Heating of the CorneaWord下载.docx

Heating of the CorneaWord下载.docx

《Heating of the CorneaWord下载.docx》由会员分享，可在线阅读，更多相关《Heating of the CorneaWord下载.docx（12页珍藏版）》请在冰豆网上搜索。

AnEngineeringReviewofElectrodesandApplicators

EnriqueJBerjano,*1EnriqueNavarro,2VicenteRibera,2JavierGorris,2andJorgeLAlió

3,4

1InstituteforResearchandInnovationonBioengineering,TechnicalUniversityofValencia,Valencia,Spain

2NepturyTechnologies,Almassora,Spain

3CorneaandRefractiveSurgeryDepartment,Vissum-InstitutoOftalmoló

gicodeAlicante,Alicante,Spain

4PathologyandSurgeryDepartment,UniversidadMiguelHerná

ndez,Elche,Spain

*AddresscorrespondencetothisauthorattheInstituteforResearchandInnovationonBioengineering,TechnicalUniversityofValencia,Valencia,Spain;

E-mail:

eberjano@eln.upv.es

Abstract

Thispaperreviewsthedifferentapplicatorsandelectrodesemployedtocreatelocalizedheatinginthecorneabymeansoftheapplicationofradiofrequency（RF）currents.Thermokeratoplasty（TKP）isprobablythebestknownofthesetechniquesandisbasedontheprinciplethatheatingcornealtissue（particularlythecentralpartofthecornealtissue,i.e.thecentralstroma）causescollagentoshrink,andhencechangesthecornealcurvature.Firstly,wepointoutthatTKPtechniquesareacomplexchallengefromtheengineeringpointofview,duetothefactthatitisnecessarytocreateverylocalizedheatinginapreciselocation（centralstroma）,withinanarrowtemperaturerange（from58to76º

C）.Secondly,wedescribethedifferentapplicatordesigns（i.e.RFelectrodes）proposedandtestedtodate.Thisreviewisplannedfromatechnicalpointofview,i.e.thetechnicaldevelopmentsareclassifiedanddescribedtakingintoconsiderationtechnicalcriteria,suchasenergydeliverymode（monopolarversusbipolar）,thermalconditions（dryversuscooledelectrodes）,lesionpattern（focalversuscircularlesions）,andapplicationplacement（surfaceversusintrastromal）.

INTRODUCTION

Localizedheatingofthecorneahasbeenemployedsince1889fordifferenttherapeuticandsurgicalobjectives.Thebestknownofthesetechniquesisprobablythermokeratoplasty（TKP）,whichisbasedontheprinciplethatheatingcornealtissue（particularlythecentralpartofthecornealtissue,i.e.thecentralstroma）causescollagentoshrink,andhencechangesthecornealcurvature[1].However,theprocesscanbeusedforothertherapeuticobjectives.TKPisacomplexchallengefromtheengineeringpointofview（seeFig.​11）.Ononehand,itisnecessarytocreateverylocalizedheatinginapreciselocation（centralstroma）,keepingtheendotheliumthermallyprotected（whichislocatednomorethan300μmdistantfromthecentralstroma）.Theendotheliumisamono-cellularlayerinthehumaneyewhichisnonregenerable,andhencethetemperatureatthispointshouldalwaysbemaintainedatasafelevel（e.g.lowerthan45º

C）.Consequently,theprocedurerequiresanextremelyhighspatialresolution.Thetemperatureattheepitheliumisnotsocritical:

someTKPtechniquescombinesurfacecoolingtocreateatemperatureprofilewithalowtemperatureattheepithelium（seesolidlineinFig.​11）.Incontrast,othertechniques（likeintrastromalapplicators）heatboththeepitheliumandthecentralstroma（seedashedlineinFig.​11）.

Fig.

（1）

Left:

Schematicdiagramofthecorneashowingtheanteriorlayer（epithelium）,theposteriorlayer（endothelium）,separatedbythestroma.Theaimofthethermokeratoplasty（TKP）procedureistocreatesafelocalizedheatinginthecentralstroma.Right:

Optimum（solidline）andsuboptimum（dottedline）thermalprofilesinthecorneaforthemokeratoplasty（TKP）.TKPtechniquesareacomplexchallengefromtheengineeringpointofview,duetorequiring:

1）anextremelyhighspatialresolution（i.e.itisnecessarytocreateverylocalizedheatinginapreciselocationofthecentralstroma–redzone–,thermallyprotectingtheendothelium–greenzone–,whichisplacednomorethan300μmdistantfromcentralstroma）;

and2）ahighresolutionofthetemperaturereachedatthetargetpoint（temperaturesrangingfrom58to76°

Carerequiredtoshrinkthecollagen,andtemperaturesover79°

Careharmful）.Sincetheepitheliumisalayerwithregenerationcapability,itcanstandheatingduringTKP（dottedline）.However,intheoptimumTKPtechniquetheepitheliumshouldbekeptcool（solidline）andtheheatfocusedonthecentralstroma.

Itisknownthatcollagenshrinkageoccursattemperaturesrangingfrom58to76º

C.However,higherthermallevels,79º

Corover,definitelyleadtorelaxationofthecollagenandcompletelossofitselasticity,inducingimportantkeratocyteproliferationandacceleratingcollagenturnover（i.e.provokingaregressionofthecorrectedrefractiveerror）[2].Therefore,theprocedurealsorequireshighresolutionofthetemperaturereachedatthetargetpoint（seeFig.​11）.

Inordertocreatecornealheating,differentkindsofenergysourceshavebeentested,suchassimplethermalconductionfrompre-heatedprobes,knownasthermokeratophores[3,4],microwaves[5-7],laser[2]andultrasound[8-10],andradiofrequency（RF）currents.However,ourinterestisfocusedontechniquesforcornealheatingbymeansofRFcurrents（≈500kHz）,thereforeinthisreviewwedescribethedifferentdesignsofapplicators（i.e.RFelectrodes）proposedandtestedtodate.Thisreviewisplannedfromatechnicalpointofview,i.e.thetechnicaldevelopmentsareclassifiedanddescribedtakingintoconsiderationtechnicalcriteria,suchasenergydeliverymode（monopolarversusbipolar）,thermalconditions（dryversuscooledelectrodes）,lesionpattern（focalversuscircularlesions）,andapplicationplacement（surfaceversusintrastromal）.Consequently,thedevelopmentsarenotnecessarilyrelatedtoeitherclinicalproceduresortrademarks.

APPLICATORSWITHSURFACECOOLING

ThefirstapplicatordesignedforapplyingRFcurrentsinthehumancorneawasdescribedbyDossandAlbillar[11]in1980.SinceitwasdevelopedatLosAlamosScientificLaboratory（NM,USA）,thedevicewasnamedtheLosAlamosKeratoplastyprobe[1].However,DossandAlbillarcalleditthecirculatingsalineelectrode（CSE）,since,whiletheactiveelectrodedeliveredRFcurrents（1.6MHz）aflowofisotonicsaline（at37º

C）wasinfusedoverthecorneasurface[11,12]（seeFig.​2B2B）.

Fig.

（2）

RFelectrodesandapplicatorsforcreatingalesionatacertainpointinthecornea.A:

Apairofelectrodescausealesionbymeansofabipolarapplication.B:

Thecirculatingsalineelectrode（CSE）worksbydeliveringRFcurrentsfromtheactiveelectrodetoadispersiveelectrodewhileaflowofisotonicsalineisinfusedoverthecorneasurface.C:

AsmallsurfaceelectrodeisplacedonthecorneaandRFcurrentsareappliedbetweenthisandadispersiveelectrode.Thelesionishenceconfinedtothecorneasurface.D:

Anintrastromalelectrodeisaneedle-shapedelectrodewhichpenetratesfromthesurfacetothecentralstroma.Thelesionhasmoredepththaninthecaseofasurfaceelectrode（C）.

ThebasicideaoftheCSEwastoimprovethetemperatureprofileobtainedbythethermokeratophoreduringthermokeratoplasty（TKP）.Thethermokeratophorewasametallicprobepreheatedtoaspecifictemperaturerange（90-130º

C）andplacedonthecorneasurface,i.e.thethermallesionwascreatedbythermalconductionfromthethermokeratophoretowardsthecornealstroma.Consequently,themaximumtemperaturewasreachedatthecorneasurface（≈75º

C）,whilethecentralstromaremainedat≈45º

C[11].Incontrast,usingtheCSE,themaximumtemperatureinthecorneawasreachedatthecentralstroma（≈70º

C）,bothepitheliumandendotheliumremainingatatemperaturelowerthan50º

C.Theapplicatorhadamonopolarsystem,i.e.theRFcurrentsweredeliveredbetweentheCSE（activeelectrode）andalargedispersiveelectrodeplacedawayfromtheCSE.Thistechniquewasfirsttestedonexcisedpigs’eyes[11],lateronaninvivomodelwithdogs’eyes（sacrificedwithinminutesofthetreatment）[13],andfinallysomepreliminaryclinicaltrialwereconductedonpatientstotreatkeratoconus[14-16].AlthoughtheCSEwasveryeffectiverightaway（thecorneaswereflattened）,itwasalsoacommonexperiencethattheflatteningofthesediseasedcorneastendedtodiminishsignificantlywithinafewweeks.Unfortunately,theprotocoldidnotallowperformingre-treatmentstodeterminewhetherlongertermstabilitycouldbeachieved（Doss,personalcommunication,Oct.11,1995）.Itisalsoimportanttopointoutthatthistechniquehasneverbeenemployedonrelatively“normal”humancorneassuchasthosefoundinastigmatismandhyperopicconditions（incontrast,inkeratoconusthecorneahasabnormalmorphologyandisalsoverythin）.

TheCSEtechniquewasalsoproposedusingabipolarsystem（i.e.withoutusingadispersiveelectrode）.Severalarrangementswithavariablenumberofelectrodeswereproposed[17]butnevertested.ThemostnovelideaofCSEwastocoolthecorneasurfaceduringheating.Infact,thesameideawaslateremployedinmicrowavethermalkeratoplasty[5-7],andmorerecently,asystemforsurfacecoolingofthecorneaduringTKPhasbeenpatented,especiallyforelectrical-inducedtechniquessuchasRFormicrowaveTKP[18].

APPLICATORSWITHOUTSURFACECOOLING（DRYAPPLICATORS）

PriortothedevelopmentoftheCSE,someexperimentalstudieswereconductedbyusingatwo-electrodeapplicatorfordeliveringRFcurrents（2MHz）inabipolarsystem（seeFig.​2A2A）.Theapplicator,knownasthelocalizedcurrentfield（LCF）device,wasalsodevelopedatLosAlamosScientificLaboratory[19].Itwasemployedintheveterinaryfieldforhyperthermictherapyforneoplasiaordegenerativecornealdiseas