoinedthenameLASIK,whichmeansremovingtissuewithinthecornea.11AnadvantageofLASIKistheavoidance

ofthecornealhazeandpainassociatedwithPRK.Itleavesthecornealepitheliumintact,avoidingthemajorityofnerveendingsandthenecessityforanteriorcornealremodeling.InLASIK,theremovaloftissueiswithinthecornealstroma(intralamellar),sovisionisoftenimprovedthedayofsurgerycomparedtoonetotwoweeksforPRK.

Femtosecond Laser Use in LASIKThehand-heldmicrokeratomeisstillinusetodayfor30-

40%oftherefractivesurgerycasesperformed;however,itisgraduallybeingreplacedbythefemtosecondlaser.LASIKwasapprovedbytheFDAin1999(Table 2, p. 22),althoughithadbeenperformedearlierintheU.S.bysurgeons(includingthisauthorin1996)asanoff-labelprocedure.

Themechanicalmicrokeratomeusesanoscillatingrazorblade that is not as dependable or accurate as the micro-precisionofafemtosecondlaser.Onrareoccasions,itmalfunc-tionsduetolossofsuction,poorbladeoscillationoroperatorerrorresultinginaloose,torn,orperforatedflap,whichcanbesight-threatening.Eventhoughthemicrokeratomewasingeniousandtheriskofperforatingtheeyewaseliminatedwiththeevolutionofthefixedplate,thefemtosecondlaserresolvedmanyofitspotentialcomplications.Duetoitshighcost($400,000and$160/eye),incomparisontothemicro-keratome($30,000andblade$30/eye),anditsinherentearlycomplications,theacceptanceofthefemtosecondlaserhasbeenparticularlyslow.Thefemtosecondlaser,however,rarelyhasproblemswithirregularcutsorperforatedorlooseflaps.

Thefemtosecondlaseristhefastestlaserintheworld,12,13workinginabillionthofatrillionthofasecond.Inthattime,lightwilltravelonly13inches.ThefemtosecondlaserwasfirstutilizedintheU.S.intheearly2000sandinJacksonvillein2003.Thislaseretchesatreatmentplanewithinthecornealstromaatadesireddepthaccuratetowithinafewmillionthsofaninch.Itisnotdependentoncornealcurvature,diam-eterorthickness,anditproducesconsistentflaps.Theearlymodels,duetotheirhighenergylevel,occasionallycauseddiffuselamellarkeratitis(inflammationofthecornealflap)andtransientlightsensitivitysyndrome(TLSS),whicharetreatedwithanti-inflammatoryagents.14,15Theseproblemshavebeenreducedwithadvancesinfemtosecondtechnology.16

Table 1 FDA Approved Lasers for PRK and Other Refractive Surgeries (Adapted from FDA website)

Company & Model Approval Number & Date

Approval Indications (D = diopters)

Summit-Apex&ApexPlus

P93003410/25/95

PRK;Myopiafrom-1.5to-7.0D

VISX-ModelB&C(Star&StarS2)

P9300163/27/96

PRK;Myopiafrom0to-6.0D


LASIK/ PRK Techniques and ImprovementsDuring LASIK, a flap is created with the femtosecond

laserormicrokeratome,andahingeismaintained.Theflapisliftedandtheprogrammedexcimerlaserisfocuseddirectlyontheeye.Theflapisthenrepositionedandheldinplacebythenaturalosmoticgradientandendothelialpumpinherentinthecornea,whichresultsinadetergescentaffect(withoutstitches).Theexcimerlaserhasatrackingdevicetoadjustformicro-saccadiceyemovementsupto200/second.Nomogramsandalgorithmsaredevelopedforthecomputer-driventreat-mentbasedontheindividualsurgeon’stechniqueandtakesintoaccounthumidity,temperature,oxygenconcentration,altitudeandothervariables.Hyperopia,myopiaandastig-matismcanbetreated.

PRKismorepopularthanLASIKinsomeEuropeancoun-tries.EventhoughPRKmaintainstheintegrityofthecorneabyavoidinganystromalcutsasinLASIK,itinvolvesamorecomplexandslowerhealingprocesswithstromalremodeling.VisualrecoveryisslowerandmoreuncomfortablethanwithLASIK.PatientsthathavePRKmustwearabandagelensforseveraldaysandmildsteroiddropsareoftenutilizedfora fewmonths. InPRK,alcoholnowenableseasyremovaloftheepitheliumanddecreasedpost-operativediscomfort.

Although LASIK has virtually replaced PRK, there isstillaplaceforPRKtoday.Itistheprocedureofchoiceforpatientswiththincorneas,potentialirregularitiesinvision,epithelial basement membrane disease and for aviators intheUSmilitaryandsportsfiguresexposedtotraumasincethereisnoflapasinLASIK,therebydecreasingtheriskofcornealrupture.However,LASIKhasnowtakentheworldbystormwithmorethan28millionproceduresperformedworldwidesince1996.17

Manycorneashaveminorirregularitiesthatmaybeexacer-batedbytraditionalrefractiveprocedures.Wavefront-guidedand wavefront-optimized treatments have improved theLASIKandPRKproceduresbyfurtherrefiningthepatient’svisionoftenleadingtoaresultasgoodorbetterthantheyhadwithcontactsorglasses.18,19

Pre-Operative AssessmentNoteveryoneisacandidateforrefractivesurgery.Technol-

ogytomeasurethecurvatureorsubtleirregularitiesinthecornea (corneal topography), the thickness of the cornea(pachymetry),andthepupilsizeindimlight(pupillometry)wasnotavailable10-20yearsago.Thesemeasurementsarecriticaltotheproperpatientselectionandlong-termsuccessoftherefractivesurgery.Cornealtopographyrevealswhichcorneasaretoosteep,flat,orirregular.Surgeryontheseeyesmayleadtoseriouscornealabnormalities5-10years later.Ultrasoundpachymetrymeasurescornealthickness.Surgeryonanexcessivelythincorneacandestabilizetheeyeresultinginkeratoconus.Thefirstexcimerlasersonlytreatedasmallcentralareaofthecorneawithresultantglareandhalosformanypatients.Theseproblemsarenowrectifiedwith theadvancedtechnologiesavailableinthecomputerprogram-mingoftheexcimerlaser.

Tearproduction,whichcandecreasewithageespeciallyinthemenopausalfemale,mustbeassessed.Dryeyesmustbetreatedpre-operativelywithartificialtears,Restasis,orpunc-tualocclusion.Thisproblemisnotsimplyalackoftearing,butoftenamildimmuneorinflammatoryproblem.20Sjorgen’sSyndrome(drymucusmembranes)isoftenacontraindicationalongwithauto-immuneillnessessuchas:Lupus,Hashimoto’s,andRheumatoidArthritis.Patientshavingtheseillnessesneedtobeevaluatedonacase-by-casebasis.Patientswithprevi-ousorconcurrenteyediseasesincludingglaucoma,retinaldetachment,herpessimplex,andkeratitisarequestionablecandidatesfortreatment.Furthermore,therearemedicationsthatcancausecornealmeltingsuchasAcutaneforacneorAmiodaroneforatrialfibrillation,socarefulhistoriesmustbeobtainedfromtheprospectivecandidates.

Goodcandidatesareusuallybetween21and70yearsofageandinrelativelygoodhealth.Thelifestyleofthepatientwillleadthesurgeontopreferoneprocedureoveranother.

Complications As safe as laser refractive surgery is, complicationsmay

stilloccur.Loose,irregularortornflapsareissuesassociatedwiththemicrokeratome.21Intra-operativedifficultieswiththefemtosecondlaserareuncommon,yet,post-operatively,

Table 2 FDA Approved Lasers for LASIK(Adapted from FDA website)

Company & Model Approval Number & Date Approval Indications(D = diopters)

VISX-StarS2

P99001011/19/99

Myopialessthan-14.0DwithorwithoutAstigmatismbetween-0.5and-5.0D

WaveLight-AllegrettoWave

P02005010/07/03

Myopiaupto-12.0DwithorwithoutAstigmatismupto-6.0D

Summit-ApexPlus

P930034/S1310/21/99

Myopialessthan-14.0DwithorwithoutAstigmatismfrom0.5to5.0D

Insert Northeast Florida Medicine Vol. 62, No. 2 2011 1

Impact of HIV on Vision

Background - Benefits that Matter!The Duval County Medical Society (DCMS) attempts to provide its members with the benefits that consistently meet your profes-

sional needs. One example of how this is being accomplished is by providing to DCMS members free Continuing Medical Education (CME) opportunities in the subject areas mandated/and or suggested by the State of Florida Board of Medicine to obtain and retain medical licensure. The DCMS would like to thank the St. Vincent’s Healthcare (SVHC) Committee on CME for reviewing and ac-crediting this activity in compliance with the Accreditation Council on Continuing Medical Education (ACCME). Helena Karnani, MD, Chair of the CME Committee; Betsy Miller, Director, Medical Staff, Quality Management; and Cindy Williamson, CME Co-ordinator, from SVHC deserve special recognition for their work on behalf of DCMS.

This issue of Northeast Florida Medicine includes an article, “Impact of HIV on Vision” authored by Michael W. Stewart, MD (see pp. 3-8), which has been approved for 1.0 AMA PRA Category 1 credit(s).™ For a full description of CME requirements for Florida physicians (MD/DO), please visit the DCMS website (http://www.dcmsonline.org/cme_requirements.aspx).

Faculty/Credentials: Michael W. Stewart, MD, is an Assistant Professor and Chair of the Department of Ophthalmology at Mayo Clinic Florida in Jacksonville, FL. Dr. Stewart received his MD degree from the McGill University School of Medicine after completing an AB degree in chemistry at Harvard University. He did residencies in the Department of Medicine at University of Miami and the Department of Ophthalmology at Emory University. He also did fellowships in vitreoretinal diseases at the Retina Research Founda-tion and the University of California.

Objectives for CME Journal Article1. Understand the major reasons for vision loss in patients with HIV/AIDS2. Understand the treatment options for the most common ocular opportunistic infections3. Know the relationship between HIV activity and likelihood of vision loss

Date of Release: June 3, 2011 Date Credit Expires: June 3, 2013 Estimated time to complete: 1 hr.

Methods of Physician Participation in the Learning Process1. Read the “Impact of HIV on Vision” article on pages 3-8

2. Complete the Post Test and Evaluation on page 2

3. Fax the Post Test and Evaluation to DCMS (FAX) 904-353-5848 OR members can also go to www.dcmsonline.org & submit test online

CME Credit EligibilityIn order to receive full credit for this activity, a minimum passing grade of 70% must be achieved. Only one re-take opportunity will be granted if a passing score is not made on the first attempt. DCMS members and non-members have one year to submit the post test and earn CME credit. A certificate of credit/completion will be emailed, faxed or USPS mailed within 4-6 weeks of submission. If you have any questions, please contact the DCMS at 355-6561, ext. 103, or [email protected].

Faculty Disclosure InformationDr. Stewart reports no significant relationships to disclose, financial or otherwise with any commercial supporter or product manufacturer associated with this activity.

Disclosure of Conflicts of InterestSt. Vincent’s Healthcare (SVHC) requires speakers, faculty, CME Committee, and other individuals who are in a position to control the content of this educational activity to disclose any real or apparent conflict of interest they may have as related to the content of this activity. All identified conflicts of interest are thoroughly evaluated by SVHC for fair balance, scientific objectivity of studies mentioned in the presentation and educational materials used as basis for content, and appropriateness of patient care recommendations.

Joint Sponsorship Accreditation StatementThis activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medi-

cal Education through the joint sponsorship of St. Vincent’s Healthcare and the Duval County Medical Society. St. Vincent’s Healthcare is accredited by the Florida Medical Association to provide continuing medical education for physicians.

The St. Vincent’s Healthcare designates this educational activity for a maximum of 1.0 AMA PRA Category 1 credit(s) .TM Physicians should only claim credit commensurate with the extend of their participation in the activity.

2 Vol. 62, No. 2 2011 Northeast Florida Medicine Insert

Impact of HIV on VisionCME Questions & Answers (Circle Correct Answer) /Free-DCMS Members/$50.00 charge non-members*

(Return by June 3, 2013 by FAX: 904-353-5848, by mail: 555 Bishopgate Lane, Jacksonville, FL 32204 OR online: www.dcmsonline.org)

1. Which of the following is true? a. Microvasculopathy occurs in all AIDS patients b. Retinopathy occurs in all AIDS patients c. Retinopathy occurs in the early stage of HIV infection d. Retinopathy usually causes significant loss of vision 2. An induction/maintenance treatment schedule is used for

each of the following drugs EXCEPT: a. Intravenous ganciclovir b. Intravenous foscarnet c. Ganciclovir implant (Vitrasert) d. Valganciclovir 3. Which of the following is true about valganciclovir? a. It is taken orally b. Venous and tissue drug levels are comparable to those achieved with intravenous ganciclovir c. Major side effects are neutropenia and gastrointestinal disturbances d. All of the above 4. Which of the following drugs has NOT been administered intravitreally? a. Valganciclovir b. Ganciclovir c. Foscarnet d. Cidofovir 5. Which of the following is true about HAART therapy? a. It does not change the immune status in most patients b. It fails to increase the CD4+ lymphocyte counts

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c. It improves immune status without changing the HIV viral load d. It decreased the prevalence of CMV retinitis by 80% 6. For patients receiving HAART, which of the following is true? a. CMV retinitis tends to be more aggressive in patients who are HAART naÏve b. CMV retinitis appears clinically different compared to HAART naÏve patients c. Development of CMV retinitis signifies a greater risk of death than for HAART naÏve patients d. They are more likely to develop CMV retinitis than are HAART naÏve patients 7. Which of the following is true regarding the selection of anti-CMV therapy? a. The ganciclovir implant should be used in all patients b. Valganciclovir is the drug of choice for most patients c. Due to their high complication rates, intravitreal injections should never be used d. Systemic therapy (oral or intravenous) alone is sufficient for all patients 8. Which of the following is true about immune recovery uveitis? (IRU) a. It is caused by the immune system’s recognition of residual CMV DNA with the retina b. It occurs in 15-25% of patients with previous CMV retinitis c. It is usually accompanied by an increase in the CD4+ T-lymphocyte count and a decrease in HIV load d. All of the above


Impact of HIV on VisionMichael W. Stewart, MD

Address Correspondence to: Michael W. Stewart, MD, Assistant Professor and Chairman, Dept. of Ophthalmology, Mayo Clinic Florida, 4500 San Pablo Rd., Jacksonville, FL 32224. Phone: 904-953-2232. FAX: 904-953-7040. Email: [email protected].

Abstract: The human immunodeficiency virus (HIV) and its associated opportunistic infections frequently target the visual system. Cytomegalo-virus (CMV) retinitis, despite an 80% decrease in incidence following the introduction of highly active anti-retrovirus therapy (HAART), remains the most frequent reason for vision loss in AIDS patients. Other major causes of vision loss include cataracts and immune recovery uveitis. Herpetic retinitis (H. simplex, H. zoster), toxoplasma retinitis, pneumocystis choroiditis, and microsporidium keratitis comprise less important causes of vision loss. Optimal care of patients with HIV related vision loss requires the coordinated efforts of both the ophthal-mologist and infectious disease specialist. Treatment of patients requires both reconstitution of the immune system by optimally suppressing HIV replication and targeted therapy for opportunistic infections. Successful reconstitution of the immune system, with elevation of CD4+ lymphocyte counts, enables the discontinuation of CMV therapy in many patients.

IntroductionThe first description of patients with the acquired immu-

nodeficiency syndrome included those with opportunistic infections that resulted in blindness. During the early years of the AIDS epidemic, cytomegalovirus (CMV) retinitis de-veloped in up to 40% of patients. The introduction of highly active anti-retroviral therapy (HAART) reduced the incidence of CMV retinitis by 80% but caused other problems such as immune recovery uveitis. Current causes of vision loss in HIV patients include CMV retinitis, cataracts, immune recovery uveitis with secondary macular edema, epiretinal membranes, and HIV retinopathy. Successful management of HIV patients with co-existing ocular disease requires close communication between the ophthalmologist and infectious disease specialist to coordinate anti-HIV therapy with specific anti-microbial therapy directed against opportunistic infections.

The 1981 reports of 5 homosexual men with unusual opportunistic infections (pneumocystis carinii pneumonia, cytomegalovirus (CMV) infections and candidiasis) ushered in the AIDS era.1,2 A subsequent manuscript that included two additional patients described both a non-infectious, occlusive retinal microvasculopathy and a progressive, necrotizing retinitis due to cytomegalovirus.3 Thus, retinal abnormalities were quickly recognized as the most common HIV-related ocular findings. Over the next 14 years, CMV retinitis af-fected 25%-42% of AIDS patients4,5 and caused more than 90% of HIV-related vision loss. Though CMV retinitis accounted for the majority of vision loss in AIDS patients, other opportunistic infections (Herpes simplex, Herpes zoster, toxoplasmosis and pneumocystis) in the aggregate accounted for substantial ocular morbidity.6

HIV MicrovasculopathyHIV-related microvasculopathy causes histopathological

changes similar to those seen in diabetic retinopathy. Though autopsy studies demonstrate this finding in all AIDS patients,7 only 50% have the retinal hemorrhages and cotton wool spots characteristic of HIV retinopathy (Figure 1).6 Factors responsible for advancement from HIV microvasculopathy to clinical retinopathy remain unknown. However, retinopathy occurs with advanced immunodeficiency, generally with CD4+ T-cell lymphocyte counts <200 cells/µL.8 Though HIV retinopathy usually does not decrease visual acuity, it predisposes patients to CMV retinitis, possibly by altering local blood flow and vascular endothelial integrity, thereby allowing blood borne CMV to access the retina. 9

Cytomegalovirus RetinitisCMV accounts for 99% of HIV-related opportunistic

retinal infections in the United States. CMV enters the eye through the bloodstream and, in contrast with other infec-tious agents, spreads from a single focus. Despite continued viremia, additional seeding of the retina is uncommon.10 In untreated patients without reconstitution of the immune system, CMV retinitis inexorably marches across the entire retina, resulting in full thickness necrosis and total loss of vision (Figure 2).

Figures 1 & 2 HIV Retinopathy and Retinitis

Numerous cot-ton wool spots typical of HIV retinopathy.

Retinitis is progressing from top to bottom: Solid line - areas of necrotic retina following reti-nitis; Dashed line - area of active retinitis; Dotted line - area of normal retina.


Anti-CMV DrugsMost CMV treatment strategies – those including ganciclo-

vir, foscarnet and valganciclovir - begin with a 2-3 week period of high-dose drug administration (induction) to control the infection, followed by an indefinite period of lower dosing (maintenance) to suppress viral replication. Invariably patients experience reactivation of the retinitis, necessitating another course of induction therapy. Generally each subsequent round of maintenance therapy is shorter than the preceding period.

Compared to intravenous ganciclovir or foscarnet, oral valganciclovir is the drug of choice for most cases of CMV rentinitis. Due to its high bioavailability (60%) and not need-ing an indwelling catheter is the primary reason why valgan-cicolir is preferred. Serious and potentially lethal side effects occur with each of the anti-CMV drugs: severe neutropenia (neutrophil count <1000 cells/µL) due to ganciclovir(34%)11 and valganciclovir (16%)12; renal toxicity due to foscarnet (17%-23%) and cidofovir (50%).

The repetitive induction/maintenance/reactivation treat-ment and disease cycle enables the emergence of drug resis-tant CMV. The incidence of viral resistance increases with larger areas of retinitis, increased loss of vision13 and longer duration of therapy (from 2.2% at 3 months to 15.3% at 18 months).14 Though the incidence of viral resistance appears to have dropped in the HAART era, (0.05 cases/patient year)15

some patients will need treatment with foscarnet or cidofovir if resistance to ganciclovir develops.

Intravitreal TherapyWeekly intraocular injections (Figure 3) of ganciclovir

or foscarnet suppress retinitis for periods that range from 8 to 20 weeks.16,17 To eliminate the need for inconvenient weekly injections, the ganciclovir implant (Vitrasert™), a semi-permeable polymer reservoir that steadily releases ganciclovir for 9 months, was developed. (Figure 4, p. 5) Patients with vision threatening zone 1 (near the macula or optic nerve) retinitis benefit most from the implant, as opposed to those with zone 3 (peripheral) disease whose vision results do not surpass standard systemic therapy alone.18 To lessen the in-cidence of contralateral retinitis and non-ocular end organ disease when receiving local therapy, patients are usually given oral (valganciclovir or ganciclovir) or intravenous (ganciclovir, foscarnet, cidofovir) anti-CMV therapy.

HAART and CMV RetinitisThe development of highly active anti-retroviral therapy

(HAART) became a watershed event in the treatment of HIV-infected patients. HAART, defined by the Department of Health and Human Services/Kaiser panel to include pro-tease inhibitors (PI), a non-nucleoside reverse transcriptase inhibitor (NRTI), one of the NRTIs (abacavir or tenofovir), an integrase inhibitor (e.g., raltegravir), or an entry inhibitor (e.g., Maraviroc or enfuvirtide).19 This drug regimen usually clears HIV from the blood, increases the levels of circulating CD4+ T-lymphoctyes and partially restores cell-mediated im-munity. Despite the institution of HAART, however, patients

remain at risk for new opportunistic infections since immune restoration may not occur for at least 3 months.

Following HAART introduction, many centers saw the incidence of CMV retinitis decrease by 80%20 to 5.6/100 person-years (PY).21 This initial decline appears to have leveled off, with new cases continually being reported.20,22

Sixty-nine percent of new CMV retinitis infections occur in patients with HAART failure or persistently elevated HIV titers.10 Most patients with newly diagnosed CMV retinitis have low CD4+ T-cell lymphocyte counts but with greater variability than in the pre-HAART era.10 Though the diagnosis of CMV retinitis indicates HAART failure, the milder ocular disease suggests that HAART beneficially modulates disease severity and vision loss. In patients on HAART therapy with CMV, retinitis recurs less frequently,23 affects contralateral eyes less, and causes fewer retinal detachments.24 Newly di-agnosed retinitis appears similar to that in the pre-HAART era, though the severity tends to be less in HAART-failure patients compared to HAART-naïve patients.10 Despite having less aggressive ocular disease, HAART patients with CMV retinitis, especially those with lower CD4+ T-lymphocyte counts, have an increased mortality rate.

Since the introduction of HAART, the focus of retinitis treatment has shifted from short-term suppression of the acute infection to long-term management of chronic CMV/HIV disease. For patients with newly diagnosed CMV retinitis, the first therapeutic intervention should concen-trate on reconstituting the immune system, since this may permanently suppress CMV retinitis in some patients. For patients already receiving HAART, optimization of the drug regimen should occur as these patients have usually been inadequately treated due to either ineffective medications or non-compliance. For HAART naïve patients, initiation of anti-HIV therapy should be considered, though many infectious disease specialists recommend delaying HAART institution to avoid precipitating acute immune-mediated uveitis. Communication between the ophthalmologist and infectious disease specialist, regarding factors such as location and extent of retinitis, helps balance the risk of vision loss due to retinitis with that due to immune-mediated uveitis. If HAART therapy is deferred in favor of anti-CMV therapy alone, patients must be carefully monitored since they face an increased risk of death during this period.25

Figure 3 Intravitreal Injection of Ganciclovir Through the Pars Plana


When initiating anti-CMV therapy, drug selection depends upon the location of the retinitis and the patient’s HAART status. Unless otherwise contraindicated, oral valganciclovir is the systemic drug of choice for most patients. For patients with zone 1 retinitis – threatening the macula or optic nerve – or HAART failure, intraocular ganciclovir, either in the form of injections or the ganciclovir implant is also recom-mended (Table 1, p.6).

Since CMV retinitis adversely affects patients’ quality of life, prevention becomes increasingly important.26 Prior to the introduction of HAART, more than 90% of vision loss in AIDS patients could be attributed to CMV retinitis.27 In the post-HAART era the longitudinal rates of vision loss among AIDS patients without baseline CMV retinitis are 1.5/100 eye-year (EY) to <20/50 (loss of reading and driving vision), 0.8/100 EY to <20/200 (legal blindness) and 2.1/100 EY for doubling of the visual angle (e.g. 20/30 to 20/60). The rate of vision impairment in patients with newly developed CMV retinitis patients is 21.0 cases/100 EY and of blindness is 8 cases/100 EY, with most of the improvement from the pre-HAART era attributed to improvement in immune status. Over a 3.5 year period, 1.9% of eyes lost vision to < 20/200. Interestingly, even CMV retinitis patients not receiving HAART have lower rates of visual impairment (0.36 cases/100 EY) and blindness (0.16 cases/100 EY) than in the pre-HAART era.28 Much of the vision loss in eyes with CMV retinitis can be attributed to the same factors (zone 1 disease involving the optic nerve or macula, retinal detachment) as in the pre-HAART era.29

Patients who develop CMV retinitis have rates of vision loss 8-10 times higher than those that do not.

Successful immune recovery allows many patients to discon-tinue anti-CMV therapy without rebound CMV reactivation. Long-term studies show that patients with non-sight threaten-ing, quiescent retinitis for 6 months and reconstitution of the immune system may discontinue anti-CMV medications. The decision to stop CMV therapy depends upon many factors: rising CD4+ T-lymphocyte counts, falling systemic HIV loads (preferably to undetectable levels), duration of HAART (at least 3 months) and inactivity of CMV lesions. The United States Centers for Disease Control (CDC) recommends that the CD4+ T-lymphocyte count be at least 100-150 cells/µl

for 3-6 months before CMV therapy is discontinued.30 Most authors, however, require more robust evidence of immune reconstitution (i.e. CD4+ T-lymphocyte counts > 200 cells/µl and a 100-fold drop in HIV blood levels) before discon-tinuing therapy.31,32 Contradicting studies report successful discontinuation of therapy despite HIV blood levels exceeding 30,000 copies/ml.33

The immune-reconstitution inflammatory syndromes, un-seen before HAART, frequently complicate HAART therapy. Though these disorders have been given several names, im-mune reconstitution inflammatory syndrome (IRIS) is the most widely accepted general term34whereas patients with ocular inflammation are said to have immune recovery uveitis (IRU). IRU occurs in 15%-25% of CMV retinitis patients receiving HAART, with the highest incidence between 8 and 16 weeks after initiation of treatment.35

IRU occurs when the recovered immune system, as measured by an increase in the CD4+ T-lymphocyte count, recognizes a large load of residual CMV DNA at the edge of previous retinitis36and then initiates a cell-mediated immune reaction. Patients with low CD4+ T-lymphocyte counts (fewer than 50 cells/µl),37 large areas of CMV retinitis (25%-30% of the retina),38 and a history of cidofovir use39 have the greatest risk of IRU. A small percentage of patients develop IRU without a CD4+ T-lymphocyte increase, suggesting that improved immunity against CMV may occur by some as yet unrecognized mechanism.40,41 CMV DNA in the blood and vitreous specimens of IRU patients becomes undetectable, though rare cases with partial immune reconstitution develop IRU in the presence of persistent CMV retinitis.41

The clinical spectrum of IRU ranges from asymptomatic vitritis, through a persistent uveitis with floaters, decreased vision, cystoid macular edema (12.3x increased risk) and epiretinal membrane (3.7x increased risk) formation.38,42

Infrequent complications include neovascularization, disc edema, proliferative vitreoretinopathy, cataract and posterior synechiae.40 Though some patients experience severe vision loss (20/200 or worse), most patients maintain visual acuities between 20/50 and 20/200.The rate of visual impairment in IRU patients is 0.17 cases/EY and the rate of blindness is 0.06 cases/EY.40

HAART treated patients diagnosed with IRU need to have other inflammatory conditions (syphilis, herpetic retinitis, drug toxicity) excluded. PCR testing of intraocular fluids may help rule out infectious etiologies (CMV, H. simplex, H. zoster, toxoplasmosis).43

The Longitudinal Study of AIDS38 reported a CMV retinitis prevalence of 22%, while other AIDS-related ocular condi-tions, including opportunistic infections, were found in <1% of patients. Of the patients noted to have CMV retinitis, 22% of them were newly diagnosed upon enrollment into the study. Of the patients with CMV retinitis, 59% had CD4+ T-lymphocyte counts >100 and 48% had discontinued anti-CMV therapy following reconstitution of the immune system. Groups both with and without CMV retinitis had

Figure 4 Sustained Release Ganciclovir Implant Sutured to the Pars Plana

(as seen through the pupil)


good (20/20) median and average visual acuities, but patients with CMV retinitis had a higher prevalence of VA worse than 20/40 (23.5%) and worse than 20/100 (14.4%). Patients with other opportunistic infections or non-infectious ocular conditions – such as retinal vein occlusions – had high rates of vision <20/40 (50.9%) and worse than 20/100 (35.1%). Among all AIDS patients, CMV retinitis accounted for 40% of vision loss (<20/200), cataracts were responsible for 25%, and in 10% the reason for vision loss could not be determined.29 Risk factors for vision loss were a low CD4+ T-cell count (<50 cells/µl) and a low Karnofsky (functional ability) score. The use of HAART decreases the incidence of vision loss by 50%, even after excluding patients with infectious retinopathies. CMV retinitis patients had relatively high prevalences of IRU (9.6%), cataracts (20%) and previous cataract surgery (21%).

Other Causes of Vision LossNine percent of AIDS patients have abnormalities in color

vision, contrast sensitivity, visual fields and electrophysiol-ogy sufficient to impair reading. Histopathologic analysis of affected eyes show damaged retinal ganglion cells with loss of optic nerve axons,44 possibly due to the cumulative effect of nerve fiber layer infarctions coupled with prolonged HIV infection. Despite the introduction of HAART therapy, the incidence of this optic neuropathy has not decreased;45 this may account for the unexplained vision loss seen in many AIDS patients.

Most other chorioretinal opportunistic infections (pneu-mocystis, toxoplasmosis, varicella zoster retinitis) also occur with advanced immune deficiency. Opportunistic ocular surface disorders, caused by microsporidium, Kaposi’s sar-coma, Herpes zoster and Molluscum contagiosum, contribute to further visual morbidity. Not surprisingly, the incidence of all these diseases has dropped in the HAART era.21 HIV patients also continue to be plagued by lesser problems such as blepharitis and dry eyes.

ConclusionThe prevalence of vision loss in AIDS cohorts equals

that found in general population-based studies, but when

compared to age-matched populations, AIDS patients have a higher risk of vision loss.46 The introduction of HAART converted AIDS into a chronic disease with many patients surviving more than 15 years. The evolving need for long-term patient management makes controlling ocular complications increasingly important.

References1. Gottlieb MS, Schroff R, Schanker HM, et al. Pneumocystis

carinii pneumonia and mucosal candidiasis in previously healthy homosexual men: evidence of a new acquired cellular immunodeficiency. N Engl J Med. 1981; 305:1425-1431.

2. Masur H, Michelis MA, Greene JB, et al. An outbreak of community-acquired Pneumocystis carinii pneumonia: Initial manifestation of cellular immune dysfunction. N Engl J Med. 1981; 305:1431-1438.

3. Holland GN, Gottlieb MS, Yee RD, et al. Ocular disorders associated with a new severe acquired cellular immunodeficiency syndrome. Am J Ophthalmol. 1982; 93:393-402.

4. Holland GN, Buhles WC, Mastre B, Kaplan HJ. A controlled retrospective study of ganciclovir treatment for cytomegalovirus retinopathy. Use of a standardized system for the assessment of disease outcome. UCLA CMV Retinopathy Study Group. Arch Ophthalmol. 1989; 107:1759-1766.

5. Studies of Ocular Complications of AIDS Research Group in collaboration with the AIDS Clinical Trials Group. Foscarnet-Ganciclovir Cytomegalovirus Retinitis Trial. 5. Clinical features of cytomegalovirus retinitis at diagnosis. Am J Ophthalmol. 1997; 124:141-157.

6. Jabs DA. Ocular manifestations of HIV infection. Trans Am Ophthalmol Soc. 1995; 93:623-683.

7. Pepose JS, Holland GN, Nestor MS, et al. Acquired immune deficiency syndrome. Pathogenic mechanisms of ocular disease. Ophthalmology. 1985; 92:472-484.

8. Kuppermann BD, Petty JG, Richman DD, et al. Correlation between CD4+ counts and prevalence of cytomegalovirus retinitis and human immunodeficiency virus-related noninfectious retinal vasculopathy in patients with acquired immunodeficiency syndrome. Am J Ophthalmol. 1993; 115(5):575-582.

Table 1 Suggested Treatment Strategy for Patients with Newly Diagnosed CMV Retinitis


9. Holland GN. AIDS and Ophthalmology: the first quarter century. Am J Ophthalmol. 2008; 145:397-408.

10. Holland GN, Vaudaux JD, Shiramizu KM, et al. Characteristics of untreated AIDS-related cytomegalovirus retinitis. II. Findings in the era of highly active antiretroviral therapy (1997 to 2000). Am J Ophthalmol. 2008;145:15-22.

11. Walmsley S, Tseng A. Comparative tolerability of therapies for cytomegalovirus retinitis. Drug Saf. 1999; 21(3):203-224.

12. Lalezari J, Lindley J, Walmsley S, et al. A safety study of oral valganciclovir maintenance treatment of cytomegalovirus retinitis. J Acquir Immune Defic Syndr. 2002;30(1):392-400.

13. Jabs DA, Martin BK, Forman MS, et al. Cytomegalovirus resistance to ganciclovir and clinical outcomes of patients with cytomegalovirus retinitis. Am J Ophthalmol. 2003:135:26-34.

14. Boivin G, Gilbert C, Gaudreau A, et al. Rate of emergence of cytomegalovirus (CMV) mutations in leukocytes of patients with acquired immunodeficiency syndrome who are receiving valganciclovir as induction and maintenance therapy for CMV retinitis. J Infect Dis. 2001;184:1598-1602.

15. Martin BK, Ricks MD, Forman MS, Jabs DA. Change over time in incidence of ganciclovir resistance in patients with cytomegalovirus retinitis. Clin Infect Dis. 2007; 44(7):1001-1008.

16. Cochereau-Massin I, Lehoang P, Lautier-Frau M, et al. Efficacy and tolerance of intravitreal ganciclovir in cytomegalovirus retinitis in acquired immune deficiency syndrome. Ophthalmology. 1991; 98:1348-1353.

17. Diaz-Llopis M, Espana E, Munoz G, et al. High dose intravitreal foscarnet in the treatment of cytomegalovirus retinitis in AIDS. Br J Ophthalmol. 1994; 78:120-124.

18. Kempen JH, Jabs DA, Wilson LA, et al. Risk of vision loss in patients with cytomegalovirus retinitis and the acquired immunodeficiency syndrome. Arch Ophthalmol. 2003; 121:466-476.

19. Johns Hopkins School of Public Health, http://statepiaps.jhsph.edu/wihs/Invest-info/Def-haart.pdf. Accessed September 2009.

20. Jabs DA. AIDS and Ophthalmology in 2004. Arch Ophthalmol. 2004; 122:1041-1042.

21. Jabs DA, van Natta ML, Holbrook JT, et al. Longitudinal study of the ocular complications of AIDS. 1. Ocular diagnoses at enrollment. Ophthalmology. 2007;114:780-786.

22. Jacobson MA, Stanley H, Holtzer C, et al. Natural history and outcome of new AIDS-related cytomegalovirus retinitis diagnosed in the era of highly active antiretroviral therapy. Clin Infect Dis. 2000; 30:231-233.

23. Jabs DA, van Natta ML, Thorne, et al. Course of cytomegalovirus retinitis in the era of highly active antiretroviral therapy: 1. Retinitis progression. Ophthalmology. 2004; 111:2224-2231.

24. Jabs DA, van Natta ML, Thorne JE, et al. Course of cytomegalovirus retinitis in the era of highly active antiretroviral therapy: 2. Second eye involvement and retinal detachment. Ophthalmology. 2004; 111:2232-2239.

25. Kempen JH, Jabs DA, Wilson LA, et al. Mortality risks for patients with cytomegalovirus retinitis and acquired immune deficiency syndrome. Clin Infect Dis. 2003; 37:1365-1373.

26. Kempen JH, Martin BK, Wu AW, et al. The effect of cytomegalovirus retinitis on the quality of life of patients with AIDS in the era of highly antiretroviral therapy. Ophthalmology. 2003; 110:987-995.

27. Holbrook JT, Jabs DA, Weinberg DV, et al. Visual loss in patients with cytomegalovirus retinitis and acquired immunodeficiency syndrome before widespread availability of highly active antiretroviral therapy. Arch Ophthalmol. 2003; 121:99-107.

28. Ortega-Larrocea G, Espinosa E, Reyes-Teran G. Lower incidence and severity of cytomegalovirus-associated immune recovery uveitis in HIV-related patients with delayed highly active antiretroviral therapy. AIDS. 2005; 19(7):735-738.

29. Thorne JE, Holbrook JT, Jabs DA, et al. Effect of cytomegalovirus retinitis on the risk of visual acuity loss among patients with AIDS. Ophthalmology. 2007; 114:591-598.

30. Benson CA, Kaplan JE, Masur H, et al. Treating opportunistic infections among HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association/Infectious Diseases Society of America. MMWR Recomm Rep. 2004; 53:1-112.

31. Holland GN. Discussion of MacDonald JC, Karavellas MP, Torriani FJ, et al. Highly active antiretroviral therapy-related immune recovery in AIDS patients with cytomegalovirus retinitis. Ophthalmology. 2000; 107:877-833.

32. Wohl DA, Kendall MA, Owens S, et al. The safety of discontinuation of maintenance therapy for cytomegalovirus (CMV) retinitis and incidence of immune recovery uveitis following potent antiretroviral therapy. HIV Clin Trials. 2005; 6:136-146.

33. Walmsley SL, Raboud J, Angel JB, et al. Long-term follow-up of a cohort of HIV-infected patients who discontinued maintenance therapy for cytomegalovirus retinitis. HIV Clin Trials. 2006; 7:1-9.

34. Murdoch DM, Venter WD, Van Rie A, Feldman C. Immune reconstitution inflammatory syndrome (IRIS): review of common infectious manifestations and treatment options. AIDS Research and Therapy. 2007; 4:9.

35. Kempen JH, Min YI, Freeman WR, et al. Risk of immune recovery uveitis in patients with AIDS and cytomegalovirus retinitis. Ophthalmology. 2006; 113:684-694.

36. Schrier RD, Song MK, Smith IL, et al. Intraocular viral and immune pathogenesis of immune recovery uveitis in patients with healed cytomegalovirus retinitis. Retina. 2006; 26:165-169.

37. Hirsch HH, Kaufmann G, Sendi P, et al. Immune reconstitution in HIV infected patients. Clin Infect Dis. 2004; 38:1159-1166.

38. Jabs DA, Van Natta ML, Holbrook JT, et al. Longitudinal study of the ocular complications of AIDS. 2. Ocular examination results at enrollment. Ophthalmology. 2007;114:787-793.


39. Kempen JH, Min YI, Freeman WR, et al. Risk of immune recovery uveitis in patients with AIDS and cytomegalovirus retinitis. Ophthalmology. 2006; 113:684-694.

40. Thorne JE, Jabs DA, Kempen JH, et al. Incidence of and risk factors for visual acuity loss among patients with AIDS and cytomegalovirus retinitis in the era of highly active antiretroviral therapy. Ophthalmology. 2006; 113:1423-1440.

41. French MA. The immunopathogenesis of mycobacterial immune restoration disease. Lancet Infect Dis. 2006; 6:461-462.

42. Karavellas MP, Plummer DJ, MacDonald JC, et al. Incidence of immune recovery vitritis in cytomegalovirus retinitis patients following institution of successful highly active antiretroviral therapy. J Infectious Dis. 1999; 179:697-700.

43. Westeneg AC, Rothova A, De Boer JH, Groot-Mijnes JD. Infectious uveitis in immunocompromised patients and the diagnostic value of polymerase chain reaction and Goldmann-Witmer coefficient in aqueous analysis. Am J Ophthalmol. 2007; 144:781-785.

44. Tenhula WN, Xu S, Madigan MC, Heller K, Freeman WR, Sadun AA. Morphometric comparisons of optic nerve axon loss in acquired immunodeficiency syndrome. Am J Ophthalmol. 1991; 113(1):14-20.

45. Freeman WR, Van Natta ML, Jabs D, et al. Vision function in HIV-infected individuals without retinitis: report of the Studies of Ocular Complications of AIDS Research Group. Am J Ophthalmol. 2008; 145(3):453-462.

46. Eye Diseases Prevalence Research Group. Causes and prevalence of visual impairment among adults in the United States. Arch Ophthalmol 2004;122:4787-485.

John A. BeAls AwArdfor medicAl reseArch

G. shAhin AwArdfor reseArch By A physiciAn in trAininG in duvAl county

Articles submitted for the Beals Award must have been written by a member of the Duval County Medical Society, based on work done in Duval County. They must have been published between January 2010 and December 2010 in a peer re-viewed periodical listed in the MEDLINE / PubMed journal database.

Articles submitted for the G. Shahin Award must have a resident or fellow in training in Duval County as the lead author. The majority of the work must have been done while the resident or fellow was training in Duval County. They must have been pub-lished between January 2010 and December 2010 in a peer reviewed periodical listed in the MEDLINE / PubMed journal database.

it’s time for the 2011 BeAls & shAhin AwArds!Beals and Shahin Awards will be considered in three categories:

• Original Investigation • Clinical Observation • Review Articles

suBmission deAdline is August 5, 2011. All winners will be recognized and receive plaques

at the DCMS / Navy Meeting in late September. Winners in the Original Investigation categories

also receive monetary awards. Please visit the DCMS website (www.dcmsonline.org) and follow the Beals / Shahin link (under “Quick Links”) to submit your article for consideration. You will be asked to complete a brief form with contact informa-tion, award category, and publication details, and if available, email a PDF file of your article as it appeared in print or electronically.

If you have questions, please contact Marigrace Doran at 355-6561 ext. 101 or [email protected].


onecanhaveinflammationofthecorneaorTransientLightSensitivitySyndrome(TLSS).Epithelialin-growth(anexten-sionofepitheliumintothestroma),22infection,glare,andhaloscanoccur.Themostcommonpostoperativecomplaintisdryeye.Thisisbestpreventedbyperformingproperanalysispre-operatively.

Regression,areturntowardtheoriginalrefractiveerror,isinfrequentwithcurrentlasers.Theworstlate-onset(rare)complication,iscornealectasia(keratoconus).Ifthecorneaistoothin,therecanbelossof itsbiomechanicalstabilitydue to bowing of the cornea and decreased vision. Thisriskisreducedwithpreoperativecornealtopographywhichmeasuresthicknessthroughoutthecornea,anddemonstratesanysubtleirregularities.Ectasiaistreatedwithrigidcontactlenses,cornealsurgery(intacs),cornealtransplant,oranewtreatmentdevelopedinEurope,butnotyetFDAapproved,called collagen cross-linking.23 The average onset of thiscomplicationisnormally12to14monthsaftersurgery,butcantakeyears.24

PresbyopiaPresbyopiaisaconditionoftheeyeinwhichtheabilityto

focusonnearbyobjectsisgraduallylostbeginningaroundage40.Thetreatmentforpresbyopiahaslongbeenmonovision.Monovision is a state inwhich thedominanteye isoftentreatedfordistanceandthenon-dominanteyeistreatedforbothreadingandcomputervision.Roughly75%ofpatientsadjusttomonovisionquitewell.Occasionallynightdrivingisproblematicduetolossofstereopsisordepthperception.Ifitisnoticeable,glassesfornightdrivingareaviableoption.Withadvancingage,thedegreeofpresbyopiaincreasesandthiscanaffecttheeyecorrectedfornearvision.

The Final FrontierThefinal frontier isfindingabetter treatment forpres-

byopia.Thereareseveralproceduresonthehorizontotreatpresbyopia.Theobjectiveistohavegooddistanceandnearvisionineacheyeratherthanmonovisioninwhichoneeyeisfordistanceandtheothereyeisfornearvision.RobertoPinelliofItalydescribedhistechniqueforpresbyLASIK,anexcimerlaser-basedproceduretocreateamultifocalcorneatoimprovedistanceandnearvision.25,26ItcanbeperformedwithPRKorLASIK.Amyopictreatmentwithasmaller,centraltreatmentzoneiscombinedwithahyperopictreatmentofalargerzoneresultinginamultifocalcornea.Althoughthisprocedureispresentlybeingperformedbysomeeyesurgeons,itisnotyetFDAapproved.

Anotherareaofresearchforpresbyopiaisintrastromallaserrefractivesurgerywiththefemtosecondlaser.Thisinvolvestheremovalofalenticleofcornealstromawithoutcreatingaflaportouchingthesurfaceofthecornea(intraCOR)creatingamultifocalcorneabymakingcircularintrastromalringsthatsteepen the central cornea improving thepatients readingvisionanddepthoffocus.Ruiztreated245eyeswiththeintraCORandreported100%improvementofnearvision.27

TheintracornealInlay,a10micronthickdeviceplacedinthemid-corneaunderaLASIKtypeflapcreatesapinhole

affectandincreasesthedepthoffocus.Anadvantageofthistechniqueisthat it isreversibleandinterchangeable28andcantreatpatientswithexcellentdistancevisionwhowishtobespectaclefreeforreading.

ConclusionOverthepastdecade,refractivesurgeryhasimprovedthe

qualityoflifeinover28millionpatientswitha>95%patientsatisfactionrate29andmadeitoneofthemostpopularelectivesurgeryproceduresinallofmedicine.ItisconsideredsafeandhasbeenapprovedbythemilitaryforNavypilotsandNASAastronautcandidates.30Presbyopiatreatmentwillcontinuetoimprove.Ifthepresentdirectionandvolumeofresearchisanyguide,alargeproportionoftomorrow’sfemtosecondtechnologicaladvancesanddiscoverieswillbebasedonourmasteryoftreatingrefractiveerrorswithouteventouchingthecornea.Alltreatmentwillbeintrastromal.

References1. SakimotoT,Rosenblatt,MI,AxarDT.Lasereyesurgeryfor

refractiveerrors.Lancet.2006,367(9520):1432-47.2. Dr. Slava Fyodorov, Sante Fe, New Mexico, Nov. 1980,

Personalconversation.3. Dr.LeoBores,SanteFe,NewMexico,Nov.1980,Personal

conversation.4. TrokelSL,SrinivasanR,BrarenB.Excimerlasersurgeryof

thecornea. AM J Ophthalmol.1983,96:710-15.5. AronsI.SummitTechnology,VisxandPillarPointPartners.

Iry Arons Journal.May2006.6. SeilerT,KahleG,KriegrowskiM.Excimerlaser(193nm)

myopic keratomileusis in sighted and blind human eyes.Refract. Corneal Surg.1990,6:383-85.

7. McDonaldMB,KaufmanHE,FrantzJMetal.Excimerlaserablationinahumaneye.Arch Ophthalmol.1989107:641-42.

8. KruegerRonaldR,Rabinowitz,YaronS,BinderPerryS.The25thAnniversaryofExcimerLasers inRefractiveSurgery, J Refract. Surg. Oct2010,26:749-60.

9. RuizL,RowseyJJ.In-situkeratomileusis,Invest.Ophthalmol. Vis. Sci.1988,29:5392.

10. BurattoL,FerrariM,GenisiC.Myopickeratomileusiswiththeexcimerlaser:one-yearfollowup.Refract Corneal Surg.1993,9:12-19.

11. Pallikaris IG, Papatzanaki ME, Stathi EZ, Frenschock O,GeorgiadisA.Laserin-situkeratomileusis.Lasers Surg Med.1990,10:463-68.

12. JuhaszT, Loesel FH, Kurtz RM, et al. Corneal refractivesurgerywithfemtosecondlasers.J Sel Topics Quantum Electron. 1999,5:902-10.

13. Ratkay-TraubI,FerinczIE,JuhaszT,etal.Firstclinicalresultswith the femtosecond neodymium-glass laser in refractivesurgery.J Refract Surg. 2003,19:94-102.

14. McLeodSD,ThamV,M-B,PhanST.Bilateraldifuselamellarkeratitisfollowingbilateralsimultaneousversussequentiallaserin-situkeratomileusis.Br. J. Ophthmol.2003,87:1086-87.

15. StoncipherKG,DishlerJG,IgnacioTS,etal.Transientlightsensitivityafterfemtosecondlaserflapcreation:clinicalfindingsandmanagement. J Cataract Refract. Surg.Jan2006,32:91-94.

16. Binder Perry. AMO’s New IFS Advanced FemtosecondLaser–Faster,Safer,MoreVersatile.Refractive Eye Care.May2008,12:16-21.


17. SolomanKD,FernandezLE,SandovalHP,etal.Lasikworldliteraturereview.Ophthalmology Annual.2009,119:691-701.

18. ChalitaMR,XuM,KruegerRR.Correlationofaberrationswithvisualsymptomsusingwavefrontanalysisineyesafterlaserin-situkeratomileusis.J Refract. Surg. 2003,19:S682-86.

19. StonecipherKG,KezirianGM.Wavefront-optimizedversuswavefront-guidedLASIK formyopic astigmatismwith theALLEGRETTOWAVE;three-monthresultsofaprospectiveFDAtrial.J Refrac. Surg.2008,24:S424-30.

20. DonnefieldE.Ocularsurfacemanagementforthecataractandrefractivesurgeon. Ocular Surg News.June25,2009,pp.12-13.

21. Nakano K, Nakano E, Oliveira M. Intraoperative micro-keratomecomplicationsin47,094laserin-situkeratomileusissurgeries. J Refract Surg. 2004,20:S723-25.

22. WangM,MaloneyR.Epithelialingrowthafterlaserin-situkeratomileusis.Am J Opthal.2000,129:746-51.

23. Witting-Silvac,WhitingM,LamoureuxE,etal.Arandomizedcontrolledtrialofcornealcollagencross-linkinginprogressivekeratoconus:preliminaryresults,J Refract Surg.2008,24(7):S720-25.

24. RadAS,JabbarvandM,SaiflN. Progressivekeratectasiaafterlaserin-situkeratomileusis. J Refract. Surg.2004,20(5):S718-22.

25. PinelliR,OrtizD,SimonettoA,etal.Correctionofpresbyopiainhyperopiawithacenter-distanceparacentral-neartechnique. J Refract. Surg.2006,22(5):49V-50V.

26. GordonM.Laserpresbyopiccorrectionswiththewavelightlaser.Cat. and Refract Surg.Mar2010,10(3):71-72.

27. RuizLA,CepedaLM,FuentesVC.Intrastromalcorrectionofpresbyopiausingafemtosecondlasersystem, J Refract. Surg.2009,25:847-54.

28. Binder P. WOC debates the future of refractive surgery.Eurotimes.June29,2008,pp.3-4.

29. SolomanKD,FernandezLE,SandovalHP,etal.Lasikworldliteraturereview.Ophthalmology Annual. 2009,116:691-701.

30. StanleyPF,TanzerDJ,SchallhornSC.Laserrefractivesurgeryin theUnitedStatesNavy.Curr. Opin. Ophthalmol. 2008,19(4):321-324.

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Taking on Glaucoma: The Role of the Primary Care PhysicianTinaN.Tillis,MD

AddressCorrespondenceto:TinaN.Tillis,MD,UniversityofFloridaEyeInstitute,580West8thStreet,Jacksonville,FL32209-6533,Phone:(904)244-9390.Email:[email protected].

Abstract: The goal of this article is to give an overview of glaucoma and describe how this disease and its treatment might affect other disease processes or organ systems. Armed with this information the primary care physician (PCP) should be able to recognize patients at greatest risk of developing glaucoma and better understand their role in the glaucoma patients’ maintenance of continuity of care with ophthalmologists.

IntroductionThediagnosisofglaucomabringsaboutasenseofdread

andalmostimmediatelystimulatesvisionsofcompleteblind-ness–nopunintended.It isoneofthe leadingcausesofirreversibleblindnessworldwide.1-4Whilecurrentlythereisnocure,glaucomaistreatableanddoesnotneedtoleadtoblindnessinmostcases.Withappropriatetreatment,glau-comapatientsarelikelytokeeptheirvisionoratleastslowtheprogressionofthediseaseandliverelativelynormallives.5

Thekey,likemostdiseaseprocesses,isearlydetectionandtreatment.Exceptforacuteangleclosureglaucoma(ACG),glaucomaislargelya“silent”diseasewithfewsymptomsorsignsbeforeithasreachedanadvancedstage.5,6Assuch,thePCPhasacriticalroleinscreeningandreferringpatientstotheophthalmologistaspartoftheiroverallhealthcare.

Epidemiology Primary Open Angle Glaucoma (POAG)–Itisestimated

that 45 million people have OAG worldwide.5Glaucoma(combinedOAGandACG)isthesecondleadingcauseofblindnessworldwide(8.4millionpeople).5IntheUS,theprevalenceofPOAGinadultsovertheageof40is2%.7,8Itisestimatedthatin2010therewere2.2millionpeopleintheU.S.withglaucomaandthatwiththeagingpopulation,thisnumberwillincreaseto3.3millionby2020.5

Therearedefinitedifferencesintheprevalenceofglaucomaamongethnicgroups.5,9-12IntheU.S.theprevalenceofglau-comainAfricanAmericansisthreetofourtimesgreaterthaninWhites.11ItistheleadingcauseofblindnessinAfricanAmericans.5HispanicsandLatinoshavesimilarprevalenceratesasAfricanAmericans.5,9,10Glaucomaisamore“aggres-sive”inBlackswhereittendstooccuratanearlierageandismorerefractorytotreatment.11Hyper-vigilanceiswarrantedinscreeningAfricanAmericansandHispanics.9,12-14

Primary Angle Closure Glaucoma (PACG)–Ofthenearly67millionpatientswithglaucomaworldwide, ithasbeenestimatedthat50%haveACG,2makingitthemostcommonformofglaucomaandtheleadingcauseofbilateralblindnessin theworld (butnot in theU.S.).2There is considerabledifferenceintheprevalenceofACGamongethnicgroups.6

PACG,theoverwhelmingpredominantformofglaucoma

inEastAsia,isresponsiblefor1.5millionor91%ofthebi-lateralblindnesscasesinChina.2TheratesareloweramongAfricanAmericansandpeopleofEuropeandecent.2,6PACGmayequalPOAGinprevalenceinsomeAsianpopulations.6Worldwide,0.7%ofpeopleovertheageof40haveACG,anditisestimatedthatby202021millionpeopleworldwidewillhaveACG.6

Risk Factors for GlaucomaBelowisalistingofsomeoftheacceptedriskfactorsfor

glaucoma:

• Intraocular Pressure (IOP): Forevery1mmHgriseriskincreased10%15-20

• Central Corneal Thickness (CCT): The thinner(especially <550 microns) the greater risk; AfricanAmericanstendtohavethinnercorneas21-27

• Optic Disc Cupping: Increased(vertical>horizontal)cup-discratio28-31

• Diabetes Mellitus (DM): ItremainscontroversialastowhetherDMisassociatedwithanincreasedriskofdevelopingglaucoma32-36

• Hypertension (HTN): AcutehypertensionincreasestheriskofglaucomawhilechronicHTNislessclearlyassociatedwithanincreasedriskofdevelopingglau-coma37-41

• Race: AfricanAmericansaremuchmorelikelytohavePOAGandrarely,havePACG(butwhenpresentinAfricanAmericansismuchmorelikelytobechronic);InuitsandAsiansaremorelikelytohavePACG42,43

• Age: OcularHypertensionTreatmentStudy(OHTS)showedincreasedriskofPOAGwithageperdecadeof22-43%(intheunivariateandmultivariateanalyses,respectively);2PACGisrare<40yearsoldbutpreva-lenceincreaseseachdecadethereafter2,44

• Gender: PCAGis2-4timesmorecommoninwomenthaninmen2,10

• Family History: First degree relative with POAGincreasesriskupto13%;5,45FirstdegreerelativewithPACGriskisdifferentamongracialgroupswith1-12%prevalenceinWhitesand>6timesriskinChinesepatientswithanyfamilyhistory2

• Refraction Error: Myopia(nearsightedness)riskfactorforPOAG;Hyperopia (farsightedness)= risk factorforPACG2,46,47

DefinitionOvertheyearsthedefinitionofglaucomahasevolvedfrom

thesimple“elevatedeyepressurethatcausesblindness”toamorecomprehensivedefinition:“amulti-factorialgroupof diseases that have in common a characteristic ‘optic

mailto:tina.tillis%40jax.ufl.edu.?subject=


neuropathy’withassociated‘visualfieldloss’forwhichelevated‘intraocularpressure(IOP)’isoneoftheprimaryriskfactors.”2

TherangefornormalIOPisnotaperfectbell-shapedGauss-iancurvebutisskewedtotheright.Ninety-fivepercentofthegeneralpopulationhasIOPsof10-22mmHgwithameanof16.2TherearepatientswithhighIOPswhodonothaveglaucomaandpatientswhohavealwayshadlowIOPswhodohaveglaucoma.DespitelowIOPs,thesepatientsstillgoontodevelopopticneuropathyleadingtoblindness(NormalorLowTensionGlaucoma—NTGorLTG).

Whileitisgenerallyacceptedthattheetiologyofglaucomaismulti-factorial,wedoknowthatIOPplaysamajorrolein its effect on the Optic Nerve (ON). Historically (andcurrently),loweringtheIOP(regardlessofhighorlowbaseIOP)topreventprogressiveneuropathyandganglioncelllosswithresultantvisualfieldlosshasbeenthebasisforglaucomatreatment.ClinicalresearchstudieshaveproventhevalidityofloweringtheIOPinpreventingorslowingtheprogressionofvisualfield(VF)loss.2,5

Whenonehearsthediagnosisofcancer,thenextlogicalquestionis,whattypeofcancer?Similarly,thediagnosisofglaucomashouldpromptthequestion,whattypeofglaucomadoesthepatienthave?Therearethreebasiccategoriesofglau-coma,andwhiletheyallsharesomecommoncharacteristics,theyalsodifferfromoneanotherinkeyareas.Thecategoriesare(1)congenital(ordevelopmental);(2)openangle;and(3)angleclosureglaucomas.Congenitalglaucomawillnotbe discussed here for the sake of brevity. Adult glaucomais generally divided into Primary Open Angle Glaucoma(POAG) and Primary Angle Closure Glaucoma (PACG).Whenthereisaknownunderlyingetiologicdiseaseprocessitiscategorizedasasecondaryglaucoma.

Clinical Glaucoma Evaluation Theelements of a goodglaucoma evaluation consist of

a thorough history (family, medical, medications, allergicdrug reactions and review of systems). The ocular examincludes determination of best-corrected visual acuity,pupillary exam, IOP measurement, gonioscopy slit lamp

exam,CCTmeasurementandcarefulretinalandopticnerveexamination.Imagingstudiesofthenervefiberlayer(NFL)andopticdischeadareoftenperformed(GDX,HRTandOCT)(Figure 1).48,49Thevisualfield(Figure 2, p.27)isusedtocheckforactuallossoffieldofvision(sometimesreferredtoas“peripheralvision”).

Open Angle vs. Angle Closure GlaucomaTheeyecanbedividedintoposteriorandanteriorchambers

separatedbythelens-irisdiaphragm.Aqueoushumor(AH)producedbytheciliarybody(CB)locatedintheposteriorchamber(PC)(Figure 3, p.28)oftheeyehelpsmaintaintheshapeandfirmnessoftheeye,providesnutrients,andclearsoutby-productsofvariousbiochemicalreactions.AHflowsfromthePCaroundthelens,throughthepupilintotheante-riorchamber(AC)andoutthroughthetrabecularmeshwork(TM)(i.e“angle”).Itistheanatomicstatusofthisanglethatdetermineswhetherglaucomais“open”or“closed”.AnythingthatobstructstheTM(eitherbycoveringitorbypushingtheperipheralirisagainstit)causestheangletoclose–hencetheterm,angleclosure(glaucoma).POAGhasan“open”angle.PACGandPOAGareusuallyhereditary.SecondaryformsofOAGandACGaretheresultofotherfactors.

POAG,includingLTG/NTGandpigmentaryglaucomaaccountsforapproximatelytwothirdsofallcasesofglaucomawhilePACGonlyaccountsfor5%ofU.S.casesofglaucoma.

Primary Angle Closure GlaucomaBecauseoftheinternalreflectionoflight,theanglecannot

bedirectlyvisualized.Amirroredgoniolens(gonioscopy)allowsvisualizationoftheangle.(Figure 4, p.29)Anyonewith>1800ofiridotrabecularcontact(ITC)inprimarygazeisatriskofangleclosure.6Ideallywewouldprefertopreventanattackratherthantreatanattack.IOPcanbedangerouslyhighandmustbereducedasquicklyaspossibletoavoidirreversiblelossofvision.ClassicsignsandsymptomsofacuteACGareseverepain,decreasedvision,headache,tearing,halosaroundlights,nausea,vomiting,conjunctivalhyperemia,mid-dilatedpupil,shallowAC,cornealedemaandextremelyhighIOP(>50-60mmHg).

Figure 1 Optic Disc Evaluation with OCT


Oral,topicalandIVmedicationmaybenecessarytomanagetheattackinitially,butunlikePOAGthedefinitivetreatmentofPACG is surgical.PACG is commonly associatedwithpupillaryblockcausedbyanteriormovementoftheaginglensagainsttheirisand“occluding”thepupil,thusblockingtheflowofAHfromthePCintotheAC.Onceblocked,alargerpressuregradientiscreatedbetweenthePCandACresultinginfurtherforwardmovementofthelens.Aviciouscycleoccurs,compoundingtheproblem,elevatingthepres-sureandleadingtoopticnervedamage.Inordertobreakthe“attack”,flowmustbeestablishedbetweenthePCandAC.Thisisusuallyaccomplishedbycreatingasmallholeintheirismostcommonlywithalaser–laserperipheraliridotomy(LPI).Thisisalmostalwaysabilateralconditiondespitethefactthat90%ofacutecasesareunilateral,soLPIsaredoneinbotheyes.6

Primary Open Angle Glaucoma TreatmentMedical –IntheU.S.,initialtherapyforPOAGisusually

medicalintheformofdropssinceglaucomamedicinesaregenerallymoreeffectivewhenapplieddirectlytotheocularsurface.Medicaltreatmentforglaucoma(Table 1, p.30) con-sistsofbeta-blockers(Timolol,Betimol,Betagan,Betaxolol,BetopticS),prostaglandinanalogs(Lumigan,Travatan,Xa-latan),alpha-agonists(Brimonidine,AlphaganP),carbonicanhydraseinhibitors(Azopt,Trusopt),andcholinergic(Pilo-carpine)medications.Inthelastdecadetheprostaglandinshavebeatenoutthebetablockerstobecomethemostcommonlyprescribedclassofdrugswiththeotherclassesmoreoftenusedasadjunctivetherapy.Combinationmedicationssuch

asCombigan(timolol+brimonidine)andCosopt(timolol+ trusopt) have been developed in hopes of helping withpatientcompliance.OralcarbonicanhydraseinhibitorssuchasDiamox(acetazolamide)andNeptazane(methazolamide)areusedinconjunctionwithdropsforrecalcitrantglaucomaandinemergencysituations.5,50,51

ItisimportantforPCPstobeawareofpotentialinteractionsoftopicaleyeandsystemicmedications.SomemedicationsprescribedbythePCPcanalsoexacerbateglaucoma.Steroidsinparticularhaveapropensitytocauseelevationofintra-ocularpressureseveninpatientswhoarenotknowntohaveglaucoma.Thesepatientsarereferredtoas“steroidrespond-ers”.Ninety-fivepercentofPOAGpatientsandfirst-degreerelativesofPOAGpatientsaresteroidresponders,whileonly5%ofthegeneralpopulationaresteroidresponders.WhiletheincreasedIOPcanoccurwithanymodeofsteroiddosing(nasal,depo-injection,topical,oral),itismuchmorecommonwith topicalmedications.Eyedrops shouldbeconsideredwhen unexplained systemic symptoms occur; specificallyCNS,cardiacandpulmonarysideeffectsorallergicreactions.

Surgical – WhileinitialtherapyofPOAGisusuallymedical,therearesomecasesbesttreatedwithinitiallasersurgeryoracombinationofmedicationsandlaser.Moreseverecasesareusuallytreatedwithincisionalsurgery.Allofthesetreat-mentsaregearedtowardsloweringtheintraocularpressureeitherbydecreasingaqueousproductionand/orincreasingtheoutflowofAHfromtheeye.

ThetwomostcommonLaserTrabecloplasty(LTP)pro-ceduresareSelectiveLaserTrabeculoplasty(SLT)andArgon

Figure 2 Humphrey Visual Fields


LaserTrabeculoplasty (ALT). The application of the laserbeamdirectlytotheTMhasbeenshowntoincreaseoutflowoftheAHfromtheeye.

IncisionalsurgeryisindicatedwhenpatientsareonmaximaltoleratedmedicationswithfailuretoachieveloweredtargetIOP;medicinesarenotwell-tolerated;progressionofvisualfieldlossand/oropticnervedamagehasoccurred;orpoorpatientcomplianceispresent.2

Severaldifferentsurgicalproceduresaredonetolowertheintraocularpressure.Theycanbedividedintononpenetrating,penetrating(trabeculectomyorfilteringprocedure,ExpressMini Shunt), various drainage tube implants (Ahmed,Molteno,Baerveldttubes)(Figure 5, p.31) andciliarybodyablation.2 The goal of filtering surgery is to create a newpathway(fistula)fortheflowofAHfromtheACthroughthesurgicaldefectinthescleraintothesubconjunctivalandsub-Tenonsspaces.2Theguarded-trabeculectomyusesthescleraofthepatient’seyetocreateatrapdoorthroughwhichaqueouscanescapeandbeabsorbedbythecirculatorysystem.

Shuntsortubesofvaryingsizes(withorwithoutvalves)areusedasexternaldrains.Withanypenetratingprocedure

thereisanincreasedriskofcomplications.Thepost-operativecareislongandlabor-intensive.Itisnotuncommonforsomepatientstorequiremorethanoneprocedureintheirlifetime.

SummaryGlaucoma can be a devastating disease. The morbidity

associated with it affects all of us from a socio-economicperspective.Thosepatientsblindedbyglaucomabecomelessindependentandlessproductivecitizens.Whenpatientslosetheirindependence,suchastheirabilitytodriveortakecareofthemselves,theentirefamilyisaffected.Thisisachronicdiseasewithnoknowncure,however treatmenthasbeenshowntobeeffectiveinslowingorpreventingprogressiontoblindness.Therefore,wehavetobemoreproactiveinfightingthisdiseaseuntilwefindacure.CollaborationbetweenPCPsandOphthalmologistsisthekeytotakingonglaucomaandhavingsomemeasureofsuccess.

References1. Congdon N, O’Colman B, Klaver CC, et al. Causes and

PrevelanceofVisualImpairmentAmongAdultsintheUnitedStates. ArchOphthalmol. 2004;122(4):477-85.

2. American Academy of Ophthalmology. Basic and ClinicalScienceCourse:Glaucoma. 2005-2006;10:3-209.

Figure 3 Anatomy of the Eye and Flow of Aqueous

(Top figure) © 2002 American Academy of Ophthalmology. Used by permission. (Bottom, left and right figures) © 2004 American Acad-emy of Ophthalmology. Used by permission.


3. Leibowitz HM, Krueger DE, Maunder LR, et al. TheFramingham Eye Study monograph: An ophthalmologicaland epidemiological study of cataract, glaucoma, diabeticretinopathy,maculardegeneration,andvisualacuityinageneralpopulation of 2631 adults, 1973-1975. Surv Ophthalmol. 1980;24(Suppl):335-610.

4. KassMA,HeuerDK,HigginbothamEJ,etal.TheOcularHypetensionTreatmentStudy:Arandomizedtrialdeterminesthattopicalocularhypertensivemedicationdelaysorpreventstheonsetofprimaryopen-angleglaucoma.Arch Ophthalmol.2002;120:701-713.

5. AmericanAcademyofOphthalmologyGlaucomaCommittee.Preferred Practice Patterns® Guidelines. Primary Open Angle Glaucoma. San Francisco, CA: American Academy ofOphthalmology,2010.

6. AmericanAcademyofOphthalmologyGlaucomaCommittee.Preferred Practice Pattern® Guidelines. Primary Angle Closure Glaucoma. San Francisco, CA: American Academy ofOphthalmology.2010.

7. TsaiJC,ForbesM.Epidemiology: Primary Open Angle Glaucoma. Medical Management of Glaucoma.2nded.WestIslip,NY:ProfessionalCommunications,Inc.2004;pp.55-61.

8. KleinBE,KleinR,SponselWE,etal.PrevalenceofGlaucoma.The Beaver Dam Eye Study. Ophthalmology. 1992 Oct.;99(10):1499-504.

9. VarmaR,Ying-LaiM,FrancisBA,etal.PrevalenceofopenangleglaucomaandocularhypertensioninLatinos:TheLosAngelesLatinoEyeStudy.Ophthalmology.2004;Aug.,111(8):1439-48.

10. RudnickaAR,Mt-IsaS,OwenCG,etal.Variationsinprimaryopen-angleglaucomaprevalencebyage,gender,andrace:ABayesianMeta-Analysis. Invest.Ophthalmol. Vis. Sci.2006Oct.;47(10):4254-4261.

11. TheEyeDiseasesPrevalenceResearchGroup.Prevalenceofopen-angleglaucomaamongadultsintheUnitedStates.Arch Ophthalmol.2004;122(4):532-538.

12. RacetteL,LiebmannJM,GirkinCA,etal.AfricanDescent

Figure 4 Gonioscopy

Use of a gonio-lens allows visualization of the “angle” and determination of whether the angle is open or closed. (Figure, left) © 2008 American Academy of Ophthalmology. Used by permission. (Figure, right) © 2006 American Academy of Ophthalmology. Used by permission.

and Glaucoma Evaluation Study (ADAGES):III. AncestryDifferences in Visual Function in Healthy Eyes. Arch Ophthalmol. 2010;128(5):551-559.

13. SamplePA,GirkinCA,ZangwillLM.TheAfricanDescentand Glaucoma Evaluation Study (ADAGES): Design andBaselineData.Arch Ophthalmol.2009;127(9):1136-1145.

14. Ryskulova A,Turczyn K, Makuc DM, et al. Self-reportedage-relatedeyediseasesandvisualimpairmentintheUnitedStates:Resultsofthe2002NationalHealthInterviewSurvey.AJPH 2008;98:454-461.

15. LeskeMC,HeijlA,HusseinM,etal.Factorsforglaucomaprogressionandtheeffectoftreatment:TheEarlyManifestGlaucomaTrial.Arch Ophthalmol.2003;121:48-56.

16. Gordon M, Beiser JA, Brandt JD, et al. The OcularHypertensionTreatmentStudy:Baselinefactorsthatpredicttheonsetofprimaryopen-angleglaucoma. Arch Ophthalmol. 2002;120:714-720.

17. AsraniS,ZeimerR,WilenskyJ,etal.Largediurnalfluctuationsinintraocularpressureareanindependentriskfactorinpatientswithglaucoma. J Glaucoma. 2000Dec;9(6):487-8.

18. NemesureB,HonkanenR,HennisA,etal.Incidentopen-angleglaucomaandintraocularpressure. Ophthalmology.2007Oct;114(10);1810-5.

19. Prata TS, De Moraes CGV, Kanadani FN, et al. Postureinducedintraocularpressurechanges:considerationsregardingbodypositioninglaucomapatients.Surv of Ophthalmol. 2010;55(5):445-453.

20. BengtssonB,LeskeCM,HymanL.Fluctuationofintraocularpressure and glaucoma progression in the Early ManifestGlaucomaTrial.Ophthalmology,2007;114:205-209.

21. HerndonLW,WeizerJS,StinnettSS.Centralcornealthicknessasariskfactorforadvancedglaucomadamage.Arch Ophthalmol.2004;122:17-21.

22. WuRY,ZhengYF,WongTY,etal.Relationshipofcentralcornealthicknesswithopticdisckparameters:TheSingaporeMalayEyeStudy.Invest.Ophthalmol. Vis. Sci.2011March;52(3):1320-1324.


Table 1 Glaucoma Medications

23. XuL,ZhangH,WangYX,etal.CentralCornealThicknessandOpticDiscHemorrhages:TheBeijingEyeStudy.Arch Ophthalmol. 2008;126(3):435-436.

24. Brandt JD. Corneal thickness in glaucoma screening,diagnosisandmanagement.Curr Opin Ophthalmol.2004Apr;15(2);85-89.

25. Touboul D, Roberts C, Kerautret J, et al. Correlationsbetween corneal hysteresis, intraocular pressure andcornealcentralpachymetry.J Cataract Refract Surg.2008;34(4);616-22.

26. DoughtyMJ,ZamanML.Humancornealthicknessanditsimpactonintraocularpressuremeasures:areviewandmeta-analysisapproach. Surv Ophthalmol. 2000Mar-Apr;44(5):367-408.

27. ShahS,ChatterjeeA,MathaiM,etal.Relationshipbetweencornealthicknessandmeasuredintraocularpressureinageneralophthalmologyclinic.Ophthalmology.1999Nov;106(11):2154-60.

28. HoffmannEM,ZangwillLM,CrowstonJG.Opticdiscsizeandglaucoma.Surv Ophthalmol.2007;52(1):32-49.

29. SpaethGL,LopesJF,JunkAK,etal.Systemsforstagingthe

amoutofopticnervedamageinglaucoma:acriticalreviewandnewmaterial.Surv Ophthalmol. 2006;51(4):293-315.

30. MartusP,StrouxA,BuddeWM,etal.Predictivefactorsforprogressiveopticnervedamageinvarioustypesofchronicopen-angleglaucoma. AJO;139(6):999-1009.

31. Jonas JB,BuddeWM,Panda-JonasS.OphthalmoscopicEvaluation of the optic nerve head.SurvOphthalmol; 43(4):293-320.

32. ChopraV,VarmaR,FrancisBA,et al.Type2diabetesmellitusandtheriskopenangleglaucomatheLosAngelesLatinoEyeStudy.Ophthalmology.2008Feb;115(2):227-232.

33. GordonMO,BeiserJA,KassMA.Isthehistoryofdiabetesmellitusprotectiveagainstdevelopingprimaryopen-angleglaucoma?Arch Ophthalmol,.2008;126(2):280-281.

34. Kass MA, Gordon MO. Diabetes and Glaucoma. Arch Ophthalmol.2008;126:746-747.

35. DeVoogdS,IkramMK,WolfsRCW,etal.IsDiabetesMellitus a Risk factor for open-angle glaucoma?: TheRotterdamStudy. Ophthalmology; 113(10):1827-1831.

36. BonovasS,PeponisV,FilioussiK.Diabetesmellitusasarisk


factorforprimaryopen-angleglaucoma:ameta-analysis. Diabetic Medicine.2004;21(6):609-614.

37. CostaVP,ArcleriES,HarrisA.Bloodpressureandglaucoma.Br J Ophthalmol 2009;93:1276-1282doi:10.1136/bjo.2008.14947.

38. BonomiL,MarchiniG,MarraffaM,etal.Vascularriskfactors for primary open angle glaucoma: The Egna-NeumarktStudy. Ophthalmology. 2000;107(7):1287-1293.

39. WerneA,HarrisA,MooreD,etal.Thecircadianvariationsin systemic blood pressure, ocular perfusion pressure,and ocular blood flow: risk factors for glaucoma? Surv Ophthalmol. 2008;53(6):559-567.

40. SultanMB,MansbergerSL,LeePP.Understandingtheimportance of IOP variables in glaucoma: a systemicreview.Surv Ophthalmol.2009;54(6):643-662.

41. Muskens R, Voogd S, Wolfs RC, et al. Systemicantihypertensive medication and incident open-angleglaucoma.Ophthalmology.2007;114(12):2221-2226.

42. TielschJM,SommerA,KatzJ,etal.Racialvariationsintheprevalenceofprimaryopen-angleglaucoma:TheBaltimoreEyeSurvey.JAMA.1991;266:369-374.

43. RacetteL,WilsonMR,ZangwillLM,etal.Primaryopen-angleglaucomainBlacks:areview.Surv Ophthalmol. 2003;48(3):295-313.

44. Chauhan BC, Mikelberg FS, Artes PH. CanadianGlaucomaStudy:3.Impactofriskfactorsandintraocular

Figure 5 Tube Shunts

Various tube shunts: 1a Molteno, single and double; 1b Baerveldt; 1c Krupin; 1d Ahmed AAO. (Figures © 2002 American Academy of Ophthalmology. Used by permission.)

pressurereductionontheratesofvisualfieldchange.Arch Ophthalmol. 2010; 128(10):1249-1255.doi:10.1001/archophthalmol.2010.196.

45. Leske CM, Connell AMS, Wu SY, et al. Risk factorsforopen-angleglaucoma:TheBarbadosEyeStudy.Arch Ophthalmol.1995;113(7):918-924.

46. KhawajaAP.Primaryopenangleglaucoma.EyeWiki.1-11.Availablefrom:http://eyewiki.aao.org/PrimaryOpen-AngleGlaucoma.Accessed:November29,1010.

47. GrodumK,HeijlA,BengtssonB.Refractive error andglaucoma.ActaOphthalmol Scand. 2001;79:560-6.

48. PabloLE,FerrerasA,SchlottmannPG.Retinalnervefiberlayerevaluationinocularhypertensiveeyesusingopticalcoherencetomographyandscanninglaserpolarimetryinthediagnosisofearlyglaucomatousdefects.Br J Ophthalmol. 2011;95:51-55.

49. KimNA,LeeES,SeongGJ,etal.Spectraldomainopticalcoherence tomography fordetectionof localized retinalnerve fiber layer defects in patients with open-angleglaucoma.Arch Ophthalmol.2010;128(9);1121-1128.

50. KarmelM.GlaucomaDrops:RxforSuccessorTrouble?EyeNet. 2009;13(3):39-43

51. PasqualeLR.Optimizingtherapyfornewlydiagnosedopen-angleglaucoma:LessonslearnedfromtheCollaborativeInitialGlaucomaTreatmentStudy.Arch Ophthalmol. 2008;126(1):125-127.

http://eyewiki.aao.org/Primary


Use of Vascular Endothelial Growth Factor Inhibitors for Retinal Disease

FredH.Lambrou,Jr.,MDandGregoryM.Lewis,MD

Address Correspondence to: Dr. Fred H. Lambrou, Jr., or Dr.GregoryM.Lewis,RetinaAssociates,PA,2ShircliffWay,Suite715,Jacksonville,FL32204.Phone:904-388-8446.

Abstract: In this paper, we will discuss the use of vascular endothelial growth factor (VEGF) inhibitors (See “Introduction” for definitions/descriptions) for the treatment of retinal vascular occlusive disease, dia-betic retinopathy, and age-related macular degeneration. Bevacizumab and ranibizumab are the most commonly used intravitreally injected VEGF inhibitors. We will review the rational and the clinical evidence supporting the use of these medications.

IntroductionVascular endothelial growth factor (VEGF) is elevated

intraocularlyinmanyblindingretinaldiseases.Bevacizumaband ranibizumab are VEGF inhibitors that can be safelyinjectedintravitreally.Theyhavebeenshowntobeeffectiveintreatmentofretinalveinocclusions,diabeticretinopathyandage-relatedmaculardegeneration.Intheseconditions,VEGFinhibitorscannotonlyreducetheriskofblindnessbutalsoimprovevision.Patientsmustbefollowedcarefullywithpossiblemonthlyinjections.

Vascular endothelial growth factor (VEGF) inhibitorshavebeenused for retinaldiseases since2004.Theyhaverevolutionizedthetreatmentofmanymaculardiseasesandhave given us treatments for blinding diseases for whichwepreviouslyhadnotherapy.VEGFcontributestoretinalvascularangiogenesis,tortuosityandhyperpermeabiltiy.1

Bevacizumab(Avastin)isafull-lengthhumanizedmonoclo-nalantibodythatbindstoallsubtypesofVEGF.2Ranibizumab(Lucentis)developedforintraocularuse,isanantigen-bindingfragment (Fab)derived fromthe sameparentmoleculeasbevacizumabthatalsobindstoallsubtypesbutwithgreateraffinitythanbevacizumab.

Intravitreal InjectionsThethoughtofanintravitreal injectionisdisconcerting

andmostpatients’first response isoften “You’re going tostickaneedleinmyeye?”However,mostpatientstoleratetheinjectionextremelywell.Thetechniqueinvolvestheuseof topicalanestheticdrops followedbyplacementofa lidspeculum.Followingthis,somepractitionersgiveasubcon-junctivalinjectionof2%lidocaine,whileothersuseviscoustetracaineand/ora4%lidocaine-soakedpledget.Theeyeisthensterilizedwith5%povidoneiodineandoftenflushedwithantibioticdrops.A30-gaugeneedleisinsertedthroughtheparsplanaintothevitreouscavityand0.05mLofsolu-tion of ranibizumab (0.5 mg) or bevacizumab (1.25 mg)is injected. Theneedle is removedand theopticnerve ischeckedforadequateperfusionbyindirectophthalmoscopy,ortheintraocularpressureischecked.Thepatientisallowed

togohomeresumingnormalactivities.Injectionsaregivenmonthlyorasneededandcarefulfollow-upisrequiredtomaintainvision.

Complicationsofintravitrealinjectionsarerare.Themostfearedcomplicationisendophthalmitis.Thishasbeenreportedtooccurinapproximately1per2000injections.Othercom-plications,suchasintraocularinflammation,retinaldetach-ment,retinaltearorvitreoushemorrhage,arealsouncommonandoccurinlessthan1%ofinjections.Themostcommoncomplicationseenissubconjunctivalhemorrhage.Thiscanbeupsettingforthepatientastheconjunctivaturnsbeetred.However,itclearsspontaneouslyandcausesnopermanentsequelae.Anotherfearedcomplicationistheoccurrenceofa cardiovascular event. In patients receiving bevacizumabintravenously for metastatic colon cancer, cardiovasculareventshavebeenshowntooccuratahigherfrequencythanpatientsonplacebo.With intravitreal injections,however,theredoesnotseemtobeanincreasedriskofcardiovasculareventswithtreatmentversusshaminjection.3

Diabetic RetinopathyDiabeticretinopathyisthemostcommoncauseofblind-

nessamongworkingageadultsintheUnitedStates,4causing12,000to24,000newcasesofblindnessannually.5 Mildtomoderatevisionlossfromdiabeticretinopathyisusuallyduetodiabeticmacularedema(DME).6Diabeticvisionlosscanalsooccurfromproliferativediabeticretinopathywhenvitreoushemorrhageortractionretinaldetachmentoccurs.

Microvasculardamageoccursindiabeticsashyperglycemiacausesapoptosisofglialcells,pericytes,andendothelialcells.Hyperglycemiaalsocausesleukostasis,increasedproductionofVEGF,andlossoftightjunctionproteins.Subsequently,retinalvesselsdevelopocclusionsandleakymicroaneurysms,leadingtoDME.7

Untilrecently,themainstayoftreatmentofDMEwaslaserphotocoagulation,studiedintheEarlyTreatmentDiabeticRetinopathyStudy(ETDRS).8Inthisstudylaserwasapplieddirectlytoleakingmicroaneurysmsandinagridpatterntoareasofmicroaneurysmclustersor capillarynonperfusionwhenmacular thickeningwas seennear the centerof themacula.Treatment was repeated 4 months later if edemapersisted. Photocoagulation reduced the risk of moderatevisuallossfromdiabeticmacularedemabyhalf,from24%to12%,3yearsafterinitiationoftreatment;however,visualimprovementwasminimal.

Thepastfewyearshaveseenanincreaseinthenumberoftreatmentoptionsavailablefortreatingdiabeticmacularedema.Intheearly2000’smanyretinaspecialistsbeganusingintravitreallyinjectedtriamcinoloneasanadjuncttolaserformacular edema.Corticosteroids inhibit inflammationand


leukostasis,upregulateproductionoftightjunctionproteins,andsuppressproductionofVEGF.9,10

Recently,however,thistreatmenthasbeguntofalloutoffavorbasedontheresultsoftheDiabeticRetinopathyClinicalResearchNetwork(DRCR.net)study,arandomized,multi-centerclinicaltrial.TheDRCR.netSteroidvs.LaserStudyforDMEstudycompared1mgand4mgpreservative-freetriamcinoloneintravitrealdosestomacularlaserphotocoagu-lation,allrepeatedevery4months,asneeded.11,12Althoughthesteroidgroupsdidbetterinthefirstfewmonths,laserwassuperiorthereafter.At3years,26%percentofpatientsinthephotocoagulationgroupgained15ormorelettersofvision(onanETDRSchart),vs.21%ofpatientstreatedwithtriamcinolone.Only8%ofpatientstreatedwithlaserlost15ormorelettersofvision,asopposedto16%ofpatientstreatedwith triamcinolone.The incidenceof cataract andincreased intraocular pressure (IOP) was lower with lasercomparedtotriamcinolone.

Unlike intravitreal triamcinolone, intravitreal injectionofanti-VEGFmedicationshasshownsuperioritytolaser.13TheBOLTstudy,reportingin2010,isa2-yearclinicaltrialsupporting theuseof intravitrealbevacizumab inpatientswithDMEcomparedtofocallaser.14Patientsreceivingbe-vacizumabgainedamedianof8ETDRSletters,comparedwiththeamedianlossof0.5ETDRSletters forthe lasergroup(P=.0002).At12months,centralmacularthicknessdecreasedfrombaselinesignificantlymoreinthebevacizumabgroupthaninthelasergroup.

The DRCR.net trial studied intravitreal ranibizumab,eitherwithpromptordeferred(24weeks)focal/gridlaser,ascomparedwithlaseraloneandwithtriamcinolonepluspromptlaser.13Atboth1and2yearsfollow-up,nearly50%ofDMEpatientswhoreceived0.5mgintravitreal ranibi-zumabpluslaserexperienced>10ETDRSlettersofvisualimprovement,vs.only28%inthelaserplusshamgroupandabout30%intheintravitrealtriamcinolonepluslasergroup.PatientsreceivingtriamcinolonealsohadahighfrequencyofincreasedIOP(50%)andcataractsrequiringsurgery(60%).Thesubgroupofpseudophakicpatientsreceivingtriamcino-lone,pluslaser,hadsimilarvisualgainstotheranibizumabgroups,butincreasedIOPwasstillamajorconcern.

TheRESTOREPhase3trialisarandomized,double-blind-ed,multicenter,laser-controlledtrialcomparingranibizumabmonotherapywithlasermonotherapyandwithranibizumabpluslaser.15Thestudyincludes345patients.Treatmentinitia-tionwithranibizumabincludesthreeconsecutivemonthlyinjections with subsequent injections given as needed. At12monthsthereisnosignificantdifferenceinmorphologicorfunctionalresponsebetweentheranibizumabmono-andcombination therapygroups. Thirty-sevenpercentof theranibizumabmonotherapygroupand43%ofthecombina-tiontherapygrouphavegained>10ETDRSlettersofvisualacuity,vs.only16%inthelasermonotherapygroup.

Bevacizumab is occasionally also used off-label to treatneovascularization in diabetic retinopathy when opaque

ocular media such as cataract, cloudy cornea, or vitreoushemorrhage, prevent panretinal photocoagulation. This isoftenhelpfulinpreparationforvitrectomysurgerytoremovevitreoushemorrhage.16

Retinal Vein OcclusionsRetinalveinocclusions(RVO)arethesecondmostcom-

montypeofretinalvasculardiseasebehinddiabeticretinopa-thy.17Theyincludebranchretinalveinocclusion(BRVO),hemiretinalveinocclusion(HRVO),andcentralretinalveinocclusion(CRVO).IntraocularVEGFlevelshavebeenfoundtobeelevatedinRVO.18,19

CRVOis themostdebilitating typeof veinocclusion.Ithasbeenknownasgivinga“bloodandthunder”pictureofthefundus,asthereismarkedintraretinalhemorrhaginginallquadrants.Itoccursin0.1%to0.5%ofadultsandisfurther subcategorized into ischemic versus non-ischemicCRVO.Visuallossisoftencausedinischemiccentralretinalveinocclusionsbythedevelopmentofretinaloririsneovas-cularization,leadingtovitreoushemorrhageorneovascularglaucoma. In non-ischemic CRVO, the altered capillarynetworkofthemaculaleadstosignificantvascularleakageand macular edema. Prior to the development of VEGFinhibitors,therapywasperformedbyphotocoagulation.Inischemiccentralveinocclusion,ischemicretinacouldundergopanretinalphotocoagulation(PRP)leadingtoregressionofneovascularization.An injectionof aVEGF inhibitor canmarkedlyandquicklycauseregressionofneovascularization.Thesepatientsmayrequiremultipleinjectionsatmonthlyintervalsinordertokeeptheneovascularizationregressed.20

The treatment of macular edema in CRVO has beenrevolutionized by the development of VEGF inhibitors.PhotocoagulationisofnobenefitinimprovingvisualacuityinpatientswithmacularedemafromCRVO.20TheCRUISEstudy,“RanibizumabfortheTreatmentofMacularEdemaAfter Central Retinal Vein Occlusion Study: EvaluationandEfficacyandSafety”,wasaphaseIII,multicentertrialcomparingintravitrealranibizumabwithshaminjection.21TheCRUISErandomizedpatientsbetweenshaminjection,0.3mgofranibizumaband0.5mgofranibizumab.Patientsreceived injections monthly for 6 injections, followed bymonthlyfollow-upintheobservationperiod.After6months,patients could receive additional ranibizumab injectionsiftheyhadevidenceofmacularedema.Theresultsofthisstudyshowedasignificantimprovementinvisualacuityinpatientsreceivingranibizumabversusshaminjections,withapproximately50%ofpatientshavingimprovedgreaterthan15-letterimprovementinvisualacuityfrombaselineintreatedpatientsversus33%inuntreatedpatients.

Bevacizumabhasalsobeenshowntobeofhelpfor thetreatmentofmacularedemainCRVO.Inonestudy,86eyeshad24monthsoffollow-up,with57%showingimprove-mentinvisualacuities.22

BRVOsarealsoacommoncauseofvisualloss.TraditionaltherapyinpatientswithmacularedemafromBRVOincludes


photocoagulationorobservation.17,23ThenaturalhistoryofBRVOindicatesthat74%mayimprovespontaneouslybytwolineswithin6months.Inpatientswhosevisiondoesnotspontaneously improve, theBranchVeinOcclusionStudyshowedthatgridlasertreatmenttothemaculacoulddecreasemacularedemaandimprovevisualacuity.24Thisimprovementwasveryslowlyachievedandonlymodestlybeneficial.Sincethepublicationofthisstudyin1984,gridphotocoagulationhasbeenthemainstayoftherapyforthiscondition.

Morerecently,theBRAVOstudyhasshownthatranibi-zumab injections dramatically improve visual acuity. LiketheCRUISEstudy,patientswererandomizedbetweenshaminjection,0.3mgofranibizumaband0.5mgofranibizumab.Theyreceivedmonthlyinjectionsfor6monthsfollowedbya6-monthobservationperiodwheretheycouldobtainad-ditionalmonthly treatment if theydemonstratedmacularedema.Theresultsindicatedthatbothdosesofranibizumabcauseanincreaseinvisualacuityinapproximately60%ofpatients. This was a statistically significant increase abovethe44%increaseinshaminjectionsat12months.LiketheCRUISEstudy,complicationswererare.24

Age Related Macular DegenerationPerhapsthemostdramaticuseofVEGFinhibitorsisin

thetreatmentofage-relatedmaculardegeneration(AMD).AMDcausessevere,irreversiblevisionlossandistheleadingcauseofblindnessinAmericansovertheageof65.25,26Itisdividedintotwosubtypes,drymaculardegenerationandneo-vascularmaculardegeneration(“wet”AMD).InneovascularAMD,choroidalneovascularizationbreaksthroughBruch’smembraneandtheretinalpigmentepithelialcellstogetintothesubretinalspace.Theretheneovascularizationcanleakserousfluidorbleedintotheretina.

VEGF inhibitors have revolutionized our treatment ofneovascularAMD.Leftuntreated,thisneovascularizationwouldgrow,bleedandformalarge,permanentscarinthecentralportionofthemacula(Figure 1).Thisleadstoalargecentralscotomawithseverevisuallossandisresponsiblefor

80%ofseverevisuallossfromAMD.Priorto2000,therewasnotreatmentwhichcouldpreventvisuallossinpatientswithneovascularAMDinwhichtheneovascularizationwasgrowinginthesubfoveallocation.

In 2000, the Food and Drug Administration approvedverteporfin (Visudyne) for use in photodynamic therapy.Usingthistechnique,thechoroidalneovascularmembranecouldbedestroyedandpreventvisuallossinapproximately60% of patients. However, visual improvement was rare,occurringinonly4%.27In2004,pegaptanibsodium(Macu-gen)wasapproved.ThisisanintravitreallyinjectedselectiveVEGFinhibitorofthe165isoformofVEGF–A.Becauseofitsselectivity,itdidnothaveprofoundinhibitoryeffect.Itsresultswere an improvement over photodynamic therapy,butitwasstilllacking.

In2006,ranibizumabwasapprovedforthetreatmentofneovascularmaculardegeneration.Twopivotalstudiesdem-onstratedthedramaticeffectofranibizumabonneovascularAMD, the MARINA study and the ANCHOR study.3,28Both studies compared ranibizumab with photodynamictherapyandbothshowedadramaticimprovementinvisionin40%ofpatientswithranibizumabascomparedto4%ofphotodynamictherapypatients.Italsoshowedthat95%ofpatientshadastabilizationofvisionwithranibizumab.Bothstudiesshowedveryfewseriousadverseeffectsofintravitrealranibizumab.

Similarlyin2006,bevacizumabwasfirstusedintravitreallyforthetreatmentofneovascularAMD.Smallstudieshaveshown similar results to the ranibizumab studies. InboththeANCHORandMARINAstudies,patientsweretreatedmonthlywithintravitrealinjections.Throughtheyears,how-ever,thegeneralfeelingofretinasurgeonswasthatmonthlyinjectionswerenotalwaysneeded.Consequently,surgeonsaroundtheworldhaveexperimentedwithalteringthedos-ingschedule,and,currently,themostcommonmethodofdosingistofollowpatientsmonthlyandtotreatonlyifthereisevidenceofactiveneovascularization.

Patients are examined clinically as well as with OpticalCoherence Tomography (OCT) to look for evidence ofactivity such as, the presence of subretinal or intraretinalfluid,orthepresenceofhemorrhage(Figure 2,p.35).Ifanyofthesefindingsarepresent,patientsaregivenaninjection;otherwise,theyareobservedandfollowed.

Another study called the PIER study looked at givingpatientsthreemonthlyinjectionsfollowedbyquarterlyin-jections.29Thisstudyshowedthat,althoughpatientscouldinitiallygetanimprovementinvisualacuity,theimprovementwaslostbytheendof12months.Forthisreason,itisvitallyimportanttofollowpatientscloselywithclinicalexaminationandOCTtomonitortheirvisualandretinalstatus.

Another controversy in the use of VEGF inhibitors iswhether bevacizumab is equivalent to ranibizumab. TheComparisonofAge-relatedmaculardegenerationTreatmentTrials(CATTstudy)comparedranibizumabandbevacizumab

Figure 1 Disciform Macular Scar

Retinal photo showing a disciform macular scar in a patient with neovascular age-related macular degeneration.


Figure 2 Optical Coherence Tomograph (OCT)

andshowedthatbevacizumabisequivalenttoranibizumabwhengivenmonthlyfor12months.Italsocomparedtheasneededdosingschedulewithmonthlyinjections.Inthisarmofthestudy,asneededbevacizumabwasslightlyinferiortoasneededranibizumab.However,thedifferencewasnotclinicallysignificant.Thedatacomparingthesafetyofbothdrugsshowednodifferencealthoughthenumbersstudiedweretoosmalltomakeanydefinitiveconclusionasseriouscomplicationsarerare.30Thisstudywillgiveretinasurgeonsconfidencetousebevacizumabasitcosts40timeslessthanranibizumab.

AnotherVEGFinhibitorhasjustcompletedphaseIIItrials.ItisaVEGFtrap(Afibercept,RegeneronPharmaceuticals,Inc.)whichbindsVEGFandpreventsitfromattachingtoitsreceptors.31TheadvantageoftheVEGFtrapisthatithasadosingscheduleallowingforinjectionseverytwomonths.The phase III study has shown it to be “non-inferior” tomonthlyranibizumab.

ConclusionVEGFinhibitorshavedramaticallyalteredretinaltreatment.

Inthe1980sand1990s,laserwasthemainstayforslowingvision loss from retinal vascular diseases, but it rarely ledtovisualimprovement.VEGFinhibitorsareatremendousbreakthroughbecausestudyafterstudyshowsimprovingvisualacuity.Theyhavealsoallowedustotreatblindingconditionswhichhadnotreatmentpriortotheirdevelopment,suchasmacularedemaincentralretinalveinocclusion.CurrentlyusedVEGFinhibitorsareverysafe,bothsystemicallyandophthalmologically,buttheneedformonthlyinjectionsisa significant obligation for many patients. Advances willcontinuetobemadewithlonger-actingdrugsonthehorizon.

References1. Arevalo, JF, Fromow-Guerra J, Quiroz-Mercado H, et al.

Primary intravitreal bevacizumab (Avastin®) for diabeticmacularedema:resultsfromthePan-AmericanCollaborative

RetinaStudyGroupat6-monthfollow-up.Ophthalmology. 2007;114:743-750.

2. EmersonMV,LauerAK.Emergingtherapiesforthetreatmentofneovascularage-relatedmaculardegenerationanddiabeticmacularedema.BioDrugs.2007;21:245-257.

3. RosenfeldPJ,BrownDM,HeierJS,etal.Ranibizumabforneovascularage-relatedmaculardegeneration.New England J Med2006;355:1432-44.

4. Practice Patterns: Diabetic Retinopathy. San Francisco, CA:AmericanAcademyofOphthalmology;2003.

5. National Diabetes Statistics, 2007. National DiabetesInformationClearinghouse,2008.

6. Bhagat N, Grigorian RA,Tutela A, Zarbin MA. Diabeticmacularedema:pathogenesisandTreatment.Surv Ophthalmol.2009;54(1):1-Preferred32.

7. SinghA,StewartJM.PathophysiologyofDiabeticMacularEdema.International Ophthalmology Clinics.2009;49(2):1-11.

8. Early Treatment Diabetic Retinopathy Study ResearchGroup. Treatment techniques and clinical guidelines forphotocoagulationofdiabeticmacularedema.EarlyTreatmentDiabeticRetinopathyStudyReportNumber2.EarlyTreatmentDiabeticRetinopathyStudyResearchGroup.Ophthalmology.1987;94(7):761-74.

9. Audren F, Tod M, Massin P, et al. Pharmacokinetic-pharmacodynamicmodelingfortheeffectoftriamcinoloneacetonideoncentralmacularthicknessinsubjectswithdiabeticmacularedema. InvestOphthalmol Vis Sci.2004;45(10):3435-3441.

10. Kuo C, Gillies M Role of Steroids in the Treatment ofDiabeticMacularEdemaInternational Ophthalmology Clinics.2009;49(2):121-134.

11. Diabetic Retinopathy Clinical Research Network. Arandomized trial comparing intravitreal triamcinoloneacetonideandfocal/gridphotocoagulationfordiabeticmacularedema.Ophthalmology.2008;115:1447-1459.

12. DiabeticRetinopathyClinicalResearchNetwork,BeckRW,Edwards AR, et al. Three-year follow-up of a randomizedtrialcomparingfocal/gridphotocoagulationandintravitrealtriamcinolonefordiabeticmacularedema.Arch Ophthalmol.2009;127:245-251.

(Top, left) OCT showing the presence of sub-retinal fluid in a pa-tient with neovascular AMD. Visual acuity is 20/200. (Top, right) OCT in the same patient following treatment with ranibizumab showing resolution of sub-retinal fluid. Visual acuity has improved to 20/30. (Left) OCT in the same patient showing recurrence of sub-retinal fluid. Visual acuity has dropped to 20/50.


13. DiabeticRetinopathyClinicalResearchNetwork.Randomizedtrialevaluatingranibizumabpluspromptordeferredlaserortriamcinolonepluspromptlaserfordiabeticmacularedema.Ophthalmology.2010;117:1064-1077.

14. MichaelidesM,KainesA,HamiltonRD,etal.Aprospectiverandomizedtrialofintravitrealbevacizumaborlasertherapyinthemanagementofdiabeticmacularedema(BOLTStudy):12-monthdatareport2.Ophthalmology.2010;117:1078-1086.

15. LangG.onbehalfoftheRESTOREstudygroup.Safetyandefficacyofranibizumabasmonotherapyoradjunctivetolaserphotocoagulationindiabeticmacularedema:12-monthresultsoftheRESTOREstudy.Late-breakerpresentationatEASDecMeeting.May22,2010.

16. NicholsonBP,SchachatAPAreviewofclinicaltrialsofanti-VEGFagentsfordiabeticretinopathy.Graefes Arch Clin Exp Ophthalmol.2010;248(7):915-30.

17. KleinR,MossSE,MeuerSM,KleinBE.The15-yearcumulativeincidenceofretinalveinocclusion:TheBeaverDanEyeStudy.Arch Ophthalmol2008;126:513-8.

18. Noma H, Funatsu H, Yamanstu M, et al. Pathogenesisof macular edema with branch retinal vein occlusion andintraocular levelsofvascularendothelialgrowth factorandinterleukin-6.AM J Ophthalmol2005;140:256-61.

19. CampachiaroPA,HufizG,ShahSM,etal.Ranibizumabformacular edemadue to retinal veinoccusions: ImplicationsofVEGFasacriticalstimulator.Mol Ther2008;16:791-9.

20. Evaluation of grid pattern photocoagulation for macularedemaincentralveinocclusion.TheCentralVeinOcclusionStudyGroupMreport.Ophthalmology1995;102:1425-33.

21. BrownDM,CampochiaroPA,SinchRP,etal.Ranibizumab

forMaculaEdemafollowingCentralRetinalVeinOcclusion:SixMonthPrimaryEndPointResultsofaPhaseIIIstudy.Ophthalmology2010;117(6):1124-1133.

22. Lihteh,W,ArevaloF,BerrocalM,etal.ComparisonofTwoDosesofIntravitrealBevacizumabasPrimaryTreatmentforMacularedemaSecondarytoCentralretinalVeinOcclusionResultsofthePanAmericanCollaborativeRetinaStudyGroupat24Months;Retina 2010;30:1002-1011.

23. Branch vein occlusion Study Group. Argon laser photocoagulationformacularedemainbranchretinalveinocclusion.Am J Ophthalmol 1984;98-271-82.

24. CampochiaroPA,HeierJS,FeinerL,etal.RanibizumabforMacularEdema followingBranchRetinalVeinOcclusion.Six-monthPrimaryEndPointResultsofaPhaseIIIStudy;Ophthalmology2010;117:1102-1112.

25. Bressler,NM.Age-relatedmaculadegenerationistheleadingcauseofblindness.JAMA2004;291:1900-1.

26. FriedmanDS,O’ColmainBJ,MonozB,etal.Prevalenceofage-relatedmaculardegenerationinTheUnitedStates.Arch Ophthalmol.2004;122:564-72.

27. Treatment of Age-related Macular Degeneration withPhotodynamicTherapy(TAP)StudyGroup.PhotodynamicTherapyofsubfovealchoroidalneovascularizationinage-relatedmaculardegenerationwithVereporfin:One-yearresultsof2randomizedclinical trials–TAPreport.Arch. Ophthalmol.1999;117:1329-45.

28. BrownDM,MichelsM,KaiserPR,etal.Ranibizumabversusverteporfinphotodynamictherapyforneovascularage-relatedmacular degeneration: Two-year results of the ANCHORstudy.Ophthalmology1009;116:57-65.

29. Regillo CD, Brown DM, Abraham P, et al. Randomized,doublemasked, sham-controlled trialof ranibizumab forneovascularage-relatedmaculadegeneration:PIERstudy1.AmJ Ophthalmol.2008;145:239-248.

30. TheCATTResearchGroupRanibizumabandBevacizumabForAge-RelatedMacularDegeneration.www.nejm.org/doi/full/10.1056/NEJMoa1102673.AccessedMay2011.

31. RegeneronPharmaceuticals,non-publisheddata.

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Figures 1-3 Normal Vision, Central Vision Loss and Peripheral Vision Loss

Evaluation and Treatment of the Low Vision Patient DianeCates,ODandKimRigdon,CLVT

Address Correspondence to: DianeM.Cates,OD,or KimRigdon,CLVT, LowVisionCenterofNortheastFlorida,2519RiversideAvenue,Jacksonville,FL 32204.Emails: [email protected], and [email protected]. Website: www.jacksonvil-lelowvision.com

Abstract: Many patients, as well as health care providers, are un-aware of the specialty service known as Low Vision (LV). The purpose of this article is to give the reader insight into the field of low vision while defining the difference between visual impairment and “legal” blindness. This will enable the reader to understand who is a candidate for a low vision evaluation while giving a glimpse of the various aspects of the low vision evaluation, devices, and services that are available to the visually-impaired patient.

Visual Impairment vs. Legal BlindnessKnowingthedifferencebetweenvisualimpairmentandthe

legaldefinitionofblindnessisimportant.Itisestimatedthatthereareapproximately300,000visuallyimpairedchildrenandbetween1.5 and3.4millionvisually impaired adultsin theUnitedStates.Thatnumber isexpected to increaseasthefirstbabyboomersturn65thisyear.Thereisadirectcorrelationbetweenagingandtheincreasedincidenceofeyedisease.1-6Morethantwo-thirdsofpersonswithlowvisionareovertheageof65,sotheneedforlowvisionserviceswillincreaseasthelargestproportionofourpopulationhitsthegoldenyears.7Aspeoplelivelonger,morewillbelivingwitheyediseaseandsomedegreeofvisualimpairment.

Visual impairmentisafunctional limitationoftheeyesorvisualsystemduetohereditaryoracquiredeyedisease,advancingage,ortraumathatcannotbecorrectedbycon-ventionaleyeglasses,contactlenses,medication,orsurgery.Thislossinvisionresultsinthepatient’sinabilitytoperformroutine activities of daily living such as reading, cooking,cleaning,maintainingpersonalhygiene,employment,and/ordriving.8-10

In contrast, the definition of legal blindness takes intoaccount the specific levelof central andperipheralvision.TheSocialSecurityActdefineslegalblindness:(1)remain-ingvisioninthebettereye,afterbestcorrection,<20/200or(2)contractionoftheperipheralvisualfield(VF)inthebettereyeeitherto<10ofromthepointoffixation;orwidestdiametersubtendsanangle<20o.11

Itisdifficulttounderstandandconceptualizewhatvisuallyimpairedpersonsseewhentheylookthrougheyesthathavebeenaffectedbymaculardegeneration,glaucoma,diabeticretinopathy,strokeorotherretinalorneurologicaldiseases.TheLighthouseInternationalwebsite(www.lighthouse.org),provides an excellent means of “experiencing” what yourpatientseesonadailybasis.AdaptedfromthewebsiteareFigures 1, 2, 3whichrepresentnormalvision,centralvisionlossandperipheralvisionlossrespectively.

Who Benefits From a Low Vision Evaluation?Patientsasyoungas3yearsoldandasoldas100+years

ofage,(averageage75),canbenefitfromalowvisionevalu-ation.Themostcommonlyseeneyeconditionsresponsibleforthedecreaseinvisionaremaculardegeneration,glaucoma,



mailto:kimrigdon%40hotmail.com?subject=

http://www.jacksonvillelowvision.com

http://www.jacksonvillelowvision.com

http://www.lighthouse.org


cataracts,diabeticretinopathy,andotherretinaldisorders.Althoughsomepatientssufferingfromprofoundvisionlossarelegallyblind,othersarelessseverelyvisually-impaired,butallsharethesamegoalsoftryingtomaintainindependentlifestylesandpositiveself-esteem.

Anyonewhohasvisionlossthatcannotbecorrectedwithconventionalglassesand/orcontactlensescanbeacandidateforaLVevaluation.Apatientwith20/50visioncanbeajustasgoodofacandidateforaLVevaluationasapatientwith20/400vision.Thedevicesandservicesrecommendedareindividualizedforeachpatient’spersonaldegreeofvisionloss,physicalandintellectualcapabilities,motivation,andvisualrequirements.

TheobjectiveoftheLVexaminationistorehabilitatethepatientwiththeuseofopticalandnon-opticaldevices.Itisnotabasic,dilatedeyeexamandshouldnotbemistakenforanexamtodiagnose,treat,ormonitoranyeyedisease.

Basic Components of the Low Vision ExamPriortotheLVevaluation,thelowvisionexaminerwill

contact the referring eye careprovider’soffice formedicalrecordstoensurethepatienthashadarecentfullexam,theconditionisrelativelystable,thedegreeofvision/visualfieldlossisdocumented,andthepatienthasbeencompliantwithrecommendedtreatmentandfollow-upcare.AtypicalLVevaluationisverydetailedandtime-intensiveandcantypicallylastuptotwohoursofone-to-onefacetimewiththeprovider.Inthecourseoftheevaluation,thepatientsareexposedtoandhavetheopportunitytotryawiderangeofLVdevicesthatrangefromthesimpletothecomplex.

PatientswhopresenttotheLVclinicareoftendepressed,anxious,orangryabouttheirvisionloss.Mostdonotwanttobe labeledas“blind”and/ordisabled.It isveryhelpfulwhenpatientshaveasupportivefamilymemberorprimarycaregiveraccompanythem,becausethefirstencountercanbe overwhelming. Addressing the psychosocial aspects ofvision loss is just as critical asprescribing the appropriateopticaldevices.The“perfect”devicemaybeavailable,butifthepatientisunwillingtouseit,orisintimidatedbythetechnology,failureisinevitable.AgoodLVprovidershouldnotonlyaddressvisualrehabilitation,butalsothesocialandpsychologicalissuesassociatedwithsignificantvisionlossinoursocietybymakingthepatientand/orhisfamilyawareofthevariousservicesandresourcesavailableinthecommunity.Itisoftenhelpfultoreferthesepatientstotrainedcounselorsand/orpeersupportgroupswhohavealsosufferedvisionlossandovercomedisability.

Patient History–Thebasicexambeginswithareviewofthesystemicandocularhistories.Thephysicalassessmentisveryimportant.Forexample,ifapatientissufferingfromParkinson’sdisease,ahandtremormayserveasacontraindi-cationtoahand-heldmagnifier.Astandmagnifierwouldbeamoresuitableoption.Thepatientwithaprofoundhearingdeficitmaynotbenefitfromatalkingdevice.Thediabeticpatient suffering from neuropathy may not benefit fromlearningBrailleduetotheirsensorydeficit.

The patient’s visual goals are discussed. The individualswhobenefitthemostfromtheLVevaluationarethosewithcleargoalsofwhatvisualtaskstheywanttomaster.Doesthepatientlivealoneordoeshe/shelivewithaspouseoradultchild?Thosewholivealoneusuallytakeadvantageofmoreofthedevicesandsocialservicesthatareavailablebecausetheyareoftenmoreself-reliant.Ifapersonismarriedandlivingwithahealthyspouse,he/sheissometimesmoredependentonthatspouseforassistancewithdailytaskssuchascooking,grocery shopping,balancing the checkbook, and/or travelarrangements.

Doesthepatientworkonacomputerorhaveadesiretolearn?Thisquestionisimportantbecausethepatient,whoiscurrentlyusingacomputer,isusuallylessintimidatedbythelowvisionelectronicreadingdevicesthanthepatientwhohasnocomputerexperience.Doesthepatienthaveproblemswithglare, require a lotof light to see,orhave eyeglassesand/or sunglasses that seemtohelp?Has thepersonusedmagnifierspurchasedoverthecounter?Manypatientshavethepreconceivednotionthatifanoverthecounter(OTC)magnifierdoesnotwork,thenneitherwillprescribeddevices.MostOTCmagnifiersprovideonly2Xmagnification;fartoolittlefortheaverageLVpatient.

Questions about difficulty with mobility are discussed,suchasproblemswithnavigatingcurbsorstairsorbump-ingintowallsorfurniturewhenwalking.Itisamazinghowpatientswillanswer“yes”tothisquestionandthendenyanyproblemswithdriving.The issueofdrivinghas tobe themostsensitivesubjectthatisdealtwithinanyeyeexam.ItoftenfallstotheLVspecialisttobetheoneto“confront”thepatientand“challenge”his/herabilityand“right”todrive.Givingupdriving represents a real loss of autonomyandindependence.Somepatientsgiveuptheactivitywillinglybecausetheyunderstandthedangers,butformostitisanintenseemotionaldiscussion.

TheminimumstandardsfordrivinginFloridarequire20/70visionineithereye,orbotheyestogetherwithorwithoutcorrectivelenses.However,ifoneeyeisblindor<20/200,theothereyemustbe>20/40.Thedrivermustalsohaveaminimum1300horizontalVF.IftheVFisinquestion,TheFloridaDepartmentofHighwaySafetyandMotorvehiclesrequiresverificationoftheperipheralvisionbythespecifiedVFmodalities.Theuseof telescopic lenses tomeetvisualstandardsisnotallowed.12

If “any physician, person, or agency has knowledge ofanylicenseddriver’smentalorphysicaldisabilitytodrive,theyareauthorizedtoreportthatdrivertotheDepartmentofHighwayandSafetyandMotorVehicles.”Thereportisconfidentialandnocivilorcriminalactionmaybebroughtagainstanyphysician,personoragencywhoprovidesinfor-mation(HSMVForm72190).Itdoesrequirethereportingentity’sname,address,andphonenumber.13Thekeywordshereare“authorized”andnot“required”,therebycreatingapotentialdilemmaforthephysician.

Continued on page 40


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differentexpensivemachinespriortopurchasingbecausethecamera,screenquality,printsize,contrastenhancementandotherfeaturescanvarytremendously.

The“best”LVclinicisonethathasavastarrayofopticalandnon-opticaldevicesavailableforhands-onusesothatanydevicesprescribedhavefirstbeentriedbythepatient.Itisverygratifyingtoseepatientsonestepclosertoachievingsomeoftheirvisualgoals.

TheLVexamalsoinvolvesworkingwiththecertifiedlowvision therapist (CLVT) who provides additional device-training, CCTV evaluations, lens tint, and optical filterselection. A demonstration of lighting requirements andanintroductiontoanddiscussionofnon-opticalaidsandcommunityresourcesisalsoundertaken.

Available Resources Therearemanyresourcesavailableforpeoplewithvision

lossbothatthelocalandnationallevels.Inmoststates(FLandGAincluded),statefundingprovidesrehabilitationfortheblind.Theseservicesareavailabletopatientswithvaryingdegreesofvisualloss.Theytendtofocusonhelpingpeoplemaintain independencedespitevision loss.Unfortunately,theamountofassistanceisdependentonfundingallocation.InFlorida, theDivisionofBlindServices (DBS)providescounselorstoassistchildrenwithaccessibilitytotheschoolsystem.VocationalRehabilitation canhelppeoplefindormaintainwork.DBSfundingfordevicesisprimarilyavail-ableforpediatricpatients,students,andadultsinthepre-Medicareagegroup.14

DBSteachesindependentlivingskillsforunemployedorretiredpersonsandrehabilitationtrainingthrough“Indepen-dentLivingfortheAdultBlind”(ILAB),auniquenon-profitorganizationlocatedatFloridaStateCollegeofJacksonville.ILAB has rehabilitation teachers who provide individualand group classes that teach necessary skills such as waystoidentifymoney,cookmeals,ambulateinthehomeandcommunityandperformpersonalgroomingskills.AtleastoneILABstaffmemberisvisually-impairedandisavailabletohelppeopleovercometheirdisabilitysufferedbyvisionlossandtoprovidecounselingthroughthatgrievingprocess.AlsoonstaffatILABaremobilityinstructorswhoteachsafetyandcanetechniquesandcomputerinstructorsthatteachthescreenenlargementsoftwareprograms.Thereisalsoatransi-tionprogramforteenagerstopreparethemfortheworkforce,college,and/orlifeafterhighschool.

Manyvisually-impairedpatientsreportmissingtheabilitytoreadmorethananythingelse.SeverallibrariesinDuvalCountyhaveaseparatesectionforlargeprintbooks.Largeprintbooksarealsoavailableforpurchaseatmostbookstoresandonline.Thenewelectronicbookreadersoffertheabilitytoenlargethefont(notnearlyasmuchaswiththemagnifiersmentionedabove)and/orlistentobooksthatareavailabletodownloadandpurchase.Itisalwaysbestforthepatienttotrythesereaderspriortopurchasingastheydifferincon-trast,fontsize,andvoice.Itisimportanttonotethatthesee-readersarenotLVdevices.

Visual Assessment–TheLVacuitydeterminationstartsatadistanceof10feet(asopposedtothe“standard”20feetviewingtheSnellenchartprojectedonascreenacrosstheroom).MostLVpatientscannotseethisfaraway,somoveablechartsareused.Theycanberepositionedascloseasneeded.Theyhavemorelinesofvisionthatcanbetestedwithmoreletters at each level of acuity represented. Each patient ischecked for scotomas (blind spots) and metamorphopsias(distortionscausing“bending”ofstraightlines).

TheLVfractionincludesatrialspectacleframeandlenseswornbythepatient.Althoughtheframeisheavyandbulky,itallowsapatienttomovetheheadandturntheeyesallowingbetterfunctionalvision.Thisisknownas“eccentric”view-ingandcomesnaturallytomanylowvisionpatients.Thephoropter,thestandardapparatususedforrefraction,doesnotallowforheadoreyemovementsnecessaryforeccentricviewing.Trialframeuseallowsthepatienttoexperiencetheneweyeglassprescriptionbeforepurchasingnewglasses.Thissameprocessisrepeatedfornear(reading)visiontodeterminewhatbifocalpowerisnecessaryandtoletthepatientknowwhatsizeprinthe/shecanrealisticallybeexpectedtoread.

Low Vision Devices –Thenextstep intheLVexamistodeterminewhatLVdevicesmightbebestsuitedforthepatient’s individualneeds andvisual goals.Dependingonthelevelofvision,ahand-heldorastand-magnifiermaybebeneficial.Sometimesthissamemagnificationcanbeusedtocreateveryhighpowereyeglasses.Atothertimes,customtelescopesandmicroscopesaredesignedforthepatient,eitherashand-heldorglasses-mounteddevices.Oneshouldchoosetheleastamountofmagnificationorpowerthatwilldothebestjob.ToomuchmagnificationrequiresthatthepatienteitherholdsthematerialtoocloseforcomfortordecreasessizeofVF.Inthiscase,thepatientwillonlybeabletoreadletterbyletter,insteadofviewingwordsandsentencesasawhole.Thisadverselyaffectsreadingcomprehension.

ClosedCircuitTelevisions(CCTVs)provideawiderfieldofvision.CCTVs(alsocalledvideomagnifiersorelectronicmagnifiers)areessentialforthosepatientswhostillwanttoreadforthemselvesandcannotusemagnifiers.Whiletheyhavebeenavailableforatleast20years,theyhavechangeddrasticallyinthelast5years.Readingmaterialsareputunderacameraandthetextismagnifiedontoascreen.Mosttypedorwrittenmaterial(i.e.mail,books,magazinesornewspapers)canbereadwithalargerfieldofviewthanwitharegularmagnifier.Itgivestheusertheability(withpractice)towritechecks,seephotos,readpillbottles,etc.

ThevastmajorityofLVpatientshaveproblemswithcon-trast.CCTVs(availableinlaptopand/ordesktopmodelsandhand-heldportabledevices)provide enhancementof text,background,color,andbrightnessandcanworkwithscreenenlargementsoftware.Eachtypehasdifferentcapabilitiesandcanbeusedfortasksfromseeingthefrontoftheclassroomtoapplyingmakeup.Itishelpfulforthepatienttotrythe

Continued from page 38


Thetalkingbookprogramisoneofthemanywonderfulfree services theNationalLibraryService (NLS)provides.The patient’s optometrist, ophthalmologist, primary careprovider,ortherapisthastoverifythatthepatientqualifiesforservices.Applicantsaregiventheopportunitytoselectthesubjectstheywouldenjoyreading.TheNLSwillmailtapesordigitalcartridgesthatreadbookswithinthechosensubjectareas.15TheNLSwillalsoprovidethequalifiedap-plicantwithatapeplayerordigitalcartridgeplayer.Whenthepersonisfinishedlisteningtothebook,itisplaceditintheoriginalgreenpackagepre-marked“freematterfortheblind”andputinthemailbox.Theentireprogramisprovidedatnochargetothepatient.

TheNLSalsooffersdescriptivevideosorDVDsthroughthesamefreemailingformat.Thisallowsvisually-impairedpeopletolistentospecificdescriptionsofactivitieshappeningthroughoutamoviethattheywouldnormallybeunabletosee.Thesedescriptionsdonotinterferewiththeenjoymentofthemovieforthosewhoaresighted.Additionally,theyalsoofferlargeprintorBraillemusicinseveralcategoriesandstyles.Thesheetmusicrangesfromvocaltoinstrumentssuchasthepianoandorgan.ManyoftheNLSmusicservicesareavailableaswebpagesortextfilesthatcanbedownloadedtoacomputer.15

VeteranshavetopprioritytobookselectionsfromNLS.TheyalsohaveaccesstoahostofotherfreeservicesthroughtheVeteransAdministrationMedicalCenter(VAMC).TheyprovideLVexams,vocationalrehabilitation,andsomeLVdevices tohonorablydischarged, legallyblindveterans re-gardlessofwhethervisionlossoccurredinthelineofduty.16

For thosepatients that areunable to read themorningnewspaper and/or those who prefer to use their auditoryskills, the National Federation for the Blind offers a freetelephone newspaper reading service which includes over300newspapers.17TheNew York Timesoffersaweeklylargeprintsubscriptiontotheirnewspaper,whichincludesalargeprintcrosswordpuzzleandpictures.18

InJacksonville,theWJCT(localNPRstation)RadioRead-ingServiceprovidesaspecialradiotothevisually-impairedpatientonwhich they can receive adaily scheduleof theFlorida Times Union.Portionsofothernewspapersandlocalliteraturearealsoread.Theseservicesaremadepossiblebylocaldonations.19

Somephonecompaniesprovidefreedirectoryassistanceforindividualswhoprovidealetterofverificationofvisualimpairmentbyaneyedoctor.Bydialing“0”or“411”theoperatorverballygivesthevisually-impairedpersonthere-questedphonenumber.Thespecialneedsdepartmentofthephonecompanycanbecontactedformoreinformation.20

Cellularphoneshavebecometheprimaryphoneformanypeople.Therearequitea fewstyles thatareeasyanduserfriendlywithlargeprintandhighcontrast.Severalcompa-niesofferfreevoicedialingservices.Othercompaniesoffersoftwarethatcanbedownloadedtoassistwithcellphoneuse.

Patientsareadvisedtocontacttheindividualcompaniestohearthefullrangeofcellphoneservicesavailableforpeoplewithvisualimpairments.21

Thecomputerpresentsnumerouspossibilitiesandchal-lengesforpeoplewithvisionloss.Therearevariousscreenmagnifiers suchasZoomtext thancanmagnifyas littleas1X-2Xandasmuchas36X.22Theyalsoprovideabolderappearancewithdifferentcolorfilteringschemes,aswellasenhancementstohelplocatethecursorandpointer.Therearealsovariousapplicationsthatprovidescreenreadingcapabili-tiesinseveralchoicesofvoicesandspeeds.

ConclusionThepurposeofthisarticlewastoprovideanoverviewof

someoftheoptionsthatareavailabletothevisually-impairedpatient.Despiteallofthetechnologyandresourcesreviewed,nothing replaces human interaction, encouragement, andpositivere-enforcement.Asphysicians,ourmostimportanttasksmaybetolistentoourpatientsandtrytoseetheworldthroughtheireyesandrealizethatwhileitmaynotbepos-sibletorehabilitatetheeyes,wecanrehabilitatethelivesofthesepatients.

References1. Vision Problems in the U.S.PreventBlindnessAmerica,National

EyeInstitute,2002.2. MassoffRW.Amodeloftheprevalenceandincidenceoflow

visionandblindnessamongadultsintheU.S.Optom and Vis Sci.2002;79(1):31-8.

3. TheEyeDiseasesPrevalenceandIncidenceResearchGroup,CausesandprevalenceofvisualimpairmentamongadultsintheUnitedStates.Arch Ophthalmology.2004;122:477-85.

4. Vitale S, Cotch MF, Sperduto RD. Prevalence of visualimpairment in the United States. JAMA. 2006; 295 (18):2158-63.

5. United States Department of Commerce, Economics andStatisticsAdministration,BureauoftheCensus.Statistical brief: 65+ in the United States.Washington,DC,December2005.

6. AmericanFoundationfortheBlindwebsite:http://www.afb.org/Section.asp? SectionID=3&TopicID=138&DocumentID=3350.Accessed2011.

7. NationalAdvisoryEyeCouncil.Visionresearch:anationalplan1999-2003.ReportoftheNationalAdvisoryEyeCouncil.DHHSpublicationno.(NIH)98-4120.Washington,DC:U.S.GovernmentPrintingOffice,1998.

8. UnitedStatesDepartmentofHealthandHumanServices.Theinternationalclassificationofdiseases,9threvision,clinicalmodification(ICD-9-CM),4thed,vol1.U.S.DHHS(PHS-HCFA).Washington,DC,1996.

9. West SK, Rubin GS, Broma AT, et al. How does visualimpairmentaffectperformanceontasksofeverydaylife?Arch Ophthalmol.2002;120:774-80.

10. FraserFreemanK,ColeRG,Faye,EE,etal.Optometric Clinical Practice Guideline Care of the Patient with Visual Impairment (LowVisionRehabilitation)ReferenceGuideforClinicians.AmericanOptometricAssociation,St.Louis,MO,2007;1-8.

11. SocialSecurityAct.UnitedStatesSocialSecurityAdministration.Code of Federal Regulations, Title 20, Ch. III, Pt. 404,Subpt.P,App.1.ListofImpairments.U.S.DHHS(SSA).Washington,DC,2006.

http://www.afb.org/Section.asp? SectionID=3&TopicID=138&DocumentID=3350




12. StateofFlorida–DivisionofBlindServiceswebsite:http:www.flhsmv.gov/ddl/fagmed.html–HSMVform72010.Accessed2011.

13. NationalLibraryServicewebsite:http:www.flhsmv.gov/ddl/fagmed.html–HSMVform72190.Accessed2011.

14. VeteransAdministrationwebsite:http://www.myflorida.com/dbs/about-us/services.php.Accessed2011.

15. NationalFoundationfortheBlindwebsite:http://www.loc.gov/nls/music/orderform.html.Accessed2011.

16. NewYorkTimeswebsite:http://www1.va.gov/BLINDREHAB/VIST.asp.Accessed2011.

17. WJCT website: http://www.nfb.org/nfb/Newspapers_by_Phone.asp.Accessed2011.

18. AT & T phone company website: http://homedelivery.nytimes.com/HDS/ LargeTypeWeeklyHome.do?mode=ChooseCountry.LargeTypeWeeklyAccessed2011.

19. AT&Twireless:http://www.wjct.org/radio/reading.Accessed2011.

20. Aisquared website: http://www.att.com/esupport/article.jsp?sid=KB403192.Accessed2011.

21. Aisquared website: http://www.wireless.att.com/learn/articles-resources/disability-resources/disability-resources.jsp.Accessed2011.

22. Aisquared website: http://www.aisquared.com/zoomtext.Accessed2011.

Dr. Jerry Maida has been setting the standard for laser vision correction for over 20 years. In 1989, Dr. Maida was one of the first in the U.S. to employ the excimer laser, which is now utilized for refractive laser surgery. He has performed over 30,000 surgeries and more than 18,000 Lasik procedures.

He is one of the few in the southeast to utilize the next generation Intralase-ifs laser in combination with the advanced Eye-Q Allegretto Laser. This results in uniquely safe, precise, and predictable Lasik surgery.

At Maida CustomVision, Dr. Maida and his exception-ally service oriented staff work diligently every day to do their utmost to improve the lives of patients, and to help them view their world with crisp, clear vision. Dr. Maida is one of Jacksonville’s most recommended Lasik surgeons based on his impeccable reputation. That is one of the many reasons why patients choose to place their vision in the hands of a trusted professional like Dr. Maida.

It is this dedication to quality patient care and innovations in refractive technology that sets Maida CustomVision apart and has attracted patients from not only across the United States, but also from continents as far as Europe and Australia.

Dr. Maida made a difference in so many lives.

Call now for your evaluation to see if LASIK is right for you. You will be glad you did.

LASIK268-EYES

Meet the Doctor

maidalaser.com

DCMS Hosts AMA President-Elect During Annual Leadership Visit

TheDCMSwelcomed(above,L)PeterCarmel,MD,President-Electof theAmericanMedicalAssociation to Jacksonville,May8-9,2011.APediatric Neurosurgeon, Dr. Carmel practicesat the University Hospital of the New JerseyMedicalSchool.PicturedwithDr.Carmelare(above,center)MalcolmFoster,Jr.,MD,DCMSPresidentand(above,R)YankD.Coble,Jr.,MD,aPastAMAPresident.WhileinJacksonville,Dr.Carmeltouredvariousmedicalinstitutions,metwithlocalmediaandotherareagroups.HewasthespeakerataDCMSMembershipDinneronMay9atEppingForestYachtClub.

http://www.flhsmy.gov

http://www.flhsmy.gov

http://www.flhsmv.gov/ddl/fragmed

http://www.flhsmv.gov/ddl/fragmed

http://www.myflorida.com/dbs/about-us/services.php

http://www.myflorida.com/dbs/about-us/services.php

http://www.loc.gov/nls/music/orderform.html

http://www.loc.gov/nls/music/orderform.html

http://www1.va.gov/BLINDREHAB/VIST.asp

http://www1.va.gov/BLINDREHAB/VIST.asp

http://www.nfb.org/nfb/Newspapers_by_Phone.asp

http://www.nfb.org/nfb/Newspapers_by_Phone.asp

http://homedelivery.nytimes.com/HDS/ LargeTypeWeeklyHome.do?mode=ChooseCountry.LargeTypeWeekly



http://www.wjct.org/radio/reading

http://www.att.com/esupport/article.jsp?sid=KB403192

http://www.att.com/esupport/article.jsp?sid=KB403192

http://www.wireless.att.com/learn/articles-resources/disability-resources/disability-resources.jsp



http://www.aisquared.com/zoomtext


Knowledge about breast health empowers patients to partner with their physicians

in order to receive the most effective healthcare possible.


DCMS Membership Applications Thesephysicians’ applications for

membership in the Duval CountyMedical Society are now being pro-cessed.Any informationoropinionsyoumayhaveconcerningtheeligibilityof the applicants listed here may bedirectedtoAshleyBoothNorse,MD,DCMSMembershipCommitteeChair(904-244-4106orBarbaraBraddock,MembershipDirector(904-355-6561x107).

Larissa S. Buccolo, MDFamilyMedicineJacksonvilleFamilyPracticeAssociates1731UniversityBlvd.S.MedicalDegree:EmoryUniv.SchoolofMedicineResidency:NHSJAXNominatedby:RobertRaspa,MD;JackGiddings,MD;NeirouzJoseph,MD

Kuo Yun Chen, MDPediatrics/UFPediatrics655W.8thSt.3rdFLLRCMedicalDegree:MedicalCollegeofGeorgiaSchoolofMedicineResidency:OrlandoRegionalMedicalCenterNominatedby:UFJP

Andrew P. Daigle, MDPalliativeMedicineCommunityPalliativeConsultants4266SunbeamRd.MedicalDegree:LSUSchoolofMedicine/NewOrleansResidency:GreenvilleHospitalSystemFellowship:UABBirminghamSchoolofMedicineNominatedby:StephenClark,MD;JerrySayre,MD;ReetuGrewal,MD

Bryan A. Farford, DOFamilyMedicine/Mayo4500SanPabloRd.MedicalDegree:NovaSoutheasternUniversityCollegeofOsteopathicMedicineResidency:MayoClinicNominatedby:JohnPresutti,MD;PaulRoberts,MD;ToddBrinker,MD

Ashwani K. Gupta, MDNephrology/UFNephrology655W.8thSt.ClinicalCenterBasementMedicalDegree:AllIndiaInstituteofMedicalScienceInternship:HarvardSchoolofPublicHealthResidency:MichiganStateUniversityMedicalSchoolFellowship:HenryFordHospitalNominatedby:UFJP

Pratibha N. Gupta, MDDiagnosticRadiology/UFRadiology

655W.8thSt.2ndFLClinicalCenterMedicalDegree:MakerereUniv.SchoolofMedicineResidency:NewJerseyUniversityofMedicine&DentistryFellowship:StonyBrookUniversityHospital&UniversityofNorthCarolinaMedicalSchoolNominatedby:UFJP

Christopher Klassen, MDRadiology/UFRadiology655W.8thSt.2ndFLClinicalCenterMedicalDegree:UniversityofMinnesotaMedicalSchoolInternship/Residency:Univ.ofTexasMedicalSchoolResidency:UniversityofMinnesotaMedicalSchoolFellowship:UFHSC/Jacksonville&UniversityofTexasSWMedicalSchoolNominatedby:UFJP

Bettina A. Kohaut, MDOB-GYNFabenOB-GYN836PrudentialDr.#1506MedicalDegree:MichiganStateUniversitySchoolofMedicineResidency:UniversityofFloridaCollegeofMedicine-JacksonvilleNominatedby:MitziBrock,MD;ToddRasner,MD;GuyBenrubi,MD

Susan H. Krieger, MDPediatrics/CommunityHospicePedsCare4266SunbeamRoadMedicalDegree:GeorgetownUniversitySchoolofMedicineResidency:VirginiaCommonwealthUniversityMedicalSchoolNominatedby:UFJP

Naeem Latif, MDHematology/OncologyUFHematology/Oncology655W.8thSt.Pavilion4thFLNorthMedicalDegree:AyubMedicalCollegeResidency:UniversityofPittsburghCollegeofMedicineFellowship:UFHSC/Jacksonville&Montefiore/EinsteinMedicalCenterNominatedby:UFJP

Fatina E. Milfred, MDNeurology/NeuroscienceInstituteAtShands580W.8thSt.9thFLTowerIMedicalDegree:UniversidadNacionalPedroHernandezVienaInternship:WoodhullMedicalCenterResidency:UFHSC/JAXNominatedby:UFJP

Mark B. Phillips, MDAnesthesiologyUFAnesthesiology655W.8thSt.2ndFLClinicalCenterMedicalDegree:Univ.ofMiamiCollegeofMedicineResidency:JacksonMemorialHospital&UCLAMedicalCenterNominatedby:UFJP

Jin Hee Ra, MDTraumaSurgery/CriticalCareMedicineUFTraumaSurgery655W.8thSt.8thFLClinicalCenterMedicalDegree:UniversityofLouisvilleSchoolofMedicineResidency/Fellowship:HospitaloftheUniv.ofPennsylvaniaNominatedby:UFJP

Luis Ramirez, MDInfectiousDiseaseRainbowCenter655W.8thSt.3rdFLClinicalCenterMedicalDegree:SanMarcosUniversityResidency:BronxLebanonHospitalCenterFellowship:SUNYUpstateMedicalUniversityNominatedby:UFJP

Daniel K. Robie, MDPediatricSurgeryNemoursChildren’sClinic807Children’sWayMedicalDegree:HahnemannUniversitySchoolofMedicineResidency:WalterReedArmyMedicalCenterFellowship:BaylorCollegeofMedicineNominatedby:AlbertWilkinson,Jr.,MD;DanielleWalsh,MD;GaryJosephson,MD

Monali Sakhalkar, MDOphthalmology/UFOphthalmology/580W.8thSt.3rdFLTowerIIMedicalDegree:BarodaMedicalCollegeInternship:StatenIslandUniversityHospitalResidency:InterfaithMedicalCenter&LSUSchoolofMedicineFellowship:DeanMcGeeEyeInstitute&UniversityofWisconsinMedicalSchoolNominatedby:UFJP

Sukhwinder Sandhu, MDRadiologyUFRadiology655W.8thSt.2ndFLClinicalCenterMedicalDegree:TheJohnsHopkinsUniversitySchoolofMedicineInternship/Residency:JacksonMemorialHospitalFellowship:MAGeneralNominatedby:UFJP

Nipa R. Shah, MDFamilyMedicineUFCommunityHealthCenter655W.8thSt.4thFLACCMedicalDegree:UniversityofIllinoisSchoolofMedicineInternship:MetrohealthHospitalResidency:UniversityofNewMexicoHospitalNominatedby:UFJP

Matthew B. Shannon, MDEmergencyMedicineUFEmergencyMedicine655W.8thSt.1stFLClinicalCenterMedicalDegree:CreightonUniversitySchoolofMedicineResidency:UniversityofIllinoisCollegeofMedicine-PeoriaNominatedby:UFJP

Stephanie V. Sims, MDPsychiatry/UFPsychiatryCen.580W.8thSt.TowerII#6005MedicalDegree:MedicalUniversityofSouthCarolinaInternship:TulaneUniversitySchoolofMedicineResidency:BaylorCollegeofMedicineFellowship:MedicalUniversityofSouthCarolinaNominatedby:UFJP

Phyliss N. Taylor, MDPsychiatry/UFPsychiatryCen.580W.8thSt.TowerII#6005MedicalDegree:MeharryMedicalCollegeResidency:EastCarolinaUniversitySchoolofMedicineNominatedby:UFJP

Paola F. Tumminello, MDNeurology/NeuroscienceInstituteAtShands580W.8thSt.9thFLTowerIMedicalDegree:FedericoIISchoolofMedicineInternship:St.AgnesHospitalResidency/Fellowship:MedicalUniversityofSouthCarolinaNominatedby:UFJP

Paul L. Wasserman, DORadiology/UFRadiology655W.8thSt.2ndFLClinicalCenterMedicalDegree:KansasCityUniv.ofMedicine&BioscienceInternship:TheWesternPennsylvaniaHospitalResidency:UniversityofPittsburghMedicalCenterFellowship:WakeForestUniversityBaptistMedicalCenterNominatedby:UFJP

Richard Westenbarger, MDEmergencyMedicineUFEmergencyMedicine655W.8thSt.MedicalDegree:UniversityofFloridaCollegeofMedicineResidency:UFHSC/JacksonvilleNominatedby:UFJP


Treasury and Payment Solutions Lending Investments Financial Planning

Deposit products and services are offered through SunTrust Bank, Member FDIC.

Securities and Insurance Products and Services: Are not FDIC or any other Government Agency Insured • Are not Bank Guaranteed • May Lose ValueSunTrust Private Wealth Management Medical Specialty Group is a marketing name used by SunTrust Banks, Inc., and the following affiliates: Banking and trust products and services are provided by SunTrust Bank. Securities, insurance (including annuities and certain life insurance products) and other investment products and services are offered by SunTrust Investment Services, Inc., an SEC-registered investment adviser and broker/dealer and a member of FINRA and SIPC. Other insurance products and services are offered by SunTrust Insurance Services, Inc., a licensed insurance agency.

©2011 SunTrust Banks, Inc. SunTrust and Live Solid. Bank Solid. are federally registered service marks of SunTrust Banks, Inc.

A financial advisor dedicated to the medical industry can help you navigate changes in your practice’s finances.

The business of medicine, much like your practice itself, is forever evolving. And with new financial opportunities and ongoing concerns — like protecting against fraud, managing risk and anticipating the impact of insurance and reimbursements on cash flow — you need the guidance of an advisor who uniquely understands your industry. At SunTrust, advisors with our Private Wealth Management Medical Specialty Group work solely with physicians and their practices to deliver solutions designed for the medical community. To schedule an appointment with an advisor, call 904.632.2854 or visit suntrust.com/medicine to learn more.


Dr. James St. George is proud to join the Jacksonville community, bringing more than 20 years experience in treating vascular disorders. The recent opening of the St Johns Vein Center provides

you with a new option for patients suffering from lower extremity venous disease including:

Your patients no longer have to drive downtown for specialist vein care. Our state-of-the-art facility is conveniently located just off the Baymeadows road exit on 9A. We provide the following treatment options:

James St. George, M.D. is a vascular specialist and a diplomat with the American Board of Radiology with a Certificate in Interventional Radiology. He completed his fellowship training at Harvard Medical School’s

Brigham and Women’s Hospital and served for 12 years as faculty at Harvard Medical School, Dartmouth Medical School and Drexal School of Medicine. He also held the position of Head of Special Procedures at Hahnemann Hospital in Philadelphia. Dr. St. George takes the time to know each patient and creates customized treatment programs to obtain the best possible results.

• Chronic venous insufficiency• Chronic distal skin changes including abnormal increased pigmentation, eczema, ulceration• Leg, ankle and foot swelling

• Leg pain, cramps, discomfort• Restless legs• Varicose veins• Spider veins

• Radiofrequency ablation• Laser ablation• Ultrasound-guided chemical ablation

• Foam sclerotherapy• Liquid sclerotherapy• Ambulatory phlebectomy

9 1 9 1 R G S k i n n e r P a r k w a y • S u i t e 3 0 3 • J a c k s o n v i l l e , F L 3 2 2 5 6

Introducing the St Johns Vein Center

We are a participating provider for Medicare, Tricare and most Commercial payers. Please visit www.stjohnsvein.com for more information or call (904) 402-VEIN (8346)

to learn more about the care we can provide for your patients.

w w w. s t j o h n s ve i n . co m • (904) 402-VEIN (8346)

904.407.6500 referral line 866.253.6681 toll-free communityhospice.com

Community Focused � Community Suppor ted � Serving Baker, Clay, Duval, Nassau and St. Johns counties since 1979

For 30 years, family medicine physicians such asDr. Stephen Clark have helped Northeast Floridaresidents and their loved ones have a better qualityof life. For patients with advanced illness whoneed specialized care, these professionals callon Community Hospice of Northeast Florida.

Community Hospice staff ensure that all patients’care needs—body, mind and spirit—are met,wherever and whenever they are needed most.These multidisciplinary experts work alongsidemedical providers to help family caregivers knowwhat to expect and make informed care choices.

To learn more about how Community Hospice canhelp your patients and their family caregiverslive better with advanced illness, call904.407.6500 to schedule anin-office or in-hospital visit.

it’s all about helping

live better

Stephen J. Clark, MDJacksonville family medicine physician andpractice owner for nearly 30 yearsJoined Community Hospice as Chief Medical Officer, June 2009

families

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Documents

Northeast Florida Medicine - Summer 2011 - Ophthamology