Primary Aberrant Oculomotor Nerve Regeneration From a Posterior Communicating Artery Aneurysm

25 Pages·2012·1.78 MB·English

CLINICOPATHOLOGICREPORTS,CASEREPORTS,ANDSMALLCASESERIES
SECTIONEDITOR:W.RICHARDGREEN,MD
Human Subconjunctival
Infection of Macacanema
formosana: The First Case
of Human Infection
Reported Worldwide
In the last few decades, the appar-
ently more frequent occurrence of
zoonotichelminthinfectionsinman
haveattractedtheattentionofpara-
sitologists.1Inparticularhavebeen
those brought about by the genus
Dirofilaria, which has been re-
portedtocausemorethan900cases
of human infection. Most of them
wereduetoDirofilariarepensandDi-
rofilaria immitis. Therefore, it is
worthreportingonarecenthuman
casecausedbyMacacanemaformo-
sana,afilarialparasiteofthecatar- Figure1.Thesubconjunctivalwormunderslitlampbiomicroscope.Itwasmotileandactive.
rhinemonkeys(Macacacyclopsis),
thatcametoourattentionandap-
parentlyhasneverbeenreportedin
humans.
ReportofaCase.Thepatientwasa
19-year-old woman who had been
livinginanurbanareaofnorthern
Taiwansincechildhood.Shevisited
theDepartmentofOphthalmology,
TaipeiVeteransGeneralHospitalin
November 1999 owing to sudden
painandrednessinherlefteye.Mild
For editorial comment
see page 634
swellingoftheleftlowereyelidwas
notedfor1monthandseveralepi-
sodesofsevereleftperiorbitalpain
happenedwithinthesefewmonths.
ShehadnevertraveledoutsideTai- Figure2.Thewholenematodemeasured7.5(cid:1)0.5cm.
wanandneverhadanimalsaspets.
Herfamilyhadaroutineannualpic- lampexaminationdisclosedasub- normal.Nomicrofilariawasfound
nicattheriversideoftheHsin-Tien conjunctivalactivewormatthenasal inbloodandurinesamples.Nole-
ShiinnorthernTaiwanuntil3years sideofherlefteyewithmarkedcon- sionwasseenonchestradiographs
previously.Shecouldnotrecallany junctivalcongestion(Figure1).In- or brain computed tomographic
unusual insect bite or any contact direct ophthalmoscopic examina- scans.
withmonkeysduringthesepicnics. tion revealed a normal fundus. Underlocalanesthesia,thecon-
Completeophthalmologicex- Findingsonexaminationoftheright junctivawasincisedanddissected.
amination was performed. Best- eye were unremarkable. The re- Thewormwasremovedaliveandin-
correctedvisualacuitywas6/4OU sultsofbloodandbiochemicaltests, tactandpreservedin5%formalde-
with Snellen distance chart. Slit- includingtheeosinophilcount,were hyde for identification. Histologi-
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arowofapproximately7caudalpa-
pillae,asymmetricallyarranged,on
eithersideofthecloaca.
Theesophaguscouldbevisu-
alizedthroughthesemitransparent
bodywall.Itwasdividedintoashort
muscularportionandamuchlonger
glandularportion.Thelateralchords
contained dark, granular material
that could be seen throughout the
lengthofthechords(Figure5).
Inthetransversesectionofthe
worm (Figure 6), the multilay-
eredstructureofthecuticlewasevi-
dentaswastheunderlyingthinhy-
podermis. The large lateral chords
displayed clusters of pigmented
granulesthatwerescatteredinthe
hypodermisaswell.Themusclecells
werecoelomyarianandnumerousin
Figure3.Thecephalicendofthenematode(originalmagnification(cid:1)60). eachquadrantofthebody.Thepseu-
docoelewasvirtuallyfilledwiththe
large genital tube packed with de-
veloping spermatozoa (spermato-
cytes).Thedigestivetubewassmall
and round and lined with a rela-
tively thick endothelium. On the
basis of these morphological char-
acteristics, the nematode can be
identifiedasanadultmaleofMaca-
canemaformosana(Nematoda,On-
chocercidae, Dirofilariinae). The
morphologicalcharacteristicstodif-
ferentiate M formosana from other
nematodes (Filarioidea, Ascari-
doid, Oxyuroidea, Strongylid, Spi-
rurid,Strongyloid,Rhabditoid,and
Trichinellae)werewelldescribedby
OrihelandAsh.1SchadandAnder-
son2hadreportedthedifferentialdi-
agnosisofMformosanawithother
Onchocercidae, in particular with
Edesonfilariamalayensis,thenema-
Figure4.Thecaudalendofthenematodewherethe2asymmetricalspicules(S)andsomepapillae(P)
canbeseen(originalmagnification(cid:1)60). todemostsimilartoMformosana.
calsectionswerepreparedforfurther therconfirmationoftheidentity.It Comment.Macacanemaformosana
studyoftheparasite.Periorbitalpain was threadlike and approximately wasfirstidentifiedanddescribedby
and conjunctival congestion re- 7.5cmlongwithamaximumdiam- SchadandAndersonin1963.2Itwas
solvedafterthesurgery.Therewas eterof510µm(Figure2).Thean- anematodeofnewgenusandspe-
nosignofrecurrentinfectionafter teriorextremity(Figure3)wassub- cies of the family Onchocercidae,
2years’follow-up. conical with a small, round oral subfamilyDirofilariinae.Theyfound
opening without lips and sur- thefilariaintheperitrachealtissue
Parasitologic Findings. The para- rounded by 2 pairs of circumoral and diaphragm of Macaca cyclop-
site was sent to the Department of papillae.Thecuticlewasthinwith sis, a monkey native to Formosa
Public Veterinary Health and Ani- fine transverse striations. The tail (Taiwan). Like all filariae, the mi-
malPathology,UniversityofBolo- (Figure4)wasshortwith2spic- crofilariaewerefoundintheblood
gna,Bologna,Italy,andtheDepart- ulesofunequallength.Thelonger ofthehost.Littlewasknownabout
mentofTropicalMedicine,Tulane one(ontheworm’sleftside)mea- thisparasiteexceptforareportpub-
UniversityMedicalCenter,NewOr- sured 512 µm and the shorter (on lished in 1968 by Bergner and
leans, La, for identification. It was the worm’s right side) one, par- Jachowski.3 They found the para-
later sent to the Museum of Natu- tially protruding from the cloaca, site in the peritracheal and man-
ral History, Paris, France, for fur- wasabout120µmlong.Therewas dibularintermuscularconnectivetis-
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sues.Therewasnosubconjunctival
infection reported in the monkey.
TheprevalencerateofMformosana
in the Taiwanese monkey was re-
portedtobeashighas42%innorth-
ern Taiwan where the patient had
picnicked.Culicoides(Insecta,Dip-
tera, Ceratopogonidae), a cosmo-
politan genus of biting midges of-
tencausinggreatannoyancetoman
and animals, was proposed as the
mostprobabletransmittingvectorof
theparasite.ManyspeciesofCuli-
coides were identified in northern
Taiwan.Thislargereservoirofthe
parasiteandtheexistenceofthevec-
tors made human infection pos-
sible.Toourknowledge,thisisthe
firstcaseofhumaninfectioncaused
by M formosana to be reported
worldwide.However,othercasesin Figure5.ThedetailofasegmentofMacacanemaformosanawherethescatteredbrownishgranules
thesameareamaywellhavetaken withinthelateralchords(L)canbeseen(originalmagnification(cid:1)60).
place,butunobserved,asseemedto
happen with D repens in endemic
zones.4Theprepatentperiodofthe
wormhasnotyetbeendetermined.
Basedonthesizeoftheworm,the
patientwouldhavebeeninfectedfor
at least 1 year and symptoms ap-
peared only after the worm mi-
grated into the subconjunctival
space.ThereportedhumanDirofi-
lariainfectionsusuallyconsistedof
asingleworm,5andtreatmentforthe
sorenessconsistedoftheworm’ssur-
gical removal. There was no evi-
denceofrecurrentinfectioninour
patientafter2years’follow-up.
CasesofsubconjunctivalDre-
pensinfectionoccurwidelythrough-
outEuropean,African,MiddleEast-
ern,andAsiancountries.However,it
hasneverbeenreportedinTaiwan.
Fromthecasesreportedandourob- Figure6.Thetransversesectionofthenematode(partial).Cindicatescuticle;I,intestine;M,muscular
servation,subconjunctivalDrepens fibers;T,testicle;andarrowheads,brownishgranulesinthelateralchord(trichrome-Masson-Goldner
and M formosana infections shared stain,originalmagnification(cid:1)250).
the characteristics of sudden onset
andweretreatedsolelybysurgicalre- nematodes,suchasMansonellaper- sible zoonotic infection should be
movaloftheworm.Fromthesizeof stansandEdesonfilariaspecies,and keptinmind.
the worms recovered, they might intheselfsameMformosana.Their
have been migrating in subcutane- origin is obscure and further stud- Ling-IngLau,MD
ous space for a period of time and ies are necessary to understand Fenq-LihLee,MD
causedsymptomsonlywhentheyap- theirnature. Wen-MingHsu,MD
peared in the subconjunctiva. The Thisis,toourknowledge,the Taipei,Taiwan
episodic periorbital pain preceding firstcasereportofhumaninfection SilvioPampiglione,MD,PhD
subconjunctivalinfectioninourpa- caused by M formosana although MariaLetiziaFioravanti,PhD
tientcouldbecausedbytheworm’s other cases may have gone by un- Bologna,Italy
migrationwithinthisarea. observedorunidentified.Sincethe
ThomasC.Orihel,PhD
Thepresenceofbrownishgran- Taiwan monkeys (Macaca cyclop-
NewOrleans,La
ules in the lateral chords is a phe- sis) have been largely involved in
nomenon that has been observed laboratory studies and have close We would like to thank Shyh-Haw
on other occasions both in other contact with human beings, pos- Tsay,MD,DepartmentofPathology,
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TaipeiVeteransGeneralHospital,and tinellymphnode(SLN)biopsysoon sioninhisleftuppereyelid,andthe
F. Rivasi, PhD, histopathologist at afterthediagnosisofhisprimarytu- areaoftheneckdissectionandpa-
ModenaUniversity,Emilia,Italy,for mor. An SLN was identified and rotidectomyhadhealed.Findingson
preparingthehistologicalsectionsof showedhistologicevidenceofMCC. thepatient’sophthalmologicexami-
the parasite; and Kin-Mu Lee, PhD, To our knowledge, this is the first nationwereessentiallynormal,with
Department of Parasitology, Na- reportedcaseofapositiveSLNsec- no clinical evidence of local or re-
tionalYangMingUniversity,Taipei, ondarytoMCCoftheeyelid. gionalrecurrenceofcancer.Hissys-
and Odile Bain, PhD, Museum of temic workup, including com-
Natural History, Paris, France, for ReportofaCase.A61-year-oldman putedtomographyoftheheadand
theirkindsuggestionsontheidentity notedanerythematouslesiononhis neck,abdomen,andpelvis,chestra-
oftheparasite. left upper eyelid in May 2001. He diography, and magnetic reso-
Presentedasaposteratthe18th went to his local ophthalmologist, nance imaging of the brain, was
CongressoftheAsia-PacificAcademy whoexcisedthelesionbutdidnot negative for tumor. A multidisci-
of Ophthalmology, Taipei, Taiwan, examine it histologically. In June plinaryteam,includinganophthal-
March10-14,2001. 2001, the lesion recurred. The re- micsurgeon,aheadandnecksur-
Corresponding author: Fenq- current lesion measured approxi- geon, a head and neck medical
Lih Lee, MD, Department of Oph- mately12mmindiameter.Thepa- oncologist,andaheadandneckra-
thalmology,TaipeiVeteransGeneral tient sought an opinion from an diation oncologist examined the
Hospital,No.201,Section2,Shih-Pai oculoplastic surgeon, who per- patient and recommended that he
Road, Shih-Pai, Taipei 11217, Tai- formedawidelocalexcisionofthe receive adjuvant external beam
wan (e-mail address: fllee@ms3 lesionwithfrozensectioncontrolof radiation therapy to the eyelid,
.hinet.net). the margins. The histologic find- parotidnodes,anddeepercervical
Reprints:Ling-IngLau,MD,De- ings were consistent with MCC of nodes. The team also recom-
partment of Ophthalmology, Taipei theeyelid(Figure,AandB).Sen- mendedthatthepatientbegiven4
VeteransGeneralHospital,No.201, tinellymphnodebiopsywassched- coursesofchemotherapywitheto-
Section 2, Shih-Pai Road, Taipei uledbuthadtobedelayedbecause poside and cisplatin after the
11217,Taiwan(e-mail:lilau@ms41 thepatientdevelopedacuteappen- completionofradiationtherapy.
.hinet.net). dicitis,necessitatinganemergentap-
pendectomy. In July 2001, the pa- Comment. In patients with MCC,
1. OrihelThC,AshLR.ParasitesinHumanTis-
tient underwent SLN biopsy using the regional lymph nodes are
sues.Chicago,Ill:AmericanSocietyofClinical
Pathologists;1995. acombinationofisosulfanbluedye thoughttobethemostcommonand
2. SchadGA,AndersonRC.Macacanemaformo- andTc99m–labeledsulfurcolloid. earliestsiteofmetastasis;thus,ad-
sanan.g.,n.sp.(Onchocercidae:Dirofilariinae)
Theafferentlymphaticswereiden- juvant treatment of the regional
fromMacacacyclopsisofFormosa.CanJZool
1963;41:797-801. tified before surgery using radio- lymphnodeshasbeenadvocatedby
3. BergnerJF,JachowskiLA.Thefilarialparasite, nucleotide imaging. Intraopera- many investigators.3,5,6 Jean et al7
Macacanemaformosana,fromtheTaiwanmon-
keyanditsdevelopmentinvariousarthropods. tively,acombinationofradiolabeled successfully identified 1 or more
FormosanSci.1968;22:1-68. sulfurcolloidandisosulfanbluedye SLNsin19of20patientswithstage
4. PampiglioneS,CanestriTrottiG,RivasiF.Hu-
wasusedtoidentifySLNs.Anarea IMCCwhounderwentSLNbiopsy
mandirofilariasisduetoDirofilaria(Noch-
tiella)repens:areviewofworldliterature.Paras- offocalradioactiveuptakewasiden- atthetimeofinitialwidelocalex-
sitologia.1995;37:149-193. tified in the left preauricular (pa- cision. The authors found that 5
5. Ruiz-MorenoJM,Bornay-LlinaresFJ,PrietoMaza
rotid)areausingahandheldgamma (26%) of the 19 patients in whom
G,MedranoM,SimonF,EberhardML.Subcon-
junctivalinfectionwithDirofilariarepens:sero- probeandwasmarkedontheskin. SLNs were successfully identified
logicalconfirmationofcurefollowingsurgery. The corresponding SLN was re- had at least 1 histologically posi-
ArchOphthalmol.1998;116:1370-1372.
moved and analyzed histologically tiveSLN.OtherisolatedcasesofSLN
using serial sectioning and immu- biopsyforMCChavealsobeenre-
nohistochemicalstaining.Thenode ported.8
Merkel Cell Carcinoma
was found to be positive for MCC Merkel cell carcinoma of the
of the Eyelid With a (Figure,CandD).Thepatientsub- eyelidisthoughttoaccountfor10%
Positive Sentinel Node sequentlyunderwentatotalparoti- ofallcasesofMCC.2Inareviewof
dectomy and completion neck allpreviouslyreportedcasesofMCC
Merkelcellcarcinoma(MCC)ofthe dissection.Theparotidectomyspe- of the eyelid, Kivela and Tarkkat-
eyelid is a rare but aggressive ma- cimenincluded1additionallymph nen2concludedthatuptotwothirds
lignancythatmetastasizesearlytore- nodethatwaspositiveforMCC.The of patients eventually develop re-
gionallymphnodes.1Mostclinical node was located in the deep lobe gionalnodalinvolvement.Thisrate
seriessuggestarateofregionalnodal oftheleftparotidglandandshowed is higher than the rate reported in
involvement between 21% and extracapsularextension. mostsingleseriesofMCCoftheeye-
66%.2-4Earlydetectionofoccultre- In September 2001, the pa- lid.Inthelargestsingleseriestodate,
gionalnodaldiseasemayallowfor tientself-referredtotheUniversity Peters et al3 reported clinical re-
earlyinstitutionofadjuvanttherapy. of Texas M. D. Anderson Cancer gionalnodalinvolvementin3(21%)
WedescribeapatientwithMCCof Center(Houston)forfurtherman- oftheir14patients.
the eyelid with clinically unin- agementofhistumor.Atthistime, Sentinellymphnodebiopsyal-
volvednodeswhounderwentsen- he had a well-healed area of exci- lowsforearlydetectionofoccultre-
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A B
C D
A,HistologicsectionofMerkelcellcarcinoma(MCC)oftheuppereyelid(primarylesion)demonstratesadiffuse,poorlycohesiveproliferationofsmallcellswith
finelydispersedchromatin,lackingprominentnucleoli,andwithoutsignificantinterveningstroma(originalmagnification(cid:1)4).B,High-poweredviewshowsround
cellswithfinelydistributedchromatin.Manyofthecellsdisplayhyperchromaticnucleiconsistentwithapoptoticbodies(originalmagnification(cid:1)40).C,Histologic
sectionofthesentinellymphnodeshowssmallfociofroundcellssimilarinappearancetotheprimarylesion(originalmagnification(cid:1)20).D,High-poweredview
ofthesamenodeimmunostainedwithantibodiesagainstcytokeratinshowspositivecytokeratinexpressionsupportingthediagnosisofmetastaticMCC(original
magnification(cid:1)40).
gional lymph node metastasis and moid carcinoma), using radiola- tion of micrometastasis in the re-
thus,moreaccuratestagingofMCC beled sulfur colloid alone. These gional nodes allows for immediate
andthepossibleinstitutionofearly authorsreportedsuccessfulidenti- institution of adjuvant therapy,
adjuvanttherapy.AlthoughSLNbi- fication of at least 1 SLN in 5 pa- whichmayincludecompletionneck
opsyhasrecentlybecomethestan- tients,althoughthetechniqueused dissection,externalbeamradiation
dard of care for most solid tumors in the latter report is believed by therapy, and adjuvant chemo-
throughoutthebody,SLNbiopsyin someinvestigatorsnotlikelytolead therapy.
theperioculararearemainsinvesti- to the correct identification of the
gational.9Toourknowledge,there sentinel nodes.12 Neither of the 2 BitaEsmaeli,MD
havebeenonly2previousreportsof previousreportsofSLNbiopsyfor AresuNaderi,MD
application of SLN biopsy tech- conjunctival and periocular tu- LillieHidaji,BS
niquesforconjunctivalandperiocu- morsfoundapositiveSLN.Toour GeorgeBlumenschein,MD
lar tumors.10,11 We described suc- knowledge, ours is the first re- VictorG.Prieto,MD,PhD
cessful identification of SLNs in a ported case in which an SLN was Houston,Tex
single patient with a conjunctival successfully identified in a patient
melanoma,usingacombinationof withaneyelidtumorandwasalso Corresponding author and reprints:
radiolabeledsulfurcolloidandiso- foundtobehistologicallypositive. BitaEsmaeli,MD,OphthalmologySec-
sulfanbluedye.10Wilsonetal11at- Thiscaseunderscoresthefeas- tion, Department of Plastic Surgery,
temptedidentificationofSLNsin5 ability and potential usefulness of Box443,M.D.AndersonCancerCen-
patientswithperioculartumors(2 SLNbiopsyasamethodforidenti- ter,1515HolcombeBlvd,Houston,TX
melanomas,2meibomianglandcar- fyingoccultmetastaticdiseasefrom 77030(e-mail:besmaeli@mdanderson
cinomas,and1caseofmucoepider- anMCCoftheeyelid.Earlydetec- .org).
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1. SinghAD,EagleRCJr,ShieldsCL,ShieldsJA. relatedmaculardegenerationwith- Clinic,Rochester,Minn,onMarch
Merkelcellcarcinomaoftheeyelids.IntOph- out observing deleterious retinal 8,2000,becauseofagrowingpig-
thalmolClin.1993;33:11-17.
2. KivelaT,TarkkanenA.TheMerkelcellandas- complications.5Theencouragingre- mentedchoroidallesionintheleft
sociatedneoplasmsintheeyelidsandperiocu- sultsinpilotstudieswithTTTinthe eye that had been observed to in-
larregion.SurvOphthalmol.1990;35:171-
management of occult choroidal crease in thickness from 2.3 to
187.
3. PetersGB,MeyerDR,ShieldsJA,etal.Man- neovascularmembraneshasledto greaterthan4mmduringaninter-
agementandprognosisofMerkelcellcarci- the development of a multicenter valof9years.
nomaoftheeyelid.Ophthalmology.2001;108:
prospectiverandomizedclinicaltrial Thevisualacuitywas20/20OD
1575-1579.
4. VictorNS,MortonB,SmithJW.Merkelcellcan- (Transpupillary Thermotherapy and20/25+3OS.Therighteyewas
cer:isprophylacticlymphnodedissectionin- [TTT]ofOccultSubfovealChoroi- normal.Resultsofexaminationofthe
dicated?AmSurg.1996;62:879-882.
5. FenigE,BrennerB,KatzA,etal.Theroleof dal Neovascularization in Patients lefteyeshowedanormalanteriorseg-
radiationtherapyandchemotherapyinthe With Age-Related Macular Degen- mentandapigmented,elevatedcho-
treatmentofMerkelcellcarcinoma.Cancer. erationTrial)inwhichpatientswith roidallesion,measuring9(cid:1)9mmin
1997;80:881-885.
6. BoyleF,PendleburyS,BellD.Furtherin- subfoveal choroidal neovascular base dimension, located approxi-
sightsintothenaturalhistoryandmanage- membranes are randomized to a mately4mmsuperonasaltothedisc
mentofprimarycutaneousneuroendocrine
(Merkelcell)carcinoma.IntJRadiatOncolBiol shamtreatmentoratreatmentwith (Figure 1). The ultrasonographic
Phys.1995;31:315-323. a single 60-second exposure of in- studiesdemonstratedasolid,dome-
7. JeanM,SolorzanoC,RossM,etal.Roleforsen- fraredlightfromthediodelaser(810 shapedtumor(B-scan)withlowin-
tinelnodebiopsyinMerkelcellcarcinomapa-
tients.ProcAmSocClinOncol.2001;20:358a. nm)usingabeamdiameterof3mm ternal reflectivity (A-scan) consis-
8. WasserbergN,FeinmesserM,SchachterJ,Fenig and 800 mW of power (Elias Rei- tentwiththediagnosisofmelanoma.
E,GutmanH.Sentinel-nodeguidedlymph-
chel,MD,oralandwrittencommu- Thethicknessofthelesionwas4.4
nodedissectionforMerkelcellcarcinoma.Eur
JSurgOncol.1999;252:444-446. nication, January 12, 2000). The mm.Asubretinalfibroticplaqueover-
9. EsmaeliB.Sentinellymphnodemappingfor uniqueopportunityaffordedbyapa- lying the central portion of the tu-
patientswithcutaneousandconjunctivalmela-
tientscheduledforenucleationfor morandasecondaryretinaldetach-
noma.OphthalmolPlastReconstrSurg.2000;
16:170-172. amalignantmelanomalocatedinthe mentoverlyingthenasalportionof
10. EsmaeliB,EicherS,PoppJ,etal.Sentinellymph nasal choroid led to this experi- thetumorwereseen.Subretinalfluid
nodebiopsyforconjunctivalmelanoma.Oph-
thalmolPlastReconstrSurg.2001;17:436-442. mentinwhichinfraredlightfroma extendedapproximately1discdiam-
11. WilsonMW,FlemingJC,FlemingRM,Haik diode laser was directed to the eterbeyondthenasalperipheryofthe
B.Sentinelnodebiopsyfororbitalandocular
macula through a contact lens us- mass. Small accumulations of exu-
adnexaltumors.OphthalmolPlastReconstrSurg.
2001;17:338-344. ingthevariablesidenticaltothose datesatthenasalboundaryofthetu-
12. EsmaeliB.Indiscussionof:WilsonMW,Flem- recommended in the TTT of Oc- morwerealsoseen.Theretinainthe
ingJC,FlemingRM,HaikB.Sentinelnodebi-
cult Subfoveal Choroidal Neovas- central macular region appeared
opsyfororbitalandocularadnexaltumors.Oph-
thalmolPlastReconstrSurg.2001;17:338-345. cularization in Patients With Age- subtlythickenedonbiomicroscopy
RelatedMacularDegenerationTrial. findings.
Thediagnosisofactivelygrow-
Report of a Case. A 65-year-old ingmalignantmelanomawasmade,
The Effect of Transpupillary womanwasreferredtotheDepart- and definitive therapy was recom-
Thermotherapy on the mentofOphthalmologyoftheMayo mended.Therapeuticoptionswere
Human Macula
Transpupillarythermotherapy(TTT)
wasintroducedbyinvestigatorsfrom
theNetherlandsin1995asanalter-
nativetreatmentforchoroidalmela-
noma.1,2 Since that time, TTT has
been used to treat small choroidal
melanomas,andpreliminaryresults
indicatingthatTTTcancontrolsmall
melanomas with follow-up of 5 or
more years have been published.3,4
However, localized retinal destruc-
tion,vascularocclusions,andnerve
fiberbundledefectsarecommonlyas-
sociatedwitheffectivetreatmentof
small melanomas with TTT. De-
spitetheseobservedretinalcompli-
cations,someinvestigatorshavere-
centlyreportedthatTTT,usingthe
samelaserintensitytotreatchoroi-
dalmelanoma,maysuccessfullytreat
Figure1.Colorfundusphotographshowingthelocationofachoroidalmelanomainthelefteye.
occult subfoveal choroidal neovas-
Aserousdetachmentofthesensoryretinawasclinicallyconfinedtotheregionoverlying
cularizations in patients with age- thenasalportionofthetumor.
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A B
C D
Figure2.Prelaserexposure.A,Colorfundusphotographofposteriorpoleshowinganormal-appearingmacularregion.B,Earlyarteriovenousphaseduring
fluoresceinangiography.C,Arteriovenousphaseduringfluoresceinangiographyshowingsubtlehyperfluorescenceintheposteriorpoleandearlycystoidedema.
D,Recirculationphaseshowingpatchydiffuseintraretinaldyestainingandpatternofsectorcystoidmacularedema.
discussed. Brachytherapy was en- the macula of the left eye was ex- dehyde. The retina and choroid in
couraged,butthepatientwascon- posed to a 3-mm beam of infrared themaculaweredissectedenbloc,
cernedaboutthepotentialforcon- laserlight(810nm)using800mW fixedinsolution,andembeddedfor
tinuingproblemswiththeeyeand ofpower.Thelaserbeamwasdeliv- transmission electron microscopy.
stronglydesiredanenucleation. ered to the posterior pole through Lightmicroscopyofthisregionwas
We obtained institutional re- astandardfunduscontactlens(Carl not performed. The remaining tis-
viewboardapprovalfortheexperi- Zeiss,Inc,Thornwood,NY),expos- suewasexaminedbymeansoflight
ment. The patient was fully in- ingthemaculatolightfromthein- microscopy.
formedregardingtheuseofinfrared frared laser for 60 seconds. Visual
laser light in the management of acuity was measured with a stan- Histopathologic Findings. Color
maculardiseaseandthepossibility dardSnellenchart,andthecentral photographsofthemacularregion
thatthetreatmentcouldcauseanal- fieldwasevaluatedwithanAmsler showed no obvious abnormality
terationofthepigmentepithelium grid3minutesafterlightexposure. (Figure2A).Thepretreatmentfluo-
and retina overlying the choroidal Fivedaysafterlaserexposure,were- resceinangiogramshowedanearly
targettissue.Sheagreedtohaveher examinedtheeye.Bestcorrectedvi- pattern of complex vascular loops
retinaexposedtolightfromthein- sualacuitywasdetermined,andthe withinthetumorandpatchyleak-
frared laser for 60 seconds using a central visual field was evaluated ageofdyefromthesesitesleading
powerof800mW.Shealsoagreed with an Amsler grid. Biomicros- toearlypatchytissuestainingofthe
toundergocolorfundusphotogra- copyandophthalmoscopywereper- tumor.Laterframesshoweddiffuse
phyandfluoresceinangiographyof formed, and the appearance of the stainingoftheretinaoverlyingthe
theretinabeforeandafterlightex- posteriorpolewasdocumentedwith tumor.Dyeleakagefromfluorescein-
posure. colorfundusphotographyandfluo- incompetentcapillariesintheperi-
Afterdocumentingtheappear- rescein angiography. The eye was fovealregionwasseen,whichpro-
anceofthetumor(Figure1)andthe enucleated approximately 3 hours duced an incomplete pattern of
maculabymeansofslitlampbiomi- laterandfixedina0.1Mphosphate- cystoid edema visible in the late
croscopy color photographs and buffered solution containing 4% framesofthestudyandarclikear-
fluoresceinangiographybeforeTTT, paraformaldehydeand1%glutaral- easofdiffuseintraretinalstainingsu-
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A B
C
Figure3.Fivedaysafterinfraredlaserexposure.A,Color
fundusphotographs5daysafter60-secondinfraredlaser
exposureofthemaculatoa3-mmbeamofinfrared
lightfromthediodelaserusing800mWofpower.
B,Arteriovenousphaseduringfluoresceinangiography
showingsubtlehyperfluorescenceinposteriorpoleandearly
sectorcystoidedema.C,Recirculationphaseshowing
diffuseintraretinaldyeleakageandsectorcystoidmacular
edema.Thefindingsareunchangedfromthosedocumented
inFigure2.
periortothefovea,temporaltothe changeintheappearanceofthefun- shapes rather than the usual oval-
fovea,andtoalesserextentinfero- dus. The fluorescein angiogram at shapedmelanosomegranules(Fig-
temporaltothefovea(Figure2B-D). the 5-day follow-up visit demon- ure4C).Focaldisruptionofcellu-
Thelargestdimensionofthestain- strated findings identical to those lar membranes and dispersion of
ingsitehadadiameterofapproxi- seen in the pretreatment angio- pigmentgranulesamongouterseg-
mately3mm(beforeandafterlaser gram (Figure 3). ments of photoreceptor cells were
exposure). Lightmicroscopyoftheenucle- seen.Vacuolationanddistensionof
During and immediately after atedeyeshowedamalignantmela- theoutersegmentsofthephotore-
transpupillaryexposureofthemacula nomalocatedintheposteriorcho- ceptorswerealsoobserved,withpar-
tolightfromtheinfraredlaser,nodis- roid, nasal to the optic disc, that tial disintegration of the lamellar
cerniblealterationintheophthalmo- formed a mass measuring 10(cid:1)10 structure with a rare thumbprint-
scopicappearanceofthefunduswas (cid:1)3 mm and consisted predomi- likeconfiguration(Figure4D).The
seen.Three minutes after light ex- nantlyofepithelioidcells.Aserous underlyingchoriocapillarisshowed
posure,thepatientnoticedabluish detachment of the sensory retina congestion,butthevesselswerenor-
discolorationinthecentralfieldof was seen overlying the nasal por- mal,withintactwallsandnormalen-
visionthatsheoutlinedontheAm- tion of the tumor. A plaque of fi- dothelial cells. The larger choroi-
sler grid. The best-corrected dis- brous tissue was visible over the dal vessels also appeared normal
tance visual acuity 3 minutes after central portion of the tumor, and (Figure4E).
lightexposurewas20/100.Whenthe cystoiddegenerationwaspresentin
patientreturned5dayslater,thecen- the overlying retina (Figure 4A Comment.Transpupillarythermo-
tralvisualacuityhadrecoveredtothe andB). therapyhasbeenusedinrecentyears
pretreatmentlevel(20/25),butshe Results of the ultrastructural as a therapeutic alternative in the
still recognized a faint bluish dis- examination of the macular and management of some choroidal
colorationinthecentralpartofher paramacularregion,whichhadbeen melanomas.1-4Wehaveshownthat
visiononAmslergridtesting.Shere- dissected and embedded for trans- effectivetreatmentofselectedsmall
ported that this dyschromatopsia mission electron microscopy, choroidal melanomas almost al-
hadbeendecreasinginintensityeach showed retinal pigment epithelial ways leads to a profound field de-
day since the exposure. Examina- cells with numerous cytoplasmic fect because of destruction of the
tionofthefundus5daysafterlaser granulesoflipofuscinandmelano- photoreceptorsandnervefibersin
exposure showed no discernible fuscin with round and irregular theretinaoverlyingthetreatedtu-
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A B
C D
E
Figure4.A,Low-powerlightmicroscopyshowingchoroidal
malignantmelanomawithalayerofheavilypigmentedspindle
cellsnearitssurface.Afibrousplaqueisvisibleoverthe
centralportionofthetumor,andtheoverlyingretinashows
markedcystoiddegeneration(hematoxylin-eosin,original
magnification(cid:1)20).B,High-powerlightmicroscopyshowing
thatthisneoplasmiscomposedofapredominanceof
epithelioidcells.Nomitosesornecrosisisseen
(hematoxylin-eosin,originalmagnification(cid:1)200).C,Electron
microscopyofthemacularregionatthesiteoflaserexposure
showingretinalpigmentepitheliumcontainingcytoplasmic
granulesoflipofuscin(arrowhead)andmelanofuscin(arrow)
withroundandirregularshapes.Focaldisruptionofcellular
membraneswithdispersionofpigmentgranulesintoouter
segmentsofphotoreceptorcellsisseen(leadcitrate,original
magnification(cid:1)25000;barindicates2µm).D,Electron
microscopyshowingvacuolizationanddistensionoftheouter
segmentsofthephotoreceptorswithpartialdisintegrationof
thelamellarstructuresandfocalthumbprintlikeconfiguration
ofsomelamellae(leadcitrate,originalmagnification(cid:1)25000;
barindicates2µm).E,Electronmicroscopyshowing
congestedbutotherwisenormal-appearingvesselswithintact
wallsinthechoroidunderlyingthemacularretinaatthesiteof
laserexposure(leadcitrate,originalmagnification(cid:1)48000;
barindicates3µm).
mor.4Whenusedfortreatmentofa multicenterrandomizedstudyofoc- generation(800mW,60secondsof
choroidalmelanoma,thesamevari- cult choroidal neovascular mem- exposure, and 3-mm beam diam-
ablesrecommendedbytheongoing branes in age-related macular de- eter)areusuallyassociatedwithex-
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tensiveretinaldamage,causingalo- pearssimilartotherelativeabsence lar region by means of ultrastruc-
calized scotoma and, frequently, a ofatakethatwehaveobservedwhen turalstudies.
wedge-shaped field defect as a re- attemptingtoprophylacticallytreat Theabsenceofrecognizablede-
sult of nerve fiber bundle destruc- normal-appearingtissueadjacentto struction of the retina and retinal
tion. Therefore, some concern ex- a pigmented choroidal melanoma. vasculatureobservedinthissingle
ists that these variables have been Takesareoftennotwellseeninthe experimentdoesnotensurethatvas-
chosen for treatment of choroidal normal-appearing tissue. For ex- cular closure and retinal destruc-
neovascular membranes. Our pa- ample, a 3-mm beam of laser light tionwillnotoccurwhenTTTisused
tient with a malignant melanoma thatisplacedsoastoequallystraddle totreatoccultchoroidalneovascu-
locatedinthenasalchoroid,sched- theedgeofapigmentedchoroidaltu- larmembrane.However,inthiscase,
uled for enucleation, consented to mor and clinically normal tissue withclinicalandangiographicevi-
have her macula exposed to light adjacenttoitoftendramaticallyout- denceofmildretinaledemaandno
fromthediodelaserusingthevari- lines the ophthalmoscopically rec- retinal or subretinal blood, a 60-
ablescitedabove.Inthispatient’saf- ognizableperimeterofthetumor.The secondexposureof800mWusing
fectedeye,subtleintraretinaledema tumor,theoverlyingretina,andthe a3-mmbeamdiameterdidnotcause
involvedtheposteriorpole,presum- retinalpigmentepitheliumbecome clinicallyrecognizabledamagetothe
ablyrelatedtotheactivelygrowing gray white, whereas the adjacent macularretina,theretinalvessels,or
melanoma located in the superior retina overlying normal-appearing theunderlyingchoriocapillarisand
nasalfundus.Thisintraretinalede- choroid frequently remains clini- otherchoroidalvessels.
ma was recognized in the macula callyunchangedoronlyminimally
beforeexposuretothelaserlight.The gray. We believe that the pigment DennisM.Robertson,MD
melanomaitselfshowedcomplexvas- withinthetumorislargelyrespon- DivaR.Saloma˜o,MD
cularpatternsonfluoresceinangi- sible for generating a considerable Rochester,Minn
ography with extensive leakage of amountofheat,whichcausesthetu-
dyethatdiffusedintotheoverlying mor,theoverlyingpigmentepithe-
retina,whereheavyfluoresceinstain- lium, and retina to turn gray more Thisstudywassupportedinpartbya
ingwasseeninthelatepartofthe readily.Inaddition,thechoriocap- grantfromResearchtoPreventBlind-
fluoresceinstudy. illarisandlargervesselsinthecho- ness,Inc,NewYork,NY,andinpart
Laser exposure of the macula roidarealteredinthepresenceofa bytheMayoFoundation,Rochester,
failedtoproduceaclinicallyrecog- melanoma,thusdecreasingtheabil- Minn.
nizable reaction in the retina dur- ityofthechoroidtoplayitsroleasa WethankBonnieRonkenforher
ing the treatment, and no changes heatsinktodisperseenergy.Theab- secretarialsupportandCherylHann,
wererecognizedonresultsofacare- senceofaheavyconcentrationofpig- MS,forhersupportwiththeelectron
ful clinical examination 5 days af- mentandthepresenceofanormal microscopystudies.
ter exposure. A fluorescein angio- choroid, providing a normal heat Corrresponding author and
gram5daysafterthelaserexposure sink, can facilitate dispersement of reprints: Dennis M. Robertson, MD,
showednodifferencefromthefluo- energy,therebyminimizingthepo- Department of Ophthalmology,
resceinangiogramobtainedimme- tential for thermal damage to the Mayo Clinic, Rochester, MN 55905
diatelybeforethelaserexposure.Al- overlyingretina. (e-mail:[email protected]).
thoughthecentralvisualacuitywas Inthisstudy,wewereunable
1. OosterhuisJA,Journee-deKorverJG,Kake-
reducedto20/100immediatelyaf- toidentifyTTT-inducedadverseef-
beeke-KemmeHM,BleekerJC.Transpupillary
terexposure,5daysafterTTT,the fectsintheretinaorthepigmentepi- thermotherapyinchoroidalmelanomas.Arch
centralvisualacuityhadrecovered theliumbymeansofclinicalexami- Ophthalmol.1995;113:315-321.
2. Journee-deKorverJG.TranspupillaryThermo-
tothepretreatmentvisualacuity. nationorfluoresceinangiography. therapy:ANewTreatmentofChoroidalMela-
Wewereunabletoseeagray- However,weobservedhistological noma.TheHague,theNetherlands:Kugler
Publications;1998.
ingoftheretinaafterexposuretola- andultrastructuralabnormalitiesin
3. ShieldsCL,ShieldsJA,CaterJ,etal.Trans-
serenergieswiththesamedosagethat thetissueaftertheeyewasenucle- pupillarythermotherapyforchoroidalmela-
ordinarilycausesagraying(“take”) ated. We believe that these abnor- noma:tumorcontrolandvisualresultsin100
consecutivecases.Ophthalmology.1998;105:
whendirectedtoachoroidalmela- malities can be explained by the
581-590.
noma.Thesubtleedemaofthemacu- presence of the preexisting retinal 4. RobertsonDM,BuettnerH,BennettSR.Transpu-
larretinainthiscasewassimilarto edema. However, some of the ob- pillarythermotherapyasprimarytreatmentfor
smallchoroidalmelanomas.ArchOphthalmol.
the mild retinal edema frequently served abnormalities could have 1999;117:1512-1519.
seen with occult choroidal neovas- beencausedbylightalone,asshown 5. ReichelE,BerrocalAM,IpM,etal.Transpupil-
larythermotherapyofoccultsubfovealchoroi-
cular membranes. However, we do by Robertson and Erickson6 and
dalneovascularizationinpatientswithage-
notbelievethatthepresenceofreti- GreenandRobertson.7Althoughwe relatedmaculardegeneration.Ophthalmology.
nal edema could explain the ob- lookedforevidenceofvascularclo- 1999;106:1908-1914.
6. RobertsonDM,EricksonGJ.Theeffectofpro-
servedabsenceofatakeintheretina sure or coagulative necrosis in the
longedindirectophthalmoscopyofthehuman
and/or retinal pigment epithelium smallcapillariesinthechoroid,we eye.AmJOphthalmol.1979;87:652-661.
during or 5 days after the laser ex- were unable to demonstrate such 7. GreenWR,RobertsonDM.Pathologicfindings
ofphoticretinopathyinthehumaneye.AmJ
posure. This absence of a take ap- changesinthechoroidinthefoveo- Ophthalmol.1991;112:520-527.
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