Midface rejuvenation with Hyaluronic Acid: A critical ... · Midface rejuvenation with Hyaluronic Acid: ... of the twelve vision disturbance cases showed improvement compared with

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MidfacerejuvenationwithHyaluronicAcid:A critical appraisal of the vascular complication risks and thedevelopment of evidence based protocols for their prevention andmanagementMary-JaneSigridRowland-WarmannQueenMaryUniversity,London2016WordCount:16836excludingreferences

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Abstract

Background:Fortunatelyrare,vascularcomplicationscausingskinnecrosisorblindnessare

feared consequences of hyaluronic acid filler treatment. Cases of skin necrosis from

intravascular injectionofhyaluronicacid fillersorvessel compressionhavebeen reported

worldwide,whereascasesofvisionlossfromhyaluronicacidfillersarelargelylimitedtoAsia.

TheauthorisgravelyconcernedabouttheinadequacyofcurrentUKlegislationsurrounding

dermalfillersandthelackoftrainingformanagementofvascularcomplications.

Objectives: A review of the literature was conducted to assess the risk areas for filler

treatment and compile evidence based methods for prevention and management in an

aestheticpracticesetting.

Methods: A comprehensive literature search was performed to include relevant articles

basedonspecifiedinclusionandexclusioncriteria.Thetypeoffillerwaslimitedtohyaluronic

acid,witharecordofcomplicationsasskinischaemia,softtissuenecrosis,visualdisturbance

orblindness.

ResultsandDiscussion:Tenarticlesrepresenting41patientswithvascularcompromisewere

identified.Datafromthesereportsincludeinjectionsite,symptoms,treatmentandoutcome.

Thetreatmentsiteassociatedwiththehighestincidenceofvascularcompromiseisthenose,

representing42%ofvisionlossand59%ofskinischaemiacases.62%ofskinischaemiacases

resolvedcompletely,irrespectiveoftimetopresentation.Themostsuccessfulmanagement

componentforskinischaemiaappearedtobeearlyinterventionwithhyaluronidase.None

of the twelve vision disturbance cases showed improvement compared with their initial

presentationwiththetreatmentmeasuresperformed.Forvisionlossthereappearstobeno

effectivemanagement.

Conclusions: Hyaluronic fillers arewidely used in aesthetic practice. It is imperative for

practitionerstobeabletoprevent,recogniseandmanagevascularcompromise.

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Acknowledgements

I’dliketothankEd,mybusinesspartner,whohashelpedmeestablishourfacialaesthetics

practice.Andmycats,whoareawelcomedistractiontoanotherwiseupsettingtopic.

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Contents

ListoffiguresListoftablesIntroduction DermalFillers Hyaluronicacid Hyaluronidase Complicationswithdermalfillerinjections Vascularcomplicationswithdermalfillertreatment Midfacerejuvenationandnosereshaping Theanatomyrelativetovascularcomplications Relatedstudies Currenttreatmentstandards

PracticeimplicationsExampleClinicalScenarioAimsandObjectives

MethodsResultsDiscussion Fillertypes Highriskareasandtheeffectonvessels Interventions Skinischaemia/necrosis Visionloss/disturbance Outcomes Practitionerstatus

Evidencebasedguidelinesforthepreventionandmanagementofvascularcomplications

Preventionprotocols Managementprotocols

TheEmergencykitFurtherstudiessuggested

ConclusionsReferences

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ListofFigures

Figure1:Thevasculatureofthemidface

Figure2:Algorithmforthemanagementskinischaemia/necrosis

Figure3:reconstitutionanddosageofhyaluronidase(Hyalase/Wockhardt)

Figure4:Vascularcomplicationreportingform

ListofTables

Table1:Overviewof10selectedpapers,theirbasicoutcomesandweaknesses

Table2:Casecollectionfromkeypapers

Table3:Preventionprotocols

Table4:managementofvisionloss

Table5:managementofskinischaemia/necrosis

Table6:Emergencykitforvascularcompromise

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Introduction

The worldwide use of dermal fillers for rejuvenation and facial reshaping is showing an

explosiveincreaseoverthelastdecade.

An 31% increase in dermal filler treatments, totalling 2,690,633 worldwide in 2014, was

recordedbyISAPSsince2013.Thissteadyincreasehasbeenseensince2011accordingto

theAmericanSocietyforAestheticPlasticSurgery,risingbyapproximately30%yearonyear

(Cavallinietal.,2016; ISAPS,2016). Closer tohome, in theUK,approximately1.5million

botulinumanddermalfillertreatmentswereperformedin2013,anincreaseof4%from2012

(Inglefieldetal.,2014). The reason for this increase is simple:dermal filler injectionsare

convenient,predictable,achievegoodresultsandarelargelysafe(Hsieh,Lin,Huang,&Yeh,

2015).

Theincreaseintheuseofdermalfillersworldwidewillmeananincreaseinthenumberof

complications,especiallysincethecomplexityoftheperformedtreatmentsisincreasingfrom

thesimpletreatmentofperiorallinesforwhichdermalfillerswereoriginallyapprovedbythe

FDA in 2003 (Abduljabbar&Basendwh, 2016;US FDA, 2016). Thus, it is imperative that

awarenessandknowledgetotreatcomplicationsareincreasedinabidtoimprovepatient

safety.

Itistooeasyandarroganttosaythatthebestwaytomanagecomplicationsisnottohave

any(Cavallinietal.,2016).Somecomplicationsareunpredictableandhappentoeventhe

most experienced clinicians. Selection of the appropriate filler, using it correctly and

conductingtheproceduresafelyareallfactorswhichmitigatetheriskofcomplications,as

improper technique and misuse of filler account for many easily avoided complications.

However,ifcomplicationsstilloccurthepractitionerhasadutytomanagethemtothebest

oftheirabilitiesintheinterestsofthepatient.

Vascular complications are certainly disproportionate to the expected outcome of the

procedure.Whilstthenumberofcasesofblindnessresultingfromdermalfillertreatmentis

approaching100worldwide,andtheincidenceofnecrosisisthoughttobelessthan0.1%of

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allproceduresperformed,underreportingbycliniciansduetoembarrassmentmeansthatthe

trueincidenceisunknown(Cohenetal.,2015;DeLorenzi,2014;Sunetal.,2015).

DermalFillers

Whenselectingdermalfillersforpatientsinpractice,itisimportantthattheproductissafe

andeffective, not allergenic andgives reproducible results. Furthermore, they shouldbe

noncarcinogenic, nonmigratory and nonteratogenic (Alijotas-Reig, Fernandez-Figueras, &

Puig,2013).Onapurelyaestheticbasis,fillersshouldprovidesupportsandstructurewhere

thefeaturesofthefaceareaffectedbyvolumeloss(Montes,2012).

IntheUSA,theFDAregulateswhichdermalfillersmaybeused.Therearecurrently24FDA

approveddermalfillersintheUSA,ofwhich13arehyaluronicacid(USFDA,2016).InEurope

regulationismuchlessstrictandpractitionerscanchoosefrommanytypesoffillers–some

of lesserquality thanothersdue to lax regulationsoverproduction,distributionanduse.

There are over 160 types of filler and over 50manufacturers in the world. Low quality

productscancontributetothemostseriouscomplicationsandpractitionersshouldremain

vigilant,ascheapproductsareoftenthosewithleastscientificresearchintotheeffectson

thehumanbody(Cavallinietal.,2016).

Hyaluronicacid

Hyaluronic acid (HA) are biodegradable fillers that injected under the dermis to cause a

temporary change in appearance before being biodegraded (Funt & Pavicic, 2013).

Hyaluronic acid is a fundamental componentof theextracellularmatrixof cells (Cavallini,

Gazzola, Metalla, & Vaienti, 2013). It is a glycosaminoglycan (GAG) made of N-acetyl

glucosamineandglucuronic acid to forma lineardisaccharidepolymer, awater retentive

naturalsugarthathelpstohydrateandvolumisetheskin(Kassir,Kolluru,&Kassir,2011).

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HAfillersarethemostcommonlyusedfillers,accountingfor78.3%ofallfillertreatmentsand

an increaseof253%since2000 (Abduljabbar&Basendwh,2016). Syntheticallyproduced

usingbacterial cultures,HA ismodifiedbyacross-linkingandstabilisingprocesswith1,4-

butanediol diglycidyl ether (BDDE) to achieve the appropriate permanence in tissues and

deliverproductsthatcanlastbetween4-12monthsonaverage(Cavallinietal.,2016).They

are described as either biphasic or monophasic, with a particle size of around 400µm.

BiphasicHAfillershavelittleornocross-linking,theirparticlesizedeterminingtheproduct

density (e.g. Restylane). MonophasicHA fillers are crosslinked to formhomogenous gels

whereHAconcentrationcombinedwithcrosslinkingdeterminesfillerdensity(e.g.Juvederm,

Belotero)(Cavallinietal.,2016).Onceintissue,HAexpandsduetoitshydrophilicproperties

(Grunebaum,BogdanAllemann,Dayan,Mandy,&Baumann,2009)

Wheninjectedintothetissues,HAcanprovidestructureandelasticitybybindingcollagen

and elastin (Kassir et al., 2011). The primary reason for its popularity in use is its

biocompatibility and reversibility (Abduljabbar & Basendwh, 2016), which is a preferable

propertywhentheimpactofHAontissuescancausedevastatingconsequences.However,

thispropertyisbynomeansamagicwand.

Hyaluronidase

Hyaluronidasecanbeusedtomanageunaestheticoutcomesandseriouscomplicationssuch

asvascularcompromiseafterdermalfillertreatment.

HyaluronidaseisanendoglycosidasewhichdepolymerisesHAfillersbyhydrolysisofthe1,4-

N-acetylglucosaminidic bond in hyaluronic acid (Cavallini et al., 2013; Hilton, Schrumpf,

Buhren,Bolke,&Gerber,2014).Originallylicensedtoimprovepermeationofintramuscular

andsubcutaneousinjectionsandinfusions,hyaluronidaseincreasesdrugdiffusionintothe

extracellularmatrixandincreasesbloodvesselpermeability(Cavallinietal.,2013;King,2014).

Theactionofhyaluronidaseisrapidandcompletewithin24-48hours.Thedisruptionthatis

causedtothedermalbarrieristransient,reformingafteraround48hours(Kassiretal.,2011).

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Thefirstreportoftheuseofhyaluronidasetomanagedermalfillercomplicationswasin2007

by Hirsch et al (Hirsch, Cohen, & Carruthers, 2007) and early injection after a vascular

complicationsignificantlyreducestheriskandextentofnecrosis.ItnotonlydegradestheHA

filler,butcanalsoreducepressureontheoccludedvesselsandreduceoedema(Beleznay,

Humphrey,Carruthers,&Carruthers,2014). Dosages inthe literatureremainvaried,with

somestudiessuggestingbetween150U(Sunetal.,2015)to200Urepeatedafteronehour

(Cohenetal.,2015),andevenashighas1000U(Cavallinietal.,2016). It is thought that

althoughhyaluronidaseisassociatedwithahighincidenceofallergy,toolittlecanresultin

scarring(Cohen,2008).FillerwithhigherHAconcentrationsmayrequiremorehyaluronidase

(Cavallinietal.,2013).

Thereismuchhypeaboutthecomplicationratewiththeuseofhyaluronidase,theincidence

ofwhichisreportedataround0.05-0.1%.However,thishasbeenshowntoincreasetoas

highas30%whenhighdosesareadministered.ThemechanismofallergicreactionisTypeI

andTypeIVmediatedhypersensitivity,andcanresultinurticarial,erythemaandoedemabut

also,moreseriously,inrash,angioedemaandanaphylaxis(Cavallinietal.,2013;Cavalliniet

al.,2016). For this reason, it isoftenadvised to testhyaluronidaseon thepatientbefore

administering it;however, inthecaseof impendingnecrosis it isthoughtthat itwouldbe

moredamagingtohesitateanddirectadministrationofhyaluronidaseisadvised(Cohenet

al.,2015).

Thereason for its immunogenicity is thesourceofhyaluronidase. It isgained fromovine

testis and thus contains animal products, but also contains lactose components in the

hyaluronidasepowder.IntheUK,ovinehyaluronidaseisavailableasHyalase(Wockhardt)in

a1500unitampouleaspowder for reconstitutionwithsalineorwith lidocaine to further

vasodilation(Cohenetal.,2015;King,2014).InAmerica,ahumanrecombinantformulation

ofhyaluronidase,Hylenex,isavailablewhichissaferandlessimmunogenic(Cavallinietal.,

2013).

When using hyaluronidase in aesthetic practice, it is important to consider that it is

antagonised by furosemide, benzodiazepines, dopamine, alpha-adrenergic agonists,

antihistamines and phenytoin, some anti-inflammatories such as indomethacin and

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antioxidantssuchasvitaminC(Cavallinietal.,2013;Cavallinietal.,2016;Glaich,Cohen,&

Goldberg,2006).

Hyaluronidaseisnotlicensedforcorrectingproblemsresultingfromfillertreatmentandis

usedoff-labelaccordingtoArticle87ofDirective2001/83/EC.Therefore,informedconsent

isrequiredfromthepatient,withathoroughoutlineofthemedicalandsurgicalalternatives

(Cavallinietal.,2016;Cohenetal.,2015;King,2014).

Complicationswithdermalfillerinjections

Non-surgicalcosmetic interventionssuchasdermal filler treatmentscarrywith themrisks

that the patientmust bemade aware of, as patient satisfaction is a significant outcome

measure.Often,sideeffectsaccompanytreatment,anddiscomfort,erythema,swellingand

haematomaarecommonplaceandtobeexpected (Kassiretal.,2011). Theseareusually

mild, transient and self-resolving, requiring no intervention except reassurance from the

treatingclinicianastotheirfiniteduration.

Complications from dermal fillers, on the other hand, are unexpected in nature and

disproportionatelynegativetotheintendedtherapeuticoutcomeeventhoughthetreatment

has been administered correctly and the product used normally. These can be

catastrophically severe and long lasting andmay result in permanent injury or aesthetic

deficitsifnottreatedcarefullyanddiligently(Cavallinietal.,2016;Y.Chenetal.,2014)

Vascularcomplicationswithdermalfillertreatment

Vascularcomplications,althoughconsideredtoberareatarateofaround0.1%,arethemost

frightening and serious consequences of dermal filler treatment (Sun et al., 2015).

Embolisationofavesselwithfillermaterialbydirectinjection,orcompressionofavesselby

the placement of product in close proximity, can progress to necrosis of tissue due to

ischaemia(Cohenetal.,2015;Kassiretal.,2011).Thiscanleadtoareasofskinsuccumbing

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tooxygendeprivation.Similarly,blockageofthevesselsthatsupplytheeyeduetoaccessof

dermal fillerparticles to theocularcirculationcancausenecrosisof the retina, leading to

blindness.

Almost all filler materials in current and historical use have been linked to vascular

complications and blindness, including paraffin, silicone oil, hyaluronic acid,

polymethylmethacrylate,calciumhydroxylapatiteandfattissue(Hsiehetal.,2015).

In the case of occlusion of an artery, pain is often immediate and striking in naturewith

blanchingofthesupplytissueorlossofvisionoftheaffectedeye.Whenvisionlossoccurs,

partial or complete loss of light perception, limitedeyemovement and retinal cherry-red

spotsmayalsobeobserved(Hsiehetal.,2015).Whenvenousocclusionhasoccurred,itis

oftenaccompaniedbyadullachingpainwithdarkviolaceouspatchesatthevesseltributary

site(Kassiretal.,2011).Thepatientmayalsoreportthatthereispaindisproportionateto

theeffectedtreatment(Inglefieldetal.,2014).However,symptomsarenotalwaysthesame

and unusual or delayed presentations can occur as a result of swelling of the tissue or a

hydrophilicfillerleadingtocompression.Vascularcomplicationsaremorelikelytooccurin

areaswherethebloodflowislimited,orwherethereisalackofcollateralcirculationaffecting

thetissuesatrisk.Thisiswhythemidfaceandnoseareofparticularrelevancewhentreating

withdermalfillers.

Midfacerejuvenationandnosereshaping

Themidfaceissubjecttoage-relatedchanges,withlossofvolumeresultinginthedescentof

fat compartments and skin laxity, and deepened nasojugal and nasolabial folds. These

changesinvolumebringaboutanagedappearance,whichisoftenthepresentingcomplaint

ofapatientatanaestheticpractice.Replacementofvolumetothefatpadsofthefaceand

lendingimprovedstructurewithadvancingagecanresultinhighsatisfactionratesofupto

75%at2years,withpatientsreportingan improvement inperceivedageofupto5years

(Few,Cox,Paradkar-Mitragotri,&Murphy,2015).

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Thenoseisnotanareaofthemidfacethatissubjecttoextremechangeswithage,butitisa

partthatisoftenthesourceofdissatisfactioninpatients.Whetheritistheshapeorsimply

adefectinthenosesuchasabumporanindentation,manypatientsseektoaugmenttheir

noses.Dermalfillertreatmentofthenoseisanexcellentsolutionforpatientswhowantto

camouflage small tomedium sized deformities of the nose but who are concerned with

financialexpense,aestheticrisk,surgerydowntimeorpermanenceoftheeffect(Humphrey,

Arkins,&Dayan,2009).Duetothenatureofthenosetissue–itisnonmobileandnotsubject

tothesamestressesasmobileandhighlyexpressionatepartsofthemidface–dermalfillers

canlastlongerthaninotherareas.

The midface and nose are considered amongst the highest risk areas for vascular

complicationsindermalfillertreatment.

Theanatomyrelativetovascularcomplications

Figure1:Thevasculatureofthemidface(from(D.Lazzerietal.,2012))

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Thefacialartery,abranchoftheexternalcarotid,isthemajorvesselsupplyingbloodtothe

superficial face. At themandible, the facial artery crosses diagonally towards the nose,

runningatortuouspathatthenasolabialfold,beforeadvancingtothelateralnasalwallin

thealarcreaseandterminatingintheangularartery.Thisrunstowardsthemedialorbital

rim.Atthejunctionbetweenthefacialandangulararteriesliesthelateralnasalartery,which

suppliesthe78%ofthebloodtothenose(nasaltipandala),andbloodtotheremaining22%

ofthenoseviathedorsalnasalartery.Compressionorocclusionofthefacialarteryinthe

nasolabialfoldorfurtheronattheangularordorsalnasalarterycanleadtoalarnecrosisor

necrosisofthetipofthenose(Kassiretal.,2011).

Thefacialvein,whichrunsalongsidethefacialartery,liesatadistanceofaround2-3cmlateral

tothealaofthenoseandsimilarlyattheleveloftheoralcommissure.Thefacialveinalso

demarcatesthemedialborderofthemedialfatpadoftheface,whichistriangularandoften

subject to volumisationwith fillers (Chinnawong, Tansatit, Phanchart,& Rachkaew, 2015;

Cotofanaetal.,2015).Compressionorocclusionofthefacialveinoritstributariescanlead

to a dull ache, dusky grey/mottled appearance and progressive ischaemia of the tissues

(Inglefieldetal.,2014).

Theanastomosisofthedorsalnasalarterieswiththeophthalmicarteriesoccursatthemedial

canthusandfromherebloodcanaccessthecentralretinalarteriesviatheophthalmicarteries

(Kassiretal.,2011;Y.J.Kim,Kim,Song,Lee,&Yoon,2011).Theophthalmicarteryisabranch

of the internal carotid, and in turn supplies its orbital group, consisting of lacrimal,

supraorbital,posteriorethmoidal,anteriorethmoidal, internalpalpebral, frontalandnasal

arteries,andtheoculargroup,consistingoflongciliary,shortciliary,anteriorciliary,muscular

andcentral retinaarteries (S.N.Kimetal.,2014). Excesspressureon theplungerabove

systolicduringinjectionoffillerstothemidfacecanovercometheanastomosisbetweenfacial

andocularcirculationandrefluxthroughtotheophthalmicarteryoritsbranches(Tansatit,

Moon,Apinuntrum,&Phetudom,2015). Resulting ischaemiaof theophthalmicarteryby

blockagewith dermal filler leading to lack of blood supply of any of the branches that it

supplies can cause palsy of oculomotor nerves, blepharoptosis, exotropis, palsy of ocular

musclesandlossofvision(Kwonetal.,2013).Afurthercatastrophicconsequenceofpressure

overcomingtheanastomosisisaresultingcerebraleventfromfillerproductretrogradeflow

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intotheinternalcarotidartery(Y.Chenetal.,2014;D.Lazzerietal.,2012).Furthermore,

highinjectionforcedepositshighervolumesoffilleratspeed,whichcanalsoleadtosudden

compressionofvessels,causing ischaemiaandsubsequentnecrosisofskin (Y.Chenetal.,

2014;D.W.Kimetal.,2011).

Theglabellahas limitedcollateralbloodflow,so it representsanotherareaathighriskof

vascular compromise. Branches from supratrochlear and supraorbital arteries supply the

glabellaandinferiorcentralforeheadandthenasalroot,withverysuperficialvessels(Glaich

etal.,2006;Kassiretal.,2011).Injectionoffillerintoeitherofthesecanresultindirectentry

intotheocularcirculationandresultantblindness,butalsoconsequencessuchasnecrosisof

theskinoftheforeheadandscalp(Kassiretal.,2011).

Relatedstudies

ThestudythatinspiredthisreviewisthecaseseriesreportbyBeleznayetalaboutvascular

complicationsindermalfillertreatment.Variousfillerswereanalysedandmethodsforthe

managementofvascularcomplicationsleadingtoimpendingskinnecrosisweredevised.This

studyisinterestingastheprotocolsdevisedweresimple,clearlysetoutandeasytofollow,

and the cases documented all had favourable outcomes (Beleznay et al., 2014). These

protocolscanbeutilisedinaestheticpracticeratherthanahospitalsettingandpiquedthe

author’sinterestindevisingmanagementprotocolsforbothskinandocularcomplications

fromfillerocclusionthatcanbeutilisedinpracticeintheUK.

Some similar reviews of the literature have been completed. In 2014, Carruthers et al

compiled a literature review of blindness. The focus was on prevention and therapy.

Autologous fat was identified as the main cause of filler blindness, but also that any

attempted interventions were unsuccessful. A technique for retrobulbar injection of

hyaluronidase was developed, in the hope that hyaluronidase injected directly into an

ophthalmicarterywouldcatabolisethecloggedvessel.Unfortunately,thistechniquewould

need to be completed by a neuroradiologist or ophthalmologist only and would not be

suitablefortheaestheticpractice(Carruthers,Fagien,Rohrich,Weinkle,&Carruthers,2014).

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Lazzerietalcompletedaliteraturereviewin2012,inwhich29articlesrepresenting32cases

ofvascularcomplicationleadingtoblindnesswereanalysed.47%wereduetoautologousfat

injection,andprecautionprotocolsweresuggested.Treatmentprotocolsincludedlowering

theintraocularpressurebyincisionwithablade,IVdiuretics,carbogen(5%carbondioxide

and 95% oxygen) rebreathing alongside corticosteroids, but all proved to be fruitless (D.

Lazzerietal.,2012).

AfurtherreviewoftheliteraturewasconductedbyOzturketalin2013,where61casesof

vascularocclusionotherthanautologousfatwereconsidereddatingfrom1991to2012.This

studyassociatedthenosewiththehighestriskwith33.3%ofcomplicationshavingtreatment

at this site. A variety of fillers are considered and several complication types other than

vascularare includedandguidelinesforthemanagementoffillercomplications ingeneral

weredevelopedwhichincludedin-practicemanagementandreferral(Ozturketal.,2013).

It appears that no reviews have focused exclusively on the prevention and treatment of

vascular complications of HA filler in an aesthetic practice setting that include papers

publishedpast2012.SinceHAisthemostwidelyusedfiller,itseemspertinenttoconsider

casesthathaveresultedfromitsuse.Evidencebasedguidelinesthatareeasytoimplement

developed from this review canbeused to favourably influence theoutcomeof vascular

complicationsandinspirefurtherresearch.

Currenttreatmentstandards

Currently there are no reliable standard treatment protocols for vision loss as a result of

dermalfillertreatment(Hsiehetal.,2015)andpreventionisamuchmoreeffectivestrategy.

Managementofimpendingskinnecrosisisamuchmorewidelyappraisedtopic,withmany

papersoutliningguidelinesformanagement.Protocols,suchasthosepublishedbyInglefield

et al in 2014, or Beleznay et al in 2014 focus on the use of hyaluronidase,massage, hot

compressesandanti-inflammatorymeasuresasatreatment(Beleznayetal.,2014;Inglefield

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et al., 2014). These recommendations appear to be realistic and the success rates and

outcomesadequate.

Practiceimplications

Patientscommittodermalfillereveryday,believingthatitisasimpleandquickprocedure.

Thisisindeedthecaseiftheprocedureisperformedsafely,byanexperiencedclinician,in

therightenvironment.IntheUK,thelegislationsurroundingtheuseofdermalfillersislax

andpatientsarepotentiallyatveryhighriskofharm.Practitionersdonotneedtoholdany

formalqualificationstopracticedermalfillers,anddonotneedtobehealthcareprofessionals

togainaccesstodermalfillerproductsoradvertisetoandtreatpatients(Keoghetal.,2013).

Asthemidfaceisthemostatriskareafordermalfillercomplications,soitwouldnotbeafar-

fetchedtaletosuggestthatavascularcomplicationcouldoccur inaestheticpracticefora

medically healthy patient undergoing cheek or nose augmentation. The patient would

requireimmediate,mediumtermandlongtermcare.Inordertogivethepatientthebest

possible care and mitigate any long term sequelae, it is important for all aesthetic

practitionerstobefamiliarwiththeprevention,identificationandmanagementofvascular

complications.

Itwassimplefortheauthortoachievetraining,completingaoneortwo-daycourseinorder

tobecertifiedcompetentintheuseofdermalfillers.However,initialtraininghadlittlefocus

onthepreventionandmanagementofdermalfillercomplications;indeedafterreviewingthe

coursematerial,itseemstohavenomentionofitwhatsoever.Itthereforeseemsthatmany

courses designed to offer practitioners a new scope of practice are leaving them poorly

equippedtodealwithanypotentialseriouscomplications,ofwhichnecrosisandblindness

arethemostworrying.

TheauthorisgravelyconcernedaboutthesafetyofmedicalaestheticsintheUK.Shechose

thetopicofcomplicationstodemonstratetherisksassociatedwithvariousproceduresand

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also in the hope that it might be taken up as a guide for practitioners to mitigate any

unintentionalharmtheymaydotheirpatients.

InlightofthegovernmentstotalfailuretotakeonboardthefindingsoftheKeoghReport,

thereisalongwaytogobeforeaseriousregulatoryframeworkcanbeestablished.Agreat

dealofrelevantregulationinourindustrywasdirectlyorindirectlyinfluencedbyEurope,and

ourrecentbreakwiththeEUcanonlyfurtherharmtheprospectsforasensibleregulatory

regimeinthenearfuture.

Itistheunfortunatecasethatactionfromgovernmentsandregulatorsdoesnotcomefrom

carefulplanningandconsiderationbutasaknee-jerk reactiontopublicandmediaoutcry

arisingfromseriousharmbeingdonetopatients.

Mostoftheworsecasesinthisresearchcomefromoverseasbutbeassuredthatsimilarly

appallingadverseeventswillstartappearingintheUKbeforelong.Itwillnotbethewealthy

orenlightenedpatientswhowillsufferbutthepatientsoflimitedmeansandinsight,whoare

arguablythosewhoneedprotectingthemost.

Askyourselfthisquestion;whatamIdoing,asathought-leaderandexpert inthisfieldto

mitigate risk? Similarly ask what am I doing to spread ideas that might protect both

practitionersandpatientsfromharm?

Illegalpractice isone issuebutsubstandardpracticemustalsobeaddressedasagrowing

problem.PerfectlygooddentistsandGPsare‘tryingtheirhand’atfacialaestheticsandare

stillverycapableofcausingharm,justassomeonewhopicksupaneedleforthefirsttimeis

capableofcausingharm.Theonlydifferencebeingthatpatientswillhavenoreasonnotto

trusttheabsoluteclinicalintegrityofamedicalpractitioner.

Everydaytheauthorseescomplicationsfromlegalandillegalpractitioners,theseverityand

frequencyofwhichareincreasingmonthonmonth.Oneofthemostharrowingfactsisthat

patients come to the author’s practice because their treating practitioners have often

disappeared,cannotbetracedorevendenyhavingbeenthetreatingpractitioneratall!

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Theauthorencouragespractitionerstotakeuptheadvicefoundinthisresearchanduseitto

make sure they are offering patients a safe and effective service in a consistent and

appropriateway.Evidencebasedguidelineshavebeenproducedinsuchaformatthatthey

cansimplybetakenandputinsurgeriesforreferenceandguidanceinanincident.

Theauthoralsoencouragesreadersofthisresearchtojoinherincampaigningforasafeand

regulatedindustrybecausethepositionasitcurrentlystandsiswoefullyinadequate.

Thosewhosayfacialaestheticsisaprofitableenterpriseeitherlackcommercialinsightorlack

personalintegrity.Aestheticsisaboutthesubtlepursuitofperfectionandstrongclinicalskills

and judgement. Those undertaking it in the hope of making money should be actively

discouraged,fortheyrepresentthegreatestrisk.

ExampleClinicalScenario

Apatientattendsanaestheticpracticeseekingrejuvenationofthemidface,complainingof

volumelossandagedappearanceofthenasolabialfolds.Hyaluronicacidfillertreatmentis

suggestedandcommenced.Duringtreatmentthepatientcomplainsofpain.Immediately

after treatment the patient complains of further pain and a violaceous patch to the left

nasolabialfoldandtheleftsideofthenoseisobserved.

Immediateandlongtermmanagementstrategiesmustbeinvokedtoappropriatelymanage

thispatient.Whataretheeffectivewaystomanagethissituation?Couldanythinghavebeen

donetopreventthiscomplication?

AimsandObjectives

Theaimsof thisdissertationare toascertain thecurrent treatment recommendations for

casesofvascularcompromiseandlossofvisionasaresultofdermalfillerinjectionandto

searchthecurrentliteratureforcasesrelatingtovascularcompromiseandblindnessafter

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treatment of the midface. A particular interest was the treatment guidelines for the

managementofbothvascularcompromiseandblindness,andwhethertherehavebeenany

changes in the commonlyacceptedprotocols todealwithvascular compromise since the

adventoftheuseofhyaluronidasein2007.Furthermore,sincethereisverylittleevidence

thatvisuallossasaresultofdermalfillertreatmentcanbeeffectivelytreatedintheclinic

setting,orindeedeveninthehospitalsetting,researchwasconductedtoassesswhetherany

useful treatment modalities for vision loss from HA fillers exist or attempts have been

documented.

The goal of this reviewwas to evaluate and construct evidence based guidelines for the

managementofvascularcomplications–bothimpendingskinnecrosisandblindness–after

treatmentwithhyaluronicacidfillersintheaestheticpracticesettingintheUK.Thehopeis

thattheywillbesimpleandaccessibletopractitioners,assisttheminthecasemanagement

andreduceasmallportionofthestressfeltbypatientandpractitionerinsuchapotentially

disastrouseventandassistinthemanagementoftheacutelycompromisedpatient.

Theaimsweredefinedasfollows;

• Toevaluatethehighriskareasfortreatmentofthemidface

• Toevaluatetheriskposedbyhyaluronicacidfillers

• Toassesstheoutcomeofinterventionstrategiesintheliterature

• Toformulateevidencebasedpreventionprotocolsforaestheticpractitionersinthe

UK

• Toformulateevidencebasedmanagementprotocolsforvascularocclusionthatcan

beeffectivelyusedinthepracticesetting

• TomakerecommendationsforimprovementintheUKpracticesetting

20

Methods

Thisisareviewoftherelevantliteratureinordertodrawconclusionsaboutcurrentaesthetic

practice,theriskstovasculatureandsightassociatedwithHAfillertreatmentofthemidface

andtoconstructevidencebasedguidelinesforthemanagementofsuchcomplications.The

complicationrateandtheirmanagementisanareathatisgainingsignificantinterestinthe

field of aesthetic medicine due to a steep increase in the number of patients treated.

Unfortunately,duetothelooselegislativeframeworkintheUKrelatingtotheuseofdermal

fillers,patientsareatasignificantriskofharm(Keoghetal.,2013).

AcomprehensiveMEDLINE,CochranedatabaseandPubMedelectronicdatabasesearchwas

performedtoincludejournalspublishedbetween2011and2016,inafive-yeardaterange.

AestheticMedicineisafastevolvingfieldandassuchanarrowdaterangehasbeenselected

forthisreason;HAfillerswerenotcommonlyuseduntil2003andtherapidincreaseintheir

usewasnotuntillater.Ozturketalconductedastudyondermalfillercomplicationswith

dateranges1991-2012,soa laterdaterangewouldserveasa fittingdevelopment,albeit

limitedtoHAfiller.Noempiricalresearchwasconductedforthefindingsinthisreview.

The initial broad search inPubMed (carriedout01Feb2016) includedkeywords “dermal

filler”and“complications”andresultedin51results.Abriefassessmentofthesearchresults

revealedthatmanyofthepapersincludeddifferenttypesofdermalfillers,butalsotechnique

specificpapers.

Thecriteriaforinclusionasakeypaperwasforprimarydatatobepublished,forexample

clinicaltrialsorcasestudies.Secondaryreviewsoftheliteraturewereexcluded.Aesthetic

medicine has a notoriously weak yet fast growing evidence base due to the worldwide

scientificandfinancialinterestinit.

The BestBETsmethodologywas used in order to formulate a three-part question for the

purposes of literature research. This was to include the target population, the possible

intervention,andtheoutcome.

21

ThefollowingBETwasdevised;

In[dermalfillertreatment]which[managementstrategies]resultin[improvedoutcomefor

vascularcomplications]

Thiswasthenrevisedtoamorefocusedtargetpopulationandintervention,asfollows;

In[patientsseekingrejuvenationofthemidface]howare[VASCULARcomplicationsmanaged]

aftertreatmentwith[hyaluronicaciddermalfillers]

Theoriginalsearchofdermalfillercomplicationswasrefinedto includethemidface. Ina

searchofMeSHterms,thisincludedthecheek,teartroughandnoseandwasdefinedas“the

portionofthefacecomprisingthenasal,maxillaryandzygomaticbonesandthesofttissues

covering these bones” (Mosby, 2013). Further narrowing of the search criteria was

performedtofocusonHyaluronicAcidfillersonly,astheseconstituteover75%ofallfillers

usedinmodernaestheticpractice(Abduljabbar&Basendwh,2016).

Only English journals were considered for the literature review. In order to formulate

evidencebasedguidelinesforthemanagementofvascularcomplicationsandtoassessthe

effectofdermalfillersandtheirriskinaestheticpractice,studiesnotconductedonhumans

wereexcluded.Theareaofinterestinthemidfaceistheanastomosisofthenasalvasculature

withtheocularvasculature,andthisisnotrepresentedinananimalmodel.Cadaverstudies

have been evaluated for the embolic channel, however these do not rovide useful

interventionsthatcanbeutilisedonapatient(Tansatitetal.,2015).Duetothenatureofthe

intervention, itwasthoughtunlikelyforrandomisedcontrolledtrialstobepublishedfora

humanpopulation.

Thesearchtermswererefinedasfollows:

(midface[AllFields]OR“midface”[AllFields]OR“mid-face”[AllFields]ORcheek[MeSHTerms]

ORcheek[AllFields]OR“teartrough”[AllFields]OR“nose”[AllFields])

AND

22

("hyaluronic acid"[MeSH Terms] OR ("hyaluronic"[All Fields] AND "acid"[All Fields]) OR

"hyaluronicacid"[AllFields])

AND

(“complication”[All Fields] OR “complications”[All Fields]OR “necrosis”[All Fields] OR

“blind*”[AllFields]OR“ocular”[AllFields]OR“vascular”[AllFields])

AND

("2011/05/02"[PDat]:"2016/05/02"[PDat]AND"humans"[MeSHTerms]ANDEnglish[lang])

42articleswerefoundintheabovesearch.

Inordertoincludeandexcludepapersfromanalysis,titlesandabstractswerereadtocheck

forrelevance.Thefinaldateforinclusionandresearchwas02May2016.

Exclusionsweremadeonthefollowingbasis:

• 7paperswerenotrelatedtoaestheticmedicine

• 19 papers focused on techniques in the treatment of themidface rather than on

complicationsortheirmanagement

• 4paperswerenotrelatedtoHAfillers

• onepaperdealtwithacomplicationthatwasnotvascular

• onepaperdealtwith imagingtechniques indermal fillercomplicationsrather than

theirmanagement

Tenpaperswereincludedfromtheinitialsearch.Ofthese,twowerenotavailableonline.

Inordertomakesurethatallrelevantpapershadbeenfound,twofurthersearcheswere

conducted,featuringskinnecrosisandblindnessasthemainkeywords. Limitationswere

placedonthedaterangeonly,toincludepapersafter2011(afiveyearrange).

Furthersearch1:

“Skinnecrosisafterdermalfillerinjection”inPubmed

23

(("skin"[MeSHTerms]OR"skin"[AllFields])AND("necrosis"[MeSHTerms]OR"necrosis"[All

Fields])ANDafter[AllFields]AND("dermalfillers"[MeSHTerms]OR("dermal"[AllFields]AND

"fillers"[All Fields]) OR "dermal fillers"[All Fields] OR ("dermal"[All Fields] AND "filler"[All

Fields]) OR "dermal filler"[All Fields]) AND ("injections"[MeSH Terms] OR "injections"[All

Fields]OR"injection"[AllFields]))AND("2011/05/02"[PDAT]:"2016/05/02"[PDAT])

returned11papers

Furthersearch2:

“Blindnessafterdermalfillerinjection”inPubmed

("blindness"[MeSH Terms] OR "blindness"[All Fields]) AND after[All Fields] AND ("dermal

fillers"[MeSHTerms]OR("dermal"[AllFields]AND"fillers"[AllFields])OR"dermalfillers"[All

Fields] OR ("dermal"[All Fields] AND "filler"[All Fields]) OR "dermal filler"[All Fields]) AND

("injections"[MeSHTerms]OR"injections"[AllFields]OR"injection"[AllFields])

returned7papers

Twofurtherpaperswereidentifiedandincludedforconsiderationandevaluation.Afurther

evaluation of these papers and their references showed significant overlap in the source

papersandthesearchwasdeemedtohavebeencarriedouttoitsfullest.

Tenpaperswerefinallyselected,asfollows:

Beleznay,K.,Humphrey,S.,Carruthers,J.,&Carruthers,A.(2014).VascularCompromisefrom

SoftTissueAugmentation.JournalofClinicalandAestheticDermatology,7(9),6.

Clinicalcaseseries,Canada.

Chen, Q., Liu, Y., & Fan, D. (2016). Serious Vascular Complications after Nonsurgical

Rhinoplasty: A Case Report. Plast Reconstr Surg Glob Open, 4(4), e683.

doi:10.1097/GOX.0000000000000668

Singlecasereport,China/London.

24

Chen,Y.,Wang,W.,Li, J.,Yu,Y.,Li,L.,&Lu,N. (2014).Fundusarteryocclusioncausedby

cosmeticfacialinjections.ChinMedJ,127,1434-1437.doi:10.3760/cma.j.issn.0366-

6999.20133254

Clinicalcaseseries,China.

Kassir,R.,Kolluru,A.,&Kassir,M.(2011).Extensivenecrosisafterinjectionofhyaluronicacid

filler:casereportandreviewoftheliterature.JournalofCosmeticDermatology,10,

224-231.

Singlecasereport,USA.

Kim, S. N., Byun, D. S., Park, J. H., Han, S.W., Baik, J. S., Kim, J. Y., & Park, J. H. (2014).

Panophthalmoplegia and vision loss after cosmetic nasal dorsum injection. J Clin

Neurosci,21(4),678-680.doi:10.1016/j.jocn.2013.05.018

Singlecasereport,SouthKorea.

Kim,Y.J.,Kim,S.S.,Song,W.K.,Lee,S.Y.,&Yoon,J.S.(2011).Ocularischaemiawithhypotony

after injectionofhyaluronicacidgel.OphthalPlastReconstrSurg,27(6),e152-155.

doi:10.1097/IOP.0b013e3182078dff


Kwon, S. G., Hong, J.W., Roh, T. S., Kim, Y. S., Rah, D. K., & Kim, S. S. (2013). Ischemic

oculomotor nerve palsy and skin necrosis caused by vascular embolization after

hyaluronic acid filler injection: a case report. Ann Plast Surg, 71(4), 333-334.

doi:10.1097/SAP.0b013e31824f21da


Park,S.W.,Woo,S.J.,Park,K.H.,Huh,J.W.,Jung,C.,&Kwon,O.K.(2012).Iatrogenicretinal

arteryocclusioncausedbycosmeticfacialfillerinjections.AmJOphthalmol,154(4),

653-662e651.doi:10.1016/j.ajo.2012.04.019

Clinicalcaseseries,SouthKorea.

25

Park,T.H.,Seo,S.W.,Kim,J.K.,&Chang,C.H.(2011).Clinicalexperiencewithhyaluronic

acid-filler complications. J Plast Reconstr Aesthet Surg, 64(7), 892-896.

doi:10.1016/j.bjps.2011.01.008

Clinicalcaseseries,SouthKorea.

Sun,Z.S.,Zhu,G.Z.,Wang,H.B.,Xu,X.,Cai,B.,Zeng,L.,...Luo,S.K.(2015).ClinicalOutcomes

ofImpendingNasalSkinNecrosisRelatedtoNoseandNasolabialFoldAugmentation

with Hyaluronic Acid Fillers. Plast Reconstr Surg, 136(4), 434e-441e.

doi:10.1097/PRS.0000000000001579

Clinicalcaseseries,China.

26

Results

TenstudieswerefinallyselectedasrepresentingvascularcomplicationsfromHAfillerinthe

midface.Asthesevascularcomplicationscanresultintissuenecrosisandblindness,studies

wereselectedthatshowedinstancesofboth.

Outofthetenpapersselected,fiveinvolvedocularcomplicationsasaresultofdermalfillers

inthemidfaceandfiveinvolvedskincompromise.Aninitialreviewofthepapersinvolved

ascertainingwhich elementswould prove useful to the central question of how vascular

complicationswithHAfillersariseandhowtomanagecomplicationsinthemidface.

TheinitialreviewoftheincludedpaperscanbefoundinTable1.

AllpapersfoundwereCEBMLevel4evidence,withmostbeingsingleormultiplecasereports.

Norandomisedcontrolledtrialswerefound.Duetothefortunatelyrareincidenceofvascular

complicationsindermalfillerpractice,samplesizesaresmall,rangingfromreportsofasingle

patientinpracticeto13patientsintheocularcomplicationsgroupand28casesinafurther

study including vascular compromise affecting skin. However, with ocular complications

papersitwasfoundthatwhilstthesinglecasesfocusedonHAfillersinthemidface,papers

withmultiplecasesincludedanarrayoffillerproducts,includingautologousfatandcollagen

(Y. Chen et al., 2014; S. W. Park et al., 2012). The studies that dealt with vascular

complications involving skin only were similar, with the Beleznay et al reporting on a

combinationofHA,CaHAandparticulatefillers(Beleznayetal.,2014).Furthertothis,Park

etalexploredalltypesofcomplicationsinamuchlargersamplesizeof28treatedwithHA

filleronly,ofwhichthreewerefoundtobevascularcomplicationsaffectingtheskin(T.H.

Park,Seo,Kim,&Chang,2011).

Inorder tocloserevaluatethedatagained fromthe includedstudies, itwasnecessary to

assimilatetherelevantcasesfromeachstudyinonetable.Factorsthatwereconsideredto

beimportantfortheevaluationofthedataandsubsequentformationofanyguidelineswere

thefollowing:

27

• Injectionsite– inordertoevaluateprocedureriskandformulateprotocols forthe

preventionofvascularcomplicationsanassessmentofthesitesmostaffectedmust

bemade

• Practitioner – itwould be interesting to ascertainwhether certain professions are

associatedwithahigherriskinvascularcomplicationandoutcome

• Injectionvolume–highervolumesinjectedareassociatedwithincreasedriskofvessel

compression,increasingtheriskofischaemia

• Injectiontechnique–usinglargerboreneedlesisassociatedwithanincreasedrisk

• Symptoms–torecognisethecomplicationinrelationtotheareatreatedandwhether

thereisastandardpresentationorwarningsignforvascularcompromise

• Timetopresentation–delayingpresentationforemergencytreatmentmayresultin

worseprognosis

• Diagnosis – a diagnosis should include the vessel affected and the result of the

occlusion.Theremaybeadifferencebetweentheinterventionandoutcomeifthe

vesselsuffersfrankocclusionorcompression

• Treatment–inordertoformulateevidencebasedguidelinesforthemanagementof

vascularcompromise,anyeffectivetreatmentmodalitiesmustbeassessed

• Outcome– to judgewhetheran interventionor treatmenthasbeeneffective, the

outcomemustbemeasured

Thesubjectsisolatedfromthetenstudiesthatmeetthecriteriaofvascularcompromisewith

HAfillerinthemidfacecausingskinorocularsymptomsarepresentedinTable2.

Itsoonbecameclearthatthequalificationofthetreatingpractitionerwasrarelyrecorded.

SNKimetal,YJKimetalandKwonetalrecordedageneralsurgeonandtwophysicians(exact

specialtyundisclosed)asthetreatingpractitionersoutof12consideredocularcomplications.

Fromthegroupofvascularcomplicationsaffectingtheskinandatotalof28cases,onlytwo

paperslistedtreatmentproviders,withKassiretalstatingtheprocedurewascompletedby

aplasticsurgeonandChenetalmadeapointofadvisingthatthelicenseandregistration

statusofthepractitionerwasunknown,withoutmakingreferencetowhetheritwasinfacta

medicalprofessional.Thuswithsuchlimiteddataontheperformers,itwouldbedifficultto

28

evaluatetheriskassociatedwithdifferentprofessionalsundertakingaestheticproceduresin

themidface.Assuch,thiscriterionwasremoved.

The classification of injection techniquewas also removed. It iswell documented that a

smallergaugeneedleisthoughttocausealowerincidenceofvascularevents,withtheuse

ofacannulareducingthisriskfurther.However,fromtheevidenceinthesestudiesalone

thisconclusioncannotbedrawn,astheinjectiontechniquewasonlyrecordedtwiceforthe

ocularcomplicationspatientsbyChenetalrecordingtheuseofa30Gneedle,andBeleznay

et al recordingneedlegaugeof28G to30G in their treatment. Themethodof injection,

whetherretrogradeoranterograde,orwhethertheproductwasplacedinabolus,fanningor

otherpattern,wasnot recorded inany studies. As such itwouldbedifficult toestablish

evidencebasedguidelinesonthesecasesalone(Beleznayetal.,2014;Y.Chenetal.,2014).

Itisclearthatthereisagreatvariationontheinclusioncriteriaforeachofthestudies.Itis

also clear thata large studyof thevascular complicationsaffectingboth sightand skin in

relationtoperformingtreatmentwithHAfillersinthemidfacehasnotbeendoneonascale

that would normally net reliable data for the formulation of proper evidence based

guidelines.However,asaestheticmedicineissuchafastevolvingandasyetunexploredfield,

the data from the individual cases,when collected and evaluated togetherwill provide a

usefulframeworkfromwhichtodrawupguidelinesforcomplicationmanagement.

29

Table1:Overviewofthetenselectedpapers,theirbasicoutcomesandweaknesses

Author/Date/Category

PatientGroup Study Type(level ofevidence)

Outcomes

KeyResults StudyWeaknesses

(Y. Chen et al.,

2014)

VASCULAR /

OCULAR

Study Number:

1

13patientswith

fundus artery

occlusion from

dermal filler

treatment

resulting in loss

of vision,

women, age

range23-47

CEBMLevel4

Casereports

Retrospective

Typeoffiller

Autologousfat7/13cases

Collagen1/13cases

HA5/13cases

• Smallstudysample

• Follow up period

shortorinconsistent

• No evidence of

injection technique

orvolumeinjected

• Statisticalassessment vague

due to high number

of variables,

tabulatedonly

• No treatment or

preventionstrategies

• Vague description ofsiteas“frontal”

Symptoms

and

presentation

Immediatepartialorcompletevisionlossunilateral

Ophthalmicarteryocclusionpresentswithseverepain

Associated

Site and

vessel

Frontalarea5/13,Periocular2/13,Temple2/13,Nose4/13

Ophthalmicarteriesandbranches

Resolution

Noimprovementin10/13cases(7autologousfat,1collagenand

2HA)

NoimprovementifOphthalmicarteryocclusion

3patientsinHAfillergroupshowedimprovement

Treatment /

intervention

Nitroglycerin,massage,eyedropstolowerintraocularpressure,

aspirin,prednisolone.

Norelationshipbetweentreatmentandsymptomresolution

(S.N.Kimetal.,

2014)

VASCULAR /

OCULAR

Study number:

2

Single case,

female, age

unknown

(“healthy young

woman”

CEBMLevel4

Casereport

Retrospective

Typeoffiller HA • Singlecase• No dosage or

treatmentoutlined

• No conclusions for

treatment can be

drawn

Symptoms

and

presentation

Immediatevisionlossunilateral

Severepain

Associated

site and

vessel

Nose:non-surgicalrhinoplasty

OcclusionofOphthalmicartery

Resolution Noimprovement

30



Outcomes


Treatment

and

Intervention

Nonerecorded

(Y. J.Kimetal.,

2011)

VASCULAR /

OCULAR

Study number:

3

Single case,

female,30.

CEBMLevel4

Casereport

Retrospective

Typeoffiller

HA • Singlecase• No discussion or

exploration of

treatmentmodalities

Symptoms

and

presentation

Visionlossunilateral

Painnotspecified

Associated

site and

vessel


Centralretinalarteryocclusion

Resolution Noimprovement

Treatment

and

Intervention

IVMethylprednisolone1gperday3D,Oralprednisolone,aspirin

100mg,dressingskinlesion

Norelationshipbetweentreatmentandresolution

(S. W. Park et

al.,2012)

VASCULAR /

OCULAR

Study number:

4

12 cases,

female, age

range18-66

CEBMLevel4

Casereports

Retrospective

Typeoffiller Autologousfat7/12cases

Collagen1/12cases

HA4/12cases

• No attempt at

treatment

• Shortfollowupof16days and under in 5

cases

• Mixed retrospective

studynotjustHAfiller

Symptoms&

presentation

Lossofvisionunilateralwithorwithoutpain.

Associated

site and

vessel

Glabella7/12cases,Nasolabialfold4/12cases,CombinedG/NL

1/12cases

Ophthalmicarteryocclusion7/12cases(1/7HA)

Centralretinalarteryocclusion2/12

Branchretinalarteryocclusion3/12(3/3HA)

Resolution IAT(urokinase)didnotimprovesymptoms

No relationship between intervention and improvement in

symptoms;NoimprovementinOAOgroupandnoimprovement

inpatientswithseverelydecreasedsight

31



Outcomes


Treatment

and

intervention

Intra-arterialthrombolysis4/12cases

Anteriorchamberparacentesis4/12cases

Conservativemanagement3/12cases

Nohyaluronidase

(Kwon et al.,

2013)

VASCULAR /

OCULAR

Study number:

5

Single case,

female,20.

CEBMLevel4

Casereport

Retrospective

Typeoffiller

HA • Singlepatientstudy• Use of unlicensed

treatments

Symptoms

and

presentation

Lossofvisionunilateral,skinnecrosis

Warningsignignoredbypractitioner

Associated

site and

vessel


Occlusionofretinalartery

Resolution Improvedvisualacuityfrom20/70to20/30

Treatment /

intervention

Nicergorline

(Kassir et al.,

2011)

VASCULAR /

SKIN

Study number:

6

Single case,

male,52.

CEBMLevel4

Casereport

Retrospective

Typeoffiller HA • Singlepatientonly• Reference to

unrelatedstudies• Mechanism of

vascular event not

identifiedexactly• Appreciation of

common treatment

modalities which

have not been

implemented

Symptoms

and

presentation

Skinnecrosis:Latepresentationafterlargefillervolume

Associated

site and

vessel

Compressionoffacialartery,transversefacialarteryandbuccal

branchofmaxillaryartery

Resolution Healedwithscarring

32



Outcomes


Treatment

and

intervention

Conservative:antibiotics,scarmanagement

(Sun et al.,

2015)

VASCULAR /

SKIN

Study number:

7

20 cases with

nose and

nasolabial fold

augmentation,

1 male (21), 19

female(21-52)

CEBMLevel4

Casereports

Retrospective

Typeoffiller HA • Dosagesnotrecorded• Experimental

medicine / herbal

remediesusedwhich

are not licensed in

US/EU

Symptoms

and

presentation

Impendingskinnecrosisofnoseandglabellartissues

Associated

site and

vessel

Nose:nonsurgicalrhinoplastyin15/20cases

NLfoldaugmentation5/20cases

Resolution 13/20caseswithfullrecovery

earlytreatmentshowedbetteroutcome

Treatment

and

intervention

Previouslyundocumentedinterventions

Treatment with hyaluronidase all except 2 late presentation

cases

(T.H.Parketal.,

2011)

28 cases, all

filler

CEBMLevel4

Typeoffiller

HA

33



Outcomes


VASCULAR /

SKIN

Study number:

8

complications.

3/28 skin

necrosis

Casereports

Retrospective

Symptoms

and

presentation

Various,but3/28patientsskinnecrosis • All types of

complications

considered

• Number of vascular

complication cases

consideredlow

• Conventionaltreatment

approachesnotused

Associated

site and

vessel

Nose,nasalsidewallandmentumforsitesofnecrosis

Resolution Notdocumentedfornecrosiscases

Treatment

and

intervention

Antibioticsandsurgicalexcision

(Beleznayetal.,

2014)

VASCULAR /

SKIN

Study number:

9

12 cases with

vascular

compromise

from soft tissue

augmentation,

aged26-69

CEBMLevel4

Casereports

Retrospective

Typeoffiller Various,including5/12withHA

• Singlecentreresults• Long duration of

study(10yearspan)–

developments in

treatment and

products in this time

+++ but also shows

risk related to total

number of

treatments

Symptoms

and

presentation

Immediate (hours) or delayed (1-5) violaceous reticulated

patches

Associated

site and

vessel

Cheek,NLF,alarcrease

Resolution Complete,withoutscarringinallHAcases

Treatment

and

intervention

Warmcompress,hyaluronidase,massage,GTNpaste2%,aspirin

andprednisolone,dailyfollowup

(Q.Chen,Liu,&

Fan,2016)

VASCULAR /

SKIN

Single case,

female,32.

CEBMLevel4

Casereports

Retrospective

Typeoffiller

HA • Singlecase• No protocol that hasbeentested

• Pooroutcomes

Symptoms

and

presentation

Intensepainandskinblanching,followedbynecrosisofskin

34



Outcomes


Study number:

10

Associated

site and

vessel

Nose:non-surgicalrhinoplasty • Contradiction of

commonly used

methods for

resolutionofHAfiller

complication without

significantevidence

Resolution

Healingwithscarring

Treatment

and

intervention

Surgical decompression nasal tip, suction drainage, hyperbaric

oxygen,thereafterwoundmanagement

35

Table2:casecollectionfromkeypapers

Reference Paper category Age Sex Inject.

site Injection

vol. Symptom Time to presentation Diagnosis Treatment Outcome

Y. Chen et al., 2014 ocular 44 F Nose unknown headache, vision loss immediate anterior ischaemic optic

neuropathy

nitroglycerin, digital massage, eye drops to lower intraocular

pressure, aspirin, prednisolone.

small improvement BCVA

Y. Chen et al., 2014 ocular 45 F Periocular 1.0ml vision loss although not

fully described immediate central retinal artery occlusion

reduced sight but not loss, no improvement

Y. Chen et al., 2014 ocular 25 F Frontal

area 2.1ml vision loss although not fully described immediate unknown resolution from hand movement to

improved visual acuity

Y. Chen et al., 2014 ocular 38 F upper

eyelid 0.6ml Ptosis, ophthalmoplegia,

dizzy, vomiting, vision loss

immediate ophthalmic artery occlusion no light perception - no improvement

Y. Chen et al., 2014 ocular 23 F Nose 0.9ml

Ptosis, ophthalmoplegia, dizzy, vomiting, vision

loss immediate ophthalmic artery occlusion no light perception - no

improvement

S. N. Kim et al., 2014 ocular NA F Nose unknown Ptosis, ophthalmoplegia,

vision loss right eye unknown central retinal artery occlusion High dose IV corticosteroids

no light perception - improvement in lateral eye movement but not

sight

Y. J. Kim, Kim, Song,

Lee, & Yoon, 2011

ocular 30 F Nose 0.8ml

(symptoms after

0.2ml)

toothache, headache, pain in left upper face,

vision loss left, necrosis of skin glabella and nose

immediate central retinal artery occlusion

IV methylprednisolone, aspirin 100mg, wound dressing.

no scarring, eyeball movement returned to normal, permanent

vision loss

S. W. Park et al., 2012 ocular 32 F Nasolabial

/ glabella unknown

vision loss right eye, ocular pain, ptosis,

exotropia, ophthalmoplegia, corneal

oedema

immediate ophthalmic artery occlusion intra-arterial thrombolysis no light perception - no improvement

S. W. Park et al., 2012 ocular 26 F Nasolabial unknown inferior visual field defect,

no ocular pain 2 weeks branch retinal artery occlusion not recorded visual acuity 1 at presentation, no

change (20/20)

36


site Injection


S. W. Park et al., 2012 ocular 26 F Glabella unknown

inferior and central visual field defect, no ocular

pain 5 hours branch retinal artery

occlusion massage and anterior chamber

paracentesis visual acuity decreased from 0.7 to

0.15 over review period

S. W. Park et al., 2012 ocular 26 F Nasolabial unknown inferotemporal visual field

defect, no ocular pain 3 weeks branch retinal artery occlusion not recorded visual acuity 1 at presentation, no

change (20/20)

Kwon et al., 2013 ocular 20 F Nose unknown

partial visual disturbance right eye, orbital pain,

nausea, vomiting, headache,

blepharoptosis, diplopia, dizziness

immediate branch retinal artery occlusion

Aspirin, Nicegorline, eye drops, IV steroids, hyaluronidase for skin lesion, wound care, IV

antibiotics

visual acuity improvement from 0.3 to 0.6, partial resolution

blepharoptosis, partial resolution limitation of eyeball movement,

minimal scarring of skin

Kassir, Kolluru, &

Kassir, 2011 skin 52 M Cheek

scar 2.0ml persistent pain, slough, necrosis, poor capillary

refill 5 days

compression of facial, transverse facial, buccal branch of maxillary artery

supply areas

topical antibiotic, IM antibiotic, wound care (silicon) healing with scarring

Sun et al., 2015 skin 24 F Nose unknown Nose skin impending

necrosis 7 days compression of vessel causing ischaemia No hyaluronidase Necrosis of skin, healing with

scarring

Sun et al., 2015 skin 22 F Nose unknown Nose and NLF impending

necrosis 7 days embolism of vessel

Hyaluronidase, antibiotics, Tanshinone, Papaverine, topical

magnesium sulphate, infrared radiation, hyperbaric oxygen,

aspirin.

Necrosis of skin, healing with scarring


necrosis 4 days compression of vessel causing ischaemia Necrosis of skin

Sun et al., 2015 skin 28 F Nose unknown

Nose, NLF, glabella, forehead impending

necrosis 1 day embolism of vessel Necrosis of skin, healing with

scarring

Sun et al., 2015 skin 25 F Nasolabial unknown Nose, NLF, lip reticulated

erythema skin 3 hours embolism of vessel Full recovery

Sun et al., 2015 skin 25 F Nose unknown Nose reticulated

erythema skin 1 day compression of vessel causing ischaemia Full recovery

37


site Injection

vol. Symptom Time to presentation Diagnosis Outcome

Sun et al., 2015 skin 38 F Nose unknown Nose, glabella, forehead

reticulated erythema 1 day embolism of vessel Full recovery

Sun et al., 2015 skin 24 F Nose unknown

Nose, NLF, glabella, forehead impending

necrosis 9 days embolism of vessel No hyaluronidase Necrosis of skin


erythema skin 2 days embolism of vessel

Hyaluronidase, antibiotics, Tanshinone, Papaverine, topical

magnesium sulphate, infrared radiation, hyperbaric oxygen,

aspirin.

Full recovery

Sun et al., 2015 skin 52 F Nasolabial unknown Nose, NLF reticulated

erythema 1 hour embolism of vessel Full recovery

Sun et al., 2015 skin 21 M Nose unknown Nose reticulated

erythema skin, pustules 2 days compression of vessel causing ischaemia Full recovery

Sun et al., 2015 skin 22 F Nose and

nasolabial unknown Nose, NLF, glabella, forehead reticulated

erythema immediate embolism of vessel Full recovery


erythema skin, pustules 2 days compression of vessel causing ischaemia Full recovery

Sun et al., 2015 skin 21 F Nose unknown Nose, glabella, forehead

reticulated erythema 5 days embolism of vessel Full recovery

Sun et al., 2015 skin 35 F Nasolabial unknown Nose, NLF reticulated

erythema, pustules 1 day embolism of vessel Full recovery


erythema skin 3 days embolism of vessel Full recovery


erythema skin 2 days embolism of vessel Full recovery

38


site Injection

vol. Symptom Time to presentation Diagnosis Outcome


necrosis 5 days compression of vessel causing ischaemia Necrosis of skin


necrosis 2.5 days compression of vessel causing ischaemia

Necrosis of skin, healing with scarring

Sun et al., 2015 skin 37 F Nose unknown Nose, NLF reticulated

erythema 1 day embolism of vessel Full recovery

T. H. Park, Seo, Kim, & Chang, 2011

skin ? ? Nose unknown tissue necrosis 3 months not made Oral antibiotics not described

T. H. Park, Seo, Kim, & Chang, 2011

skin ? ? Nasolabial unknown alar necrosis 7 days not made Oral antibiotics not described

Beleznay, Humphrey, Carruthers,

& Carruthers,

2014

skin 69 ?

Pre-jowl sulcus, lip

corner, right

lateral cheek

1.0ml violaceous reticulated patch right NLF, pain

right upper lip, numbness, ecchymosis

2 days vascular compromise -

presumed compression of vessel or embolisation (if

immediate) Massage, warm compress complete resolution


& Carruthers,

2014

skin 65 ? Nasolabial 1.0ml violaceous reticulated patch left NLF, pain 2 hours

vascular compromise - presumed compression of vessel or embolisation (if

immediate) Massage, hyaluronidase complete resolution


& Carruthers,

2014

skin 31 ? Nasojugal 2.0ml violaceous reticulated patch right cheek, pain 5 days


immediate)

Massage, warm compress, hyaluronidase complete resolution


& Carruthers,

2014

skin 50 ? Nasolabial 2.0ml violaceous reticulated patch left NLF and alar

crease, pain 1 day


immediate)

Massage, warm compress, hyaluronidase, prednisolone complete resolution

39


site Injection



& Carruthers,

2014

skin 58 ? Nasolabial and cheek

0.5ml HA but also

3ml CaHA to NLF

and cheek

violaceous reticulated patch and blanching left

NLF immediate


immediate)

Massage, warm compress, nitroglycerin paste,

hyaluronidase, prednisolone, aspirin

complete resolution

Q. Chen, Liu, & Fan,

2016 skin 32 F Nose unknown

grey discolouration forehead, nasal sidewalls

(bilat), nasal triangles (bilat)

2 days vascular compromise surgical decompression, suction

drainage, hyperbaric oxygen, wound management

healing with extensive scarring

40

Discussion

Vascular complications are fortunately rare, and occur at a rate of around 0.001% of all

performeddermalfillertreatments(Cohenetal.,2015).

Beleznayetalreportariskrateofaround0.05%forvascularcomplicationsintheirpractice,

whichmaybeduetoahighercomplexityofproceduresundertaken(Beleznayetal.,2014).

However,whentheadverseeventrequiresreferral toacentresuchas thatbyParketal,

around10%ofallthosereferredarenecrosiscases(T.H.Parketal.,2011).

Whilstarterialocclusionisofsuddenonset,oftenaccompaniedbyseverepainandblanching

of the affected skin, venousobstruction can result in delayedpresentationof violaceous,

reticulatedpatchesontheareaoftissuedrainedbytheobstructedvein(Daines&Williams,

2013).Visionlossisoftentheformer,whereanembolusoccludesanocularsupplyartery

leadingto ischaemiaoftheorbitandassociatedmuscles,whereascomplications involving

theskincanbeeitherduetofillerembolusaffectinganartery,orcompressionofanarteryor

veincausingischaemiaofthetissuewithdelayedonset.Pressurenecrosiscanresultfrom

thesheervolumeoffillerintroducedintothetargettissue,suchasthecasebyKassiretal

where2.0mlofHAfiller injectedintoanalreadypoorlyperfusedscarresultedinnecrosis,

furtherexacerbatedbydelayedexpansiontoHAfillerasaresultofitshydrophilicproperties

(Grunebaumetal.,2009;Kassiretal.,2011;Sunetal.,2015).Thetimetopresentationisa

useful indicatorof thenatureof thevascularaccident– inthestudybyBeleznayetal for

example,threeoutofthefiveHAfillercasespresentedat24hoursormore,suggestingthat

thecomplicationisduetocompressionorembolizationofavein,whichisofsloweronset

(Beleznayetal.,2014).Sunetalspecifiedthedifferencebetweenvesselembolizationand

compression in their findings, however how these were distinguished has not been

elaboratedupon–itisassumedthatimagingprocedureswereusedtoidentifythecauseof

thecompromise inadditiontotheareasuppliedbeingdemarcatedbytheareawhichthe

vesselshouldsupply.Asfarastheauthorisaware,thereisnohardandfastwaytoeasily

distinguish between embolization and compression at the point of diagnosis. However,

compression may be easier to resolve with liberal injection of hyaluronidase to relieve

pressureonthevesselinquestion.

41

Allstudiesexaminedwereretrospectivecasereviews.Chenetal,ParketalandBeleznayet

al all reported larger sample size in the papers analysed, with 13, 12 and 12 cases,

respectively. However, these studies all considered various types of fillers, including

autologousfat,collagen,unidentifiedparticulatefillersandHA(Beleznayetal.,2014;Y.Chen

etal.,2014;S.W.Parketal.,2012).TheonlystudytofocusentirelyonHAfillercomplications

wasbySunetal,with20subjectsrecordedinaretrospectivecaseseriesexaminingimpending

necrosisoffacialtissues(Sunetal.,2015).Conclusionsrelevanttotheclinicalquestioncould

onlybedrawnfromcasesthatweretreatedwithHAfillersinthemidface,whichhavebeen

presentedinTable2andwhichwillbereferredtohenceforth.Therewereatotalof12ocular

complicationsand29skincomplicationsassociatedwithHAfillertreatmentinthetenstudies

includedforanalysis.Allcaseswereaccountedforfrompresentationtooutcome.

Fillertypes

Therelevanceofdifferentfillertypesisintheircapacitytooccludevesselsoftheeye.The

particle sizeofHA fillers is around400µm,which isof sufficient size toblock the smaller

vesselssuchastheretinalarteriesmeasuringaround160µmdiameterbutnotlargeenough

to block the main ophthalmic arteries at around 2mm diameter, unless a large bolus is

injectedatspeed. Incasesofvision lossresultingfromHAfiller,theretinalarteryand its

brancheswereinvolvedin64%wheretheaffectedvesselwasdocumented.Chenetaland

Park et al compared this with the occlusion of vessels by other types of filler, especially

autologousfatwheretheparticlesizeisextremelyvariableandoftenlarger,andnotedthat

autologousfatoccludedlargervesselssuchastheophthalmicarterymorefrequently. HA

fillerocclusionoftheocularvesselsisthereforeassociatedwithbetteroutcomeastheinitial

blockageofthevesselislikelytobeasmallerone,supplyinglesstissue(Y.Chenetal.,2014;

S.W.Parketal.,2012).

ThestudiesbyParketalandChenetalconsiderverysimilarcasesofocularcomplications.

Whencomparing the two, the incidentsofocular complications for thedifferent typesof

fillers resulted insimilarpercentages for incidentsofHAversusAutologous fat fillers. HA

42

fillersrepresentfiveandfourcasesineachseries,respectively.Autologousfataccountsfor

sevencasesoutofthe13casesbyChenandsevenoutof12casesbyPark(Y.Chenetal.,

2014;S.W.Parketal.,2012).Autologousfatthereforeaccountsformorecasesofvisionloss

inbothreferralcentres,eventhoughthenumberofHAfillertreatmentsfaroutweighthe

numberofautologousfattreatments.Comparingthiswiththe2014ISAPSdata,therewere

965,727 treatments with autologous fat versus 2,690,633 with HA filler. However, the

instancesofreportedvisionlossforautologousfatinthestudiesbyChenetalandParketal

arehigherthanHAfillerbyafactorofalmost2.Ifthepatientgroupinthesetwostudiescan

beusedasarepresentativeaverageofwhatreallyoccursintermsofcomplicationrate,then

extrapolating these values relative to the ISAPS data means that autologous fat is

approximatelyfivetimesmorelikelytocauseblindnessthanHAfillers(ISAPS,2016).

Highriskareasandtheeffectonvessels

Theresultsgainedfromtheincludedpapersgaveaveryclearindicationofthehighriskareas

fortreatmentwithdermalfillers.SunetalintheirstudyfocusingonHAfillers,75%ofthe

cases of skin necrosiswere due to treatment of the nose and the remaining 25%due to

treatmentofthenasolabialarea,andallofthesubjectspresentedwithskinnecrosisofthe

nose,regardlessofwhereinthemidfacethetreatmentsitehadbeen(Sunetal.,2015).In

thecollated12ocularcomplicationscasesfromallpapersconsidered,thenosewastreated

in42%ofcases,withnasolabialandglabella treatmentbothbeingresponsible for25%of

vision loss cases each. A staggering 59% of the collated 29 skin necrosis cases from all

consideredkeypapershadhadtreatmentofthenose,followedbytreatmentofnasolabial

foldswith34%ofcases.Thisclearlyoutlinesthenose,nasolabialandglabellaastopthree

sitestoresultinvascularcomplications.

Noseaugmentation is thereforeclassedas thehighest riskprocedure in themidface. It is

perhapsnocoincidencethatseveralofthepapershail fromChinaandKorea,wherenose

reshaping in order to westernise the patient’s appearance is a procedure that is on the

increase(S.W.Parketal.,2012).Whilstthenoseisregardedasatreatmentareathatonly

experiencedpractitionersshouldapproach,nasolabialfoldaugmentationisoneofthefirst

43

treatmentstaughtonmanyone-daycourses,especiallyintheUK–thisposesaseriousrisk

for patients and aworry to experienced practitioners receiving referrals for complication

management.

It has already been established that treatment of the nose is usually due to a desire to

reshape, rather than for rejuvenation purposes. Considering the incidence of ocular

complicationshowever,theredoesseemtobeaweightingtowardscomplicationsinyounger

individuals–allsubjectsdocumentedwithvisionlossasaresultofHAfillertreatmentwere

undertheageof45.Thismaynotbeacoincidence.Itisthoughtthatyoungerindividuals

may be at increased risk of ocular complications due to an increased number of patent

cutaneous arterial anastomoses. In a cadaver study by Tansatit et al, injection of facial

arterieswithdyeledtothedyebeingextrudedintotheglobe.Inmuchthesameway,filler

can causeocular complications. Large facial cutaneousarteries canbeeasily accidentally

cannulatedinfillertreatment.Whenpressureisexertedontheplunger,andthisissufficient

tocauseretrogradeflow,theophthalmicarterycanbereachedfromaugmentationsitesin

noseandnasolabialareas(Y.Chenetal.,2014;Tansatitetal.,2015).

Chenetalreportedthatinadditiontolossofvisioninonecase,thepatientexhibitedsigns

ofacerebralaccidentasaresultoffillertreatment,evidencedbymagneticresonanceimaging

(Y.Chenetal.,2014).Cerebralinfarctionhaspreviouslybeendocumentedinafurtherstudy

byHsiehetal,thoughttobecausedbypressureexceedingsystoliconinjectioncausingreflux

offillerembolustothemiddlecerebralartery.Thiscanhavetrulydevastatingconsequences

(Hsiehetal.,2015).Excesspressureoninjectionisthereforeasignificantriskfactorindermal

fillertreatment.

Thefirstcaseofpermanentvision lossasaresultofHAfillernon-surgicalrhinoplastywas

2011byKimetal(Y.J.Kimetal.,2011).By2013,thetotalnumberofcasesofvisionloss

associatedwithalltypesoffillertreatmentwasaround60.Therearearangeofwarningsigns

forvisionlossasaresultoffillertreatment,withocularpainandptosispresentinginalarge

number of cases. Associated loss of movement of the eye is due to occlusion of the

ophthalmicarteryandlackofperfusiontotheoculomotornerves(Y.Chenetal.,2014).In

thestudybyKwon,thepractitionerdocumenteda“bursting”sensationafterinitialinjection,

44

whichwasignored,shortlyafterwhichthepatientreportedlossofvision(Kwonetal.,2013).

Othersymptomsincludedtoothacheandpainononesideoftheface(Y.J.Kimetal.,2011).

Parketal linkedocclusionoftheophthalmicarterytoseverepain,whereascentralretinal

arteryocclusionandbranchretinalarteryocclusioncanpresentwithoutpain(S.W.Parket

al.,2012).Itappearsthatthesmallerthevesseloccluded,thelesspainresultsduetoless

tissuesupplied.ExaminationoftheretinainthestudiesbyKimetalandChenetalrevealed

cherry-redspotsassociatedwithophthalmicarteryocclusionandthinningofthefundus.The

outcomeforthesepatientswasnoimprovementinlightperception,withophthalmicartery

occlusionhavingtheworstprognosisandmostseveresymptoms(Y.Chenetal.,2014;Y.J.

Kimetal.,2011).

Interventions

Skinischaemia/necrosis

Earlyinterventionwithimpendingskinnecrosisislinkedtoafavourableoutcome;Sunetal

claim that when treatment is started within two days, the patient suffers a significantly

reduced incidenceof scar formation (Sunetal.,2015). Outof the29casesof impending

necrosisoftheskinanalysedfromtheliterature,17weretreatedintwodaysorless.Ofthese

17,two,or12%,sufferedadegreeofscarringafterhealing.Thiscanbecomparedtothose

thatreceivedtreatmentaftertwodays,afterwhich58%ofpatientssufferedscarringafter

vascularcompromise.Althoughtwodaysisanarbitrarytimespan,thisdoesappeartomark

the divide between excellent and mediocre outcome for resolution of necrosis of skin.

However,thecorrelationbetweentreatmenttimeandoutcomeneedstobemoreextensively

studiedtodemarcateoptimumoutcomeversustimetopresentation(Sunetal.,2015).

Astudyconductedin2007byHirschetalwasthefirstcaseinliteraturethatHyaluronidase

wasusedtosuccessfullymanagevascularcomplicationfromHAfillerandithasbeenusedto

routinelytreatvascularcomplicationsendangeringskinsince(Hirschetal.,2007).Ithasbeen

showneffectiveinthemanagementofimpendingskinnecrosis,butnotinthemanagement

ofocularcomplications.Outofthe29casesaffectingtheskin,22(76%)weretreatedwith

45

hyaluronidase,ofwhich17(59%)hadagoodoutcome.Theremainingfivepatientswhodid

not have a good outcome with necrosis and scarring a consequence of the vascular

complication,presentedat1day,2.5days,4days,5daysand7daysposttreatment.Sunet

aladvisedthatearlytreatmentisessential,anddescribethisaswithintwodaysoftreatment.

Considering the results from the collected studies, there is a significant improvement in

outcomewhentreatmentisstartedwithhyaluronidaseintheearlypresenter. Comparing

thiswiththeindividualsinthecasegroupsthatdidnotreceivehyaluronidase,onlyoneout

of7patientshadagoodoutcomewithoutscarring.Thelackofuseofhyaluronidaseseems

tobeinpartduetothelatepresentationofthepatientsof5dayspost-operativelyormore.

Atthisstagetissuenecrosisismostlikelyatanadvancedstageandtheprognosisisseverely

compromised (Beleznayetal., 2014; Sunetal., 2015). It can thereforebeconcluded the

incidence of scarring and long term sequelae can be reduced when hyaluronidase is

administeredimmediatelyorattheveryleastwithintwodaysoftheproceduretoimprove

outcome.

Intheircasereportseriesinvestigatingimpendingskinnecrosis,Sunetalexploredtheuseof

Tanshinone and Papaverine alongside commonly used methods to improve vascular

compromise(Sunetal.,2015).TanshinoneisaChineseherbalremedyderivedfromSalvia

miltiorrhiza,whichhasbeenusedtotreatavarietyofcerebralandcardiovasculardisorders.

Tangetalinvestigateditseffectivenessinreperfusionofcerebralischaemiainrats,showing

thatithasaprotectiveeffectandimprovescerebralbloodflowintheanimalmodel(Tanget

al.,2014).However,itsuseinpreventionofnecrosisasaresultofHAfillerhasonlybeen

documentedinthestudybySunetal.Papaverineisanopiumalkaloidantispasmodicand

cerebralandcoronaryvasodilator(Fusi,Manetti,Durante,Sgaragli,&Saponara,2016),and

waspresumablybySunetaltoimproveperfusionoftheischaemictissue.Unfortunately,as

thevariableshavenotbeenseparatedandallinterventivemethodsincludinghyaluronidase,

papaverineandtanshinonewereallcombinedonthesamesubjects,itisdifficulttoascertain

whether the two novel interventions had any significant effect on the outcome for the

patient.Intheabsenceofdatatothecontrary,andgiventhattheoutcomesinthestudyby

Beleznay et al were similarly good with complete resolution of the skin lesions without

scarring, itmustbeassumedthattanshinoneandpapaverinedidnotsignificantly improve

46

outcomeforthepatientsaboveandbeyondwhatwouldhavebeenobtainedwiththeuseof

hyaluronidaseandstandardtreatmentmethodsalone(Beleznayetal.,2014;Sunetal.,2015).

Intheirsinglecasereport,Chenetalillustratedhowover-aggressivemanagementwithout

implementingcommonlyusedprotocolsforthemanagementofvascularcomplicationscan

leadtopooroutcome.Thepatientpresentedmoderatelylate,at2days,andinsteadofusing

hyaluronidase,massageoranyvasodilatingtreatments,surgicaldecompressionandsuction

drainagewasperformed.Itisdebateablewhetherthissurgicalinterventionmayhavecaused

furthertissueswelling,leadingtoexacerbationoftheareaofischaemia.Theoutcomeforthe

patientwasextensivescarringtothenoseandglabella.Chenetalconsidered,muchtothe

patient’sdetriment,thattheuseofhyaluronidaseatdaytwowouldnotbeofuse.Thisis

contrarytotheresultsachievedbyBeleznayetalwhereinthecaseoftwoindividualswitha

similarpatternofischaemiaat2daysand5days,completeresolutionwasachievedwiththe

useofhyaluronidaseandadefinedmanagementprotocol(Beleznayetal.,2014;Q.Chenet

al.,2016).

Incaseswhereischaemiahasledtonecrosisofskin,theoutcomecanbepositivelyinfluenced

byappropriatewoundmanagement.Siliconedressingshavebeenshowntoimprovehealing

of the necrotic tissue and wounds (Lansdown & Williams, 2007). Furthermore, where

accessible,hyperbaricoxygentreatmentcanimproveskinresolution.Itisoftenusedingraft

healing after cancer or trauma surgery and for the treatment of nonhealing wounds by

increasingendothelialcells,fibroblasts,keratinocytemigrationanddifferentiation,butcan

poseanexcesscost,riskandinconvenience(Grunebaumetal.,2009;Kassiretal.,2011).With

smallareasofnecrosisitisthoughtthatitposesnoadditionalbenefit.Indeed,thestudyby

Sun et al failed to provide any concrete evidence that recovery was better than the

straightforwardprotocolappliedbyBeleznayetalintermsofhealingwithoutscarring.Whilst

itmaysupplysomebenefitasanadjunctivetreatment,usinghyperbaricoxygenasafirstline

treatment in the case reportedbyChenetal showedworseoutcome. Itwould certainly

representasignificantfinancialinvolvement;lowcostinterventionsincludinghyaluronidase,

massageandaspirinhavebeenshowntohavemorefavourableoutcomeswhicharemore

easilyimplementable(Beleznayetal.,2014;Q.Chenetal.,2016;Sunetal.,2015).

47

Visionloss/disturbance

UrokinasewasadministeredtoonepatientinthecaseseriesbyParketalinordertoachieve

intra-arterialthrombolysisandreduceclotformationwithinthevesselwalls(S.W.Parketal.,

2012).Inmuchthesamewayaswhenadministeredforthetreatmentofischaemicstrokes

withinthefirstfewhoursafterthecardiovascularaccident,itwashopedthatreperfusionof

the vessel would be achieved, leading to the patient regaining some or all of their sight

(Wardlaw,Murray,Berge,&delZoppo,2014).However,therewasnoimprovementinlight

perception and no improvement in sight for this patient, leading to the conclusion that

urokinasewas ineffective. Indeed, itwouldbeunlikely to remedyaHA filler embolus as

urokinasewouldnotbeabletodegradehyaluronicacid.Inordertorulethisinterventionout

fully, however, further interventions with intra-arterial thrombolysis would need to be

documented.

NicergolinewasusedbyKwonetaltomanageacaseofbranchretinalarteryocclusionand

subsequent decreased sight resulting from HA filler treatment. Nicergoline was used in

conjunctionwithaspirin,IVsteroidsandhyaluronidasefortheskinlesion(Kwonetal.,2013).

Itisadrugthatcandecreasevascularresistanceandhasbeenusedtotreatcerebralinfarction

andacuteandchronicperipheralcirculationdisorders,amongstothers.Itactstopromote

cerebralmetabolicactivity,resultinginincreasedmetabolismofglucoseandoxygen,andis

antithromboticbyinhibitingplateletphospholipaseandinterferingwithplateletaggregation.

The patient treated with the combination of steroids, aspirin and nicergoline showed

improvement in sight and partial resolution of blepharoptosis and eyeball movement.

Unfortunately,however,theEuropeanmedicinesagencyhaverestrictedtheuseofallergot

derivatives including nicergoline due to concerns about the safety profile of these drugs.

Whilstthetreatmentcombinationmayhavebeeneffectiveforthispatient,afurtherlarger

case serieswouldneed toutilise this treatment;even if thisproved successful theuseof

nicergolinewouldberestrictedintheUK(Kwonetal.,2013;Saletu,Garg,&Shoeb,2014).

Chenetalpresentedacaseseriesinwhichtreatmentwithnitroglycerin,digitalmassage,eye

drops,aspirinandprednisolonewasused.Inonecase,apatientshowedanimprovementin

48

bestcorrectedvisualacuity(BCVA).Asecondcaseinthisseriesimprovedinsightfromhand

movementto“improvedvisualacuity”.Itisnotspecifiedwhethernitroglycerinwasapplied

topically, as it isoftenwith skin ischaemia,or systemically. Nitroglycerin relaxesvascular

smoothmuscleleadingtovasodilation,whichisthoughttoassistinreperfusionofthetissues

affectedbyvascularcompromise(Kukovetz,Holzmann,&Romanin,1987).Theroleofaspirin

isantiplatelet,whereaseyemassageisthoughttohelpdislodgetheclotandprednisoloneto

reduceinflammation.Unfortunately,theimprovementmayalsobeacoincidence–thecase

wasdiagnosedasanteriorischaemicopticneuropathy,andthereforemuchlessseverethan

fullocclusionoftheophthalmicartery.Forthesecondcase,thedataondiagnosisismissing

andtheoutcomeisrathervague,soconclusionsabouttheeffectivenessoftheintervention

cannotbedrawn.TheremainingcasesinthesameseriesbyChenetalthatweretreated

with the sameprotocolafterdiagnosiswithophthalmicarteryocclusionor central retinal

artery occlusion showed no improvement in symptoms (Y. Chen et al., 2014). Indeed,

consideringthethreecasesofcentralretinalarteryocclusionandthreecasesofophthalmic

arteryocclusion fromthestudiesconsidered,noneof the interventionsbroughtaboutan

improvement.

Aninterventionbestperformedinahospitalsettingbyaspecialistophthalmologist,Parket

aldescribedtheuseofanteriorchamberparacentesistotreatvisionlossasaresultoffiller

treatment(S.W.Parketal.,2012).Anteriorchamberparacentesishassincebeenusedina

study by Rajabi et al to alleviate central retinal artery occlusion in a patient who had

undergoneorbitaltumourresection.However,inthisstudy,theinterventionwasperformed

immediately,inadditiontosystemicmannitolandintravenousacetazolamidetherapy,and

partial resolution to 1m counting finger was achieved (Rajabi, Naderan, Mohammadi, &

Rajabi,2015). Chenetalwereunable toachieve improvement for theirpatientwhohad

visionlossasaresultofdermalfillers.Thedifferencebetweenthetwocasesmaybedueto

thetimetotreatment–Rajabi’spatientwastreatedimmediately(indeedwasalreadyina

hospitalsetting),whereasChen’spatienthadafive-hourdelay,butalsoduetotheoccluding

material– fillerversusbloodclot. It isknownthat retinal ischaemiabecomes irreversible

after90minutes,soquickactiononbehalfofthereferringpractitionermayhaveimproved

theoutcome.Thisiscertainlyahospital-basedprocedureandnotonethatcanbesuggested

foruseinpractice,butitmayhavescopeyet.

49

Unfortunately,nointerventionshavebeenfoundthatwillreliablyinfluencetheoutcomeof

visualdisturbanceasaresultofHA(orany)fillertreatmentandcanbeusedinpractice.Even

largecentressuchasthosebyChenetalandParketalhaveshownthatthedevelopment

andimplementationisnotrelatedtofunding,butsimplybecausetheredoesnotcurrently

seemtobeareliableremedyforfiller-inducedblindness(Y.Chenetal.,2014;S.W.Parket

al.,2012).

Outcomes

In all cases considered, the exposure to the filler treatment preceded the vascular

complication,andnootherfactorscouldhavebroughtabouttheonsetofsymptoms.Itis

knownthatinjectionoffillercanleadtovisionlossortissueischaemia.

Outof29casesofskinischaemia,62%progressedtoafullrecovery.Consideringthetwelve

casesofocularcomplications,threecases(25%)showedslightimprovementinsightfroma

state of decreased sight, but no cases returned to normal and no cases with vision loss

showedanyimprovement.Acaseoflossofvisionisthereforesignificantlymoreconcerning

forthepatient’slongtermwellbeing.

Unfortunately, the three cases of decreased sight that showed improvement had a high

numberofvariablesincludinginterventionandfollowupandlittledocumentationaboutthe

dosesinvolvedintreatment.Also,thevesselsinvolvedweresmallerandthesymptomsless

severe(orsimplyunrecordedinonecase),whichcouldmeanthattheinterventionhadno

effectorthebodysimplydealtwiththeocclusion.

There has been no reproducibility in the outcome of vision loss as a result of HA filler

treatment.Therefore,ratherthanattempttochangeguidelinestonovelinterventionsthat

havebeensparselystudied,itmaybebettertocontinuewithexistinginterventionsthatare

notconsideredharmfultothepatient(butmayalsoresultinlittlebenefit).Impendingskin

necrosis treatment on the other hand has been studied and adequate, reproducible

50

interventions have been performed and documented by Beleznay et al and Sun et al

especially.PartsofthestudybySunetalwhichconsidernovelherbalremediesshouldbe

furtherinvestigatedforsafetyandefficacy(Beleznayetal.,2014;Sunetal.,2015).

BeleznayetalreportfivecasesofHAfillerinducedvascularcomplicationoveratenyearspan.

Whilst themanagement resulted in adequate resolution for all of their cases, the author

raisesthefollowingobservationsforthiscaseseries.Thefirstisthatthetreatingpractitioners

inthiscaseseriesareextremelyexperiencedandperformaverylargenumberofdermalfiller

treatments, yet they appear tohave ahigher thanaverage vascular complication rate, at

0.05%.Thiscouldbeduetohighernumbersofhighriskproceduresperformedbythiscentre,

althoughalloftheircaseswererelatedtotreatmentofthenasolabialfoldandnotthesite

considered tobe thehighest risk (thenose). Given theexperienceof thepractitioners in

question,itisunlikelytobeduetotechnique.Thisriskratemaybetheactual“honest”risk

rateforvascularcomplications;honestyinreportingisanissuethatisacauseforconcernin

theaestheticindustry,andmanysuspectthattheactualincidenceofvascularcomplicationis

muchhigherthanthe0.001%quotedbyCohenetal(Cohenetal.,2015). Theauthorhas

certainly never heard of non-healthcare providers of aesthetic treatments coming clean

willinglyabouttheircomplications.Afurtherobservationaboutthiscaseseriesisthetime

span over which the cases were reported. Technology in dermal fillers has come along

significantlyover the10-year timeperiod inwhich thecasesconsideredbyBeleznayetal

presented;unfortunately,thepresentationofthecasesalongthistimespanisnotrecorded.

Modernfillersmaynowperformbetterforthepurposeforwhichtheyareintended,andas

suggestedbyInglefieldetal,afactorinminimisingcomplicationsisselectingtheappropriate

filler–withsomanyonthemarket,fillerperformanceisimproving.

The larger centre studieswithmultiple cases in this reviewdemonstrated clearly defined

outcomes,whereasthesmallerstudiesincludedinthereviewareusuallyone-offcasereports

of adverseoutcomeswhichwere less reliabledue to the small amountofdata collected.

Noneofthestudieshadcomparisongroupsfortheintervention.Inordertoarriveatreliable

interventionstrategies,furtherinvestigationwithalargeramountofcaseswouldneedtobe

completedforvisionlossasaresultofHAfillertreatment.

51

Practitionerstatus

Unfortunately, the studies that were considered did not give adequate insight into

practitionersmostatriskofcausingvascularcomplications,asthiswasonlydocumentedin

9outofthe41casesincludedintheanalysis,andinthesethepractitionersweremedically

qualified, i.e.surgeonsorphysicians. Indeed,noresearchhasfocusedspecificallyonthis.

Chenetalbrieflytouchedonthequestionablelicensingstatusoftheperformingpractitioner

in their study. However, in this study it became evident that even thosewith specialist

medicaltrainingcanproveill-equippedtodealwiththecomplicationathand.Inthiscaseit

appears thatwhilstmedically qualified, the surgeonswere not trained to deal with filler

complications.Thepatientwaspassedfromoneinadequatepractitionertothenext,failing

to implement simple protocols including hyaluronidase in favour of a surgical approach,

resultinginapooroutcomeforthepatient

EspeciallyintheUK,whereKeoghdescribedfillersas“acrisiswaitingtohappen”(Keoghet

al.,2013),dermalfillertreatmentcanbeperformedbyanyone,whethermedicallytrainedor

not.Non-medicallyqualifiedindividualsoftenpracticewithnoclinicalsupportwhatsoever,

andindeedtheymaypracticeanywhere(Bruce&Jollie,2014).Unfortunately,non-medical

practitionersoftendonotfeelboundbythesamecodeofethicsthatmedicalprofessionals

must subscribe to, and clinical data on the outcomes of treatment by lesser licensed

individualsmaybedifficulttoachieve.

52

Evidencebasedguidelinesforthepreventionandmanagementofvascularcomplications

Vascular complications involving HA fillers can result in permanent disfigurement. The

following guidelines have been devised by assessing the relevant literature in relation to

favourableoutcomes.Theauthordoesnotconsideritreasonabletoexperimentwithnovel

techniques in practice setting, and any interventions have been devised in line with

techniquesandtreatmentsthathavebeendemonstratedaseffective.

Preventionprotocols

Preventionstrategiesshouldbeconstantlyreferredtobytheaestheticpractitioner.Table3

outlineshowsimplemeasurescanavertseriouscomplications.

53

Table3:PreventionprotocolsforvascularcompromisePreventionstrategiesandin-treatmentprecautionsforVascularComplicationsPatient • Detailedmedicalandpsychologicalhistory

• Aesthetictreatmenthistory–previousrhinoplastiesincreaserisk• Assessmentofanatomicalsites• Validinformedconsent• Documentationofrisks,benefitsanddiscussions• Pre-operativephotographs

Filler • Viscosity/propertiescorrectfortreatmentarea• Reversibilitywithhyaluronidase

HighRiskAreas • Knowyouranatomy• Nasalala:avoidifpossible,extremelyhighrisk• Nasolabialandnose:caution,relativerisk

Technique • Smallestpossibleneedlesizepreventsexcessproductinjection• Aspirationpriortoinjectiontocheckforintra-vascularposition• Retrogradeinjection• Lowinjectionforce–smallersyringesrequirelesspressure• Smallestpossiblevolumes• Stopandreassess ifneedlebecomesblockedor injectionrequires

higherpressurethananticipated• Cannulausedecreasestraumatovessel,especiallyinnose• Placementofproductatmidlineinnose,belowmusculoaponeurotic

layer• Superficialinjectiontechniqueinnasolabialfold• Compression of supply artery during procedure: upper nasolabial

fold,sideofnose,oralcommissure,• Compressionofanastomosis siteduringprocedure: superiornasal

corner

Pain • Investigatepainthatisdisproportionatewithtreatment• Counselpatienttoreportpain• Sharp,suddenpain:queryarterialocclusion• Dull,throbbingpain:queryvenousocclusion

PatientObservationandAftercare

• Blanchingorskinchangesmustbemonitoredtoresolution• Counselpatienttoreportskinorsensorychanges• Fullpost-operativeinstructionsgivenverballyandwritten• Outofhoursemergencynumberavailabletopatients

54

Managementprotocols

Unfortunately, fewstudieshavebeenpublishedthatfocusonthedevelopmentofnewor

improvedprotocolsratherthanjustreportingcases.Evenwiththecasesexaminedinthis

review,highnumbersofvariablesandlownumbersofsubjectsmakethedevelopmentofany

novelguidelinesverydifficult.Managementprotocolscanbeformulatedfromthosecases

thatshowfavourableoutcome,combinedwithhistoricallyeffectiveinterventions.

Lossofvision

Thisislikelytobeaterribledayforboththepatientandthepractitioner.

Retinalnecrosisbecomesirreversiblesome90minutesaftertreatmentandearlyrecognition

ofthecomplicationandrapidtreatmentinductionisessential.Thegoalistoregainsightand

reperfusionoftheretinaiscentraltothis;alleffortsmustbecentraltothis(S.Lazzerietal.,

2013).

Unfortunately,officebasedremediesthataestheticpractitionersarelikelytohaveattheir

disposal prove to be largely fruitless if occlusionof the ocular vessels has occurred. It is

impossible to remove the embolus as it is simply not accessible andhyaluronidase is not

suitable for lysis of emboli in vessels (Kwon et al., 2013). Whilst hyaluronidase is

recommendedimmediately,itwillmostlikelyonlyactontheareaofischaemiaaffectingthe

skinratherthanremedythelossofvision.

Reducingintraocularpressureisdifficultinpractice;eyemassage,alsoknownaseye-CPR,can

beperformedinordertoattempttodislodgetheclot(Y.Chenetal.,2014). Anybladeor

needle incisions to reduce intraocular pressure should be left for consultant

ophthalmologists.Itisperhapsbettertonotattemptanyheroicinterventionsinpractice–

practitionersshouldactwithintheircompetenceandscopeofpracticeandrecognietheneed

for early referral. It is important to have an immediate referral pathway to an

ophthalmologist or the nearest emergency room where treatment with IV

55

methylprednisolone1gfor3days,highdoseoralprednisoloneandaspirin100mgperdaycan

bestarted.Thisishoweverlikelytosimplyreducetheaccompanyingeffectsontheskin(Y.J.

Kimetal.,2011).Thepractitionershouldaccompanythepatientandexplainwhathascaused

thevisionlossandhowthismayhavehappened.

Table 4 outlines the limited possible treatment options available to practitioners in the

practicesetting.

Table4:managementofvisionlossManagementofvisionloss

Identifythecomplication CheckforeyemovementCheckfordecreasedorlossofvision+/-pain

Immediatemanagement • Stoptreatment• Hyaluronidaseupto1000Ualonginjectionsite• Aspirin2x325mg• Eye-CPRtoattempttodislodgeclot

ImmediateReferral • ToA&E/Ophthalmology• Accompanypatientandassisttoexplainhowevent

occurredImpendingnecrosisofskin

Whenthevascularocclusionoccurs,treatmentshouldbeswiftandaggressive.Beleznayet

al produced effective and simple guidelines for treatment that can be used in aesthetic

practicewithoutbeingtoocostlyorconfusingforthepractitioner(Beleznayetal.,2014).

Theprotocolintable5andfollowingalgorithminfigure2isdevisedtoenableathreefold

approachtotissuerecovery,includingdissolutionoftheproduct,vasodilationandincreased

bloodflow.Theimmediateapplicationofheatwithawarmcompresswillaidbloodflowto

thearea.Whilsteffectiveforvasodilation,theuseofnitroglycerin(GTN)pasteiscontroversial

–itmaycauseorthostatichypotension,potentiationofvasodilationwithalcoholandother

vasodilatorssuchassildenafil,andcancauserashes,dizzinessandheadaches(Cohenetal.,

56

2015;Glaichetal.,2006).Nevertheless,theriskofthelikelyoutcomeofnecrosisandscarring

isthoughtbymanytobegreaterthanthetransientsideeffectsfromitsapplication(Edwards,

Wiholm,&Martinez,1996).

Hyaluronidase reverses HA filler and should be used without delay to dissolve filler and

decompressvessels.Anallergytestisnotthoughttobenecessaryinanemergencysituation.

Figure3outlinesthedilutionanduseofhyaluronidasewhenreconstituting1500iUpowder,

suchasHyalase(Wockhardt)intheUK.Someauthors,namelyCavallinietal,advocatethe

useofmuchhigherdosesinordertoachievedissolutionandimproveoutcome(Cavalliniet

al.,2016).

Aspirinblocksplateletaggregationandinananti-inflammatory.Itshouldbegivenwithout

delay.Adjunctivetreatmentmayalsoconsidertheuseofprednisolonetofurtherreducethe

inflammatory response. Other, lesswidelyused interventionsmay include theuseof the

vasodilatorsildenafiltofurtherincreasebloodflow,orlowmolecularweightheparininorder

topreventthrombosis(Beleznayetal.,2014)

Wherenecrosisislargeorwoundsareexhibitingsignsofhealingbysecondaryintent,referral

forhyperbaricoxygentreatmentmaybeconsidered(DeLorenzi,2013).

Similarlytothesituationofvisionloss,itisimportantforthepractitionertorecognisewhen

improvementisnotbeingachieved.Ifthepatientdoesnotseemtobegettingbetterwithin

30-60minutes,itisadvisabletofollowtheguidanceinfigure2andrefertoanemergency

room.Thepractitionershouldaccompanythepatienttoadviseandassistinsteadofsending

ananonymousreferral. It isadvisable toprior tosuchasituationoccurring,practitioners

exploretheiroptionsforreferral–preparationandcommunicationwiththenearesthospital

priortosuchasituationwillalleviatesignificantstressintherealevent.

57

Table5:Managementofskinischaemia/necrosis

ManagementofimpendingskinnecrosisIdentifythecomplication Checkforwarningsigns!

Blanchingandpain:possiblearterialocclusionViolaceousreticulated:possiblevenousocclusion

ImmediatemanagementThreefoldapproach:DissolutionVasodilationIncreasedBloodflow

• Stoptreatment• warmcompress• topical2%nitroglycerinGTNpasteorGTNpatch• massageaffectedareafirmly• hyaluronidase:injecteddeepdermalandsubcutaneous

alongpathofvesselandfillerinjectionarea• 2x325mgaspirin• ifnoimprovementin60minutes:repeathyaluronidase

andconsiderreferral(seefigure2below)• Highflowoxygen• Consideroralprednisolone20-40mg

Adjunctivetreatment • Highflowoxygen• Consideroralprednisolone20-40mg,3-5days• Considersildenafilforvasodilation

24hours • 75mgaspirindaily• reviewandreassure• continueprednisolone,ifstarted

Day1-7 • 75mgaspiringdaily• ApplyGTNeverydayuntilresolved• Dailyfollowupappointment• Woundcareifnecrotictissueandescharformation• Continueprednisoloneuntilday5,ifstarted

Woundcareifnecrosis • Siliconedressing• Minimizebacterialcontamination• Observe for secondary infection, treat if appropriate

withtopicalororalantibiotics• Consider Hyperbaric oxygen if slow healing or large

necrosis(ifaccessible)Day7-14

• Aspirin75mg• Dailyfollowupuntilresolution(maytakemorethan2

weeks)

58

Figure2:Algorithmforthemanagementskinischaemia/necrosis

59

Figure3:reconstitutionanddosageofhyaluronidase(Hyalase/Wockhardt)

60

TheEmergencykit

Inordertomanageacomplicationeffectively,anemergencybagforvascularocclusionshould

beavailableinthepractice,andsuggestedcomponentsareoutlinedinTable6below.

Table6:EmergencyKitforvascularcompromiseEmergencyKitBagforVascularCompromiseDrug ActionHyaluronidase DissolutionofHAfillerGTNpaste vasodilatorAspirin Anti-inflammatory,antiplateletPrednisolone20mgtablets Anti-inflammatoryOxygen (sufficient for 15-20 minutes highflow,recommendedCDcylindersize)

Improvedtissueperfusion

Sildenafil(optional) vasodilationAntihistamines IncaseofallergyAdrenaline Incaseofallergy

61

Furtherstudiessuggested

Mostofthestudiesrecordingvascularcomplicationsinvolveaverysmallsampleofpatients.

ThelargercasenumbersbyChenetal,Parketal,SunetalandBeleznayetalweremostly

referralcentresfordermalfillercomplications,whilstisolatedcentresdocumentsinglecase

reports.

Unfortunately, all studies that have been analysed for this review have been conducted

outsidetheUKandmaynotbeanaccuraterepresentationoftheprotocolsthatUK-based

practitionersareawareof. Inaddition to this, theUKhas someof the laxest regulations

governing theuseofdermal fillersandmanypractitionersare completelyunlicensedand

haveverylittleformalmedicaloranyothertraining,makingtheriskrateintheUKpotentially

higher(Keoghetal.,2013).Thismakesgatheringanyusefulinformationforstudypurposes

extremelydifficult.

In order for UK-based research into the prevention and management of vascular

complicationsaffectingvisionandskintobecompleted,thefollowingaresuggested:

1. A UK-wide dermal filler complications referral centre, consisting of a range of

appropriatelytrainedandexperiencedprofessionalsfromdental,medicalandnursing

backgrounds. A“centre”doesnotnecessarilyhavetobeonelocation,butmorea

body who will accept referrals, treat to a prescribed consistent guideline, share

information, and from this information develop and enhance interventions for

complications.Recommendationsandguidelinescouldbeformulatedfromthis.

2. AUK-widecomplicationsreportingmethod,whichrequirescompletionofareporting

cardwhichcanbesenttoadatacollectioncentre(thismaybethereferralcentre).A

similarsystemhasbeendevelopedbytheMHRA,knownastheyellowcardscheme,

toreportadversereactionstomedicines(MHRA,2016).Astructuredform,suchas

theexampledevelopedbytheauthorseeninfigure4,couldbeusedtoreportthe

incidentorreferthepatienttothereferralcentre,shouldthisbenecessary.Detailed

formssuchasthiswouldfocusthereferringpractitionertoreporttherelevantdata

andassistinanyonwardtreatment. Practitionersshouldbeencouragedtoreport;

theoptionofananonymisedformmayimprovepractitionercompliance.Awareness

62

ofsuchaschemecouldbepromotedbyusingorganisationssuchasSafeFace,IHAS,

cosmeticinsuranceprovidersandpharmaceuticalcompanies.Itdoesnot,however,

commitunscrupulouspractitionerstoreportingadverseeventsandthecooperation

fromnon-healthcarepractitionersshouldbeencouragedatthepointofproductsale.

Figure4:vascularcomplicationreportingform

63

VascularComplicationReportingFormAboutthePatient

Name(Onlyfortreatmentreferral;anonymiseifusingthisformtoreportdata)

Age Sex

Aboutthetreatment

DermalFillerused

BatchNumber

Pleaseusediagrambelowtodetailinjectionsitesandquantities

Injectionsite

Injectionmethod(needle/cannula)

Injectionvolume

Aboutthecomplication

Symptoms

Diagnosis

Timetosymptoms/presentation Treatmentalreadyadministeredandoutcome

Aboutthepractitioner

Name

Profession/Qualification

Referralsfortreatment:sendpatientwithform,accompanywherepossibleReferralsfordatacollection:omitnamesofpractitionerandpatient

64

Conclusions

Itistimetofacetherealissue:fillerblindnessintheUKisnotamatterofifbutwhen.Cases

ofskinnecrosisarealreadyincreasinginincidence.Practitionersmustdobetterinorderto

preventadevastatingoutcomeforthepatient.

Asaestheticmedicineadvances,sodoesthecomplexityoftreatments;fillerrhinoplastiesare

notonlyblurringthelinebetweensurgicalandnon-surgical,butarefastbecomingthemost

dangerousprocedureinthemidface,analreadyhighriskarea.

Theauthorhasrecognisedsignificantshortcomingsinapproachestovascularcomplication

managementintheaestheticpracticeasaresultofthisreview.Progressisslow,withlittle

usefulinputsincethedevelopmentofthefirstprotocolbyHischetalin2007(Hirschetal.,

2007). Nevertheless,effectiveprotocols for themanagementof impendingnecrosishave

beendeveloped,andfurtherdocumentedinthisreview.Earlyinterventionwithintwodays

oftheeventwithuseofhyaluronidaseisaprovenwaytoreducethelongtermsequelaefor

thepatient.Thetreatmentofvisionlossasaresultoffiller,however,isaproverbialstabin

thedark.Therearenoprovenandeffectivemethodstocombatfillerblindnessthatcanbe

effectivelyusedintheaestheticpracticesetting.Theprognosisisoftenhopelessandthere

appeartobenoremediesforthisonthehorizonasnovelconceptshavenotbeenproven

enoughtointegrateintopractice.Hospitalinterventionsareequallyuntested,andtheonus

is on the referring practitioner to convey the patient to an appropriately qualified

ophthalmologist with the right experience before irreversible ocular damage sets in.

Recognisingthecomplicationearlyisthereforeacentralpillartomanagement.

Guidelineshavelargelybeendevelopedinaresponsivefashion,withtheincreasingnumber

ofdermalfillercasualtiespromptingamovetowardsdevelopmentofpreventionprotocols.

Hyaluronicacidfillermaybereversible,butitisstilldangerous,andpractitionersshoulddo

everythingintheirpowertomitigatetherisktothepatient.

ThestateofUKlegislationisamatterofconcern.Practitionersembarkontreatmentwith

littleorno formal training,anddue to lax lawssurrounding theuseofdermal fillersnon-

65

healthcare providers with little accountability are a further risk to patients in an already

potentiallydangerousfield. Ignoranceisbliss,andmanypractitionersattempttreatments

thataresimplyoutsideoftheircompetenciesandwithoutproperpreventionormanagement

strategiesinplace.Itisforthisreasonthattheevidencebasedguidelinesandchartsinthis

reviewweredevisedassimple,easytounderstandprotocolstouseinaestheticpractice.

As we embrace aesthetic treatments in the field of medicine, we must be prepared to

encounterthevascularcomplicationsthatwillundoubtedlycomewithit.AUK-widesupport

orreferralsystemwouldserveasaneffectivehelpforthepatientswhoaremostatneed,

whilst providing data for the development of strategies to improve outcome for those

affectedbyvascularevents.

Thereisadifficultroadaheadwiththetrueincidenceofvascularcomplicationsunknownbut

undoubtedlyrising.Itishopedthatthisreviewwillclarifyandfacilitatetheirtreatment,and

take away some of the stress and anguish felt by practitioner and patient by providing

structureandguidanceinatimeofchaos.

66

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