Intravitreal Antivirals in the Management of Patients With Acquired Immunodeficiency Syndrome ...

19 Pages·2012·0.94 MB·English

CLINICOPATHOLOGICREPORTS,CASEREPORTS,ANDSMALLCASESERIES
SECTIONEDITOR:W.RICHARDGREEN,MD
carcinomaandmetastaticlivercan-
Branch Retinal Artery cer 2 years previously and had un-
dergonetotalgastrectomyandpartial
Occlusion Caused
resectionoftheliver.Hehadnohis-
by an Embolus of
toryofhypertension,diabetesmelli-
Metastatic Gastric
tus,heartdisease,orcerebralinfarc-
Adenocarcinoma
tion.Onexamination,thecorrected
visualacuitywas20/30ODandlight
We report a case of branch retinal perception OS. Intraocular pres-
artery occlusion caused by an em- sures were 13 mm Hg OD and 10
bolus of metastatic gastric adeno- mmHgOS.Arelativeafferentpupil-
carcinoma. A 67-year-old man lary defect was observed in the left
soughttreatmentforsuddenvisual eye.Externalandslitlampexamina-
lossinhislefteye.Hehadamedi- tions were unremarkable bilater-
Figure1.Afunduscopicphotographshows
calhistoryofgastriccancerwithliver ally. Funduscopic examination re-
milky-whiteretinaledemainthesupratemporal
metastasis. Findings on fundu- vealed milky-white retinal edema quadrant,whichiscompatiblewithbranch
scopicexaminationincludedlocal- consistent with branch retinal ar- retinalarteryocclusion.Notealsothe
yellowish-whitesubretinalmasssurroundedby
izededemaoftheinnerretinacon- teryocclusioninthesupratemporal
shallowretinaldetachmentsuperiortothe
sistentwithasupratemporalbranch quadrantandayellowish-whitesub- equatorofthelefteye.
retinal artery occlusion and a yel- retinalmasssurroundedbyshallow
lowish-white subretinal mass sur- retinal detachment in the superior croscopic examination of the tu-
roundedbyshallowretinaldetach- quadrantofthelefteye(Figure1). mor disclosed extensive infiltra-
ment superior to the equator. Ultrasonography disclosed a tionofthechoroidalstromabycords
Histopathologicalandimmunohis- masswithstronginternalechoesin and lobules of a malignant epithe-
tochemicalexaminationsoftheeye thesameregion,suggestiveofasub- lialneoplasmconsistentwithmeta-
obtainedpostmortemshowedposi- retinal tumor. The provisional di- static mucin-secreting adenocarci-
tive staining of the choroidal tu- agnosisofthemasslesionwasmeta- noma. The tumor cells formed
mor for epithelial membrane and staticadenocarcinomatothechoroid tubules and glandular structures
carcinoembryonic antigens. In ad- associated with branch retinal ar- (Figure2A),andtheperiodicacid–
dition,anembolusoftumorcellswas tery occlusion. Fluorescein angio- Schiff and alcian blue stains con-
foundtocauseocclusionofthereti- graphic and computed tomo- firmedthepresenceofnumerousin-
nalartery. graphicexaminationscouldnotbe tracytoplasmic vacuoles of mucin
Occlusionoftheretinalartery performed because of the patient’s (Figure 2B). Immunohistochemi-
is mostly ascribed to either embo- poorgeneralcondition.Laboratory cal stains showed intense positive
lus, thrombus, or vasculitis. It is values included a carcinoembry- immunoreactivity for epithelial
stronglyassociatedwithcarotidath- onicantigenlevelof722ng/mL(ref- membraneantigen(Figure3A)and
eromatousplaqueorcardiacvalvu- erencelevel,(cid:1)5ng/mL)andacar- carcinoembryonic antigen (Figure
lardiseaseswithvegetation.Other bohydrateantigen19-9levelof2567 3B). The histopathological find-
causes,suchasatrialmyxoma,tem- U/mL(referencelevel,(cid:1)37U/mL). ingsofthechoroidalmetastasisre-
poralarteritis,periarteritisnodosa, Culturesofarterialbloodwerenega- sembled the patient’s primary tu-
andsystemiclupuserythematosus, tiveforbacteria,andsplenomegaly mor(Figure4)andwereconsistent
have been described but are rela- was absent. A chest radiograph with a moderately well-differenti-
tively rare.1 Embolism caused by showed no concrete evidence of a atedgastricadenocarcinoma.Ami-
neoplasticcellsisextremelyrare.2,3 metastatic tumor. Three weeks af- crometastasiswasalsoidentifiedin
We report a case of gastric adeno- ter admission, the patient died be- the ciliary body inferior to the
carcinomathatmetastasizedtothe causeofthedeteriorationofhisgen- muscle.Inaddition,anembolusof
choroidandoccludedabranchreti- eral condition. Both eyes were tumorcellswasfoundtototallyoc-
nal artery with an embolus of car- obtainedpostmortem,fixedinfor- cludethelumenofthesupratempo-
cinomacells. maldehyde, and processed rou- ralretinalarterioleneartheopticdisc
tinelyforlightmicroscopy.Macro- (Figure 5). The cytological char-
ReportofaCase.A67-year-oldman scopicexaminationdisclosedasolid acteristics of the tumor embolus
was referred to our clinic for sud- tumor with a mottled dark-brown were quite similar to those of the
denvisuallossinhislefteye.Hehad colorthatmeasured12mm(cid:2)6mm choroidaltumor.Therighteyewas
beendiagnosedwithgastricadeno- in the choroid of the left eye. Mi- normal on gross examination, and
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A B
Figure2.A,Hematoxylin-eosinstainingshowsthetumortobeamoderatelywell-differentiatedadenocarcinomabasedonthepresenceoftubulelikeorglandlike
structures.B,Positiveperiodicacid–Schiffstainingisindicativeofmucinproductionbycarcinomacells,especiallybycellsformingglandlikestructures(original
magnification(cid:2)180).
A B
Figure3.A,Positiveimmunostainingforepithelialmembraneantigenonthemembraneofcellsisrelatedtothetubulelikeorglandlikestructuresofthetumor.
B,Diffuseandstronglypositiveimmunostainingforcarcinoembryonicantigenofthetumorisshown(originalmagnification(cid:2)180).
Figure4.Arepresentativemicrophotographshowsmoderately Figure5.Theretinalarteryiscompletelyoccludedbyatumorembolus
well-differentiatedadenocarcinomaofthestomach.Thesectionwastaken (originalmagnification(cid:2)180).
fromthesurgicalspecimen(originalmagnification(cid:2)180).
therewerenoparticularhistopatho- metastaticadenocarcinoma.Histo- pathological and immunohisto-
logicalchanges. pathologicalexaminationalsocon- chemical studies, including posi-
firmedthatthesupratemporalreti- tive immunoreactivity markers for
Comment.Thepresentstudyclearly nal arteriole was occluded by an epithelial membrane antigen and
showsthatthechoroidaltumorwas embolusoftumorcells.Thehisto- carcinoembryonicantigen,arecon-
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sistent with metastatic gastric ad- nomatothechoroidthathadbranch bothimplants,thoughthepatientre-
enocarcinoma;aprimarytumorwith retinalarteryocclusionduetoatu- portedminimalvisualdeficit.Wethen
knownhepaticmetastasishadbeen mor embolus. Ophthalmologists investigatedtheeffectofrifabutinon
treated2yearsearlier.Thepatient should be aware of this cause of 3differentcommonIOLmaterialsand
ispresumedtohavediedfromwide- acute visual loss in their differen- foundthatitonlyaffectedsilicone.
spread systemic metastases be- tial diagnoses of retinal artery oc- Though rifabutin is well known to
causepostmortemexaminationwas clusioninpatientswithahistoryof causediscolorationofbodyfluidsand
limitedtotheeyes. malignancy. softcontactlenses,thiscaseillustrates
To our knowledge, retinal ar- thisprocessoccurringinIOLimplants.
tery occlusion caused by an embo- HisashiMasuda,MD Rifabutinisindicatedforpro-
lismoftumorcellsisveryrare,and AkihiroOhira,MD,PhD phylaxis against Mycobacterium
there are only a few reports that YuzoShibuya,MD aviumcomplex(MAC),whichispri-
clearlydescribethiscondition.Oc- TaijiTakanashi,MD marilyseenasacoinfectionwithhu-
clusionofthecentralretinalarteryby LiliamPineda,MD manimmunodeficiencyvirus(HIV).
chondrosarcomaandbronchialcar- TakayukiHarada,MD,PhD Showntocausediscolorationincer-
cinomacellswasdescribedbyBurde Izumo,Japan tainbodyfluids,includingtears,sa-
andHenkind2andTarkkanenetal,3 liva,andperspiration,rifabutinpre-
respectively.Zamoraetal4reported Theauthorshavenoproprietaryin- scribing guidelines specifically
acaseofbranchretinalarteryocclu- terestinanyaspectofthisreport. cautionthatsoftcontactlensesmay
sioninapatientwithpapillaryfibro- Corresponding author and re- be permanently stained subse-
elastomaofthemitralvalve,butthere prints:AkihiroOhira,MD,PhD,De- quent to its use.1 However, to our
wasnohistopathologicaldemonstra- partmentofOphthalmology,Shimane knowledge,theoccurrenceinanIOL
tionoftheembolus.Metastasisofcar- MedicalUniversity,89-1Enya,Izumo, has not been documented. We de-
cinomacellstotheretinaaloneap- Shimane 693-8501, Japan (e-mail: scribeapatientwhodevelopedabi-
pearstobearareevent.Smoleroffand [email protected]). lateraldiscolorationofhersilicone
Agatston5reportedacaseofgastro- IOLs.
esophagealcarcinomathatmetasta- 1. RosMA,MagargalLE,UramM.Branchretinal
arteryobstruction:areviewof201eyes.AnnOph-
sizedintothenervefiberlayerofthe Report of a Case. A 63-year-old
thalmol.1989;21:103-107.
retina.Shieldsetal6studied520eyes 2. BurdeRM,HenkindP.Retinalarteryocclusion womanhadbilateralcataractextrac-
withuvealmetastasisandfoundonly intheabsenceofacherryredspot.SurvOph- tions with silicone IOL implants
thalmol.1982;27:181-186.
5 to have metastatic lesions in the 3. TarkkanenA,MerenmeiesL,MakinenJ.Em- (model SI30NB; Allergan Inc, Ir-
retina. bolismofthecentralretinalarterysecondaryto vine,Calif)inearly1995.Shortlyaf-
However,therewasnodescrip- metastaticcarcinoma.ActaOphthalmol.1973; teranormaleyeexamination,shebe-
51:25-33.
tionofarterialocclusionintheirse- 4. ZamoraRL,AdelbergDA,BergerAS,etal.Branch gana101⁄2-monthcourseof300mg
ries.Inpatientswithend-stagedis- retinalarteryocclusioncausedbyamitralvalve ofrifabutin,bymouth,oncedailyfor
papillaryfibroelastoma.AmJOphthalmol.1995;
ease, particularly those with chronicpulmonaryMAC.Atannual
119:325-329.
malignancies,embolismduetobac- 5. SmoleroffJW,AgatstonSA.Metastaticcarci- follow-up,bothIOLswerenotedto
terial endocarditis, nonbacterial nomaoftheretina:reportofacase,withpatho- bediscolored,andrifabutintherapy
logicobservations.ArchOphthalmol.1934;12:
thromboticendocarditis,orthrombi 359-365. wasdiscontinued.
formedwithdisseminatedintravas- 6. ShieldsCL,ShieldsJA,GrossNE,etal.Survey Slitlampexaminationrevealeda
cularcoagulationsyndromemaybe of520eyeswithuvealmetastases.Ophthalmol- distinct rose-color in both IOLs
ogy.1997;104:1265-1276.
encounteredintheretinalartery.7,8 7. DeppischLM,FayemiAO.Non-bacterialthrom- (Figure1).Theremainderoftheex-
In the present case, there was no boticendocarditis.AmHeartJ.1976;92:723-
729.
strong clinical or laboratory evi-
8. CoganDG.Ocularinvolvementindissemi-
dence of infection, valvular dis- natedintravascularcoagulopathy.ArchOphthal-
eases,ordisseminatedintravascular mol.1975;93:1-8.
9. WeissL.Celladhesionmolecules:acriticalex-
coagulation.Completeobstructionof aminationoftheirroleinmetastasis.InvasionMe-
thearteriallumenbythetumorem- tastasis.1994-1995;14:192-197.
bolusasshowninourcaseisuncom-
mon, whereas venous and lym-
phaticinvasionbymalignantcellsis
morecommonbecauseitcanbeob-
Discoloration of Intraocular
served in routine surgical speci-
mens. A major factor that contrib- Lens Subsequent
utestotheformationoftumoremboli to Rifabutin Use
is the expression of adhesion mol-
ecules,9butemboligenicfactorssuch A63-year-oldwomandevelopeddis-
as those mentioned above may ac- colorationofthesiliconeintraocular
celeratetheirformation. lens(IOL)implantsinbotheyesaf- Figure1.Slitlampphotographofthelensshows
Inconclusion,wereportaclini- terreceiving300mgofrifabutinby rose-coloreddiscolorationoftheintraocularlens
(doublearrows)contrastedagainstcapsular
copathologicalcorrelationofacase mouth,oncedaily,for101⁄2months. remnantsthatarenotcoveredbytheintraocular
of metastatic gastric adenocarci- Examinationrevealedarosecolorto lens(singlearrows).
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sionofOphthalmology,FletcherAllen
A B C D
HealthCare,UHCFourthFloor,Bur-
lington,VT05405(e-mail:airwin@
vtmednet.org).
1. Physicians’DeskReference.53rded.Montvale,NJ:
MedicalEconomicsCo;1999:2501-2502.
2. KnightPM.Discolorationofasiliconeintraocu-
larlens6weeksaftersurgery[letter].ArchOph-
E
thalmol.1991;109:1494-1496.
3. CentersforDiseaseControlandPreventionWeb
site.NontuberculousMycobacteriaReportedtothe
PublicHealthLaboratoryInformationSystemby
StatePublicHealthLaboratories:UnitedStates,
1993-1996.NTMReport1999:1-51.Availableat:
http://www.cdc.gov/ncidod/dastlr/TB
Figure2.Comparisonphotographof4intraocularlensesafterimmersioninconcentratedrifabutin /ntmfinal.pdf.AccessedAugust30,2001.
solutionat24hours.A,Silicon(AllerganSI30NB;AllerganInc,Irvine,Calif).B,Silicon(AA4204VF; 4. ZimmerliW,WidmerAF,BlatterM,FreiR,
StaarSurgical,Monrovia,Calif).C,Acrylic(MA30BA;AlconSurgical,ForthWorth,Tex).D,Polymethyl OchsnerPE.Roleofrifampinfortreatmentof
methacrylate(UV80F2;CibaVisionOphthalmics,Duluth,Ga).E,CrosssectionofAllerganlens. orthopedicimplant-relatedstaphylococcalin-
fections:arandomizedcontrolledtrial.JAMA.
1998;279:1537-1541.
aminationwasunremarkable,withvi- sonal communication, G. Kropid-
sualacuitycorrectableto20/20OU. lowski, Allergan Inc). Finally, sili-
ThatbothIOLswereequallyand cone IOLs placed in a rifabutin
Delayed Luxation
simultaneouslystainedislikelytoac- solutionmaydramaticallydiscolor.
countforthelackofperceivedcolor In a laboratory investigation, of a Lens Nucleus
shift.NofurtherchangeinIOLcolora- lensesfrom4differentmanufactur- After Vitrectomy
tionhasbeennotedsincediscovery. ersrepresenting3materialswereim-
Thus,theIOLswerenotremoved. mersedfor1weekinaconcentrated Accidentallensdamageoccursless
rifabutinsolution.Thediscoloration than 1% of the time during vitrec-
Comment. Silicone IOL engineer- fullypenetratedthelens,ratherthan tomy for diabetic retinopathy and
ing has achieved a high degree of layeringonasafilm(Figure2).Only maynecessitateconcurrentlensec-
long-termopticalclaritysothatre- thesiliconelensesplacedinthisso- tomy.1,2Wereportanunusuallate
ports of decreased clarity have be- lutiondiscolored. complicationofparsplanavitrecto-
comerare(approximately0.07%).2 These findings have potential my—delayed luxation of the lens
Thiscaserepresentsapotentiallysig- implications for our elderly popu- nucleus.
nificanteffectonthepatient’squal- lation,asmanyoftheseindividuals
ityoflifebecausethestainedlenses mayhavealreadyreceivedsilicone ReportofaCase.A52-year-oldman
areintraocular. IOLsbythetimethattheydevelop with a 20-year history of diabetes
Therifamycinsarerecognized MAC or infection from implanta- mellitus sought treatment at the
as “standard-of-care” drugs against tion of orthopedic hardware. Phy- Parkland Memorial Hospital Oph-
both tuberculous and atypical my- siciansshouldbethuscautionedin thalmologyClinic,Dallas,Tex,be-
cobacterial infections. Use of these theiruseofrifabutininpatientswith causeofrednessandphotophobiain
drugsisincreasingbecausetheinci- silicone IOLs, and that acrylic or thelefteyefor3days.Oneyearpre-
dence of MAC has dramatically in- polymethylmethacrylatelensesmay viously, he underwent vitrectomy
creasedamongbothHIV-infectedand bebettersuitedforpatientsinwhom inthelefteyeforproliferativedia-
immunocompetentindividualsdur- opportunisticinfectionsarelikely. betic retinopathy complicated by
ingthelastdecade.Highratesofin- nonclearing vitreous hemorrhage
creasearecurrentlybeingreportedin DanielFullerJones,MD and neovascular glaucoma. Four
patientsolderthan50years.3Addi- AlanEmoryIrwin,MD monthspriortothecurrentdevel-
tionally,thesedrugsarebeingproven Burlington,Vt opment, he underwent a second
usefulagainstStaphylococcusinor- vitrectomy in the same eye for re-
thopedic cases such as after im- WewishtothankLindaRitchie,LPN- current vitreous hemorrhage. The
planteddevicesorosteomyelitis.4 COA,FernandoCorrada,CRA,Kem- surgeon noted no intraoperative
Multiplefactorspointtorifabu- per Alston, MD, and Fletcher Allen complications,includinglenstouch
tinasthemostlikelycauseofstain- HealthCarePharmacy,Burlington,Vt. with the instruments. On the first
ing here. First, rifabutin has been Neither Dr Jones nor Dr Irwin dayafterthesecondvitrectomy,best-
shown to stain soft contact lenses hasanyproprietaryorcommercialin- correctedvisualacuitywas20/400
(typicallysilicone).Noneofthepa- terest in any company manufactur- OS,andanewposteriorsubcapsu-
tient’sothermedicationsareknown ing any of the drugs or IOLs named larcataractwasnoted.
to cause discoloration of body flu- inthiscasereport. Onexaminationofthelefteye,
ids.Thetimingofthestaining,rela- DrJonesisnowapathologyresi- best-correctedvisualacuitywashand
tive to her initiation of rifabutin dentatJeffersonMedicalCollegeHos- motion at 1 ft. Circumcorneal hy-
therapy,isconsistentwithrifabutin pital,Philadelphia,Pa. peremiaandkeraticprecipitateswere
asthecause.Allerganhasreceivedno Corresponding author and re- noted on slitlamp biomicroscopy.
similarreportsofdiscoloration(per- prints:AlanEmoryIrwin,MD,Divi- Theanteriorchamberwasdeep,with
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Figure1.Aslitlampphotographofthelefteye
showsawrinkledanteriorlenscapsulewith
anopacifiedwhiteanteriorlenscortex.
a moderate inflammatory reaction
and visible lens particles. Neovas-
cularizationoftheiriswaspresent
Figure2.AB-scanultrasonogramofthelefteyeshowsalensnucleusthatisdislocated
atthepupillarymarginbutnotinthe intotheposteriorsegment.
angleoftheanteriorchamberongo-
nioscopy. The anterior lens cap-
sule was displaced posteriorly and formingcataractextractionaftervi- sis(LASIK)indicatesthatmostaredi-
waswrinkledwithanopacifiedan- trectomy. rectlyattributabletothecreationof
terior cortex, obstructing the view a corneal flap.1,2 In their examina-
ofthefundus(Figure1).Thelens DavidH.Ren,MD,PhD tionof1000consecutivecasesofpa-
nucleusandposteriorlenscapsule PrestonH.Blomquist,MD tients who had undergone LASIK,
werenotseen.Intraocularpressure SuriN.Appa,MD Gimbelandcolleagues1identified32
was12mmHg.B-scanultrasonog- KamelM.Itani,MD intraoperativeand18postoperative
raphyrevealedthatthelensnucleus Dallas,Tex complications,mostofwhichcould
wasrestingontheretina(Figure2). berelatedtoissuesofflapanatomy,
Thepatientwastreatedwitha Thisstudywassupportedinpartbyan including incomplete passes, thin
topicalcorticosteroidandcyclople- unrestricted grant from Research to flaps,buttonholes,flapshrinkageand
giaforphacoantigenicuveitisandun- PreventBlindness,Inc,NewYork,NY. flapdislocationwithsubsequentde-
derwentparsplanalensectomy5days The authors have no propri- velopmentofstriae,andepithelialin-
later.Atthetimeoftheoperation,the etaryorfinancialinterestinthema- growth.Stultingandcolleagues2re-
anteriorcapsuleandzonuleswerein- terialdiscussedinthisarticle. portedcomplicationsencounteredin
tact,butalargerentwasfoundinthe Corresponding author and re- aseriesof1062casesofpatientswho
inferiorposteriorcapsule. prints:PrestonH.Blomquist,MD,De- had undergone LASIK, and identi-
partmentofOphthalmology,Univer- fied 27 intraoperative and 40 post-
Comment.Afterlens-sparingvitrec- sity of Texas Southwestern Medical operativecomplications,allofwhich
tomy,thelenstendstofallslightly Center,5323HarryHinesBlvd,Dal- weredirectlyrelatedtothecorneal
posteriorly,makingaccidentallens las,TX75390-9057(e-mail:preston flapwiththeexceptionof2casesof
touchmorelikelyduringrepeatvi- [email protected]). keratitis.
trectomy.3Ourpatientlikelyhadan Although most complications
iatrogenicdefectintheposteriorcap- 1. OyakawaRT,SchachatAP,MichelsRG,RiceTA. canberesolvedwithacceptablevi-
sulepriortoluxation.Theacuteand Complicationsofvitreoussurgeryfordiabetic sual outcomes, persistent flap ir-
retinopathy,I:intraoperativecomplications.Oph-
persistentposteriorsubcapsularcata- thalmology.1983;90:517-521. regularity or opacification will re-
ract seen after the second vitrec- 2. NovakMA,RiceTA,MichelsRG,AuerC.The sult in decreased vision. Since
crystallinelensaftervitrectomyfordiabeticreti-
tomyinourpatientwaslikelydue epithelialization of the underlying
nopathy.Ophthalmology.1984;91:1480-1484.
todirecttraumatotheposteriorlens. 3. FaulbornJ,ConwayBP,MachemerR.Surgical stromal bed might provide a more
Wetheorizethatincreasedintracap- complicationsofparsplanavitreoussurgery. regularsurface,amputationoftheof-
Ophthalmology.1978;85:116-125.
sularvolumesecondarytolenshy- fendingflapmightbeconsidereda
drationcausedextensionofthepos- reasonable intervention to address
teriorcapsuledefectandallowedthe persistentflapproblems.Itisthere-
Refractive, Topographic,
lens nucleus to fall into the poste- fore important to understand the
and Visual Effects of Flap
riorsegmentoftheeye. healing pattern of the corneal bed
Luxationofthelensnucleusis Amputation Following Laser following flap creation and ex-
anunusuallatecomplicationofvi- In Situ Keratomileusis cimerlaserablationintermsoflens
trectomy.Cataractsurgeonsshould power,topography,regularity,and
beawareofthepossibilityofoccult A review of complications associ- scar formation. In our experience,
posteriorcapsuledamagewhenper- atedwithlaserinsitukeratomileu- mostcasesofflapamputationhave
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ciscoRefractiveSurgeryServicefor
furtherconsultationinMay2001,ap-
proximately2yearsafterLASIKand
flapamputationofthelefteye.Atthat
Right Eye Left Eye time,shecomplainedoffluctuating
visioninthelefteyethatatitsbestre-
mained blurred. She also reported
ghostingandglare.Examinationdis-
closedanuncorrectedvisualacuityof
20/25ODand20/80OS.Thevision
ofthelefteyeimprovedto20/25with
arefractionof–3.25+3.25(cid:2)70.
Slitlampbiomicroscopicexami-
nationoftherighteyeshowedawell-
positioned, nasally hinged corneal
flap,butcoarse,diffuseepitheliopa-
thy.Therewasnoevidenceofsub-
epithelial or stromal haze or scar-
ring,exceptforanormaldegreeof
scar formation outlining the edges
Figure1.Case1.Cornealtopographyofbotheyes.Althoughtheoverallpowersofthecentralcorneal ofthecornealflap.Slitlampexami-
curvaturesaresimilar,thelefteyeshowsgreaterirregularity,asrepresentedbytheelevatedsurface nationofthelefteyeshowedasubtle,
asymmetryindex(SAI).SimKindicatessimulatedkeratometry;MinK,minimumkeratometry;PVA,
vertically oriented elevation of the
predictedvisualacuity;CYL,cylinder;andSRI,surfaceregularityindex.
corneal surface at the hinge of the
amputated flap. There was no evi-
followedinfectiouskeratitisandflap tended toward the entrance pupil. dence of subepithelial or stromal
meltingthatresultsinsomedegree Theflapwaselevatedandtheinter- scarring,eitherattheformerloca-
ofscarringandopacificationofthe faceepithelium,removed.Approxi- tionoftheflapedgeoroverthecen-
underlying corneal bed. Conse- mately2weekslater,theepithelial tral cornea. However, there was a
quently,ithasbeendifficulttopre- ingrowthhadrecurred,sotheflap moderatedegreeofepithelialirregu-
dictwhattheopticalqualitiesofthe wasamputated. larityevidentwithoutinstillationof
uninflamedstromalbedmighthave Thepatientwastreatedwitha fluorescein sodium dye. Fluores-
been.Wedocumenthereinthecor- bandagecontactlens,andciprofloxa- ceinsodiumstainingrevealedcoarse,
nealfindingsin2patientswhoun- cinhydrochloridesolutionwasap- diffuse epitheliopathy concen-
derwent early flap amputation for plied every 3 hours. No corticoste- tratedoverthecentralcorneaandan
noninflammatory epithelial in- roidswereapplied.Duringthenext areaofirregularsurfacecontourthat
growthfollowingLASIK. 5days,theepithelialdefectcreatedby appearedtoinvolvethecentralarea
removaloftheflapclosed,theban- ofcornealdissectionthatproduced
ReportofCases. Case1.A46-year- dagecontactlenswasremoved,and theamputatedflap.
oldwomanwithahistoryofrecur- the patient was prescribed diclo- Computerized corneal map-
rentcornealerosionandanexami- fenac sodium solution for occa- ping(Figure1)confirmedtherela-
nationfindingconsistentwithmap- sional use up to 3 times daily and tiveirregularityofthelefteye.Ato-
dot-fingerprintdystrophyunderwent artificial tears for lubrication. Ap- pographic map of the right eye
bilateralLASIKforthecorrectionof proximately1weekafterclosureof (TomeyTopographicModelingSys-
an error of –6.75+0.50(cid:2)100 OD the epithelial defect, the uncor- tem, version 2.3.6J; Tomey Corp,
and –7.00+0.25(cid:2)072 OS. An au- rectedvisualacuityinthelefteyewas Waltham, Mass) showed a simu-
tomated microkeratome (Auto- 20/100.Automatedrefractioniden- lated keratometry reading of
mated Corneal Shaper [ACS]; tifiedanerrorof–5.50+3.50(cid:2)159, 40.01(cid:2)41.07@91° with a surface
Bausch & Lomb Surgical, Roches- butthecorrespondingvisualacuity regularityindexof0.52andasur-
ter,NY)wasusedtocreatethecor- wasnotrecorded.Topicalcorticoste- faceasymmetryindexof0.18.How-
neal flaps with nasally located roids were prescribed for applica- ever,atopographicmapoftheleft
hinges,followedbyablationwithan tion3timesdailyanddiscontinued eyeproducedasimulatedkeratom-
excimerlaser(VISXStar;VISX,Inc, after 1 month. During the next 6 etryreadingof40.90(cid:2)42.51@103°
SantaClara,Calif).Anepithelialde- months,thecornealhazeintheleft with a surface regularity index of
fectwasproducedduringsurgeryin eye was not recorded as being any 0.50 and a surface asymmetry in-
thelefteye.Abandagesoftcontact greaterthan1+.However,at9months dexof1.25.Oncomparingtheright
lens was placed, but a defect per- after flap amputation, the uncor- andlefteyes,amarkedlyasymmetri-
sistedatthefirstfollow-upvisit1day rected vision was recorded as 20/ calreflexwasalsoobservedonreti-
later.Approximately3weekslater, 100, correcting to 20/40 with a re- noscopywithsignificantlygreaterir-
epithelialingrowthalongtheinter- fractionof–1.50+0.25(cid:2)171. regularitynotedinthelefteye.
faceofthecornealflapandthebed Thepatientwasreferredtothe Althougharelativelyhighde-
wasidentifiedatthehingeandex- University of California, San Fran- greeofastigmatismwasnotedinthe
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lefteye,thesphericalequivalentwas
calculatedtobe–1.625diopters(D).
Sincetherefractionintherighteye
was–1.50+1.00(cid:2)090,anisometro-
piawaslimited,sospectacleswere
prescribedtoimprovevisualfunc-
tion.
Case2.A33-year-oldmanun-
derwentbilateralLASIKforthecor-
rectionofanerrorof–1.75+0.50(cid:2)30
ODand–2.00+0.25(cid:2)160OS.Anau-
tomatedmicrokeratome(ACS;Bausch
&LombSurgical)wasusedtocreate
thecornealflaps.Alargeepithelialde-
fectwascreatedinthelefteye,sothe
flapwasrepositionedwithoutexcimer
laserablation.Abandagecontactlens
wasplacedtopromoteepithelialheal-
ing.Approximately2monthslater,the
patientreturnedtosurgery.Acorneal Figure2.Case2.Slitlampphotographofthelefteye.Notewithintheslitbeamabandofscarringthat
flapwithanasalhingewascreatedin outlinestheperimeteroftheflap,butrelativeclearingofthecentralcorneaoverlyingtheentrancepupil.
theleftcorneausinganautomatedmi-
crokeratome(ACS;Bausch&Lomb
Surgical),andtheablationwasper- duced to 1 drop per day and then Theirregularityofthelefteye’s
formedusinganexcimerlaser.Anepi- discontinued. corneal surface was confirmed by
thelialdefectwasnotedattheendof Thepatientcomplainedofpoor computerized corneal mapping
theprocedure,andabandagecontact visionandnighttimeglareandhalo (Figure3).Atopographicmapof
lenswaskeptinplaceforthenext3 and was referred to the University therighteyeproducedasimulated
days.Oneweekaftersurgery,uncor- ofCalifornia,SanFranciscoRefrac- keratometry reading of 42.27 (cid:2)
rectedvisionwas20/40OS,correct- tive Surgery Service for consulta- 43.32@84°,withasurfaceregular-
ing to 20/25 with a refraction of tioninMay2001,approximately18 ityindexof0.11andasurfaceasym-
–1.00+1.50(cid:2)20.Nosignificantepi- months after LASIK and subse- metryindexof0.50.However,ato-
thelialingrowthwasnoted. quentflapamputationofthelefteye. pographicmapofthelefteyeshowed
Twoweekslater,thepatientre- Examinationatthattimedisclosed asimulatedkeratometryreadingof
turnedwiththecomplaintofocular anuncorrectedvisualacuityof20/25 43.57(cid:2)46.40@115°, with a sur-
discomfort in the left eye. Uncor- OD, correcting to 20/20 with a re- face regularity index of 1.62 and a
rectedvisionwas20/30−.Epithelial fractionof–0.50+0.50(cid:2)55,andan surfaceasymmetryindexof0.86.On
ingrowthwasnotedalongthenasal uncorrected visual acuity of 20/60 comparingtherightandlefteyes,a
hinge,withextensiontowardtheen- OS,correctingto20/20−withare- markedly asymmetrical reflex was
trancepupil.Atthatvisit,theflapwas fraction of –3.75+3.75(cid:2)97. alsoobservedonretinoscopy,with
liftedtoremovetheinterfaceepithe- Pachymetryreadingswere532µm markedlygreaterirregularitynoted
lium, and the epithelium overlying ODand439µmOS. inthelefteye.
theflapwasnotedtobefriable.On Slitlampbiomicroscopicexami- Sincetheacuityinthelefteye
the basis of anticipated difficulties nationoftherighteyeshowedawell- couldbecorrectedto20/20−witha
with recurrent epithelial ingrowth, positioned,nasallyhingedcornealflap relativelylowdegreeofanisometro-
the flap was amputated and a ban- withmildcentralsubepithelialopaci- pia based on spherical equivalent,
dagecontactlenswasplaced.Cipro- fication,whereasslitlampexamina- spectacles were recommended, but
floxacin and diclofenac solutions tionofthelefteyewasremarkablefor thepatientadamantlyrefusedtocon-
were prescribed 4 times daily. The mildverticallinearelevationatthesite siderspectaclecorrection.Rigidcon-
epithelial defect healed during the ofthetransectedhinge,asemicircle tactlenseswerealsosuggested,but
nextfewdays,and1weekafterflap ofsubepithelialhazereminiscentof thepatientelectedtoforgofitting.
amputationtheuncorrectedvisual surfacephotorefractivekeratectomy
acuity was 20/200, correcting to (PRK)–associated scarring that ap- Comment. Thefindingsfromlarge
20/60 with a refraction of –5.00 pearedtooutlinetheperimeterofthe reportedseriesofcomplicationsseen
+1.50(cid:2)100.Theciprofloxacinso- flap, and a relatively lucent central inconsecutivecasesofpatientswho
lutionwasdiscontinued,andcorti- corneaoverlyingtheentrancepupil. haveundergoneLASIKsuggestthat
costeroid drops were prescribed (Figure2)Thesurfaceofthecen- most complications can be attrib-
foruse3timesdaily.Twomonths tralcorneaappearedtoberelatively utedtoabnormalitiesofthecorneal
later, the uncorrected vision was smooth,butuponinstillationoffluo- flap that translate to irregularity or
20/100,correctingto20/50−witha resceinsodiumsolution,inspection opacification of the anterior cor-
refraction of –4.75+2.00(cid:2)105. ofthetearfilmpatternindicatedan nea.1,2Ifamputationofthecornealflap
Thecorticosteroidtherapywasre- irregularsurface. werefollowedbyreepithelialization
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nificant corneal smoothing occurs
from 3 months to 12 months after
PRK,presumablyasaresultofstro-
malhealingandremodeling.Using
Right Eye Left Eye veryhigh-frequencyultrasoundscan-
ning, Reinstein and colleagues5 ex-
aminedcorneasthathadundergone
LASIKandreportedregionalvaria-
tions in epithelial thickness that
tended to compensate for underly-
ingstromalirregularity,therebyre-
ducingcornealirregularity.Inthe2
caseswepresent,itisdiscouraging
that reduced best spectacle-cor-
rectedvisualacuitywithcorrespond-
inglyelevatedindicesofasymmetry
and irregularity was evident 18
monthsand2yearsafterflapampu-
tation.Therefore,itisquestionable
howmuchfurtherimprovementin
Figure3.Case2.Cornealtopographyofbotheyes.Thelefteyeshowssignificantastigmatismwiththe surfaceregularitymightoccurdur-
ruleandelevatedirregularitycomparedwiththerighteye,asrepresentedbyelevatedsurfaceregularity ingsubsequentmonthsoryears.
(SRI)andsurfaceasymmetryindices(SAI).OtherabbreviationsareexplainedinthelegendtoFigure1.
In neither case was there sub-
stantialscarringofthecornealstroma
and smoothing of the corneal sur- whichresultsinirregularastigma- overlyingtheentrancepupilthatwas
face(analogoustocornealhealingaf- tism that limits best spectacle- subjectedtoexcimerablation.High
tersurfacePRK)withouttheintro- correctedvision. degreesofrefractiveerrorcorrected
duction of significant scarring, Under normal circumstances, bysurfacePRKareexpectedtobeas-
refractiveerror,orirregularity,then irregularityofthesurfaceofthestro- sociatedwithagreaterriskofscar-
thisapproachmightproveusefulin malbedisexpectedtobematched ring,andithasbeensuggestedthat
addressing most postsurgical com- bycorrespondingirregularityofthe thisscarringisrelatedtothedepth
plicationsofLASIK.Unfortunately, undersurfaceoftheflap,sothatifan of the ablation performed.6 How-
fewreportsintheliteratureprovide irregularflapiscreatedandthenre- ever, after flap amputation, rela-
aguidetotheclinicalcoursethatcan placed precisely with a “lock and tivelydeeplayersofthecorneawere
beexpectedafterflapamputationin key”effect,littlechangeonthean- exposedtotheepitheliumafterheal-
theuninfectedcornea.Patelandcol- teriorcornealsurfaceisexpected.If ing,andnosignificanthazewasre-
leagues3 recentlyreportedacaseof aregularrefractiveablationisper- corded throughout the healing pe-
traumaticflapdislocationthatwasfol- formedontheexposedstromalbed, riod.Thisfindingsuggeststhatthe
lowedbylossoftheflap.Afterheal- some degree of underlying irregu- riskforhazeformationinPRKprob-
ingofthestromalbed,thepatient’s larityshouldbetranslatedthrough ably goes beyond simple consider-
uncorrected vision was 20/40, im- theablationsothatasthesurfaces ations of exposure of the deeper
provingto20/20witharefractionof are reapposed precisely, matching stroma devoid of Bowman mem-
–1.00+1.00(cid:2)135. thebedtotheundersideoftheflap, branetohealingepithelium.Rather,
However,asour2casesdem- thecompositeeffectonthesurface thesecasessuggestthatflapampu-
onstrate,itcannotbeassumedthat oftheeyeshouldbeattenuationof tationisnotnecessarilyfollowedby
aregularsurfacewillresultafterre- theirregularity.Asour2casessug- significantcentralcornealhazeand
movaloftheflap.Theirregularmy- gest,thisattenuatingeffectislostif scarring.
opic astigmatism we observed im- the flap is removed to expose the Nevertheless,therefractiveand
plies that the curvature of the stromalbed. topographic outcomes of our 2 pa-
stromalbedmightnotpreciselyre- Over time, remodeling of the tientsindicatethatthereisasubstan-
flect that of the anterior surface of epitheliummighthaveasmoothing tialriskforrefractivechangeandin-
theoverlyingflap.Thisfindingsug- effectontheexposedstromalbed,im- duction of irregular astigmatism
gests that the flap might vary in provingbestspectacle-correctedvi- followingflapamputation.Anychar-
thickness from one region to an- sualacuity.Afterthisimprovement, acteristic pattern of induced astig-
other, leading to variability in the residualregularspherocylindricaler- matismisprobablyrelatedtothepath
curvature of the stromal bed cre- rorcanbecorrectedwithspectacles, followed by the microkeratome in
ated.Patternsofvariabilityinthick- hydrophiliccontactlenses,orastan- creatingtheflap,whichinturnwill
ness may well differ from one mi- dard spherocylindrical excimer la- berelatedtotheparticulardesignof
crokeratome to another, and this ser treatment. In a topographic ex- themicrokeratome.Sincetherewere
variability is expected to contrib- amination of eyes treated with no other flap-related abnormalities
utetothedevelopmentofirregular- excimer laser, Abbas and col- beyondepithelialingrowthinthese
ityinthecontourofthestromalbed, leagues4havedemonstratedthatsig- cases,wesurmisethatflapamputa-
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tion was performed because it was 7. DastgheibKA,ClinchTE,MancheEE,HershP, 200ODand20/20OS.Adilatedfun-
seenasadefinitivetreatmentofthe RamseyJ.Sloughingofcornealepitheliumand dusexaminationoftherighteyere-
woundhealingcomplicationsassociatedwithla-
ingrowththatwouldproduceaccept- serinsitukeratomileusisinpatientswithepi- vealed a nonischemic CRVO with
ablesurfacesmoothingovertime. thelialbasementmembranedystrophy.AmJOph- significantly increased macular
thalmol.2000;130:297-303.
Thefirstpatientwedescribehad edema(Figure1A).Opticalcoher-
a history of recurrent erosion syn- encetomography(OCT)revealeda
drome,whichpresentsanincreased diffuselythickenedretinaaswellas
riskforepithelialingrowth,keratoly- cystic foveal changes (Figure 1B).
Intravitreous Triamcinolone
sis,flapmelting,andlossofbestcor- Thepatientwasobservedforanad-
rected visual acuity.7 For this rea- Acetonide as Treatment ditionalmonth,andwhentherewas
son,LASIKisnotrecommendedin for Macular Edema no improvement in the degree of
thesettingofanteriorbasementmem- From Central Retinal macular thickening or visual acu-
brane disease, and PRK should be Vein Occlusion ity,anintravitreousinjectionof4mg
considered. Such severe complica- (40mgin1.0mL)oftriamcinolone
tionsmightindeedultimatelyneces- Central retinal vein occlusion acetonidewasgivenintherighteye.
sitateflapamputation,butnosuch (CRVO)isacommonretinalvascu- Follow-up 1 month later
progressionwasseeninthecasesre- lardisorderthatcanleadtosignifi- showedareturnofvisualacuityto
ported herein. Therefore, based on cant visual disability. Persistent 20/25 OD, with complete resolu-
the observed long-term clinical macularedemaisoneofthemajor tionofmacularedemaonbothclini-
course, we suggest that in the ab- complications associated with cal examination (Figure 2A) and
senceofcompellingindications(such CRVO. The Central Vein Occlu- OCT(Figure2B).Intraocularpres-
as gross flap irregularities or inter- sionStudy1evaluatedtheefficacyof sure was unchanged, and the im-
faceinfectioninwhichtheflapmight macular grid laser photocoagula- provementinvisualacuityandclini-
limit antibiotics penetration), flap tioninpatientswithmacularedema calexaminationresultsremainedat
amputationshouldbealastresortin causedbyCRVO.Thisstudydidnot the6-monthfollow-up.
the management of flap complica- findadifferenceinvisualacuitybe- Case2.A67-year-oldmanhad
tions. tweentreatedanduntreatedeyesat a1-monthhistoryofdecreasedvi-
anystageduringthefollow-uppe- sualacuityinthelefteye.Examina-
StephenD.McLeod,MD riod.Therefore,thereiscurrentlyno tion revealed a best-corrected vi-
DouglasHolsclaw,MD proven management for macular sualacuityof20/20ODand20/200
SalenaLee,OD edemainthesettingofCRVO.The OS.Anteriorsegmentexamination
SanFrancisco,Calif purposeofthisinterventionalcase results were remarkable for 2+
report is to describe the clinical nuclearsclerosisinbotheyes.Hisin-
course of 2 patients with macular traocular pressure was 10 mm Hg
Corresponding author: Stephen D.
edemasecondarytoCRVOwhoun- OU.Adilatedfundusexamination
McLeod,MD,DepartmentofOphthal-
derwentintravitreousinjectionoftri- revealedanormalfundusintheright
mology,UniversityofCaliforniaSan
amcinoloneacetonide. eye.Examinationoftheleftfundus
Francisco,10KirkhamSt,K-301,San
revealed findings consistent with
Francisco,CA94143(e-mail:smcleod
ReportofCases. Case1.A57-year- an ischemic CRVO. Foveal thick-
@itsa.ucsf.edu).
old man had a 2-month history of ness was greater than 600 µm on
1. GimbelHV,PennoEE,vanWestenbruggeJA, decreasedvisualacuityinhisright OCT.
FerensowiczM,FurlongMT.Incidenceandman- eye.Oninitialexamination,hisbest- Thepatientwasfollowedupat
agementofintraoperativeandearlypostopera-
correctedvisualacuitywas20/40OD 2-month intervals for the next 8
tivecomplicationsin1000consecutivelaserin
situkeratomileusiscases.Ophthalmology.1998; and 20/20 OS. Results of anterior months. Although the intraretinal
105:1839-1847. segmentexaminationwereremark- hemorrhage cleared significantly,
2. StultingRD,CarrJD,ThompsonKP,WaringGO
3rd,WileyWM,WalkerJG.Complicationsof ableonlyfor2+nuclearsclerosisin therewasneitherimprovementinvi-
laserinsitukeratomileusisforthecorrectionof botheyes.Intraocularpressurewas sual acuity nor a decrease in the
myopia.Ophthalmology.1999;106:13-20.
15mmHgODand19mmHgOS. amountofmacularedemanotedon
3. PatelCK,HansonR,McDonaldB,CoxN.Late
dislocationofaLASIKflapcausedbyafinger- A dilated fundus examination re- clinicalexaminationorOCT.
nail[publishedcorrectionappearsinArchOph- vealed findings consistent with Because there was no clinical
thalmol.2002;120:180].ArchOphthalmol.2001;
nonischemicCRVOintherighteye. improvement, an intravitreous in-
119:447-449.
4. AbbasUL,HershPS,andtheSummitPRK Macular edema was present. Fun- jectionof4mgoftriamcinoloneace-
StudyGroup.Latenaturalhistoryofcorneal dus examination results were nor- tonide(40mgin1.0mL)wasgiven.
topographyafterexcimerlaserphotorefractive
keratectomy.Ophthalmology.2001;108:953- malinthelefteye. Figure3showstheextensivemacu-
959. Slitlamp biomicroscopy re- lar edema noted on both slitlamp
5. ReinsteinDZ,SilvermanRH,SuttonHF,Cole-
vealedsomeimprovementinthede- biomicroscopyandOCT5daysbe-
manDJ.Veryhigh-frequencyultrasoundcor-
nealanalysisidentifiesanatomiccorrelatesofop- greeofmacularedemaintheright foretreatment.Threeweeksfollow-
ticalcomplicationsoflamellarrefractivesurgery: eyeduringthenext2months.How- ingtreatment,hisvisualacuityim-
anatomicdiagnosisinlamellarsurgery.Ophthal-
ever, 8 months after initial exami- provedto20/100OS,andafundus
mology.1999;106:474-482.
6. Moller-PedersenT,CavanaghHD,PetrollWM, nation, his visual acuity had de- examination revealed a significant
JesterJV.CornealhazedevelopmentafterPRK creasedfurther.Examinationatthat decreaseinmacularedema.Foveal
isregulatedbyvolumeofstromaltissuere-
moved.Cornea.1998;17:627-639. timerevealedavisualacuityof20/ thicknessmeasuredwithOCTwas
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A B
Figure1.A,Colorfundusphotographoftherighteyeshowsnonischemiccentralretinalveinocclusioncomplicatedbymacularedemabeforeintravitreous
injectionoftriamcinoloneacetonide.Visualacuitywas20/200.B,Opticalcoherencetomogramoftherighteyeshowsadiffuselythickenedretina(to600µm)
beforeintravitreousinjectionoftriamcinoloneacetonide.
A B
Figure2.A,Colorfundusphotographoftherighteye1monthfollowingintravitreousinjectionoftriamcinoloneacetonideshowsresolutionofmacularedema.
B,Opticalcoherencetomogramoftherighteye1monthfollowingintravitreousinjectionoftriamcinoloneacetonideshowsrestorationofnormalfoveal
architecture.Thecentralfovealthicknessmeasured100µm.
A B
Figure3.A,Colorfundusphotographofthelefteyeshowsischemiccentralretinalveinocclusioncomplicatedbymacularedemabeforeintravitreous
injectionoftriamcinoloneacetonide.Thisphotographwastaken8monthsafterinitialexamination,andalthoughtherewasreductionintheamount
ofintraretinalhemorrhage,significantmacularedemapersisted.Visualacuitywas20/200.B,Opticalcoherencetomogramofthelefteyeshowscystic
fovealchangesandadiffuselythickenedretina(to(cid:3)600µm)beforeintravitreousinjectionoftriamcinoloneacetonide.
100µm.Atthe2-monthfollow-up, 20/400. Macular edema was noted Comment. Triamcinolone ace-
therecontinuedtobeareductionin onslitlampbiomicroscopy,andfo- tonideisacorticosteroidthatiscom-
macular edema on clinical exami- vealthicknesswas500µmonOCT. merciallyavailable,inexpensive,and
nationandOCT(Figure4). No further intervention was at- commonlyusedasaperiocularin-
The patient did well until 3 tempted at this point, and the pa- jectionforthetreatmentofcystoid
months following the injection, tient has been observed with no macular edema occurring second-
whenhisvisualacuitydecreasedto changeinhisclinicalstatus. ary to uveitis or resulting from in-
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